以手術相關因子、慢性肝炎形態探討肝切除手術肝癌患者長期預後與醫療利用

研究目的本研究主要探討肝癌病患接受肝切除手術之預後，包含：腹腔鏡與傳統開腹式之兩術式間手術預後、長期療效以及醫療資源利用是否有所差異，以及腫瘤切割安全距離是否影響預後及長期療效，並探討合併慢性肝炎形態之差異是否影響到病患手術預後以及長期療效，最後探討影響醫療資源利用相關因子。研究方法本研究為一回溯性研究，蒐集2000年至2007年7月底，臺灣南部地區兩家區域教學級以上醫院確診為原發性肝癌，並為初次接受手術切除患者為本研究樣本，每名樣本至少六個月以上追蹤期，研究終止期為2008年1月底。根據三個主要目的，將病患細分為1)手術術式：腹腔鏡(n=67)、傳統開腹式(n=258)。2)腫瘤切割安全距離：狹窄組(n=253)、寬闊組(n=139)。3)慢性肝炎：NBNC(n=56)、HBV(n=218)、HCV(n=130)、HBCV(n=33)。所有資料來源包括：病歷審查、中央健康保險住院清單明細檔(DD檔)、內政部死亡檔。統計分析數據資料以平均值±標準差或次數(%)呈現，連續性資料以獨立t test、One-way ANOVA分析，類別變項以χ2 test以及Fisher exact test分析，以Kaplan-Meier method計算累積存活率以及累積無復發存活率，並進一步使用log-rank test 探討組間之差異；利用Cox proportional hazard model探討影響長期預後的危險因子；利用Multiple linear regression探討影響醫療資源利用因子，p<0.05為達到統計上顯著差異。研究結果控制相關因子後，腹腔鏡與開腹式之肝切除手術兩組之長期療效沒有差異，而腹腔鏡總住院天數較傳統開腹式少3.85天，總住院費用無顯著差異；腫瘤切割安全距離狹窄組(≦1公分)其整體存活率和寬闊組(>1公分)無顯著差異，但在無復發存活率兩組間達到顯著差異，狹窄組其復發風險高出1.37倍；合併慢性肝炎形態並不影響到術後整體存活率以及無復發存活率；影響總住院費用因子為手術年齡、切除範圍、輸血量、BUN、併發症(肝衰竭、腎衰竭、成人呼吸窘迫症候群)、腫瘤數目、腫瘤切割距離，影響總住院天數因子為ALK-P、BUN、Creatinine、albumin、手術時間、手術術式、併發症(大量腹水、肝衰竭、延長高膽色素血症、靜脈瘤出血)、合併症，影響術後一年住院費用因子為合併症、術後一年復發、術後一年死亡、當次手術切除範圍。結論與建議研究發現腹腔鏡與傳統開腹式手術兩組間預後無差異，而腹腔鏡手術總住院天數較低於傳統開腹式，整體費用腹腔鏡甚至低於傳統開腹式，並且腹腔鏡手術過程亦較為安全，因此，本研究中認為控制相關因子後，腹腔鏡可考慮為肝切除手術優先考量術式；腫瘤切割安全距離與累積無復發存活率有顯著相關，大於1公分切除邊緣可降低術後復發率；合併慢性肝炎四組其長期預後無差異，但HBCV及HCV預後明顯較差於其他兩組；研究亦發現影響醫療資源利用最強的因子為併發症，併發症的產生延長了病患住院天數以及必須負擔額外龐大的醫療支出，因此改善病患照護流程，降低術後併發症的產生是必要的。

關鍵字

肝癌；肝切除術；腹腔鏡；腫瘤切割安全距離；慢性肝炎；長期療效；醫療資源利用

並列摘要

Objective The aims of the study are analyses of HCC (Hepatocellular carcinoma) patients who underwent the hepatectomy, including long-term outcome and medical resource utilizations of laparoscopic versus open liver resection, surgical safety margin, and different patterns of viral Hepatitis. Methods From January 2000 to July 2007, 438 primary HCC patients who never received liver resection before and diagnosed in a medical center and a regional medical teaching hospital in the South of Taiwan. The periods of follow-up were until January 2008. The patients were categorized into three groups:1) surgical type: laparoscope (n=67), open (n=258) 2) surgical safety margin: narrow (n=253), wide (N=139) 3) chronic hepatitis: NBNC(n=56), HBV(n=219), HCV(n=130), HBCV(n=33).The data were collected in the following manners: medical chart review, National Health Insurance Research Database from the National Health Insurance institution Taiwan and mortality data bank established by the Statistics Office, Department of Health, Taiwan. Statistical analysis All data are presented as percentages of patients or the Mean ±SD. Statistical analyses were performed using univariate tests (Student’s t test or ANOVA analysis, χ2 analysis and Fisher’s exact test ) to test for differences in variables. The Kaplan-Meier method was used to calculate the overall cumulative survival rates and disease-free survival rates. Differences in survival were examined using the log-rank test. For evaluation of outcome predicator, Cox proportional hazard model were used. For the evaluation of medical utility consumption predictors, multiple linear regression analyses were used. A p-value less than 0.05 was considered significant. Results Under adjusting relative factors, there is no difference between laparoscopic liver resection and open liver resection. The length of stay in laparoscopic liver resection group was shorter than open liver resection group (mean 3.85 days).There was no difference in total admission medical expense. Overall outcome was no difference between narrow group (≦1cm) and wide group (>1cm), but free survival rate in narrow group was 1.37 fold to wide group. Different hepatitis patterns do not influence overall outcome and free survival rate. The relative factors of admission medical expense were age, tumor size, and volume of blood transfusion, BUN, complications (hepatic failure, renal failure, and adult respiratory distress syndrome), tumor number, and surgical safety margin. The relative factors of total the length of stay were ALK-P, BUN, Creatinine, albumin, operation time, surgical type, complications (massive ascites, hepatic failure, prolong hyperbilirubinemia, bleeding varices). The relative factors of admission medical expense in the one year after surgery were comorbidity, recurrence and death in the one year after surgery, and the exsection extent of the surgery. Conclusion and suggestion Our study revealed that there was no difference between laparoscopic liver resection and open liver resection, but total length of stay is shorter in laparoscopic group. The medical cost was lower and the procedure was much safety in laparoscopic group. Therefore, we suggest under adjusting relative factors, laparoscopic liver resection could be the first choice of the surgical type. There was significant differences between surgical safety margin and cumulative no recurrence survival rate, ＞1cm safety margin could decrease recurrence rate. Hepatitis patterns were no difference in long-term outcome in four groups, but HBV and HCV group were worse. The most powerful influence factor of the medical cost was complications, it delay the discharge of the patient and so offer extra cost. Therefore, it is necessary to improve patient care procedure and decrease occurrence of the complications. Key word: Hepatocellular carcinoma, liver resection, laparoscopic, surgical safety margin, chronic hepatitis, long-term outcome, medical utilization