熊紹平 王亮
[摘要] 目的 系統評價肝臟分隔結合門靜脈結扎的分步肝切除(ALPPS)與傳統分步肝切除術如門靜脈栓塞(PVE)和二步肝切除(TSH)的圍術期療效差異。 方法 通過計算機檢索知網、萬方、PubMed、Cochrane、Embase、中國生物醫學文獻數據庫,檢索時限為2011年1月1日至2019年12月31日,收集國內外ALPPS與PVE/TSH的臨床對比研究,采用RevMan 5.3軟件進行Meta分析。 結果 共納入8篇研究,共涉及732例患者。Meta分析結果顯示,ALPPS與PVE/TSH在FLR增長率、二步手術完成率及R0切除率方面比較,差異均有統計學意義(P<0.05)。ALPPS的圍術期并發癥總發生率高于PVE/TSH,但差異無統計學意義(P>0.05)。ALPPS的90 d死亡率略高于PVE/TSH,但差異無統計學意義(P>0.05)。 結論 ALPPS的FLR增長率、二步手術完成率和R0切除率均高于PVE/TSH,在把握適應證的前提下,ALPPS有效可行。
[關鍵詞] 肝臟分隔結合門靜脈結扎的分步肝切除術;門靜脈栓塞;二步肝切除;Meta分析
[中圖分類號] R61? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-9701(2021)11-0021-05
Meta-analysis of ALPPS and traditional stepwise hepatectomy
XIONG Shaoping? ?WANG Liang
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou? ?121000, China
[Abstract] Objective To systematically evaluate the difference in perioperative efficacy between associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) and traditional stepwise hepatectomy, such as portal vein embolization(PVE) and two-step hepatectomy(TSH). Methods A computer search was conducted on CNKI, Wanfang, PubMed, Cochrane, Embase and Chinese Biomedical Literature Database to collect the data on comparative clinical studies of ALPPS and PVE/TSH domestic and overseas from January 1, 2011 to December 31, 2019. The RevMan 5.3 software was used for Meta-analysis. Results A total of 8 studies were included, involving 732 patients. Meta-analysis results showed that there were statistically significant differences in FLR growth rate, two-step surgery completion rate and R0 resection rate between ALPPS and PVE/TSH(P<0.05). ALPPS had a higher incidence of total perioperative complications than PVE/TSH, but the difference was not statistically significant(P>0.05). The 90-day mortality was slightly higher in the ALPPS group than in the PVE/TSH group, but the difference was not statistically significant(P> 0.05). Conclusion ALPPS has a better FLR growth rate, higher two-step surgery completion rate and R0 resection rate than PVE/TSH. Under the premise of grasping the indications, ALPPS is effective and feasible.
[Key words] Associating liver partition and portal vein ligation for staged hepatectomy; Portal vein embolization; Two-step hepatectomy; Meta-analysis
肝切除術已成為治療肝癌最有效的方法之一,但分期較晚的肝癌仍然是外科手術的主要挑戰。限制肝切除術的主要原因是剩余肝臟體積(Future liver remnant,FLR)不足導致的術后肝功能衰竭[1]。在良好的患者選擇和改善圍術期管理的情況下,大范圍肝切除術可以安全進行[2]。在此背景下,采用門靜脈栓塞(Portal vein embolization,PVE)、兩步肝切除(Two-stage hepatectomy,TSH)或肝臟分隔聯合門靜脈結扎的分步肝切除(Associating liver partition and portal vein ligation for staged hepatectomy,ALPPS)等方式均可減少術后肝功能衰竭(Post hepatectomy liver failure,PHLF)[3]。術前PVE或TSH被認為是肝切除前FLR不足患者的常用方法,但其FLR增長速度并不出色,很多患者由于疾病進展失去手術機會[4-5]。據報道,ALPPS具有較理想的FLR增長率,但伴隨高并發癥發生率及死亡率[6]。本研究通過收集國內外ALPPS和PVE/TSH用于原發性或繼發性肝癌患者的臨床研究資料,評估ALPPS和PVE/TSH術式圍術期的安全性及有效性,現報道如下。
1 資料與方法
1.1 一般資料
檢索PubMed、Embase、Cochrane、知網、萬方及中國生物醫學文獻數據庫。英文檢索詞:liver partition、liver transection、portal vein embolization、PVE、portal vein ligation、PVL、associating liver partition and portal vein ligation for staged hepatectomy、ALPPS、staged hepatectomy、staged liver resection、two-stage hepatectomy、TSH。中文檢索詞:門靜脈栓塞、PVE、門靜脈結扎、PVL、肝臟分隔聯合門靜脈結扎的分步肝切除、ALPPS、傳統分步肝切除、兩步肝切除、TSH、肝癌、肝臟腫瘤、肝轉移癌。檢索時限定義為2011年1月1日至2019年12月31日。
1.2 方法
1.2.1 文獻納入標準? ①原發性或繼發性肝腫瘤患者行ALPPS與PVE/TSH的臨床對照研究;②研究中至少有一個以下對比結果:如再生效率、兩個階段的時間間隔、二期手術完成率、R0切除率、90 d死亡率等;③患者為成年人,年齡>18歲;④患者手術前沒有放化療的限制。
1.2.2 文獻排除標準? ①綜述、病例報告、社論、信函、會議記錄;②動物實驗;③無法從合并結果中提取數據的研究;④沒有全文的研究。
1.2.3資料提取和質量評估? 兩位研究者獨立提取并總結以下數據:患者特征、研究設計、納入和排除標準及報告的結果,任何分歧均由第三方共同解決。采用NOS(Newcastle-Ottawa scale)量表對納入的隊列研究進行質量評估,在患者的選擇、組間可比性和結果三方面進行評分,得分≥6分的研究被認為具有良好的質量[7]。用改良Jadad量表對隨機對照研究進行質量評估,得分≥4分的文獻被認定為質量較高[8]。
1.3 統計學方法
采用RevMan 5.3軟件進行Meta分析。首先采用I2統計量進行異質性檢驗,如果I2不大于50%,認為研究間異質性較小,選用固定效應模型進行數據合并,反之則認為納入研究間的異質性較大,采用隨機效應模型。合并的數據如果為連續變量,采用均數差(Mean deviation,MD)及其95%可信區間(Confidence interval,CI)進行統計學分析,如果為二分類變量則采用比值比(Odds ratio,OR)及其95%CI進行統計學分析,以P<0.05為差異有統計學意義。
2 結果
2.1 文獻納入及基本情況
文獻檢索結果和研究選擇如圖1所示,最終納入8篇相關研究[9-16],共涉及732例患者。其中比較ALPPS與PVE的研究有4篇,比較ALPPS與TSH的研究有4篇;PVE組313例,TSH組202例,ALPPS組217例。納入的8篇研究的特點如表1所示,研究質量評分均良好。
2.2 Meta分析結果
2.2.1 肝切除前FLR增長率? 總結納入的5項研究中504例患者的FLR增長率,異質性定量檢驗I2=46%,異質性較小,采用固定效應模型。結果顯示,ALPPS的FLR增長率高于PVE/TSH,差異有統計學意義(MD=43.07;95%CI:39.97~46.17;P<0.05)。
2.2.2 二步手術完成率? 總結納入的7項研究中710例患者的二步手術完成率,異質性定量檢驗I2=0%,無異質性,采用固定效應模型。結果顯示,ALPPS的二步手術完成率為96.65%,高于PVE/TSH的68.06%,差異有統計學意義(OR=12.89,95%CI:6.19~26.86,P<0.05)。
2.2.3 R0切除率? 總結納入的4項研究中242例患者的R0切除率,異質性定量檢驗I2=14%,異質性不明顯,采用固定效應模型。結果顯示,ALPPS組的R0切除率為77.78%,高于PVE/TSH的65.87%,差異有統計學意義(OR=2.28,95%CI:1.08~4.79,P<0.05)。
2.2.4 圍術期并發癥總發生率? 總結納入的6項研究中348例患者的圍術期并發癥總發生率。異質性定量檢驗I2=0%,無異質性,采用固定效應模型。結果顯示,ALPPS的圍術期并發癥總發生率高于PVE/TSH,但差異無統計學意義(OR=1.07,95%CI:0.63~1.80,P>0.05)。
2.2.5 90 d死亡率? 總結納入的5項研究中372例患者的90 d死亡率,異質性定量檢驗I2=0%,同質性較高,采用固定效應模型。結果顯示,ALPPS的90 d死亡率為10.56%,略高于PVE/TSH的6.96%,但差異無[4] Giglio MC,Giakoustidis A,Draz A,et al.Oncological outcomes of major liver resection following portal vein embolization:A systematic review and meta-analysis[J].Ann Surg Oncol,2016,23(11):3709-3717.
[5] Wicherts DA,Miller R,de Haas RJ,et al.Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases[J].Ann Surg,2008,248(6):994-1005.
[6] Kambakamba P,Linecker M,Schneider M,et al.Impact of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)on growth of colorectal liver metastases[J].Surgery,2018,163(2):311-317.
[7] Stang A.Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in Meta-analyses[J].Eur J Epidemiol,2010,25(9):603-605.
[8] Jadad A,Moore R,Carroll D,et al.Assessing the quality of reports of randomized clinical trials:Is blinding necessary[J].Control Clin Trials,1996,17(1):1-12.
[9] Shindoh J,Vauthey JN,Zimmitti G,et al.Analysis of the efficacy of portal vein embolization for patients with extensive liver malignancy and very low future liver remnant volume,including a comparison with the associating liver partition with portal vein ligation for staged hepatectomy approach[J].J Am Coll Surg,2013,217(1):126-134.
[10] Croome KP,Hernandez-Alejandro R,Parker M,et al.Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant?A multicentre analysis[J].HPB(Oxford),2015,17(6):477-484.
[11] Schadde E,Ardiles V,Slankamenac K,et al.ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies:Results of a multicenter analysis[J].World J Surg,2014,38(6):1510-1519.
[12] Adam R,Imai K,Castro BC,et al.Outcome after associating liver partition and portal vein ligation for staged hepatectomy and conventional two-stage hepatectomy for colorectal liver metastases[J].Br J Surg,2016,103(11):1521-1529.
[13] Matsuo K,Murakami T,Kawaguchi D,et al.Histologic features after surgery associating liver partition and portal vein ligation for staged hepatectomy versus those after hepatectomy with portal vein embolization[J].Surgery,2016, 159(5):1289-1298.
[14] Chia D,Yeo Z,Loh S,et al.Greater hypertrophy can be achieved with associating liver partition with portal vein ligation for staged hepatectomy compared to conventional staged hepatectomy,but with a higher price to pay[J].Am J Surg,2018,215(1):131-137.
[15] Sandstrom P,Rosok B,Sparrelid E,et al.ALPPS improves resectability compared with conventional twostage hepatectomy in patients with advanced colorectal liver metastasis:Results from a scandinavian multicenter randomized controlled trial(LIGRO Trial)[J].Ann Surg,2018, 267(5):833-840.
[16] Chan A,Zhang W,Chok K,et al.ALPPS versus portal vein embolization for hepatitis-related hepatocellular carcinoma:A changing paradigm in modulation of future liver remnant before major hepatectomy[J].Ann Surg,2019, 127(6):873-880.
[17] Kwon YJ,Lee KG,Choi D.Clinical implications of advances in liver regeneration[J].Clin Mol Hepatol,2015, 21(1):7-13.
[18] Vauthey JN,Dixon E,Abdalla EK,et al.Pretreatment assessment of hepatocellular carcinoma:Expert consensus statement[J].HPB(Oxford),2010,12(5):289-299.
[19] Linecker M,Kambakamba P,Reiner CS,et al.How much liver needs to be transected in ALPPS?A translational study investigating the concept of less invasiveness[J].Surgery,2017,161(2):453-464.
[20] Li J,Kantas A,Ittrich H,et al.Avoid all-touch by hybrid ALPPS to achieve oncological efficacy[J].Ann Surg,2014, 263(1):1080-1085.
[21] Santibanes E,Alvarez FA,Ardiles V,et al.Inverting the ALPPS paradigm by minimizing first stage impact:The mini-ALPPS technique[J].Langenbecks Arch Surg,2016, 401(4):557-563.
[22] Cillo U,Gringeri E,Feltracco P,et al.Totally laparoscopic microwave ablation and portal vein ligation for staged hepatectomy:A new minimally invasive two-stage hepatectomy[J].Ann Surg Oncol,2015,22(8):2787-2796.
[23] Robles R,Parrilla P,Lopez-Conesa A,et al.Tourniquet modification of the associating liver partition and portal ligation for staged hepatectomy procedure[J].Br J Surg,2014,101(9):1129-1134.
[24] Truant S,El Amrani M,Baillet C,et al.Laparoscopic partial ALPPS:Much better than ALPPS[J].Ann Hepatol,2019,18(1):269-273.
[25] 王瑞濤,劉昌,張曉剛,等.ALPPS在肝泡型包蟲病中的應用[J].中華肝臟外科手術學電子雜志,2018,7(2):127-132.
[26] Oldhafer KJ,Stavrou GA,Van Gulik TM,et al.ALPPS where do we stand,where do we go?Eight recommendations from the first international expert meeting[J].Ann Surg,2016,263(5):839-841.
(收稿日期:2020-07-09)