張輝 張振 張海濤 張其坤 王孟龍
·論 著·(臨床實踐)
肝門部膽管癌根治術(shù)前經(jīng)內(nèi)鏡鼻膽管引流和經(jīng)皮經(jīng)肝膽管造影引流術(shù)的臨床效果觀察
張輝 張振 張海濤 張其坤 王孟龍
目的 對比經(jīng)內(nèi)鏡鼻膽管引流術(shù)(endoscopic nasobiliary drainage,ENBD)和經(jīng)皮經(jīng)肝膽管造影引流術(shù)(percutaneous transhepatic cholangiography and drainage,PTCD)作為術(shù)前減黃對肝門部膽管癌根治術(shù)的不同效果。方法 回顧性分析2008年1月至2016年8月,首都醫(yī)科大學(xué)附屬北京佑安醫(yī)院普通外科中心20例行ENBD并完成肝門部膽管癌根治術(shù)病人的臨床資料,與同期31例行PTCD并完成肝門部膽管根治術(shù)病人的臨床資料進行比較。比較兩組以下指標的差異:病人減黃時間,減黃前及術(shù)前、術(shù)后肝功能指標(血總膽紅素、血直接膽紅素、天冬氨酸轉(zhuǎn)氨酶、丙氨酸轉(zhuǎn)氨酶、白蛋白水平),術(shù)中情況(手術(shù)時間、出血量、輸血量),術(shù)后并發(fā)癥。結(jié)果 ENBD組與PTCD組均能夠顯著降低膽紅素水平(P<0.05);PTCD組除了能夠降低膽紅素水平外,肝功能酶學(xué)水平也顯著降低(P<0.05);ENBD組肝功能酶學(xué)減黃前后差異無統(tǒng)計學(xué)意義(P>0.05);術(shù)中兩組手術(shù)時間、術(shù)中出血量及術(shù)后血總膽紅素、血直接膽紅素、天冬氨酸轉(zhuǎn)氨酶、丙氨酸轉(zhuǎn)氨酶、術(shù)后住院時間、住院總費用比較,差異均無統(tǒng)計學(xué)意義(均P>0.05);PTCD組與ENBD組圍手術(shù)期并發(fā)癥發(fā)生率比較差異無統(tǒng)計學(xué)意義(74.2%比60.0%,P>0.05),其中PTCD組術(shù)后膽管炎發(fā)生率更高(48.4%比20.0%),差異有統(tǒng)計學(xué)意義(P=0.036)。結(jié)論 ENBD和PTCD均能夠有效降低術(shù)前膽紅素水平,PTCD引流更充分,減黃時間更短,肝功能恢復(fù)效果更好,ENBD術(shù)后膽管炎并發(fā)癥更低;肝門部膽管癌術(shù)前應(yīng)結(jié)合病人的具體情況選擇合適引流方式,從而增加手術(shù)安全性,減少術(shù)后并發(fā)癥發(fā)生率。
肝門部膽管癌; 經(jīng)內(nèi)鏡鼻膽管引流術(shù); 經(jīng)皮經(jīng)肝膽管造影引流術(shù)
肝門部膽管癌是起源于膽管上皮的惡性腫瘤,也稱Klatskin瘤,位于膽囊管開口以上的膽總管和左右肝管,約占所有膽管癌的60%~70%。目前認為根治性的手術(shù)切除(R0切除)是唯一可能獲得較長生存期的方法[1]。為了獲得充分的陰性切緣,多數(shù)學(xué)者主張聯(lián)合半肝(擴大的半肝)切除,然而肝門部膽管癌病人多合并梗阻性黃疸及不同程度的肝功能損害[2]。術(shù)前減黃(preoperative biliary drainage,PBD)作為改善圍手術(shù)期肝功能的一種方法目前仍然有爭議,一般認為當(dāng)梗阻性黃疸病人血總膽紅素>200 μmol/L且同時需要大范圍肝切除(切除肝葉>全肝體積60%)、合并膽管炎、營養(yǎng)風(fēng)險大、需做選擇性門靜脈栓塞的肝門部膽管癌病人應(yīng)考慮給予術(shù)前膽道引流[3]。肝門部膽管癌PBD方式主要有:經(jīng)內(nèi)鏡鼻膽管引流術(shù)(endoscopic nasobiliary drainage,ENBD)、經(jīng)皮經(jīng)肝膽管造影引流術(shù)(percutaneous transhepatic cholangiography and drainage,PTCD),經(jīng)內(nèi)鏡膽管內(nèi)引流術(shù)(endoscopic retrograde biliary drainage,ERBD)容易引起膽管炎,不建議術(shù)前使用[4-5]。盡管已經(jīng)有很多關(guān)于惡性腫瘤致梗阻性黃疸PBD方式的研究,關(guān)于肝門部膽管癌PBD方式選擇的文獻較少。本文通過對2008年1月至2016年8月首都醫(yī)科大學(xué)附屬佑安醫(yī)院術(shù)前行PTCD或ENBD并最終完成肝門部膽管癌根治術(shù)的病人進行回顧性研究,探討兩種減黃方式對肝門部膽管癌圍手術(shù)期的不同影響。
一、臨床資料
收集我院普通外科中心88例確診肝門部膽管癌并行手術(shù)切除病人的臨床資料(術(shù)后病理證實為肝門部膽管癌),術(shù)前行減黃處理51例,根據(jù)減黃方式不同分為兩組:ENBD組20例,男性10例,女性10例,年齡53~74歲,平均年齡(61±7)歲;PTCD組31例,其中男性20例,女性11例,年齡34~77歲,平均年齡(57±11)歲。術(shù)前一般資料包括:腫瘤分型(依據(jù)Bismuth-Corlette分型)、減黃時間、入院時血總膽紅素(TBIL)、血直接膽紅素(DBIL)、天冬氨酸轉(zhuǎn)氨酶(AST)、丙氨酸轉(zhuǎn)氨酶(ALT)、白蛋白水平,兩組術(shù)前資料比較差異無統(tǒng)計學(xué)意義(表1)。所有病人術(shù)前均未進行經(jīng)皮門靜脈栓塞(PVE)、放化療等其他處理。ENBD組2例因引流不充分行PTCD術(shù),PTCD組1例因引流管阻塞再次更換PTCD管。
二、研究方法
所有病人術(shù)前采用彩超、CT、MRI或MRCP等影像學(xué)檢查輔助診斷,常規(guī)減黃前1 d、手術(shù)前1 d及手術(shù)后3 d檢查血常規(guī)、肝功能生化、凝血功能檢查,評估病人肝腎功能水平。通過觀察記錄術(shù)前減黃時間,減黃前、手術(shù)前及手術(shù)后3 d肝功能酶學(xué)、血膽紅素指標,白蛋白,手術(shù)時間,術(shù)中失血量,術(shù)后并發(fā)癥,圍手術(shù)期病死率,術(shù)后住院時間,總住院費用,綜合評價兩種減黃方式效果對手術(shù)的影響。
我院進行術(shù)前減黃標準:重度黃疸(血總膽紅素>200 μmol/L)、持續(xù)時間較長(大于2周)、伴有膽道感染(甚至發(fā)生急性梗阻性化膿性膽管炎)、凝血功能障礙、一般狀況較差。
1.ENBD 先行ERCP檢查,確定病變部位及引流部位,在造影導(dǎo)管引導(dǎo)下插入導(dǎo)絲,而后留置導(dǎo)絲退出導(dǎo)管,經(jīng)導(dǎo)絲將鼻膽管插入引流部位,并將鼻導(dǎo)管從口中引出。 另選一根導(dǎo)管經(jīng)鼻插入至口腔,在其引導(dǎo)下將鼻膽管從鼻腔引出并固定。
2.PTCD 在B超引導(dǎo)下,根據(jù)肝內(nèi)膽管情況確定穿刺位置,局部麻醉,行經(jīng)皮經(jīng)肝穿刺放置8F膽道外引流管。對于膽管引流部位的選擇,一般首選預(yù)留肝葉單側(cè)引流。但對引流前手術(shù)方式難以確定的病人,或在單側(cè)引流后血膽紅素降低緩慢、并發(fā)膽管炎者,行雙側(cè)膽管完全引流(本組3例因單側(cè)引流不充分,行雙側(cè)引流,均為BismuthⅣ型病人)。
3.肝門部膽管癌根治術(shù) ENBD組行單純膽管癌切除術(shù)+膽腸吻合術(shù)4例;左半肝切除+尾狀葉切除+膽腸吻合術(shù)6例,右半肝切除術(shù)+尾狀葉切除+膽腸吻合術(shù)5例,肝方葉切除+膽腸吻合術(shù)2例,肝方葉+尾狀葉切除3例;PTCD組行單純膽管癌切除術(shù)+膽腸吻合術(shù)4例;左半肝切除+尾狀葉切除+膽腸吻合術(shù)13例,左三肝+尾狀葉切除+膽腸吻合術(shù)1例;右半肝切除術(shù)+尾狀葉切除+膽腸吻合術(shù)6例,擴大右半肝切除術(shù)+尾狀葉切除+膽腸吻合術(shù)1例,肝方葉切除+膽腸吻合術(shù)2例,肝方葉+尾狀葉切除+膽腸吻合術(shù)4例。根治性切除定義為距腫瘤5 mm切斷膽管殘端,且病理證實為切緣陰性。
4.術(shù)后并發(fā)癥及病死率 術(shù)后并發(fā)癥包括膽系感染、膽瘺、肝衰竭、肺部感染、腹腔出血、消化道出血。膽瘺定義為引流管持續(xù)3 d(或以上)膽汁引流量超過50 ml[6];肝衰竭定義為術(shù)后5 d(或以上)持續(xù)國際標準化比值(international normalized ratio,INR)及膽紅素水平持續(xù)升高[7];所有的并發(fā)癥為我院行PBD(排除外院行PBD病人)并行肝門部膽管根治術(shù)后住院期間發(fā)生;圍手術(shù)期手術(shù)死亡定義為術(shù)后30 d內(nèi)發(fā)生的死亡[8]。
三、統(tǒng)計學(xué)處理
利用SPSS(18.0版)統(tǒng)計軟件對臨床數(shù)據(jù)進行處理,組間比較采用成組t檢驗,同組前后比較采用配對t檢驗,計數(shù)資料采用卡方檢驗,了解病人手術(shù)前后肝功能酶學(xué)及膽紅素改變情況,術(shù)后并發(fā)癥情況,肝門部膽管癌根治術(shù)術(shù)中情況,術(shù)后恢復(fù)情況及預(yù)后等。P<0.05為差異有統(tǒng)計學(xué)意義。
本研究病例中,ENBD組20例,R0切除率為85.0%(17/20),PTCD組31例,R0切除率為83.9%(26/31),兩組比較差異無統(tǒng)計學(xué)意義(P=1.000)。術(shù)前ENBD組與PTCD組一般資料差異無統(tǒng)計學(xué)意義(均P>0.05)(表1)。
膽紅素引流前后變化情況:兩組膽紅素引流前后變化差異有統(tǒng)計學(xué)意義:TBIL(P<0.05),DBIL(P<0.05);其中PTCD組除了能夠降低膽紅素水平外,肝功能酶學(xué)水平也有較顯著降低,差異有統(tǒng)計學(xué)意義(P<0.05);ENBD組ALT、AST水平降低差異無統(tǒng)計學(xué)意義(P>0.05)(表2、表3);兩組白蛋白變化情況差異無統(tǒng)計學(xué)意義。
ENBD組與PTCD組手術(shù)時間、術(shù)中出血量以及術(shù)后的TBIL、DBIL、ALT、AST、ALB、住院時間和住院總費用比較,差異均無統(tǒng)計學(xué)意義(表4)。
術(shù)后并發(fā)癥:術(shù)后35例病人有手術(shù)并發(fā)癥(ENBD組12例,PTCD組23例),有的病人有多個并發(fā)癥(表5)。ENBD組圍手術(shù)期間無死亡病例。PTCD組圍手術(shù)期間死亡2例:1例因失血性休克,急性腎損傷、呼吸功能衰竭術(shù)后7 d死亡;1例因膽系感染、急性腎損傷、呼吸功能衰竭術(shù)后8 d死亡。
表1 ENBD組與PTCD組術(shù)前一般情況比較
表2 ENBD減黃前后膽紅素酶學(xué)變化情況比較±s)
表3 PTCD減黃前后膽紅素酶學(xué)變化情況比較±s)
表4 ENBD組與PTCD組手術(shù)情況及相關(guān)指標比較±s)
表5 術(shù)后并發(fā)癥與死亡情況比較[例(%)]
目前認為聯(lián)合肝臟切除的是肝門部膽管癌根治術(shù)的標準術(shù)式[9],梗阻性黃疸的病人行半肝切除甚至是擴大的半肝切除術(shù)后并發(fā)癥發(fā)生率約10%,其中肝衰竭的風(fēng)險較高[10]。PBD有效性存在爭議,支持者認為梗阻性黃疸常導(dǎo)致肝功能不全、凝血功能障礙以及梗阻性膽管炎的發(fā)生,PBD能夠有效降低膽紅素水平、改善圍手術(shù)期肝功能[11-12]。
肝門部膽管癌PBD的方法主要有PTCD、ENBD、ERBD。ERBD作為內(nèi)引流方式,可減少膽汁丟失引起的電解質(zhì)紊亂、消化吸收功能下降以及脂溶性維生素的吸收障礙,改善病人食欲、精神和體力[13-14],但術(shù)后支架阻塞及反流性膽管炎發(fā)生率較高[15],尤其對于Bismuth Ⅱ~Ⅳ病人[16];PTCD和ENBD屬于外引流,它們共同點是將膽汁引流身體之外,減少膽腸反流的風(fēng)險[17]。PTCD因操作簡捷,痛苦小,設(shè)備要求相對較低,技術(shù)更易掌握,逐漸成為肝門部膽管梗阻減黃治療中的主要術(shù)式,但有引起腫瘤播散種植、易出血等缺點,而且經(jīng)皮經(jīng)肝穿刺對病人肝內(nèi)膽管擴張要求較高,全志偉等[18]建議如肝內(nèi)三級膽管內(nèi)徑≥5 mm者,首選超聲引導(dǎo)經(jīng)皮經(jīng)肝膽管引流(UPTBD);而內(nèi)徑<5 mm則考慮采用ENBD[18];與PTCD比較,ENBD經(jīng)過人體的自然通道,避免了腫瘤瘺道種植的風(fēng)險,但ENBD技術(shù)要求相對較高,對于肝門部膽管癌引起的高位梗阻(尤其是Ⅳ型肝門部膽管癌)成功率較低,往往需要行額外的PTCD術(shù);而且有研究表示ENBD也有膽管炎的發(fā)生[19]。
本研究中,ENBD組與PTCD組均能夠明顯降低術(shù)前膽紅素水平。在肝功能恢復(fù)方面,PTCD組效果確切,這可能因為PTCD引流管短粗,成功率高,便于及時調(diào)整,引流更充分,而且左右肝管不連通時可行雙側(cè)肝管置管甚至多根置管引流。
本研究ENBD組與PTCD組手術(shù)時間、術(shù)中出血量及術(shù)后膽紅素、肝功能、術(shù)后住院時間比較差異均無統(tǒng)計學(xué)意義,說明ENBD與PTCD對肝門部膽管癌手術(shù)安全性及術(shù)后肝功能恢復(fù)效果基本相同。
術(shù)后并發(fā)癥比較:PTCD組與ENBD組術(shù)后總體并發(fā)癥比較差異無統(tǒng)計學(xué)意義(74.2%比60.0%,P=0.286),其中PTCD組膽道感染并發(fā)癥較ENBD組高(48.4%比20.0%),且差異有統(tǒng)計學(xué)意義(P=0.036)。二組圍手術(shù)期死亡率比較差異均無統(tǒng)計學(xué)意義(6.5%比0.0%,P=0.247),圍手術(shù)期2例病人(1例行擴大左半肝切除,1例行右半肝切除)死亡,均為PTCD引流組病人。Aly等[20]回顧性分析了1980~2000年梗阻性黃疸術(shù)前減黃英文文獻,指出可切除梗阻性黃疸病人中,常規(guī)術(shù)前減黃對于伴有感染、凝血功能障礙及一般狀況較差的可切除病人有益,但是并不能改善病人術(shù)后并發(fā)癥發(fā)生率及病死率。Xiong等[21]研究表明術(shù)前TBIL>170 μmol/L、分型和肝切除范圍可能是影響術(shù)后并發(fā)癥的獨立危險因素,而與術(shù)前減黃與否無關(guān)[20]。
結(jié)合國內(nèi)外研究及我中心經(jīng)驗總結(jié):①術(shù)前減黃應(yīng)結(jié)合病人具體病情決定:對一般狀況差、持續(xù)梗阻性黃疸或合并有膽管炎病人行擴大半肝切除時行術(shù)前減黃;②術(shù)前減黃方式的選擇和腫瘤侵犯膽管程度有關(guān),應(yīng)該綜合考慮腫瘤解剖結(jié)構(gòu)及病人接受程度[22];③一般術(shù)前減黃首選PTCD引流術(shù),當(dāng)梗阻部位以上膽管穿刺困難時,可選擇性進行ENBD引流;④對于Bismuth Ⅳ型病人行ENBD引流效果較差的病人,可選擇行PTCD術(shù)引流;⑤PBD引流術(shù)應(yīng)該嚴格遵循無菌操作進行,盡量減少操作所引起膽管炎發(fā)生;⑥外引流出來的膽汁可適當(dāng)經(jīng)消化道回輸;⑦術(shù)前可行膽道造影,判斷膽管受侵程度,規(guī)劃手術(shù)方式,但是造影應(yīng)該嚴格限制進行;⑧術(shù)前應(yīng)該積極進行營養(yǎng)支持、改善凝血、預(yù)防感染,根治性手術(shù)應(yīng)在肝功能充分恢復(fù)后進行;⑨應(yīng)根據(jù)腫瘤的浸潤情況及殘肝容積大小決定手術(shù)具體范圍。
總之,作為肝門部膽管癌術(shù)前減黃的方式,ENBD和PTCD均能夠有效降低術(shù)前膽紅素水平,改善和恢復(fù)肝功能,其中PTCD效果更好;ENBD引流術(shù)后膽管炎并發(fā)癥更低。肝門部膽管癌術(shù)前減黃應(yīng)該結(jié)合病人具體情況,選擇合適引流方式,從而增加手術(shù)安全性,減少術(shù)后并發(fā)癥發(fā)生率。
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Comparison of clinical effects about hilar cholangiocarcinoma operation of patients after preoperative biliary drainage by ENBD and PTCD
ZhangHui,ZhangZhen,ZhangHaitao,ZhangQikun,WangMenglong.
DepartmentofHepatobiliarySurgery,BeijingYouanHospital,CapitalMedicalUniversity,Beijing100071,China
Correspondingauthor:WangMenglong,Email:mlwangwangml2000@yahoo.com
Objective To compare the different effects about hilar cholangiocarcinoma (HC) operation of the patients after preoperative biliary drainage by percutaneous transhepatic cholangiography and drainage (PTCD) and endoscopic nasobiliary drainage (ENBD).Methods The clinical data of 56 HC patients admitted to Beijing Youan Hospital, Capital Medical University between January 2008 and August 2016 were retrospectively analyzed. Preoperative biliary drainage was applied (ENBD or PTCD) and HC operation was conducted. There were 20 cases in ENBD group and 31 cases in PTCD group. The reducing obstruction time, hepatic enzyme and bilirubin index before reducing obstruction, before operation and 3 days postoperation (TBIL, DBIL, ALT, AST, ALB), operative time, intraoperative blood loss and blood transfusion, postoperative complications were compared.Results ENBD and PTCD could reduce bilirubin levels remarkably (P<0.05). The liver function enzyme levels in PTCD group were also significantly lower after reducing obstruction than those before reducing obstruction (P<0.05). However, there was no significance in ENBD group before and after reducing obstruction (P>0.05). The operative time, blood loss and postoperative TBIL, DBIL, ALT and AST levels, postoperative hospital stay, and hospitalization cost showed no significant differences between two groups (74.2%vs. 60.0%,P>0.05). The incidence of postoperative cholangitis in PTCD group was significantly higher than in ENBD group (48.4%vs. 20.0%,P=0.036).Conclusions ENBD and PTCD can effectively reduce the preoperative bilirubin level. For PTCD, drainage effect is better, bilirubin reducing time is shorter, and liver function recovery effect is better. For ENBD, the incidence of cholangitis complications was lower. Therefore, the rational preoperative biliary drainage patterns are chosen according to the individualized situations of the patients, thereby increasing the safety of the operation and reducing the incidence of postoperative complications.
Hilar cholangiocarcinoma; Endoscopic nasobiliary drainage; Percutaneous transhepatic cholangiography and drainage
北京市醫(yī)院管理局臨床技術(shù)創(chuàng)新項目(XMLX201509)
100071 北京,首都醫(yī)科大學(xué)附屬北京佑安醫(yī)院肝膽外科
王孟龍,Email:mlwangwangml2000@yahoo.com
R657.3
A
10.3969/j.issn.1003-5591.2017.03.013
2016-09-16)