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影響腹腔鏡保留腎單位手術(shù)術(shù)后腎功能恢復(fù)的因素分析

2015-03-19 22:17:06王云鵬陳光富張旭王保軍馬鑫史立新李宏召王春楊艾青楊國強(qiáng)
微創(chuàng)泌尿外科雜志 2015年6期
關(guān)鍵詞:腎動(dòng)脈分支腎功能

王云鵬 陳光富 張旭 王保軍 馬鑫 史立新 李宏召 王春楊 艾青 楊國強(qiáng)

1中國人民解放軍總醫(yī)院泌尿外科 100853 北京

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影響腹腔鏡保留腎單位手術(shù)術(shù)后腎功能恢復(fù)的因素分析

王云鵬1陳光富1張旭1王保軍1馬鑫1史立新1李宏召1王春楊1艾青1楊國強(qiáng)1

1中國人民解放軍總醫(yī)院泌尿外科 100853 北京

微創(chuàng)腎部分切除術(shù)目前已廣泛開展,較根治性腎切除有明顯改善腎功能的優(yōu)勢。其技術(shù)難題是阻斷腎血管后腎臟創(chuàng)面止血及重建,難免引起腎缺血損傷。學(xué)者們通過分析各種因素盡量改善患腎功能,但觀點(diǎn)不一。這些因素主要有:年齡、合并癥評分、身體質(zhì)量指數(shù)、術(shù)前腎功能、腫瘤位置及大小、合并癥、腎缺血時(shí)間及剩余腎體積比例等等?,F(xiàn)簡要總結(jié)目前報(bào)道的影響術(shù)后腎功能恢復(fù)因素,并期待有簡單有效的腎功能保護(hù)技術(shù),促進(jìn)微創(chuàng)腎部分切除術(shù)的進(jìn)一步發(fā)展和普及。

腎部分切除術(shù);根治性腎切除;腎功能保護(hù);機(jī)器人;腹腔鏡

腎癌是泌尿系統(tǒng)常見的惡性腫瘤,全球每年約有27萬新發(fā)病例,11.6萬人死亡,其中90%為透明細(xì)胞癌。其惡性度高,遠(yuǎn)處轉(zhuǎn)移率為20%~30%,約20%患者行腎切除手術(shù)治療后出現(xiàn)復(fù)發(fā)或進(jìn)展[1]。腎部分切除術(shù)(parcial nephrectomy, PN)可以得到和腎癌根治術(shù)(radical nephrectomy, RN)相同的腫瘤學(xué)效果,并能夠保留腎單位,減少慢性腎病(chronic kidney disease, CKD)和心血管疾病發(fā)生率,生存時(shí)間長,生活質(zhì)量高,已成為腎癌手術(shù)治療的金標(biāo)準(zhǔn)[2]。隨著腹腔鏡腎部分切除術(shù)(laparoscopic parcial nephrectomy, LPN)的成熟和機(jī)器人輔助技術(shù)(robot assisted parcial nephrectomy, RAPN)的應(yīng)用,相比于開放腎部分切除術(shù) (open parcial nephrectomy, OPN)趨于微創(chuàng)化,出血少、減輕疼痛并縮短住院時(shí)間。最近,歐洲泌尿外科協(xié)會(huì)指南推薦T1期腎腫瘤由有豐富腹腔鏡經(jīng)驗(yàn)的外科醫(yī)生行LPN[3]。如何提高手術(shù)技巧、保留足夠的腎功能(renal function, RF)從而改善腎癌的預(yù)后,成為當(dāng)今泌尿外科一大熱點(diǎn)和難點(diǎn)。

對于RF的測定方法,血清肌酐(sCr)受年齡、性別、肌肉量和對側(cè)正常腎代償?shù)扔绊?,雖然常用于臨床,但并不理想。而125I直接測定腎小球?yàn)V過率(glomerular filtration rate, GFR)是反映RF的金標(biāo)準(zhǔn)。MDRD (the modification of diet in renal disease)和CKD-EPI (the chronic kidney disease epidemiology collaboration)公式計(jì)算的eGFR (estimation of glomerular filtration rate)被認(rèn)為是相對準(zhǔn)確的GFR估計(jì)值[4]。研究發(fā)現(xiàn)有25%腎腫瘤患者,雖然sCr正常同時(shí)有正常的健側(cè)腎,卻伴有至少中度CKD(eGFR<60 ml·min-1·1.73 m-2),且eGFR下降約30%之前,sCr不會(huì)有明顯升高[5, 6]。

目前認(rèn)為,影響PN術(shù)后RF的因素主要有:術(shù)前因素,如年齡、性別、腫瘤大小及復(fù)雜性、術(shù)前“基礎(chǔ)”RF、是否孤立腎等等;術(shù)中因素,如手術(shù)方式、缺血類型及時(shí)間、剩余腎組織體積等等[6]。其中術(shù)前“基礎(chǔ)”RF主要由年齡、合并癥、身體狀態(tài)和既往有無腎臟手術(shù)史決定;剩余腎組織體積由腫瘤大小、位置及供血情況決定[7],外科醫(yī)生可努力改善的是術(shù)中因素。

1 腎臟缺血時(shí)間問題存在爭議

如何最大程度地減少腎臟缺血再灌注損傷是PN手術(shù)的關(guān)鍵點(diǎn)。缺血類型可分為腎臟熱缺血和冷缺血。減少腎缺血損傷的手段主要包括縮短腎缺血時(shí)間和減小腎缺血范圍。對于前者,傳統(tǒng)觀念認(rèn)為腎臟熱缺血時(shí)間(warm ischemia time, WIT)應(yīng)<30 min,而更長時(shí)間的腎缺血RF是否明顯下降 ,相關(guān)動(dòng)物實(shí)驗(yàn)和小樣本、回顧性臨床試驗(yàn)研究發(fā)現(xiàn)即使腎缺血時(shí)間>30 min,術(shù)后RF也可以恢復(fù)[8]。臨床主動(dòng)脈瘤修補(bǔ)術(shù)中腎臟WIT≥30 min,術(shù)后60%患者無明顯腎損傷,55%患者可在一段時(shí)間后恢復(fù)原有RF水平[9]。Parekh等[10]一項(xiàng)關(guān)于腎臟耐受缺血時(shí)間的臨床研究,發(fā)現(xiàn)40例患者中的82.5%腎缺血時(shí)間>30 min,甚至達(dá)到61 min, 術(shù)后早期未出現(xiàn)急性腎損傷(acute kidney injury, AKI)或僅輕微RF改變。但是許多研究發(fā)現(xiàn),長時(shí)間的腎缺血RF會(huì)明顯下降。

1.1 腎臟缺血時(shí)間可以很長

Lane等[11]對2 402例連續(xù)的T1期腎腫瘤行PN和RN的對比研究,發(fā)現(xiàn)術(shù)后中重度CKD(eGFR<45 ml·min-1·1.73 m-2)的發(fā)生率,在PN中腎臟WIT<30 min時(shí)為11%,腎臟WIT>30 min時(shí)為19%,而RN術(shù)后中重度CKD的發(fā)生率可達(dá)35% 。Porpiglia等用99mTc-MAG-3核素腎掃描分析18例WIT>30 min的LPN患者,發(fā)現(xiàn)雖然術(shù)后3個(gè)月總體RF無明顯下降(eGFR:91.6vs.79.1 ml·min-1·1.73 m-2;P≥0.05),但患側(cè)RF由術(shù)前48.3%, 降至術(shù)后第5天36.9%,術(shù)后3個(gè)月40.6%,術(shù)后1年只恢復(fù)到42.8%。術(shù)后RF恢復(fù)由術(shù)中切除腎組織的最大厚度和WIT決定,WIT>30 min時(shí)患側(cè)RF只能部分恢復(fù),而更長時(shí)間的熱缺血尤其是WIT>32 min則會(huì)出現(xiàn)RF的永久性喪失[12]。

1.2 術(shù)后腎功能變化有時(shí)間節(jié)段性

Porpiglia等[13]發(fā)現(xiàn)雙腎患者PN術(shù)后RF短期下降,在術(shù)后3周~3個(gè)月可恢復(fù)至一個(gè)新的較高的水平 。其對54例雙腎患者LPN術(shù)后患側(cè)RF進(jìn)行了4年的長期觀察,發(fā)現(xiàn)術(shù)后3個(gè)月患側(cè)RF明顯下降,下降時(shí)間越長,GFR恢復(fù)程度越差。隨后,患腎RF在術(shù)后3個(gè)月~4年維持一個(gè)穩(wěn)定期。 Porpiglia等[14]還發(fā)現(xiàn)患者年齡和WIT是術(shù)后3個(gè)月患側(cè)腎功能變化的獨(dú)立預(yù)測因素,長期的預(yù)測因素只有WIT。

1.3 腎缺血時(shí)間短能保護(hù)腎功能

腎缺血時(shí)間縮短對RF的影響 ,多數(shù)學(xué)者認(rèn)為[6, 13, 15~17],WIT在20~25 min時(shí)腎臟損傷是暫時(shí)和可逆的,PN術(shù)后近、遠(yuǎn)期RF無明顯改變。一些研究證明[13, 16, 18]WIT在25~30 min,術(shù)后RF明顯惡化,說明WIT是其預(yù)測因素之一。近期Becker等[17]學(xué)者建議腎臟WIT應(yīng)控制在20 min內(nèi)。更有報(bào)道[15]每增加一分鐘的腎缺血,就會(huì)增加5%~6%發(fā)生AKI的概率,進(jìn)而導(dǎo)致嚴(yán)重的CKD,這對LPN或RAPN具有較高的技術(shù)挑戰(zhàn)。隨著技術(shù)逐漸成熟和新方法的應(yīng)用,如“早松鉗”(early unclamping)技術(shù)[19]及“滑夾”(sliding-clip)等技術(shù)[20]均明顯縮短WIT,LPN的WIT由31 min降至14 min,WIT的縮短與術(shù)后RF改善明顯相關(guān),eGFR下降幅度由20.3%改善至10.6%[20]。Gill等的“零缺血”(zero ischemia)技術(shù)是高選擇分離腎動(dòng)靜脈分支結(jié)合控制性降壓,使WIT降至0,術(shù)后6個(gè)月放射性核素測定患腎GFR下降10%,平均切除腎組織體積18%[21]。Thompson等[22]選擇解剖不復(fù)雜、外科容易處理的體積小、位置淺表或外生型腎腫瘤,應(yīng)用擠壓瘤旁腎組織而不阻斷腎動(dòng)脈的“無缺血”(No ischemia)技術(shù)對孤立腎患者行OPN和LPN術(shù)后近、遠(yuǎn)期RF進(jìn)行研究,發(fā)現(xiàn)WIT平均21 min的熱缺血組(n=362)比無缺血組(n=96)發(fā)生AKI和新發(fā)CKD的概率明顯升高。另一項(xiàng)對雙腎患者行OPN術(shù)的類似研究,發(fā)現(xiàn)腎動(dòng)脈阻斷組(n=164)與不阻斷組(n=64)CKD的發(fā)生率分別為24.4%和12.5%[23]。Kaczmarek等[24]對多中心886例RAPN的研究發(fā)現(xiàn),腎動(dòng)脈不阻斷組(n=66)雖然出血較多,但手術(shù)時(shí)間明顯縮短,術(shù)后eGFR下降幅度較腎動(dòng)脈阻斷組小(2%vs.6%,P=0.008)??梢钥隙ǖ氖牵s短腎缺血時(shí)間可明顯改善LPN術(shù)后的RF。

2 腎缺血范圍同樣重要

如何減小腎缺血范圍,與傳統(tǒng)的腎動(dòng)脈主干阻斷技術(shù)相比,分支動(dòng)脈阻斷的技術(shù)被提出[25],根據(jù)術(shù)前影像學(xué)血管成像分析,高選擇性阻斷腫瘤區(qū)供血的分支動(dòng)脈,腫瘤的切除以及創(chuàng)面的縫合都在局部腎實(shí)質(zhì)缺血的情形下完成。 “健康”的剩余腎組織保持正常的血供,對于RF的保護(hù)和術(shù)后恢復(fù),有顯著的優(yōu)勢。術(shù)后RF結(jié)果與阻斷腎動(dòng)脈分支數(shù)量明顯相關(guān),阻斷的分支越少,腎功能恢復(fù)越好。Simone等[26]應(yīng)用術(shù)前高選擇栓塞腎腫瘤滋養(yǎng)動(dòng)脈,隨后行不阻斷腎血管的LPN,觀察到患側(cè)RF在術(shù)后3個(gè)月下降9%,術(shù)后1年下降5%。Desai等[27]將121例RAPN分為高選擇阻斷腎動(dòng)脈分支組和腎動(dòng)脈主干阻斷組,雖然前者瘤體偏大且更復(fù)雜,但術(shù)后剩余腎體積比腎動(dòng)脈主干阻斷組略多(95%vs.90%,P=0.07),出院時(shí)eGFR下降明顯較少(0%vs.11%,P=0.01),隨訪4~6個(gè)月最終eGFR下降較少(11%vs.17%,P=0.03)。雖然精確的靶分支腎動(dòng)脈的確定可憑術(shù)前DSCTA(dual source computed tomograghy angiography, DSCTA)以及術(shù)中肉眼觀察腎組織缺血變白來判斷,但因主觀性過強(qiáng),缺乏客觀的依據(jù),可能會(huì)造成血管漏扎或多扎等情形,尤其是后者,會(huì)損失正常的剩余腎組織。于是Gill[28]提出判斷剩余腎組織動(dòng)脈灌注的客觀方法,即腹腔鏡實(shí)時(shí)多普勒超聲記錄波形和靜注ICG(indigo cyanine green)輔以機(jī)器人紅外線成像。故此,分支腎動(dòng)脈阻斷的技術(shù)仍有爭議。

3 腎臟溫度直接影響術(shù)后腎功能

低溫保護(hù)是常用的預(yù)防腎缺血再灌注損傷方法,優(yōu)點(diǎn)是變熱缺血為冷缺血,使腎臟代謝降低,許多酶系統(tǒng)的活性也降低,減少ATP的消耗,有效保護(hù)RF,明顯延長手術(shù)時(shí)限,尤其適用于復(fù)雜腎腫瘤和不熟練的術(shù)者。研究證實(shí)冷缺血時(shí)間(cold ischemia time, CIT)比WIT手術(shù)時(shí)限延長,對腎臟保護(hù)作用明顯[29]。Lane等[7]的一項(xiàng)多中心研究,對660例孤立腎PN手術(shù)的回顧研究,其中300例冷缺血和360例熱缺血患者術(shù)后3個(gè)月平均eGFR分別下降21%和22%(P=0.7),而術(shù)中冷缺血時(shí)間和熱缺血時(shí)間平均為45 min和22 min(P<0.001)。且腎臟可以耐受更長時(shí)間的冷缺血,腎移植手術(shù)中,尸腎可低溫保存20 h,移植成功后eGFR能恢復(fù)至45~50 ml·min-1·1.73 m-2。研究發(fā)現(xiàn)腎臟適宜的保護(hù)溫度是15°,而腎臟降溫至20~25°即可達(dá)到耐受3 h缺血的效果[30]。Iida等[31]發(fā)現(xiàn)CIT<44 min可顯著預(yù)防腎功能下降,eGFR恢復(fù)至45 ml·min-1·1.73 m-2。但Becker等[17]認(rèn)為即使是冷缺血也不應(yīng)超過2 h,最好是在35 min內(nèi)。Yossepowitch等[32]對592例OPN患者資料進(jìn)行多因素分析,證實(shí)CIT<35 min較為安全,可導(dǎo)致術(shù)后早期eGFR下降,術(shù)后12個(gè)月未見eGFR明顯改變。在傳統(tǒng)的開放性手術(shù)中最常用的方法是腎周加冰屑降溫[33],夾閉腎動(dòng)脈后表面冰屑降溫,10 min后開始切除腫瘤。雖然腎臟周圍加冰屑的方法在LPN[34]和RAPN[35]中也有應(yīng)用,但是主要缺點(diǎn)是:冷卻的不均質(zhì)性;反復(fù)進(jìn)行冰屑添加,延長了手術(shù)時(shí)間;降溫后影響手術(shù)視野;有局部腎皮質(zhì)壞死的可能。而腹腔鏡下腎部分切除術(shù)降溫方式有:動(dòng)脈插管灌注[36]、經(jīng)輸尿管逆行灌注冰水降溫方法[37]、腎臟表面冰袋降溫等等。其中經(jīng)腎動(dòng)脈插管灌注降溫法效果確切,但灌注前需要進(jìn)行腎動(dòng)脈血管造影,需要相關(guān)科室合作,且對腎臟血管損傷大,操作風(fēng)險(xiǎn)性高。而經(jīng)輸尿管逆行灌注冰水的方法,利用腎臟原有的管道系統(tǒng),通過向集合系統(tǒng)內(nèi)灌注冰水,無須特殊的器械,簡單易行,可使腎髓質(zhì)溫度降至21°,腎皮質(zhì)溫度降至24°。缺點(diǎn)是灌注量和壓力不易控制,壓力過高可會(huì)造成腎單位的破壞,而早期腎皮質(zhì)腫瘤降溫效果欠佳。Crain等[38]應(yīng)用F12雙腔套管為灌注引流管道,改善了灌注情況。顯然,低溫技術(shù)對RF的保護(hù)作用是肯定的。

4 剩余腎體積比是另一種評估方法

近期有學(xué)者認(rèn)為,剩余腎體積比傳統(tǒng)認(rèn)為的WIT更能預(yù)測PN術(shù)后近、遠(yuǎn)期RF結(jié)果[39, 40]。Simmons等[41]提出減少腎缺血時(shí)間和低溫技術(shù)對RF保護(hù)作用不大,尤其是對遠(yuǎn)期RF的影響,WIT和腎實(shí)質(zhì)保留體積(percent functional volume preservation, PFVP)可能與近期最低GFR相關(guān),術(shù)前Charlson伴隨癥狀評分和PFVP才與最終GFR相關(guān)。認(rèn)為最重要的是精細(xì)的腫瘤切除和腎臟重建,包括:高分辨率的術(shù)前腎腫瘤影像定位;精準(zhǔn)的活體成像引導(dǎo)下切除腫瘤;避免阻斷鄰近的動(dòng)脈分支;重建時(shí)避免縫合過度正常腎組織等。

5 孤立腎研究發(fā)現(xiàn)術(shù)前腎功能至關(guān)重要

孤立腎研究可以消除健腎對術(shù)后RF的代償影響,雖然有研究表明孤立腎比雙腎更加耐受缺血[42]。Lane等[7]對660例孤立腎的多中心研究,分支結(jié)扎腎動(dòng)脈腎部分切除術(shù),發(fā)現(xiàn)術(shù)后RF結(jié)果取決于術(shù)前“基礎(chǔ)”RF和術(shù)后剩余腎組織體積,即腎的“質(zhì)”和“量”,而不是WIT。為證實(shí)其結(jié)論,Thompson等[43]一項(xiàng)關(guān)于孤立腎腎部分切除術(shù)的多因素分析,證明術(shù)前“基礎(chǔ)”RF(P<0.001)、術(shù)后剩余腎組織體積(P=0.009)和WIT(P=0.021)與術(shù)后短期RF下降、導(dǎo)致AKI和是否需要透析明顯相關(guān);“基礎(chǔ)” RF (P<0.0001)、術(shù)后剩余腎組織體積(P<0.001)和WIT是否超過25 min(hazard ratio:2.27;P=0.049)與遠(yuǎn)期RF恢復(fù)和新發(fā)Ⅳ期CKD (eGFR15~30 ml·min-1·1.73 m-2)相關(guān)。說明術(shù)前RF比術(shù)后剩余腎體積預(yù)測術(shù)后RF作用更強(qiáng),可能與剩余腎單位加倍濾過,以代償損傷的腎單位有關(guān)。

6 理想的腎功能保護(hù)方法

究竟哪個(gè)因素對術(shù)后RF影響最大 ,Gill[28]認(rèn)為幾種影響因素互為因果。WIT仍是重要的指標(biāo),尤其對于孤立腎。其與腫瘤復(fù)雜性和切除腎體積明顯相關(guān)。腎腫瘤越復(fù)雜,切除腎體積越大,同時(shí)WIT越長。腎的“質(zhì)”取決于患者自身和腫瘤因素,外科醫(yī)生可以努力改善的是WIT和保留腎的“量”。理想的PN是:完整切除腫瘤,精細(xì)保留瘤旁少量腎組織,保證切緣陰性和創(chuàng)面安全,盡量減少剩余腎的缺血,減少并發(fā)癥,迅速恢復(fù)RF。并提出首先考慮腎動(dòng)脈,其次才是腫瘤的解剖學(xué)概念。腎血管解剖清晰可運(yùn)用更精準(zhǔn)的手術(shù)技巧。優(yōu)勢是僅保留1~2 mm的瘤旁腎組織,可以最大限度保留剩余正常腎組織,盡量減少腎缺血引起的AKI和CKD。

總之,隨著機(jī)器人和高新影像技術(shù)的引入,腎腫瘤位置及供血?jiǎng)用}術(shù)前準(zhǔn)確定位分析,術(shù)中高選擇阻斷分支腎動(dòng)脈,腫瘤得到精準(zhǔn)切除,盡可能保留正常腎組織,保證切緣陰性,開發(fā)術(shù)后能夠計(jì)算剩余腎體積的影像學(xué)技術(shù),尋求更客觀的腎功能掃描和生物學(xué)指標(biāo),及時(shí)準(zhǔn)確判斷腎功能下降情況,可以更好的預(yù)防腎損傷,降低心血管事件及死亡率,提高患者生存率及生活質(zhì)量。

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Protection of renal function after laparoscopic partial nephrectomy

WangYunpeng1ChenGuangfu1ZhangXu1WangBaojun1MaXin1ShiLixin1LiHongzhao1WangChunyang1AiQing1YangGuoqiang1

(1Department of Urology, Chinese PLA General Hospital, Beijing 100853, China)

Zhang Xu, xzhang@foxmail.com

Minimal invasive surgery is widely performed, and partial nephrectomy has the advantage of more significantly improving renal function than radical nephrectomy. The technique problem is the hemostasis and reconstruction of the kidney after blocking renal blood vessels, which causes renal ischemia injury. Scholars have analyzed various factors to improve the renal function, but the opinions are controversial. These factors mainly include age, Charlson score(CS), body mass index (BMI), preoperative renal function, tumor size, location, complications, renal ischemia time and percent functional volume preservation, etc. This review briefly summarizes the factors influencing the postoperative recovery of renal function currently reported. It is expected to have a simple and effective protective measure for renal function, which can promote the further development of minimally invasive partial nephrectomy and popularization.

partial nephrectomy; radical nephrectomy; renal function protection; robot; laparoscope

張旭,xzhang@foxmail.com

2015-08-26

R737.11

A

2095-5146(2015)06-380-05

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