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目的 用脈沖式分光光度法觀察肝切除圍手術(shù)期肝功能的變化,進(jìn)一步研究此變化與腫瘤及被切除的肝組織體積之間的關(guān)系。方法 肝癌病人18例(31-67歲),分別于術(shù)前、術(shù)后第3天和第7天用脈動(dòng)光密度儀測(cè)定血漿吲哚氰綠清除率(K)。病人接受常規(guī)的部分肝切除術(shù),被切除的肝臟組織塊和腫瘤本身的體積由水排法測(cè)定,腫瘤周圍組織的體積為前兩者之差。對(duì)術(shù)后ICG K值較術(shù)前的變化與腫瘤和腫瘤周圍組織體積比,以及瘤周組織本身的體積之間進(jìn)行了相關(guān)性分析。結(jié)果 肝部分切除后,ICG K 值由術(shù)前的0.192±0.021下降至術(shù)后第3天的0.135±0.019(P<0.01), 術(shù)后第7天仍保持在一個(gè)較低的水平(0.144±0.025,P<0.05),而術(shù)后兩次的測(cè)得值之間沒有明顯差異。術(shù)后第7天ICG K值的變化與腫瘤和瘤周肝組織的體積比之間呈直線相關(guān)關(guān)系(r=0.845,P<0.001),而與瘤周肝組織的體積之間則無(wú)顯著相關(guān)性(r=-0.143, P>0.05)。結(jié)論 肝癌病人肝部分切除術(shù)后K明顯下降;與術(shù)前比較,術(shù)后K值的變化與腫瘤、丟失的正常肝組織體積之間的比值有關(guān)。
[關(guān)鍵詞]:吲哚氰綠(ICG indocyanine green)脈動(dòng)式分光光度法 肝切除術(shù)
Perioperative Liver Function in Hepatectomy and Its relationship with Resected Mass: a Preliminary Evaluation with ICG Pulse Spectrophotometry
Ai-Qun Zhang, Ning-Xin Zhou, Xiang-Qian Zhao, Bin Ni, Lan-Ying Zhang, Li-Jie Gao, Wen-Zhi Zhang
Institute of Hepatobilliary Surgery, Chinese PLA General Hospital, Beijing, 100853
[Abstract] Objective: To reevaluate the changes of liver function in early postoperative period after hepatectomy and its relationship with the size of tumor and resected liver tissue mass.
Methods: Besides regular biochemical tests of blood samples, liver function reserve indicated by plasma clearance rate of ICG(K) was measured with pulse-dye densitometry before operation and 3, 7 days postoperatively in 18 patients aged 31-67 years, who were diagnosed as hepatocarcinoma and underwent liver resection of various extent. Volumes of resected tissue mass including tumor and its peripheral liver tissue were measured by displacing water ,and the volume of peripheral liver tissue was obtained as the total volume minus the tumor one. The changes of K after operation and its relationship with the resected tissue volume were analyzed statistically.
Results: There was a significant drop in K , from 0.192±0.021 before operation to 0.135±0.019 on postoperative day 3 (P<0.01), and then it remained low on postoperative day 7 (0.144±0.025, P<0.05). However, there was no significant difference between values obtained on postoperative day 3 and those on day 7. The difference in K between preoperation and post-operative day 7 showed a significant linear correlation with the volume ratio of tumor to peripheral liver tissue (r=0.845,P<0.001), but not with volume of the latter which was resected simultaneously with tumor (r=-0.143, P>0.05).Conclusions: The perioperative assessment of ICG clearance rate by pulse-dye densitometry in patients with hepatocarcinoma revealed a significant decrease in early postoperative period, and the decline may not only depend on liver tissue loss during the operation, but also on the size of resected tumor.
[Key words] :indocyanine green; pulse spectrophotometry; hepatectomy
二十世紀(jì)六十年代初,Hunton[1]等首先利用吲哚氰綠評(píng)價(jià)肝臟功能;盡管學(xué)者們一直在尋找各種肝臟功能的檢查方法,但是吲哚氰綠排泄試驗(yàn)被認(rèn)為是評(píng)價(jià)肝臟儲(chǔ)備功能的重要試驗(yàn)方法之一。有研究表明,術(shù)前利用吲哚氰綠排泄試驗(yàn)評(píng)價(jià)肝臟功能對(duì)于指導(dǎo)術(shù)中切除肝臟實(shí)質(zhì)量有幫助,即切除肝臟實(shí)質(zhì)量的大小會(huì)影響預(yù)后[2,3]。
但是,由于傳統(tǒng)ICG試驗(yàn)在操作技術(shù)上相對(duì)不方便,影響了在臨床上的推廣。本研究使用脈動(dòng)式ICG檢測(cè)儀觀察肝臟部分切除術(shù)圍手術(shù)期患者肝臟功能的改變及探討腫瘤本身對(duì)試驗(yàn)結(jié)果是否有影響。
對(duì)象和方法
一、研究對(duì)象:
2004年6月至8月于我科行肝臟部分切除手術(shù)的患者。年齡31-67歲,平均56歲,僅1人為女性。18例中16例肝癌,2例膽管癌。所有病例腫瘤為II期或未達(dá)II期,所有病例均無(wú)膽道梗阻,其中12例經(jīng)切除的組織病理學(xué)診斷為肝硬化。
肝臟切除術(shù)的手術(shù)方式取決于腫瘤侵犯的范圍和腫瘤位置,以及其他臨床、生化指標(biāo)如ICG試驗(yàn)、血總膽紅素、腹水。
二、試驗(yàn)方法:
1. 儀器和試劑:DDG-3300K(日本光電工業(yè)株式會(huì)社生產(chǎn)),用805nm和940nm持續(xù)檢測(cè)血中ICG濃度;ICG注射液(25mg/支)購(gòu)于遼寧省遼陽(yáng)第三制藥廠。
2. 測(cè)定ICG血漿消失率(K)的方法:
患者至少空腹4小時(shí)以上,用注射蒸餾水將ICG稀釋成5mg/ml,每例病人使用20mg ICG經(jīng)上臂靜脈團(tuán)注,使用DDG-3300K配備的手指探頭檢測(cè)血中ICG濃度。注射ICG后大約6分鐘自動(dòng)計(jì)算出血漿ICG消失率(K)。每例患者分別在術(shù)前、術(shù)后第3天和術(shù)后第7天進(jìn)行ICG試驗(yàn)。
3腫瘤及周圍肝組織體積測(cè)定:
切除的肝臟組織包括腫瘤和腫瘤周圍的肝臟組織,它們的體積分別由水排法測(cè)定。
三、數(shù)據(jù)統(tǒng)計(jì)分析:
數(shù)據(jù)以均值±標(biāo)準(zhǔn)差的形式表達(dá),Wilcoxon相關(guān)檢驗(yàn)處理相關(guān)性分析,以P<0.05有統(tǒng)計(jì)學(xué)差異。
結(jié)果
1.手術(shù)預(yù)后:
所有研究對(duì)象均行部分肝臟切除手術(shù),術(shù)后無(wú)并發(fā)癥和死亡。
2.吲哚氰綠血漿清除率(K)的術(shù)前、術(shù)后變化情況:
使用DDG-3300檢測(cè)K值,檢測(cè)過(guò)程順利。術(shù)后K較術(shù)前下降(見圖1),由術(shù)前的0.192±0.021降至術(shù)后第3天0.135±0.019,術(shù)后7天時(shí)為0.144±0.025;術(shù)后第3天、術(shù)后第7天分別與術(shù)前K值相比均有統(tǒng)計(jì)學(xué)差異,分別為P<0.01、P<0.05。
3 .K值之差(術(shù)后第7天與術(shù)前)和切除的肝臟腫瘤體積與周圍肝臟組織體積比值(TV/LV)的相關(guān)性:
K值之差與(TV/LV)比值相關(guān)性好(r=0.845,P<0.001),見圖2。
4. K值之差(術(shù)后第7天與術(shù)前)與切除的腫瘤周圍肝臟組織體積的相關(guān)性:
K值之差與切除的腫瘤周圍肝臟組織體積無(wú)相關(guān)性(r=-0.143, P>0.05),見圖3。
圖1 術(shù)后第3天、術(shù)后第7天K較術(shù)前K下降,分別與術(shù)前K比較有統(tǒng)計(jì)學(xué)差異
(分別為P<0.05、P<0.01).
圖2 術(shù)后第7天與術(shù)前K的差值(△K)和TV/LV的相關(guān)性(Y=0.025X-0.043; r=0.845, P<0.001.)。
圖3術(shù)后第7天與術(shù)前K的差值(△K)和手術(shù)切除的腫瘤周圍肝臟組織體積的相關(guān)性
(無(wú)相關(guān)性,r=-0.143, P>0.05)。
討論
肝臟部分切除手術(shù)是治療肝臟腫瘤的有效手段,手術(shù)結(jié)果與手術(shù)方式、圍手術(shù)期護(hù)理和肝臟儲(chǔ)備功能密切相關(guān)。肝臟原有的疾病、殘肝體積是肝臟儲(chǔ)備功能的決定因素。術(shù)前評(píng)價(jià)肝臟儲(chǔ)備功能有助于篩選手術(shù)適應(yīng)癥,有助于降低手術(shù)風(fēng)險(xiǎn)[4,5]。ICG試驗(yàn)是術(shù)前評(píng)價(jià)肝臟儲(chǔ)備功能的常用試驗(yàn),有些中心以將其列為肝臟手術(shù)的術(shù)前常規(guī)檢查[6]。
DDG分析儀是近年來(lái)開發(fā)的,依據(jù)的色素稀釋法和脈動(dòng)分光光度原理,可以動(dòng)態(tài)、微創(chuàng)和方便檢測(cè)血中ICG濃度。有學(xué)者研究使用此儀器檢測(cè)的K與傳統(tǒng)ICG試驗(yàn)的結(jié)果相關(guān)性良好[7]。
本研究中術(shù)后7天K呈下降趨勢(shì),且第7天時(shí)最低;這與其他報(bào)道相符。這種下降趨勢(shì)與采用的手術(shù)方式無(wú)關(guān)[8,9]。
術(shù)后K下降與正常肝質(zhì)減少有主要關(guān)系,其他如肝臟血流、血容量的改變也會(huì)影響K值[10]。
如果術(shù)后早期殘肝門靜脈血流改變明顯[11]、血容量不穩(wěn)定,那么術(shù)后第7天的K值對(duì)于判斷術(shù)后肝臟儲(chǔ)備功能將根更加可靠。
另外,應(yīng)該考慮肝臟腫瘤本身對(duì)ICG試驗(yàn)的影響。肝臟的實(shí)質(zhì)性腫瘤富有結(jié)構(gòu)和功能上非正常的血管網(wǎng)[12],這將導(dǎo)致腫瘤組織內(nèi)的血流動(dòng)力學(xué)改變;據(jù)此推想,這可能是肝臟實(shí)質(zhì)性腫瘤相對(duì)于正常肝組織清除ICG較慢的原因[13,14]。
因此,可以推斷術(shù)前由ICG試驗(yàn)判斷的肝臟儲(chǔ)備功能可能偏低,但是本研究病例數(shù)較少,仍需大樣本驗(yàn)證研究。尤其重視肝臟腫瘤的大小和組織類型對(duì)K的影響程度,這對(duì)肝臟手術(shù)治療的將至關(guān)重要。
參考文獻(xiàn)
1 Hunton DB, Bollman JL, Hoffman HN. Studies of hepatic function with indocyanine green.Gastroenterology 1960,39:713-724.
2 Fan ST, Lai ECS, Lo CM, et al. Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis. Arch Surg,1995,130:198-203.
3 Ozawa K. Hepatic function and liver resection. J Gastroenterol Hepatol ,1990,5:296-309.
4 Hemming AW, Scudamore CH, Shackleton CR, et al. Indocyanine green clearance as a predictor of successful hepatic resection in cirrhotic patients. Am J Surg, 1992,163:515-518.
5 Koneru B, Leevy CB, Klein KM, et al . Clearance of indocyanine green in the evaluation of liver donors. Transplantation,1994,58:729-731.
6 Poon RTP and Fan ST. Hepatectomy for hepatocellular carcinoma: patient selection and postoperative outcome. Liver Transpl ,2004,10:S39-S45.
7 Imai, T, Takahashi K, Goto F, et al. Measurement of blood concentration of indocyanine green by pulse dye densitometry—Comparison with the conventional spectrophotometric method. J Clin Monit ,1998,14: 477-484.
8孫力勇,黃曉強(qiáng),黃志強(qiáng)。肝癌切除圍手術(shù)期肝臟儲(chǔ)備功能的研究。肝膽外科雜志,1997,5:226-230.
9 Okochi O, Kaneko T, Sugimoto H, et al. ICG pulse spectrophotometry for perioperative liver function in hepatectomy. J Surg Res 2002,103:109-113.
10 Wilkinson GR and Shand DG. A physiological approach to hepatic drug clearance. Clin Pharmacol Ther ,1975,18:377-390.
11 Kin Y, Nimura Y, Hayakawa N, Kamiya J, et al. Doppler analysis of hepatic blood flow predicts liver dysfunction after major hepatectomy. World J Surg, 1994,18:143-149.
12 Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science,2005,307:58-62.
13 Intes X, Ripoll J, Chen Y, et al. In vivo continuous-wave optical breast imaging enhanced with indocyanine green. Med Phys,2003,30:1039-1047.
14 Ohata T, Abe Y, Miura T, et al. An experimental study for tumor detection by indocyanine green with near-infrared topography. Nippon Igaku Hoshasen Gakkai Zasshi (Jpn) 2002,62:284-286.
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