姜?jiǎng)P，蘇明，劉洋，趙向前，陳永衛(wèi)，張文智，王敬，董家鴻，黃志強(qiáng)

腹腔鏡下保留膽囊的毗鄰膽囊肝細(xì)胞癌一次性完全射頻消融治療

姜?jiǎng)P，蘇明，劉洋，趙向前，陳永衛(wèi)，張文智，王敬，董家鴻，黃志強(qiáng)

目的評(píng)估腹腔鏡下對(duì)毗鄰膽囊的肝細(xì)胞癌進(jìn)行一次性完全射頻消融(RFA)治療的可行性與安全性。方法選取毗鄰膽囊周邊不同部位的肝細(xì)胞癌患者5例，腫瘤直徑2.5～4.2cm，采用腹腔鏡輔助射頻消融治療，腹腔鏡下對(duì)膽囊不作分離與切除，射頻消融過程保中持膽囊壁的連續(xù)完整。術(shù)后通過B超及CT了解腫瘤有無復(fù)發(fā)，并觀察患者生存狀況。結(jié)果術(shù)后3d行B超檢查見膽囊壁近消融區(qū)處邊緣增厚，厚度0.3～0.5cm，CT顯示膽囊壁密度增高。術(shù)后6個(gè)月增強(qiáng)CT顯示5例患者腫瘤邊緣均無強(qiáng)化，膽囊完整，達(dá)到腫瘤一次性完全消融。隨訪18～36個(gè)月，所有患者均生存良好。結(jié)論腹腔鏡下對(duì)毗鄰膽囊的肝細(xì)胞癌達(dá)到一次性完全消融并保持膽囊壁的連續(xù)與完整在技術(shù)上是安全可行的。

癌，肝細(xì)胞；射頻消融術(shù)；腹腔鏡

射頻消融(radiofrequency ablation，RFA)是治療某些肝細(xì)胞癌(hepatocellular carcinoma，HCC)的有效手段[1]。對(duì)于肝臟特殊部位的腫瘤，射頻消融治療可引起出血、膽汁漏、膽囊穿孔等嚴(yán)重并發(fā)癥[2-4]，需要聯(lián)合酒精注射進(jìn)行補(bǔ)充治療[5]。對(duì)于毗鄰膽囊的HCC，切除膽囊后再進(jìn)行射頻消融是安全的，但是，當(dāng)腫瘤與膽囊密切相連無法分離，或因重度肝硬化而無法進(jìn)行膽囊切除時(shí)，在保留膽囊的情況下能否達(dá)到腫瘤的一次性完全射頻消融目前尚未見文獻(xiàn)報(bào)道。本文對(duì)5例此類典型患者進(jìn)行射頻消融治療，探討保留膽囊、腹腔鏡下毗鄰膽囊HCC一次性完全射頻消融治療的理論基礎(chǔ)、技術(shù)要點(diǎn)及并發(fā)癥情況。

1 資料與方法

1.1一般資料 選取腫瘤毗鄰膽囊0～0.5cm的 HCC典型病例5例，均為男性，年齡43～70歲，腫瘤直徑2.5～4.2cm，具體資料見表1。

1.2射頻消融治療過程 射頻消融設(shè)備使用Ra-dionics Cool-tipTMRF Ablation System(Valleylab，USA)，采用內(nèi)置的水冷系統(tǒng)保持射頻電極尖端溫度低于20℃。5例患者均全身麻醉，射頻消融治療過程如下：①腹腔鏡探查腹腔內(nèi)有無腹水和(或)腫瘤轉(zhuǎn)移，肝臟硬化程度，膽囊壁表現(xiàn)(有無水腫)，以及膽囊與腫瘤表面之間的血管聯(lián)系(病例1、2、4腫瘤與膽囊壁之間有多支血管交通支，直徑0.2～0.3cm，圖1C)；②分離膽囊與大網(wǎng)膜或結(jié)腸之間的粘連，使膽囊與結(jié)腸完全隔離；根據(jù)術(shù)前CT或MRI影像評(píng)估結(jié)果，確定置入電極的方向及深度，避免穿刺損傷膽囊下后方右側(cè)的門靜脈及膽管；③自腫瘤遠(yuǎn)離膽囊壁的一側(cè)邊緣，將單射頻電極(3cm active-tip cooled)準(zhǔn)確斜穿置于腫瘤底部，使電極與膽囊壁距離1.5～2.0cm；避免電極直接穿入膽囊臟面的任何部位；④射頻消融初始能量輸送90W，預(yù)熱10min后，將設(shè)備能量增至最大值(200W)，自動(dòng)反饋平衡調(diào)節(jié)，能量變化范圍96～142W，持續(xù)至20min時(shí)，腹腔鏡實(shí)時(shí)監(jiān)測(cè)腫瘤表面血管內(nèi)氣體流動(dòng)方向，若氣泡沿腫瘤與膽囊間的血管流向膽囊底部，則以腹腔鏡吸引器適當(dāng)加壓阻斷血管，避免河流效應(yīng)對(duì)膽囊的整體損傷作用；⑤腫瘤消融過程中，以吸引器對(duì)腫瘤向遠(yuǎn)離膽囊的方向適當(dāng)加壓，使電極與腫瘤組織密切接觸，提高輸出功率的有效作用時(shí)間；⑥若腹腔鏡觀察發(fā)現(xiàn)腫瘤所在肝段表面顏色與周圍肝臟差別較大，則以集束射頻電極(2.5cm active-tip cooled)繼續(xù)以最高能量持續(xù)消融12～24min，直至將該顏色變暗區(qū)域肝段完全消融；⑦治療過程中應(yīng)始終密切觀察膽囊壁的顏色變化，避免突然的高溫使受損膽囊壁破裂；應(yīng)對(duì)膽囊底部及體部靠近肝臟或腫瘤的一側(cè)進(jìn)行射頻消融使之產(chǎn)生熱損傷(顏色變?yōu)闇\黑色或深褐色)，膽囊壁的損傷距腫瘤＜1.5cm(圖1D)；⑧當(dāng)腫瘤表面與周圍血管內(nèi)氣體流動(dòng)的現(xiàn)象消失后，腫瘤組織色澤變?yōu)闇\褐色或深褐色，此時(shí)停止消融及冷循環(huán)，測(cè)得射頻電極尖端溫度范圍76～82℃；⑨仔細(xì)檢查穿刺針道有無出血及膽汁漏，并及時(shí)進(jìn)行壓迫、電凝或封堵處理；⑩將大網(wǎng)膜以氰基丙烯酸鹽黏合膠(α-cyanoacrylate，廣州白云醫(yī)用生物膠有限公司)粘連于膽囊熱損傷的創(chuàng)面；觀察15min，確認(rèn)無膽汁漏。術(shù)后禁食水并胃腸減壓3d。

表1 5例患者的臨床與影像學(xué)表現(xiàn)Tab. 1 Clinical and image characteristics of 5 patients

2 結(jié) 果

5例患者均采用射頻消融對(duì)膽囊壁毗鄰腫瘤的局部進(jìn)行完全或不完全損傷(膽囊壁距肝臟損傷1.0～1.5cm)。射頻消融術(shù)后7d，復(fù)查肝功能指標(biāo)均接近術(shù)前水平。病例2、4術(shù)后1d出現(xiàn)右上腹部輕度疼痛，2～3d后癥狀消失。所有患者術(shù)后3d復(fù)查B超均提示膽囊壁近消融區(qū)處水腫增厚，厚度0.3～0.5cm，周圍無積液，同時(shí)增強(qiáng)CT見消融范圍完全覆蓋病變，膽囊壁密度增高、連續(xù)完整。

5例患者術(shù)后1個(gè)月復(fù)查B超及CT，結(jié)果顯示靠近腫瘤處的膽囊壁回聲增強(qiáng)、密度增高，周圍無積液；術(shù)后6個(gè)月肝臟增強(qiáng)CT顯示無腫瘤復(fù)發(fā)，膽囊壁連續(xù)完整，達(dá)到腫瘤一次性完全消融。隨訪18～36個(gè)月，所有患者均生存良好，病例2術(shù)后36個(gè)月Ⅵ段與Ⅶ段交界處發(fā)現(xiàn)新生腫瘤(大小1.9cm×1.8cm)。病例1術(shù)后不同時(shí)間CT復(fù)查腫瘤與膽囊表現(xiàn)見圖1E－H。

圖1 毗鄰膽囊Ⅳa段HCC的射頻消融治療與復(fù)查表現(xiàn)Fig. 1 Manifestation of RFA treatment to HCC in Segment Ⅳa adjoining to gallbladderA. Contrast enhanced CT: The tumor (T) with complete capsule was showed enhanced in arterial phase (white hollow arrow), and arteriovenous fistula was indicated by white solid arrow; B. Left margin of tumor (T) adjoined to body and fundus of GB (white solid arrow), and thickening of GB wall was seen (black solid arrow); C. Tumor (T) and gallbladder (G) connected closely, and serosa of G and capsule of T stretched with visible communicating vessel (white solid arrow); D. At the end of RFA, the tumor (T) turned into dark yellow among ablated region (2.0cm in range, white hollow arrow); and fundus of gallbladder (G, white solid arrow) changed into dark brown, 1.5cm away from T, meanwhile, G wall near the ablated region swollen slightly (black solid arrow); capsule of T and wall of G kept continuing and complete; E. Contrast enhanced CT 3 days after RFA: The ablated region (5.6×5.3cm) completely covered the tumor (T), and stretched to Sg. Ⅳa (white hollow arrow); thickened GB wall with enhanced density in arterial phase was seen in boundary (white solid arrow) and right GB wall was intact (black solid arrow); F. 1.5cm inferior layer of C: High density and thickening of GB wall (white solid arrow) adjoined to tumor was visible and the rest part of GB wall showed no change (black solid arrow); G. 18 months after RFA: Complete ablation and decreased tumor (T) with no obvious recurrence. The higher density of boundary of GB wall adjoined to previous tumor which was prominent inside GB bed, showing the continuity and completeness of GB wall (brown solid arrow); H. 1.5cm inferior layer of E: The continuity and completeness of GB wall (white solid arrow) was indicated by higher density than the other side of GB wall (black solid arrow)

3 討 論

毗鄰膽囊(距離＜0.5cm)部位被認(rèn)為是HCC經(jīng)皮穿刺射頻消融治療中危險(xiǎn)的特殊位置之一[1,5]。關(guān)于特殊位置的腫瘤，一般認(rèn)為是指毗鄰肝內(nèi)主要膽管與血管，或位于肝臟表面且毗鄰重要器官的腫瘤，以及消融治療可能引起嚴(yán)重并發(fā)癥部位的腫瘤[1,6-8]。但這一概念是相對(duì)而言的，比如對(duì)于非外科條件來說，肝臟臟面與膈面的位置是特殊的，但在外科條件下，借助腹腔鏡的輔助，這些部位的消融又是相對(duì)簡(jiǎn)單安全的[2,9]；同時(shí)，假如不能達(dá)到腫瘤完全消融的目的，這些部位的腫瘤也不能稱為真正意義上的特殊位置腫瘤。

因此，基于外科手術(shù)局部切除腫瘤的原則，我們認(rèn)為，特殊位置應(yīng)該定義為位于肝內(nèi)或肝表面，毗鄰重要血管與膽管，或與臟器關(guān)系密切且無法隔離治療，在進(jìn)行一次性完全消融時(shí)可能引起嚴(yán)重并發(fā)癥的部位。對(duì)于毗鄰膽囊的腫瘤來說，剝離或切除膽囊后再進(jìn)行腫瘤射頻消融治療是安全的，因?yàn)檫@一做法使腫瘤的特殊位置變?yōu)槠胀ㄎ恢?。然而，Levit等[2]對(duì)距膽囊＜1cm的腫瘤在術(shù)前進(jìn)行經(jīng)皮穿刺膽囊內(nèi)膽汁引流，術(shù)中采用腹腔鏡輔助射頻消融聯(lián)合病灶剝離，但仍有部分患者存在腫瘤殘留，需要再次行射頻消融治療。

重度肝硬化時(shí)膽囊的病理生理學(xué)改變具有特殊性。一方面，作為門靜脈高壓癥的側(cè)支循環(huán)代償，膽囊與肝臟之間的靜脈代償性增粗、壓力升高；另一方面，因門靜脈高壓及低蛋白血癥，膽囊壁出現(xiàn)明顯的水腫、增厚。前者因存在術(shù)中大出血的可能，不利于腹腔鏡下膽囊的分離及切除[8]，而后者為射頻消融治療提供了更大的消融范圍，且可降低膽囊壁被完全毀損的可能。本組中病例1、2合并有重度肝硬化，膽囊壁水腫明顯，同時(shí)膽囊與肝臟腫瘤之間出現(xiàn)增生代償?shù)撵o脈回流血管，在對(duì)腫瘤進(jìn)行射頻消融的過程中，熱量隨增粗的血管流向膽囊壁的漿膜外層，持續(xù)高熱可能對(duì)整個(gè)膽囊壁造成損傷，因此，術(shù)中以吸引器頭端對(duì)存在明顯氣泡流動(dòng)的血管給予加壓阻斷[10]，使膽囊壁的損害限于游離膽囊壁1.5cm以內(nèi)，確保腫瘤周圍組織的消融范圍達(dá)到1.0cm以上(圖1D)。當(dāng)合并輕到中度肝硬化時(shí)，膽囊壁正?；蛏栽龊?。因不存在膽囊壁的血管代償性增粗，射頻消融容易毀損膽囊壁漿膜層的血管，膽囊壁完全毀損后形成硬痂，因膽囊未破裂而保持了膽囊壁與血管壁的連續(xù)完整；同時(shí)，受損膽囊壁神經(jīng)末梢被完全毀損，因神經(jīng)反射導(dǎo)致的臨床癥狀可減輕或消失。本組病例3、4、5的膽囊壁及血管完全毀損，術(shù)后未出現(xiàn)相應(yīng)的急性膽囊炎癥狀。病例3腫瘤位于膽囊床的后方肝臟實(shí)質(zhì)之內(nèi)，由于膽囊與肝臟接合處保持完整，即使膽囊床處的膽囊壁完全消融壞死，膽汁也不會(huì)進(jìn)入腹腔。病例2、4之所以術(shù)后第1天出現(xiàn)右上腹輕度疼痛癥狀，可能與膽囊周圍組織廣泛毀損，高熱量對(duì)膽囊處腹膜的刺激有關(guān)。

大網(wǎng)膜在膽囊炎性穿孔時(shí)具有積極的保護(hù)性粘連反應(yīng)，因此，我們將這種反應(yīng)提前至術(shù)中用于即時(shí)保護(hù)，以氰基丙烯酸鹽黏合膠將大網(wǎng)膜粘連于受損的膽囊壁處，使膽囊壁損傷后可能發(fā)生的膽囊穿孔急性過程變?yōu)槭鼙Ｗo(hù)后的慢性過程。本組消融術(shù)后3～5d行B超檢查發(fā)現(xiàn)除消融邊緣膽囊壁水腫增厚(0.3～0.5cm)外，未發(fā)現(xiàn)膽囊周圍的滲出表現(xiàn)。術(shù)后1個(gè)月B超及CT檢查顯示靠近腫瘤處的膽囊壁回聲增強(qiáng)、密度增高，與膽囊壁完全消融凝固有關(guān)。術(shù)后6個(gè)月復(fù)查肝臟CT，5例患者腫瘤消融處未發(fā)現(xiàn)任何復(fù)發(fā)征象，膽囊整體完整性良好，表明毗鄰膽囊(0～0.5cm)的HCC達(dá)到了一次性完全消融。

綜上所述，本組結(jié)果顯示，射頻消融過程中保持膽囊壁的連續(xù)及完整性，不進(jìn)行膽囊分離，在腹腔鏡下對(duì)毗鄰膽囊的肝細(xì)胞癌進(jìn)行一次性完全消融是安全可行的。

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Laparoscopy-assisted and gallbladder-preserved one-off radiofrequency ablation for hepatocellular carcinoma adjoining gallbladder

JIANG Kai, SU Ming, LIU Yang, ZHAO Xiang-qian, CHEN Yong-wei, ZHANG Wen-zhi, WANG Jing, DONG Jiahong*, HUANG Zhi-qiang
Department of Hepatobiliary Surgery, General Hospital of PLA, Beijing 100853, China

*Corresponding author, E-mail: dongjh301@163.com

This work was supported by the National Key Technology Research and Development Program of China (2012BAI06B01)

ObjectiveTo evaluate the feasibility and safety of laparoscopy-assisted one-off complete radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) adjoining gallbladder.MethodsFive cases of HCC adjacent to different location of gallbladder were involved in present study. The tumor diameter ranged from 2.5 to 4.2cm. Laparoscopy-assisted radiofrequency ablation was performed without isolation or resection of gallbladder so as to maintain its anatomical integrity. The patients were followed up with the aid of ultrasonography and computed tomography postoperatively, at the same time the surviving quality was assessed.ResultsThree days after the operation, ultrasound examination showed that the gallbladder wall close to the ablated area was increased by 0.3-0.4cm, and the CT images showed that the density of gallbladder wall was increased. Six months after the operation, the contrast enhanced CT images showed that the gallbladder was intact and no high density area was observed in every patient, implying that the tumor was one-off ablated completely. All the patients lived a life with good quality during the follow-up period of 18-36 months.ConclusionLaparoscopy-assisted one stage radiofrequency ablation for hepatocellular carcinoma adjoining gallbladder with maintenance of the anatomical integrity of gallbladder is technically safe and feasible.

carcinoma, hepatocellular; radiofrequency ablation; laparoscopy

R735.7

A

0577-7402(2013)05-0359-04

2013-02-26；

2013-03-22)

(責(zé)任編輯：熊曉然)

國家科技支撐計(jì)劃項(xiàng)目(2012BAI06B01)

姜?jiǎng)P，醫(yī)學(xué)博士，副主任醫(yī)師。主要從事肝癌的外科臨床與基礎(chǔ)研究工作以及射頻消融的臨床治療

100853 北京 解放軍總醫(yī)院肝膽外科(姜?jiǎng)P、蘇明、劉洋、趙向前、陳永衛(wèi)、張文智、王敬、董家鴻、黃志強(qiáng))

董家鴻，E-mail：dongjh301@163.com