胰十二指肠切除术后胰瘘的预防

吴传有，刘长安，李生伟

(重庆医科大学附属第二医院，重庆 400010)

胰十二指肠切除术由德国外科医生Kausch在1909年首次实施[1]。Whipple等[2]于1935年报告3例胰十二指肠切除病案之后，胰十二指肠切除术就成为壶腹部肿瘤外科治疗的选择方式。而今，胰十二指肠切除术已经作为胰头癌和壶腹周围癌治疗的标准手术方式。随着手术技术的改进和术后管理的提高，已经使胰腺切除术后死亡率减少到5%以下，然而术后并发症的发生率却改变很小，仍然在30%～40%范围[3-4]。术后胰瘘、腹腔出血、腹腔脓肿形成以及胃排空障碍等并发症时有报道。术后胰瘘依然是胰十二指肠切除术后最常见、最严重的并发症[5]，其发生率从2%～40%不等[5-6]。而这些并发症的发生往往需要药物或再次手术干预，以致延长住院时间，增加住院费用，甚至导致患者死亡。胰十二指肠切除术后胰瘘的风险因素包括一般因素(年龄[7]、性别[8]、黄疸指数[9]、营养状况)、疾病因素(胰腺病理学、胰腺质地[10-12]、胰管扩张程度[13-14]、胰液输出量)和手术因素(手术时间、切除类型、吻合技术/方式[15-16]、术中出血量)。此外,外科医生的经验已经被证明是与胰腺吻合口瘘有关的因素(如消化道重建方式、胰管支撑引流与否),预防性应用生长抑素也与胰瘘相关[17]。本文从胰十二指肠切除术后消化道重建、胰管支撑引流等方面为术后胰瘘的预防作一综述。

1 消化道重建

1.1 胰胃吻合与胰肠吻合 胰十二指肠切除术后消化道重建与术后并发症的发生率、死亡率以及患者的生活质量有着密切的关系。目前主要有两种方式来完成胰十二指肠切除术后消化道重建。自1941年Hun和他的同事第一次报道胰肠套入式吻合术后，胰肠吻合就成为胰十二指肠切除术后消化道重建的主要手术方式；Waugh等[18]于1946年第一次报道了胰胃吻合术。Oida等[19]认为胃肠吻合有3个优点：①胃壁厚且血流丰富；②胰液的出口靠近胃的背侧；③胃里面没有肠激酶，胰液不易被激活。McKay等[20]认为胰胃吻合术后胰瘘的发生，以及并发症的发生，总的死亡率明显比胰肠吻合术后低。Topal等[21]通过对胰胃吻合与胰肠吻合的多中心随机对照研究显示：胰胃吻合能够降低术后胰瘘的发生，但不能降低术后总的并发症，且在胰胃吻合术后一旦发生胰瘘，将明显增加患者的死亡风险及延长住院时间。Watanabe等[22]通过对81个中心、3 109例胰十二指肠切除术后病人的分析认为：胰胃吻合与胰肠吻合术后吻合口瘘的发生率(胰胃吻合11.0%，胰肠吻合13.3%)、腹腔内出血、腹腔脓肿形成、总的死亡率没有明显差别。He等[23]通过对1966—2011年胰胃吻合与胰肠吻合的随机对照研究和临床观察研究的数据分析显示，尚没有足够的证据证明胰胃吻合比胰肠吻合更安全，胰胃吻合与胰肠吻合术后总的死亡率相近。比起胰肠吻合，胰胃吻合可能减少术后胰瘘的发生和腹腔脓肿的形成，但却增加术后腹腔出血的风险。Daisuke等[24]最近研究认为：胰胃吻合与胰肠吻合术后胰瘘发生无明显不同，甚至在胰腺质地较软的患者来说也是如此。

1.2 几种常用的胰肠吻合 几种常见的胰腺空肠吻合术包括：套入式胰腺空肠端端吻合、胰管空肠黏膜端端吻合、胰腺空肠端侧吻合、胰管空肠黏膜端侧吻合、胰管栓塞结扎法、捆绑式胰肠吻合术。胰管空肠黏膜吻合术由Cattle于1943年第一次使用，它允许胰管与空肠黏膜直接接触，防止胰液与胰腺残端直接接触，促进黏膜愈合，保护嵌入空肠黏膜下吻合口，所以胰管空肠黏膜吻合理论上能够防止术后胰瘘的发生。Poon等[25]发现胰管空肠黏膜吻合是一种安全的吻合方式。Marcus等[26]发现胰管空肠吻合用于胰腺质地较硬、胰管扩张的低危患者，术后胰瘘的发生率低；而端端吻合用于胰腺质地较软、胰管不扩张的高危患者较安全。胰管栓塞结扎术因为废除胰腺的外分泌功能，且术后胰瘘发生率也很高而不常用[27]。捆绑式胰肠吻合近来常被报道[28-31]。Hashimoto等[31]对传统胰肠吻合与捆绑式胰肠吻合系统性分析认为：胰胃吻合与胰肠吻合术后胰瘘发生无明显不同，甚至在胰腺质地较软的患者来说也是如此。

2 胰管支撑引流

一些研究[32-34]认为胰十二指肠切除术后暂时性的胰管支撑引流能减少术后胰瘘的发生。Poon等[32]通过对120例胰肠吻合术后胰管支撑外引流与不引流的研究认为：胰管支撑外引流组术后胰瘘的发生率明显低于非引流组(6.7%比20%，P=0.032)，且引流组的住院时间明显短于非引流组(平均17 d比23 d，P=0.039)，但总的术后并发症的发生率(31.7%比38.3%，P=0.444)和死亡率(1.7%比5%，P=0.309)没有明显的差别。Pessaux等[34]认为胰管支撑外引流可减少术后胰瘘的发生，尤其适用于那些胰腺质地较软、胰管无明显扩张的胰十二指肠切除。Winter等[35]通过对234例接受胰十二指肠切除、胰肠吻合、胰管支撑内引流与非引流的前瞻性随机对照研究显示：胰管支撑内引流组对比非引流组在预防胰瘘方面无明显优势，而且对于那些胰腺质地较软、胰管无明显扩张的患者来说，胰管支撑内引流增加术后胰瘘的发生率(21.0%比10.7%，P=0.13)。Tani等[36]研究认为胰十二指肠切除术后胰管支撑内引流与外引流比较，术后胰瘘的发生率无明显差别，引流方式也不受胰腺质地影响，且简化了术后管理，缩短住院时间。Zhou等[37]对胰十二指肠切除术胰管支撑内/外引流与不引流的Meta分析认为：胰管支撑外引流能减少术后胰瘘的发生，而胰管支撑内引流则不能减少胰瘘的发生，尤其是对胰腺质地较软，胰管无明显扩张的患者；最近的研究还认为，胰管支撑内引流不但不能减少术后胰瘘的发生，而且还有可能增加软胰术后胰瘘的发生。

3 其他方式

此外，一些文献已经报道了用大网膜、镰状韧带包裹吻合口亦可有效地预防术后胰瘘的发生[38-39]，但是因为胰液中脂肪酶的作用，若发生胰瘘，则易形成腹腔脓肿。生长抑素及其类似物可以抑制胰腺的内分泌和外分泌，从而降低术后胰瘘的发生[40]。

4 结 论

总结胰十二指肠切除术后消化道重建的各种手术方式及术后的管理，我们认为：胰胃吻合与胰肠吻合术后胰瘘发生无明显不同，两种重建消化道方式各有利弊；文献报道和外科医生习惯更倾向于选择胰肠吻合行胰十二指肠切除术后消化道重建；胰管空肠黏膜端侧吻合，胰管支撑外引流能减轻胰液对吻合口的腐蚀，防止吻合口的梗阻，明显降低术后胰瘘的发生率；用大网膜行胰肠吻合口包裹，术后常规使用生长抑素抑制胰腺分泌功能等，均能降低术后胰瘘及并发症的发生率，我们推荐使用。

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