腹腔镜胃癌手术：目前的证据和未来的观点

概要
腹腔镜胃切除术已被广泛接受作为治疗早期胃腺癌的标准替代方案，因为其有利的短期结果。尽管存在争议，例如建立明确的适应症，适当的术前分期和肿瘤安全性，但是经验丰富的外科医生和机构已经将这种方法与各种类型的功能保留手术一起用于治疗晚期胃癌。随着技术的进步和最先进的仪器的出现，预计腹腔镜胃切除术的适应症将扩大到局部晚期胃癌。腹腔镜胃切除术似乎很有希望;然而，仍然需要收集必要的科学证据，以便将这种方法推广到所有相关患者和护理提供者的标准治疗方法。在高发病率国家正在进行一些多中心，前瞻性随机试验，这些试验的结果将突出该方法的短期和长期结果。在这篇综述中，作者描述了关于胃癌腹腔镜胃切除术的最新发现和关键问题。

关键词：胃切除术，腹腔镜切除术，早期胃癌，胃肿瘤，晚期胃癌，微创手术
核心提示：腹腔镜胃切除术已被广泛接受为开放性胃切除术治疗早期胃癌的标准替代方案。其临床适应症正在扩大，包括更广泛的外科手术以及更复杂的保存或保留功能的外科手术。尽管一些争议限制了该程序的广泛应用，包括缺乏肿瘤安全性证据以及高发病率和低发病率国家之间的差异，腹腔镜胃腺癌的胃切除术可能会成为新技术，改进的手术技术以及正在进行的多中心的证据试验出现了。

介绍
手术切除是治疗胃腺癌的主要治疗方式。虽然这种多学科方法也可以为胃癌患者提供有效和个性化的护理，但它仅显示出改善生存的渐进性进展。同时，在过去二十年中，胃癌的手术方式已经以各种方式显著改变和改善，从而限制了对患者的手术损伤，从而促进了恢复[1,2]。使用腹腔镜胃切除术治疗东部国家的早期胃癌，检测正在增加，可以加快这种方法的发展和传播，以治疗胃癌[3-5]。在这篇综述中，作者描述了目前促进胃腺癌腹腔镜胃切除术的证据以及对其使用的担忧。

腹腔镜手术的适应症
早期胃癌在治疗性手术切除和淋巴结清扫术后具有良好的长期生存率。当肿瘤局限于粘膜层时，长期存活率几乎为99％;当肿瘤局限于粘膜下层时，存活率为96％[6,7]。理想情况下，内镜下粘膜切除术或内镜黏膜下剥离术是保持患者生活质量的最佳方法。然而，这种方法只能应用于符合严格标准的有限数量的患者，并且只能在高发国家的专门中心进行谨慎治疗[8]。胃腺癌腹腔镜手术的初步适应症是局限于胃中下部粘膜下层的肿瘤，没有区域淋巴结转移的证据，不一定需要扩大淋巴结清扫，除了那些适合内镜治疗的病例[9,10]。腹腔镜全胃切除术适用于近端病变，如T1N0 [10]。在东亚国家，目前腹腔镜胃切除术的适应症已经扩展到血清阴性的晚期癌症，有或没有有限的胃周淋巴结受累[11]。然而，经验丰富的外科医生已经探索了超出这些适应症的腹腔镜手术治疗晚期胃癌[12-14]，并且与开放式常规手术相比，腹腔镜手术用于选择的晚期癌症没有任何不利影响。尽管有这种早期的承诺，来自精心设计的研究的数据仍然太少，无法推荐在需要广泛淋巴结清扫治疗晚期胃癌的病例中使用这种方法。表11 [15-22]列出了腹腔镜胃切除术与胃癌开腹胃切除术结果的随机临床试验。

表格1
最近的腹腔镜与开腹胃切除术治疗胃癌的随机临床试验

LND：淋巴结清扫术; LADG：腹腔镜辅助远端胃切除术; TLDG：完全腹腔镜远端胃切除术; ODG：开放性远端胃切除术;LAG;腹腔镜辅助胃切除术; OG：开胃切除术; DG：远端胃切除术; TG：全胃切除术; PG：近端胃切除术; LN：淋巴结; NE：未评估。显示了每个值中的有利组。

在早期胃癌中使用腹腔镜手术的证据
自第一篇关于腹腔镜胃切除术治疗早期胃癌的报告[2]以来，许多回顾性研究和小型随机临床试验显示腹腔镜胃切除术对开放式常规手术的短期益处和两者之间具有可比性的长期结果[ 1,11,16,17,23,24]。一些荟萃分析也证实，腹腔镜胃切除术是一种与传统开放手术相当的方法[25-28]。然而，这些报告主要是通过随机临床试验和远端胃大部切除术进行的。一般来说，与开放式常规手术相比，腹腔镜远端胃切除术引起的失血量更少，住院时间更短或相似，并发症发生率更低，死亡率相当[11,25]。然而，减少的淋巴结数量以及更长的手术时间是该方法的弱点[25]。对来自术前诊断为早期胃癌的最大随机临床试验的179例腹腔镜和161例开腹胃切除术患者进行了中期分析（完成入组：1416例患者; 705例腹腔镜与711例开放性远端胃切除术），发现两组之间的并发症和死亡率相似[11] 。

在所有胃癌病例中，与腹腔镜远端胃切除术相比，腹腔镜全胃切除术的穿透率相当低，因为其技术难度 - 即使对于有经验的外科医生 -  [27,29-33];这种低使用率可能特别归因于淋巴结清扫和吻合的困难[31,33-37]。因此，关于这一程序的精心设计的试验很少，只有一些有经验的外科医生在回顾性分析中报告了腹腔镜淋巴结清扫术及其吻合方法的安全性和可行性[34,38,39]。韩国的一项多中心，单臂，II期临床试验预计将突出I期癌症的长期结果，以及腹腔镜全胃切除术的可行性和安全性[韩国腹腔镜胃肠外科研究（KLASS）03试验， NCT01584336。

对于晚期胃癌使用腹腔镜手术的证据
对于晚期胃癌的治疗，应完全切除肝总动脉（LN 8），腹腔轴（LN 9）和脾动脉（LN 11p）周围的淋巴结，肝动脉周围的淋巴结也应如此（ LN 12a）在远端胃大部切除术的情况下，以及在全胃切除术的情况下脾动脉远端部分（LN＃11d）和脾门（LN＃10）周围的那些，根据日本指南[40,41]。图11显示了腹腔镜远端胃大部切除术与D2淋巴结切除术治疗晚期胃癌的术中视图。无论东西方国家对晚期癌症的淋巴结清扫是什么构成差异，使用腹腔镜进行淋巴结清扫术在技术上都是无可挽回的[8,40,42]。腹腔镜淋巴结清扫术的困难可能解释了最近的荟萃分析报告显示腹腔镜检查中淋巴结较少，而不是开腹手术[25,27,28,43]。然而，这一发现在临床上可能并不重要，因为每组中的比例没有显著差异，有15个或更多的淋巴结被检索以进行适当的分期[25]。此外，评估腹腔镜胃切除术治疗晚期癌症的研究报告，当有经验的外科医生进行手术时，可接受的短期结果[12,17,44-47]。尽管有证据尚为初步，但D2淋巴结清扫的腹腔镜胃切除术显示出血和术后疼痛减少，住院时间缩短，并发症和总生存率相似[48]。正在进行的大规模II期或III期多中心试验正在评估东部国家腹腔镜手术治疗晚期癌症的可行性和安全性：KLASS 02（NCT 01456598），日本腹腔镜胃外科研究组（JLSSG0901; UMIN-CTR 000003420） ），以及中国腹腔镜胃肠外科研究（CLASS01; NCT01609309）。研究中T阶段入选标准相似（T2-T4a）;然而，关于N期，更高级的疾病包括在JLSSG和CLASS试验中。 KLASS和CLASS试验的主要结果是3年无病生存，而吻合口漏和胰瘘（II期）和无复发生存（III期）的发生率是JLSSG试验的主要结果。这些精心设计的临床试验可以为腹腔镜远端胃切除术治疗晚期胃癌的短期和长期安全性提供答案。在腹腔镜全胃切除术治疗晚期胃癌方面，一些有经验的外科医生在回顾性分析中报告了开放常规手术的类似短期结果[49-53]。然而，他们的数据包括肿瘤浸润深度，淋巴结受累程度，肿瘤大小和邻近器官侵入状态的选定病例;因此，结果是有偏见的。更加困难的腹腔镜全胃切除手术的可行性和安全性，例如那些需要切除笨重，坚硬或固定的肿瘤或淋巴结，多器官切除和残胃手术的手术，即使是最有经验的外科医生也应该进行阐明[34] 54-57]。到目前为止，还没有大规模的多中心随机对照试验来评估腹腔镜全胃切除术治疗晚期近端胃癌的作用。


图1
D2淋巴结清扫远端胃大部切除术中的术中观察。A：大网膜的划分; B：LGEA和LGEV的分离; C：RGEA，RGEV和ASPDV的暴露; D：RGA的分离; E：解剖肝十二指肠韧带，暴露PV并分离LGV; F：LGA的分离和连接; G：沿SPA和SPV解剖; H：D2淋巴结清扫术后的胰腺外视图。 RGEA：右胃网膜动脉; LGEA：左胃网膜动脉; LGEV：左胃网膜静脉; RGEV：右胃网膜静脉; ASPDV：前上胰十二指肠静脉; RGA：右胃动脉; LGA：左胃动脉; SPA：脾动脉; SPV：脾静脉; CHA：肝总动脉; GDA：胃十二指肠动脉; IPA：幽门下动脉; LGV：左胃静脉; PHA：肝动脉正常; PV：门静脉; SGA：胃短动脉; SGV：胃短静脉。

技术考虑因素
腹腔镜辅助胃切除术需要微型剖腹手术切除标本和体外吻合术。它仍然被广泛应用并应用于大多数临床试验中。然而，这种方法很麻烦，特别是在肥胖患者中[37,58,59]。体内吻合术使这种手术成为所谓的“完全腹腔镜手术”，可以实现更复杂的重建方法。它可以减少手术时间，减少小剖腹手术的长度，并切换脐下方的标本取出切口，从而减少与切口相关的疼痛[60,61]。在体内Billroth I吻合术安全地进行三角形吻合术后，完全腹腔镜远端胃大部切除术获得了普及[62,63]。在全胃切除术中，还进行了许多努力以在体内恢复食管空肠吻合术[36,37,64-68]。最近，引入了使用线性钉的体内侧对侧食管空肠吻合术，证明了其安全性和可行性[37,69]。手工缝合吻合不再是手术的有吸引力的选择;然而，重建方法根据每位外科医生的偏好而有所不同。腹腔镜手工缝制技术仍然通常用于在体内吻合期间闭合内颌骨吻合器的共同进入孔。

大多数外科医生使用至少五个套管针进行腹腔镜胃切除术。然而，凭借先进的技术和改进的技术，减少了端口甚至单端口（切口）腹腔镜胃切除术已经安全地进行[70-73]。然而，由于这些程序是由经验丰富的外科医生或特别高规模的机构报告的，因此该程序的技术可行性，安全性和标准化尚未完全阐明[72,73]。到目前为止，在术后临床结果方面，很难评估缩小端口或单切口胃切除术是否比传统腹腔镜手术侵入性更小[74]。然而，最近50例单端口腹腔镜远端胃切除术与50例多端口手术的比较表明，单端口手术的短期效果更好，包括术中出血量减少，术后第1天和术后第1天疼痛评分降低术后第5天使用肠外镇痛药较少，C反应蛋白水平较低，尽管单口手术中手术损伤的减少并未延长到缩短住院时间[73]。

使用腹腔镜进行有限的外科手术
限制手术的范围是微创胃切除术的目标，因为它具有保持患者功能的能力。因此，腹腔镜技术有可能减轻患者的康复，并且已经在前哨淋巴结导航手术，保留幽门的胃切除术和近端胃切除术中进行了可行性和有效性的研究。

用哨点盆淋巴结清扫小部分T1N0M0癌的部分切除胃目前适用于胃癌的前哨淋巴结导航手术[75,76]。使用术中染料注射方法的随机临床试验（JCOG 0302）显示较高的假阴性率（46％），因此停止了患者应计[77]。一些荟萃分析也指出前哨淋巴结导航手术的假阴性率不令人满意[78-80]。然而，Kitagawa等[75]最近的一项临床试验突出了可接受的结果，检测淋巴结转移的准确率为93％，假阴性率仅为7％。学习曲线效应可能会降低假阴性率。需要对手术标准化和相关资源进行广泛采用胃癌前哨淋巴结导航手术。腹腔镜前哨淋巴结活检和保胃手术的多中心III期试验[Sentinel Node Oriented Tailored Approach（SENORITA）试验，NCT01804998]已经启动，以检查前哨淋巴结导航手术与传统腹腔镜胃切除术相比的益处。该试验的适应症包括术前诊断为小于3 cm的T1N0肿瘤，并接受腹腔镜节段或楔形切除术，并进行前哨淋巴结清扫术。主要终点是3年无病生存。

另一种能够保持功能的方法是保留幽门的胃切除术。基于作者对幽门周围淋巴结转移模式的理解，该程序已经谨慎开发。在已经进行手术的选定患者中，在幽门上皮（LN 5）和幽门下（LN 6）区域淋巴结转移的可能性非常小[81-85]。保留幽门的胃切除术适用于距离幽门4厘米以上的中间三期cT1N0期癌症[81-83]。与传统远端胃大部切除术相比的优点包括倾倒综合征，胆汁反流和胆结石形成的发生率降低[81,82,86]。如果由经验丰富的外科医生对精心挑选的患者进行手术，则长期肿瘤学结果显示可接受的存活率[87,88];因此，应通过精心设计的多中心试验来阐明营养谱的优势和对患者生活质量的长期影响。

近端胃切除术是近端早期胃癌的一种合适选择，可在术后保留胃功能;全胃切除术后患者术后并发症发生率较高，长期营养恶化[89-91]。然而，腹腔镜下近端胃切除术 - 特别是其重建方法 - 尚未标准化，并且没有显示出超过传统全胃切除术的显著益处[92]。其主要缺点包括涉及食管空肠吻合术（即狭窄）的并发症，反流性食管炎和营养状况的微不足道的改善。最近一项关于营养概况和倾倒综合征相关方面的多中心回顾性比较研究显示，近端胃切除术优于全胃切除术[93]。然而，研究期间体重没有显著变化。因此，上述功能保留手术应首先在技术上和概念上进行标准化，并通过多中心临床试验进行评估。

胃癌腹腔镜胃切除术的未来前景
随着外科技术和最先进技术的改进，将开发和改进许多创新程序，以提高接受胃癌胃切除术的患者的生活质量。高容量中心的经验丰富的外科医生已经将腹腔镜方法应用于由于安全问题和缺乏有力证据而曾一度禁忌的复杂病例。预计东亚国家的几项重要的多中心随机临床试验将对腹腔镜胃切除术相关问题给出答案。看看这种方法的发展和扩展程度将会非常有趣。另一方面，很少有高层证据表明腹腔镜胃切除术治疗胃癌。到目前为止，腹腔镜远端胃大部切除术治疗早期胃癌是传统开腹手术的唯一标准替代方法。在技​​术可行性，肿瘤安全性，指定患者的正确选择，成本，教育和资格认证方面，有许多问题需要解决。因此，应该在精心挑选的患者中实施上述新开发的手术技术，确保患者理解手术。

结论
由于新技术的出现和改进的手术技术，胃腺癌的腹腔镜胃切除术已经发展。随着更复杂，更节约的手术，临床适应症正在扩展到更广泛的外科手术。尽管高发病率和低发病率国家腹腔镜治疗胃癌的适当环境的差异阻碍了无偏见，大规模临床试验的实施和程序的大量应用，但在采用前应严格确认腹腔镜检查在胃癌治疗中的应用。

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