肝脏切除术围手术期多学科临床管理指南(2025版)

国际肝胆胰协会中国分会;中华医学会外科学分会肝脏外科学组;中国抗癌协会加速康复肿瘤外科专业委员会

中国普通外科杂志 ›› 2025, Vol. 34 ›› Issue (09) : 1801 -1841.

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中国普通外科杂志 ›› 2025, Vol. 34 ›› Issue (09) : 1801 -1841. DOI: 10.7659/j.issn.1005-6947.250547
指南与共识

肝脏切除术围手术期多学科临床管理指南(2025版)

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Guidelines for multidisciplinary clinical management of perioperative period of hepatectomy (2025 edition)

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摘要

肝脏切除术已成为肝胆外科疾病最重要的治疗方法。肝切除术的围手术期管理与其安全性和疗效密切相关。围手术期管理包括术前、术中及术后对病人病情诊疗的系统化评估和处理,其原则和方法近年来发展较快。2017年中华医学会外科学分会肝脏外科学组发布《肝切除术围手术期管理专家共识》。在此基础之上,编审委员会梳理已有的循证医学研究证据,结合国内外众多肝脏外科中心的最新临床实践经验,组织国内相关领域多学科专家团队进行研讨、修订形成《肝脏切除术围手术期多学科临床管理指南(2025版)》。该指南涵盖肝脏切除术术前、术中和术后相关病情系统评估和处理的原则和方法,并给出具体推荐意见,旨在促进该领域临床实践的规范化和精细化,提高肝脏切除术的安全性和临床疗效,为肝脏外科相关的临床专业人员提供指导和参考。

Abstract

Hepatectomy has become the most important treatment method for hepatobiliary diseases. The perioperative management of hepatectomy is closely related to its safety and efficacy. Perioperative management includes systematic evaluation and management of the patient′s condition before, during, and after surgery, and its principles and methods have developed rapidly in recent years. In 2017, the Group of Liver Surgery of Surgical Society of Chinese Medical Association released the "Expert consensus on perioperative management of hepatectomy". On this basis, the editorial committee has reviewed existing evidence-based medicine research evidence, combined with the latest clinical practice experience of numerous liver surgery centers at home and abroad, organized a multidisciplinary expert team in relevant fields in China for discussion, and revised to formulate the Guidelines for multidisciplinary clinical management of perioperative period of hepatectomy (2025 edition). This guideline covers a systematic assessment, treatment principles, and methods for relevant conditions before, during, and after hepatectomy, and provides specific recommendations. The revision of the guidelines aims to promote the standardization and refinement of clinical practice in this field, improve the safety and clinical efficacy of liver resection, and provide guidance and reference for clinical professionals related to liver surgery.

关键词

肝切除术 / 围手术期 / 临床管理 / 指南

Key words

Hepatectomy / Perioperative period / Clinical Governance / Guidelines

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国际肝胆胰协会中国分会;中华医学会外科学分会肝脏外科学组;中国抗癌协会加速康复肿瘤外科专业委员会. 肝脏切除术围手术期多学科临床管理指南(2025版)[J]. 中国普通外科杂志, 2025, 34(09): 1801-1841 DOI:10.7659/j.issn.1005-6947.250547

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肝脏切除术(以下简称肝切除术)已成为肝胆外科疾病,尤其是肝脏肿瘤最重要的治疗方法。随着对肝脏解剖的深入了解,血流控制技术、三维可视化评估技术的逐渐完善,以及新型离断肝实质器械的发明,肝切除术已日臻成熟。同时,加速术后康复(enhanced recovery after surgery,ERAS)理念的推广和实践也赋予了肝切除术新的内涵和要求。目前国内外肝切除术的手术死亡率虽已下降至5%以下,但术后并发症发生率仍较高(15%~50%)。降低并发症发生率和提高肝切除术的安全性仍然是肝脏外科面临的重要课题。肝切除术的围手术期管理与病人术后并发症的发生乃至手术死亡率密切相关。围手术期管理包括术前、术中及术后对病人病情诊疗的系统化评估和处理,其原则和方法近年来发展较快。2017年中华医学会外科学分会肝脏外科学组发布《肝切除术围手术期管理专家共识》,获得了同行的高度肯定和认可,已在临床得到广泛推广应用。8年来,肝切除术围手术期管理的理念与技术方法不断更新,专家共识和指南的编撰方法也在不断进步。目前,国内外尚无公认的针对肝切除术围手术期管理的临床指南发布。因此,基于现有的循证医学研究证据,结合国内外最新临床实践经验,国际肝胆胰协会中国分会、中华医学会外科学分会肝脏外科学组和中国抗癌协会加速康复肿瘤外科专业委员会共同组织国内相关领域多学科专家团队进行研讨,编撰《肝脏切除术围手术期多学科临床管理指南(2025版)》(以下简称本指南),旨在促进该领域临床实践的规范化和精细化,提高肝切除术的安全性和临床疗效。
本指南已在国际实践指南注册平台(Practice guideline Registry for transPAREcy,PREPARE,http://www.guidelines.registry.cn)注册,注册号为PREPARE⁃2024CN116。指南使用者与应用的目标人群为施行肝切除术的外科医师、麻醉医师、临床药师、影像诊断医师及与肝切除诊疗和管理相关的专业人员。本指南推荐意见的应用目标人群为接受肝切除术的病人。本指南采用国际通用的GRADE分级标准(grading of recommendations,assessment,develop⁃ment and evaluation,GRADE)评估推荐意见和用于证据评价(表1)。(1) 推荐意见包括推荐使用(强推荐)和建议使用(弱推荐),本指南将“推荐使用”采用1表示,“建议使用”采用2表示。(2) 证据评价:根据证据中的偏倚风险、不一致性、间接性、不精确性和发表偏倚,将证据质量分为高、中、低和极低4个水平,分别采用A、B、C、D表示。(3) 当证据质量低或缺乏直接证据时,采用德尔菲法(匿名投票)采纳专家们的投票建议,最终形成推荐意见,使用最佳实践声明(good practice statement,GPS)表示。

1 肝切除术的术前管理

1.1 全身状况评估

1.1.1 术前体能状态评估

目前国际上多项诊疗指南均将体能状态作为术前评估的重要指标。美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)-活动状态(performance status,PS)评分可以准确反映病人的术前体能情况[1]

ECOG-PS评分≥1,术后并发症发生率显著升高;ECOG-PS评分≥2时手术应基于病人年龄与身体状况慎重处理[2-4]。心肺运动试验可客观反映不同负荷水平下发生的病理生理变化及功能受损程度,从而综合评价心肺等器官系统整体功能和储备能力。术前通过心肺运动试验测定峰值摄氧量、CO2通气当量、无氧阈等数据,可评估病人手术风险,预测近期及远期死亡率,特别是可筛查出术前静息状态下心肺功能正常的高风险人群[5-6]

推荐意见1:术前采用ECOG-PS评估病人体能状态,ECOG-PS评分≥2时手术需慎重(1A)。心肺运动试验可用来评估病人手术风险(2B)。

1.1.2 术前营养评估

肝切除病人术前营养风险与手术预后密切相关[7]。肝切除术前应对病人进行营养风险筛查,对存在营养风险的病人及时干预。目前国际上广泛应用的营养风险筛查工具包括营养风险筛查(nutritional risk screening,NRS)-2002评分表[8],营养不良通用筛查工具[9],病人自评主观全面评定量表[10],营养风险指数(nutritional risk index,NRI)[11]和预后营养指数(prognostic nutritional index,PNI)[12]等。有研究证实,NRS-2002评分、NRI和PNI与肝癌肝切除术预后相关[7]。其中NRS-2002评分表简便实用,容易掌握,临床有效性被充分验证[13],被国内外多个临床营养学会推荐为成人住院病人营养风险筛查的首选工具[14-15]。对于NRS-2002评分<3的病人,均应在围手术期进行营养支持治疗;NRS⁃2002评分为3~5,建议口服营养补充;如NRS⁃2002评分>5,或近6个月内体质量下降10%~15%,或BMI<18.5 kg/m2伴一般情况差,或血清白蛋白(ALB)<30 g/L(无肝肾功能障碍)则为营养高风险人群[16],需推迟手术1~2周以进行营养支持治疗[17]。有Meta分析结果证实,对严重营养不良病人进行术前营养支持可以降低术后并发症发生率[18]

推荐意见2:术前可使用NRS-2002评分表作为营养筛查工具。NRS-2002评分≥3需进行营养支持治疗(1A)。

1.1.3 术前心理状况评估

研究表明术前11%~80%的择期手术病人表现出显著的焦虑和抑郁状态等负面情绪,而负面心理状态显著影响病人术后恢复和生命质量[19-21]。术前可对病人进行心理筛查,术前焦虑评估可采用状态-特质焦虑问卷、住院焦虑和抑郁量表、抑郁自评量表等比较常用的评估工具[22]。对术前抑郁或焦虑病人采用术前教育、松弛想象训练或者药物干预,可改善围手术期病人的心理状态,有利于术后康复和生命质量的提高[23-24]。严重的精神疾病和人格异常应列为肝切除术的禁忌证。

推荐意见3:术前可对心理状态不稳定病人进行心理筛查,对术前抑郁或焦虑病人及时进行心理干预(2B)。

1.2 基础肝病状况的评估

肝切除术的病人大多有慢性肝病背景,术前需对基础肝病进行评估,主要包括肝病致病因素、活动性炎症、肝硬化门静脉高压相关合并症等。

慢性乙型肝炎和慢性丙型肝炎是常见的病毒性肝炎。肝切除术前需进行乙型肝炎病毒(HBV)抗原、丙型肝炎病毒(HCV)抗体检测,明确病原后需进一步检测HBV⁃DNA[25]、HCV⁃RNA水平[26]

丙氨酸氨基转移酶(ALT)是肝脏炎症损伤最敏感的指标,天门冬氨酸氨基转移酶(AST)、胆红素是肝脏活动性炎症的标志[27]。酒精性肝病(alcohol-associated liver disease,ALD)病人ALT可正常或仅轻微升高,AST升高更为明显,常见AST/ALT比值>1.5~2.0[28]。自身免疫性肝炎主要表现血清ALT和AST水平升高,碱性磷酸酶(ALP)和γ-谷氨酰转移酶(GGT)水平基本正常或轻微升高[29]

建议采用无创方法评估肝纤维化和肝硬化。显著肝纤维化的诊断标准为AST与血小板(PLT)比值指数(APRI评分)=[AST/AST正常值上限(ULN)]×100/PLT(109/L)>0.5或肝脏瞬时弹性成像(transient elasto⁃graphy,TE)>7.0 kPa;肝硬化的诊断基于临床证据或无创指标(APRI评分>1.0或TE>12.5 kPa)。诊断为失代偿期肝硬化的病人,肝切除术术后死亡率和并发症发生率明显升高,不建议或慎行肝切除术。肝切除术术前评估还应关注基础肝病所造成的肝脏功能受损和肝脏储备功能降低[30]

推荐意见4:术前应进行肝病病因、肝脏活动性炎症以及肝硬化的评估(1A)。

1.3 肝癌的分期及术后复发风险预测

肝癌临床分期对于治疗方法的选择和预后评估具有重大意义。目前全球普遍使用的分期包括巴塞罗那肝癌临床分期(Barcelona Clinic Liver Cancer,BCLC)[31]、美国肿瘤联合会TNM分期[32]、意大利肝癌计划评分[33]、中国肝癌分期(China Liver Cancer,CNLC)等[34]。上述分期多基于当地患病人群建立,由于病因、基础疾病及人种差异,各种肝癌预后预测模型的评估效果在不同地区的队列间存在差异。但多项队列研究提示,各种分期系统对于整体肝癌肝切除病人预后的判断并无显著差异[35-36]

CNLC分期综合评估病人身体状况(ECOG-PS评分),肝功能(Child-Pugh评分)和肿瘤特征,可准确评估肝癌病人预后。相较于BCLC分期,CNLC分期提供的治疗策略更为积极,介入及手术切除的指征更宽,强调以手术为基础的多种手段综合治疗策略,更符合中国肝癌治疗的实践[37]。回顾性研究提示CNLC分期可准确预测中国人群肝癌手术后长期生存和复发[38]。另有回顾性研究发现CNLC分期对中国人群预后和复发风险的预测优于BCLC和TNM分期[39]。因此,CNLC分期在中国肝癌人群中应作为优先推荐。

推荐意见5:术前应进行肝癌临床分期以判断预后并制订相应的治疗策略(1A)。推荐采用CNLC分期系统,亦可同时参照BCLC分期系统(1C)。

1.4 肝脏可切除性评估和手术规划

1.4.1 肝脏功能的初步评估

良好的肝脏功能是保证肝切除术安全的先决条件。术前应对病人肝功能进行精准评估。Child⁃Pugh评分是临床应用最广泛的肝功能评估标准,也是肝癌分期的重要指标。Child-Pugh评分C级是肝切除的禁忌证;Child-Pugh评分B级的病人,经护肝治疗肝功能好转为A级可考虑手术;经过护肝治疗Child⁃Pugh评分接近A级(7分)且肝切除范围较小时也可考虑手术治疗[40-42]。Child-Pugh评分中腹水和肝性脑病的评估主观性较大。白蛋白-胆红素(albumin bilirubin,ALBI)评分通过对ALB和胆红素定量分析,消除主观指标的影响,可以弥补Child-Pugh评分的不足,对评估肝癌病人预后[43]、预测肝切除术后肝衰竭(post hepatectomy liver failure,PHLF)的发生率具有重要作用[44]。ALBI评分2、3级病人PHLF的发生率显著升高[44-45],手术后远期预后也较差[46]。终末期肝病评分模型(model for end-stage live disease,MELD)在肝切除术中成为Child-Pugh评分的重要补充。术前MELD评分<9,PHLF发生率较低;术前MELD评分>11,PHLF的发生率较高[42]。既往合并肝硬化、门静脉高压症、脾功能亢进常被视为接受肝切除术的相对禁忌证。然而,有研究表明,经过严格筛选,对于合并上述疾病,但肝功能正常的病人,同期进行肝切除和脾切除手术可以显著提高病人无瘤生存率[47-49],缓解病人脾功能亢进症状并改善肝功能,且不影响短期恢复。但严重肝功能损害仍是肝切除术的禁忌证。

推荐意见6:术前应采用Child-Pugh评分、ALBI评分或者MELD评分对肝脏基本功能进行初步评估,严重肝功能损害是肝切除术的禁忌证(1A)。

1.4.2 肝脏储备功能评估

通过评估肝脏储备功能,可以预测病人对不同范围肝切除的耐受性,有助于手术规划,预防PHLF的发生。临床应用最广的肝脏储备功能检测是吲哚菁绿(indocyanine green,ICG)排泄试验。通常以ICG R15作为量化评估肝脏储备功能的指标[50]。将ICG R15与剩余肝体积/标准肝体积比值相对应,可初步估计病人耐受肝切除范围。对于Child⁃Pugh评分A级的正常肝脏,预留肝体积与标准肝体积比值应该≥30%;对于Child⁃Pugh评分A级的肝硬化病人,若ICG R15<10%,预留肝体积与标准肝体积比值应该≥40%;若ICG R15为10%~20%,预留肝体积与标准肝体积比值应该≥60%;若ICG R15为21%~30%,预留肝体积与标准肝体积比值应该≥80%;若ICG R15为31%~40%,只能行限量肝切除;若ICG R15>40%或Child⁃Pugh评分B级,建议只能行肿瘤剜除术[34]。转化治疗(靶向治疗、免疫治疗、化疗、放疗、介入治疗等)会导致肝细胞损害,为充分保证手术安全性,术后剩余肝体积标准可适度提高[51]。任何影响肝脏有效血流(门静脉栓塞、肝内动静脉分流)和胆道梗阻的因素都可能导致ICG清除率下降,无法准确反映肝脏储备功能。此时需结合其他指标如血清胆固醇水平、前白蛋白水平、PLT计数等综合评估肝脏储备功能。钆塞酸二钠增强MRI检查可通过肝脏相对强化程度(relative liver enhancement,RLE)评估肝脏整体储备功能,并可对不同解剖区域单独量化评估,预测PHLF的效力优于ICG R15[52]。但是目前尚无公认的RLE阈值。99Tcm标记的半乳糖人血清白蛋白显像技术和99Tcm标记的亚氨基二乙酸显像技术也可用于定量、定位评估肝脏储备功能[53-54],可在有条件的单位开展。

糖耐量试验、氨基比林代谢试验、利多卡因代谢试验等通过不同原理定量反映肝脏储备功能,但效果尚未取得公认,在临床上未能广泛开展。基于FibroScan的肝脏硬度测定(liver stiffness measurement,LSM)可用于评估术前肝脏硬化程度,多项研究表明LSM的升高是PHLF的独立危险因素,但目前尚没有公认的预测阈值,因此限制了其广泛应用[55-56]

推荐意见7:应根据Child-Pugh评分、ICG R15和剩余肝体积与标准肝体积比值等多种肝脏储备功能评估方法,综合判断病人可耐受肝切除的范围(1B)。

1.4.3 基于手术规划的剩余肝体积评估

术前精确测量拟切除和剩余肝体积,对合理选择手术方式和确定肝脏切除安全限量具有重要价值[57-58]。多项回顾性研究结果显示,使用直接测量法获得的剩余肝体积与切除标本质量的相关性良好[59]。随着影像学技术发展,三维成像技术在术前准确估算切除的肝脏体积同时,还能计算门静脉分支流域的肝体积[60-61]。半自动化肝体积测量软件在测量肝脏体积同时识别肝内结构,并允许手动纠正[62]。半自动化肝体积测量法比直接测量法计算更准确,并且其测量结果具有更好的重复性[63]。但也有研究指出,半自动化肝体积测量法很难区分门静脉和肝静脉,因为两者具有相似的对比度[64]。全自动化的体积测量法不需要人为校正就可完成测量,其与半自动化肝体积测量法以及直接测量法具有高度一致性,且需时间更短[65]。但全自动方法测量单个肝段体积的准确率仍需进一步评估[61]

推荐意见8:在术前剩余肝体积评估中,可使用直接、半自动及全自动肝体积测量法以准确、高效评估剩余肝体积(2B)。

1.4.4 三维可视化技术对肝切除术的评估价值

三维可视化技术将二维平面图像转化成三维立体图像,直观、清晰地显示出肝脏脉管系统,尤其是血管变异情况,为肝脏手术术前规划和术中导航提供全新视野[66]。一项回顾性队列研究结果显示,在肝内胆管结石需行肝切除术病人中,运用三维可视化辅助肝切除术可获得更低的结石残留率以及输血率[66]。Au等[67]的研究提出,相比常规腹腔镜肝切除术,运用三维可视化技术辅助肝切除术可以更有效应对复杂肝段切除术,并且术后并发症发生率更低以及住院时间更短。Zhang等[68]指出,在肝包虫病行手术治疗病人中,术前三维可视化重建技术可以提高病人手术依从性,减少术中出血量以及降低术后胆汁漏发生率。一项Meta分析[69]结果显示,三维可视化辅助肝切除术可有效缩短手术时间、减少术中出血量和术后并发症的发生。

推荐意见9:推荐采用三维可视化技术进行术前规划和术中导航,可降低术后并发症发生率(2B)。

1.4.5 PHLF预测模型

PHLF是肝切除术后病人死亡的主要原因,其发生率为8%~12%[70-71]。PHLF主要与有效剩余肝体积有关[71]。此外,MELD评分≥11可作为肝硬化病人PHLF的预测指标[72],但也有研究指出MELD评分用于预测PHLF价值有限[71]。与MELD评分相比,ALBI评分、PLT-ALB-胆红素分级、AST-PLT评分是更好的PHLF预测指标[43,73-74],但仍需要大样本、多中心研究进一步验证。回顾性研究结果显示,剩余肝体积、术前血清ALB水平和基于CT图像的细胞外容积构建的模型预测PHLF的准确率高于ALBI评分模型[75]。Notake等[76]的研究提出,肝细胞钆塞酸二钠摄取率用于预测Child-Pugh评分B级或C级的PHLF准确率显著高于ICG清除率和剩余肝体积。Xu等[77]的研究表明,基于术前CT图像的深度学习模型能有效预测PHLF,总体准确率为84.15%。与ALBI评分相比,机器学习模型预测PHLF的准确率更高,但深度学习模型和机器学习的普适性仍需要进一步验证[78]

推荐意见10:剩余肝体积、ALBI评分和影像学衍生的预测模型在预测PHLF中具有重要指导价值(2C)。

1.5 术前准备要点

1.5.1 术前宣教

术前教育通常包括术前的准备工作、手术过程的介绍、术后护理和康复指导等内容,通过详细的术前教育可减少病人焦虑,提高手术的配合度和效果[79-81]。目前没有专门针对肝切除术前宣教的随机对照试验(randomized control trial,RCT)研究。一项针对腹部外科手术的RCT研究结果显示,术前咨询和研讨会对病人和护理人员的培训有益,能预防术后并发症的发生,改善病人健康结局指标[82-83]。另一项系统综述也指出,术前宣教对腹部手术的快速康复有积极作用[84]。ERAS指南[85]针对不同病人推荐采用手册、卡片、多媒体、展板等形式重点介绍麻醉及手术过程、术后及围手术期处理等情况,包括术后早期进食、早期活动等,可缓解其紧张、焦虑及恐惧情绪[86],获得病人及其家属的理解和配合。

推荐意见11:病人术前接受肝切除术的相关信息和教育有利于术后康复,并建议全程宣教(GPS-C)。

1.5.2 术前戒酒、戒烟与呼吸系统功能锻炼

吸烟是围手术期心脑血管意外、肺部并发症、伤口感染和愈合延迟等主要不良事件发生的独立危险因素,并导致病人住院时间延长、医疗费用提高、围手术期死亡率增加[87]。国内外指南均建议在肝切除术前4~8周戒烟,且戒烟时间越长可能越有效[88]

酒精性肝病是肝脏手术后并发症发生的危险因素[89]。因此,应在围手术期停止饮酒。与非饮酒病人比较,重度饮酒病人感染发生风险高73%,呼吸困难发生风险高80%,入住重症监护病房(ICU)的风险高29%[90]。有研究[85,89-90]结果显示,术前4~8周戒酒可降低术后并发症发生率[91]。国内外指南也建议在肝切除术前4~8周戒酒。

术前对高危病人(高龄、吸烟、肥胖、充血性心力衰竭、阻塞性睡眠呼吸暂停综合征、慢性阻塞性肺疾病、哮喘、急性呼吸道感染等)进行呼吸功能锻炼,包括运动训练、呼吸练习等,可减少术后肺部和血栓性并发症的发生,改善肺功能[92-94]。一项系统回顾研究表明,术前呼吸肌训练可降低术后肺炎和肺不张发生风险[95]。另一项研究结果显示,呼吸肌训练可提高术后肺功能,缩短住院时间[96]。建议病人术前进行深呼吸练习,有效咳嗽、排痰,吹气球,每日活动目标行走距离≥1 000 m(或者>2 000步)等[97]

推荐意见12:术前计划性戒烟和戒酒,且戒烟、戒酒时间越长,围手术期相关并发症发生风险越低,同时术前应进行呼吸功能训练(1A)。

1.5.3 肝脏基础疾病的处理

接受肝切除术的病人多数合并肝脏基础疾病,术前应进行全面评估,必要时给予规范治疗[98]。慢性乙型肝炎是最常见的肝脏基础疾病,其病毒DNA复制不仅可导致肝脏炎症,而且增加手术风险和影响肝癌病人预后[99]。同时,肝切除术的创伤也存在激活乙型肝炎病毒复制的风险[100]。因此,对于乙型肝炎病毒表面抗原(HBsAg)阳性的肝硬化肝癌病人,无论HBV⁃DNA数值和转氨酶是否升高,均需术前及时启动并长期抗病毒治疗[101]。目前,尚无HBV-DNA定量数值降低至何种程度才可以实施肝切除术的循证医学证据,但已明确尽早抗病毒治疗有助于降低手术风险和改善病人预后[99]。此外,对于合并丙型肝炎病毒感染且HCV-RNA阳性的肝癌病人,抗丙型肝炎病毒药物治疗可推迟到肝癌根治性切除术后4~6个月开始,治疗终点为治疗结束后12周,采用敏感检测方法检测不到血清或血浆中HCV-RNA[102-103]

除上述针对病因的抗病毒治疗外,还需高度重视对术前的肝损伤治疗。术前ALT升高2×ULN(正常值2倍)以上,须尽早给予针对肝损伤的药物治疗。术前ALT在(2~10)×ULN,应在护肝治疗1周后复查肝功能,如果ALT显著下降可按期手术,反之则应当延期手术;对于术前ALT高于10×ULN,应暂缓手术[100]

推荐意见13:对于HBsAg阳性肝硬化肝癌病人,无论HBV⁃DNA数值和转氨酶是否升高,均需术前及时启动并长期抗病毒治疗(1A)。

1.5.4 梗阻性黄疸的处理

术前胆道引流(preoperative biliary drainage,PBD)有助于缓解梗阻性黄疸、胆管炎、营养不良、凝血功能紊乱以及为接受新辅助治疗或手术可能延迟的病人改善肝脏功能,促进剩余肝脏再生等[104-105]。目前多数研究推荐常规行剩余肝实质的胆道引流[106]。长时间胆汁淤积所致的肝功能不全与肝切除术后死亡率增高密切相关[107]。Moole等[108]的Meta分析结果显示,与直接手术相比,术前PBD能够明显降低术后严重并发症的发生。美国肝胆胰协会在对肝门部胆管癌的专家共识中推荐,术前有胆管炎、高胆红素所致的营养不良、肝肾功能不全、术前接受化疗或门静脉栓塞的病人建议术前进行PBD[109]。中国研究型医院学会肝胆胰外科专业委员会在《肝门部胆管癌诊疗指南(2025年版)》中提出,肝门部胆管癌根治性手术前PBD理想情况,总胆红素(TBIL)应<51 μmol/L。引流部位首选预留肝叶单侧。对手术方式不确定或单侧引流效果不佳病人,考虑双侧胆管引流[110]。但有三项Meta分析[111-113]结果显示,肝门部胆管癌术前行或不行PBD,死亡率差异并无统计学意义,但PBD增加了胰腺炎、胆管炎和手术部位感染等并发症发生率。

内镜下胆道引流(endoscopy biliary drainage,EBD)和经皮经肝胆管穿刺引流(percutaneous transhepatic cholangial drainage,PTCD)是两种主要PBD策略。目前最佳PBD方法仍存争议,需依据病人状况与医疗条件选择。多项Meta分析[114-115]结果显示,PTCD在胰腺炎、胆管炎等总并发症发生率低于EBD,成功率高于EBD。然而,另有研究结果显示,PTCD组的肿瘤种植转移发生率高于EBD组,且EBD组在可切除的肝门部胆管癌病人的总生存期优于PTCD组[116-118]

PBD持续时间尚不明确。部分医学中心建议PBD持续保留到TBIL下降至30~51 μmol/L[109]。研究发现PBD后仅有2/3病人的TBIL能够恢复正常。长时间的PBD导致并发症发生率增高,并增加手术等待时间,甚至失去手术机会[119-120]。一项研究结果显示,>2周的PBD对减少术后并发症的发生并无益处,反而增加引流相关并发症发生风险和延长住院时间[121]

推荐意见14:对于梗阻性黄疸病人,需行大范围肝切除术(切除肝叶>60%)、合并胆管炎、营养风险大、拟行新辅助治疗、需行门静脉栓塞建议行PBD(1B)。胆道引流的方法应根据病人情况和医疗技术条件选择行EBD或PTCD (1C)。

1.5.5 术前胃肠道准备

欧洲临床营养和代谢学会(The European Society for Clinical Nutrition and Metabolism,ESPEN)外科营养指南、美国麻醉医师协会指南以及国内外ERAS指南均建议对于非急诊、无胃食管反流或胃排空延迟疾病的择期手术病人,需术前禁饮2 h,禁食6 h[122-123]。传统禁食、禁饮时间过长会产生饥饿性损伤,诱发一系列突发的代谢变化,引起低血糖症,抑制ALB合成,并激活炎症应激系统[124]。病人在择期手术麻醉前2 h可饮用透明液体,包括咖啡和茶,尽量减少口渴引起的不适和戒断症状引起的头痛[125]

肝切除术前不推荐常规放置鼻胃管。留置鼻胃管会增加肺部并发症的发生,延缓胃肠道功能恢复[126]。两项RCT结果显示,术前预防性放置鼻胃管对术后恢复没有益处,并可能导致接受择期肝切除术的病人发生肺部并发症,延长住院时间[127-128]

推荐意见15:术前6 h禁食,2 h禁饮;不推荐常规行鼻胃管插管,如有特殊情况需留置,可在麻醉清醒后拔除(1A)。

1.5.6 术前碳水化合物补充

术前禁食、禁饮有可能引起病人术后身体和心理不适[129]。术前补充碳水化合物可减少焦虑、术后胰岛素抵抗及恶心、呕吐,缩短住院时间[130]。最近一项系统综述得出结论,术前2 h补充碳水化合物是安全的,且可降低胰岛素抵抗[131]。另一项研究及ESPEN外科营养指南均推荐,术前1晚和术前2~4 h给予碳水化合物饮料,可有效维持胰岛素敏感性,确保水分和减少胰岛素抵抗,改善肝功能紊乱病人的营养情况,提升病人围手术期舒适度的同时,有利于维持基本的胃肠功能[132]。如果不存在禁忌证,建议术前1晚摄入适量碳水化合物饮料,术前2~4 h仍可摄入适量碳水化合物饮料[133]

推荐意见16:术前1晚和术前2~4 h建议补充适量的碳水化合物饮料(1B)。

1.5.7 术前预防性抗菌药物的使用

在皮肤切开前0.5~1 h内或麻醉开始时静脉给药。抗菌药物的有效覆盖时间应包括整个手术过程。手术时间>3 h或超过所用药物半衰期的2倍以上,或成人出血量>1 500 mL,术中应追加1次。过度延长用药时间,如预防用药时间>48 h,耐药菌感染机会增加。肝切除术可能的污染菌是革兰阴性杆菌、厌氧菌(如脆弱拟杆菌),可选择抗菌药物包括:第一、第二代头孢菌素或头孢曲松和(或)甲硝唑,或头霉素类。有循证医学证据的第一代头孢菌素主要为头孢唑啉,第二代头孢菌素主要为头孢呋辛。如果病人对β-内酰胺类抗菌药物过敏,可用克林霉素+氨基糖苷类,或氨基糖苷类+甲硝唑。

推荐意见17:预防性使用抗菌药物应在皮肤切开前0.5~1 h内或麻醉开始时静脉给药,抗菌药物的有效覆盖时间应包括整个手术过程。手术时间>3 h或超过所用药物半衰期的2倍以上,或成人术中出血量>1 500 mL,术中应追加1次(1B)。

1.5.8 术前抗血栓药物管理

肝切除术作为高出血风险的外科治疗,术前应积极做好抗血栓药物管理。抗血栓治疗的核心策略包含抗PLT治疗和抗凝治疗。常用的抗PLT药物及其特性见表2[134-135]。目前对于围手术期抗PLT药物管理尚缺乏充足的循证医学证据。对于使用抗PLT药物治疗的动脉粥样硬化性心血管疾病、缺血性脑卒中、短暂性脑缺血及周围动脉疾病的病人,术前应根据缺血的发生风险,决定是否停药或行桥接治疗。对于低缺血风险病人可直接停用抗PLT药物;对于中缺血风险病人,术前需停用阿司匹林或P2Y12受体抑制剂,但尽量缩短停药时间,通常术前氯吡格雷需停药5 d,替格瑞洛需停药3~5 d,中断阿司匹林治疗的时间≤7 d;目前尚无确切证据支持在外科手术前应用短效抗血小板药物行桥接治疗。对于高缺血风险病人,经多学科会诊,确需停用阿司匹林和P2Y12受体抑制剂,可考虑静脉使用抗PLT药物(替罗非班或依替巴肽)桥接治疗,该桥接必须在ICU且监测充分的条件下进行。术后根据病人出血情况,尽早恢复使用抗PLT药物。

常用的口服抗凝药物包括维生素K拮抗剂(华法林)和新型口服抗凝剂(novel oral anticoagulants,NOAC)[136-137]。NOAC包括凝血因子Xa抑制剂(利伐沙班、阿哌沙班、艾多沙班)以及凝血因子Ⅱa抑制剂(达比加群)。长期口服华法林病人,若凝血国际标准化比值(international normalized ratio,INR)为1.5~1.9,应在肝切除术前3~4 d停药;若INR为2.0~3.0,肝切除术前需停用5 d;若INR>3.0,应在术前≥5 d停药[138]。对于低风险静脉血栓栓塞(venous thromboembolism,VTE)病人,术前无需行桥接治疗,停药后术前INR可恢复到接近正常范围(INR<1.5);对于有中度VTE风险的病人,术前可每12 h皮下注射预防剂量5 000 IU肝素或预防剂量的低分子肝素;VTE风险高危病人,当INR下降时(降至目标范围以下),开始全剂量普通肝素或低分子肝素治疗,应用普通肝素者至术前6 h停药,或皮下注射低分子肝素至术前24 h停用[139]。术后恢复抗凝的时间,应根据病人的出血与血栓形成的相对风险确定。长期服用阿哌沙班、利伐沙班或艾多沙班,术前应停药2 d,相当于最后1次给药与手术间隔60~68 h。达比加群的用药需根据肾功能决定,肌酐清除率(creatinine clearance,CrCl)≥50 mL/min的病人停药策略与沙班类药物相同,30 mL/min≤CrCl<50 mL/min的病人在肝切除术前停用达比加群4 d[140]

推荐意见18:长期使用抗PLT药物,合并心脏高缺血风险的病人,肝切除术前停用阿司匹林和P2Y12受体抑制剂,需经多学科会诊后,静脉使用抗PLT药物桥接治疗;长期口服华法林病人,根据INR情况决定停药时间,对于中、高风险VTE病人,术前应采用低分子肝素桥接治疗;长期口服抗凝药病人不需要进行桥接治疗,在CrCl≥50 mL/min情况下,术前需停药2 d(2B)。

1.5.9 胃十二指肠黏膜病变的评估和处理

门静脉高压性胃病是继发于门静脉高压症的胃肠道黏膜血管病变[141]。对于无症状门静脉高压性胃病病人,可给予非选择性β受体阻滞剂(non-selective β-blockers,NSBB)降低门静脉压力[142]

食管胃底静脉曲张(gastroesophageal varices,GOV)是发生食管胃底静脉曲张破裂出血(esophagogas⁃tric variceal hemorrhage,EGVB)的解剖基础[143]。胃镜是诊断GOV的金标准[144],增强CT检查也可用于评估GOV[145],同时可通过对图像数据后处理显示门静脉属支,对经颈静脉肝内门腔静脉分流术(transjugular intrahepatic portosystemic shunt,TIPS)具有指导意义。

中、重度GOV和出血风险较大的轻度GOV病人使用NSBB治疗[146],例如卡维地洛,可有效降低肝血管张力和阻力[147]。多项Meta分析[148-149]结果显示,卡维地洛可降低肝硬化食管静脉曲张病人的全因死亡率和首次食管静脉曲张破裂出血风险。或可行内镜下曲张静脉套扎术(endoscopic esophageal varix ligation,EVL),但EVL并发症的发生风险较高[148]。最新的一项前瞻性研究[150]表明,在Child-Pugh评分B、C级肝硬化合并高危GOV的病人中,卡维地洛联合EVL用于一级预防EGVB的效果优于单独应用卡维地洛或EVL。肝切除术前发生EGVB的病人在维持血流动力学稳定的前提下,可采用EVL、内镜下曲张静脉硬化剂注射、TIPS等措施治疗EGVB[151-152]

推荐意见19:术前建议对门静脉高压症病人行胃镜检查明确GOV程度;中、重度GOV伴出血风险较大病人可采用NSBB联合EVL预防EGVB(2B)。

1.5.10 增加剩余肝体积

术前剩余肝体积不足或者处于临界状态的病人建议采取促进剩余肝体积增生的治疗手段,例如门静脉栓塞(portal vein embolization,PVE)、两期肝切除术(two-staged hepatectomy,TSH)和门静脉结扎术(portal vein ligation,PVL)、肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)+PVE、放射栓塞术(transarterial radioembolization,RE)、肝脏离断和门静脉结扎的二步肝切除术(associating liver partition and portal vein ligation for staged hepa⁃tectomy,ALPPS)、PVE联合肝静脉栓塞术。尽管这些手段作为术前促进剩余肝体积增生的策略取得了成功,但其局限性依旧存在[153]。多项研究证实,ALPPS与其他手术方式比较,其诱导剩余肝体积增生更快,肿瘤切除率更高,但ALPPS后并发症发生率和病死率也更高。在总体生存和R0切缘率方面,几种手术方式比较,无明显统计学差异[154-155]。多项RCT研究[156-157]结果显示,ALPPS在剩余肝体积诱导增生和肿瘤切除率显著优于门静脉栓塞二步肝切除术,而两者手术安全性比较,差异无统计学意义。Tustumi等[158]的Meta分析结果显示,TACE+PVE与PVL/PVE安全性相似,ALPPS在PHLF、并发症发生和死亡率方面具有较高风险,RE与TACE+PVE具有相似的切除率和总生存期,但并发症发生率更高。

ALPPS为无法切除的肝肿瘤病人提供了一定的切除机会,是现有手术技术的补充。但由于其较高的并发症发生率和死亡率,以及相对较高的复发率应谨慎实施。对于剩余肝体积不足病人的最佳选择,核心问题是更高的肿瘤可切除性是否能够转化为生存率的提高,这还需更大样本的多中心研究验证[159]

推荐意见20:ALPPS为无法切除的肝肿瘤病人提供了一定的切除机会,其诱导剩余肝体积增生更快,肿瘤切除率更高。但因其并发症发生率、死亡率和肿瘤复发率较高,需严格筛选病人并由经验丰富的团队实施(2B)。

1.5.11 预康复

两项针对肝切除术的预康复研究(一项前瞻性研究和一项倾向评分匹配研究)发现,通过包括物理治疗师、营养师、病例管理人员以及外科和麻醉的预康复管理,能够减少术后并发症的发生以及缩短住院时间[160-161]。Walcott-Sapp等[162]在关于大范围肝切除术前预康复的研究中建议术前应进行营养评估和精神状态的改善,包括实施营养干预和运动训练在内的预康复训练计划。Doherty等[163]在关于脂肪肝病人肝切除的研究中提出术前4~6周进行包括饮食干预在内的减少肝内脂肪的预康复,能够改善肝内脂肪变程度和术后的结局。一项关于老年病人(>70岁)接受肝胆胰手术快速康复的研究[164]中发现,老龄化常与肌肉减少和营养不良相关,体弱的老年病人可能在预康复计划中受益最多。最近一项对72例拟接受包括大范围肝切除在内的病人进行术前2~3周的多模式预康复训练(包括运动、营养咨询和心理支持)研究[165]发现,以门诊为基础的一站式多学科预康复训练是安全、有效的,病人的活动能力、营养状况以及蛋白质摄入量均有所提高。然而,两项针对肝胆胰手术病人预康复的Meta分析结果显示,预康复训练减少术后并发症的发生、缩短住院时间尚缺乏有力证据[166-167]。多项针对腹部大手术的Meta分析[168-169]结果显示,接受预康复训练的病人术后并发症减少,但纳入研究的异质性较高,证据质量较低。

推荐意见21:对于老年、营养不良或超重、大范围肝切除病人在肝切除术前可进行预康复训练(2C)。

1.6 术前麻醉风险评估

肝切除术病人常合并多器官系统的病理生理改变,术前应针对心、肺、肾等多脏器功能进行评估。合并心脏疾病是肝切除术后严重心血管不良事件的独立危险因素,可采用纽约心脏学会分级以及代谢当量评估病人心功能,结合专科检查明确心脏疾病的严重程度[170-172]。急性呼吸系统感染以及术前低血氧饱和度是术后肺部并发症(postoperative pulmon⁃ary complications,PPC)的独立危险因素[173-174]。建议术前行肺功能检测,择期手术推迟到呼吸系统感染治愈1~2周后进行。临床研究Meta分析显示,慢性肾脏病会导致肝切除术后并发症发生率增高[175-176]。与血肌酐(SCr)相比,肾小球滤过率预测术后发生急性肾功能衰竭的可靠性更高[177-178]。一项系统性综述指出,衰弱是预测肝切除术后并发症发生的危险因素,因此,评估老年病人衰弱状态可用于识别高危病人[179]。美国麻醉医师协会(American Society of Anesthesiologists,ASA)分级是广泛用于评估病人基础身体状况与手术风险的指标,根据不同器官系统的功能状态进行总体评分。临床研究表明随着ASA分级增加,肝切除术后并发症发生率也逐渐升高[180]

推荐意见22:术前行心、肺、肾等重要器官系统功能评估、衰弱评估,确定ASA分级,可预判术后并发症发生风险(1B)。

1.7 血液制品的使用

接受肝切除术的部分病人常合并贫血、PLT低下、凝血功能异常等情况,为提高手术安全性,应于术前常规评估病人是否需要使用血液制品[181]。如术前血红蛋白(Hb)<100 g/L,建议输注红细胞(RBC)以纠正贫血[182]。但相关研究结果显示,肝切除术围手术期Hb<70 g/L时,给予输注RBC至Hb上升至70~90 g/L,可以获得与Hb<100 g/L即启动输注RBC同样的效果[183]。如PLT<50×109/L,建议在术前输注PLT的同时口服升PLT药物,至PLT升至50×109/L以上,再经严格评估后实施手术[183]。对于凝血功能异常的病人,需输注血浆和(或)凝血物质以改善凝血功能。此外,对于复杂肝切除等预计术中出血量多、血源紧张的情况,经严格评估后可采用术前储血、术中回输去白红细胞自体血的方案保证术中供血[184]

推荐意见23:肝切除术前应评估病人是否需要使用血液制品,严格把握血液制品使用指征(2C)。

1.8 多学科诊疗模式的应用

由于肝脏解剖结构复杂、合并基础肝病等原因,导致肝切除术围手术期具有较高风险和并发症发生率[185]。因此,建议有条件单位在复杂肝切除术前组织多学科综合讨论,参与专科包括但不限于外科、影像、麻醉、介入、内科、病理、营养等专科医师,通过多学科全面评估肝脏解剖、肿瘤负荷(肿瘤数量、体积、是否合并血管侵犯和远处转移)、肝功能分级以及体能状态评分、全身器官功能等情况,明确手术指征[186]。多学科诊疗模式的应用,有助于制订科学的手术规划和合理的围手术期并发症防治措施,确保围手术期顺利恢复和治疗效果[187]

推荐意见24:复杂肝切除术前应组织多学科讨论,制订科学的手术规划和合理的围手术期并发症防治措施(1C)。

2 肝切除术的术中管理

2.1 手术中的麻醉管理

2.1.1 术中监测

常规监测病人心电图、无创血压、脉搏血氧饱和度、呼气末CO2、尿量,有条件者,可进行潮气量、呼吸力学、氧浓度及吸入麻醉药浓度等监测[188]。手术时间长或大出血高风险者,行外周动脉穿刺置管实时监测血压、实时动脉血气分析;中心静脉穿刺置管监测中心静脉压力进行容量管理。有研究指出术中体温管理可以避免术中低体温,改善病人预后[189]。一项系统性综述推荐麻醉深度监测指导镇静药物使用以促进术后快速恢复[190]。其他特殊监测需根据病人的合并症和肝切除范围进行选择,包括肌松监测[191]、漂浮导管与心排量监测[192]、经食管超声心动图、凝血功能、组织氧饱和度等。

推荐意见25:术中监测项目除常规监测外,还包括有创动脉压、中心静脉压及体温监测,有条件者可行麻醉深度监测、肌松监测等。根据病人的合并症和手术计划进行针对性特殊监测(1A)。

2.1.2 术中输液及循环管理

术中循环管理应根据病人的合并症、手术方式(腹腔镜或开腹)、肝切除范围和出血风险等进行充分准备、动态监测及针对性调整,以维持术中循环稳定及组织器官灌注。根据预计的术中出血量,可以采用相应的血液保护技术,包括自体血回收、急性血液稀释等。前瞻性RCT研究结果显示,急性等容血液稀释技术可以减少大范围肝切除术病人异体输血量[193]。临床研究结果证实目标导向液体治疗策略可安全用于肝切除术并降低术后并发症发生率[194]。该策略是在适当补液的前提下,配合血管活性药物维持循环稳定,避免液体过负荷。目标导向液体治疗需在心排量监测下,以动态指标(如每搏量变异率)为导向,评估和预测容量反应性,维持最佳前负荷[195-196]。循环管理应在监测压力的基础上,结合氧输送及代谢相关参数(如血乳酸、中心静脉或混合静脉血氧饱和度)以及尿量变化,指导血管活性药物的使用[197]

推荐意见26:术中采用目标导向液体治疗策略,合理使用血管活性药物,维持循环稳定及组织器官灌注(1A)。

2.1.3 麻醉方法、麻醉药物与抗应激管理

肝切除术麻醉方式以全身麻醉为主,临床研究表明复合区域阻滞可减少术中阿片类药物用量,促进术后快速康复[198]。麻醉诱导和维持应选择代谢快、蓄积少以及对肝血流影响小的药物。优先选择肝外代谢的麻醉药物,如顺式阿曲库铵、瑞芬太尼。低蛋白血症和肝功能受损病人应控制药物剂量。吸入性麻醉药氟烷会损害肝脏功能,应避免使用;七氟烷、地氟烷等体内代谢率低,可安全选用。肝切除术要求良好的肌松效果,但一项系统综述指出深度肌松并不能改善病人预后[199]。肌松监测可以指导肌松药使用以及术后肌松拮抗。

肝切除术中应激可能诱发全身炎症反应综合征。常用抗炎药物有糖皮质激素和广谱水解酶抑制剂。RCT结果证实糖皮质激素可减轻手术应激、促进恢复[200],但也会增加切口愈合不良风险,需谨慎使用。Meta分析[201]表明,广谱水解酶抑制剂可以减少肝切除术病人的应激反应。联合硬膜外镇痛技术可满足手术无痛的需求并抑制手术创伤所致的应激反应[202]

推荐意见27:以全身麻醉为主,可复合区域阻滞;选择短效、肝外代谢以及对肝血流影响小的药物;使用广谱水解酶抑制剂减少手术应激(1B)。

2.1.4 低中心静脉压(low central venous pressure,LCVP)的控制

RCT研究结果显示,术中采用麻醉管理策略(如加深麻醉、联合硬膜外阻滞麻醉)、限制性输液、药物(血管活性药物如硝酸甘油、利尿剂如呋塞米等)、反Trendelenburg体位等方法将中心静脉压控制在0~5 cmH2O(1 cmH2O=0.098 kPa)范围内,即LCVP[203-204],可减少术中出血量,为术者提供良好手术视野[205]

然而,LCVP的实施可能造成气体栓塞及组织器官灌注不足。术中应监测呼气末CO2,若术中呼气末CO2陡然下降,尤其是伴有血流动力学的改变,应高度怀疑发生气体栓塞,必要时采用经食管超声心动图对气体栓塞进行监测。空气栓塞的防治措施包括降低气腹压力[206]、用湿纱布压迫创面、改头低左侧卧位、使用血管活性药物维持循环稳定、通过颈内静脉导管抽吸气体等。此外,有研究[207-208]指出:肾功能不全是LCVP并发症之一,但是否由LCVP导致值得进一步研究。实施LCVP时,应保证肾脏灌注[维持收缩压>90 mmHg(1 mmHg=0.133 kPa)或平均动脉压>60 mmHg]且尿量≥25 mL/h,可在肝切除后立即扩容并输注小剂量多巴胺。

推荐意见28:术中将中心静脉压控制在0~5 cmH2O可以减少肝切除术中的出血量(1A)。

2.1.5 术中体温管理

临床试验结果显示,腹部手术中避免低体温可降低外科感染发生率、缩短住院时间[209]。一项包含54项研究的Meta分析[210]结果显示,主动体表加温可以减少伤口感染、减少输血、避免术后寒战并提高病人满意度。术中体温管理原则为重视围手术期体温监测(鼻咽或者直肠),积极预防低体温(<36 ℃)[211]。系统性综述以及临床研究指出,围手术期应采取保温措施,联合多种方法预防术中低体温,包括维持手术室的环境温度;使用暖风机、加温毯、液体加温装置等主动式升温措施;腹腔冲洗液加温后使用,重视非手术区和四肢的皮肤覆盖、尽量减少伤口和体腔暴露以避免体温丢失[212]

推荐意见29:术中采用多模式体温保护策略,维持核心温度≥36 ℃(1A)。

2.1.6 术中肺保护策略

肺保护性通气策略(lung-protective ventilation strategy,LPVS)主要包括小潮气量通气、呼气末正压通气(positive end-expiratory pressure,PEEP)和间断肺复张。目前多推荐使用6~8 mL/kg潮气量[213]来改善肺功能和降低PPC发生率,对于ARDS病人建议使用≤6 mL/kg。然而长时间的小潮气量通气可能引起CO2蓄积和肺不张。2019年欧美多中心专家小组建议采取间断容量控制机械通气复张法以达到充分肺复张,包括肺活量法、压力控制法和容量控制法,其中肺活量法最常用,即持续35~50 cmH2O正压通气20~40 s[214];个体化PEEP可以改善肺功能,尤其对于肥胖病人、腹腔镜手术、俯卧位或头低位病人,初始设定值为5 cmH2O。有RCT研究证实6~8 mL/kg小潮气量和6~10 cmH2O PEEP能有效改善病人术后肺不张、降低PPC发生率[215-216],改善氧合、肺顺应性和呼气末肺容积[217],超过12 cmH2O PEEP对于改善PPC无意义,反而可能增加血流动力学波动,导致术中低血压[218]。一项RCT结果发现6~8 mL/kg小潮气量通气联合1次/30 min手法肺复张策略不仅降低了术后PPC,同时明显减少了腹腔镜肝切除术中出血量[219]

推荐意见30:术中应采用小潮气量(6~8 mL/kg)和个体化PEEP(6~10 cmH2O)联合间断肺复张的LPVS(1B)。

2.1.7 术中脑保护策略

围手术期神经功能障碍是老年病人麻醉和手术后常见并发症,包括术后谵妄(postoperative delirium,POD)和术后认知功能障碍(postoperative cognitive dysfunction,POCD)。研究[220-221]证明术中采用脑电双频指数(bispectral index,BIS)监测并维持麻醉深度(40~60)有助于减少POD和POCD,无创脑氧饱和度监测并维持在50%以上可以明显降低POCD[222]。然而也有研究报道指出BIS监测与术后POD和POCD相关性不大[223],脑氧饱和度监测下的循环管理可以减少POCD,但是不能减少POD发生。一项RCT研究结果显示,术中低血压与老年病人POCD无明显关系,但围手术期低血压可能引起大脑低灌注导致缺血缺氧,尤其容易发生于老年病人中,老年病人围手术期血压波动应控制在术前基线20%以内。研究指出,神经阻滞[224]、硬膜外阻滞复合全身麻醉[225]较全身麻醉明显降低了POD发生率,有助于脑功能恢复。Su等[226]的研究结果显示,小剂量右美托咪定在ICU病人[0.1 μg/(kg·h)]和非心脏手术[0.5 μg/(kg·h)]中应用可以有效降低POD发生率,并提高病人术后3年生存情况和认知功能。对患有术前认知功能障碍病人行非心脏手术的研究[227]中提示,急性疼痛是导致POD的重要因素,应加强术后疼痛管理,降低POD的发生。

推荐意见31:术中尤其是针对老年病人,可采用脑电BIS监测并维持适宜麻醉深度、无创脑氧监测及目标导向血压管理等脑保护策略(1B)。

2.1.8 术中血糖、电解质及酸碱平衡调控

肝病病人糖原储备少,长时间手术易发生低血糖,而手术、麻醉等应激状态可能导致血糖增加,控制血糖平衡有利于肝切除术后病人恢复。两项RCT研究[228-229]结果显示,肝胆胰手术中,将血糖控制在较低水平(4.4~6.1 mmol/L或<6.7 mmol/L),病人术后感染、胰瘘发生率均显著降低,且生存率明显提高。多项回顾性研究结果显示,肝移植、普通外科手术、血管手术中,血糖水平>11.1 mmol/L与病人术后发生感染、急性肾损伤、心血管并发症和死亡率密切相关[230]。肝病病人由于肝功能障碍、术前肠道准备、禁食、禁饮等情况可能导致低钠血症;术中反复肝门阻断、出血及大量库存血输注也可能引起高钾血症和低钙血症;反复阻断肝门开放后大量酸性物质入血,循环功能不稳定导致组织灌注不足,都可能引起酸碱失衡。

血气分析作为临床常用监测设备,术中具有指导输血,纠正酸碱失衡、电解质紊乱,监控血糖,评估呼吸功能,判断组织氧供和病人预后的重要作用。在肝切除术中应常规行血气分析,对血糖、电解质和酸碱平衡进行监测并调控。

推荐意见32:术中应常规行血气分析并指导血糖、电解质和酸碱平衡有效管理(1B)。

2.1.9 术中凝血功能监测及输血要求

凝血功能监测包括基础的标准实验室检测、高级的血栓弹力图(thrombelastogram,TEG)和旋转血栓弹力图(rotational thromboelastometry,ROTEM)检测。多项指南推荐术中采用TEG和ROTEM检测可以诊断围手术期凝血功能障碍[231-232],适用于围手术期血液管理指导,在肝移植手术中进行凝血监测可有效减少术中出血量和血液制品的输注[233]。多项RCT研究及输血指南指出术中应采取限制性输血策略,建议输血阈值为70~80 g/L,其中有血液或肿瘤疾病的病人输血阈值为70 g/L,心脏手术的病人为75 g/L,骨科手术或有心血管疾病的病人为80 g/L[234-235]。一项肝切除术中输血回顾性研究结果显示,对于无心脏疾病病人,Hb 70 g/L;有心脏疾病病人,Hb 80 g/L时应输注RBC。

当术中出血量>500 mL应考虑输注氨甲环酸,行TEG监测并进行指导性血液成分补充(目标导向凝血治疗);当大量出血导致失血性休克时,为了防治稀释性凝血病应采取大量输血方案:新鲜冰冻血浆、PLT、RBC(1∶1∶1)[236],同时监测TEG,并及时补充纤维蛋白原,每输入库存血6 U时,需补充1 g氯化钙或3 g葡萄糖酸钙。

推荐意见33:常规使用标准实验室检查监测凝血功能;对于有出血性病史或服用特殊药物影响凝血功能的病人,建议行高级凝血功能监测并进行目标导向凝血治疗;术中采用限制性输血策略,Hb 70 g/L,建议积极输注RBC,Hb在70~100 g/L,根据病人心肺代偿功能决定是否输注RBC(2B)。

2.2 损伤与感染控制

合并肝脏基础疾病可影响病人抵抗力,同时肝切除手术过程复杂、手术时间相对较长、创伤较大,需在肝切除术中高度重视损伤和炎症反应的控制[237]。相关研究结果显示,手术时间>3 h可导致术后感染发生率增加1倍,>8 h导致术后感染风险增加6倍[238]。一项倾向性评分匹配研究[180]表明,术中出血可增加肺部等器官感染发生率,同时导致肝脏及消化道缺血,引起肠道菌群移位进而诱发感染。因此,在彻底清除目标病灶同时,确保剩余肝脏组织解剖结构完整和功能性肝脏体积最大化,尽量减少术中出血和胆汁漏造成腹腔污染,可最大限度降低手术创伤和感染[239]

推荐意见34:术中应精细操作,在彻底清除病灶的同时最大限度保留功能性肝体积、减少术中出血和缺血再灌注损伤,有助于控制手术造成的损伤和感染(2C)。

2.3 手术规划和术中操作

2.3.1 手术切除范围和入路

Shi等[240]的研究结果显示,在孤立性肝细胞癌病人中行宽切缘(≥2 cm)切除显著降低术后复发率并提高生存率,而窄切缘组(≤1 cm)病人的肿瘤复发率更高,生存期更短,故更推荐宽切缘的肝切除手术方式。系统综述与Meta分析[241-242]结果显示,虽然解剖性肝切除(anatomic resection,AR)与非解剖性肝切除(non-anatomic resection,NAR)的术中出血量、住院时间以及并发症发生情况比较,差异均无统计学意义,但AR在增加肿瘤切除边缘宽度、降低复发风险上展现出明显优势。这表明,从长期肿瘤控制视角来看,AR具备更显著的临床价值。Witowski等[243]通过一项前瞻性观察性研究发现三维打印模型和术中超声信息的提供使68%的病人改变了手术计划,其中术中超声在47%的病例中检测到CT和三维打印模型未检测到的额外病变。Alomari等[244]通过一项RCT研究结果显示,在腹腔镜肝切除术中使用ICG荧光影像确定AR的边界可以提高手术的精确度和成功率。

Meta分析[245]提示,前入路在减少术中出血量和输血需求方面表现更好,并且与传统入路相比,提高了无病生存期和总生存率。Rahbari等[246]的一项RCT研究结果显示,前入路可能减少术中肿瘤细胞的血行播散,但与传统入路相比,生存率和无病生存期均无显著差异。

推荐意见35:肝切除范围应达到R0切除标准并尽量保留足够切缘,同时尽可能保证剩余肝脏出入肝血流通道的完整性。建议应用术中超声或荧光引导,以利于更精准确定解剖结构部位和切除边界(1A)。

2.3.2 肝血流的阻断

Lee等[247]通过两项RCT研究结果显示,全入肝血流阻断(Pringle)法较非Pringle 法在原发性肝癌病人中具有更好的总生存率,尤其是对于肝硬化病人,单次阻断时间尽量控制在16~30 min。但也有Meta分析[248-249]表明,Pringle法并未降低1、3、5年总生存率或无复发生存率,且间歇性Pringle法在减少术中出血和输血需求方面并无显著优势。Fu等[250]的一项RCT研究结果显示,接受半肝血流阻断或主门静脉血流阻断的病人比采用Pringle法的病人在术后肝功能早期恢复方面反应更好。有研究[251-252]表明,与Pringle法相比,半肝血流阻断法在减少术中出血量方面虽无明显优势,但可减少肝切除术后肝损伤。

一项RCT研究结果[253]提示,肝下下腔静脉阻断法可减少术中血流动力学不稳定性,但肺栓塞发生率增加。但也有Meta分析[254]认为肝下下腔静脉阻断并不增加术后肺栓塞的发生率。

Makino等[255]的研究结果显示,术中行选择性门静脉阻断的肝细胞癌病人在术后的无病生存期方面优于全门静脉阻断,特别是在肿瘤直径<5 cm的病人中,选择性门静脉阻断显著延长无病生存期。

推荐意见36:肝切除手术应常规预置肝血流阻断带,阻断方法需综合考虑切除范围、手术时间和肝脏功能等因素进行决定(1B)。

2.3.3 肝实质离断方法

肝实质离断除传统的钳夹法外,还可以使用高效的切割和止血器械,如超声刀、百克钳、单/双极电凝,彭氏多功能手术解剖器、超声吸引刀、Ligasure、微波刀、水刀、射频止血刀和切割闭合器等,以实现精确切割和即时止血[256-257]。Kamarajah等[258]的一项RCT对比近10种肝实质切断技术在肝切除术中的应用,结果表明,双极电凝在减少术中出血量方面最有优势,并且手术时间最短。而超声刀则在总体和降低并发症发生率方面表现更佳。Rahbari等[259]的一项RCT研究比较水刀和超声刀在腹腔镜肝切除术中的效果,结果显示,两种技术在术中出血量、手术时间和术后住院时间方面比较,差异均无统计学意义,但水刀的设备成本更低。Efanov等[257]的前瞻性随机单中心研究提示,水刀和超声吸引刀在腹腔镜肝切除术中对肝实质的切断具有相似的有效性和安全性。

推荐意见37:根据肝脏质地、病变特点、手术方式以及术者熟练程度等可综合考量选择高效的肝实质离断方法(1B)。

2.3.4 脉管重建技术

Meta分析与RCT研究结果显示,肝动脉切除与重建可能增加术后并发症发生率和死亡率,除非明确肿瘤侵犯肝动脉,否则不建议常规进行。部分处于晚期的恶性肿瘤病人,仍有机会通过动脉重建实现R0切除[259-260]

对于门静脉癌栓未侵袭至门静脉主干(程氏分型Ⅰ型和Ⅱ型)的肝细胞癌病人,局部切除和部分肝切除术安全、可行,而对于门静脉癌栓扩展至门静脉主干(程氏分型Ⅲ型)的病人,建议行联合门静脉切除和重建[260-261]。有两项Meta分析结果显示,肝切除中联合门静脉切除和重建能够改善病人预后,但与非切除组相比,手术并发症发生率和死亡率均较高。Durairaj等[262]的一项RCT研究结果显示,术中使用受体原生门静脉或聚四氟乙烯移植物进行肝静脉重建在早期通畅率和90 d内的全因死亡率方面无显著差异,且两者均为有效的重建材料。但肝静脉血栓形成是影响术后生存的独立危险因素。

Feng等[263]的Meta分析比较不同手术技术对肝细胞癌合并胆管癌栓病人肝切除术后胆管重建的影响,结果显示,胆管切除重建组病人的5年总生存率和无病生存率均具有显著优势,但术后并发症发生率较高。同时提示对于需要胆道重建的肝切除术病人,使用Roux-en-Y肝管空肠吻合术,可降低胆汁漏发生率,提高术后生命质量。

推荐意见38:当肿瘤累及门静脉主干时可行门静脉切除与重建,但肝动脉切除重建需谨慎施行。对于需要胆道重建的肝切除病人,应采用Roux⁃en⁃Y肝管空肠吻合术(2B)。

2.3.5 引流管的放置

Dezfouli等[264]的Meta分析评估了肝切除术后预防性放置引流管的价值,结果显示,预防性放置腹腔引流管能显著降低术后并发症发生率。Anweier等[265]通过Meta分析发现,常规放置腹腔引流管与非常规放置腹腔引流管相比,常规放置组显著降低了术后并发症总体发生率和胆汁漏发生率,同时减少了住院时间。Fuster等[266]的一项RCT研究评估了腹腔引流管在肝癌切除术中的效果,结果显示,引流管组在减少腹水和缩短住院时间方面有显著优势,尤其是在有门静脉高压症的肝硬化病人中优势更加明显。Gurusamy等[267]的一项Meta分析研究评估了常规放置腹腔引流管在肝切除术后的效果,结果显示,引流组术后并发症发生率显著降低,尤其是在术后出血和胆汁漏方面,常规放置腹腔引流管更利于肝切除术后的监测和治疗。Inoue等[268]通过一项倾向评分匹配研究,提出基于术后引流液胆红素浓度和术中情况的引流管管理标准,发现合理管理引流管可以减少术后并发症的发生和缩短住院时间。

推荐意见39:术中应常规放置腹腔引流管,有助于监测及降低术后出血和胆汁漏等并发症发生率(1B)。

3 肝切除术的术后管理

3.1 术后早期的监护和处理

3.1.1 血流动力学维护

一项回顾性分析[269]评估术后平均动脉压对肝切除术后手术并发症的影响,发现肝切除术后第1天和(或)第2天平均动脉压<81.1 mmHg是术后并发症的独立预测因子。另有一项多中心、前瞻性、随机研究发现:基于动脉血压变异、连续心脏指数的围手术期血流动力学治疗减少了大型腹部手术的术后并发症,该组病人术后早期血压平均值为(90.8±19.0)mmHg[270]。目前尚无相关临床研究推荐肝切除术后选用何种升压药更优。去甲肾上腺素主要作用于外周阻力血管上的α受体,能够收缩动静脉血管,减少分流,使更多的血液回流至重要脏器,纠正低血压与缺血缺氧状态,改善组织器官灌注,从而增强肝代谢乳酸能力,减少乳酸形成[271]。相关研究还发现,与多巴胺相比,去甲肾上腺素显著减少了心律失常事件,并且在心源性休克病人中,去甲肾上腺素降低了病人28 d死亡率[272]

推荐意见40:建议维持平均动脉压>80 mmHg以维持肝脏及组织灌注,必要时优先使用去甲肾上腺素(2C)。

3.1.2 呼吸管理

目前尚缺乏肝切除术后病人呼吸管理策略的直接证据。一项涉及709例腹部手术病人的Meta分析[273]结果显示,术后早期持续气道正压通气可降低肺不张发生率、肺炎发生率及再次插管率,但在术后死亡率、严重低氧血症或需要侵入性通气方面作用尚不明确。而另一项涉及6 108例上腹部手术病人的Meta分析[274]结果显示,术后常规提供预防性无创正压通气(noninvasive positive pressure ventilation,NIPPV)可能无法有效减少PPC。2005年一项NIPPV研究因疗效显著而提前结束,在研究过程中发现与接受标准氧疗的病人相比,NIPPV组病人的再插管发生率降低了90%,肺炎风险也显著降低[275]。另一项RCT研究[276]也有类似发现。然而,另一项临床研究将220例腹部手术术后病人随机分配接受高流量鼻导管氧疗或标准氧疗,结果显示,与标准氧疗相比,拔管后早期预防性应用高流量鼻导管氧疗并未改善肺部结局[277]。2020年中华医学会麻醉学分会制订《围手术期肺保护性通气策略临床应用专家共识》,针对上腹部和胸部等大手术病人的术后呼吸管理,建议给予小潮气量通气(6~8 mL/kg)以及最佳PEEP设定。一项Meta分析[278]结果显示,慢性阻塞性肺疾病病人在有创机械通气拔管后序贯NIPPV能够降低死亡率。

推荐意见41:术后早期未拔管时建议给予小潮气量及最佳PEEP通气策略,同时清理呼吸道分泌物避免肺不张。慢性阻塞性肺疾病病人拔管后建议给予NIPPV作为序贯治疗(2C)。

3.1.3 术后镇痛策略

多项临床实践指南推荐围手术期采用多模式镇痛策略改善病人疼痛管理及降低阿片类药物的不良反应[279-280]。阿片类药物是治疗中-重度急慢性疼痛的最常用药物,但是会增加其药物相关不良事件风险,主要用于手术切口大的病人术后镇痛,且应从小剂量开始应用;非甾体抗炎药(nonster-oidal anti-inflammatory drugs,NSAID)是治疗轻到中度疼痛的有效药物。一项大型数据分析[281]结果显示,NSAID与阿片类药物合用,可以增强镇痛效果,减少阿片类药物使用剂量,降低其相关不良反应,减少围手术期并发症。目前应用最广泛的镇痛措施包括切口局部浸润、区域神经阻滞和病人自控镇痛[282]。神经阻滞包括单次椎旁神经阻滞和腹横肌平面阻滞,单次椎旁神经采用0.375%~0.5%罗哌卡因15~20 mL[283],腹横肌平面阻滞采用0.2%~0.25%罗哌卡因(总量≤3 mg/kg)[284]。病人自控镇痛是目前最常用和最理想的术后镇痛方法,主要包括静脉自控镇痛和硬膜外自控镇痛。

推荐意见42:术后可采用药物镇痛、神经阻滞或硬膜外阻滞、病人自控镇痛等多种方法联合使用的多模式镇痛策略(1B)。

3.1.4 恶心、呕吐的预防

术后恶心、呕吐(postoperative nausea and vomiting,PONV)是常见并发症,在普通人群中发生率为30%,高危人群中高达80%。PONV危险因素包括女性、吸入麻醉、腹腔镜手术、PONV或晕动病史、不吸烟病人、手术时间以及阿片类药物使用。有两项Meta分析结果显示,丙泊酚静脉麻醉可以降低PONV发生率[285-286]。多项回顾性Meta分析和RCT研究证明全身麻醉复合硬膜外阻滞[287-288]、对乙酰氨基酚、NSAID、选择性α2受体拮抗剂(右美托咪定)等药物使用[289-290]可减少阿片类药物用量,显著降低PONV发生率。5-羟色胺受体拮抗剂具有预防PONV作用,其中以第二代代表药物帕洛诺司琼(0.075 mg,静脉注射)、雷莫司琼(0.3 mg,静脉注射)预防效果最佳[291]。糖皮质激素、NK-1受体拮抗剂阿瑞匹坦、多巴胺受体拮抗剂(氟哌利多)可以作为PONV预防药物,多种药物联合使用效果更佳[292-293]。术前评估有1~2项PONV风险病人,可以给予1~2项干预措施,大于2项风险者给予3~4项干预措施以减少PONV发生。

推荐意见43:术前应进行PONV危险因素评估,术中可采用静脉全麻复合硬膜外阻滞、非阿片类镇静镇痛药物并联合使用5-羟色胺受体拮抗剂、糖皮质激素等预防性药物,降低PONV发生(1A)。

3.1.5 胃十二指肠黏膜应激性病变(stress related mucosal disease,SRMD)的预防与治疗

肝切除术造成的手术创伤会导致病人应激状态,结合病人慢性肝病背景,胃十二指肠黏膜SRMD风险极大增加。从预防高危因素入手,采用ERAS措施有助于减轻手术应激。目前,质子泵抑制剂(proton pump inhibitors,PPI)广泛用于应激性胃黏膜病变的预防和治疗。Meta分析[294]表明,PPI可降低消化性溃疡疾病及其并发症发生风险。针对重症病人的Meta分析[295-296]证实应用PPI可降低胃肠道出血事件发生率,但证据质量和数量不足,且PPI对肺炎、心肌缺血及艰难梭菌肠炎的影响仍无定论。对于肝切除术病人,建议自肝切除术前1 d开始静脉应用常规剂量的PPI,应注意奥美拉唑和艾司奥美拉唑对药物代谢酶CYP2C19的抑制作用,当合并用药较多时,应优先选择对药物代谢影响小的泮托拉唑[297]。亦有Meta分析[298]表明术后早期肠内营养亦有助于预防SRMD。

一旦发生SRMD出血,应立即控制出血,推荐使用艾司奥美拉唑迅速提高胃内pH值(pH值≥6)[299],首剂80 mg静脉推注,以后8 mg/h静脉泵入维持;视情况联合应用生长抑素类药物、止血药物;药物治疗无法止血者,应进行内镜检查及内镜下止血治疗,如仍无效可考虑行介入或手术治疗[300]

推荐意见44:自肝切除术前1 d应用PPI预防胃十二指肠黏膜SRMD,可优先选择对药物代谢影响小的PPI,术后早期肠内营养亦有助于预防胃十二指肠黏膜SRMD(2B)。

3.2 术后液体管理和治疗

3.2.1 术后液体管理

肝切除术后病人肝功能不良,易出现水和电解质紊乱,术后液体治疗有利于快速康复[301]。病人循环不稳定或者外周灌注不足、血乳酸升高时,结合液体负荷试验、脉压变异度、每搏量变异度、被动抬腿试验等功能性血流动力学指标综合评估病人容量反应性,可给予液体治疗[302]。如血流动力学稳定、容量反应性消失、出现液体过负荷,则应考虑停止液体治疗[303]。总体而言,限制性液体管理、偏低的中心静脉压水平获益更多,但应避免血容量不足[304]。术后液体复苏以晶体液为主,可降低恶心呕吐等并发症,且晶体缓冲液有利于降低高氯血症、酸中毒等代谢紊乱[305-306]

推荐意见45:术后应结合病人循环情况和容量反应性指标综合决定是否给予液体治疗。如需液体治疗,推荐以晶体缓冲液为主(2B)。

3.2.2 合理使用利尿剂

液体负荷过重会引起组织器官水肿,减少脏器灌注,推荐使用利尿剂。2021年Gut上发表的《肝硬化腹水管理指南》[307]指出对于需要快速利尿的肝硬化腹水病人,一线药物治疗为螺内酯和呋塞米联用,初始剂量分别为螺内酯100 mg/d(可增加至400 mg/d)和呋塞米40 mg/d(可增加至160 mg/d)。另有临床研究证明加用托伐普坦有利于降低肝切除术后胸腔积液发病率,缩短术后住院时间[308]。在心脏手术术后早期加用托伐普坦还可以在不引起肾脏功能衰竭的情况下维持正常尿量,有效减少肾功能衰竭的发生[309]。但也有研究指出在结直肠术后早期静脉输注呋塞米并不能改善病人住院时间,反而延长了肠道功能恢复[310]。研究还发现,经生物电阻抗分析可计算病人的水肿指数(细胞外水量/总体水量),该指标可用于预测肝切除术后腹水的发生风险,或可以作为术后早期利尿剂使用的指征[311]。目前肝切除术后关于使用利尿剂的指征、种类、时机以及用法用量等有待更多的临床证据。

推荐意见46:肝切除术后可根据是否存在液体负荷过重及水肿指数决定是否使用利尿剂(2D)。

3.2.3 术后肝功能的监测和护肝治疗

(1) 术后肝功能监测:术后肝功能的监测和早期干预有助于预防肝功能不全的发生[98]。肝脏酶谱的变化(包括ALT、AST等),尤其是术后前2~3 d,常反映手术的机械损伤对于肝细胞的破坏,并不一定意味着严重的肝功能不全,但随后若发生严重的酶学改变(如ALT>10×ULN),有可能是继发的肝功能不全。因此,对于持续而严重的肝脏酶学改变且合并胆红素不断升高的病人,应警惕术后肝功能不全,甚至有进展为PHLF的可能[312-313]。用于诊断肝切除术后PHLF的“50-50标准”为肝切除术后第5天凝血酶原指数<50%(INR 1.7)及血清TBIL 50 μmol/L(3 mg/dL)。但“50-50标准”仅考虑凝血情况(INR)及胆红素水平,未考虑其他临床指标,所以只适用于早期PHLF的诊断。2011年,国际肝脏外科研究小组(ISGLS)提出PHLF的统一定义:肝切除术后肝脏合成、分泌、解毒等功能受损,在排除胆道梗阻之后,术后第5天或之后INR和TBIL数值升高且大于术前值时可诊断为PHLF[314]。此外,相关研究表明肝癌肝部分切除病人术后低血小板计数(<100×109/L)与肝功能恢复延迟相关,术后低血小板计数可作为肝癌术后肝功能恢复差的预测指标[315]。(2) 术后肝损伤治疗药物的合理使用:术后肝损伤的治疗药物旨在保护肝功能、促进肝细胞修复与再生、减轻肝脏炎症反应。目前临床常用药物种类多样,其作用机制各异,需根据损伤类型和病人情况合理选用。抗炎类药物,如甘草酸制剂,具备显著的糖皮质激素样抗炎效应,可有效减轻肝脏炎症反应,降低升高的血清氨基转移酶(如ALT、AST)水平,代表性药物为异甘草酸镁注射液、甘草酸二铵肠溶胶囊、复方甘草酸苷等,在使用过程中需注意监测血压、血钾等指标。抗氧化类药物,如还原型谷胱甘肽,其活性巯基可直接清除自由基、过氧化物等活性氧类物质,减轻氧化应激对肝细胞的损伤,保护肝细胞膜结构和功能的稳定性;多烯磷脂酰胆碱作为肝细胞膜关键组成成分(磷脂)的来源,可特异性地整合至受损的肝细胞膜,促进肝细胞膜的修复、再生与稳定,恢复膜流动性及膜相关酶的功能,有助于改善肝脏的代谢功能;利胆类药物,如腺苷蛋氨酸,作为甲基提供的前体,有助于防止胆汁淤积;熊去氧胆酸能够促进胆汁酸分泌,优化胆汁流动性,缓解胆汁淤积,对胆管细胞起到保护作用,具备多重利胆护肝功效,针对胆汁淤积引发的肝损伤具有较好疗效。肝脏切除术后造成的肝损伤,治疗药物的选用需综合考量病人肝功能状况以及药物作用机制合理选择[316]。对于肝功能损伤较轻者,可选用一种抗感染治疗;若肝功能损伤较重,应在抗炎药物基础上联合不同作用机制的药物以增强治疗效果,但机制相同或相似的药物不应联用[317]。治疗过程中需监测血压、电解质紊乱等药物不良反应。(3) 术后PHLF的治疗:肝切除术后一旦发生PHLF,可参考ISGLS PHLF分级标准及时启动基础监测和分级处理措施,包括吸氧、改善凝血功能、维持水电解质及酸碱平衡、控制蛋白摄入、营养支持治疗、停用或减量肝毒性药物、应用肝损伤治疗药物和促进肝细胞再生的药物,预防应激性溃疡等并发症发生,必要时进行血浆置换、生物人工肝等治疗(表3)。

推荐意见47:术后应定期监测肝功能、凝血功能和相关临床表现。可参照ISGLS提出的肝功能衰竭诊断标准诊断PHLF(1A)。

推荐意见48:术后护肝药物应以抗炎类为基础,可根据病人肝损伤的具体情况,合理选择抗炎、抗氧化、利胆等不同作用机制的肝损伤治疗药物,必要时联合用药(2C),但机制相同或相似的药物不应联用(1B)。

推荐意见49:肝切除术后发生PHLF可参考ISGLS PHLF分级标准及时针对性治疗(1A)。

3.2.4 术后感染的预防和治疗

肝切除术后感染与病人的原发疾病、术前全身及肝功能状态以及手术范围和术中出血等因素密切相关[318]。术前控制潜在的感染病灶,维护肝脏结构(入肝血流、出肝血流及胆管引流)和功能,术中精细操作,避免大量出血和长时间肝血流阻断是预防术后感染的重要措施[319]。对于术前合并胆道、腹腔或其他局部化脓性感染的病人,在控制感染的同时应尽可能在术前获得细菌学和药物敏感试验结果,以便正确指导术后用药[320]

肝切除术后容易导致感染的并发症是腹腔积液和胆汁漏。对于术后出现的腹腔积液,均应鉴别是否为感染性积液。对于疑似的感染性积液,建议进行诊断性穿刺;对于明确的感染性积液或积液量较大,推荐进行穿刺引流,并根据细菌学证据,及时选择敏感的抗菌药物治疗。同时应该维持胃肠道功能,控制肠道菌群易位和肠源性内毒素血症[321]。术后胆汁漏的非手术治疗(含内镜和介入)包括抗感染、控制饮食和营养支持,同时进行有效的腹腔、胆道引流。当非手术治疗无条件实施或治疗无效时,推荐选择外科手术清除感染灶,建立充分的腹腔外引流,同时通畅胆道,降低胆道压力并适当修补漏口[322]

肝切除术后出现感染性疾病常提示病情复杂,推荐在科室(病区)启动或参与抗菌药物管理项目,并设立专人管理[323]。初始经验性治疗选择广谱抗菌药物,应覆盖革兰氏阴性菌肠杆菌、革兰氏阳性菌球菌及常见厌氧菌等。规范的抗感染治疗方案可降低病人病死率,不规范或未能覆盖常见厌氧菌的经验性治疗方案可能提高初始治疗失败率及病人病死率[324]。腹腔源性脓毒症危重病人行针对性降级治疗后病死率下降,提示降阶梯治疗安全、可行。研究表明约10%的术后腹腔感染是真菌所致,腹腔念珠菌感染提示预后不良。确诊为真菌感染病人,经抗真菌治疗临床症状改善后,至少应继续抗真菌治疗10~14 d[325]

推荐意见50:术后早期抗感染治疗和引流可以降低感染性休克相关病死率(2B)。

3.2.5 术后低蛋白血症的治疗

外源性补充人血ALB是公认的纠正肝切除术后低蛋白血症的有效方法[326]。术后应用人血ALB,可以纠正低白蛋白血症、减少腹水形成及治疗腹水并发症,加速术后病人康复。一项单中心的前瞻性研究结果显示,术后第1天血清ALB浓度降低幅度(ALB≥10 g/L)与术后整体并发症的发生风险增加3倍相关[327]。另一项双中心的回顾性研究也显示,肝切除术后病人△ALB值越大,提示术后并发症发生率越高[328]。此外,国际多中心回顾性研究证明肝切除术后低白蛋白血症病人发生腹水的风险是ALB正常病人的2.5倍[42]。肝切除术后低白蛋白血症还是手术部位感染和(或)腹腔感染的独立预后因素[329]。近年来,在肝切除术后合理使用人血ALB越来越被提倡[330],推荐肝脏手术后血清ALB<30 g/L时可输注人血ALB,并应维持血清ALB水平≥30 g/L[331]

推荐意见51:外源性补充人血ALB是纠正肝切除术后低蛋白血症的有效方法。推荐肝脏手术后血清ALB 30 g/L时输注人血ALB(1B)。

3.2.6 术后预防性抗血栓治疗

任何引起静脉损伤、静脉血流停滞及血液高凝状态的原因都是发生VTE的危险因素。基于6项临床研究[332-333]结果建议,对外科大手术病人VTE药物预防的启动时间,可以选择早期(术后12 h内)给药,也可以晚期(术后>12 h)给药。除伴有出血性疾病或明显正在出血的病人外,肝切除术病人应在充分评估出血风险的基础上,考虑对VTE进行预防。预防方法推荐选择1种机械和(或)1种药物预防措施,并及时调整预防策略。机械预防措施包括弹力袜和间歇充气加压泵。若CrCl>30 mL/min,药物预防措施包括普通肝素、低分子肝素、磺达肝癸钠;若CrCl为15~30 mL/min,可考虑使用普通肝素,低分子肝素(根据说明书调整剂量)预防;若CrCl<15 mL/min,可考虑使用普通肝素预防。通常手术病人推荐预防7~14 d或直至出院,对恶性肿瘤等VTE高危病人,推荐使用低分子肝素预防4周。对于VTE高风险但无大出血风险的病人,若出现肝素诱导的血小板减少症,在无明确血栓的情况下,可考虑使用磺达肝癸钠或NOAC(利伐沙班,阿哌沙班)预防;若病人确诊为肝素诱导的血小板减少症,且有明确血栓形成的病人,尤其是在血栓形成初期,应使用母体非肝素抗凝剂治疗,如比伐卢定,阿加曲班等[334]。对于已确诊下肢深静脉血栓的病人,不推荐下腔静脉滤器置入作为围手术期VTE常规预防措施。

对于长期服用抗血栓药物并需要行肝切除的病人,若术前服用阿司匹林、氯吡格雷和替格瑞洛等抗PLT药物治疗,且为中高缺血风险,术后出血停止,24 h内可以重启抗PLT治疗;若术前服用华法林抗凝治疗,术后出血停止,24 h内可以重启华法林治疗,根据术后出血风险,如有需要,可在24~72 h内行低分子肝素桥接治疗;若病人术前服用NOAC,术后出血停止,48~72 h重启全量NOAC治疗[335-336]

推荐意见52:肝切除术病人在充分评估出血风险的基础上,术后可选择1种机械和(或)1种药物预防VTE(1B)。

3.3 ERAS措施在肝切除术后的应用

3.3.1 术后早期活动

术后早期下床活动可以减少肌肉损失、肺部感染、压力性损伤、深静脉血栓形成等并发症的发生,促进呼吸、胃肠功能等多系统功能恢复[85,337-338]。一项120例肝切除术后病人的RCT研究[339]结果显示,术后早期活动是安全的,可减轻病人疼痛和经济负担,增加舒适感,提高满意率。早期活动可改善腹部肿瘤病人术后心肺耐力、减少疲劳症状、改善肌肉力量和生命质量[340]。2篇系统评价均将术后早期活动作为快速康复重要措施之一,明确在肝切除术后早期活动安全、有效[341-342]

针对下床活动时间,两项系统评价[341,343]结果显示,如果病人条件允许,推荐术后第1天开始下床活动。一项RCT研究[339]结果显示,术后第1天开始活动,术后胃肠功能恢复明显加快。

推荐意见53:病人术后清醒即可在床上适量活动或采用半卧位,如病情允许,术后第1天可下床活动(1A)。

3.3.2 术后进食和营养

多项研究[344-345]结果显示,术后早期进食可降低肝切除术后并发症发生率并显著缩短住院时间,且未增加死亡率、肠功能延迟恢复等风险。

术后早期经口进食是肝切除术后病人的首选营养方式[16]。ESPEN外科营养学指南推荐,大多数病人应在术后数小时内开始口服,包括透明液体[16]。行肝切除术的病人在术后早期应选择富含支链氨基酸的饮食,尽量减少术后代谢相关疾病的发生率[132,346]。相关国外指南推荐无特殊情况病人术后4~6 h饮水;根据病人耐受情况,术后24~72 h恢复流食或半流食;肛门排气后恢复正常饮食[16]。通过营养风险筛查量表和危重病营养风险评分[8,347]筛查存在术后营养不良的病人,建议术后24 h内开始肠内营养[16]。Richter等[348]的Meta分析结果显示,与肠外营养组相比,肠内营养组创面感染及导管相关并发症发生率明显降低。参考能量25~30 kcal/(kg·d)(1 kcal=4.18 kJ)蛋白质1.2~1.5 g/(kg·d)进行经验估算[349-352]能量需求,如果仅通过口服和肠内摄入>7 d不能满足需求(<能量需求50%),则建议在肠内营养基础上给予补充性肠外营养[353]

推荐意见54:根据病人情况,术后早期经口进食。对营养不良病人,优先推荐肠内营养;如果能量不达标,建议补充肠外营养(1A)。

3.3.3 术后贫血

肝切除术后贫血发生率约为32%[354],肝脏手术的输血率为9.72%~18.61%[355]。规范的病人血液管理可减少异体血输注、病死率和医疗费用,同时有利于缩短住院时间,促进病人康复[182]。多项研究结果显示,肝脏恶性肿瘤病人术后输异体血液与远期预后呈负相关[356-358],自体输血并不影响肝癌病人的远期预后[359]。自体输血并非“血液回输”,而是术前预存血液,术中输注自体血液。因此,推荐在肝切除围手术期推广自体输血技术[360]

肝切除术后维持平均动脉压>80 mmHg有利于维持正常的器官功能,术后贫血有可能影响病人血流动力学稳定[269]。国际公认肝切除术后输注RBC的“渥太华标准”:(1) 术后即刻Hb≤75 g/L。(2) 术后病情稳定,无贫血相关症状的病人,Hb≤70 g/L(若合并冠心病则≤80 g/L)。(3) 术后存在出血或可疑出血,Hb较前下降≥15 g/L。(4) 经液体扩容后血流动力学不稳定的病人[361]。当PT、活化部分凝血活酶时间、凝血INR>正常上限的1.5倍时,建议输注新鲜冰冻血浆;当纤维蛋白原<1.5 g/L时,建议输注纤维蛋白原浓缩物或冷沉淀;当PLT<50×109/L,建议输注PLT[362]

除输血外,还可以使用止血药物、纠正缺铁或刺激RBC生成[363]。POISE-3试验推荐对所有术中出血量>500 mL的病人使用氨甲环酸(除非有禁忌证)优化止血,推荐用1 g静脉推注10 min,8 h后可追加1 g[364]。HepciFer试验表明,肝切除术后贫血病人静脉输注羧基麦芽糖铁(15 mg/kg)虽不能提升Hb水平,但可以提高血清铁蛋白和转铁蛋白浓度,降低铁调素和C-反应蛋白水平[354]。促RBC生成素联合铁剂可以提高肝切除术后贫血病人的Hb水平,但仅推荐用于良性疾病[365]

推荐意见55:规范的病人血液管理可减少异体血输注、病死率和医疗费用,同时有利于缩短住院时间(1B)。

3.3.4 引流管管理

肝切除术后留置腹腔引流管最主要的意义在于观察术后早期有无创面继发出血和胆汁漏,而非为了引流腹水[366-367]。对于留置腹腔引流管的病人,如无出血、胆汁漏、腹腔感染等发生,应在术后3~4 d拔除腹腔引流管。一项单中心RCT研究结果表明遵从“3×3”法则(术后3 d+引流液胆红素浓度≤51 μmol/L)拔除腹腔引流管,较传统方法(引流量≤100 mL/d)可以降低术后疼痛,缩短住院时间并减少术后并发症的发生[368]

未联合胃肠道重建手术的肝切除病人,不推荐放置胃管或最迟于手术结束时拔除胃管;联合胃肠道重建手术病人,根据引流情况推荐于术后第1~2天拔除胃管[369]。肝切除术后长期留置胃管可增加病人发热、肺不张、肺炎、胃食管反流等并发症发生率[370]。同时,长期留置导尿管有增加尿路感染等风险。建议对于没有前列腺病变的病人,术后第1~2天拔除导尿管,无须常规进行膀胱功能锻炼[126,371]

推荐意见56:腹腔引流管可用于观察术后有无创面出血和胆汁漏,早期拔除腹腔引流管可使病人获益。肝切除术后应早期拔除胃管和(或)尿管(1B)。

3.3.5 术后并发症的处理

对于症状较轻的PONV病人可以选择等待观察。症状明显者可采用大剂量甲氧氯普胺(25 mg或50 mg)或联合地塞米松才能有效[372]。PONV的治疗使用5-HT3受体拮抗剂、NK1受体拮抗剂、糖皮质激素、抗多巴胺能药物、抗组胺药物、抗胆碱能药物等的联合用药效果优于单一用药[373]。此外,PDO法(奋乃静8 mg、地塞米松4 mg、昂丹司琼4 mg)是一种有效且性价比高的治疗方案[374]。当治疗效果不佳时,推荐咨询麻醉医师。针灸、按摩、透皮电神经刺激、穴位刺激和催眠等非药物治疗措施也可产生治疗效果[375]

高龄、糖尿病、肝硬化门静脉高压、恶性肿瘤、术中频繁肝门阻断和长时间肝门阻断、合并门静脉重建手术、右三肝或右半肝切除、合并脾切除以及术后胆汁漏、腹腔感染等是肝切除术后发生门静脉血栓(portal vein thrombosis,PVT)的危险因素[376]。明确诊断PVT后,应立即使用静脉或皮下注射低分子肝素5.0 U/12 h快速抗凝处理,时间为2~3周[377]。使用维生素K拮抗剂时,应调整凝血INR至2.0~3.0。TriNetX公共数据库分析发现:直接口服抗凝药物(IIa因子抑制剂、Xa因子抑制剂等)效果优于维生素K拮抗剂[378]。PVT形成72 h内行介入溶栓治疗,可以经肠系膜上动脉灌注溶栓药物,也可以通过经颈静脉肝内门体静脉分流术进行局部碎栓联合溶栓。

肝切除术后第3天引流液(或经皮腹腔穿刺引流液)中胆红素>正常血清值3倍,可诊断为术后胆汁漏,发生率为3.0%~8.7%[323]。术后胆汁漏可以通过术后超声、CT、磁共振胆胰管成像等检查明确胆汁漏部位。流量较小的胆汁漏可通过引流、支持治疗等非手术方法治愈,若合并难治性腹腔积液或腹腔感染时,常需要介入、内镜甚至二次手术等方式协助治疗,导致病人术后康复时间延长[379]

肝切除术后腹腔积液影响病人术后康复,其主要危险因素有肝硬化、术后剩余肝体积较小、术后肝功能不全、大范围肝切除、术前辅助放化疗、长时间肝门阻断、大量出血、术中输血等[380]。控制输液量,补充ALB及胶体,适当利尿和降低门静脉压等措施有助于减少腹腔积液,除非有明确的腹腔感染或消化道瘘,通常不主张行腹腔穿刺引流腹腔积液[381]

推荐意见57:根据病人具体情况有针对性地处理肝切除术后PONV、PVT、胆汁漏和腹腔积液等并发症(2B)。

3.3.6 术后心理辅导和应用

肝切除术后,心理干预是一个连贯的过程[382-383]。有研究[384]证实心理因素与癌症病人的生存率有关,抑郁、绝望和情绪抑制是癌症病人生存时间缩短的预测因素[385]。发现抑郁倾向可采用Zung抑郁自评量表[382-384]对病人进行评估。该量表自20世纪80年代引入国内以来,长期处在我国心理测评量表应用排行的前列,具有良好的信效度[386-389]。一项RCT研究[390]结果显示,综合教育和护理方案可减少肝癌手术病人的焦虑和抑郁,提高生命质量和生存率。一项RCT研究结果显示,有效心理教育干预的主要内容包括为病人提供卫生保健相关任务、照顾者的自我效能和压力管理,以及关系和应对技能[391]。强化心理干预能够有效改善肝癌病人的生命质量,调节心理平衡、减轻精神压力等不良心理状态,有益于病人术后康复[389,391-393]

推荐意见58:建议术后对心理状态不稳定病人进行心理评估,必要时进行心理干预直至病人出院(2B)。

3.3.7 出院标准

设定合理的出院标准并严格执行是ERAS实践的重要一环。目前尚无关于肝切除术后科学统一出院标准的临床研究证据。本指南参与专家的统一意见认为,出院标准可设定:肝切除术后病人精神尚可,能够自由活动,生活基本能够自理或恢复术前状态,进食半流质饮食或普通饮食,无须补液治疗,排气排便通畅;症状方面,体温正常,无发热,疼痛缓解或口服NSAID能良好控制;实验室指标方面,白细胞计数正常或趋近正常,Hb、PLT和凝血功能基本正常或恢复术前状态。对于出院时肝功能尚未完全恢复正常的病人,可出院后继续口服护肝药物。

对于国家医学中心/国家区域医疗中心(“双中心”)和已建立双向转诊的城市医疗集团或医联体单位,可适当放宽出院标准,将病情相对稳定的病人转至相关医院继续治疗[391]

推荐意见59:各单位和(或)医学中心应践行ERAS理念,设定合理的出院标准并严格执行(2C)。

3.3.8 术后抗肝炎药物用药指导

对于HBV相关性肝细胞癌病人,抗病毒治疗有助于提高总生存率、降低复发率、改善肝功能[393],且具有较好的成本效益[394]。一项回顾性研究表明,围手术期抗HBV治疗可通过促进术后肝功能恢复提高围手术期安全性[395]。另有一项RCT研究[396]证明抗HBV治疗可减少肝癌复发。亦有一项Meta分析[397]指出,抗HBV治疗可降低根治性肝切除术后肝癌复发率。在肝细胞癌手术切除前后均需进行抗病毒治疗,对于术前未进行规范抗HBV治疗者,确诊HBV相关性肝细胞癌时应立即启动恩替卡韦、富马酸替诺福韦酯或丙酚替诺福韦抗HBV治疗[398-400],术后启动肠内营养时即恢复口服抗病毒治疗。肝切除手术可导致HBV再激活[98],术后应监测乙肝五项和HBV-DNA,如果有证据提示HBV再激活,则建议调整抗病毒药物或再次启用抗病毒治疗。

对于HCV相关性肝细胞癌病人,美国胃肠病学会建议肝细胞癌行肝切除或消融治疗后完全缓解的病人需接受直接抗病毒药物(direct antiviral agents,DAA)治疗[103],治疗时间可在术后4~6个月后。一项纳入1 820例HCV相关性肝细胞癌病人(接受局部消融515例)的Meta分析[401]提示,至少在肿瘤完全缓解后6个月开始DAA治疗。德国肝癌联盟也建议,HCV相关性肝细胞癌病人接受根治性治疗后最早术后6个月接受DAA治疗[402]。目前,仅有一项研究探讨接受RFA的HCV相关性肝细胞癌病人DAA治疗时机,结果发现:肝细胞癌行RFA治疗与接受DAA治疗的间隔时间是抗病毒治疗后肝细胞癌复发的唯一预测因子[403]。延迟DAA治疗可以延长现有微小肝细胞癌克隆的免疫监视时间,还可以创造更长的时间以验证肝细胞癌是否完全缓解,从而最大限度地减少错误分类的机会[103]。目前缺乏更深入的相关研究,也有专家认为,围手术期后立即开始治疗,尽快清除HCV,减少由HCV引起炎-癌转化,减少肝纤维化进展,降低复发率[404]

推荐意见60:HBV相关性肝细胞癌病人术后尽早启动核苷(酸)类似物治疗(1A)。HCV相关性肝细胞癌病人建议完成肝切除术后再启动DAA治疗(1B)。

肝切除术的开展必须进行术前评估,术中监测和术后管理。手术质量的评价需要平衡手术获益与手术风险,围手术期并发症发生率和5年总生存率是核心考量目标[200,206]。术后并发症如PHLF[405]、胆汁漏、出血和感染等是影响病人术后恢复的重要因素,严重者可直接影响手术结局。术后住院时间、总住院时间等是围手术期康复效率的常用评价指标[406-407]。虽然术后总生存时间已超越围手术期的范畴,但其长短也仍然与手术的实施有着潜在的联系。另外,卫生经济学的因素也是围手术期管理中需要考虑的重要环节。因此,在ERAS理念的指导下加强围手术期的管理至关重要,同时也应关注成本效益,兼顾技术可及性[406]

《肝脏切除术围手术期多学科临床管理指南(2025版)》编审委员会名单

主任委员:陈孝平(华中科技大学同济医学院附属同济医院)

主审专家:樊嘉(复旦大学附属中山医院),窦科峰(中国人民解放军空军军医大学西京医院),夏强(上海交通大学医学院附属仁济医院)

委员(按姓氏汉语拼音排序):艾军华(南昌大学第一附属医院),白雪莉(浙江大学医学院附属第一医院),毕新宇(中国医学科学院肿瘤医院),卜阳(宁夏医科大学总医院),蔡建强(中国医学科学院肿瘤医院),蔡秀军(浙江大学医学院附属邵逸夫医院),曹景玉(青岛大学附属医院),车旭(首都医科大学附属北京同仁医院),陈进宏(复旦大学附属华山医院),陈林(华中科技大学同济医学院附属协和医院),陈琳(华中科技大学同济医学院附属同济医院),陈敏(中国人民解放军陆军军医大学第一附属医院《中华消化外科杂志》编辑委员会),陈敏山(中山大学肿瘤防治中心),陈伟(苏州大学附属第二医院),陈雄(新疆维吾尔自治区人民医院),陈亚进(中山大学孙逸仙纪念医院),陈彦(华中科技大学同济医学院附属同济医院),陈志华(北京陈志华律师事务所),程树群[中国人民解放军海军军医大学第三附属医院(上海东方肝胆外科医院)],仇毓东(南京大学医学院附属鼓楼医院),戴朝六(中国医科大学附属盛京医院),杜锡林(中国人民解放军空军军医大学第二附属医院),范瑞芳 中国人民解放军联勤保障部队第九四〇医院,范伟(贵州省人民医院),方驰华(南方医科大学珠江医院),冯晓彬(北京清华长庚医院),高强(复旦大学附属中山医院),耿小平(安徽医科大学第一附属医院),耿智敏(西安交通大学医学院第一附属医院),郭文治(郑州大学第一附属医院),韩风(河南省肿瘤医院),郝存毅(北京大学肿瘤医院),洪德飞(浙江大学医学院附属邵逸夫医院),黄平(重庆医科大学附属第一医院),黄志勇(华中科技大学同济医学院附属同济医院),嵇武(中国人民解放军东部战区总医院),江斌(湖北医药学院附属太和医院),靳斌(山东大学齐鲁第二医院),靳迺诗(中国人民解放军陆军军医大学第一附属医院),康德英(四川大学华西医院),匡铭(中山大学第一附属医院),赖佳明(中山大学第一附属医院),李斌奎(中山大学肿瘤防治中心),李川江(南方医科大学南方医院),李德宇(河南省人民医院),李敬东(川北医学院附属医院),李靖(中国人民解放军陆军军医大学第二附属医院),李强(天津医科大学附属肿瘤医院),李绍强(中山大学第一附属医院),李相成(江苏省人民医院),李晓武(深圳大学附属总医院),李汛(兰州大学第一医院),梁廷波(浙江大学医学院附属第一医院),廖锐(重庆医科大学附属第一医院),刘斌(昆明医科大学第一附属医院),刘昌(西安交通大学第二附属医院),刘娇(上海交通大学医学院附属瑞金医院),刘景丰(复旦大学附属肿瘤医院福建医院),刘军(山东省立医院),刘连新[中国科学技术大学附属第一医院(安徽省立医院)],刘青光(西安交通大学第一附属医院),刘荣(中国人民解放军总医院),刘颖斌(上海交通大学医学院附属仁济医院),刘永安(上海交通大学医学院附属瑞金医院),刘作金(重庆医科大学附属第二医院),卢绮萍(中国人民解放军中部战区总医院),鲁开智(中国人民解放军陆军军医大学第一附属医院),陆荫英(中国人民解放军总医院第五医学中心),罗鸿萍(华中科技大学同济医学院附属同济医院),吕毅(西安交通大学第一附属医院),麻勇(哈尔滨医科大学附属第一医院),毛先海(湖南省肿瘤医院),毛一雷(北京协和医院),孟兴凯(内蒙古医科大学附属医院),潘耀振(贵州医科大学附属肿瘤医院),彭创(湖南省人民医院),彭涛(广西医科大学第一附属医院)浦涧(右江民族医学院附属医院),钱叶本(安徽医科大学第一附属医院),秦磊(苏州大学附属第一医院),邱琰(中国人民解放军陆军军医大学第一附属医院),商昌珍(中山大学孙逸仙纪念医院),沈锋[中国人民解放军海军军医大学第三附属医院(上海东方肝胆外科医院)],宋天强(天津医科大学肿瘤医院),孙备(哈尔滨医科大学附属第一医院),孙倍成(安徽医科大学第一附属医院),孙惠川(复旦大学附属中山医院),孙志伟(云南省第一人民医院),邰升(哈尔滨医科大学附属肿瘤医院),谭广(大连医科大学附属第一医院),汤朝晖(上海交通大学医学院附属新华医院),唐腾骞(中国人民解放军陆军军医大学第一附属医院),陶开山(中国人民解放军空军军医大学西京医院),万赤丹(华中科技大学同济医学院附属协和医院),万仁华(南昌大学第一附属医院),王坚(上海交通大学附属瑞金医院),王葵[中国人民解放军海军军医大学第三附属医院(上海东方肝胆外科医院)],王立明(大连医科大学附属第二医院),王鲁(复旦大学附属肿瘤医院),王文涛(四川大学华西医院),王震侠(内蒙古医科大学附属医院),王郑封(郑州大学第一附属医院),王芝(陆军军医大学第一附属医院),王志明(中南大学湘雅医院),魏小勇(江西省肿瘤医院),文天夫(四川大学华西医院),吴泓(四川大学华西医院),夏锋(中国人民解放军陆军军医大学第一附属医院),夏杰(中国人民解放军陆军军医大学第一附属医院),向邦德(广西医科大学肿瘤医院),项灿宏(北京清华长庚医院),邢宝才(北京大学肿瘤医院),徐骁(浙江大学医学院附属第一医院),徐新建(新疆医科大学第五附属医院),晏冬(新疆医科大学附属肿瘤医院),杨含腾(兰州大学第二医院),杨家印(四川大学华西医院),杨威(西安交通大学第一附属医院),杨尹默(北京大学人民医院),姚尚龙(华中科技大学同济医学院附属协和医院),尹大龙(中国科学技术大学附属第一医院),尹新民(湖南省人民医院),尹震宇(厦门大学附属中山医院),喻超(贵州医科大学附属医院),袁玉峰(武汉大学中南医院),张水军(郑州大学第一附属医院),张雅敏(天津市第一中心医院),张永辉(中国人民解放军陆军军医大学第一附属医院),张宇(四川省人民医院),张志波(福建医科大学第一附属医院),张志伟(华中科技大学同济医学院附属同济医院),周俭(复旦大学附属中山医院),周杰(南方医科大学南方医院),周伟平[中国人民解放军海军军医大学第三附属医院(上海东方肝胆外科医院)],曾永毅(福建医科大学孟超肝胆医院),曾勇(四川大学华西医院),曾仲(昆明医科大学第一附属医院),左石(贵州医科大学附属医院)

执笔专家夏锋中国人民解放军陆军军医大学第一附属医院),唐腾骞中国人民解放军陆军军医大学第一附属医院),陈琳华中科技大学同济医学院附属同济医院),尹大龙中国科学技术大学附属第一医院),鲁开智中国人民解放军陆军军医大学第一附属医院),陆荫英中国人民解放军总医院第五医学中心),李川江南方医科大学南方医院),商昌珍中山大学孙逸仙纪念医院),王郑封郑州大学第一附属医院),陈林华中科技大学同济医学院附属协和医院),刘永安上海交通大学医学院附属瑞金医院),邱琰中国人民解放军陆军军医大学第一附属医院

秘书组:唐腾骞(中国人民解放军陆军军医大学第一附属医院),赵蕾(中国人民解放军陆军军医大学第一附属医院/《中华消化外科杂志》编辑委员会),霍佳丽(中国人民解放军陆军军医大学第一附属医院/《中华消化外科杂志》编辑委员会)

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基金资助

重庆市自然科学基金资助项目(CSTB2023NSCQ-MSX0563)

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