以功能保留为核心的胆道肿瘤多阶段治疗体系：微创、动态功能评估与康复整合

Function-preserving multistage management for biliary tract cancers: integration of minimally invasive surgery, dynamic functional assessment, and rehabilitation

摘要

胆道肿瘤的长期生存仍依赖R₀切除，但梗阻性黄疸、胆管炎、肝储备不足及系统治疗相关肝损伤，使围手术期风险集中于“胆汁淤积—感染—功能衰竭”链条，单纯依赖微创技术难以弥补由此带来的功能代价。基于最新指南与循证证据，本文提出以“功能可切除性”为核心的胆道肿瘤多阶段诊疗路径，涵盖转化/新辅助治疗、术前功能再评估、功能导向手术以及术后康复与长期随访。术前决策以未来肝残余“体积+功能”综合评估为基础，必要时联合^99mTc-mebrofenin SPECT/CT及吲哚菁绿（ICG）清除试验进行区域功能定量，并通过选择性胆道引流、感染控制、营养与凝血优化及门静脉栓塞建立“功能安全窗”。术中整合ICG荧光、术中超声及三维重建以提高R₀切除率并优化重建质量；术后依循加速康复外科理念管理，以肝切除后肝功能衰竭、术后临床相关胰瘘及患者报告结局为核心终点评价疗效。该路径强调“功能优先、微创其次”，通过动态评估、主动干预与结局量化的闭环管理，在保证肿瘤学根治性的同时最大程度保留器官功能与生活质量。

Abstract

Radical resection remains the cornerstone of long-term survival in biliary tract cancers (BTC). However, obstructive jaundice, cholangitis, impaired hepatic reserve, and treatment-related liver injury concentrate perioperative risks along a "cholestasis-infection-functional failure" cascade, and minimally invasive access alone cannot offset these functional costs. Based on current guidelines and emerging evidence, we propose a multistage care pathway centered on the concept of functional resectability, encompassing conversion/neoadjuvant therapy, preoperative functional reassessment, function-oriented surgery, and postoperative rehabilitation with long-term follow-up. Preoperative decision-making is anchored to combined "volume-plus-function" evaluation of the future liver remnant. When necessary, regional liver function is quantified using ^99mTc-mebrofenin SPECT/CT and indocyanine green clearance testing, while selective biliary drainage, infection control, nutritional and coagulation optimization, and portal vein embolization are applied to establish a functional safety window. Intraoperatively, indocyanine green fluorescence imaging, intraoperative ultrasound, and three-dimensional planning are integrated to facilitate R₀ resection and optimize reconstruction. Postoperatively, ERAS-based management is adopted, and key endpoints-including post-hepatectomy liver failure, clinically relevant postoperative pancreatic fistula, and patient-reported outcomes-are used to evaluate treatment benefit. This pathway emphasizes a "function-first, minimally invasive second" strategy, forming a closed loop of dynamic assessment, proactive intervention, and outcome measurement to maximize functional preservation and quality of life while maintaining oncological radicality.

Graphical abstract

关键词

胆道肿瘤 / 功能可切除性 / 最小侵入性外科手术 / 术后加速康复 / 患者报告结局

Key words

Biliary Tract Neoplasms / Functional Resectability / Minimally Invasive Surgical Procedures / Enhanced Recovery After Surgery / Patient‑Reported Outcomes

胆道肿瘤（biliary tract cancers，BTC）包括肝内胆管癌（intrahepatic cholangiocarcinoma，ICC）、肝门部胆管癌（hilar cholangiocarcinoma，HCCA）、远端胆管癌（distal cholangiocarcinoma，DCC）以及胆囊癌（gallbladder cancer，GBC），在亚洲高发，起病隐匿且常伴梗阻性黄疸/胆管炎，初诊可切除率有限^[1-2]。长期生存仍依赖R₀切除与规范清扫并结合综合治疗，但围手术期风险集中于“胆汁淤积—感染—肝储备下降”功能链条，需同时守住肿瘤学与器官功能边界^[1-3]。微创技术在肝胆胰复杂手术中快速发展，但入路必须服从R₀与功能安全^[4-5]。笔者主张以“功能可切除性”为决策基石：围绕未来肝残余（future liver remnant，FLR）“体积+功能”评估[必要时用^99mTc‑mebrofenin SPECT/计算机断层扫描（computed tomography，CT）与吲哚菁绿（indocyanine green，ICG）清除试验]，并通过选择性胆道引流、感染控制、营养/凝血纠正与门静脉栓塞（portal vein embolization，PVE）建立“功能安全窗”^{[3, 6-7]}。据此构建贯穿转化/新辅助—术前功能再评估—功能导向手术—加速康复外科（enhanced recovery after surgery，ERAS）与长期随访的多阶段路径（图1），并以标准化结局集和学习曲线/转开腹标准操作流程（standard operating procedure，SOP）驱动持续质量改进。

1 功能保留视角下的适应证与分层决策

1.1 三维评估与进入手术窗口的“硬门槛”

1.1.1 解剖维度（影像与R₀可及性）

以增强CT+磁共振成像（magnetic resonance imaging，MRI）/磁共振胰胆管成像（magnetic resonance cholangio-pancreatography，MRCP）为基础，必要时超声内镜（endoscopic ultrasound，EUS）评估血管受累。存在引流指征时行内镜逆行胰胆管造影（endoscopic retrograde cholangiopancreatography，ERCP）。影像结论用于界定R₀可及性与是否需血管/胆道重建^{[3, 8]}。

1.1.2 功能维度（体积+功能并重）

采用“两步式”评估—先以15 min ICG潴留率（indocyanine green retention at 15 minutes，ICG‑R15）初筛全肝功能（>10%~14%提示高风险；>20%避免大范围切除或先优化），对黄疸、基础肝病或拟行扩大切除者升级至^99mTc‑mebrofenin SPECT/CT，量化FLR区域功能，并以功能阈值而非单纯体积作为进入手术窗口的硬门槛。FLR功能不足者优先选择PVE，4~6周后复测功能再判定时机^{[6, 9-13]}。

1.1.3 全身维度（胆道通畅、感染、营养/凝血）

对需扩大肝切除、伴胆管炎或胆红素明显升高者，实施选择性胆道引流（优先引流FLR），在总胆红素（total bilirubin，TBIL）降至约<51.3 μmol/L、感染受控与国际标准化比值（international normalized ratio，INR）正常化后择期手术。围手术期按欧洲临床营养与代谢协会与ERAS建议进行营养与凝血优化 ^{[3, 9, 14-15]}。

1.1.4 进入手术窗口的判定

需同时满足“R₀可及+FLR功能达标+胆汁淤积/感染受控+营养/凝血纠正”四要素；任何一项不达标，应先行优化后再评估 ^{[3, 6, 8-9, 13-15]}（评估流程见图2）。

1.2 转化/新辅助与“再评估—择期”框架

1.2.1 适应场景与复评频率

对边界可切除或局部进展病例，可采用化疗/免疫/靶向的转化或新辅助策略，欧洲肿瘤内科学会建议每6~8周进行1次以“解剖+功能+炎症”三维为核心的再评估，以免仅凭影像缩小而忽视功能风险^[8]。

1.2.2 肝毒性与免疫相关肝炎的识别与处理

系统治疗期间需警惕药物性肝损伤/免疫相关性肝炎；在排除胆道梗阻等非免疫性病因后，按欧洲肝病学会与美国国立综合癌症网络免疫毒性指引分级处理，≥2级应暂停治疗并启动糖皮质激素，密切监测合成功能^[16-17]。

1.2.3 辅助治疗与时机

根治性切除后优先考虑卡培他滨等辅助治疗；应在术后4~6周、功能状态稳定时启动，避免过度延迟影响生存获益^{[3, 18]}。

2 分病种路径与适应证分层

在功能保留视角下，适应证分层应以“解剖可切除性、功能可切除性与中心能力”三维框架统筹：前者界定R₀可及性及是否需血管/胆道重建，中者以FLR与区域功能的匹配为核心，后者强调学习曲线、开放救援与重建质量控制的组织化能力。微创仅是手段而非目的，只有在同时满足“R₀可及、FLR功能达标、炎症/淤胆受控、团队胜任”的前提下，方可进入微创窗口^[19-21]（分层算法见图3）。在FLR策略上，非肝硬化患者通常需FLR≥20%~30%；合并胆汁淤积或基础肝病时应提高至≥40%，并以^99mTc‑mebrofenin SPECT/CT等区域功能达标作为硬门槛；当FLR不足时优先行PVE并在4~6周后再评估，肝门静脉结扎联合肝实质分离（associating liver partition and portal vein ligation for staged hepatectomy，ALPPS）虽可快速增容但在胆汁淤积/基础肝病背景下并发症发生率与死亡率更高，应极为谨慎，仅作为无法通过PVE达标时的少数备选^{[6, 12, 20, 22-23]}。一旦在微创路径中出现切缘或清扫质量受限、需复杂血管或多腔重建或因暴露/止血不安全而威胁肿瘤学与器官功能边界，应果断中转开腹，以避免“全微创”取代肿瘤学与功能学本质^{[19-21, 24-25]}。

2.1 ICC

2.1.1 病灶定位与平台选择

外周型ICC、无需复杂血管/胆道重建且R₀可及者，可在成熟中心实施微创解剖性肝切除；靠近肝门或预期需血管/胆道重建者，以开放或分期策略为主^[19-21]。

2.1.2 功能门槛与增容

除体积外应量化FLR功能（mebrofenin SPECT/CT）；FLR不足优先PVE并“干预—再评估”；在胆汁淤积/基础肝病背景下，ALPPS虽增容快但并发症发生率与病死率更高，慎用^{[6, 12, 22-23]}。

2.2 DCC

2.2.1 入路与资质

随机对照试验（randomized controlled trial，RCT）显示跨越学习曲线后，腹腔镜胰十二指肠切除（laparoscopic pancreato-duodenectomy，LPD）在R₀切除率与总体并发症发生率上不劣于开放胰十二指肠切除（open pancreatoduodenectomy，OPD），但LEOPARD‑2研究^[24]提示早期存在安全信号；微创PD仅宜在高体量、设有转开腹SOP与外部质控的中心实施^[24-26]。机器人平台在深部重建上具有优势，但同样依赖中心化培训与量效积累^[27-28]。

2.2.2 血管受累

合并SMV/PV受累时，开放路径下的联合切除与重建更可控；微创联合血管重建不作常规，仅限具备开放血管重建救援能力的成熟中心选择性探索^[29-30]。

2.2.3 重建与并发症控制

术中以胰瘘风险评分（fistula risk score，FRS）进行胰瘘风险分层，匹配吻合与引流策略。Blumgart式胰空肠与套入式胰胃在术后临床相关胰瘘（clinically relevant postoperative pancreatic fistula，CR‑POPF）等关键结局上相当，强调“流程稳定”重于“术式名目”^[31-33]。

2.2.4 幽门处理

保留幽门的PD（PPPD）与经典PD总体结局相当，并将延迟胃排空风险一并考量，是否保幽门按侵犯范围与营养需求权衡^[34-35]。

2.3 HCCA

2.3.1 适应证分层

Bismuth-Corlette Ⅰ/Ⅱ型、无明显血管侵犯、FLR功能达标且预计可实现R₀切除者，可在高体量中心选择性开展微创；Bismuth-Corlette Ⅲ~Ⅳ型或需血管/多支胆肠吻合等复杂重建者以开放为主^{[4, 36-37]}。

2.3.2 证据概述

多中心回顾与系统综述显示，严格筛选下微创HCCA短期结局与R₀切除率可接近开放，但对血管重建与多腔复杂重建的证据不足^{[4, 36]}。

2.3.3 血管处理

门区SMV/肝动脉（hepatic artery，HA）受累以开放下的选择性重建为主；一旦微创路径下暴露与重建质量不达标，应果断转换^[38]。

2.4 GBC

2.4.1 早期病变

T1a可行微创单纯胆囊切除；T1b及以上需扩大切除与区域淋巴结清扫，微创仅在不牺牲肿瘤学质量的前提下由具资质中心实施^[39]。

2.4.2 ≥T2病变

标准为肝床扩大切除±胆管切除重建与系统清扫；多项国际与多中心真实世界研究^[40-42]提示，规范化微创路径在R₀切除率与短期结局上可接近开放，但病例选择与无瘤操作至关重要。

2.4.3 执行要点

(1) 以“体积+功能”双门槛锁定ICC/HCCA的安全切除范围；FLR不足先PVE，ALPPS仅作极少数最后选项^{[6, 13, 23]}。(2) DCC的微创PD需“中心化+分级实施+转开腹SOP”；血管受累优先开放联合重建；胰肠重建以风险分层与流程稳定为纲^{[24-25, 30, 32]}。(3) HCCA微创仅限Bismuth-Corlette Ⅰ/Ⅱ型且FLR功能达标的高度选择病例；一旦涉及血管/多腔重建，开放为标准路径^[36-37]。(4) GBC遵循分期导向与“根治优先”；任何可能降低R₀切除率或清扫质量的“微创执念”应当被避免^{[39, 41]}。

2.4.4 不同术式的R₀切除率及短期结局比较

现有研究显示，在严格病例选择及规范化技术路径下，微创BTC根治术在R₀切除率及主要短期结局方面总体可达到与开放手术相当的水平。多项多中心回顾性研究及系统综述提示，微创手术在术中出血量及住院时间方面可能具有一定优势，但其安全性和可重复性高度依赖中心经验、病例选择及团队学习曲线。对于需要复杂血管重建或多腔胆肠重建的病例，开放手术仍是更为稳妥的标准路径。不同术式在R₀切除率及主要短期结局方面的证据类型及适用边界见表1。

3 关键技术：微创手术中的“损伤控制与功能维持”

3.1 复合导航与平台匹配：把“看得清、做得稳”作为安全底线

3.1.1 复合导航工具箱

以ICG荧光+术中超声（intraoperative ultrasound，IOUS）+三维（three-dimensional，3D）重建为基础，前者用于肝段/胆道与灌注评估，后两者用于切线校正与深部解剖确认。任何时点均以R₀切除与安全止血优先；当导航结论与术野冲突时，切缘优先并果断转开腹^[48-49]。

3.1.2 平台与团队匹配

机器人在深部精细缝合与复杂重建上更稳，腹腔镜在肝实质离断与区域清扫更高效；平台选择服从“R₀切除与功能保留”，并与团队能力匹配。项目实施需中心化与分级培训，配套SOP、视频质控与带教（proctorship），预设“转开腹SOP”；血管重建不应纳入早期学习曲线^{[26, 50]}。

3.2 切缘—清扫—重建一体化：以R₀切除为纲，靠流程稳定降并发症

3.2.1 切缘与清扫

以R₀切除为硬目标，ICG+IOUS用于实时边界校正；淋巴清扫强调站群化与整块完整性，质量优先于“数量”，建议同步报告阳性淋巴结与总淋巴结比例以提升可比性^[48]。

3.2.2 胆肠/胰肠重建

重建要义是“低张力、良好灌注、精准对合”，而非术式名目。胆肠吻合追求宽大、无扭曲的黏膜对黏膜对合，并按国际胰外科研究组（International Study Group of Pancreatic Surgery，ISGPS）分级对胆汁漏进行分层处置^[51]。胰肠重建基于FRS风险分层选择技术并统一按ISGPS 2016口径上报，微创路径仅应在高体量、完成资质准入与规范化培训的中心推进^{[26, 50]}。

3.3 血管与转开腹阈值：把“可控重建”和“及时止损”写进SOP

3.3.1 血管处理

涉及主干PV/SMV/HA时，以开放下的选择性联合切除重建为主；微创血管重建不作常规，仅限具备开放救援能力的成熟中心在预设红线下选择性开展^[38]。

3.3.2 转开腹触发点

R₀不可及或暴露/止血不安全、活动性大出血、预计多腔复杂重建质量受限等，均应立即触发转开腹，避免“微创执念”侵蚀肿瘤学与功能学边界^{[26, 38, 50]}。

3.3.3 围手术期关键阈值及触发干预策略

围手术期管理需要依托一系列可量化指标进行动态监测，以便在功能恶化或并发症发生前及时启动干预措施。针对肝功能储备、胆道感染控制、凝血状态及营养状况等关键环节，应设置相应的预警阈值，并在达到阈值时及时采取针对性干预措施，如强化抗感染治疗、优化胆道引流策略、加强营养支持或必要时调整手术时机等。通过建立“指标监测—阈值判断—触发干预”的标准化管理路径，可在一定程度上降低围手术期并发症发生风险并提高手术安全性。围手术期关键阈值及其对应的触发行动见表2。

4 围手术期综合管理：ERAS 2.0与器官功能保留

4.1 术前优化与再评估：用“体积+功能+通畅/感染+营养/凝血”锁定手术窗口

4.1.1 功能安全窗与复评节奏

(1) 硬门槛“四要素”：R₀可及性确认+FLR体积/功能达标+胆道通畅/感染受控+营养与凝血纠正；任一未达标先优化后再评估^{[8-9, 13]}。(2) FLR评估：常规以体积评估结合ICG-R15初筛；黄疸/基础肝病/拟行扩大切除或边界病例，升级至^99mTc‑mebrofenin SPECT/CT进行区域功能定量，更能预测肝切除后肝功能衰竭（post‑hepatectomy liver failure，PHLF）风险^{[6, 11, 13]}。FLR功能不足者优先PVE，4~6周后复测“功能而非仅体积”决定时机；HCCA建议先选择性减黄，使TBIL<85 μmol/L后再实施PVE^[37]。

4.1.2 减黄路径与技术选择

(1) 何时减黄：TBIL>250~300 μmol/L或合并胆管炎；拟大范围肝切除或FLR临界者优先“选择性引流FLR”，目标是TBIL<51.3 μmol/L且稳定、感染受控后择期手术^{[8-9, 67]}。(2) 如何减黄：DCC优先ERCP（短期拟手术者多选塑料支架）；高位梗阻（HCCA）以ENBD/PTBD靶向引流FLR为主，ERCP失败或不可行时可选内镜超声引导胆道引流^{[14, 54-58]}。

4.1.3 感染控制与凝血/营养优化

(1) 胆管炎处置：尽快有效引流+早期广谱抗菌，复发/难治根据胆汁培养与药敏调整；“先控感染，再谈手术/增容”^{[8, 14, 67]}。(2) 凝血/营养：补充维生素K与脂溶性维生素，优先免疫营养^{[9, 15]}。(3) 围手术期优化与预康复：结合运动/营养/贫血与血糖管理、静脉血栓栓塞（venous thromboembolism，VTE）预防与戒烟减酒等打包实施，以提升耐受窗并降低并发症^{[9, 15, 68]}。

4.1.4 运行与质控要点

建议中心级监测ERAS依从度（≥70%为基线），按季度复盘“TBIL<51.3 μmol/L达标率、感染控制达标率、国际标准化比值（INR）纠正达标率、PVE后功能达标率”，作为进入手术窗口的过程关键绩效指标^[9]。

4.2 术后器官功能维持：目标导向复苏+引流与并发症算法+标准化结局上报

4.2.1 目标导向复苏与代谢管理

低并发症液体策略：目标导向补液（小剂量晶体液反应性评估；无反应及早血管活性药物），优先平衡晶体液，避免过量补液致肝/肠水肿；强化血糖管理（<180 mg/dL）与VTE预防，多模式镇痛减少阿片相关胃肠抑制，支撑早期肠内营养与活动^{[9, 15, 68]}。

4.2.2 引流与并发症防控

(1) 胆汁漏：术中坚持“低张力+良好灌注+精准对合”，必要时ICG查漏；术后以引流液胆红素>血清3倍等判定并分级管理，B/C级合并感染优先经皮/内镜引流，尽量避免早期再手术^{[9, 51]}。(2) 胰瘘：术中FRS分层选择吻合与引流策略；PD术后第1天引流液淀粉酶<5 000 U/L可早拔，≥5 000 U/L高危者延迟拔管并强化监测^{[32, 59, 69]}。(3) PHLF预防与识别：动态监测TBIL与INR，术后第5天后TBIL>50 μmol/L并INR升高定义PHLF，需结合综合并发症指数（comprehensive complication index，CCI）评估全身累积负担并早期多学科干预^[70-72]。(4) 出血预警：引流液持续鲜红、24 h>500 mL或Hb快速下降即启动影像/介入/复手术通道，避免等待性恶化^[9]。

4.2.3 结局上报与质量改进

统一口径：PHLF（ISGLS）^[71]、CR‑POPF（ISGPS 2016）^[32]、胆汁漏（ISGLS）^[51]、Clavien‑Dindo ^[73]、CCI^[70]、30 d/90 d再入院与死亡；作为跨中心可比与持续改进的核心数据集^[9]。

4.3 ERAS 2.0与长期康复：早期肠内—胆汁酸/微生态—PRO—治疗时机

4.3.1 早期肠内与功能恢复

(1) 24 h内启动经口/空肠管喂养^{[9, 59]}。(2) 脂溶性维生素常规补充^{[9, 15]}。

4.3.2 胆汁酸—微生态支持

通过早期肠内营养“重建胆汁入肠”与屏障修复；短程考来烯胺应对胆汁酸性腹泻，必要时合并洛哌丁胺；药物性胆汁淤积/瘙痒可试用熊去氧胆酸；个体化使用益生菌/可溶性纤维^{[9, 15, 67]}。

4.3.3 随访、PRO与系统治疗时机

(1) 影像学与检验：症状驱动复查（黄疸复现/发热/肝酶异常时行超声/CT/MRCP），常规监测肝功能与CA19‑9，避免无指征的影像学过度随访^{[3, 8, 67]}。(2) PRO：建议采用QLQ-C30、BIL21于30/90 d、6/12个月评估，并以MID（多数域评分5~10）判读临床意义，作为康复计划迭代依据^[64-65]。(3) 辅助治疗时机：根治术后4~6周、肝功能稳定且无活动性胆汁漏/感染时启动，尽量避免>12周延迟；真实世界支持在约7~8周内启动更可行^{[18, 74]}。(4) 脆弱/高龄患者：开展综合老年评估，在肿瘤控制与功能维持间个体化权衡^[75-76]。(5) 关于“功能性恢复时间”（time to functional recovery，TFR）：BTC领域尚缺一致的功能性恢复复合终点定义，当前应依ERAS核心指标+PRO的“过程+结局”双维管理，谨慎解释TFR外推证据^{[59, 77]}。

5 专家观点与未来方向

5.1 功能优先、微创其次

决策以“R₀可及+功能安全窗”为先：需同时满足R₀可及、FLR体积—功能达标、减黄/控感染、营养—凝血纠正后再择期手术^{[3, 6, 9]}。微创是手段不是目的：一旦R₀或重建稳定性存疑，或暴露/止血不安全，立即转开腹，避免“微创执念”^{[3, 9]}。FLR优化路径：FLR边界者优先选择性减黄与PVE，4~6周按“区域功能（而非仅体积）”再评估；ALPPS仅作为极少数备选^{[6, 9]}。

5.2 技术与能力：从器械到体系

学习曲线与中心化是前提：随机证据提示LPD在学习曲线早期存在安全风险，微创PD仅宜在高体量中心并设置转开腹SOP下开展^[24]。导航与流程胜于术式名目：ICG/IOUS/3D规划用于“看得清、做得稳”；重建强调“低张力、良好灌注、精准对合”。技术升级服务于稳定流程与可复制质量。

5.3 中国路径与研究重点

坚持病例选择+无瘤操作：在“功能可切除性”与团队能力边界内，微创GBC与选择性微创HCCA的R₀切除率与短期结局可接近开放，是否实施以功能与安全为先^{[36, 39]}。结局导向升级：用PHLF（ISGLS）与PRO（QLQ‑C30/QLQ‑BIL21；参考MID判读）联动ERAS与康复随访，少堆过程指标，多看“功能与生活质量”^{[9, 65, 71]}。证据建设优先级：以全国注册/真实世界平台为抓手，聚焦“功能结局+生存”的综合比较；围绕学习曲线、ERAS依从度与转开腹触发点开展外部质控 ^[9]。

5.4 结语

把“功能保留”确立为BTC外科的共同语言：目标锁定R₀与长期功能，路径依托中心化团队与标准化流程，技术创新服务于更好的功能、生活质量与生存，而非单纯“更微创”。

参考文献

[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263. doi:10.3322/caac.21834 .

[2] Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(9):557-588. doi:10.1038/s41575-020-0310-z .

[3] Benson AB, 3rd D'Angelica MI, Abrams T, et al. Biliary tract cancers, version 2.2025, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2025, 23(9):403-418. doi:10.6004/jnccn.2025.0042 .

[4] Li JD, Xiong YF, Gang Y, et al. Minimally invasive surgery for hilar cholangiocarcinoma: a multicenter retrospective analysis of 158 patients[J]. Surg Endosc, 2021, 35(12):6612-6622. doi:10.1007/s00464-020-08161-8 .

[5] Fichtinger RS, Aldrighetti LA, Abu Hilal M, et al. Laparoscopic versus open hemihepatectomy: the ORANGE Ⅱ PLUS multicenter randomized controlled trial[J]. J Clin Oncol, 2024, 42(15):1799-1809. doi:10.1200/JCO.23.01019 .

[6] Arntz PJW, Deroose CM, Marcus C, et al. Joint EANM/SNMMI/IHPBA procedure guideline for [(99m)Tc] Tc-mebrofenin hepatobiliary scintigraphy SPECT/CT in the quantitative assessment of the future liver remnant function[J]. HPB (Oxford), 2023, 25(10):1131-1144. doi:10.1016/j.hpb.2023.06.001 .

[7] Zhou J, Tan ZG, Sun B, et al. Application of indocyanine green fluorescence imaging in hepatobiliary surgery[J]. Int J Surg, 2024, 110(12):7948-7961. doi:10.1097/JS9.0000000000001802 .

[8] Vogel A, Bridgewater J, Edeline J, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up[J]. Ann Oncol, 2023, 34(2):127-140. doi:10.1016/j.annonc.2022.10.506 .

[9] Joliat GR, Kobayashi K, Hasegawa K, et al. Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) society recommendations 2022[J]. World J Surg, 2023, 47(1):11-34. doi:10.1007/s00268-022-06732-5 .

[10] Makuuchi M, Kosuge T, Takayama T, et al. Surgery for small liver cancers[J]. Semin Surg Oncol, 1993, 9(4):298-304. doi:10.1002/ssu.2980090404 .

[11] Olthof PB, Coelen RJS, Bennink RJ, et al. ^99mTc-mebrofenin hepatobiliary scintigraphy predicts liver failure following major liver resection for perihilar cholangiocarcinoma[J]. HPB (Oxford), 2017, 19(10):850-858. doi:10.1016/j.hpb.2017.05.007 .

[12] de Graaf W, van Lienden KP, van Gulik TM, et al. ^99mTc-mebrofenin hepatobiliary scintigraphy with SPECT for the assessment of hepatic function and liver functional volume before partial hepatectomy[J]. J Nucl Med, 2010, 51(2):229-236. doi:10.2967/jnumed.109.069724 .

[13] Primavesi F, Maglione M, Cipriani F, et al. E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy[J]. Br J Surg, 2023, 110(10):1331-1347. doi:10.1093/bjs/znad233 .

[14] Elmunzer BJ, Maranki JL, Gómez V, et al. ACG clinical guideline: diagnosis and management of biliary strictures[J]. Am J Gastroenterol, 2023, 118(3):405-426. doi:10.14309/ajg.0000000000002190 .

[15] Weimann A, Braga M, Carli F, et al. ESPEN practical guideline: Clinical nutrition in surgery[J]. Clin Nutr, 2021, 40(7):4745-4761. doi:10.1016/j.clnu.2021.03.031 .

[16] European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-induced liver injury[J]. J Hepatol, 2019, 70(6):1222-1261. doi:10.1016/j.jhep.2019.02.014 .

[17] Thompson JA, Schneider BJ, Brahmer J, et al. NCCN guidelines® insights: management of immunotherapy-related toxicities, version 2.2024[J]. J Natl Compr Canc Netw, 2024, 22(9):582-592. doi:10.6004/jnccn.2024.0057 .

[18] Shroff RT, Kennedy EB, Bachini M, et al. Adjuvant therapy for resected biliary tract cancer: ASCO clinical practice guideline[J]. J Clin Oncol, 2019, 37(12):1015-1027. doi:10.1200/JCO.18.02178 .

[19] Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka[J]. Ann Surg, 2015, 261(4):619-629. doi:10.1097/SLA.0000000000001184 .

[20] Abu Hilal M, Aldrighetti L, Dagher I, et al. The southampton consensus guidelines for laparoscopic liver surgery: from indication to implementation[J]. Ann Surg, 2018, 268(1):11-18. doi:10.1097/SLA.0000000000002524 .

[21] European Association for the Study of the Liver. EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma[J]. J Hepatol, 2023, 79(1):181-208. doi:10.1016/j.jhep.2023.03.010 .

[22] Arntz P, Olthof PB. Assessment of liver function before major hepatectomy[J]. Br J Surg, 2023, 110(12):1588-1589. doi:10.1093/bjs/znad216 .

[23] Li J, Moustafa M, Linecker M, et al. ALPPS for locally advanced intrahepatic cholangiocarcinoma: did aggressive surgery lead to the oncological benefit? an international multi-center study[J]. Ann Surg Oncol, 2020, 27(5):1372-1384. doi:10.1245/s10434-019-08192-z .

[24] van Hilst J, de Rooij T, Bosscha K, et al. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial[J]. Lancet Gastroenterol Hepatol, 2019, 4(3):199-207. doi:10.1016/S2468-1253(19)30004-4 .

[25] Wang M, Li D, Chen R, et al. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours: a multicentre, open-label, randomised controlled trial[J]. Lancet Gastroenterol Hepatol, 2021, 6(6):438-447. doi:10.1016/S2468-1253(21)00054-6 .

[26] Liu R, Abu Hilal M, Besselink MG, et al. International consensus guidelines on robotic pancreatic surgery in 2023[J]. Hepatobiliary Surg Nutr, 2024, 13(1):89-104. doi:10.21037/hbsn-23-132 .

[27] Zureikat AH, Beane JD, Zenati MS, et al. 500 minimally invasive robotic pancreatoduodenectomies: one decade of optimizing performance[J]. Ann Surg, 2021, 273(5):966-972. doi:10.1097/SLA.0000000000003550 .

[28] Jones LR, Zwart MJW, de Graaf N, et al. Learning curve stratified outcomes after robotic pancreatoduodenectomy: International multicenter experience[J]. Surgery, 2024, 176(6):1721-1729. doi:10.1016/j.surg.2024.05.044 .

[29] Giovinazzo F, Turri G, Katz MH, et al. Meta-analysis of benefits of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma[J]. Br J Surg, 2016, 103(3):179-191. doi:10.1002/bjs.9969 .

[30] Maeta T, Ebata T, Hayashi E, et al. Pancreatoduodenectomy with portal vein resection for distal cholangiocarcinoma[J]. Br J Surg, 2017, 104(11):1549-1557. doi:10.1002/bjs.10596 .

[31] Callery MP, Pratt WB, Kent TS, et al. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy[J]. J Am Coll Surg, 2013, 216(1):1-14. doi:10.1016/j.jamcollsurg.2012.09.002 .

[32] Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After[J]. Surgery, 2017, 161(3):584-591. doi: 10.1016/j.surg.2016.11.014 .

[33] Dorcaratto D, Garcés-Albir M, Palomares-Casasús S, et al. Blumgart anastomosis versus invaginating pancreatogastrostomy for reconstruction after pancreatoduodenectomy: a randomized controlled trial[J]. Ann Surg, 2025, 282(5):699-708. doi:10.1097/SLA.0000000000006873 .

[34] Tran KTC, Smeenk HG, van Eijck CHJ, et al. Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors[J]. Ann Surg, 2004, 240(5):738-745. doi:10.1097/01.sla.0000143248.71964.29 .

[35] Klaiber U, Probst P, Strobel O, et al. Meta-analysis of delayed gastric emptying after pylorus-preserving versus pylorus-resecting pancreatoduodenectomy[J]. Br J Surg, 2018, 105(4):339-349. doi:10.1002/bjs.10771 .

[36] de Hondt J, Zwart MJW, Uijterwijk BA, et al. Minimally invasive liver surgery for perihilar and intrahepatic cholangiocarcinoma: systematic review and meta-analysis of comparative studies[J]. Surg Endosc, 2025, 39(11):7141-7159. doi:10.1007/s00464-025-11900-4 .

[37] Liu S, Jiang J, Jian Q, et al. Chinese multicenter expert consensus on the diagnosis and treatment of hilar cholangiocarcinoma: 2025 edition[J]. Biosci Trends, 2025, 19(4):379-403. doi:10.5582/bst.2025.01233 .

[38] Poletto E, Olthof PB, Hoogwater FJH, et al. Operative and oncological outcomes of vascular resection and reconstruction for perihilar cholangiocarcinoma[J]. Ann Surg Oncol, 2025, 32(13):9597-9607. doi:10.1245/s10434-025-18137-4 .

[39] Palepu J, Endo I, Chaudhari VA, et al. 'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer[J]. HPB (Oxford), 2024, 26(11):1311-1326. doi:10.1016/j.hpb.2024.07.411 .

[40] Hale J, Landrum KR, Agala C, et al. Minimally invasive vs. open radical cholecystectomy for gallbladder cancer: 30-day NSQIP outcomes analysis[J]. Surg Endosc, 2025, 39(6):3873-3882. doi:10.1007/s00464-025-11755-9 .

[41] Cremona S, Ielpo B, di Martino M, et al. Textbook outcomes and minimally invasive techniques in resectable gallbladder cancer: a global cohort study[J]. Eur J Surg Oncol, 2025, 51(10):110284. doi:10.1016/j.ejso.2025.110284 .

[42] Law JH, Raptis D, Leong EKF, et al. Outcomes and safety of minimally invasive surgery in gallbladder cancer: international, multicenter cohort study[J]. Int J Surg, 2025. doi: 10.1097/JS9.0000000000004129 . [Online ahead of print]

[43] Mantzavinou A, Uppara M, Chan J, et al. Robotic versus open pancreaticoduodenectomy, comparing therapeutic indexes: a systematic review[J]. Int J Surg, 2022, 101:106633. doi:10.1016/j.ijsu.2022.106633 .

[44] Nagino M, Hirano S, Yoshitomi H, et al. Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition[J]. J Hepatobiliary Pancreat Sci, 2021, 28(1):26-54. doi:10.1002/jhbp.870 .

[45] Cillo U, Perri G, Gringeri E, et al. Technical aspects of patch reconstruction during open and robotic pancreatoduodenectomy with venous resection: preserving venous axis and collaterals without sacrificing radicality[J]. Ann Surg Oncol, 2025, 32(13):9974-9978. doi:10.1245/s10434-025-18148-1 .

[46] Zhou W, Li P. ALPPS vs traditional two-stage hepatectomy[A]//Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS)[M]. Singapore: Springer Nature Singapore, 2025: 171-186. doi:10.1007/978-981-96-7364-3_16 .

[47] Byrne M, Ruffolo LI, Hernandez-Alejandro R. ALPPS and the endless pursuit of hepatic resectability[J]. Hepatobiliary Surg Nutr, 2022, 11(5):732-734. doi:10.21037/hbsn-22-357 .

[48] Wang X, Teh CSC, Ishizawa T, et al. Consensus guidelines for the use of fluorescence imaging in hepatobiliary surgery[J]. Ann Surg, 2021, 274(1):97-106. doi:10.1097/SLA.0000000000004718 .

[49] Ratti F, Serenari M, Corallino D, et al. Augmented reality improving intraoperative navigation in minimally invasive liver surgery: an interplay between 3D reconstruction and indocyanine green[J]. Updates Surg, 2024, 76(7):2701-2708. doi:10.1007/s13304-024-01857-9 .

[50] Wang J, Lu P, Armstrong M, et al. Advancing minimally invasive hepato-pancreato-biliary surgery: ensuring safety with implementation[J]. Surg Endosc, 2024, 38(8):4365-4373. doi:10.1007/s00464-024-10957-x .

[51] Koch M, Garden OJ, Padbury R, et al. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery[J]. Surgery, 2011, 149(5):680-688. doi:10.1016/j.surg.2010.12.002 .

[52] Kubota K, Makuuchi M, Kusaka K, et al. Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors[J]. Hepatology, 1997, 26(5):1176-1181. doi:10.1053/jhep.1997.v26.pm0009362359 .

[53] Seyama Y, Kokudo N. Assessment of liver function for safe hepatic resection[J]. Hepatol Res, 2009, 39(2):107-116. doi:10.1111/j.1872-034X.2008.00441.x .

[54] Farges O, Regimbeau JM, Fuks D, et al. Multicentre European study of preoperative biliary drainage for hilar cholangiocarcinoma[J]. Br J Surg, 2013, 100(2):274-283. doi:10.1002/bjs.8950 .

[55] Kawakami H, Kuwatani M, Onodera M, et al. Endoscopic nasobiliary drainage is the most suitable preoperative biliary drainage method in the management of patients with hilar cholangiocarcinoma[J]. J Gastroenterol, 2011, 46(2):242-248. doi:10.1007/s00535-010-0298-1 .

[56] Al Nakshabandi A, Ali FS, Albustami I, et al. Biliary drainage in hilar and perihilar cholangiocarcinoma: 25-year experience at a tertiary cancer center[J]. Gastrointest Endosc, 2024, 99(6):938-949. doi:10.1016/j.gie.2023.12.006 .

[57] Ishiwatari H, Sato J, Sakamoto H, et al. Current status of preoperative endoscopic biliary drainage for distal and hilar biliary obstruction[J]. Dig Endosc, 2024, 36(9):969-980. doi:10.1111/den.14786 .

[58] Chen YN, Sahai A, Donatelli G, et al. Endoscopic ultrasound-guided biliary drainage of first intent with a lumen-apposing metal stent vs endoscopic retrograde cholangiopancreatography in malignant distal biliary obstruction: a multicenter randomized controlled study (ELEMENT trial)[J]. Gastroenterology, 2023, 165(5):1249-1261. doi:10.1053/j.gastro.2023.07.024 .

[59] Hwang DW, Kim HJ, Lee JH, et al. Effect of Enhanced Recovery After Surgery program on pancreaticoduodenectomy: a randomized controlled trial[J]. J Hepatobiliary Pancreat Sci, 2019, 26(8):360-369. doi:10.1002/jhbp.641 .

[60] Ricci C, Ingaldi C, Alberici L, et al. Blumgart anastomosis after pancreaticoduodenectomy. a comprehensive systematic review, meta-analysis, and meta-regression[J]. World J Surg, 2021, 45(6):1929-1939. doi:10.1007/s00268-021-06039-x .

[61] Calabrese EC, Kumar S, Shehata D, et al. SAGES 2025 guidelines for fluorescence image-guided gastrointestinal surgery using indocyanine green[J]. Surg Endosc, 2025, 39(12):7935-7957. doi:10.1007/s00464-025-12356-2 .

[62] Benson AB, D'Angelica MI, Abbott DE, et al. Hepatobiliary cancers, version 2.2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(5):541-565. doi:10.6004/jnccn.2021.0022 .

[63] 中国研究型医院学会放射学专业委员会, 上海市医学会放射科专科分会. 3D可视化技术在肝胆外科中的临床应用专家共识(2022年版)[J]. 肿瘤影像学, 2023, 32(1):89-99. doi:10.19732/j.cnki.2096-6210.2023.01.015 .

[64] Radiology Committee of Chinese Research Hospital Association;Radiology Committee of Shanghai Medical Association. Expert consensus on clinical application of 3D visualization in hepatobiliary surgery(2022 edition)[J]. Oncoradiology, 2023, 32(1):89-99. doi:10.19732/j.cnki.2096-6210.2023.01.015 .

[65] Kaupp-Roberts SD, Yadegarfar G, Friend E, et al. Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder[J]. Br J Cancer, 2016, 115(9):1032-1038. doi:10.1038/bjc.2016.284 .

[66] Musoro JZ, Coens C, Sprangers MAG, et al. Minimally important differences for interpreting EORTC QLQ-C30 change scores over time: a synthesis across 21 clinical trials involving nine different cancer types[J]. Eur J Cancer, 2023, 188:171-182. doi:10.1016/j.ejca.2023.04.027 .

[67] Cocks K, Wells JR, Johnson C, et al. Content validity of the EORTC quality of life questionnaire QLQ-C30 for use in cancer[J]. Eur J Cancer, 2023, 178:128-138. doi:10.1016/j.ejca.2022.10.026 .

[68] Wang X, Bai Y, Chai N, et al. Chinese national clinical practice guideline on diagnosis and treatment of biliary tract cancers[J]. Chin Med J, 2024, 137(19):2272-2293. doi:10.1097/CM9.0000000000003258 .

[69] Cooper SL, Panesar P, Davidson J. Preoperative optimization and enhanced recovery after surgery[J]. Surg Oxf, 2022, 40(12):790-795. doi:10.1016/j.mpsur.2022.10.018 .

[70] Wu Y, Peng B, Liu JH, et al. Textbook outcome as a composite outcome measure in laparoscopic pancreaticoduodenectomy: a multicenter retrospective cohort study[J]. Int J Surg, 2023, 109(3):374-382. doi:10.1097/JS9.0000000000000303 .

[71] Slankamenac K, Graf R, Barkun J, et al. The comprehensive complication index: a novel continuous scale to measure surgical morbidity[J]. Ann Surg, 2013, 258(1):1-7. doi:10.1097/SLA.0b013e318296c732 .

[72] Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS)[J]. Surgery, 2011, 149(5):713-724. doi:10.1016/j.surg.2010.10.001 .

[73] Calthorpe L, Rashidian N, Cacciaguerra AB, et al. Using the comprehensive complication index to rethink the ISGLS criteria for post-hepatectomy liver failure in an international cohort of major hepatectomies[J]. Ann Surg, 2023, 277(3):e592-e596. doi:10.1097/SLA.0000000000005338 .

[74] Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey[J]. Ann Surg, 2004, 240(2):205-213. doi:10.1097/01.sla.0000133083.54934.ae .

[75] Peng Y, Xia G, Li Y, et al. Postoperative adjuvant chemotherapy and chemoimmunotherapy after radical resection for biliary tract cancer: a retrospective study[J]. Oncologist, 2025, 30(6):oyaf163. doi:10.1093/oncolo/oyaf163 .

[76] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Older Adult Oncology (Version 1.2025-December 9, 2024) 2024.

[77] Sedrak MS, Freedman RA, Cohen HJ, et al. Older adult participation in cancer clinical trials: a systematic review of barriers and interventions[J]. CA Cancer J Clin, 2021, 71(1):78-92. doi:10.3322/caac.21638 .

[78] Lassen K, Soop M, Nygren J, et al. Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations[J]. Arch Surg, 2009, 144(10):961-969. doi:10.1001/archsurg.2009.170 .