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摘要:目的
探讨围肝门外科技术治疗弥漫型肝胆管结石病的临床疗效。
方法采用回顾性描述性研究方法。收集2010年1月至2015年12月湖南省人民医院收治的122例弥漫型肝胆管结石病病人的临床病理资料；男39例,女83例；中位年龄为51岁,年龄范围为21~82岁。所有病人行围肝门切除术显露高位胆管后,行1~3级胆管切开；通过胆管拼合整形、内吻合解除狭窄后,直视下多种方法结合取尽结石；沿肝脏萎缩或胆管狭窄平面切除严重萎缩肝脏后,行T管或肝胆管盆式内引流。观察指标：（1）手术情况。（2）狭窄解除及结石清除情况。（3）随访情况。采用微信、电话或门诊方式随访。术后第1年每3个月门诊随访1次,行肝功能及腹部B超检查。随后每年复查1次肝功能和腹部B超。怀疑胆管炎或结石复发时行磁共振胰胆管成像和CT检查,了解结石复发情况和病人生存情况。随访时间截至2020年7月。正态分布的计量资料以x±s表示,偏态分布的计量资料以M（范围）表示。计数资料以绝对数或百分比表示。
结果（1）手术情况：122例病人手术时间为（253±71）min、肝门阻断时间为15 min（14~38 min）、术中出血量为200 mL（100~1 100 mL）、术后住院时间为（12±5）d。122例病人中,40例发生术后并发症,其中切口感染9例、胆汁漏8例（肝断面胆汁漏5例和胆肠吻合口漏3例）、败血症8例、胸腔积液7例、腹腔脓肿5例、肝衰竭3例、胆道出血1例（部分病人合并多种并发症）。122例病人中,术后死亡2例,其中1例为术后肝衰竭、1例为胆肠吻合口漏并发脓毒血症导致弥散性血管内凝血。胆汁漏及腹腔脓肿病人经B超引导下穿刺置管引流后好转；胆道出血病人为胆肠吻合口出血,经肝右动脉介入栓塞止血；其余并发症经保守治疗后好转。（2）狭窄解除及结石清除情况：88例合并胆管狭窄病人中,85例狭窄解除,狭窄解除率为96.59%（85/88）。122例病人中,103例结石彻底清除,19例残留结石,术后即刻结石清除率为84.43%（103/122）。19例残留结石病人中,3例拒绝行胆道镜取石,16例行T管窦道胆道镜取石碎石术（7例结石清除、9例仍残留结石）。122例病人中,110例最终结石清除,12例最终残留结石,最终结石清除率为90.16%（110/122）。（3）随访情况：122例病人中,120例获得随访（110例最终结石清除、10例残留结石）,随访时间为（78±14）个月。120例获得随访病人的1、3、5年结石复发率分别为0.83%（1/120）、6.67%（8/120）、9.17%（11/120）。110例最终结石清除病人的1、3、5年结石复发率分别为0、5.45%（6/110）、5.45%（6/110）。10例残留结石病人的1、3、5年结石复发例数分别为1、2、5例。120例获得随访的病人中,1例因终末期肝病死亡,其余病人生存状态良好。
结论围肝门外科技术治疗弥漫型肝胆管结石病安全、有效。
Abstract:ObjectiveTo investigate the clinical efficacy of perihilar surgical techniques for diffuse hepatolithiasis.
MethodsThe retrospective and descriptive study was conducted. The clinicopathological data of 122 patients with diffuse hepatolithiasis who were admitted to Hunan Provincial People's Hospital from January 2010 to December 2015 were collected. There were 39 males and 83 females, aged from 21 to 82 years, with a median age of 51 years. After perihilar hepatectomy, the first, second and third divisions of hepatic ducts were opened longitudinally. Strictures in the bile ducts were relieved by stricturoplasty and internal bile duct anastomosis, and stones were removed by multiple methods under direct vision. After resection of severe atrophic liver segment along the plane of hepatic atrophy or bile duct stricture, T-tube or hepaticojejunos-tomy was used for internal drainage. Observation indicators: (1) surgical situations; (2) stricture relief and stone removal. (3) Follow-up. Follow-up was conducted by Wechat, telephone interview or outpatient examination. Patients were followed up once every 3 months in the postoperative 1 year through liver function and abdominal B-ultrasound examination. Subsequently, liver function and abdominal B-ultrasound were reexamined once a year. Magnetic resonance cholangiopancreato-graphy and computed tomography were performed when cholangitis or stone recurrence was suspected to analyze stone recurrence and patient survival. The follow-up was up to July 2020. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers or percentages.
Results(1) Surgical situations: for the 122 patients, the operation time, hepatic portal occlusion time, volume of intraoperative blood loss, duration of postoperative hospital stay were (253±71)minutes, 15 minutes(range, 14‒38 minutes), 200 mL(range, 100‒1 100 mL), (12±5)days. Postoperative complications occurred to 40 of 122 patients. There were 9 cases of incision infection, 8 cases of bile leakage (5 cases of bile leakage at hepatic section, 3 cases of choledochojejunostomy leakage), 8 cases of septicemia, 7 cases of pleural effusion, 5 cases of abdominal abscess, 3 cases of liver failure, 1 case of biliary bleeding. Some patients had multiple complications. Among the 122 patients, 2 cases died after operation, including 1 case of postoperative liver failure and 1 case of disseminated intravascular coagulation caused by biliary-intestinal anastomotic leakage complicated with sepsis. Patients with bile leakage and abdominal abscess were improved after puncture and drainage under the guidance of B-ultrasound. Patients with cholangiojejunal anastomotic bleeding were embolized through the right hepatic artery. The other complications were improved after conservative treatment. (2) Stricture relief and stone removal: 85 of 88 patients with biliary stricture were relieved, with the stricture relief rate of 96.59%(85/88). Among the 122 patients, 103 cases had stones completely removed and 19 cases had residual stones. The immediate stone clearance rate was 84.43%(103/122). Of the 19 patients with residual stones, choledochoscopy was refused in 3 cases and choledochoscope lithotripsy was performed in 16 cases, of which 7 cases were removed and 9 cases were still residual stones. Of the 122 patients, 110 cases were finally removed stones, 12 cases were eventually residual stones, and the final stone clearance rate was 90.16%(110/122). (3) Follow-up: among the 122 patients, 120 cases including 110 cases with find stone removal and 10 cases with residual stones were followed up for (78±14)months. The 1-, 3, 5-year stone recurrence rates of 120 patients were 0.83%(1/120), 6.67%(8/120), 9.17%(11/120), respectively. The 1-, 3-, 5-year stone recurrence rates of 110 patients with final stone removal were 0, 5.45%(6/110), 5.45%(6/110), respectively. The number of cases with stone recurrence at postoperative 1-, 3- and 5-year of 10 patients with residual stones were 1, 2, 5 cases, respectively. Of 120 patients with follow-up, 1 case died of end-stage liver disease, and the other patients had good survival.
ConclusionPerihilar surgical techniques for diffuse hepatolithiasis is safe and effective.
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肝胆管结石病是我国西南地区的常见病、多发病[1]。其可引起反复胆道感染、胆汁性肝硬化、胆管癌等系列并发症,治疗十分棘手[2‑4]。“切除病肝、取尽结石、解除狭窄、矫正畸形、通畅引流”的系统治疗原则,极大地提高我国肝胆管结石病的治疗水平[5]。复杂肝胆管结石病的术后复发率及再手术率仍较高,尤其是弥漫型肝胆管结石病[6]。弥漫型肝胆管结石病由于弥散分布的结石、高位狭窄的胆管、肝门解剖的旋位、肝萎缩‑肥大复合征等导致第一肝门深在而处理困难[7]。其治疗面临常规途径无法入肝、狭窄无法解除、大范围肝切除受限、残留结石、胆肠吻合口受压等问题[8‑10]。随着围肝门外科技术的发展,基于可视化、可量化及可控化,依照胆管优先、狭窄胆管为断肝平面的原则,临床上逐步实现弥漫型肝胆管结石病治疗中病灶清除、肝脏保护及损伤控制的平衡[11‑12]。本研究回顾性分析2010年1月至2015年12月我科收治的122例弥漫型肝胆管结石病病人的临床病理资料,探讨围肝门外科技术治疗弥漫型肝胆管结石病的临床疗效。
资料与方法
一、一般资料
采用回顾性描述性研究方法。收集122例弥漫型肝胆管结石病病人的临床病理资料；男39例,女83例；中位年龄为51岁,年龄范围为21~82岁。122例病人中,肝功能Child‑Pugh A级104例,Child‑ Pugh B级18例；有胆道手术史72例,合并胆管狭窄88例,合并胆管变异13例,合并严重肝脏萎缩26例,合并急性梗阻性化脓性胆管炎并行内镜鼻胆管引流术（endoscopic nasobiliary drainage,ENBD）或PTCD 11例,合并乙型和（或）丙型病毒性肝炎11例,合并肝硬化54例。同一病人合并多种疾病。本研究通过我院医学伦理委员会审批,批号为2019‑10。病人及家属均签署知情同意书。
二、纳入标准和排除标准
纳入标准：（1）影像学检查明确诊断为弥漫型肝胆管结石病[13]。（2）综合应用围肝门外科技术。（3）术后随访≥5年。（4）临床病理资料完整。
排除标准：（1）区域性结石病。（2）胆管恶变。（3）合并门静脉海绵样变性。（4）肝功能不全。（5）临床病理资料缺失。
三、治疗方法
（一）术前管理
胆管炎病人术前给予抗菌药物抗感染治疗。急性梗阻性化脓性胆管炎行PTCD、ENBD或T管引流控制感染,感染控制1~3个月后再择期行手术治疗。疑似或确诊厌氧菌感染的病人行高压氧治疗。术前常规检查包括肝功能、凝血功能、腹部超声、上腹部增强薄层CT（图1）和MRCP检查（图2）。PTCD或ENBD带管病人常规行术前胆道造影检查。合并高位胆管狭窄、肝萎缩‑肥大复合征病人行三维重建,明确胆管、门静脉、动脉的三维位置及胆管狭窄部位。
（二）手术方法
病人呈平卧位,行右季肋区J型切口,降低肝门板。探查确认肝内结石分布及肝脏萎缩纤维化部位及程度。采用“四边法”打开胆总管,取尽胆总管内结石,探查Oddi括约肌。向上劈开肝总管至肝门隆突,探查肝内胆管狭窄。对比三维重建结果,术中B超检查引导下,确定肝内胆管狭窄平面及3级胆管起始部,沿其肝脏表面投影电刀标记预切线显示围肝门切除平面（图3）。中心静脉压控制在0~2 cmH2O（1 cmH2O=0.098 kPa）,选择Pringle法行入肝血流阻断,采用阻断15 min后开放5 min模式,微口钳夹或超声刀离断,行肝S4b段和（或）S5段整体或部分切除,完全显露左右肝蒂（图4）。沿左右肝管向上纵行劈开1级、2级胆管,4‑0可吸收缝线悬吊牵引,完全暴露3级胆管开口（图5,6）。3级胆管开口狭窄或相对狭窄行“V”字型或“U”字型切除后行“内吻合”整形解除狭窄[14]（图7）。反复“掏、挖、灌、洗”取石,胆道镜探查,确认是否残留结石及有无胆管狭窄。必要时行术中分支胆道造影或B超检查辅助定位,采用网篮取石、胆道镜碎石、肝实质切开沟通肝门等方法取尽残石。对于萎缩肝脏,则沿肝脏萎缩或胆管狭窄平面行节段性肝切除。胆管狭窄部位行纵切横缝并用可吸收缝线外翻整形（图8）。对于胆管扩张明显且Oddi括约肌功能良好的病人行单纯T管引流。若存在以下情况需行肝胆管盆式内引流术：（1）Oddi括约肌松弛或狭窄。（2）合并胆总管囊肿。（3）胆总管或双侧肝内主要胆管狭窄。（4）管状狭窄[15]。
（三）术后管理
围手术期管理遵循加速康复外科原则[16]。若T管胆汁引流量>400 mL/d,予以口服回输。术后第3天常规复查CT（图9）,术后第7天开始渐进式夹闭T管。除胆汁漏病人外,其余病人于术后2个月内行T管造影检查。术后2~3个月行胆道镜检查。出院后,嘱病人高蛋白饮食,胆固醇结石病病人给予熊去氧胆酸500 mg/d 1年[17]。
四、观察指标和评价标准
观察指标：（1）手术情况包括手术方式、手术时间、肝门阻断时间、术中出血量、术后住院时间、手术吻合方式、术后并发症发生、病人围手术期死亡和并发症治疗情况。（2）狭窄解除及结石清除情况：狭窄解除情况、即刻结石清除情况、最终结石清除情况。（3）随访情况：获得随访的例数、随访时间、结石复发情况和生存情况。
评价标准：肝胆管结石病分型参照《肝胆管结石病微创手术治疗指南（2019版）》[13]。结石复发定义为结石完全清除区域新发肝内或肝外结石[8‑10]。结石清除定义为术中胆道镜检查未见结石且术后复查B超或CT未见结石。即刻结石清除率=术后残留结石病人例数/病人总例数×100%；最终结石清除率=胆道镜取石后仍残留结石病人例数/病人总例数×100%[8‑10]。
五、随访
采用微信、电话或门诊方式随访。术后第1年每3个月门诊随访1次,行肝功能及腹部B超检查。随后每年复查1次肝功能和腹部B超。怀疑胆管炎或结石复发时行MRCP和CT检查,了解结石复发情况和病人生存情况。随访时间截至2020年7月。
六、统计学分析
应用SPSS 26.0统计软件进行分析。正态分布的计量资料以x±s表示,偏态分布的计量资料以M（范围）表示。计数资料以绝对数或百分比表示。
结果
一、手术情况
122例病人均顺利施行围肝门切除术,手术时间为（253±71）min、肝门阻断时间为15 min（14~38 min）、术中出血量为200 mL（100~1 100 mL）、术后住院时间为（12±5）d。122例病人中,40例发生术后并发症,其中切口感染9例、胆汁漏8例（肝断面胆汁漏5例和胆肠吻合口漏3例）、败血症8例、胸腔积液7例、腹腔脓肿5例、肝衰竭3例、胆道出血1例（部分病人合并多种并发症）。122例病人中,术后死亡2例,其中1例为术后肝衰竭、1例为胆肠吻合口漏并发脓毒血症导致弥散性血管内凝血。胆汁漏及腹腔脓肿病人经B超引导下穿刺置管引流后好转；胆道出血病人为胆肠吻合口出血,经肝右动脉介入栓塞止血；其余并发症经保守治疗后好转。
二、狭窄解除及结石清除情况
88例合并胆管狭窄病人中,85例狭窄解除,狭窄解除率为96.59%（85/88）。122例病人中,103例结石彻底清除,19例残留结石,术后即刻结石清除率为84.43%（103/122）。19例残留结石病人中,3例拒绝行胆道镜取石,16例行T管窦道胆道镜取石碎石术（7例结石清除、9例仍残留结石）。122例病人中,110例最终结石清除,12例最终残留结石,最终结石清除率为90.16%（110/122）。
三、随访情况
122例病人中,120例获得随访（110例最终结石消除、10例残留结石）,随访时间为（78±14）个月。120例获得随访病人的1、3、5年结石复发率分别为0.83%（1/120）、6.67%（8/120）、9.17%（11/120）。110例最终结石清除病人的1、3、5年结石复发率分别为0、5.45%（6/110）、5.45%（6/110）。10例残留结石病人的1、3、5年结石复发例数为1、2、5例。
120例获得随访的病人中,1例因终末期肝病死亡,其余病人生存状态良好。
讨论
弥漫型肝胆管结石病常因合并胆管狭窄、形态比例失调、解剖变异导致处理非常棘手[18‑19]。既往关于复杂的双侧肝内胆管结石系列研究结果显示：单侧肝切除术后即刻结石清除率、最终结石清除率和累积结石复发率分别为65.9%、81.7%和34.1%[20]。双侧肝切除术后即刻结石清除率、最终结石清除率和累积结石复发率分别为56.1%~84.2%、75.6%~95%和7.9%~22.6%[20‑23]。35%~96%的肝胆管结石病病人合并胆管狭窄,术后狭窄解除率为79%[24]。残留结石病人术后结石复发率为57%,术后狭窄未解除病人结石复发率达52%[25]。传统肝切除术治疗弥漫型肝胆管结石病因无法彻底解除胆管狭窄、结石无法取尽、结石复发率高等问题导致应用受限。此外,虽然肝移植是弥漫型肝胆管结石病的有效治愈方法,但其适应证严格,目前只作为终末期弥漫型肝胆管结石病的最终治疗方法[26⁃27]。
本研究中,笔者团队应用围肝门外科技术治疗弥漫型肝胆管结石病,最终结石清除率和结石复发率与既往研究结果相似[20‑23]。但综合应用围肝门外科技术具有以下优点：（1）围肝门切除术后肝衰竭的发生率最低。而在传统肝切除术中,没有结石或明显萎缩的肝实质常被连带切除[28]。（2）围肝门切除术降低了手术操作难度,围肝门切除的肝门阻断时间最短,这可能降低肝脏缺血再灌注损伤程度[29]。（3）围肝门切除术后,胆肠吻合建立在狭窄胆管之上,可以避免增生肥大的肝脏对胆肠吻合口的压迫[8]。（4）与传统肝切除术比较,以萎缩平面为界切除严重萎缩的肝实质,不会增加术后胆管癌的发生率[30]。
弥漫型肝胆管结石病行单侧肝切除后对侧高位狭窄解除和取石仍受限。残留结石只能通过胆总管、肝断面胆管和肝实质切开等途径用取石钳、胆道镜及肾镜探查取石[31⁃32]。围肝门外科技术的综合应用则有利于狭窄的彻底解除。围肝门切除后可充分显露左右肝蒂,使直视下纵行切开1~3级胆管狭窄及胆管内吻合成为现实。将每一段的胆管开口显露于手术视野,利于取石并避免分支胆管的遗漏导致残留结石。通过直视下拼合胆管狭窄环上下扩张胆管壁,从而解除膜状狭窄；管状狭窄则横断胆总管,将胆肠吻合口建立在狭窄以上,避免术后狭窄导致引流不畅,防止结石复发。尽管目前对内镜下狭窄切除、钬激光消融、球囊扩张、胆道支架等技术进行了新探索,但上述技术的安全性及有效性有待进一步研究证实[10,33⁃34]。
本研究存在以下局限：（1）研究为样本量较小的单中心回顾性研究。（2）围肝门切除术后高位胆管切开增加了胆肠内引流病人的占比。（3）不能准确评估狭窄成形术后原胆管狭窄部位的状态。
综上,综合应用围肝门外科技术治疗弥漫型肝内胆管结石病安全、有效。
所有作者均声明不能存在利益冲突李佳, 李国光, 胡脉涛, 等. 围肝门外科技术治疗弥漫型肝胆管结石病的临床疗效[J]. 中华消化外科杂志, 2021, 20(8): 883-889. DOI: 10.3760/cma.j.cn115610-20210810-00389.http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.cn115610-20210810-00389
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