Application value of indocyanine green fluorescence-guided laparoscopic anatomical monosegmentectomy in pediatric living donor liver transplantation
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摘要:目的
探讨吲哚菁绿荧光引导腹腔镜解剖性肝段获取术在小儿活体肝移植中的应用价值。
方法采用回顾性描述性研究方法。收集2019年12月至2020年1月首都医科大学附属北京友谊医院收治的2例行活体肝移植患儿和2例供者的临床资料。病例1,女,年龄为1岁,体质量为8.7 kg。供者为患儿父亲,年龄为35岁,体质量为93.1 kg。病例2,男,年龄为1岁,体质量为7.5 kg。供者为患儿父亲,年龄为39岁,体质量为84.0 kg。2例供者均行吲哚菁绿荧光引导腹腔镜解剖性肝段获取术获取供肝。观察指标：（1）供者手术情况。（2）供者术后情况。（3）受者术后情况。（4）随访情况。采用电话、门诊、短信、微信方式进行随访。供者于术后第1、3、6个月随访1次,了解肝功能恢复情况。受者于术后每周随访1次,了解移植物功能情况,以及排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症发生情况。随访时间截至2020年7月。
结果（1）供者手术情况。病例1供者总手术时间为234 min,供肝减体积处理时间为40 min,术中出血量为60 mL,未输血。经减体积处理后供肝实际质量为225.2 g。病例2供者总手术时间为220 min,供肝减体积处理时间为40 min,术中出血量为40 mL,未输血。经减体积处理后供肝实际质量为178.0 g。（2）供者术后情况。病例1供者丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBil）于术后第2天达到峰值,分别为493 U/L、186.0 U/L、30.66 μmol/L,于术后第3天下降为388 U/L、90.9 U/L、22.57 μmol/L；术后首次下床活动时间为术后2 d、术后首次进食流质食物时间为术后1 d、术后拔除腹腔引流管时间为术后3 d、术后住院时间为4 d、围术期无≥Clavien-Dindo Ⅱ级并发症发生。病例2供者ALT、AST、TBil于术后第1天达到峰值,分别为602 U/L、454.6 U/L、30.49 μmol/L,于术后第4天下降为355 U/L、55.7 U/L、20.65 μmol/L；术后首次下床活动时间为术后2 d、术后首次进食流质食物时间为术后1 d、术后拔除腹腔引流管时间为术后3 d、术后住院时间为5 d、围术期无≥Clavien-Dindo Ⅱ级并发症发生。（3）受者术后情况。病例1 ALT、AST、TBil于术后第1天达到峰值,分别为670 U/L、288.7 U/L、22.13 μmol/L,于术后第14天下降为54 U/L、33.0 U/L、5.75 μmol/L；术后住院时间为20 d,围术期无≥Clavien-Dindo Ⅱ级并发症发生。病例2 ALT、AST、TBil于术后第1天达到峰值,分别为520 U/L、93.9 U/L、31.42 μmol/L,于术后第14天下降为87 U/L、60.8 U/L、11.51 μmol/L；术后住院时间为25 d,围术期无≥Clavien-Dindo Ⅱ级并发症发生。（4）随访情况。2例供者均获得术后1、3、6个月随访,术后1个月随访肝功能恢复至正常水平,术后3个月及6个月随访肝功能未见异常。2例受者均获得术后每周随访。随访期间,移植物功能均正常,均未发生排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症。
结论吲哚菁绿荧光引导腹腔镜解剖性肝段获取术应用于小儿活体肝移植安全、可行,可由具有丰富腹腔镜供肝获取手术经验的团队施行。
Abstract:ObjectiveTo investigate the application value of indocyanine green fluorescence(ICG)-guided laparoscopic anatomical monosegmentectomy in pediatric living donor liver transplantation.
MethodsThe retrospective and descriptive study was conducted. The clinical data of 2 pediatric recipients undergoing living donor liver transplantation and 2 donors who were admitted to the Beijing Friendship Hospital Affiliated to Capital Medical University from December 2019 to January 2020 were collected. Case 1 was female, aged 1 year, weighted 8.7 kg. The living donor was the father of case 1, aged 35 years and weighted 93.1 kg. Case 2 was male, aged 1 year, weighted 7.5 kg. The living donor was the father of case 2, aged 39 years and weighted 84.0 kg. Both of 2 donors underwent ICG-guided laparoscopic anatomical monosegmentectomy to obtain the graft. Observation indicators: (1) surgical situations of donors; (2) postoperative situations of donors; (3) postoperative situations of recipients; (4) follow-up. Follow-up was conducted using telephone interview, outpatient examination, mobile short message or the WeChat. Donors were followed up at postoperative 1, 3, 6 months to detect recovery of liver function. Recipients were followed up once a week postoperatively to detect graft function and complications including rejection, bile leakage, biliary stenosis, thrombosis, vascular stenosis up to July 2020.
Results(1) Surgical situations of donors: the total operation time, time of preparing reduced-size grafts, volume of intraoperative blood loss of the donor of case 1 were 234 minutes, 40 minutes, 60 mL, respectively. There was no blood transfusion during the operation and the final graft weight was 225.2 g after reducing size. The total operation time, time of preparing reduced-size grafts, volume of intra-operative blood loss of the donor of case 2 were 220 minutes, 40 minutes, 40 mL, respectively. There was no blood transfusion during the operation and the final graft weight was 178.0 g after reducing size. (2) Postoperative situations of donors: on the postoperative second day, the levels of alanine amino-transferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil)of the donor of case 1 reached the peak of 493 U/L, 186.0 U/L, 30.66 μmol/L, respectively, and then decreased to 388 U/L, 90.9 U/L, 22.57 μmol/L on the postoperative third day. The time to postoperative out-of-bed activity, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, duration of postoperative hospital stay of the donor of case 1 were 2 days, 1 day, 3 days, 4 days, respectively. There was no Clavien-Dindo grade Ⅱ-Ⅴ complication occurred during the perioperative period. On the postoperative first day, the level of ALT, AST, TBil of the donor of case 2 reached the peak of 602 U/L, 454.6 U/L, 30.49 μmol/L, respectively, and then decreased to 355 U/L, 55.7 U/L,20.65 μmol/L on the postoperative fourth day. The time to postoperative out-of-bed activity, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, duration of postoperative hospital stay of the donor of case 2 were 2 days, 1 day, 3 days, 5 days, respectively. There was no Clavien-Dindo grade Ⅱ-Ⅴcomplication occurred during the perioperative period. (3) Postoperative situations of recipients: on the postoperative first day, the levels of ALT, AST, TBil of case 1 reached the peak of 670 U/L, 288.7 U/L, 22.13 μmol/L, respectively, and then decreased to 54 U/L, 33.0 U/L, 5.75 μmol/L on the postoperative fourteenth day. The duration of postoperative hospital stay of case 1 was 20 days and there was no Clavien-Dindo grade Ⅱ-Ⅴ complication occurred during the perioperative period. On the postoperative first day, the levels of ALT, AST, TBil of case 2 reached the peak of 520 U/L, 93.9 U/L, 31.42 μmol/L, respectively, and then decreased to 87 U/L, 60.8 U/L, 11.51 μmol/L on the postoperative fourteenth day. The duration of postoperative hospital stay of case 2 was 25 days and there was no Clavien-Dindo grade Ⅱ-Ⅴ complication occurred during the perioperative period. (4) Follow-up: 2 donors were followed up at postoperative 1, 3, 6 months. The liver function of 2 donors recovered to normal level at postoperative 1 month, and no abnormal liver function was found at postoperative 3 months or 6 months. Two recipients were followed up weekly after. During the follow-up, both recipients had normal graft function and no complication such as rejection, bile leakage, biliary stricture, thrombosis or vascular stenosis emerged.
ConclusionICG-guided laparoscopic anatomical mono-segmentectomy is safe and feasible in pediatric living donor liver transplantation, which can be performed by a team with rich experience in laparoscopic liver graft acquisition.
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随着手术器械与手术技术的不断发展和日益提高,小儿肝移植行腹腔镜活体肝左外叶获取术已被全世界公认为安全的标准手术方式[1- 2]。Kasahara等[3]的研究结果显示：对于部分小月龄、体质量较低的肝移植患儿,当供肝左外叶体积过大,即移植物质量与受者体质量比（graft to recipient weight ratio,GRWR）>4.0%时,受者术后死亡风险增加。Kitajima等[4]的研究结果显示：当GRWR>4.0%或供肝左外叶最大前后径与受者腹上区前后径比值>1.0时,需进行供肝减体积处理。目前常用的供肝减体积处理方案由日本学者提出：（1）单纯削减肝左外叶厚度。（2）非解剖性肝左外叶减体积手术。（3）保留门静脉肝脏Ⅲ段分支的改良肝脏Ⅱ段移植物获取术[3-4]。本研究回顾性分析2019年12月至2020年1月我中心收治的2例行活体肝移植患儿和2例供者的临床资料,探讨吲哚菁绿荧光引导腹腔镜解剖性肝段获取术在小儿活体肝移植中的应用价值。
资料与方法
一、一般资料
采用回顾性描述性研究方法。收集2例行小儿活体肝移植患儿和2例供者的临床资料。病例1,女,年龄为1岁,体质量为8.7 kg,术前诊断胆道闭锁、肝硬化失代偿期、门静脉高压症,行葛西术后,需行肝移植。供者为患儿父亲,年龄为35岁,体质量为93.1 kg。病例2,男,年龄为1岁,体质量为7.5 kg,术前诊断鸟氨酸氨甲酰基转移酶缺乏症、代谢性脑病、神经系统发育迟滞,需行肝移植。供者为患儿父亲,年龄为39岁,体质量为84.0 kg。2例供者均行吲哚菁绿荧光引导腹腔镜解剖性肝段获取术获取供肝。本研究通过我院医学伦理委员会审批,病例1批号为BJFH-EC-L/2019-045,病例2批号为BJFH-EC-L/2019-123。供者、受者符合国际移植学会指南。供者、受者家属均签署知情同意书。
二、供者术前评估
2例供者术前肝功能检查均为Child-Pugh A级,增强CT检查肝脏血管三维重建均未见肝动脉、门静脉及肝静脉解剖变异,且未发现起自胃左动脉的副肝左动脉解剖变异。病例1供者肝左外叶体积为387.5 cm3,病例2供者肝左外叶体积为417.75 cm3；2例供者术前MRCP检查均未发现确切胆道解剖变异,术前1 d ICG R15检查均<10%。
三、受者术前评估
病例1术前彩色多普勒超声检查结果示肝脏脂肪变性；术前评估GRWR为4.5%,供肝左外叶最大前后径与受者腹上区前后径比值为1.1,需进行供肝减体积处理,经IQQA®-3D Liver肝脏评估和治疗计划辅助系统（V2.0）评估,供肝左外叶减去肝脏Ⅲ段后,剩余供肝体积为245.3 cm3,此时受者GRWR为2.8%,满足手术要求。
病例2术前彩色多普勒超声检查结果示肝脏脂肪变性；术前评估GRWR为5.6%,供肝左外叶最大前后径与受者腹上区前后径比值为1.3,需进行供肝减体积处理,经IQQA®-3D Liver肝脏评估和治疗计划辅助系统（V2.0）评估,供肝左外叶减去肝脏Ⅲ段后,剩余供肝体积为188.3 cm3,此时受者GRWR为2.5%,满足手术要求。
四、手术步骤
1.供者体位：依据笔者前期的临床实践[5]。建立CO2气腹,压力维持在13 mmHg（ 1 mmHg=0.133 kPa）,供者取30°头高足低位和30°左侧卧位,主刀医师位于供者右侧,一助及扶镜手位于供者左侧；于脐上切口建立腹腔镜观察孔,分别于右侧锁骨中线肋下3 cm,左侧锁骨中线肋下1 cm穿刺建立12 mm Trocar操作孔,分别于右侧腋前线脐平面及左侧锁骨中线肋下6 cm穿刺建立5 mm Trocar操作孔。
2.术中操作：（1）沿镰状韧带右侧劈离供肝左外叶。离断肝圆韧带后,充分游离左半肝；切开小网膜,辨别Arantius管。于肝左静脉根部离断Arantius管后显露肝左静脉外侧缘及背侧。解剖第一肝门,以从左至右、由浅入深的顺序解剖并以血管牵引带悬吊肝左动脉,门静脉左支。沿镰状韧带右侧1 cm处肝脏膈面肝组织作切肝标记。确认肝总管位置,向头侧轻度解剖其表面覆盖的结缔组织,显露左肝管肝外走行后,于肝方叶肝组织表面作标记点,确定肝脏脏面切肝线。置入尼龙牵引带悬吊肝十二指肠韧带,于左侧腹壁打孔,牵引出体外。经由塑料套管行间断入肝血流阻断,每次阻断时间为15 min,中间间隔5 min。超声刀沿镰状韧带右侧劈离肝脏表面实质（图1A）,深部组织应用超声吸引刀配合超声刀劈离。术中应用百克钳辅助止血,以Hem-o-lok夹闭肝脏Ⅳ段Glisson分支后离断（图1B）,较小Glisson分支及较小肝静脉回流支,以超声刀双次凝闭后离断。劈离肝实质至第一肝门显露肝门板后方,至第二肝门显露肝中静脉与肝左静脉汇合部（图1C）,肝左外叶与肝尾状叶间完全离断,至此,完成供肝左外叶劈离过程。
（2）供肝减体积处理。经肝圆韧带入路,沿镰状韧带左侧从足侧向头侧解剖出左支矢状部发出的肝脏Ⅲ段Glisson分支,以Hem-o-lok夹闭（图 2A, 2B）。由外周静脉注入吲哚菁绿染色液（0.9%氯化钠溶液稀释至10 mL,0.025 mg/kg）,吲哚菁绿荧光显像确定肝脏Ⅱ段、Ⅲ段界限,其中肝脏Ⅱ段呈绿色荧光染色（图2C,2D）,肝脏Ⅲ段因缺乏血供呈反染。离断肝脏Ⅲ段Glisson分支,应用超声吸引刀配合超声刀解剖性劈离肝脏Ⅲ段（图2E,2F）。完成肝实质劈离后,关闭CO2气腹,耻骨联合上方3 cm处横行切开皮肤,纵行切开腹白线进腹,放置切口保护套。开启CO2气腹后经由手套指端置入取物袋,将供肝置入其中。吲哚菁绿荧光实时引导下,确认左右肝管分叉水平,以Hem-o-lok夹闭左肝管并离断。分别以Hem-o-lok夹闭肝左动脉、门静脉左支近端并离断,以直线切割吻合器离断左肝静脉,收紧取物袋,自腹下区切口取出供肝,放置腹腔引流管。修肝台灌注供肝后,完成后续肝移植操作。
五、观察指标和评价标准
观察指标：（1）供者手术情况,包括总手术时间、供肝减体积处理时间、术中出血量、输血情况、供肝实际质量。（2）供者术后情况：术后肝功能恢复情况、术后首次下床活动时间、术后首次进食流质食物时间、术后拔除腹腔引流管时间、术后住院时间、围术期并发症情况。（3）受者术后情况：术后肝功能恢复情况、术后住院时间、围术期并发症情况。（4）随访情况：供者随访时间及其肝功能恢复情况,受者随访时间以及排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症发生情况。
评价标准：围术期并发症评估参照Clavien-Dindo分级系统[6]。
六、随访
采用电话、门诊、短信、微信方式进行随访。供者于术后第1、3、6个月随访1次,了解肝功能恢复情况。受者于术后每周随访1次,了解移植物功能情况,以及排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症发生情况。随访时间截至2020年7月。
一、供者手术情况
病例1供者总手术时间为234 min,供肝减体积处理时间为40 min,术中出血量为60 mL,未输血。经减体积处理后供肝实际质量为225.2 g。
病例2供者总手术时间为220 min,供肝减体积处理时间为40 min,术中出血量为40 mL,未输血。经减体积处理后供肝实际质量为178.0 g。
二、供者术后情况
病例1供者ALT、AST、TBil于术后第2天达到峰值,分别为493 U/L、186.0 U/L、30.66 μmol/L,于术后第3天下降为388 U/L、90.9 U/L、22.57 μmol/L；术后首次下床活动时间为术后2 d、术后首次进食流质食物时间为术后1 d、术后拔除腹腔引流管时间为术后3 d、术后住院时间为4 d、围术期无≥Clavien-Dindo Ⅱ级并发症发生。
病例2供者ALT、AST、TBil于术后第1天达到峰值,分别为602 U/L、454.6 U/L、30.49 μmol/L,于术后第4天下降为355 U/L、55.7 U/L、20.65 μmol/L；术后首次下床活动时间为术后2 d、术后首次进食流质食物时间为术后1 d、术后拔除腹腔引流管时间为术后3 d、术后住院时间为5 d、围术期无≥Clavien-Dindo Ⅱ级并发症发生。
三、受者术后情况
病例1 ALT、AST、TBil于术后第1天达到峰值,分别为670 U/L、288.7 U/L、22.13 μmol/L,于术后第14天下降为54 U/L、33.0 U/L、5.75 μmol/L；术后住院时间为20 d,围术期无≥Clavien-Dindo Ⅱ级并发症发生。
病例2 ALT、AST、TBil于术后第1天达到峰值,分别为520 U/L、93.9 U/L、31.42 μmol/L,于术后第14天下降为87 U/L、60.8 U/L、11.51 μmol/L；术后住院时间为25 d,围术期无≥Clavien-Dindo Ⅱ级并发症发生。
四、随访情况
2例供者均获得术后1、3、6个月随访,术后1个月随访肝功能恢复至正常水平,术后3个月及6个月随访肝功能未见异常。2例受者均获得术后每周随访。随访期间,移植物功能均正常,均未发生排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症。
讨论
一、腹腔镜供肝获取术的开展
随着腹腔镜肝脏外科手术技术的进步和成熟,全腹腔镜活体肝移植供肝获取术已在越来越多的移植中心开展。目前,笔者中心已完成各类腹腔镜活体肝移植供肝获取术80例,包括肝左外叶切取术、左半肝切取术、右半肝切取术及解剖性在体减体积肝段切取术。
在保证供者生命安全的前提下,腹腔镜活体肝移植供肝获取术能减少疼痛对供者的影响,加速术后康复,且与传统开腹手术比较,未明显增加并发症发生率及住院费用,并能显著缩短术后住院时间,改善供者对手术的主观耐受能力[7-14]。
二、解剖性肝段获取术
对于体质量较低、腹腔体积较小的儿童受者,传统的非解剖性肝左外叶减体积手术不能充分削减供肝厚度。当供肝厚度>儿童受者腹上区最大前后径时,关腹后会导致腹腔压力增大和供肝受压、入肝血流受限,从而引起术后严重血管并发症或移植物功能障碍,导致受者术后感染,尤其是腹壁感染和呼吸系统相关并发症风险增高[15-16]。而解剖性肝段获取术能有效避免因供肝厚度过大导致的相关风险[4]。施行解剖性肝左外叶肝段获取术时,可选择肝脏Ⅱ段或Ⅲ段作为肝段移植物。有研究结果显示：施行解剖性肝左外叶肝脏Ⅱ段获取术时,因术中需要经肝圆韧带对脐裂进行更深入地解剖,导致肝门板内肝脏Ⅱ段门静脉分支损伤风险增高。因此,肝脏Ⅱ段获取术技术难度和手术风险均高于肝脏Ⅲ段获取术[17-18]。
笔者认为：术前行增强CT检查肝脏血管三维重建能精确评估门静脉左支矢状部发出的门静脉肝脏Ⅱ段或Ⅲ段分支位置及走行,从而降低术中行解剖性肝左外叶肝脏Ⅱ段获取术时,损伤门静脉肝脏Ⅱ段分支的风险；同时,由于肝左静脉主干通常走行于门静脉肝脏Ⅱ段和Ⅲ段分支之间,术中解剖性劈离肝脏Ⅱ段时,易损伤肝左静脉主干,导致移植物流出道损伤。因此,笔者认为：术中以门静脉肝脏Ⅲ段分支作为解剖标记,解剖性劈离肝脏Ⅲ段,获取肝脏Ⅱ段更为安全。
三、吲哚菁绿荧光引导腹腔镜解剖性肝段获取术
日本学者率先将吲哚菁绿荧光成像技术应用于肝切除术中,实时识别肝肿瘤和肝段边界[19-23]。目前,基于门静脉流域的肝脏分段更符合肝脏实际解剖情况[24]。利用吲哚菁绿荧光染色引导腹腔镜解剖性肝段获取术,术中可在肝脏表面很好地显示肝段与肝段之间的分界线,且在离断肝实质过程中,肝段与肝段之间的交界面也可完美显示[25]。
笔者团队在施行吲哚菁绿荧光引导腹腔镜解剖性肝段获取术时,选择肝圆韧带入路,能够较容易识别并解剖门静脉肝脏Ⅲ段分支。阻断该分支血流后,经外周静脉注射吲哚菁绿染色液,待劈离的肝脏Ⅲ段因缺乏血供呈反染,在荧光腹腔镜下不呈现绿色荧光,而肝脏Ⅱ段因入肝血流正常而呈现绿色荧光,因此,可精确确定肝脏Ⅱ段、Ⅲ段劈离界限[26-29]。此时,因已完全阻断门静脉肝脏Ⅲ段分支血流,肝脏Ⅱ段、Ⅲ段劈离界限不会因为时间延长而显示不清晰。这也为后续肝实质离断中,识别肝段间交界面提供方便。同时,在进行肝段间肝实质离断过程中,利用吲哚菁绿荧光胆道显像作用,可较好识别肝脏Ⅱ段和Ⅲ段胆道位置和走行,以及是否存在胆管变异情况,从而保护肝脏Ⅱ段胆管免受手术损伤。
本研究中,2例供者供肝减体积处理时间均为40 min,由于阻断门静脉肝脏Ⅲ段分支血流,术中在体解剖性劈离肝脏Ⅲ段过程中,未明显增加术中出血量。供肝经减体积处理后,能满足后续受者肝移植要求。2例受者术后随访过程中,移植物功能均正常,均未发现排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症发生。
综上,吲哚菁绿荧光引导腹腔镜解剖性肝段获取术应用于小儿活体肝移植安全、可行,可由具有丰富腹腔镜供肝获取手术经验的团队施行。
所有作者均声明不存在利益冲突李宏宇, 魏林, 朱志军, 等. 吲哚菁绿荧光引导腹腔镜解剖性肝段获取术在小儿活体肝移植中的应用价值[J]. 中华消化外科杂志, 2021, 20(1): 118-124. DOI:http://dx.doi.org/10.3760/cma.j.cn115610-20201028-00679.http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.issn.1673⁃9752.2021.01.019
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