由于胆道肿瘤对肝细胞功能和胆管上皮细胞均可造成较为严重的影响,对胆道肿瘤患者的肝功能状况的评估,与肝细胞肝癌、转移性肝癌等恶性肿瘤存在较大的不同,应依据其病理生理特点对肝功能和肝储备功能进行系统性评估。
患者未合并梗阻性黄疸时,临床多采用Child-Pugh评分 [1] 和吲哚菁绿滞留率试验(ICGR15) [2] 对肝功能进行评估。Child-Pugh评分能够评估肝脏合成和分泌功能(表2-2-1),吲哚菁绿滞留率试验可对肝脏储备功能进行评估。
表2-2-1 肝功能Child-Pugh评分
对于无慢性肝炎等基础肝病背景的患者,术前Child-Pugh评分提示A级(肝功能正常),结合吲哚菁绿15分钟滞留率<15%,行肝切除后剩余肝实质最小量应达到肝切除前体积的30%以上。
在合并慢性肝炎、严重脂肪肝、酒精性肝病的患者,或术前经过多个疗程的化疗、大范围肝脏放疗的患者,提示肝储备功能及肝再生功能均较正常低下,剩余肝实质最小体积须保留达肝切除术前的40%~50%以上 [3-5] ;对于肝切除术前Child-Pugh评分提示A级、但吲哚菁绿15分钟滞留率≥15%时,提示肝脏储备功能有限,不宜行大范围肝切除术,即肝切除范围应<3个肝段。
当患者合并梗阻性黄疸时,由于受到高胆红素血症的干扰,采用Child-Pugh评分和吲哚菁绿滞留率试验(ICG-R15)均难以精准评估肝脏合成功能和储备功能 [6,7] 。
梗阻性黄疸导致的高胆红素血症,胆道内压力的增高导致肝细胞和胆管细胞连接的破坏,进而导致胆汁逆流入肝血窦引起肝实质炎症反应;有胆盐淤积的毒性反应激活了肝细胞凋亡;门静脉血流的减少影响肝脏有效血供(肝动脉缓冲反应仅能增加约50%的动脉血供);肝细胞的生长因子生成减少;肝细胞的胆汁排泌功能受到抑制,肝细胞及毛细胆管炎症水肿,肠道黏膜水肿、菌群移位将会诱发全身炎症反应的发生。在上述级联反应的相互累加效应下,肝功能逐步恶化。
因此,在梗阻性黄疸未解除时,目前临床应用的各种肝功能评估方法均存在局限性。当胆道引流后,如血清总胆红素浓度及胆管压力降至正常范围,可明显改善肝功能,肝切除范围扩大至70%的安全性大为提高 [8-11] 。但考虑到术前多个限制性因素,如选择性肝段胆管引流而非全肝充分引流导致血清总胆红素浓度难以降至正常水平,加之肿瘤性疾病术前准备时间不宜过久等综合因素,编者建议依照下述路径选择手术时机:当患者无慢性肝炎等肝病背景时,如果手术拟残留肝体积/术前总肝体积(FLR/TLV)>50%,可于胆道引流、总胆红素降至85μmol/L以下时,进行大范围肝切除术;如果拟残留肝体积/术前总肝体积(FLR/TLV)<50%,可通过选择性门静脉栓塞(portal vein embolization,PVE)等措施,增加拟残留肝体积至FLR/TLV>50%时,再进行肝切除术。实施PVE需评估肿瘤恶性进展速度,考量实施PVE的可行性及合理性,以及联合实施TAE、放疗等措施控制肿瘤生长速度的必要性和可行性。
对于肝内胆管结石、胆管囊肿等合并严重肝实质炎症和胆管炎症的患者,即使肝切除术术前无梗阻性黄疸、Child-Pugh评分和吲哚菁绿滞留率试验(ICG-R15)提示正常,在肝实质炎症和胆管炎症未获得有效改善时,行大范围肝切除发生肝衰竭的风险仍极高,应通过胆道内引流或外引流(对已发生萎缩的肝叶无需此措施)、抗感染治疗、营养支持等综合措施改善肝脏储备功能,提高手术的安全性。
胆道系统疾病诊疗往往需涉及肝脏、胆道、胰腺、肠道等多个器官系统。包括Child-Pugh评分和吲哚菁绿滞留率试验(ICG-R15)及 13 C-氨基比林呼气试验、利多卡因清除试验、半乳糖清除容量、白蛋白合成等在内的多种评估方法,目前在评估患者能否耐受肝切除或肝脏可切除量方面均无法体现出全面性和精准性,因此增添了胆道系统疾病患者肝功能和肝储备功能评估的复杂性,编者建议可结合图2-2-1的流程评估肝功能及肝储备功能,重点考量以下因素,个体化制订肝切除方案:
1.有无合并梗阻性黄疸?
2.有无慢性肝病背景?
3.有无合并严重的肝实质炎症和胆管炎症?
4.拟切除肝叶范围,是规则性肝切除或非规则性肝切除?是小范围肝切除或大范围肝切除?
图2-2-1 肝功能及肝储备功能评估流程
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