Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.
Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Lancet Gastroenterol Hepatol. 2018 Oct;3(10):681-690. doi: 10.1016/S2468-1253(18)30234-6. Epub 2018 Aug 17.
In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma.
We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 μmol/L [2·9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243.
From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3·67, 95% CI 1·15-11·69; p=0·03). Three of the 11 deaths among patients in the percutaneous transhepatic biliary drainage group occurred before surgery. The proportion of patients with severe preoperative drainage-related complications was similar between the groups (17 [63%] patients in the percutaneous transhepatic biliary drainage group vs 18 [67%] in the endoscopic biliary drainage group; relative risk 0·94, 95% CI 0·64-1·40). 16 (59%) patients in the percutaneous transhepatic biliary drainage group and ten (37%) patients in the endoscopic biliary drainage group developed preoperative cholangitis (p=0·1). 15 (56%) patients required additional percutaneous transhepatic biliary drainage after endoscopic biliary drainage, whereas only one (4%) patient required endoscopic biliary drainage after percutaneous transhepatic biliary drainage.
The study was prematurely stopped because of higher all-cause mortality in the percutaneous transhepatic biliary drainage group. Post-drainage complications were similar between groups, but the data should be interpreted with caution because of the small sample size. The results call for further prospective studies and reconsideration of indications and strategy towards biliary drainage in this complex disease.
Dutch Cancer Foundation.
在可切除的肝门部胆管癌患者中，推荐进行胆道引流以治疗梗阻性黄疸，并在肝切除术前优化临床状况。关于胆道引流的首选初始方法，证据有限。因此，我们调查了在潜在可切除的肝门部胆管癌患者中，内镜胆道引流或经皮经肝胆道引流的严重引流相关并发症的发生率。
我们在荷兰的四个学术中心进行了一项多中心、随机对照试验。纳入标准为年龄至少 18 岁、有潜在可切除的肝门部胆管癌且需要进行主要肝切除术、以及未来肝段有胆道梗阻（定义为胆红素浓度>50 μmol/L[2.9 mg/dL]）的患者。患者被随机分配（1:1）接受内镜胆道引流或经皮经肝胆道引流，使用计算机生成的分配方法。随机分配由试验协调员进行，按先前（尝试过的）胆道引流、胆管受累程度和入组中心进行分层。患者由参与中心的临床医生纳入。主要结局是意向治疗人群中随机化至手术之间的严重并发症数量。该试验在荷兰国家试验注册处（NTR4243）注册。
从 2013 年 9 月 26 日至 2016 年 4 月 29 日，共有 261 名患者接受了参与筛查，54 名符合条件的患者被随机分配至内镜胆道引流组（n=27）或经皮经肝胆道引流组（n=27）。由于经皮经肝胆道引流组的死亡率较高（27 名患者中有 11 名[41%]），研究提前终止，而内镜胆道引流组中只有 3 名（27 名患者中的 11%）（相对风险 3.67，95%CI 1.15-11.69；p=0.03）。经皮经肝胆道引流组中有 3 名患者在术前死亡。两组术前严重引流相关并发症的患者比例相似（经皮经肝胆道引流组 17 名[63%]，内镜胆道引流组 18 名[67%]；相对风险 0.94，95%CI 0.64-1.40）。经皮经肝胆道引流组 16 名（59%）患者和内镜胆道引流组 10 名（37%）患者发生术前胆管炎（p=0.1）。15 名（56%）经皮经肝胆道引流组患者在接受内镜胆道引流后需要额外的经皮经肝胆道引流，而只有 1 名（4%）患者在接受经皮经肝胆道引流后需要进行内镜胆道引流。
由于经皮经肝胆道引流组的全因死亡率较高，研究提前终止。两组术后并发症相似，但由于样本量较小，数据应谨慎解释。结果呼吁进一步进行前瞻性研究，并重新考虑在这种复杂疾病中进行胆道引流的适应证和策略。
荷兰癌症基金会。
