The safety and efficacy of percutaneous intraductal radiofrequency ablation in unresectable malignant biliary obstruction: A single-institution experience

Patients with malignant biliary obstruction due to different types of tumors, including pancreatic, bile duct, gallbladder, and hepatocellular carcinomas, frequently have a poor prognosis in terms of quality of life and survival. These cancers are often surgically unresectable at the time of diagnosis, and those that are resected have high recurrence rates [ 1]. Placement of self-expandable metal stents (SEMS) is the standard of care in the palliative management of patients with malignant biliary strictures if their life expectancy is at least 3 months [ 2]. However, maintaining patency is a problem, with tumor overgrowth, epithelial hyperplasia, biofilm deposition, and sludge formation limiting the median patency of metal stents to a mere 6 months [ 3].

Despite attempts to find a potential solution to the problem of SEMS occlusion, including the use of covered stents, different stent designs, and biliary intraluminal irradiation stents, little progress has been made in terms of improving the duration of stent patency [ 4– 7]. Although photodynamic therapy (PDT) has been reported as an alternative capable of increasing the rate of stent patency, it is expensive and time consuming, and is associated with cholangitis and photosensitivity [ 8, 9]. Recently, a Percutaneous Endobiliary Radiofrequency catheter (Habib™ PERF; EMcision Ltd., London, UK) was developed specifically to attempt to solve the problem of stent occlusion. Studies using ex-vivo and in-vivo pig models have clarified the effectiveness of the Habib PERF catheter, with an output power of 7–10 W and an ablation time of 2 min recommended for clinical treatment [ 10, 11]. An open-label pilot study involving 22 patients with malignant biliary strictures confirmed the safety and feasibility of this radiofrequency ablation (RFA) technique for clinical use [ 12]. The technique has shown promising results in the palliative treatment of malignant biliary strictures, preventing stent occlusion [ 13– 18], clearing blocked metal stents [ 7], prolonging stent patency [ 19], and improving patient survival [ 20]. We previously reported our early experience in managing patients with unresectable Bismuth types III and IV hilar cholangiocarcinoma using biliary RFA, and demonstrated that the long-term efficacy and safety is promising [ 21]. Here, we describe a broader experience in managing 50 patients using biliary RFA in an effort to improve long-term stent patency in unresectable malignant biliary obstruction. We also examined the prognostic factors for stent patency in these patients.

We conducted a retrospective study of consecutive patients with malignant biliary obstruction who underwent biliary RFA and stent placement at the First Affiliated Hospital of Sun Yat-sen University between 2013 and 2015. Malignant biliary obstruction was diagnosed in all cases on the basis of the characteristic clinical features (jaundice and/or clay colored stool), laboratory tests (elevated bilirubin levels and alkaline phosphatase levels), and imaging findings. Access to the database and the methods used for data retrieval and analysis were approved by the ethics committee of our hospital, and written informed consent was obtained from each participant in accordance with the Declaration of Helsinki.

We report the efficacy and complications encountered at our institution for 50 patients treated with percutaneous intra-ductal RFA for unresectable malignant biliary obstruction. Compared to the 3 to 6-month patency of metal stents alone, the median stent patency of 7.0 months observed in this study is promising and highlights the urgent need for the use of the procedure in select patients [ 3]. Until now, PDT was the only evidence-based treatment other than stenting that improved the quality of life and survival of such patients [ 27]. Recently, Daniel [ 25] reported that RFA and PDT are associated with comparable survival in the treatment of unresectable cholangiocarcinoma. Therefore, these studies all suggest a possible survival benefit in the use of RFA. However, the results must be interpreted cautiously, because of the retrospective design with many sources of bias. The improvements of SEMS patency, cost-effectiveness, and survival advantages should be confirmed by further randomized controlled trials, if any. The main limitations of our study included its retrospective nature, the fact that it was a single-center experience with heterogeneous etiologies, and lack of a control group.

The potential therapeutic effect of combined RFA and stent placement has only been evaluated in a few studies to date, with mixed findings reported [ 9, 19, 20, 28, 29]. The 7-month stent patency reported here (95% CI: 5.3, 8.7) is in agreement with the results of the study reported by Werner et al. (median metal stent patency: 7.3 months) [ 29] but is higher than that reported by Tian-Tian et al. (stent patency: 5.0 months) [ 28]. Our study and that reported by Werner et al. had higher rates of cholangiocarcinoma (50% and 88%, respectively) and sequential chemotherapy (14% and 41%, respectively) compared with the rates in the trial reported by Tian-Tian et al. (48% and 4%, respectively), which is a possible explanation for this discrepancy. Therapeutically, intraluminal RFA and stent placement offers several benefits. Foremost, the local thermal effect can destroy the malignant biliary stricture, resulting in a local coagulation necrosis that has the potential to delay tumor growth and, therefore, prolong the duration of stent patency [ 16]. This local effect on tumor tissue was confirmed by Monga et al. [ 13], who reported the disappearance of tumor blood vessels and enlargement of the lumen following RFA. Moreover, RFA can be used to clear the occlusion of a previously deployed metal stent, and restore the biliary flow without the need to insert a new stent inside the obstructed stent [ 7]. As the use of RFA is not restricted to a single session, repeated treatments and multiple sessions can be performed to increase tumor destruction and improve the stent patency, which is an independent prognosis factor for patient survival (Table 4). Successful biliary drainage and long-term stent patency are important to alleviate clinical symptoms, confer some benefits to improve liver function (Fig. 1), improve performance status scores, and provide an opportunity for subsequent treatment of the primary tumor. However, the median OS (5.0 months) is shorter than the stent patency (7.0 months). This is likely because many patients still had patent stents at the time of the last follow-up or death. Furthermore, due to local tumor progression, many patients in our study died of disease progression but not recurrent stent obstruction, and only a few patients received repeat-ablation. In the Cox analysis, OS was improved in patients who received more than one intervention compared to those who received only one intervention (log-rank P = 0.007). The RFA heat penetration depth is limited and the coagulation zone is too small in patients who have tumors that involve the bile duct but do not originate from the bile duct epithelium (such as pancreatic cancer, enlarged hilar node). Therefore, the indications of intra-ductal RFA remain controversial, and the basic theory of this technique as a palliative treatment in extra-luminal biliary compression should also be further studied. Additionally, previous studies mostly utilized the endoscopic approach with this technique for the treatment of malignant biliary obstruction. Whether the endoscopic approach is better than the percutaneous route warrants further study.

Considering that covered SEMS are associated with increased risk of pancreatitis and cholecystitis but have comparable benefits to uncovered stents, uncovered SEMS placement was performed for all patients in our study. There were no severe complications, such as bile duct perforation, bile leak, or acute pancreatitis. However, we observed atrial fibrillation and sudden onset of chronic heart failure in one patient after the procedure, which might be a relative contraindication for this technique. We do emphasize that the incidence of cholangitis (32%) was very high in our group and two patients died within 30 days after the RFA procedure, both due to cholangitis and septic shock. Accordingly, we fully support the prophylactic administration of antibiotics before stent placement to lower the risk of cholangitis [ 19, 20]. Additionally, in univariable analysis, previously cholangitis was an independent poor prognosis factor for recurrent biliary obstruction (Table 3).

In conclusion, percutaneous RFA and stent placement is a technically safe and feasible therapeutic option for the palliative treatment of malignant biliary obstruction. We present more of our experiences with the use of this technique for select patients, and demonstrate the feasibility, with a satisfactory safety profile.