Interventional procedure overview of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction

Bokemeyer A, Matern P, Bettenworth D et al. (2019) Endoscopic Radiofrequency ablation prolongs survival of patients with unresectable hilar cholangiocellular carcinoma - a case-control study. Scientific reports 9(1): 13685

Case control (retrospective)

N=42 (RFA plus stent, n=32 [20 included in the case-control analysis]; stent alone, n=22)

ERFA therapy significantly prolonged survival in patients with unresectable Bismuth type III and IV hilar cholangiocellular carcinoma. As an effective and safe method, ERFA should be considered as a palliative treatment for all these people.

Small sample

Buerlein RCD, Strand DS, Uppal DS et al. (2022) Endobiliary ablation improves survival in patients with unresectable perihilar cholangiocarcinoma compared to stenting alone. Techniques and Innovations in Gastrointestinal Endoscopy 24(3): 226-33

Non-randomised comparative study (retrospective)

N=59 (ERCP-directed biliary ablation [RFA and/or PDT] and stenting, n=30; biliary stenting alone, n=29)

Endobiliary ablation (with RFA and/or PDT or RFA alone) followed by stenting was associated with significantly improved survival compared to biliary stenting alone in people with unresectable perihilar CCA without an increase in adverse events and should be offered as first-line palliative therapy.

Small sample (ERCP-directed biliary ablation using RFA, n=20)

Dutta AK, Basavaraju U, Sales L et al. (2017) Radiofrequency ablation for management of malignant biliary obstruction: a single-center experience and review of the literature. ExpertRev Gastroenterol Hepatol, 11: 779-84

Non-randomised comparative study

N=31 (RFA plus stent, n=15; stent only, n=16)

Biliary RFA is a technically feasible with a low adverse event rate and is associated with increased survival. Multi-centre RCTs are required.

More recent studies with larger samples or better designs included in the key evidence

Galindo Orozco MC, Hernandez Guerrero A, Alonso Larraga JO et al. (2020) Efficacy and safety of radiofrequency ablation in patients with unresectable malignant biliary strictures. Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva 112(12): 921-924

Non-randomised comparative study

N=40 (RFA plus stent, n=12; stent alone, n=28)

The radiofrequency group had a 3-month increase in survival, which did not reach statistical significance.

Studies with larger samples or better designs included in the key evidence.

Inoue T, Ibusuki M, Kitano R et al. (2023) Long-term disease control by endobiliary radiofrequency ablation in localized extrahepatic cholangiocarcinoma: a first case report. Clinical journal of gastroenterology 16(6): 908-12

Case report

N=1

This is the first report of a stent-free status and long-term survival in a patient with localised extrahepatic CCA that was achieved using only endobiliary RFA without any other antitumour treatment. Although several problems and issues associated with endobiliary RFA remain unelucidated, it may be a useful therapeutic option for early and localised extrahepatic cholangiocarcinoma in poor surgical candidates.

Small sample

Inoue T, Ibusuki M, Kitano R et al. (2023) Endoscopic radiofrequency ablation for ingrowth occlusion after bilateral metal stent placement for malignant hilar biliary obstruction: a prospective pilot study. Gastrointestinal endoscopy 97(2): 282-290e1

Case series (retrospective)

N=41

The study showed that endobiliary RFA with bilateral SEMS placement achieved good results, but selection of patients with an appropriate stricture length may be needed to obtain a sufficient ablative effect.

Studies with larger samples or better designs included in the key evidence.

Inoue T, Ibusuki M, Kitano R et al. (2023) Endoscopic radiofrequency ablation for ingrowth occlusion after bilateral metal stent placement for malignant hilar biliary obstruction: a prospective pilot study. Gastrointestinal endoscopy 97(2): 282-290e1

Case series

N=30

Follow up: median 179 days

Endoscopic biliary RFA elicited promising results, with good long-term stent patency and without the need of any additional stent placement, for the palliation of ingrowth occlusion after bilateral SEMS placement. However, the clinical success rate was insufficient, necessitating improvements in the future.

Studies with larger samples or better designs included in the key evidence.

Inoue T, Ibusuki M, Kitano R et al. (2022) Endobiliary radiofrequency ablation using a short-type balloon enteroscope in patients with surgically altered anatomy. Digestive diseases and sciences 67(8): 4181-4187

Case series

N=37

This study demonstrated the technical safety and feasibility as well as good long-term outcomes of endobiliary RFA combined with metal stent placement under balloon enteroscope guidance. This approach may be a useful option for treating MBO in people with surgically altered anatomy.

Studies with larger samples or better designs included in the key evidence.

Inoue T, Naitoh I, Kitano R et al. (2022) Endobiliary radiofrequency ablation combined with gemcitabine and cisplatin in patients with unresectable extrahepatic cholangiocarcinoma. Current oncology (Toronto, Ont.) 29(4): 2240-51

Non-randomised comparative study (retrospective)

N=50 (gemcitabine plus cisplatin therapy with RFA, n=25; gemcitabine plus cisplatin therapy only, n=25)

Endobiliary RFA prolonged the patency period of uncovered SEMS combined with gemcitabine plus cisplatin therapy in patients with extrahepatic CCA. Although RFA also yielded survival benefits, its effect was restricted to locally advanced tumours.

Studies with larger samples or better designs included in the key evidence.

Kadayifci A, Atar M, Forcione DG et al. (2016) Radiofrequency ablation for the management of occluded biliary metal stents. Endoscopy, 48(12): 1096-101

Non-randomised comparative study (retrospective)

N=50 (RFA, n=25; plastic stent, n=25)

The application of RFA for occluded SEMS improves stent patency. RFA is an alternative treatment of tissue ingrowth in malignant biliary obstruction.

More recent studies with larger samples or better designs included in the key evidence

Kim EJ, Cho JH, Kim YJ et al. (2019) Intraductal temperature-controlled radiofrequency ablation in malignant hilar obstruction: A preliminary study in animals and initial human experience. Endoscopy International Open 7(10): e1293-e1300

Case series

N=11

This study suggests that ID-RFA performed using a short-length probe with settings of 80 °C, 7W and 60 – 120 s is a safe and feasible palliative treatment for malignant hilar obstruction.

Small sample

Kim EJ, Chung DH, Kim YJ et al. (2018) Endobiliary radiofrequency ablation for distal extrahepatic cholangiocarcinoma: A clinicopathological study. PloS one 13(11): e0206694

Case series (retrospective)

N=8

Endobiliary RFA partially ablated human cancer tissue and preoperative endobiliary RFA might be a safe and feasible in patients with distal extrahepatic CCA who require a delayed operation. Ablation of the target lesion longer than the estimated length by fluoroscopy may improve the efficacy of endobiliary RFA.

Small sample

Laleman W, van der Merwe, Schalk, Verbeke L et al. (2017) A new intraductal radiofrequency ablation device for inoperable biliopancreatic tumors complicated by obstructive jaundice: the IGNITE-1 study. Endoscopy 49(10): 977-82

Case series

N=18

Follow up: mean 213 days

Intraductal RFA using a new device in patients with inoperable biliopancreatic cancer complicated by jaundice appeared feasible and safe with acceptable biliary patency. Randomised trials with prolonged follow-up are warranted.

Small sample; more recent studies included in the key evidence.

Liang H, Peng Z, Cao L et al. (2015) Metal stenting with or without endobiliary radiofrequency ablation for unrespectable extrahepatic cholangiocarcinoma. Journal of cancer therapy, 6: 981-92

Non-randomised comparative study

N=76 (RFA plus SEMS, n=34; SEMS only, n=42)

ERFA is effective for unresectable extrahepatic CCA and may improve metal stent patency and patient survival for unresectable extrahepatic CCA with biliary obstruction. RCTs will be needed to confirm these findings.

Mixed approaches (ERCP and PTC); more recent studies with larger samples or better designs included in the key evidence.

Lee YN, Jeong S, C HJ et al. (2019) The safety of newly developed automatic temperature-controlled endobiliary radiofrequency ablation system for malignant biliary strictures: A prospective multicenter study. Journal of gastroenterology and hepatology 34(8): 1454-1459

Case series

N=30

Follow up: mean 208 days

Automatic temperature-controlled endobiliary RFA using a newly developed catheter was safely applied in patents with extrahepatic malignant biliary stricture. Further prospective studies are needed to confirm the efficacy of endobiliary RFA for MBS.

Small sample

Marti Romero L, Martinez Escapa V, Castello Miralles I et al. (2019) Intraductal ablation by radiofrequency for inoperable biliopancreatic neoplasms with jaundice: experience at a regional hospital. Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 111(6): 485-7

Case reports

N=3

Follow up: 10 months

Preliminarily data suggest that the application of intraductal biliary RFA in people with non-resectable or inoperable neoplasia that causes bile duct stenosis apparently does not increase technical difficulty. However, it does extend the duration of the examination. Thus, the evidence suggests that it is feasible and safe due to the absence of immediate complications. However, more cases and long-term monitoring are pending. This previously non-existent treatment option provides people with metal biliary stents that improve the quality of life and prevent repeated admissions due to obstructive jaundice or cholangitis.

Small sample

Mohring C, Khan O, Zhou T et al. (2023) Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy. Frontiers in Oncology 13: 1227036

Non-randomised comparative study (retrospective)

N=63 (systemic chemotherapy and endobiliary RFA, n=28; systemic chemotherapy and endobiliary PDT, n=22; systemic chemotherapy and endobiliary RFA and PDT, n=13)

Additional endobiliary ablative therapies in combination with systemic chemotherapy were feasible. Both modalities, endobiliary RFA and endobiliary PDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best overall survival indicating a possible synergism between both ablative therapeutic techniques.

Studies with larger sample or better designs included in the key evidence.

Nair P, Rao HB, Koshy AK et al. (2021) Safety and efficacy of endobiliary radio frequency ablation in hilar cholangiocarcinoma. Journal of Gastroenterology and Hepatology Research 11(1): 3658-3664

Non-randomised comparative study (retrospective)

N=49 (endobiliary RFA plus stenting, n=22; stenting alone, n=27)

Follow up: 236 days

Patients who underwent endobiliary RFA were found to have a significant survival advantage as compared to standard treatment options. Endobiliary RFA was found to be technically feasible, safe and can be a useful adjunct to endoscopic palliation in patients with hilar cholangiocarcinoma.

Studies with larger samples or better designs included in the key evidence.

Nayar MK, Oppong KW, Bekkali NLH et al. (2018) Novel temperature-controlled RFA probe for treatment of blocked metal biliary stents in patients with pancreaticobiliary cancers: Initial experience. Endoscopy International Open 6(5): e513-e517

Case series

N=7

Follow up: mean 194 days

These are the first reported data on use of a RFA catheter in humans to treat blocked metal biliary stents. The device is safe but further randomised trials are required to establish the efficacy and survival benefits of this probe.

Small sample

Oh D, Chong J, Song TJ et al. (2022) The usefulness of endobiliary radiofrequency ablation before metal stent placement in unresectable malignant hilar obstruction. Journal of gastroenterology and hepatology 37(11): 2083-2090

Non-randomised comparative study (retrospective)

N=79 (RFA plus SEMS, n=28; SEMS only, n=51)

SEMS placement after endobiliary RFA in malignant hilar obstruction was not associated with improvement in the stent patency or patient survival. Further prospective randomized studies are necessary to establish the effectiveness of EB-RFA with stents in malignant hilar obstruction.

Studies with larger sample or better designs included in the key evidence.

Ogura T, Onda S, Sano T et al. (2017) Evaluation of the safety of endoscopic radiofrequency ablation for malignant biliary stricture using a digital peroral cholangioscope (with videos). Digestive endoscopy: official journal of the Japan Gastroenterological Endoscopy Society 29(6): 712-7

Case series (retrospective)

N=12

Follow up: median 107 days

RFA for malignant biliary stricture may be safe. To confirm the feasibility and efficacy of RFA, additional cases, prospective studies, and a comparison study between with and without endobiliary RFA are needed.

Small sample; more recent studies included in the key evidence.

Park N, Jung M Kyu, Kim EJ et al. (2023) In-stent radiofrequency ablation with uncovered metal stent placement for tumor ingrowth/overgrowth causing self-expandable metal stent occlusion in distal malignant biliary obstruction: multicenter propensity score-matched study. Gastrointestinal endoscopy 97(4): 694-703e2

Propensity score-matched study

N=48 (in-stent RFA plus SEMS, n=14; SEMS only, n=34)

In-stent RFA followed by an uncovered SEMS is safe and feasible and may improve time to recurrent biliary obstruction as a stent revision for occluded SEMSs in pancreatobiliary cancer.

Studies with larger samples or better designs included in the key evidence.

Rebhun J, Shin CM, Siddiqui UD et al. (2023) Endoscopic biliary treatment of unresectable cholangiocarcinoma: a meta-analysis of survival outcomes and systematic review

Systematic review and meta-analysis

N=307 (6 studies: endoscopic RFA, 4 studies; percutaneous RFA, 2 studies

While further prospective, randomised studies are needed to assess efficacy of ERFA, meta-analysis showed that this technique offers endoscopists a reasonable palliative method by which to treat unresectable CCA that results in longer survival as compared to biliary stenting alone, percutaneous RFA with biliary stenting and photodynamic therapy with biliary stenting as well as an acceptable adverse event profile based on available data.

Of the 4 relevant studies, 3 were included in Cha (2021) and 1 case-control study with a small sample (n=25).

Sandru V, Ungureanu BS, Stan-Ilie M et al. (2022) Efficacy of endobiliary radiofrequency ablation in preserving survival, performance status and chemotherapy eligibility of patients with unresectable distal cholangiocarcinoma: a case-control study. Diagnostics 12(8): 1804

Case control

N=25 (RFA plus stenting, n=8; stenting alone, n=17)

Follow up: 6 months

Given the isolated adverse events and the impact on the patient survival, performance, and laboratory profile, RFA can be considered safe and efficient in the management of patients with unresectable distal cholangiocarcinomas.

Small sample

Sharaiha RZ, Natov N, Glockenberg KS et al. (2014) Comparison of metal stenting with radiofrequency ablation versus stenting alone for treating malignant biliary strictures: is there an added benefit? Digestive Diseases & Sciences 59: 3099–102

Non-randomised comparative study

N=66 (RFA plus SEMS, n=26; SEMS only, n=40

Follow up: median 29 months

RFA appears to improve survival in people with end-stage CCA and pancreatic cancer. In a disease with limited treatment options, this modality may prove to be beneficial compared to stenting alone. RCTs and evaluation of quality-of-life measures should be performed to confirm these findings.

More recent studies with larger samples or better designs included in the key evidence

Sofi AA, Khan MA, Das A et al. (2018) Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis. Gastrointestinal endoscopy, 87: 944-51

Systematic review and meta-analysis

N=505 (9 studies [ERCP-guided RFA in 4 studies, PTC-guided RFA in 4 studies, both approaches in 1 study])

In the light of this limited data based on observational studies, RFA was found to be safe and was associated with improved stent patency in patients with malignant biliary strictures. In addition, RFA may be associated with improved survival in these patients.

Mixed approaches (ERCP and PTC), limited outcomes relating to ERCP-guided RFA reported; more recent studies and systematic review and meta-analysis included in the key evidence.

Tarar ZI, Farooq U, Gandhi M et al. (2023) Effect of radiofrequency ablation in addition to biliary stent on overall survival and stent patency in malignant biliary obstruction: an updated systematic review and meta-analysis. European journal of gastroenterology & hepatology 35(6): 646-53

Systematic review and meta-analysis

N=1766 (14 observational studies and 3 RCTs; ERCP for RFA in 12 studies and PTC for RFA in 5 studies)

RFA treatment, in addition to stent placement in MBO, potentially improves OS and stent patency duration.

Of the 12 relevant studies, 3 RCTs and 4 observational studies included in Cha (2021) and 1 observational study (Xia 2021) included in the key evidence. Subgroup analysis was done to determine the effect of the procedure used to deliver RFA (ERCP versus PTC) on stent patency so no other outcomes of interest relating to the ERCP approach only were reported.

Yang J, Wang J, Zhou Hb et al. (2020) Endoscopic radiofrequency ablation plus a novel oral 5-fluorouracil compound versus radiofrequency ablation alone for unresectable extrahepatic cholangiocarcinoma. Gastrointestinal endoscopy 92(6): 1204-1212e1

RCT

N=75 (RFA plus S-1, n=37; RFA, n=38)

For the treatment of locally advanced extrahepatic CCA, endoscopic RFA combined with S-1 is associated with longer survival and stent patency and improved functional status than RFA alone.

This study focused on the effect of S-1.

Yang J, Han S, Zhou H et al. (2022) The efficacy and safety of endoscopic papillectomy combined with endobiliary radiofrequency ablation for ampullary neoplasms with intraductal biliary extension. Techniques and Innovations in Gastrointestinal Endoscopy 24(3): 240-5

Case series (retrospective)

N=8

Follow up: mean 28.5 months

Endoscopic papillectomy combined with intraductal RFA may be an effective and safe treatment for ampullary neoplasms with intraductal extension, particularly for patients who are poor surgical candidates. Given the risk of recurrence, indefinite surveillance is recommended.

Small sample