Skip Navigation
Skip to contents

Clin Endosc : Clinical Endoscopy

Search
Advanced Search
OPEN ACCESS
mobile search button mobile menu button

Articles

Page Path
HOME > Clin Endosc > Volume 54(1); 2021 > Article
Original Article Survival Benefit of Intraductal Radiofrequency Ablation for Malignant Biliary Obstruction: A Systematic Review with Meta-Analysis
Byung Hyo Cha1,,*orcid, Myoung-Jin Jang2,*orcid, Sang Hyub Lee3orcid
Clinical Endoscopy 2021;54(1):100-106.
DOI: https://doi.org/10.5946/ce.2020.254
Published online: January 15, 2021

1Division of Internal Medicine, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates

2Medical Research Collaborating Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

3Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Correspondence: Byung Hyo Cha Division of Internal Medicine, Department of Gastroenterology, Sheikh Khalifa Specialty Hospital, Al Shohadaa Road, Ras Al Khaimah, United Arab Emirates Tel: +971-7-201-1412, Fax: +971-7-203-2222, E-mail: doctorhyo@gmail.com
*These authors contributed equally to this study.
• Received: September 16, 2020   • Revised: October 15, 2020   • Accepted: October 27, 2020

Copyright © 2021 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 4,897 Views
  • 168 Download
  • 21 Web of Science
  • 21 Crossref
  • 22 Scopus
prev next
Full Article

Download PDF Download PDF

  • Background/Aims
    Cholangiocarcinoma (CCA) is a rare but aggressive disease with a poor survival. Recent trials have shown improved survival with intraductal radiofrequency ablation (RFA) therapy. We performed a systematic review with meta-analysis to determine the survival benefit of endoscopic RFA for unresectable extrahepatic CCA with malignant biliary obstruction (MBO).
  • Methods
    A systematic search from 1970 to 2020 was performed in MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials. gov. We selected eligible studies reporting relative risks, hazard ratios (HRs), or odds ratios, adjusted by controlling for confounding factors of survival rate and stent patency duration, among patients with extrahepatic CCA with MBO treated with RFA with stent insertion or stent insertion only.
  • Results
    A total of eight trials (three randomized and five nonrandomized) with a total of 420 patients were included in the metaanalysis. Pooled overall survival analysis favored RFA treatment with stent insertion (HR, 0.47; 95% confidence interval [CI], 0.34– 0.64; I2=47%; p=0.09); however, no significant difference was found in the duration of stent patency between the groups (HR, 0.79; 95% CI, 0.57–1.09; I2=7%; p=0.36).
  • Conclusions
    RFA therapy with stent insertion may confer a survival benefit compared with stent insertion only in patients with CCA and MBO.
  • Keywords: Cholangiocarcinoma; Malignant biliary obstruction; Meta-analysis; Radiofrequency ablation; Survival rates
Cholangiocarcinoma (CCA) is an uncommon, aggressive, malignant disease with a poor prognosis. It accounts for 3% of all gastrointestinal malignancies [1,2]. The overall incidence from 2001 to 2015 was 1.26 per 100,000 people per year in the United States [3]. CCA can be classified into three categories according to anatomical location: intrahepatic, perihilar, and distal CCA. Perihilar CCA accounts for 60%, distal CCA accounts for 30%, and intrahepatic CCA accounts for the remaining 10% of the cases. The prognosis of patients with CCA is poorer than that of patients with other malignant diseases of the gastrointestinal tract. The mortality rate is high because of late diagnosis and limited chances for curative surgery, and the resection rate at the initial diagnosis has been reported to be 20%–30% [4,5]. In a previous prospective study of inoperable cases, the 1- and 2-year overall survival rates of CCA were 22.4% and 3.4%, respectively [6].
For a long time, metallic or plastic biliary stenting has been considered the best palliative treatment for unresectable CCA or malignant biliary obstruction (MBO) caused by pancreatic cancer. However, several attempts have been recently made to improve clinical outcomes using local tumor treatments. Radiofrequency ablation (RFA) is a regional direct tumor ablation treatment for unresectable CCA or MBO due to metastatic biliary tumors, in which radiofrequency energy is delivered through endoscope channels. This technique has yielded outstanding outcomes in some prospective studies over the last decade [7,8]. Therefore, the aim of this meta-analysis and systematic review was to determine the effect of endobiliary RFA therapy on the survival outcome of patients with unresectable extrahepatic CCA with MBO.
Search methods for identification of studies
A systematic review of published articles from 1970 through 2020 was conducted by searching MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov. Selection was restricted to studies written in English. The keywords used to search for relevant articles in the different databases are described in Appendix 1. References listed in the retrieved articles were reviewed for eligible studies.
Article selection
Eligible studies were determined according to the following criteria: (1) studies that analyzed patients with extrahepatic CCA or MBO, (2) studies that compared treatment outcomes between endobiliary RFA with stent insertion and stent insertion only, (3) randomized controlled trials (RCTs) and case– control studies with adjustment for confounding variables, and (4) studies reporting the relative risks or odds ratios of survival rate and stent patency duration in an RFA with stent group and a stent-only group.
Data extraction
The following information was extracted from each article: publication year, country, study design, case number, age of patients, sex of patients, presence of gallstones, tumor-node-metastasis stages, treatment methods, surgical outcomes, and survival times. Covariates were adjusted for in the statistical analysis. Among several case series reports, we extracted the same data from each case reference.
Assessment of risk of bias
The risk of bias (RoB) was independently assessed by two reviewers (BHC and MJJ) using the Cochrane RoB Tool for RCTs [9] and ROBINS-I (RoB in Nonrandomized Studies [NRSs] of Interventions) for NRSs [10]. The RoB for RCTs was graded as “low” for low risk, “high” for high risk, and “unclear” when the available information was not sufficient for a risk judgment. For NRSs, each domain of the RoB was rated as “low”, “moderate”, “serious”, or “critical” for RoB, and the overall RoB was determined according to the judgment for each domain. Any disagreements between the reviewers were resolved through a discussion among the three authors.
Quality of included studies
Among the RCTs, two studies (Yang et al. [7] and Kang et al. [11]) were rated as low for all RoB domains, whereas the other study (Hu et al. [8]) was rated as low for two domains (random sequence generation and incomplete outcome data) and as unclear for the other domains. All five NRSs [12-16] were graded as having an overall moderate RoB. In the domain of RoB due to confounding, four studies [12-15] used matching for confounding adjustment and one study [16] showed similar distributions of confounding covariates between groups. The RoB for this item was rated as moderate. The other RoB items were graded as low (Appendix 2).
Statistical analysis
The effects of treatments (RFA plus stent vs. stent only) on overall survival and stent patency were examined on the basis of pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The HRs and 95% CIs for these outcomes were extracted from the results of each study, or estimated based on available information such as log-rank test results and Kaplan–Meier curves [17]. Pooled HRs among studies and their 95% CIs and p-values were calculated using the random-effect model. Statistical heterogeneity between the studies was assessed using Cochran’s Q-test and I2 statistics. I2 values of 25%, 50%, and 75% were considered to indicate low, moderate, and high heterogeneity, respectively, as previously suggested [18]. A funnel plot and Egger’s test for asymmetry were applied to assess the possibility of publication bias among the studies for overall survival, but not for stent patency because of the small number of included studies. All analyses were performed using R version 3.5.1 (meta package). Two-sided p-values of <0.05 were considered statistically significant.
A total of 631 articles were reviewed for eligibility, and 600 studies were excluded according to criteria (Fig. 1). Among 31 eligible studies, we selected 3 RCTs and 5 retrospective trials that reported HRs adjusted for various confounding factors (3 case–control and 2 observational studies). Therefore, a total of eight studies with 420 participants (190 cases treated with RFA plus stent and 230 controls treated with stent insertion only) were included in the meta-analysis. The baseline descriptions of all enrolled studies are listed in Table 1. The most common tumor site was the extrahepatic bile duct (61.8%, hilar and distal CCA). Pancreatic cancer, gallbladder cancer, and metastatic biliary cancer accounted for 33.7%, 2.2%, and 1.2%, respectively. All studies involved ablation with endoscopic retrograde cholangiopancreatography (ERCP), except for the study by Wang et al., which used the percutaneous transhepatic route [14]. For RFA treatment, six of the enrolled studies mentioned using the same thermal probe (e.g., Habib probe) from the same manufacturer; however, one study [11] used the ELRATM (EndoLuminal Radiofrequency Ablation; Taewoong Medical, Seoul, Korea) probe and Hu et al. [8] did not describe the RFA devices in detail. Differences were noted in the type of stent used in each study after RFA. Two RCTs inserted only plastic stents [7,8], another study [11] inserted self-expandable metallic stents (SEMSs), whereas all retrospective trials used SEMSs in most of their cases [12-16].
The pooled HR for overall survival in the case group treated with RFA with stent was 0.47 (95% CI, 0.34–0.64; Fig. 2). A moderate heterogeneity was detected among the included studies (I2=44%). Only four articles (two RCTs and two observational studies) reported stent patency results. The pooled HR for stent patency was 0.79 (0.57–1.09), with a low heterogeneity (I2=7%; Fig. 3). All included studies reported mild-to-moderate adverse reaction profiles among their case groups.
Abdominal pain (3 cases), pancreatitis and hyperamylasemia (3 cases), cholangitis regardless of symptoms (34 cases), and cholecystitis (8 cases) were reported. All these complications were treated with antibiotics and conservative therapy, and no procedure-related mortality was reported. One case of intestinal perforation with pneumothorax occurred in one study; however, the authors commented that it was not related to the RFA procedure but rather to the scope device. No study demonstrated significant differences in terms of adverse events between the RFA plus stent group and the stent-only group. No significant publication bias was noted in the funnel plot for overall survival (Egger’s test p=0.2869; Fig. 4).
Although CCA is not a common malignant disease, the clinical outcomes are poor and the mortality rate is high because it is usually detected in an advanced stage at diagnosis. Surgical resection can provide the best curative treatment; however, most cases are unresectable or are poor candidates for surgery. Various types, designs, compositions, and sizes of stents have been developed; however, no survival improvement has been reported, except for the observation that stents with larger diameters may have a longer patency duration [19]. In this context, researchers have introduced many local treatments, including RFA and photodynamic therapy for MBO for the palliative treatment of advanced CCA.
RFA is a locoregional cancer treatment that delivers thermal energy generated by high-frequency alternating electrical current; however, it causes burn injuries that lead to protein denaturation, cell desiccation, and coagulative necrosis [20]. Two types of thin probe catheters have been introduced for endobiliary RFA treatment through ERCP scope channels: Habib EndoHPB (EMcision Ltd., London, UK; Boston Scientific, Marlborough, MA, USA) and ELRATM (Taewoong Medical). Since the first human study that reported successful decompression of bile duct obstruction [21], this therapy has been considered a palliative treatment for unresectable cases with MBO. However, some studies during the last decade reported that this challenging therapy enhanced not only the patency of the biliary tract but also the survival times of patients. These promising data suggest that sustained bile duct patency could prolong survival in patients with MBO. We investigated the clinical outcomes of local ablative treatment for MBO by performing a meta-analysis of eight clinical studies. We observed a survival benefit among patients who were treated with RFA with stent insertion compared with the stent-only group.
The mechanism of the survival benefit of this local ablation treatment may be explained by its ability to relieve biliary obstruction and prevent recurrent cholangitis, the leading cause of mortality. However, we found two interesting features from the enrolled articles. First, the results of Kallis et al. showed that stent patency was better in the stent-only group than in the RFA with stent group; however, the overall survival rate of the RFA with stent group was superior to that of the other group [13]. Sharaiha et al. found a survival improvement after adjustment for confounding factors, including stricture improvement [12]. Although data supporting this phenomenon are insufficient, these results suggest that mechanisms other than stent patency improve survival outcomes. Other research data in various solid tumor treatments support this hypothesis. Hansler et al. reported on the tumor-specific cytolytic activity of CD8(+) T cells after RFA therapy in patients with hepatocellular carcinoma and colorectal liver metastasis, suggesting that RFA may play a role through indirect anti-tumor effects [22]. den Brok et al. found that in situ tumor destruction provided a useful antigen source for the induction of antitumor immunity [23].
In terms of adverse events, we confirmed no serious perioperative or postoperative complications in our enrolled studies, except for mild-to-moderate cholangitis, pancreatitis, and a few cases of cholecystitis, all of which were medically treated. Nevertheless, there have been a few reports of critical adverse events in other retrospective studies. Tal et al. reported two deaths due to hemobilia, and thereby suggested insertion of SEMSs after RFA instead of plastic stents [24]. Roque et al. emphasized that a 1-min delay in removing the probe after RFA ablation to prevent tissue adhesion caused by heated electrodes might be a cause of tissue or vascular injury, possibly leading to hemobilia during withdrawal [25], citing the study method described by Dolak et al. [26] One rare case of liver infarction after treatment, which was conservatively managed, was also reported [25]. The authors recommended performing more careful preprocedural imaging analysis to avoid vascular or biliary injury [26].
Few studies with higher evidence levels and that explored the relationship between RFA treatment and survival improvement in patients with CCA are available. The number of studies included in our systematic review was very small: the pooled analysis for overall survival was performed using eight studies (three RCTs and five observational studies), and stent patency was reported in only four of these studies. Moreover, all our enrolled studies included a considerable number of patients with pancreatic cancer and gallbladder cancer with biliary invasion, although the proportions were not high. The survival benefit should be compared in different ways because different primary cancer sites would cause different clinical outcomes. However, we could not compare the pooled HRs because the original studies did not report the data for each subgroup. In this regard, further studies with subgroup analysis in terms of different primary cancer origins are warranted in the future.
Despite these limitations, our systematic review with meta-analysis, of three RCTs and five retrospective studies with control for confounding factors, demonstrates that endobiliary RFA treatment confers a survival benefit to patients with MBO caused by unresectable CCA or pancreatic cancer. More well-designed studies are warranted to elucidate the mechanism of these beneficial effects and to compare the outcomes in various individual primary cancers.
Fig. 1.
Schematic flowchart of study enrollment, including identification, screening, eligibility, exclusion, and analysis inclusion, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines 2009. RCTs, randomized controlled trials.
ce-2020-254f1.jpg
Fig. 2.
Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of overall survival rates between two groups (endobiliary radiofrequency ablation with stent vs. stent only) among patients with cholangiocarcinoma with malignant biliary obstruction (random-effect model, eight studies with 420 participants). NRS, non-randomised study; RCT, randomized controlled trial.
ce-2020-254f2.jpg
Fig. 3.
Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of stent patency between two groups (endobiliary radiofrequency ablation with stent vs. stent only) among patients with cholangiocarcinoma with malignant biliary obstruction (random-effect model, four studies with 205 participants). NRS, non-randomised study; RCT, randomized controlled trial.
ce-2020-254f3.jpg
Fig. 4.
Funnel plot and Egger’s test for asymmetry for survival outcome analyses of eight enrolled studies. HR, hazard ratio.
ce-2020-254f4.jpg
Table 1.
Summarized Study Designs, Outcomes and Adverse Events among the Eight Enrolled Studies
Study Study design No. of patients
 Outcome Median time (95% CI, mo)
 HR (95% CI) for RFA Adverse events
RFA+S Stent RFA+S Stent
Sharaiha et al. (2014) [12] Retrospective 26 40 Overall survival 5.9 for both groups (not reported for each group) 0.29 (0.11–0.76) Abdominal pain 3; Pancreatitis 1; Cholecystitis 1
Kallis et al. (2015) [13] Retrospective 23 46 Overall survival 7.5 4.1 0.66 (0.410–1.063) Hyperamylasemia 1; Cholangitis 1
Stent patency 15.7 10.8 1.186 (0.536–2.656)
Hu et al. (2016) [8] RCT 32 31 Overall survival 10.4 (8.0–12.7) 57.3 (4.8–6.6) 0.48 (0.27–0.85)a) Bleeding 1; Cholangitis 20; Cholecystitis 7
5 (3.0–7.1) 3.9 (2.6–5.2) 0.90 (0.52–1.55)a)
Wang et al. (2016) [14] Retrospective 18 18 Overall survival 6.1 (4.8–15.2) 5.8 (4.2–16.5) 0.598 (0.324– Cholangitis 3
Stent patency 5.8 (2.8–11.5) 4.5 (2.4–8.0) 0.49 (0.25–0.93)a)
Dutta et al. (2017) [15] Retrospective 15 16 Overall survival 7.3 4.9 0.39 (0.17–0.92) Pancreatitis 1; Cholangitis 1
Yang et al. (2018) [7] RCT 32 33 Overall survival 13.2±0.6b) 8.2±0.5b) 0.182 (0.08–0.322) Cholangitis 2
Stent patency 6.8 (3.6–8.2) 3.4 (2.4–6.5) N/Ac)
Bokemeyer et al. (2019) [16] Retrospective 20 22 Overall survival 11.4 7.4 0.54 (0.29–0.99)a) Cholangitis 6; panceratitis 2; Intestinal perforation 1d)
Kang et al. (2021) [11] RCT 24 24 Overall survival 8.3 (3.9–12.3) 6.0 (0.9–11.1) 0.71 (0.38–1.33) Cholangitis 1
Stent patency 4.4 (3.3–5.5) 3.9 (1.1–5.9) 0.80 (0.45–1.42)

CI, confidence interval; HR, hazard ratio; N/A, not available; RCT, randomized controlled study; RFA, radiofrequency ablation; RFA+S, radiofrequency ablation plus stent.

a)HR calculated from a log-rank p-value and number of event.

b)Mean survival time±standard error.

c)Information not available for estimation of HR.

d)One intestinal perforation with pneumothorax occurred in one study, however, authors commented that it was not related with RFA procedure, rather than by the scope device.

  • 1. Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis 1994;14:109–114.ArticlePubMed
  • 2. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Dicker D, et al. The global burden of cancer 2013. JAMA Oncol 2015;1:505–527.PubMedPMC
  • 3. Patel N, Benipal B. Incidence of cholangiocarcinoma in the USA from 2001 to 2015: A US cancer statistics analysis of 50 states. Cureus 2019;11:e3962.ArticlePubMedPMC
  • 4. Zografos GN, Farfaras A, Zagouri F, Chrysikos D, Karaliotas K. Cholangiocarcinoma: principles and current trends. Hepatobiliary Pancreat Dis Int 2011;10:10–20.ArticlePubMed
  • 5. Esnaola NF, Meyer JE, Karachristos A, Maranki JL, Camp ER, Denlinger CS. Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma. Cancer 2016;122:1349–1369.ArticlePubMed
  • 6. Mihalache F, Tantau M, Diaconu B, Acalovschi M. Survival and quality of life of cholangiocarcinoma patients: a prospective study over a 4 year period. J Gastrointestin Liver Dis 2010;19:285–290.PubMed
  • 7. Yang J, Wang J, Zhou H, et al. Efficacy and safety of endoscopic radiofrequency ablation for unresectable extrahepatic cholangiocarcinoma: a randomized trial. Endoscopy 2018;50:751–760.ArticlePubMed
  • 8. Hu B, Gao DJ, Zhang X, Zhang YC. Endobiliary radiofrequency ablation improve overall survival of cholangiocarcinoma: a multi-center randomized control study. Gastrointest Endosc 2016;83(5 Suppl):AB126.Article
  • 9. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.ArticlePubMedPMC
  • 10. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016;355:i4919.ArticlePubMedPMC
  • 11. Kang H, Chung MJ, Cho IR, et al. Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL. Surg Endosc 2021;35:63–73.ArticlePubMed
  • 12. Sharaiha RZ, Natov N, Glockenberg KS, Widmer J, Gaidhane M, Kahaleh M. Comparison of metal stenting with radiofrequency ablation versus stenting alone for treating malignant biliary strictures: is there an added benefit? Dig Dis Sci 2014;59:3099–3102.ArticlePubMed
  • 13. Kallis Y, Phillips N, Steel A, et al. Analysis of endoscopic radiofrequency ablation of biliary malignant strictures in pancreatic cancer suggests potential survival benefit. Dig Dis Sci 2015;60:3449–3455.ArticlePubMed
  • 14. Wang J, Zhao L, Zhou C, et al. Percutaneous intraductal radiofrequency ablation combined with biliary stent placement for nonresectable malignant biliary obstruction improves stent patency but not survival. Medicine (Baltimore) 2016;95:e3329.ArticlePubMedPMC
  • 15. Dutta AK, Basavaraju U, Sales L, Leeds JS. Radiofrequency ablation for management of malignant biliary obstruction: a single-center experience and review of the literature. Expert Rev Gastroenterol Hepatol 2017;11:779–784.ArticlePubMed
  • 16. Bokemeyer A, Matern P, Bettenworth D, et al. Endoscopic radiofrequency ablation prolongs survival of patients with unresectable hilar cholangiocellular carcinoma - a case-control study. Sci Rep 2019;9:13685.ArticlePubMedPMC
  • 17. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007;8:16.ArticlePubMedPMC
  • 18. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.ArticlePubMedPMC
  • 19. Loew BJ, Howell DA, Sanders MK, et al. Comparative performance of uncoated, self-expanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial. Gastrointest Endosc 2009;70:445–453.ArticlePubMed
  • 20. Goldberg SN, Gazelle GS. Radiofrequency tissue ablation: physical principles and techniques for increasing coagulation necrosis. Hepatogastroenterology 2001;48:359–367.PubMed
  • 21. Steel AW, Postgate AJ, Khorsandi S, et al. Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction. Gastrointest Endosc 2011;73:149–153.ArticlePubMed
  • 22. Hansler J, Wissniowski TT, Schuppan D, et al. Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases. World J Gastroenterol 2006;12:3716–3721.ArticlePubMedPMC
  • 23. den Brok MH, Sutmuller RP, van der Voort R, et al. In situ tumor ablation creates an antigen source for the generation of antitumor immunity. Cancer Res 2004;64:4024–4029.ArticlePubMed
  • 24. Tal AO, Vermehren J, Friedrich-Rust M, et al. Intraductal endoscopic radiofrequency ablation for the treatment of hilar non-resectable malignant bile duct obstruction. World J Gastrointest Endosc 2014;6:13–19.ArticlePubMedPMC
  • 25. Roque J, Ho SH, Reddy N, Goh KL. Endoscopic ablation therapy for biliopancreatic malignancies. Clin Endosc 2015;48:15–19.ArticlePubMedPMC
  • 26. Dolak W, Schreiber F, Schwaighofer H, et al. Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications. Surg Endosc 2014;28:854–860.ArticlePubMed
APPENDICES

Appendix 1. Search key words.

MEDLINE

(radiofrequency ablation OR (radiofrequency OR ablation)) AND (cholangiocarcinoma OR ((bile duct OR biliary) AND (cancer OR tumor OR malignancy)) OR (malignant biliary obstruction OR cholestasis))

EMBASE

*survival; *patient; *human; *bile duct carcinoma; *radiofrequency ablation; therapy; diagnosis; chemoradiotherapy; Kaplan–Meier method; endoscopic retrograde cholangiopancreatography; overall survival; surgery; medical record review; tissue necrosis; randomized controlled trial; retrospective study; survival rate; procedures; biliary stent; distant metastasis; classification; hospital patient; hepatobiliary system

Cochrane Library

“radiofrequency ablation” in Title Abstract Keyword AND cholangiocarcinoma in Title Abstract Keyword
Appendix 2.
Quality assessment of risk of bias among the included studies (Tables 1, 2).
Table 1.
Quality Assessment Using the Cochrane Risk of Bias Tool for Randomized Controlled Trials
Study Random sequence generation Allocation conceal- ment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Other sources of bias Overall
Hu et al. (2016) [8] Low Unclear Unclear Unclear Low Unclear Unclear Unclear
Yang et al. (2018) [7] Low Low Low Low Low Low Low Low
Kang et al. (2021) [11] Low Low Low Low Low Low Low Low
Table 2.
Quality Assessment Using Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) for Nonrandomized Studies
Study Bias due to confounding Bias in selection of participants for the study Bias in measurement of interventions Bias due to departures from intended interven- tions Bias due to missing data Bias in measurement of outcomes Bias in selection of the reported result Overall
Sharaiha et al. (2014) [12] Moderatea) Low Low Low Low Low Low Moderate
Kallis et al. (2015) [13] Moderateb) Low Low Low Low Low Low Moderate
Wang et al. (2016) [14] Moderatec) Low Low Low Low Low Low Moderate
Dutta et al. (2017) [15] Moderated) Low Low Low Low Low Low Moderate
Bokemeyer et al. (2019) [16] Moderatee) Low Low Low Low Low Low Moderate

a)Matched for age, diagnosis, performance status, and palliative chemotherapy, and adjusted for age, chemotherapy, and stricture improvement.

b)Matched for age, sex, comorbidity, American Society of Anesthesiologists category, and presence of metastasis.

c)Matched for tumor type, location of obstruction, tumor stage, and Child-Pugh class status.

d)Matched for age, sex, disease type, and disease stage, and adjusted for age, tumor site, tumor type, stent type (covered or uncovered), disease stage, and oncological treatment.

e)Similar distributions between groups in terms of age, extent of disease, use of endoprostheses, and application of systemic palliative chemotherapy.

Figure & Data

REFERENCES

    Citations

    Citations to this article as recorded by  
    • Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis
      Matheus de Oliveira Veras, Diogo Turiani Hourneaux de Moura, Thomas R. McCarty, Guilherme Henrique Peixoto de Oliveira, Rômulo Sérgio Araújo Gomes, Davi Lucena Landim, Felipe Giacobo Nunes, Tomazo Antônio Prince Franzini, Marcos Eduardo Lera dos Santos, W
      Endoscopy International Open.2024; 12(01): E23.     CrossRef
    • Reply to Chandrasekhara and Aggarwal
      Matheus de Oliveira Veras, Diogo Turiani Hourneaux de Moura, Eduardo Guimarães Hourneaux de Moura
      Endoscopy International Open.2024; 12(05): E640.     CrossRef
    • Consensus statements on endoscopic radiofrequency ablation for malignant biliary strictures

      Journal of Digestive Diseases.2024; 25(1): 2.     CrossRef
    • The Impact of Radiofrequency Ablation on Survival Outcomes and Stent Patency in Patients with Unresectable Cholangiocarcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
      Daniele Balducci, Michele Montori, Francesco Martini, Marco Valvano, Federico De Blasio, Maria Eva Argenziano, Giuseppe Tarantino, Antonio Benedetti, Emanuele Bendia, Marco Marzioni, Luca Maroni
      Cancers.2024; 16(7): 1372.     CrossRef
    • Impact of temperature-controlled endobiliary radiofrequency ablation for inoperable hilar cholangiocarcinoma: A propensity score–matched analysis
      Il Sang Shin, Jong Ho Moon, Yun Nah Lee, Jun Ho Myeong, Tae Hoon Lee, Jae Kook Yang, Young Deok Cho, Sang-Heum Park
      Endoscopy International Open.2024; 12(04): E535.     CrossRef
    • Percutaneous endobiliary radiofrequency ablation and stent placement for unresectable malignant biliary obstruction: a propensity score matching retrospective study
      Wei Cui, Jing-Zhi Huang, Qi Wang, Feng Shi, Qing Gou, Xiao-Ming Chen, Jing Zhang, Jia-Ping Li, Rongde Xu
      BMC Gastroenterology.2024;[Epub]     CrossRef
    • Biliary stents for active materials and surface modification: Recent advances and future perspectives
      Yuechuan Li, Kunshan Yuan, Chengchen Deng, Hui Tang, Jinxuan Wang, Xiaozhen Dai, Bing Zhang, Ziru Sun, Guiying Ren, Haijun Zhang, Guixue Wang
      Bioactive Materials.2024; 42: 587.     CrossRef
    • Chinese national clinical practice guideline on diagnosis and treatment of biliary tract cancers
      Xu’an Wang, Yongrui Bai, Ningli Chai, Yexiong Li, Enqiang Linghu, Liwei Wang, Yingbin Liu
      Chinese Medical Journal.2024; 137(19): 2272.     CrossRef
    • Feasibility and safety of trans-biliary cryoablation: Preclinical evaluation of a novel flexible cryoprobe
      Chao Zhang, Linzhong Zhu, Shousheng Tang, Jukun Wang, Yu Li, Xin Chen, Chunjing Bian, Dongbin Liu, Guokun Ao, Tao Luo
      Cryobiology.2023; 111: 40.     CrossRef
    • Efficacy and Safety of Radiofrequency Ablation Plus Stent Versus Stent-alone Treatments for Malignant Biliary Strictures
      Hayat Khizar, Yufei Hu, Yanhua Wu, Kamran Ali, Junaid Iqbal, Muhammad Zulqarnain, Jianfeng Yang
      Journal of Clinical Gastroenterology.2023; 57(4): 335.     CrossRef
    • Development of novel biliary metal stent with coil-spring structure and its application in vivo swine biliary stricture model
      In Rae Cho, Sang Hyub Lee, Jin Ho Choi, Namyoung Park, Min Woo Lee, Joo Seong Kim, Seok Jeong, Don Haeng Lee, Tae-Won Jeong, Byoung-Yun Ki, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim
      Frontiers in Oncology.2023;[Epub]     CrossRef
    • 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
      Namyoung Park, Min Kyu Jung, Eui Joo Kim, Woo Hyun Paik, Jae Hee Cho
      Gastrointestinal Endoscopy.2023; 97(4): 694.     CrossRef
    • ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures
      B. Joseph Elmunzer, Jennifer L. Maranki, Victoria Gómez, Anna Tavakkoli, Bryan G. Sauer, Berkeley N. Limketkai, Emily A. Brennan, Elaine M. Attridge, Tara J. Brigham, Andrew Y. Wang
      American Journal of Gastroenterology.2023; 118(3): 405.     CrossRef
    • 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
      Zahid Ijaz Tarar, Umer Farooq, Mustafa Gandhi, Ghulam Ghous, Saad Saleem, Faisal Kamal, Zaid Imam, Laith Jamil
      European Journal of Gastroenterology & Hepatology.2023; 35(6): 646.     CrossRef
    • Impact of endobiliary radiofrequency ablation on survival of patients with unresectable cholangiocarcinoma: a narrative review
      Elena Di Girolamo, Andrea Belli, Alessandro Ottaiano, Vincenza Granata, Valentina Borzillo, Luca Tarotto, Fabiana Tatangelo, Raffaele Palaia, Corrado Civiletti, Mauro Piccirillo, Valentina D’Angelo, Francesco Fiore, Pietro Marone, Guglielmo Nasti, Frances
      Frontiers in Oncology.2023;[Epub]     CrossRef
    • Endoluminal radiofrequency ablation in patients with malignant biliary obstruction: a randomised trial
      Jana Jarosova, Lea Zarivnijova, Ivana Cibulkova, Jan Mares, Peter Macinga, Alzbeta Hujova, Premysl Falt, Ondrej Urban, Jan Hajer, Julius Spicak, Tomas Hucl
      Gut.2023; 72(12): 2286.     CrossRef
    • Is endoscopic radiofrequency ablation plus stent placement superior to stent placement alone for the treatment of malignant biliary obstruction? A systematic review and meta-analysis
      Chenming Liu, Jiaming Dong, Yuxing Liu, Siyuan Zhang, Ruanchang Chen, Haijun Tang
      Journal of International Medical Research.2023;[Epub]     CrossRef
    • Intraductal Therapies for Cholangiocarcinoma
      Abhishek Agnihotri, David E. Loren
      Techniques and Innovations in Gastrointestinal Endoscopy.2022; 24(2): 200.     CrossRef
    • Silver Nanofunctionalized Stent after Radiofrequency Ablation Suppresses Tissue Hyperplasia and Bacterial Growth
      Yubeen Park, Dong-Sung Won, Ga-Hyun Bae, Dae Sung Ryu, Jeon Min Kang, Ji Won Kim, Song Hee Kim, Chu Hui Zeng, Wooram Park, Sang Soo Lee, Jung-Hoon Park
      Pharmaceutics.2022; 14(2): 412.     CrossRef
    • Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma—A Systematic Review and Meta-Analysis
      David M. de Jong, Jeska A. Fritzsche, Amber S. Audhoe, Suzanne S. L. Yi, Marco J. Bruno, Rogier P. Voermans, Lydi M. J. W. van Driel
      Cancers.2022; 14(9): 2079.     CrossRef
    • Evaluation and Management of Malignant Biliary Obstruction
      Nadia V. Guardado, Kaysey Llorente, Benoit Blondeau
      Surgical Oncology Clinics of North America.2021; 30(3): 491.     CrossRef

    • PubReader PubReader
    • ePub LinkePub Link
    • Cite
      CITE
      export Copy Download
      Close
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Survival Benefit of Intraductal Radiofrequency Ablation for Malignant Biliary Obstruction: A Systematic Review with Meta-Analysis
      Clin Endosc. 2021;54(1):100-106.   Published online January 15, 2021
      DOI: https://doi.org/10.5946/ce.2020.254
      Close
    • XML DownloadXML Download
    Figure
    • 0
    • 1
    • 2
    • 3
    Related articles
    Survival Benefit of Intraductal Radiofrequency Ablation for Malignant Biliary Obstruction: A Systematic Review with Meta-Analysis
    Image Image Image Image
    Fig. 1. Schematic flowchart of study enrollment, including identification, screening, eligibility, exclusion, and analysis inclusion, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines 2009. RCTs, randomized controlled trials.
    Fig. 2. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of overall survival rates between two groups (endobiliary radiofrequency ablation with stent vs. stent only) among patients with cholangiocarcinoma with malignant biliary obstruction (random-effect model, eight studies with 420 participants). NRS, non-randomised study; RCT, randomized controlled trial.
    Fig. 3. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of stent patency between two groups (endobiliary radiofrequency ablation with stent vs. stent only) among patients with cholangiocarcinoma with malignant biliary obstruction (random-effect model, four studies with 205 participants). NRS, non-randomised study; RCT, randomized controlled trial.
    Fig. 4. Funnel plot and Egger’s test for asymmetry for survival outcome analyses of eight enrolled studies. HR, hazard ratio.

    Fig. 1.

    Fig. 2.

    Fig. 3.

    Fig. 4.

    Survival Benefit of Intraductal Radiofrequency Ablation for Malignant Biliary Obstruction: A Systematic Review with Meta-Analysis
    Study Study design No. of patients
    		 Outcome Median time (95% CI, mo)
    		 HR (95% CI) for RFA Adverse events
    RFA+S Stent RFA+S Stent
    Sharaiha et al. (2014) [12] Retrospective 26 40 Overall survival 5.9 for both groups (not reported for each group) 0.29 (0.11–0.76) Abdominal pain 3; Pancreatitis 1; Cholecystitis 1
    Kallis et al. (2015) [13] Retrospective 23 46 Overall survival 7.5 4.1 0.66 (0.410–1.063) Hyperamylasemia 1; Cholangitis 1
    Stent patency 15.7 10.8 1.186 (0.536–2.656)
    Hu et al. (2016) [8] RCT 32 31 Overall survival 10.4 (8.0–12.7) 57.3 (4.8–6.6) 0.48 (0.27–0.85)a) Bleeding 1; Cholangitis 20; Cholecystitis 7
    5 (3.0–7.1) 3.9 (2.6–5.2) 0.90 (0.52–1.55)a)
    Wang et al. (2016) [14] Retrospective 18 18 Overall survival 6.1 (4.8–15.2) 5.8 (4.2–16.5) 0.598 (0.324– Cholangitis 3
    Stent patency 5.8 (2.8–11.5) 4.5 (2.4–8.0) 0.49 (0.25–0.93)a)
    Dutta et al. (2017) [15] Retrospective 15 16 Overall survival 7.3 4.9 0.39 (0.17–0.92) Pancreatitis 1; Cholangitis 1
    Yang et al. (2018) [7] RCT 32 33 Overall survival 13.2±0.6b) 8.2±0.5b) 0.182 (0.08–0.322) Cholangitis 2
    Stent patency 6.8 (3.6–8.2) 3.4 (2.4–6.5) N/Ac)
    Bokemeyer et al. (2019) [16] Retrospective 20 22 Overall survival 11.4 7.4 0.54 (0.29–0.99)a) Cholangitis 6; panceratitis 2; Intestinal perforation 1d)
    Kang et al. (2021) [11] RCT 24 24 Overall survival 8.3 (3.9–12.3) 6.0 (0.9–11.1) 0.71 (0.38–1.33) Cholangitis 1
    Stent patency 4.4 (3.3–5.5) 3.9 (1.1–5.9) 0.80 (0.45–1.42)
    Study Random sequence generation Allocation conceal- ment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Other sources of bias Overall
    Hu et al. (2016) [8] Low Unclear Unclear Unclear Low Unclear Unclear Unclear
    Yang et al. (2018) [7] Low Low Low Low Low Low Low Low
    Kang et al. (2021) [11] Low Low Low Low Low Low Low Low
    Study Bias due to confounding Bias in selection of participants for the study Bias in measurement of interventions Bias due to departures from intended interven- tions Bias due to missing data Bias in measurement of outcomes Bias in selection of the reported result Overall
    Sharaiha et al. (2014) [12] Moderatea) Low Low Low Low Low Low Moderate
    Kallis et al. (2015) [13] Moderateb) Low Low Low Low Low Low Moderate
    Wang et al. (2016) [14] Moderatec) Low Low Low Low Low Low Moderate
    Dutta et al. (2017) [15] Moderated) Low Low Low Low Low Low Moderate
    Bokemeyer et al. (2019) [16] Moderatee) Low Low Low Low Low Low Moderate
    Table 1. Summarized Study Designs, Outcomes and Adverse Events among the Eight Enrolled Studies

    CI, confidence interval; HR, hazard ratio; N/A, not available; RCT, randomized controlled study; RFA, radiofrequency ablation; RFA+S, radiofrequency ablation plus stent.

    HR calculated from a log-rank p-value and number of event.

    Mean survival time±standard error.

    Information not available for estimation of HR.

    One intestinal perforation with pneumothorax occurred in one study, however, authors commented that it was not related with RFA procedure, rather than by the scope device.

    Table 1. Quality Assessment Using the Cochrane Risk of Bias Tool for Randomized Controlled Trials

    Table 2. Quality Assessment Using Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) for Nonrandomized Studies

    Matched for age, diagnosis, performance status, and palliative chemotherapy, and adjusted for age, chemotherapy, and stricture improvement.

    Matched for age, sex, comorbidity, American Society of Anesthesiologists category, and presence of metastasis.

    Matched for tumor type, location of obstruction, tumor stage, and Child-Pugh class status.

    Matched for age, sex, disease type, and disease stage, and adjusted for age, tumor site, tumor type, stent type (covered or uncovered), disease stage, and oncological treatment.

    Similar distributions between groups in terms of age, extent of disease, use of endoprostheses, and application of systemic palliative chemotherapy.

    Table 1.

    Table 1.

    Table 2.

    Clin Endosc : Clinical Endoscopy Twitter Facebook
    © Korean Society of Gastrointestinal Endoscopy.
    Close layer
    TOP