Original Article

Intraductal radiofrequency ablation for refractory benignbiliary stricture: Pilot feasibility study

Bing Hu, Dao-Jian Gao, Jun Wu, Tian-Tian Wang, Xiao-Ming Yang and Xin Ye

Department of Endoscopy, Eastern Hepatobiliary Hospital, The Second Military Medical University,Shanghai, China

Background and Aim: Endoscopic management of benignbiliary stricture (BBS) remains challenging. There is no reportedmethod for the amelioration of biliary fibroplasia endoscopically.We report our initial experience of radiofrequency ablation (RFA)for the management of BBS.

Methods: Nine patients with BBS (postoperation stricturefour, liver transplant three, and chronic inflammation two),seven of whom had previously unsuccessful endoscopic orpercutaneous interventions, were enrolled. Intraductal bipolarRFA was delivered at power of 10 W for 90 s per stricturesegment, followed by balloon dilatation with/without stentplacement.

Results: All patients had immediate stricture improvementsafter RFA. No severe adverse event occurred except for one

patient with mild post-endoscopic retrograde cholangiopancrea-tography pancreatitis. During median (SD) follow-up duration of12.6 (3.9) months, BBS resolution without the need for furtherstenting was achieved in four patients whereas two patients hadstent(s) in situ waiting scheduled removal. However, one patienthad stricture relapse after initial resolution, one underwentsurgery, and another patient died of other cause.

Conclusions: Endobiliary RFA appears to be safe and effectivefor the treatment of BBS, especially for refractory cases. Furtherstudies are warranted.

Key words: biliary stricture, endoscopic retrograde cholangi-opancreatography (ERCP), radiofrequency ablation (RFA), self-expandable metallic stent (SEMS)

INTRODUCTION

THERE ARE DIFFERENT causes for benign biliarystrictures (BBS); among them the commonest causes

are iatrogenic injury during surgery, anastomotic stricturefollowing liver transplantation (LT) and chronic pancreatitis.Pathologically fibrous tissue hyperplasia leads to strictureformation.1–3 Endoscopic management of BBS can be tech-nically challenging. Although aggressive dilation combinedwith maximal stent placement can expand biliary narrowing,the procedure does not ameliorate fibrosis. To the best of ourknowledge, there is no reported method for the ablation ofbiliary fibroplasia endoscopically. We hereby describe ourinitial experience in the treatment of BBS with bipolarradiofrequency ablation (RFA).

METHODS

THE BIPOLAR RADIO frequency (RF) probe(HABIB™ EndoHPB; EMcision, London, UK), 8 Fr in

diameter and 1.8 m in length, has two ring electrodes pro-viding local coagulation over 2.5 cm in length. The probewas connected to a RF generator (ESG 100; Olympus,Tokyo, Japan) at the mode of RF coagulation plus resistancecontrolled automatic power (RCAP), the energy of whichcould be adjusted with tissue resistance. The energy wasdelivered at 10 W for 90 s per segment. If the stricture waslonger than 2.5 cm or involved different hepatic ducts,sequential RFA were applied to cover all stricture segments.

Patients with BBS, especially unsuccessful in prior inter-ventions, underwent endoscopic retrograde cholangiopan-creatography (ERCP). If the BBS persisted (narrowing<50% of duct size), a sphincterotomy was made followed byinitial dilation using an 8.5-Fr catheter dilator. The RF probewas inserted over the guidewire (0.035 inch, Jagwire™;Boston Scientific, Marlboro, MA, USA) and energy deliv-ered to the stricture segment. After RFA treatment, accordingto bile duct size, a 6–10-mm balloon dilator (Hurricane™;Boston Scientific) was introduced to dilate the stricturesegment. Then, repeat cholangiography was made to confirm

Corresponding: Bing Hu, Department of Endoscopy, EasternHepatobiliary Hospital, The Second Military Medical University,225 Changhai Road, Shanghai 200438, China. Email: drhubing@aliyun.comThe paper was presented in part as a poster during Digestive DiseaseWeek in Orlando, Florida, USA, 19–22 May, 2013, and the abstractwas published in Gastrointestinal Endoscopy 2013; 77(5): AB320.Received 7 November 2013; accepted 3 December 2013.

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Digestive Endoscopy 2014; 26: 581–585 doi: 10.1111/den.12225

© 2014 The AuthorsDigestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society

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resolution of BBS and to decide whether further stenting wasrequired. If the stricture had been resolved completely, nofurther stent was placed and a nasobiliary drain was given fortemporary drainage. If the narrowing was still obvious,further stenting was arranged. When the stricture involvedthe hepatic hilum, multiple plastic stents were placed toensure bile drainage from both sides. If a low stricture wasencountered, at least 1.5 cm from the hilar bifurcation, aremovable covered self-expandable metallic stent (SEMS)was placed crossing the stenosis below the bifurcation.

Post-procedure management was as usual. Broad-spectrumantibiotics (ciprofloxacin and metronidazole) were given i.v.for 3 days. Blood routine examination, liver function andamylase were monitored. Any discomfort, complaints oradverse events were recorded. All patients were followed upthrough the clinic or by telephone. Patients with stent(s) insitu were recommended to return for stent removal in 6–12months. Stricture resolution was defined as an increase instenotic region >50% of lumen size and an inflated balloonwas able to pass through easily.

The study protocol was approved by the InstitutionalReview Board (IRB) for human research of the Eastern Hepa-tobiliary Hospital (EHBH) and all patients gave informedconsent to participate in the study.

RESULTS

BETWEEN DECEMBER 2011 and July 2013, ninepatients, six men and three women, mean (SD) age 52.8

(11.1) years, underwent ERCP and RFA therapy. Amongthem, causes of BBS included post-cholecystectomy injury infour, anastomotic stricture after LT in three, chronic inflam-mation in one and chronic pancreatitis in one. The strictureswere located in the distal common bile duct (one), commonhepatic duct (three), and both intra- and extrahepatic ducts(five), with a length of 0.5 cm to 5 cm (median 1 cm). Sixpatients had previously undergone endoscopic stent therapy

and one patient had a percutaneous procedure without com-plete stricture resolution. Median serum bilirubin was 36.3(range 3.5–170.5) μmol/L before the procedure. After RFAand balloon dilation, the stenoses of all patients significantlyimproved (Fig. 1) and five patients met the criteria of strictureresolution. Among them, three cases needed no further stent-ing, whereas the remaining six patients still received stentplacement, three with multiple plastic stents and two withremovable fully covered SEMS. One patient with distal bileduct stricture as a result of chronic pancreatitis, and who hadbeen fitted with an uncovered SEMS in a another hospital, wasfound to have severe tissue hyperplasia inside the stent.Although the lumen had been large enough for bile drainageafter RFA therapy, removal of SEMS was unsuccessful. Thepatient underwent open surgery for stent retrieval and biliary-enteric bypass 2 months later.

After the procedure, acute pancreatitis occurred in onepatient who was successfully managed with conservativetreatment within 3 days. Two patients had mild abdominalpain that resolved after a single dose of analgesic. Twopatients had transient leukocytosis that decreased to normalwithout additional treatment within 2 days. Serum bilirubinreturned to normal in all patients 1 month after the procedure.

By September 2013, two patients with BBS as a resultof injury underwent endoscopic reintervention and stentremoval. Cholangiography confirmed resolution of the stric-tures (Fig. 2). One LT recipient, having initial BBS resolu-tion, had recurrence of sepsis as a result of stricture relapse 4months after RFA. Endoscopic reintervention was arrangedand started with stent therapy. Two patients still had theirstent(s) in situ waiting for scheduled removal.Another patientwith stent in situ died of cancer recurrence 12 months afterRFA without biliary symptoms. Thus, to date, a total of fourpatients in this series achieved stricture resolution without theneed for stenting at a median (SD) follow up of 12.6 (3.9)months. Patient characteristics and outcomes are shown inTable 1.

A B C D

Figure 1 Female patient (case 2) hadsevere hepatic duct strictures (arrows)as a result of cholecystectomy. (a) Per-cutaneous intervention failed to resolvethe stricture. (b) Endobiliary radio-frequency ablation was carried out,followed by (c) balloon dilation.(d) Significant stricture improvementwas achieved immediately afterendotherapy.

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DISCUSSION

ENDOSCOPIC THERAPY HAS gained acceptance as afirst-line treatment for BBS because of its less invasive

nature and lower morbidity as compared with surgery.4,5 Thestandard endoscopic strategy is to insert an increasingnumber of plastic stents over a period of 1 year. Long-termfollow up with this strategy indicates approximately 80%resolution of postoperative strictures.6–8 Covered SEMSplacement has recently gained popularity in this settingbecause it requires fewer interventional sessions. Severalseries reports have revealed that covered SEMS therapy canachieve 65–90% resolution of extrahepatic strictures.9–12

Although the dilating and stenting method has allowed suc-cessful resolution of regional BBS in most cases, 10–40% ofBBS do not respond well to this strategy and stricture relapsemay occur in 10–30% of cases after initial resolution.1,4,5 Itwould be desirable to explore some new approaches for thesalvage of such refractory cases.

BBS arise from a heterogeneous group of diseases andmost BBS are secondary to fibrous tissue hyperplasia or scarformation pathologically.13,14 Stiffness of the scar tissue mayprevent it from complete resolution through dilating andstenting. Radiofrequency techniques can deliver heat energyto the tissue. When high-frequency alternating electricalcurrent is applied through the probe electrodes, rapid move-ment of intracellular ions is created towards opposite direc-tions. In turn, ionic motion creates frictional forces thatgenerate heat around the probe and, eventually, the sur-rounding tissue.15 We hypothesize that the thermal effectcreated by RF can either destroy or soften benign biliaryfibrous tissue, making further dilating and stenting mani-pulation easy, and ultimately improve the efficacy ofendotherapy.

The bipolar RFA probe, HABIB™ EndoHPB (EMcision),is a novel device designed for the ablation of biliary-pancreatic malignancies. In animal studies, both ex vivo andin vivo, this device can effectively deliver RF energy intra-luminally in the porcine liver and bile duct.16,17 This devicewas recently reported in clinical palliation of unresectablebiliary cancer showing excellent ablation of tumor tissue inseveral small cases series.18–21 However, the application ofRFA for the treatment of BBS has not been reported.

In the current study, we realized the ease of RFA manipu-lation with the bipolar probe. With the guide of a standardguidewire and prior dilation, the RF catheter can be easilyintroduced to the biliary tract and accurately positioned atthe stricture lesion. Visible electrodes can deliver energy fortissue ablation according to the pre-setting and can be auto-matically terminated if certain impedance is exceeded. AfterRFA, all nine patients in our group showed immediateimprovement in biliary narrowing. The procedure appears tobe safe. We did not encounter serious adverse events asso-ciated with RF manipulation. Our preliminary experienceshowed impressive feasibility and safety of this novel tech-nique. Although unable to obviate subsequent dilating andstenting strategy, the combined RFA technique is likely to bea promising method in the future management of BBS, espe-cially for refractory cases.

The generator setting is critical for RFA. A power settingthat is too high may cause injury to the bile duct and sur-rounding structures, whereas a power setting that is too lowmay have little effect on the lesion. In the present study,using Steel et al.’s suggestion of 10 W for 1.5 min,18 ourresults showed this setting may also be suitable for the treat-ment of BBS. Nevertheless, the RFA probe we used wasdesigned primarily for the treatment of malignant strictures.The distance between the two electrodes was 2.5 cm in

A B C D E

Figure 2 (a) One patient (case 1) withpostoperative biliary stricture failedprior stenting therapy. (b) Radiofre-quency ablation (RFA) probe wasadvanced to the narrowed duct for ame-lioration of biliary fibrosis. (c) Immediatestricture improvement was achievedafter RFA. (d) Two plastic stents werethen placed. (e) Two months later, com-plete stricture resolution was achieved.

Digestive Endoscopy 2014; 26: 581–585 RFA for benign biliary strictures 583

© 2014 The AuthorsDigestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society

length, usually longer than that of a BBS. The extra energydelivered might introduce thermal injury to the adjacentnormal bile duct wall. We highly recommend the manufac-turer provide an additional probe with shorter electrodes thatmay be more suitable for the management of BBS.

The present study was a pilot feasibility study withobvious limitations. Number of patients enrolled was smalland the etiologies of strictures were heterogeneous. Thefollow-up duration may have been inadequate to demonstratethe long-term efficacy of this novel technique. Furtherstudies are required to confirm our results.

ACKNOWLEDGMENTS

THE AUTHORS THANK Professor James Y.W. Lau ofPrince of Wales Hospital, the Chinese University of

Hong Kong, for his help with the manuscript. The studywas supported by research grants from the Science& Technology Commission of Shanghai Municipality(114119a6600) and the Shanghai Municipal Health Bureau(XBR2011009).

CONFLICT OF INTERESTS

AUTHORS DECLARE NO conflict of interests for thisarticle.

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© 2014 The AuthorsDigestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society