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Review ArticleEndoscopic Ultrasound-Guided Radiofrequency Ablation ofthe Pancreatic Tumors: A Promising Tool in Management ofPancreatic Tumors

Kinesh Changela,1 Rashmee Patil,2 Sushil Duddempudi,1 and Vinaya Gaduputi3

1Department of Gastroenterology, The Brooklyn Hospital Center-Clinical Affiliate of Mount Sinai Hospital, Brooklyn, NY 11201, USA2Department of Internal Medicine, Mount Sinai West, New York, NY, USA3Department of Gastroenterology, St. Barnabas Hospital, Bronx, NY, USA

Correspondence should be addressed to Kinesh Changela; [email protected]

Received 9 February 2016; Revised 4 May 2016; Accepted 14 June 2016

Academic Editor: Kevork M. Peltekian

Copyright © 2016 Kinesh Changela et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Objective. Radiofrequency ablation is a well-established antitumor treatment and is recognized as one of the least invasivetherapeutic modalities for pancreatic neoplasm. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) delivery canbe used to treat both pancreatic cancer and asymptomatic premalignant pancreatic neoplasms and may serve as a less invasivealternative to surgical resection. This is an appealing option that may result in less morbidity and mortality. The aim of this reviewwas to summarize and evaluate the clinical and technical effectiveness of EUS-guided RFA of pancreatic neoplasms. Methods. Athrough literature review was performed to identify the studies describing this novel technique. In this review article, we havesummarized human case series. The indications, techniques, limitations, and complications reported are discussed. Results. Atotal of six studies were included. Overall, a 100% technical success rate was reported in human studies. Complications relatedto endoscopic ultrasound-guided radiofrequency ablation delivery have been described; however, few cases have presented life-threatening outcomes. Conclusion. We believe that this novel technique can be a safe and effective alternative approach in themanagement of selected patients.

1. Introduction

Pancreatic cancer carries a poor prognosis, with a 5-yearoverall survival rate of <5% and a median survival of <6months.Though resection provides a chance for cure in somecases and increases life expectancy, only one-fifth of patientspresent with resectable disease. Established treatmentmodal-ities such as chemotherapy or chemoradiation therapy areoptions for patients with pancreatic cancer; however, theydo little for overall outcomes [1, 2]. New modalities, suchas radiofrequency ablation (RFA), are described in litera-ture for the treatment of pancreatic cancer. Radiofrequencyablation (RFA) is a well-established antitumor treatmentand is recognized as one of the least invasive therapeuticoptions for pancreatic cancer. RFA works by emitting energyresulting in coagulative necrosis of the surrounding tissue

[3]. RFA is considered a safe and potentially curative methodand has been used widely for the treatment of tumors ofthe liver, lung, and kidney but not for the treatment ofthe pancreas. The reluctance of clinicians to use RFA forpancreatic cancer may be related to the fear of adverse events,such as thermal injury-induced pancreatitis, thermal damageto structures around the pancreas (stomach, duodenum,portal vein, superior mesenteric vessels, and bile duct), andtechnical limitations. Furthermore, pancreatic cancer usuallyhas diffuse margins making it difficult to ablate completelywith just one procedure [4–7].

Recent studies have shown that RFA is feasible in patientswith unresectable pancreatic cancer in an open, laparoscopic,or percutaneous setting. The delivery of ablative agents anddevices to localized malignancies has become increasinglypossible through a number of developments. Particularly,

Hindawi Publishing CorporationCanadian Journal of Gastroenterology and HepatologyVolume 2016, Article ID 4189358, 5 pageshttp://dx.doi.org/10.1155/2016/4189358

2 Canadian Journal of Gastroenterology and Hepatology

EUS-guided RFA (EUS-RFA) allows real-time imaging ofthe pancreatic neoplasm, where RFA may result in safetissue ablation. EUS-RFA has been described by using amodified EUS needle and a commercial RF needle. RFAprovides localized tissue ablation that ranges from 1 to 3 cmfrom the needle catheter [8–10]. For pancreatic EUS-RFA,several studies have reported the feasibility and safety of theprocedure in animals. Overall, these studies have concludedthat EUS-RFA of the pancreatic head with either monopolaror bipolar probes was well tolerated in the porcine pancreasand resulted in aminimal amount of pancreatitis.The studiesalso reiterated that the procedure was technically feasible,effective, and relatively safe in these animal models [4, 7, 9].

More recently, the feasibility and safety of EUS-RFA havebeen described in human studies. This review article willsummarize the results of these studies.

2. Materials and Methods

An extensive English language literature search was con-ducted using PubMed, Medline, and Google to identify peer-reviewed original and review articles using the keywords“endoscopic ultrasound,” “radiofrequency ablation,” “pan-creas,” “solid tumor,” and “EUS-RFA.” Human articles wereselected. The references of pertinent studies were manuallysearched to identify additional relevant studies. The indica-tions, procedural details, technical and clinical success rates,complications, and limitations were considered as part ofthe inclusion criteria. Search results yielded mostly smallsample sized prospective studies and retrospective studieswhich limited statistical analysis in the form ofmeta-analysis.

3. Results

Six original articles published were considered appropriateto be included in the review article. All were human caseseries from India [12], UK [8, 13], SouthKorea [10], andChina[14] or a case report from Italy [11]. All studies have beensummarized in Tables 1 and 2.

3.1. Demographics. All studies were human studies. In thesestudies, a total of 28 patients were included. 18/28 (64%)patients were male and 10/28 (36%) were female. The averageage of patients included was 61 years (see Table 1).

3.2. Indications. In all human studies, patients includedpresented with a pancreatic lesion. 17/28 (61%) of patientshad proven adenocarcinoma of the pancreas. 6/28 (21%) werefound to have a pancreatic neuroendocrine tumor and threeof these patients included in the study by Lakhtakia et al. had asymptomatic insulinoma. Other pathologies of the pancreasincluded a mucinous cyst and a microcystic adenoma. Theaverage size of the lesion in human studies was 37.8mm.

3.3. Technique. In all studies included in the review article,RF catheter was utilized to deliver the EUS-RFA. A summaryof details of the techniques used in human versus animalstudies is given in Table 2. In 4/6 (67%) of the studies, thenovel Habib catheter [Habib EUS-RFA catheter, EMcision

Figure 1: Habib� EUS-RFA probe (reproduced from manufac-turer’s website with appropriate permission [4]).

Figure 2: Endoscopic ultrasound view showing EUS-RFA probeinserted into the porcine pancreas (the porcine pancreatic tissue wasablated with RFA after placing EUS-guided 19-gauge Wilson Cookneedle into the pancreas via transduodenal approach) (reproducedfrom an open access article under terms of the Creative CommonsAttribution License [4]).

Ltd., London] was placed through a 19-gauge or 22-gaugefine needle aspiration (FNA) needle. The Habib EUS-RFA isa 1 Fr wire that can be inserted through the biopsy channelof an echoendoscope (Figure 1). To coagulate tissue in thepancreas, RF power is applied to the electrode at the endof the wire. Though our studies focused on EUS-RFA in thepancreas, the same modality could also be used in the liver.The Habib EUS-RFA is a monopolar device and is used inconjunction with a patient grounding/diathermy pad. Thisnovel system comes in dispensing sheath and the catheteris removed from the dispensing sheath and connected tothe adaptor cable, which is then connected to the generator.Power in the generator is set to the required wattage and apatient grounding/diathermy pad is applied as close to theoperating field as possible, since the catheter is monopolar.Once the catheter is placed through EUS control and by usinga 19-gauge biopsy needle with a stylet, RF energy is thenapplied for 90–120 s inmost cases at the setwattage (Figure 2).In larger lesions, the Habib EUS-RFA probe and needle arepulled back as one unit and repositioned to ablate the lesion.This process can be repeated as many times as needed toensure complete ablation of the lesion [12–14].

Another device that was utilized in Carrara et al. wasa new flexible bipolar hybrid ablation device (ERBE Elek-tromedizin, Tubingen, Germany). This hybrid cryotherm

Canadian Journal of Gastroenterology and Hepatology 3

Table 1: Characteristics of studies describing endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA).

Study, location Total subjects Sex, male/female Age Study typeArmellini et al., Italy [11] 1 1/0 76 Case reportLakhtakia et al., India [12] 3 patients 3/0 45 Case seriesPai et al., UK [8] 8 patients 7/1 65 Case seriesSong et al., South Korea [10] 6 patients 1/5 62 Case seriesPai et al., UK [13] 7 patients 4/3 69 Case seriesWang et al., China [14] 3 patients 2/1 63 Case seriesN/A: not applicable.

Figure 3: Pathological specimen of porcine pancreas (on the 6th dayafter procedure, the pigs were euthanized. The pancreas of the pigswas immediately excised surgically for gross examination of damageand tissue response) (reproduced from an open access article underterms of the Creative Commons Attribution License [4]).

probe (CTP) combined bipolar RF ablationwith cryotechnol-ogy.Abipolar systemablateswith less collateral thermal dam-age than a monopolar system but with less efficiency overall.The cryotechnology in this probe is used both to combinethe advantages of the two approaches and to overcome thedisadvantage of less efficiency: the more effective cooling bycryogenic gas increases the RF-induced effects [7]. Studiesnot using the Habib EUS-RFA or ERBE utilized the VIVA RFgenerator (STARmed, Koyang, Korea).This device utilized an18G FNA needle to introduce the catheter but otherwise hada similar approach to the Habib EUS-RFA catheter.

3.4. Technical and Clinical Success Rate. Technical successwas reported as 100% in human studies. In Lakhtakia et al.EUS-RFA proved effective for symptom relief in symptomaticpancreatic insulinoma for 3/3 (100%) of patients. In Pai etal. [8] the response ranged from complete resolution of thepancreatic lesion to a 50% reduction in the diameter of thelesion. Figure 3 shows pathological specimen of porcine pan-creas revealing tissue response after pigs were euthanized. InWang et al. EUS-RFAof pancreatic carcinomawas technicallyeasy and safe and well tolerated by the patients and achieveda considerable reduction in tumor size and CA19-9 levels.

In animal studies, clinical success rates were measured moreby complications and adverse outcome rates of the proce-dure.

3.5. Complications and Adverse Outcomes. In all six humanstudies, no major clinical complications or adverse outcomeswere reported. Pai et al. [8] and Song et al. reported mildabdominal pain in 25% and 33% of patients, respectively. Paiet al. [13] reported a case of mild pancreatitis in 1 out of 7patients (14%). In animal studies that have been reported inthe literature but not included in our tables, clinical compli-cations were reported postmortemwhen assessing pancreatictissue and other surrounding structures. In Gaidhane et al.,2/5 (40%) of pigs hadmoderate pancreatitis, while in Carraraet al., one pig was reported to have necrotic pancreatitiswith peritonitis. Another common complication reported inanimal studies was fibrosis and adhesions.

3.6. Limitations. Thus far, clinically successful cases havebeen published with few complications reported, but thismay be due to a publication bias as the procedure is fairlynew. As more cases that are technically and clinically relevantare published, further data may be assessed regarding thepotential efficacy and safety of EUS-RFA in the treatment ofpancreatic tumors.

4. Summary and Future Directions

RFA is a well-recognized, safe, and effective modality for thetreatment of pancreatic neoplasms, including unresectablepancreatic carcinoma. The technique is minimally invasiveand has very good tolerability. EUS-RFA can be used to treatpremalignant, asymptomatic, pancreatic lesions instead ofsurgical resection, and this is promising as surgical proce-dures are commonly associated with major morbidity andsome mortality. Despite surgical and oncological advancesin the treatment of pancreatic cancer, the prognosis remainspoor partially because only 10% of patients have a chance toreceive curative surgery [8]. EUS-RFA, as an alternative tosurgery, is a well-established antitumor treatment using localthermal-induced coagulative necrosis [1]. In our review of the6 articles published in the literature, technical success wasreported as 100% in human studies. EUS-RFA provided effec-tive symptomatic relief in patients with pancreatic lesions andsignificantly reduced the tumor size in the patients includedin these studies.

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Canadian Journal of Gastroenterology and Hepatology 5

Though EUS-RFA is technically successful in many cases,there have been clinical complications associated with thetechnique.The pancreas is a very thermosensitive organ, andwhen heat is applied on the normal pancreas, it producesan inflammatory response causing edema and later fibrosisand occasionally cystic transformation. In general, adverseevents are more associated with the duration of ablation.Using lower energy may allow for multiple ablations withlower morbidity [2–5]. Adverse events related to EUS-RFAmay include acute pancreatitis, pancreatic leaks, infectionof necrotic pancreatic tissue, and posttreatment bleeding.Furthermore, it should be considered that the pancreas isdifferent from other organs like the liver and RFA protocolfor the liver cannot be used in the pancreas; the optimalthermal kinetic characteristics for the pancreas have not beendetermined, so there is still no standardized protocol forpancreatic RFA. The pancreas is also surrounded by manyvital structures and pancreatic RFA has a risk of thermalinjury to these surrounding organs including vasculatures.Finally, it is difficult to ablate pancreatic cancer completelyand two or more procedures may be necessary in many cases[7–9]. In our review article, no major clinical complicationsor adverse outcomes were reported in human subjects. Pai etal. [8] and Song et al. reported mild abdominal pain in 25%and 33% of patients, respectively. Pai et al. [13] reported a caseof mild pancreatitis in 1 out of 7 patients (14%). In animalstudies, however,more serious complications such as necroticpancreatitis with peritonitis and fibrosis and adhesions caus-ing obstruction have been reported [4, 7]. Compared tostudies on intraoperative RFA, most studies of EUS-RFA areanimal studies testing for feasibility, safety, and efficacy of theprocedure. In the studies included in our review, the authorsconcluded that EUS-RFA was feasible and safe in vivo inmost cases, though occasionally more serious side effects didoccur.

Until now, the feasibility and safety of EUS-RFA for thetreatment of advanced pancreatic cancer and other pancreaticlesions have not been addressed. As the results of our reviewarticle have shown, EUS-RFA can be a technically feasibleand safe option for patients with unresectable pancreaticcancer and may serve as an adjunct to treatment methods forunresectable disease.These preliminary data results compiledfrom our review suggest that the procedure is technically easyand safe. The responses to EUS-FNA ranged from completeresolution of a pancreatic lesion to a 50% reduction in diam-eter to symptomatic relief in patients and animal subjects.Further multicenter experience is required to identify itsyield and safety in different stages of pancreatic cancer. Insummary, we believe that further prospective studies arenecessary to demonstrate the overall survival benefit of EUS-RFA for pancreatic cancer before widespread use of this novelprocedure.

Competing Interests

The authors have no competing interests or financial rela-tionships with the company that produces or distributes thedevices described in the review article.

References

[1] W. R. Brugge, “EUS-guided tumor ablation with heat, cold,microwave, or radiofrequency: will there be a winner?” Gas-trointestinal Endoscopy, vol. 69, no. 2, pp. S212–S216, 2009.

[2] S. Varadarajulu,N.C. Jhala, andE. R.Drelichman, “EUS-guidedradiofrequency ablationwith a prototype electrode array systemin an animal model (with video),” Gastrointestinal Endoscopy,vol. 70, no. 2, pp. 372–376, 2009.

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[4] M. Gaidhane, I. Smith, K. Ellen et al., “Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) of the pancreas ina porcine model,” Gastroenterology Research and Practice, vol.2012, Article ID 431451, 6 pages, 2012.

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[7] S. Carrara, P. G. Arcidiacono, L. Albarello et al., “Endoscopicultrasound-guided application of a new hybrid cryothermprobe in porcine pancreas: a preliminary study,” Endoscopy, vol.40, no. 4, pp. 321–326, 2008.

[8] M. Pai, N. Habib, H. Senturk et al., “Endoscopic ultrasoundguided radiofrequency ablation for pancreatic cystic neoplasmsand neuroendocrine tumors,”World Journal of GastrointestinalSurgery, vol. 7, no. 4, pp. 52–59, 2015.

[9] H. J. Kim, D.-W. Seo, A. Hassanuddin et al., “EUS-guided radio-frequency ablation of the porcine pancreas,” GastrointestinalEndoscopy, vol. 76, no. 5, pp. 1039–1043, 2012.

[10] T. J. Song, D. W. Seo, S. Lakhtakia et al., “Initial experience ofEUS-guided radiofrequency ablation of unresectable pancreaticcancer,” Gastrointestinal Endoscopy, vol. 83, no. 2, pp. 440–443,2016.

[11] E. Armellini, S. F. Crino, M. Ballare, and P. Occhipinti, “Endo-scopic ultrasound-guided radiofrequency ablation of a pancre-atic neuroendocrine tumor,” Endoscopy, vol. 47, pp. E600–E601,2015.

[12] S. Lakhtakia, M. Ramchandani, R. Gupta, S. Venugopal, D.Galasso, and N. Reddy, “EUS-guided radiofrequency ablation(EUS-RFA) using a novel internally cooled needle electrode forpancreatic insulinoma: a case series in humans,”GastrointestinalEndoscopy, vol. 81, no. 5, supplement, p. AB440, 2015.

[13] M. Pai, J. Yang, X. Zhang et al., “Endoscopic ultrasound guidedradiofrequency ablation (EUS-RFA) for pancreatic ductal ade-nocarcinom,” Gut, vol. 62, supplement 1, p. A153, 2013.

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