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Radiofrequency ablation for intraductal extension of ampullary neoplasms
ORIGINAL ARTICLE
Radiofrequency ablation for intraductal extension of ampullary neoplasms Tarun Rustagi, MD,1 Shayan Irani, MD,2 D. Nageshwar Reddy, MD,3 Barham K. Abu Dayyeh, MD, MPH,1 Todd H. Baron, MD,4 Christopher J. Gostout, MD,1 Michael J. Levy, MD,1 John Martin, MD,1 Bret T. Petersen, MD,1 Andrew Ross, MD,2 Mark D. Topazian, MD1 Rochester, Minnesota; Seattle, Washington; Chapel Hill, North Carolina, USA; Hyderabad, India
Background and Aims: Extension of ampullary adenomas into the common bile duct (CBD) or pancreatic duct (PD) may be difficult to treat endoscopically. We evaluated the feasibility, safety, and efficacy of endoscopic radiofrequency ablation (RFA) in the management of ampullary neoplasms with intraductal extension. Methods: This was a multicenter, retrospective analysis of all patients with intraductal extension of ampullary neoplasms treated with endoscopic RFA between February 2012 and June 2015. Treatment success was defined as the absence of detectable intraductal polyps by ductography, visual inspection, and biopsy sampling. Results: Fourteen patients with adenoma extension into the CBD (13 7 mm, n Z 14) and PD (7 2 mm, n Z 3) underwent a median of 1 RFA sessions (range, 1-5). Additional modalities (thermal probes, argon plasma coagulation, and/or photodynamic therapy) were also used in 7 patients, and prophylactic stents were routinely placed. Thirteen assessable patients underwent a median of 2 surveillance ERCPs after completion of treatment over a median follow-up of 16 months (range, 5-46), with intraductal biopsy specimens showing no neoplasm in 12 patients at the conclusion of endoscopic treatment. Treatment success was achieved in 92%, including 100% of those treated with RFA alone. Adverse events occurred in 43% and included ductal strictures (5 patients) and retroduodenal abscess (1 patient), all of which were successfully treated endoscopically. Conclusions: Endoscopic RFA, alone or in combination with other modalities, may effectively treat intraductal extension of ampullary neoplasms. Ductal strictures were common after RFA but responded to endoscopic stent therapy. RFA may be appropriate in selected patients, particularly when the main treatment alternative is pancreaticoduodenectomy. (Gastrointest Endosc 2016;-:1-7.)
Abbreviations: APC, argon plasma coagulation ablation; CBD, common bile duct; PD, pancreatic duct; RFA, radiofrequency ablation. DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. Copyright ª 2016 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2016.11.002 Received May 26, 2016. Accepted November 2, 2016. Current affiliations: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA (1), Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA (2), Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India (3), Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA (4). Reprint requests: Mark D. Topazian, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. If you would like to chat with an author of this article, you may contact Dr Topazian at [email protected]
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Ampullary adenomas are the most common ampullary tumors and are increasingly detected because of the widespread use of upper GI endoscopy and CT.1,2 Complete resection of ampullary adenomas is advised because they are premalignant lesions that may undergo malignant transformation through the adenoma–carcinoma sequence.3 Currently, endoscopic papillectomy is a preferred approach for management of ampullary adenomas not known to contain invasive cancer. Intraductal extension of ampullary adenomas into the common bile duct (CBD) or pancreatic duct (PD) is challenging to treat endoscopically and may be considered a contraindication to endoscopic therapy.4-7 Intraductal biliary radiofrequency ablation (RFA) is an ablative therapy that has been used to treat malignant biliary strictures and tumor ingrowth into biliary self-expandable metal stents.8-12 The aim of this study was to evaluate the feasibility, safety, and efficacy of endoscopic RFA in the management of ampullary neoplasms with intraductal extension. Volume
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METHODS This is a multicenter, retrospective analysis of all patients with ampullary neoplasms with intraductal extension treated with an endoscopic biliary RFA catheter at 3 referral centers between February 2012 and June 2015. The study was approved by the respective institutional review boards. Data were collected regarding (1) patient demographics, (2) initial indication for ERCP, (3) ampullary adenoma characteristics, (4) details of adenoma therapy and extent of eradication, (5) number of procedures necessary for complete adenoma eradication, (6) adverse events, and (7) follow-up after eradication. ERCP was performed with standard duodenoscopes (Olympus, Center Valley, Pa) either under moderate sedation or with anesthesia support. A cholangiogram and pancreatogram were performed to determine the presence and the extent of intraductal involvement. The length of intraductal involvement was determined from magnetic resonance, EUS, or ERCP images, depending on which modality most clearly showed the extent of the intraductal polyp. The duodenal portion of the polyp was snare-resected en bloc or in piecemeal fashion by using standard electrosurgical generators (ERBE ICC200EA, ERBE USA, Marietta, GA; or Beamer, ConMed, Utica, NY, USA). After ampullectomy, biliary and/or pancreatic sphincterotomies were performed as appropriate. In some cases of suspected intraductal polyp extension, endoscopic balloon dilation of the bile duct and/or PD orifices was performed to a diameter of 4 to 10 mm (Hurricane Rx balloon dilators; Boston Scientific, Natick, Ma or Quantum TTC biliary balloon dilators, Cook Endoscopy, Winston-Salem, NC) to directly visualize the polyp in the affected ducts. Biopsy specimens of polypoid tissue within the distal CBD or PD were obtained, with endoscopic treatment at the same time and/or during subsequent ERCP procedures. Single-use, disposable, bipolar RFA catheters (HabibTM EndoHPB, EMcision Ltd, London, U.K. [12 patients] or STARmed Co. Ltd, Korea [2 patients]) suitable for endoluminal delivery of RFA were passed into the biliary tree over a .035-inch guidewire and centered in the bile duct. The entire linear extension of the intraductal neoplasm was treated, with overlapping applications if necessary. When less than 2 cm of duct required treatment, the probe was positioned with its proximal electrode visible endoscopically at the ductal orifice or several millimeters into the duodenal lumen, and the duodenal lumen was deflated by constant suction during RFA. The catheter was connected to an electrosurgical generator (RITA 1500X [Angiodynamics, Latham, NY], Erbe [Surgical Technology Group, Hampshire, England, U.K.], or Beamer [ConMed]). To ensure effective delivery of RF energy, we instilled saline solution into the bile duct before treatment to remove air from the duct, limited insufflation before RFA, and suctioned air from the duodenum before and during each application. 2 GASTROINTESTINAL ENDOSCOPY Volume
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After RFA, repeat cholangiography or pancreatography was performed to assess response to treatment. Biliary (plastic or metal) stents were placed based on endoscopist preference. Prophylactic 5F or 7F PD stents (length 3 or 5 cm, Geenen PD stent; Cook Endoscopy) were placed routinely. A follow-up ERCP with intraductal biopsy sampling was performed as clinically indicated to evaluate for and treat residual polyp tissue until no remaining adenoma was identified. A variety of other non-RFA thermal therapies, alone or in combination, including snare resection, 10F heater probe (HPU/HPU20; Olympus) ablation, 7F and 10F bipolar electrocoagulation probes (Gold probe; Boston Scientific), argon plasma coagulation (APC) ablation (Erbe APC 300 with an end-fire probe at .7- to 1.0-L flow and 30-60 W), and photodynamic therapy (1-cm cylindrical diffusing fiber at a power output of 400 mW/cm in 1 application for a total dose of 80 J/cm2, Pinnacle Biologics, Chicago, Ill) were used as adjunctive therapies for intraductal extension based on the response to RFA, availability of modalities, and endoscopist preference. Typically, APC and thermal probes were used to treat either the polyp around the ductal orifices during the same session in which RFA was performed or the noncircumferential intraductal polyp that was within ready endoscopic view during follow-up examinations. Successful endoscopic treatment was defined as the absence of adenomatous tissue or detectable recurrence by visual inspection, ductography, and follow-up biopsy sampling, regardless of the number of treatment sessions required. Annual surveillance ERCP was advised after all adenoma had apparently been eradicated.
RESULTS Fourteen patients (mean age, 68 7.3 years; 64% women) who underwent endoscopic RFA treatment for intraductal extension of ampullary adenoma between February 2012 and June 2015 were identified, 1 of whom was mentioned in a previous publication.2 The clinical presentation included jaundice in 6 patients and abdominal pain in 7, and 3 patients were asymptomatic with incidentally detected lesions. Evaluation before endoscopic treatment included CT in 8, magnetic resonance imaging in 7, EUS in 13, and ERCP in 14 patients. Balloon dilation of the distal bile duct or PD to facilitate assessment of the intraductal polyp was performed in 7 patients. Polyp features, histology, intraductal extension characteristics, treatment modalities, and follow-up are shown in Table 1, and representative magnetic resonance and ERCP images are shown in Figures 1 and 2, respectively. The mean size of the ampullary lesions was 2.4 1 cm. A sessile extension into the CBD was present in all 14 patients for a mean of 13 7 mm, and extension to PD was present in 3 patients for a mean of 7 2 mm. Nine of 14 patients www.giejournal.org
Rustagi et al
RFA for intraductal extension of ampullary neoplasms
TABLE 1. Clinical characteristics of 14 patients with intraductal extension of ampullary neoplasms treated with endoscopic RFA
Patient no.
Adenoma size (mm)
Adenoma pathology
Duct (s) involved
Intraductal extension length (mm)
Worst ductal pathology
No. of RFA sessions
Concomitant therapies
Final follow-up pathology
Follow-up duration (mo)*
1
20
TV
CBD
10
TV
2
BE
Normal
6
2
30
TV-HGD
CBD
10
TA
1
APC
Normal
12
3
30
TV-HGD
CBD
10
TV-HGD
1
Normal
6
4
20
TA-HGD
CBD
30
TV-HGD
5
5
15
TA
CBD
8
TA
1
6
10
AC
CBD, PD
5, 8
AC
3
7
20
AC
CBD
10
TV-HGD
2
8
20
TA-HGD
CBD, PD
15, 5
TA
1
9
40
TA
CBD
6
TA
1
10
45
TVA-HGD
CBD
20
TVA
1
APC
Normal
5
11
10
TV
CBD
15
TV
1
APC
TV
18
12
20
TV
CBD, PD
12, 8
TV
1
Normal
13
13
20
TA
CBD
10
TA
1
Normal
14
14
30
TA-HGD
CBD
20
TA-HGD
2
Normal
11
APC
APC, BE
APC
Normal
7
Normal
20
y
y
Normal
16
Normal
6
Normal
8
TV, Tubulovillous adenoma; BE, bipolar electrocoagulation; HGD, high-grade dysplasia; TA, tubular adenoma; AC, adenocarcinoma; CBD, common bile duct; PD, pancreatic duct; RFA, radiofrequency ablation. *Time between the first ERCP that showed no residual adenoma to the most recent ERCP. yNo follow-up ERCP because patient died from an unrelated cardiac event.
(64%) had endoscopic visualization of the normal duct above the intraductal polyp after balloon dilation. Intraductal adenoma extension was documented histologically on intraductal biopsy specimens in 13 patients with the finding of high-grade dysplasia in 4 and intramucosal adenocarcinoma in 1. Before RFA, 4 patients underwent APC, 3 bipolar electrocoagulation, and 6 snare resection of the intraductal polyp but had persistent intraductal neoplasms. Figures 2 and 3 show a representative sequence of images depicting diagnosis and treatment of intraductal extensions of ampullary adenomas. The application of RFA was facilitated by maximal biliary sphincterotomy and endoscopic papillary balloon dilation, which aid in visualization of the intraductal polyp, instillation of saline solution into the bile duct before RFA, and continuous suctioning of the duodenal lumen during RFA. Patients underwent a median of 1 RFA sessions (range, 1-5), which were performed at a median interval of 13 weeks (range, 6-32) between sessions. Median RFA applications per session was 1 (range, 1-3). Median energy used for RFA in the bile duct was 10 W (range, 7-10) for a median duration of 90 seconds (range, 60-140) for each application; in the PD median energy was 7 W (range, 7-8) for a duration of 90 seconds in all cases. Of the 14 patients, 3 received biliary RFA at 7 W during their initial treatment session and 2 of the 3 patients required additional biliary RFA; all remaining 11 patients received biliary RFA at 10 W during their initial treatment session, and 3 required additional biliary RFA (P Z .51 for comparison of 7 vs 10 W). The mean number of RFA sessions required was significantly higher in the 5 patients with high-grade www.giejournal.org
Figure 1. Magnetic resonance cholangiography showing an intraductal (biliary) polyp successfully treated with radiofrequency ablation (patient no. 1).
dysplasia or intramucosal carcinoma (2.6 1.5) than in the other 9 patients (1.1 .3; P Z .011). Concomitant APC and bipolar electrocoagulation were used during 8 and 2 RFA sessions, respectively, to treat endoscopically visible polyps near and around the ductal orifice. Prophylactic PD stent placement was performed in 21 of 23 RFA sessions, and prophylactic CBD stents (fully covered metal stents in 9 and plastic stents in 10) were placed after 19 RFA sessions. Two patients did not receive a PD stent, and another 2 did not receive a biliary stent after initial RFA treatment. Stents were left in place for a Volume
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Figure 2. Fluoroscopic images demonstrating sequence of RFA treatment. A, Initial cholangiogram shows a distal bile duct polyp. B, Papillary balloon dilation to facilitate endoscopic visualization of the polyp. C, Radiofrequency ablation catheter in the distal bile duct (patient no. 10).
Figure 3. Endoscopic images demonstrating sequence of RFA treatment (same patient as in Fig. 2). A, Endoscopic view of a sessile bile duct polyp after ampullectomy, duodenal polpectomy, pancreatic stent placement, and papillary balloon dilation. B, Appearance after RFA. Some polyp remains around the bile duct orifice. C, Appearance after concomitant APC treatment. APC, argon plasma coagulation ablation; RFA, radiofrequency ablation.
median of 3 months (range, 0-8) after the final RFA session. Two patients with persistent intraductal adenoma after 1 and 5 RFA sessions were treated during subsequent ERCPs with additional APC (n Z 1) or photodynamic therapy (n Z 1), respectively. Altogether, 7 patients were treated with RFA alone and 7 received concomitant or subsequent treatment with other modalities. One patient died of an unrelated cardiac event 3 months after her last RFA session and did not have a follow-up ERCP to assess response. The other 13 patients underwent a median of 2 surveillance ERCPs after completion of treatment over a median follow-up period of 16 months (range, 5-46), with intraductal biopsy specimens showing no intraductal neoplasm in 12 (92%) and recurrent adenoma of the 4 GASTROINTESTINAL ENDOSCOPY Volume
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CBD in 1. The patient with residual adenoma who underwent 1 RFA treatment session with concomitant treatment with APC had poor functional status and declined further endoscopic or surgical interventions. In 7 patients treated with RFA alone the success rate was 100% at the end of RFA and at the most recent follow-up. In the remaining 6 patients treated with RFA and other concomitant or subsequent endoscopic modalities, the success rate was 4 of 6 (66.7%) at the end of RFA and 5 of 6 (83.3%) at the most recent follow-up. Overall, the treatment success rate among the 13 patients was 85% after RFA and 92% after all endoscopic treatment. Adverse events occurred in 6 of 14 patients (43%), of which 4 (29%) were symptomatic. Two patients presented www.giejournal.org
Rustagi et al
RFA for intraductal extension of ampullary neoplasms
TABLE 2. Characteristics of patients with and without post-RFA bile duct strictures Patients who developed strictures (n [ 5)
Patients without strictures (n [ 9)
P value
Mean 12.8 9.8
Mean 13.4 5.2
.88
Mean 2 1.7, Median 1 (range, 1-5)
Mean 1.4 .7, Median 1 (range, 1-5)
.36
1/5
0/9
.36
Additional modalities (yes)
1/5
6/9
.27
Prophylactic biliary stenting for at least 3 months (yes)
2*/5
5/9
1
Post-RFA fully covered metal stent (yes)
2/5
4/9
1
Intraductal adenoma length, mm Number of RFA sessions Overlapping RFA applications (yes)
RFA, radiofrequency ablation; CBD, common bile duct. *Both strictures were asymptomatic and noted as mild distal CBD narrowing on cholangiography during follow-up stent exchange.
with jaundice secondary to benign distal CBD strictures, one 7 months after RFA, and the other 16 months after RFA and 10 months after photodynamic therapy. These strictures were treated with multiple plastic stents for 8 months in 1 patient and fully covered metal stents for 12 months in 1 patient, with resolution in both cases. Three additional patients were found to have an asymptomatic distal CBD stricture on follow-up cholangiography, treated with multiple plastic stents for a median of 5 months (range, 3-7), with resolution in all cases. One additional patient presented with fever and nausea 4 weeks after biliary RFA, with CT showing a 4.3-cm retroduodenal abscess that was successfully treated with EUS-guided transduodenal drainage. Cholangiography at the time of abscess drainage showed no biliary leak or fistula. One patient who had undergone 1 session of biliary RFA developed recurrent acute pancreatitis attributed to a stent-related PD stricture that was treated endoscopically. As shown in Table 2, we were unable to identify a clinical variable associated with a likelihood of biliary stricture after RFA. Seven patients underwent prophylactic biliary stenting for at least 3 months (range, 3-8.4) after their final RFA session, and none developed a symptomatic biliary stricture during follow-up, although asymptomatic strictures were seen in 2 of these patients during stent exchanges.
DISCUSSION An estimated 3000 ampullary tumors present annually in the United States, with autopsy series reporting prevalence rates of .04% to .12%.13-15 Ampullary adenomas are the most common ampullary tumor with risk of malignant transformation through an adenoma-to-carcinoma sequence. The reported incidence of cancer within sporadic adenomas at the time of diagnosis ranges from 25% to 30%.15,16 In addition, cancer is missed by endoscopic biopsy sampling and is found only in resection specimens in 6% to 26% of adenomas undergoing papillectomy,17-19 and is more likely in patients with high-grade dysplasia or ductal dilatation.19 Surgical pancreaticoduodenectomy effectively treats ampullary adenomas but with significant morbidity (50%-60%) and www.giejournal.org
mortality (1%-9%).4,20-25 Surgical transduodenal ampullectomy has been associated with high recurrence rates (30%).4,20-24 Endoscopic resection of ampullary polyps is a minimally invasive alternative to surgical therapy in appropriately selected patients. Endoscopic papillectomy was first described in 1983 by Suzuki et al26 and has become a preferred treatment option for ampullary adenomas because of lower morbidity and mortality and costeffectiveness compared with surgery.4,16,17,26,27 Endoscopic treatment of ampullary adenomas achieves cure rates ranging from 76% to 90% in patients without intraductal extension.4,16,17,27 However, intraductal extension of adenoma has been associated with lower cure rates and a greater need for surgery for incomplete adenoma removal. Several investigators have cited intraductal adenoma growth as a contraindication to endoscopic therapy.4-7 Limited data have shown that <1 cm of extension into the CBD or PD does not preclude endoscopic therapy because tissue invading to this level may be exposed to endoscopic view after sphincterotomy and ablated.4,28,29 However, limited or poor visualization, presence of circumferential intraductal polyp, and inability to accurately target the intraductal polyp may lead to suboptimal treatment results of endoscopic treatment. By using endoscopic RFA, often in combination with other modalities, we were able to achieve complete intraductal adenoma eradication in 12 of 13 assessable patients (92%), albeit with a 43% rate of adverse events in this small series. Detection of the presence and full extent of intraductal adenomas can be difficult. ERCP, MRCP, EUS, intraductal US, and direct cholangioscopy or pancreatography may all facilitate assessment for intraductal extension of adenoma. ERCP should be performed at the time of endoscopic papillectomy to assess for evidence of extension into either ductal system. Endoscopic balloon dilatation of the periampullary ducts after papillectomy and sphincterotomy (Fig. 2) allows direct endoscopic visualization of intraductal polyp and immediate assessment of treatment effect and was commonly used in this series.2 A major limitation of endoscopic intraductal treatment is the inability to ensure that tiny foci of undetected adenoma remain after treatment. Direct cholangioscopy Volume
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might improve the assessment of treatment adequacy but was not used in this series, in part because the treated segments of duct were typically visible from the duodenum after balloon dilation of ductal orifices and in part because most of our patients were treated before the recent advent of disposable digital cholangioscopes. There have been 2 recent reviews on endoscopic biliary RFA.9,30 The RFA catheter features 2 electrodes spaced 8 mm apart and induces coagulative necrosis in an oblong treatment zone centered on the electrodes. In ex vivo experiments, the length of the treatment zone along the catheter axis varies from 22 to 29 mm and perpendicular to the catheter from 4.3 to 11.3 mm, depending on the energy used and the duration of treatment.31 Most studies have applied RF energy of 7 to 10 W for a duration of 90 to 120 seconds for each intrabiliary application. Endobiliary RFA has been shown in several studies and case series to be a technically feasible adjunct therapy for biliary cancer palliation before or after metal stent placement. The use of RFA as a primary treatment for intraductal adenoma has been previously reported in a patient with a right main duct adenoma who was not a surgical candidate.32 In addition, Mehendiratta and Desilets33 reported using RFA to successfully eradicate residual ampullary adenoma in 1 patient. Recently, Valente et al34 reported 3 cases that were treated with RFA: 1 had intraductal recurrence after endoscopic papillectomy and the other 2 had intraductal adenoma. In some of our cases the zone of RFA ablation probably extended proximal to the intraductal polyp and included the normal duct wall. Transmural necrosis of normal bile ducts by RFA was reported in a porcine model and can occur because the cylindrical RFA ablation zone extends up to 4.1 mm from the sides of the probe depending on the energy settings and duration used, whereas the normal bile duct wall is typically no more than 1 mm thick.31,35 Transmural injury is probably less common when bulky biliary malignancies are treated with RFA but has been reported after RFA treatment of intrahepatic biliary adenoma.36 We did not observe any cases of acute ductal perforation after RFA, probably because the ductal segments we treated are retroperitoneal and surrounded by pancreatic parenchyma, and prophylactic stents were routinely placed. However, 1 patient did develop a retroduodenal abscess despite prophylactic placement of a fully covered metal biliary stent after RFA, suggesting full-thickness bile duct injury. Infectious adverse events have been commonly reported after RFA in patients with biliary malignancies.30 Ductal strictures were the most common adverse event. Bile duct strictures related to RFA developed in 5 patients (36%); however, only 2 (14%) were symptomatic. One of the patients with an asymptomatic biliary stricture also developed a stent-related PD stricture, leading to acute pancreatitis. All of these strictures were treated endoscopically with complete resolution in all 6 GASTROINTESTINAL ENDOSCOPY Volume
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patients. Symptomatic bile duct strictures did not occur in patients who received prophylactic stenting for at least 3 months after RFA. Improvements in biliary RFA technology (such as the ability to alter the length and depth of the treatment zone) might decrease the incidence of adverse events. Limitations of our study include its retrospective nature, small number of patients, selection and referral biases, heterogeneous treatment including multimodality therapy in 50%, nonstandardized RFA energy delivery, and a short (16 month) median duration of patient follow-up. In the absence of long-term follow-up and digital cholangioscopy, we cannot know whether small undetected foci of intraductal adenoma remained in our patients. We chose RFA treatment settings based on published ex vivo and in vivo data but do not know whether lower RFA energy settings would be equally efficacious and result in fewer adverse events. In some patients we performed balloon dilation before RFA for visualization of intraductal polyp, and we do not know whether this impeded the efficacy of RFA by increasing ductal diameter. Despite these limitations, our data establish the feasibility of RFA therapy for intraductal polyp extension and provide a basis for considering RFA therapy and discussing this treatment option with patients. In conclusion, endoscopic RFA may be an effective modality for treatment of intraductal extension of ampullary neoplasms. RFA should be used selectively in patients for whom treatment of an intraductal lesion is appropriate, other endoscopic modalities are likely to be insufficient, and the main treatment alternative is pancreaticoduodenectomy. RFA may cause transmural bile duct injury and should be used with caution. Ductal strictures were common after RFA but responded to endoscopic stent therapy; prophylactic biliary stenting may decrease the likelihood of this adverse event.
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Rustagi et al 8. Rustagi T, Jamidar PA. Endoscopic treatment of malignant biliary strictures. Curr Gastroenterol Rep 2015;17:426. 9. Rustagi T, Jamidar PA. Intraductal radiofrequency ablation for management of malignant biliary obstruction. Dig Dis Sci 2014;59:2635-41. 10. 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;73:149-53. 11. 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;28:854-60. 12. Pozsar J, Tarpay A, Burai J, et al. Intraductal radiofrequency ablation can restore patency of occluded biliary self-expanding metal stents. Z Gastroenterol 2011;49:A70. 13. Goodman MT, Yamamoto J. Descriptive study of gallbladder, extrahepatic bile duct, and ampullary cancers in the United States, 1997-2002. Cancer Causes Control 2007;18:415-22. 14. Sato T, Konishi K, Kimura H, et al. Adenoma and tiny carcinoma in adenoma of the papilla of Vater–p53 and PCNA. Hepatogastroenterology 1999;46:1959-62. 15. Martin JA, Haber GB. Ampullary adenoma: clinical manifestations, diagnosis, and treatment. Gastrointest Endosc Clin North Am 2003;13:649-69. 16. El Hajj II, Cote GA. Endoscopic diagnosis and management of ampullary lesions. Gastrointest Endosc Clin N Am 2013;23:95-109. 17. Napoleon B, Gincul R, Ponchon T, et al. Endoscopic papillectomy for early ampullary tumors: long-term results from a large multicenter prospective study. Endoscopy 2014;46:127-34. 18. Mathur A, Paul H, Ross S, et al. Transduodenal ampullectomy for ampullary adenomas: a safe and effective procedure with long-term salutary outcomes. Am Surg 2014;80:185-90. 19. Kim HN, Kim KM, Shin JU, et al. Prediction of carcinoma after resection in subjects with ampullary adenomas on endoscopic biopsy. J Clin Gastroenterol 2013;47:346-51. 20. Posner S, Colletti L, Knol J, et al. Safety and long-term efficacy of transduodenal excision for tumors of the ampulla of Vater. Surgery 2000;128:694-701. 21. Di Giorgio A, Alfieri S, Rotondi F, et al. Pancreatoduodenectomy for tumors of Vater’s ampulla: report on 94 consecutive patients. World J Surg 2005;29:513-8. 22. de Castro SM, van Heek NT, Kuhlmann KF, et al. Surgical management of neoplasms of the ampulla of Vater: local resection or pancreatoduodenectomy and prognostic factors for survival. Surgery 2004;136:994-1002.
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RFA for intraductal extension of ampullary neoplasms 23. Winter JM, Cameron JL, Olino K, et al. Clinicopathologic analysis of ampullary neoplasms in 450 patients: implications for surgical strategy and long-term prognosis. J Gastrointest Surg 2010;14:379-87. 24. Cahen DL, Fockens P, de Wit LT, et al. Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of Vater diagnosed before operation. Br J Surg 1997;84:948-51. 25. Tran TC, Vitale GC. Ampullary tumors: endoscopic versus operative management. Surg Innov 2004;11:255-63. 26. Suzuki K, Kantou U, Murakami Y. Two cases with ampullary cancer who underwent endoscopic excision. Progress of Digestive Endoscopy 1983;23:236-9. 27. Irani S, Arai A, Ayub K, et al. Papillectomy for ampullary neoplasm: results of a single referral center over a 10-year period. Gastrointest Endosc 2009;70:923-32. 28. Kahaleh M, Shami VM, Brock A, et al. Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia. Am J Gastroenterol 2004;99:2335-9. 29. Bohnacker S, Seitz U, Nguyen D, et al. Endoscopic resection of benign tumors of the duodenal papilla without and with intraductal growth. Gastrointest Endosc 2005;62:551-60. 30. Mensah ET, Martin J, Topazian M. Radiofrequency ablation for biliary malignancies. Curr Opin Gastroenterol 2016;32:238-43. 31. Itoi T, Isayama H, Sofuni A, et al. Evaluation of effects of a novel endoscopically applied radiofrequency ablation biliary catheter using an exvivo pig liver. J Hepatobil Pancreat Sci 2012;19:543-7. 32. Mavrogenis G, Deprez PH, Wallon J, et al. Bile duct adenoma causing recurrent cholangitis: diagnosis and management with targeted Spyglass access and radiofrequency ablation. Endoscopy 2012;44(Suppl 2 UCTN):E290-1. 33. Mehendiratta V, Desilets DJ. Use of radiofrequency ablation probe for eradication of residual adenoma after ampullectomy. Gastrointest Endosc 2015;81:1055-6. 34. Valente R, Urban O, Del Chiaro M, et al. ERCP-directed radiofrequency ablation of ampullary adenomas: a knife-sparing alternative in patients unfit for surgery. Endoscopy 2015;47(Suppl 1 UCTN):E515-6. 35. Zacharoulis D, Lazoura O, Sioka E, et al. Habib EndoHPB: a novel endobiliary radiofrequency ablation device. An experimental study. J Invest Surg 2013;26:6-10. 36. Topazian M, Levy MJ, Patel S, et al. Hepatic artery pseudoaneurysm formation following intraductal biliary radiofrequency ablation. Endoscopy 2013;45(Suppl 2 UCTN):E161-2.
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Radiofrequency ablation for intraductal extension of ampullary neoplasms Tarun Rustagi, MD,1 Shayan Irani, MD,2 D. Nageshwar Reddy, MD,3 Barham K. Abu Dayyeh, MD, MPH,1 Todd H. Baron, MD,4 Christopher J. Gostout, MD,1 Michael J. Levy, MD,1 John Martin, MD,1 Bret T. Petersen, MD,1 Andrew Ross, MD,2 Mark D. Topazian, MD1 Rochester, Minnesota; Seattle, Washington; Chapel Hill, North Carolina, USA; Hyderabad, India
Background and Aims: Extension of ampullary adenomas into the common bile duct (CBD) or pancreatic duct (PD) may be difficult to treat endoscopically. We evaluated the feasibility, safety, and efficacy of endoscopic radiofrequency ablation (RFA) in the management of ampullary neoplasms with intraductal extension. Methods: This was a multicenter, retrospective analysis of all patients with intraductal extension of ampullary neoplasms treated with endoscopic RFA between February 2012 and June 2015. Treatment success was defined as the absence of detectable intraductal polyps by ductography, visual inspection, and biopsy sampling. Results: Fourteen patients with adenoma extension into the CBD (13 7 mm, n Z 14) and PD (7 2 mm, n Z 3) underwent a median of 1 RFA sessions (range, 1-5). Additional modalities (thermal probes, argon plasma coagulation, and/or photodynamic therapy) were also used in 7 patients, and prophylactic stents were routinely placed. Thirteen assessable patients underwent a median of 2 surveillance ERCPs after completion of treatment over a median follow-up of 16 months (range, 5-46), with intraductal biopsy specimens showing no neoplasm in 12 patients at the conclusion of endoscopic treatment. Treatment success was achieved in 92%, including 100% of those treated with RFA alone. Adverse events occurred in 43% and included ductal strictures (5 patients) and retroduodenal abscess (1 patient), all of which were successfully treated endoscopically. Conclusions: Endoscopic RFA, alone or in combination with other modalities, may effectively treat intraductal extension of ampullary neoplasms. Ductal strictures were common after RFA but responded to endoscopic stent therapy. RFA may be appropriate in selected patients, particularly when the main treatment alternative is pancreaticoduodenectomy. (Gastrointest Endosc 2016;-:1-7.)
Abbreviations: APC, argon plasma coagulation ablation; CBD, common bile duct; PD, pancreatic duct; RFA, radiofrequency ablation. DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. Copyright ª 2016 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2016.11.002 Received May 26, 2016. Accepted November 2, 2016. Current affiliations: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA (1), Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA (2), Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India (3), Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA (4). Reprint requests: Mark D. Topazian, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. If you would like to chat with an author of this article, you may contact Dr Topazian at [email protected]
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Ampullary adenomas are the most common ampullary tumors and are increasingly detected because of the widespread use of upper GI endoscopy and CT.1,2 Complete resection of ampullary adenomas is advised because they are premalignant lesions that may undergo malignant transformation through the adenoma–carcinoma sequence.3 Currently, endoscopic papillectomy is a preferred approach for management of ampullary adenomas not known to contain invasive cancer. Intraductal extension of ampullary adenomas into the common bile duct (CBD) or pancreatic duct (PD) is challenging to treat endoscopically and may be considered a contraindication to endoscopic therapy.4-7 Intraductal biliary radiofrequency ablation (RFA) is an ablative therapy that has been used to treat malignant biliary strictures and tumor ingrowth into biliary self-expandable metal stents.8-12 The aim of this study was to evaluate the feasibility, safety, and efficacy of endoscopic RFA in the management of ampullary neoplasms with intraductal extension. Volume
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METHODS This is a multicenter, retrospective analysis of all patients with ampullary neoplasms with intraductal extension treated with an endoscopic biliary RFA catheter at 3 referral centers between February 2012 and June 2015. The study was approved by the respective institutional review boards. Data were collected regarding (1) patient demographics, (2) initial indication for ERCP, (3) ampullary adenoma characteristics, (4) details of adenoma therapy and extent of eradication, (5) number of procedures necessary for complete adenoma eradication, (6) adverse events, and (7) follow-up after eradication. ERCP was performed with standard duodenoscopes (Olympus, Center Valley, Pa) either under moderate sedation or with anesthesia support. A cholangiogram and pancreatogram were performed to determine the presence and the extent of intraductal involvement. The length of intraductal involvement was determined from magnetic resonance, EUS, or ERCP images, depending on which modality most clearly showed the extent of the intraductal polyp. The duodenal portion of the polyp was snare-resected en bloc or in piecemeal fashion by using standard electrosurgical generators (ERBE ICC200EA, ERBE USA, Marietta, GA; or Beamer, ConMed, Utica, NY, USA). After ampullectomy, biliary and/or pancreatic sphincterotomies were performed as appropriate. In some cases of suspected intraductal polyp extension, endoscopic balloon dilation of the bile duct and/or PD orifices was performed to a diameter of 4 to 10 mm (Hurricane Rx balloon dilators; Boston Scientific, Natick, Ma or Quantum TTC biliary balloon dilators, Cook Endoscopy, Winston-Salem, NC) to directly visualize the polyp in the affected ducts. Biopsy specimens of polypoid tissue within the distal CBD or PD were obtained, with endoscopic treatment at the same time and/or during subsequent ERCP procedures. Single-use, disposable, bipolar RFA catheters (HabibTM EndoHPB, EMcision Ltd, London, U.K. [12 patients] or STARmed Co. Ltd, Korea [2 patients]) suitable for endoluminal delivery of RFA were passed into the biliary tree over a .035-inch guidewire and centered in the bile duct. The entire linear extension of the intraductal neoplasm was treated, with overlapping applications if necessary. When less than 2 cm of duct required treatment, the probe was positioned with its proximal electrode visible endoscopically at the ductal orifice or several millimeters into the duodenal lumen, and the duodenal lumen was deflated by constant suction during RFA. The catheter was connected to an electrosurgical generator (RITA 1500X [Angiodynamics, Latham, NY], Erbe [Surgical Technology Group, Hampshire, England, U.K.], or Beamer [ConMed]). To ensure effective delivery of RF energy, we instilled saline solution into the bile duct before treatment to remove air from the duct, limited insufflation before RFA, and suctioned air from the duodenum before and during each application. 2 GASTROINTESTINAL ENDOSCOPY Volume
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After RFA, repeat cholangiography or pancreatography was performed to assess response to treatment. Biliary (plastic or metal) stents were placed based on endoscopist preference. Prophylactic 5F or 7F PD stents (length 3 or 5 cm, Geenen PD stent; Cook Endoscopy) were placed routinely. A follow-up ERCP with intraductal biopsy sampling was performed as clinically indicated to evaluate for and treat residual polyp tissue until no remaining adenoma was identified. A variety of other non-RFA thermal therapies, alone or in combination, including snare resection, 10F heater probe (HPU/HPU20; Olympus) ablation, 7F and 10F bipolar electrocoagulation probes (Gold probe; Boston Scientific), argon plasma coagulation (APC) ablation (Erbe APC 300 with an end-fire probe at .7- to 1.0-L flow and 30-60 W), and photodynamic therapy (1-cm cylindrical diffusing fiber at a power output of 400 mW/cm in 1 application for a total dose of 80 J/cm2, Pinnacle Biologics, Chicago, Ill) were used as adjunctive therapies for intraductal extension based on the response to RFA, availability of modalities, and endoscopist preference. Typically, APC and thermal probes were used to treat either the polyp around the ductal orifices during the same session in which RFA was performed or the noncircumferential intraductal polyp that was within ready endoscopic view during follow-up examinations. Successful endoscopic treatment was defined as the absence of adenomatous tissue or detectable recurrence by visual inspection, ductography, and follow-up biopsy sampling, regardless of the number of treatment sessions required. Annual surveillance ERCP was advised after all adenoma had apparently been eradicated.
RESULTS Fourteen patients (mean age, 68 7.3 years; 64% women) who underwent endoscopic RFA treatment for intraductal extension of ampullary adenoma between February 2012 and June 2015 were identified, 1 of whom was mentioned in a previous publication.2 The clinical presentation included jaundice in 6 patients and abdominal pain in 7, and 3 patients were asymptomatic with incidentally detected lesions. Evaluation before endoscopic treatment included CT in 8, magnetic resonance imaging in 7, EUS in 13, and ERCP in 14 patients. Balloon dilation of the distal bile duct or PD to facilitate assessment of the intraductal polyp was performed in 7 patients. Polyp features, histology, intraductal extension characteristics, treatment modalities, and follow-up are shown in Table 1, and representative magnetic resonance and ERCP images are shown in Figures 1 and 2, respectively. The mean size of the ampullary lesions was 2.4 1 cm. A sessile extension into the CBD was present in all 14 patients for a mean of 13 7 mm, and extension to PD was present in 3 patients for a mean of 7 2 mm. Nine of 14 patients www.giejournal.org
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TABLE 1. Clinical characteristics of 14 patients with intraductal extension of ampullary neoplasms treated with endoscopic RFA
Patient no.
Adenoma size (mm)
Adenoma pathology
Duct (s) involved
Intraductal extension length (mm)
Worst ductal pathology
No. of RFA sessions
Concomitant therapies
Final follow-up pathology
Follow-up duration (mo)*
1
20
TV
CBD
10
TV
2
BE
Normal
6
2
30
TV-HGD
CBD
10
TA
1
APC
Normal
12
3
30
TV-HGD
CBD
10
TV-HGD
1
Normal
6
4
20
TA-HGD
CBD
30
TV-HGD
5
5
15
TA
CBD
8
TA
1
6
10
AC
CBD, PD
5, 8
AC
3
7
20
AC
CBD
10
TV-HGD
2
8
20
TA-HGD
CBD, PD
15, 5
TA
1
9
40
TA
CBD
6
TA
1
10
45
TVA-HGD
CBD
20
TVA
1
APC
Normal
5
11
10
TV
CBD
15
TV
1
APC
TV
18
12
20
TV
CBD, PD
12, 8
TV
1
Normal
13
13
20
TA
CBD
10
TA
1
Normal
14
14
30
TA-HGD
CBD
20
TA-HGD
2
Normal
11
APC
APC, BE
APC
Normal
7
Normal
20
y
y
Normal
16
Normal
6
Normal
8
TV, Tubulovillous adenoma; BE, bipolar electrocoagulation; HGD, high-grade dysplasia; TA, tubular adenoma; AC, adenocarcinoma; CBD, common bile duct; PD, pancreatic duct; RFA, radiofrequency ablation. *Time between the first ERCP that showed no residual adenoma to the most recent ERCP. yNo follow-up ERCP because patient died from an unrelated cardiac event.
(64%) had endoscopic visualization of the normal duct above the intraductal polyp after balloon dilation. Intraductal adenoma extension was documented histologically on intraductal biopsy specimens in 13 patients with the finding of high-grade dysplasia in 4 and intramucosal adenocarcinoma in 1. Before RFA, 4 patients underwent APC, 3 bipolar electrocoagulation, and 6 snare resection of the intraductal polyp but had persistent intraductal neoplasms. Figures 2 and 3 show a representative sequence of images depicting diagnosis and treatment of intraductal extensions of ampullary adenomas. The application of RFA was facilitated by maximal biliary sphincterotomy and endoscopic papillary balloon dilation, which aid in visualization of the intraductal polyp, instillation of saline solution into the bile duct before RFA, and continuous suctioning of the duodenal lumen during RFA. Patients underwent a median of 1 RFA sessions (range, 1-5), which were performed at a median interval of 13 weeks (range, 6-32) between sessions. Median RFA applications per session was 1 (range, 1-3). Median energy used for RFA in the bile duct was 10 W (range, 7-10) for a median duration of 90 seconds (range, 60-140) for each application; in the PD median energy was 7 W (range, 7-8) for a duration of 90 seconds in all cases. Of the 14 patients, 3 received biliary RFA at 7 W during their initial treatment session and 2 of the 3 patients required additional biliary RFA; all remaining 11 patients received biliary RFA at 10 W during their initial treatment session, and 3 required additional biliary RFA (P Z .51 for comparison of 7 vs 10 W). The mean number of RFA sessions required was significantly higher in the 5 patients with high-grade www.giejournal.org
Figure 1. Magnetic resonance cholangiography showing an intraductal (biliary) polyp successfully treated with radiofrequency ablation (patient no. 1).
dysplasia or intramucosal carcinoma (2.6 1.5) than in the other 9 patients (1.1 .3; P Z .011). Concomitant APC and bipolar electrocoagulation were used during 8 and 2 RFA sessions, respectively, to treat endoscopically visible polyps near and around the ductal orifice. Prophylactic PD stent placement was performed in 21 of 23 RFA sessions, and prophylactic CBD stents (fully covered metal stents in 9 and plastic stents in 10) were placed after 19 RFA sessions. Two patients did not receive a PD stent, and another 2 did not receive a biliary stent after initial RFA treatment. Stents were left in place for a Volume
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Figure 2. Fluoroscopic images demonstrating sequence of RFA treatment. A, Initial cholangiogram shows a distal bile duct polyp. B, Papillary balloon dilation to facilitate endoscopic visualization of the polyp. C, Radiofrequency ablation catheter in the distal bile duct (patient no. 10).
Figure 3. Endoscopic images demonstrating sequence of RFA treatment (same patient as in Fig. 2). A, Endoscopic view of a sessile bile duct polyp after ampullectomy, duodenal polpectomy, pancreatic stent placement, and papillary balloon dilation. B, Appearance after RFA. Some polyp remains around the bile duct orifice. C, Appearance after concomitant APC treatment. APC, argon plasma coagulation ablation; RFA, radiofrequency ablation.
median of 3 months (range, 0-8) after the final RFA session. Two patients with persistent intraductal adenoma after 1 and 5 RFA sessions were treated during subsequent ERCPs with additional APC (n Z 1) or photodynamic therapy (n Z 1), respectively. Altogether, 7 patients were treated with RFA alone and 7 received concomitant or subsequent treatment with other modalities. One patient died of an unrelated cardiac event 3 months after her last RFA session and did not have a follow-up ERCP to assess response. The other 13 patients underwent a median of 2 surveillance ERCPs after completion of treatment over a median follow-up period of 16 months (range, 5-46), with intraductal biopsy specimens showing no intraductal neoplasm in 12 (92%) and recurrent adenoma of the 4 GASTROINTESTINAL ENDOSCOPY Volume
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CBD in 1. The patient with residual adenoma who underwent 1 RFA treatment session with concomitant treatment with APC had poor functional status and declined further endoscopic or surgical interventions. In 7 patients treated with RFA alone the success rate was 100% at the end of RFA and at the most recent follow-up. In the remaining 6 patients treated with RFA and other concomitant or subsequent endoscopic modalities, the success rate was 4 of 6 (66.7%) at the end of RFA and 5 of 6 (83.3%) at the most recent follow-up. Overall, the treatment success rate among the 13 patients was 85% after RFA and 92% after all endoscopic treatment. Adverse events occurred in 6 of 14 patients (43%), of which 4 (29%) were symptomatic. Two patients presented www.giejournal.org
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RFA for intraductal extension of ampullary neoplasms
TABLE 2. Characteristics of patients with and without post-RFA bile duct strictures Patients who developed strictures (n [ 5)
Patients without strictures (n [ 9)
P value
Mean 12.8 9.8
Mean 13.4 5.2
.88
Mean 2 1.7, Median 1 (range, 1-5)
Mean 1.4 .7, Median 1 (range, 1-5)
.36
1/5
0/9
.36
Additional modalities (yes)
1/5
6/9
.27
Prophylactic biliary stenting for at least 3 months (yes)
2*/5
5/9
1
Post-RFA fully covered metal stent (yes)
2/5
4/9
1
Intraductal adenoma length, mm Number of RFA sessions Overlapping RFA applications (yes)
RFA, radiofrequency ablation; CBD, common bile duct. *Both strictures were asymptomatic and noted as mild distal CBD narrowing on cholangiography during follow-up stent exchange.
with jaundice secondary to benign distal CBD strictures, one 7 months after RFA, and the other 16 months after RFA and 10 months after photodynamic therapy. These strictures were treated with multiple plastic stents for 8 months in 1 patient and fully covered metal stents for 12 months in 1 patient, with resolution in both cases. Three additional patients were found to have an asymptomatic distal CBD stricture on follow-up cholangiography, treated with multiple plastic stents for a median of 5 months (range, 3-7), with resolution in all cases. One additional patient presented with fever and nausea 4 weeks after biliary RFA, with CT showing a 4.3-cm retroduodenal abscess that was successfully treated with EUS-guided transduodenal drainage. Cholangiography at the time of abscess drainage showed no biliary leak or fistula. One patient who had undergone 1 session of biliary RFA developed recurrent acute pancreatitis attributed to a stent-related PD stricture that was treated endoscopically. As shown in Table 2, we were unable to identify a clinical variable associated with a likelihood of biliary stricture after RFA. Seven patients underwent prophylactic biliary stenting for at least 3 months (range, 3-8.4) after their final RFA session, and none developed a symptomatic biliary stricture during follow-up, although asymptomatic strictures were seen in 2 of these patients during stent exchanges.
DISCUSSION An estimated 3000 ampullary tumors present annually in the United States, with autopsy series reporting prevalence rates of .04% to .12%.13-15 Ampullary adenomas are the most common ampullary tumor with risk of malignant transformation through an adenoma-to-carcinoma sequence. The reported incidence of cancer within sporadic adenomas at the time of diagnosis ranges from 25% to 30%.15,16 In addition, cancer is missed by endoscopic biopsy sampling and is found only in resection specimens in 6% to 26% of adenomas undergoing papillectomy,17-19 and is more likely in patients with high-grade dysplasia or ductal dilatation.19 Surgical pancreaticoduodenectomy effectively treats ampullary adenomas but with significant morbidity (50%-60%) and www.giejournal.org
mortality (1%-9%).4,20-25 Surgical transduodenal ampullectomy has been associated with high recurrence rates (30%).4,20-24 Endoscopic resection of ampullary polyps is a minimally invasive alternative to surgical therapy in appropriately selected patients. Endoscopic papillectomy was first described in 1983 by Suzuki et al26 and has become a preferred treatment option for ampullary adenomas because of lower morbidity and mortality and costeffectiveness compared with surgery.4,16,17,26,27 Endoscopic treatment of ampullary adenomas achieves cure rates ranging from 76% to 90% in patients without intraductal extension.4,16,17,27 However, intraductal extension of adenoma has been associated with lower cure rates and a greater need for surgery for incomplete adenoma removal. Several investigators have cited intraductal adenoma growth as a contraindication to endoscopic therapy.4-7 Limited data have shown that <1 cm of extension into the CBD or PD does not preclude endoscopic therapy because tissue invading to this level may be exposed to endoscopic view after sphincterotomy and ablated.4,28,29 However, limited or poor visualization, presence of circumferential intraductal polyp, and inability to accurately target the intraductal polyp may lead to suboptimal treatment results of endoscopic treatment. By using endoscopic RFA, often in combination with other modalities, we were able to achieve complete intraductal adenoma eradication in 12 of 13 assessable patients (92%), albeit with a 43% rate of adverse events in this small series. Detection of the presence and full extent of intraductal adenomas can be difficult. ERCP, MRCP, EUS, intraductal US, and direct cholangioscopy or pancreatography may all facilitate assessment for intraductal extension of adenoma. ERCP should be performed at the time of endoscopic papillectomy to assess for evidence of extension into either ductal system. Endoscopic balloon dilatation of the periampullary ducts after papillectomy and sphincterotomy (Fig. 2) allows direct endoscopic visualization of intraductal polyp and immediate assessment of treatment effect and was commonly used in this series.2 A major limitation of endoscopic intraductal treatment is the inability to ensure that tiny foci of undetected adenoma remain after treatment. Direct cholangioscopy Volume
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might improve the assessment of treatment adequacy but was not used in this series, in part because the treated segments of duct were typically visible from the duodenum after balloon dilation of ductal orifices and in part because most of our patients were treated before the recent advent of disposable digital cholangioscopes. There have been 2 recent reviews on endoscopic biliary RFA.9,30 The RFA catheter features 2 electrodes spaced 8 mm apart and induces coagulative necrosis in an oblong treatment zone centered on the electrodes. In ex vivo experiments, the length of the treatment zone along the catheter axis varies from 22 to 29 mm and perpendicular to the catheter from 4.3 to 11.3 mm, depending on the energy used and the duration of treatment.31 Most studies have applied RF energy of 7 to 10 W for a duration of 90 to 120 seconds for each intrabiliary application. Endobiliary RFA has been shown in several studies and case series to be a technically feasible adjunct therapy for biliary cancer palliation before or after metal stent placement. The use of RFA as a primary treatment for intraductal adenoma has been previously reported in a patient with a right main duct adenoma who was not a surgical candidate.32 In addition, Mehendiratta and Desilets33 reported using RFA to successfully eradicate residual ampullary adenoma in 1 patient. Recently, Valente et al34 reported 3 cases that were treated with RFA: 1 had intraductal recurrence after endoscopic papillectomy and the other 2 had intraductal adenoma. In some of our cases the zone of RFA ablation probably extended proximal to the intraductal polyp and included the normal duct wall. Transmural necrosis of normal bile ducts by RFA was reported in a porcine model and can occur because the cylindrical RFA ablation zone extends up to 4.1 mm from the sides of the probe depending on the energy settings and duration used, whereas the normal bile duct wall is typically no more than 1 mm thick.31,35 Transmural injury is probably less common when bulky biliary malignancies are treated with RFA but has been reported after RFA treatment of intrahepatic biliary adenoma.36 We did not observe any cases of acute ductal perforation after RFA, probably because the ductal segments we treated are retroperitoneal and surrounded by pancreatic parenchyma, and prophylactic stents were routinely placed. However, 1 patient did develop a retroduodenal abscess despite prophylactic placement of a fully covered metal biliary stent after RFA, suggesting full-thickness bile duct injury. Infectious adverse events have been commonly reported after RFA in patients with biliary malignancies.30 Ductal strictures were the most common adverse event. Bile duct strictures related to RFA developed in 5 patients (36%); however, only 2 (14%) were symptomatic. One of the patients with an asymptomatic biliary stricture also developed a stent-related PD stricture, leading to acute pancreatitis. All of these strictures were treated endoscopically with complete resolution in all 6 GASTROINTESTINAL ENDOSCOPY Volume
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patients. Symptomatic bile duct strictures did not occur in patients who received prophylactic stenting for at least 3 months after RFA. Improvements in biliary RFA technology (such as the ability to alter the length and depth of the treatment zone) might decrease the incidence of adverse events. Limitations of our study include its retrospective nature, small number of patients, selection and referral biases, heterogeneous treatment including multimodality therapy in 50%, nonstandardized RFA energy delivery, and a short (16 month) median duration of patient follow-up. In the absence of long-term follow-up and digital cholangioscopy, we cannot know whether small undetected foci of intraductal adenoma remained in our patients. We chose RFA treatment settings based on published ex vivo and in vivo data but do not know whether lower RFA energy settings would be equally efficacious and result in fewer adverse events. In some patients we performed balloon dilation before RFA for visualization of intraductal polyp, and we do not know whether this impeded the efficacy of RFA by increasing ductal diameter. Despite these limitations, our data establish the feasibility of RFA therapy for intraductal polyp extension and provide a basis for considering RFA therapy and discussing this treatment option with patients. In conclusion, endoscopic RFA may be an effective modality for treatment of intraductal extension of ampullary neoplasms. RFA should be used selectively in patients for whom treatment of an intraductal lesion is appropriate, other endoscopic modalities are likely to be insufficient, and the main treatment alternative is pancreaticoduodenectomy. RFA may cause transmural bile duct injury and should be used with caution. Ductal strictures were common after RFA but responded to endoscopic stent therapy; prophylactic biliary stenting may decrease the likelihood of this adverse event.
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