Editorial
579
Author
Raf Bisschops
Institution
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1392105 Endoscopy 2015; 47: 579–581 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X
Over the past decade, endoscopic resection of early mucosal neoplasia with subsequent ablation of the remainder of the Barrett’s epithelium has replaced subtotal esophagectomy as the first-line treatment for early mucosal Barrett’s-associated neoplasia. Endoscopic resection has been shown to be oncologically safe and comparable to surgery [1]. However, metachronous lesions develop in up to 30 % of patients, and therefore a two-step approach involving the removal of all visible neoplasia followed by ablation of the remaining Barrett’s mucosa is adopted in order to reduce this risk significantly [2]. In this issue of Endoscopy, Canto et al. [3] report, for the first time, long-term efficacy and safety data on carbon dioxide (CO2) cryotherapy for the ablation of Barrett’s esophagus, through a retrospective analysis of prospectively collected data. Consecutive patients with high grade dysplasia or early adenocarcinoma after removal of visible lesions were included in the study. Patients were stratified into two groups: those receiving cryotherapy as primary treatment for residual Barrett’s esophagus after endoscopic resection of visible lesions (n = 21), and those receiving cryotherapy as a rescue therapy after failed endoluminal treatment including endoscopic resection, photodynamic therapy (PDT), and radiofrequency ablation (RFA) (n = 47). For the entire group, complete remission for dysplasia at 1 year was 89 % (95 % for primary treatment and 86 % for rescue treatment). At 3-year follow-up, complete remission for dysplasia and early cancer was 100 % for primary treatment and 82 % for rescue treatment. Complete remission of intestinal metaplasia after 1 year was 55 % (70 % for primary treatment and 48 % for rescue treatment). This improved at the 3-year follow-up, where 67 % of the whole group were disease free (85 % for primary treatment and 59 % for rescue treatment). The study also showed a favorable safety profile for CO2 cryotherapy, with adverse events being limited to
Corresponding author Raf Bisschops, MD, PhD Department of Gastroenterology University Hospitals Leuven Herestraat 49 3000 Leuven Belgium Fax: +32-16-344419 [email protected]
Please see related article from Canto et al. p. 582.
postprocedural pain in four patients (6 %) and stricture in one patient (2 %). Two serious adverse events were reported and required hospitalization: one suspected perforation (minute sub-diaphragmatic air) and one postprocedural bradycardia. Buried glands during follow-up were noted in 7 % of patients. What does this study add to our knowledge of treatment for dysplastic Barrett’s esophagus? First, the safety data appear to be very favorable, especially given that 48 % of the patients had a history of upper gastrointestinal bleeding or were at risk of bleeding, including one patient with esophageal varices. No bleeding occurred after CO2 cryotherapy. Therefore, there might be a place for this technique in patients who are at a higher risk of bleeding or when RFA is contraindicated in patients with varices. Second, the majority of patients underwent a rescue treatment for failed endoluminal therapy. These are the first results to show that CO2 cryotherapy may be useful in patients who are refractory to other treatments. However, it has to be emphasized that 1) it is not clear from the study how proton pump inhibitor intake had been controlled during previous RFA treatment and 2) three treatments of RFA would not have been considered a failure in the EURO-II, AIM dysplasia, or SURF trials, where a maximum of five RFA sessions was permitted [4 – 6]. Third, the study confirms that meticulous follow-up after treatment of patients with degenerated Barrett’s esophagus is mandatory to ensure a good oncological outcome. In the Canto study, the risk of dysplasia in recurrent intestinal metaplasia was as high as 40 %. This is much higher than what is reported for APC and RFA, but may very well be due to the selection of patients with refractory disease in 68 % of the cohort. A variety of methods for ablation of Barrett’s esophagus has been assessed over past decades. The ideal ablation tool should be safe, easy to apply, and have excellent long term outcomes for
Bisschops Raf. What is the ideal ablation therapy for Barrett’s esophagus? … Endoscopy 2015; 47: 579–581
Downloaded by: Rutgers University. Copyrighted material.
What is the ideal ablation therapy for Barrett’s esophagus?
Editorial
sustained endoscopic and histological remission of all intestinal metaplasia. A perfect tool with a 100 % remission rate and 0 % complication rate does not exist. In the era of evidence-based medicine, a literature search reveals clearly that the best scientific data and systematic assessment of an ablation technique are only available for RFA [4 – 11]. Indeed, the technique has been assessed from the bench [12, 13] and feasibility studies [7] to wellconducted randomized controlled trials and prospectively controlled multicenter trials, showing high efficacy and safety for ablation of flat high grade dysplasia [6], low grade dysplasia [5], and, recently, for ablation of residual Barrett’s mucosa after endoscopic resection of visible lesions [4, 6]. The company behind the RFA technique has set a new benchmark against which the efficacy and safety of future promising techniques must now be assessed. However, the study by Canto et al. exemplifies the shortcomings of the manufacturers in terms of device testing. For a long time, companies have been bombarding endoscopists with new CE-labelled or FDA-approved devices, exposing patients to techniques that have not been comprehensively assessed in a clinical study. The fact that long term data are the result of a retrospective analysis from a single centre, and that the study combined dosimetry assessment with clinical outcome, merely illustrate Dr Canto’s merit in gathering and analyzing the data in order to overcome the shortcomings of companies that failed to properly investigate this new, possibly promising, device. To answer the question of the best ablation tool for Barrett’s esophagus, only one randomized controlled trial has compared two different techniques [14]. Stepwise radical endoscopic resection has been compared with staging endoscopic resection of visible lesions followed by RFA. Both techniques had a comparable outcome in terms of complete removal of dysplasia and Barrett’s esophagus; however, stepwise endoscopic resection was technically more challenging and resulted in significantly more stenoses and, as a consequence, a higher number of interventions compared with RFA. For other ablation methods, there are currently no comparative data available to make a final conclusion on whether one ablation device is better than another. However, PDT has shown insufficient efficacy for complete remission of intestinal metaplasia and was associated with an unacceptable rate of complications, mainly stenosis and phototoxicity. In addition, there is a significant cost associated with PDT and it is no longer widely used [15]. Recently, a randomized controlled trial showed a significant reduction of recurrent metachronous disease after argon plasma coagulation (APC) of residual Barrett’s mucosa in patients after endoscopic resection for high grade dysplasia and early mucosal cancer [2]. After a mean of 4 APC sessions, complete removal of Barrett’s esophagus was achieved in 26 /33 patients (79 %). The study by Canto et al. [3] suggests a similar efficacy for CO2 cryotherapy but provides a longer follow-up period. Although the device cost of APC and CO2 cryotherapy may be lower compared with RFA, other factors need to be taken into account, such as operator dependency of the technique and number of treatment sessions. In the study by Canto et al., the goal of each treatment session was to freeze all visible columnar mucosa and perform focal or circumferential ablation in patients with a Barrett’s segment length of up to 8 cm. Although 68 % of patients had previously undergone other ablation treatments, the median number of sessions for Barrett’s segments of 3 – 8 cm was 4, increasing to 7 sessions for segments > 8 cm. This is in contrast to RFA data where a median of 2 – 3 treatments were required for complete
remission [6, 8, 10]. Even for long Barrett’s segments, complete remission was achieved in 83 % of patients after a median of three RFA ablation sessions [11]. Similarly, it seems that APC as a spotby-spot ablation technique would be too time-consuming in long-segment Barrett’s esophagus. In addition, CO2 cryotherapy, and in particular APC, are very operator dependent both for energy settings and delivery. This may explain the variable results for APC in the literature [16]. To date, good efficacy data have been provided mainly by single-center or single-operator studies, and results need to be confirmed in multicenter prospective trials. Considering the simplicity of the RFA technique, the fact that energy delivery is operator independent, and the excellent long term clinical results, it appears that, at this time, RFA will be hard to beat as the preferred ablation tool for long Barrett’s segments. Even with the publication of studies assessing the effect of new ablation devices, the jury is still out as to which device is preferable for focal ablation of residual Barrett’s esophagus or short Barrett’s segments. Only studies with a head-to-head comparison, assessing hard clinical end points and cost effectiveness, will provide a definitive answer to this question. Competing interests: Professor Bisschops is a consultant for Covidien and has received research support from ERBE.
Acknowledgment !
Professor Bisschops is supported by a grant from the Research Foundation – Flanders (FWO).
References 1 Pech O, Bollschweiler E, Manner H et al. Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett’s esophagus at two high-volume centers. Ann Surg 2011; 254: 67 – 72 2 Manner H, Rabenstein T, Pech O et al. Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term followup study of argon plasma coagulation vs. surveillance (APE study). Endoscopy 2014; 46: 6 – 12 3 Canto M, Shin E, Khashab M et al. Safety and efficacy of carbon dioxide cryotherapy for treatment of neoplastic Barrett’s esophagus. Endoscopy 2015; 47: 582 – 591 4 Phoa KN, Pouw RE, Bisschops R et al. Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II). Gut 2015: DOI 10.1136/gutjnl-2015-309298 (in press) 5 Phoa KN, van Vilsteren FG, Weusten BL et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and lowgrade dysplasia: a randomized clinical trial. JAMA 2014; 311: 1209 – 1217 6 Shaheen NJ, Sharma P, Overholt BF et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360: 2277 – 2288 7 Fleischer DE, Sharma VK. Endoscopic ablation of Barrett’s esophagus using the Halo system. Dig Dis 2008; 26: 280 – 284 8 Pouw RE, Wirths K, Eisendrath P et al. Efficacy of radiofrequency ablation combined with endoscopic resection for Barrett’s oesophagus with early neoplasia. Clin Gastroenterol Hepatol 2010; 8: 23 – 29 9 Bulsiewicz WJ, Kim HP, Dellon ES et al. Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett’s esophagus. Clin Gastroenterol Hepatol 2012; 11: 636 – 642 10 Phoa KN, Pouw RE, van Vilsteren FG et al. Remission of Barrett’s esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study. Gastroenterology 2013; 145: 96 – 104
Bisschops Raf. What is the ideal ablation therapy for Barrett’s esophagus? … Endoscopy 2015; 47: 579–581
Downloaded by: Rutgers University. Copyrighted material.
580
Editorial 14 van Vilsteren FG, Pouw RE, Seewald S et al. Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett’s oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. Gut 2011; 60: 765 – 773 15 Overholt BF, Panjehpour M, Halberg DL. Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: longterm results. Gastrointest Endosc 2003; 58: 183 – 188 16 Kahaleh M, Van Laethem JL, Nagy N et al. Long-term follow-up and factors predictive of recurrence in Barrett’s esophagus treated by argon plasma coagulation and acid suppression. Endoscopy 2002; 34: 950 – 955
Downloaded by: Rutgers University. Copyrighted material.
11 Alvarez Herrero L, van Vilsteren FG, Pouw RE et al. Endoscopic radiofrequency ablation combined with endoscopic resection for early neoplasia in Barrett’s esophagus longer than 10 cm. Gastrointest Endosc 2011; 73: 682 – 690 12 Herrero LA, van Vilsteren FG, Visser M et al. Simultaneous use of endoscopic resection and radiofrequency ablation is not safe in an esophageal porcine model. Dis Esophagus 2015; 28: 25 – 31 13 Schölvinck DW, Alvarez Herrero L, Visser M et al. Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model. Dis Esophagus 2014: DOI 10.1111/dote.12225 (in press)
581
Bisschops Raf. What is the ideal ablation therapy for Barrett’s esophagus? … Endoscopy 2015; 47: 579–581
579
Author
Raf Bisschops
Institution
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1392105 Endoscopy 2015; 47: 579–581 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X
Over the past decade, endoscopic resection of early mucosal neoplasia with subsequent ablation of the remainder of the Barrett’s epithelium has replaced subtotal esophagectomy as the first-line treatment for early mucosal Barrett’s-associated neoplasia. Endoscopic resection has been shown to be oncologically safe and comparable to surgery [1]. However, metachronous lesions develop in up to 30 % of patients, and therefore a two-step approach involving the removal of all visible neoplasia followed by ablation of the remaining Barrett’s mucosa is adopted in order to reduce this risk significantly [2]. In this issue of Endoscopy, Canto et al. [3] report, for the first time, long-term efficacy and safety data on carbon dioxide (CO2) cryotherapy for the ablation of Barrett’s esophagus, through a retrospective analysis of prospectively collected data. Consecutive patients with high grade dysplasia or early adenocarcinoma after removal of visible lesions were included in the study. Patients were stratified into two groups: those receiving cryotherapy as primary treatment for residual Barrett’s esophagus after endoscopic resection of visible lesions (n = 21), and those receiving cryotherapy as a rescue therapy after failed endoluminal treatment including endoscopic resection, photodynamic therapy (PDT), and radiofrequency ablation (RFA) (n = 47). For the entire group, complete remission for dysplasia at 1 year was 89 % (95 % for primary treatment and 86 % for rescue treatment). At 3-year follow-up, complete remission for dysplasia and early cancer was 100 % for primary treatment and 82 % for rescue treatment. Complete remission of intestinal metaplasia after 1 year was 55 % (70 % for primary treatment and 48 % for rescue treatment). This improved at the 3-year follow-up, where 67 % of the whole group were disease free (85 % for primary treatment and 59 % for rescue treatment). The study also showed a favorable safety profile for CO2 cryotherapy, with adverse events being limited to
Corresponding author Raf Bisschops, MD, PhD Department of Gastroenterology University Hospitals Leuven Herestraat 49 3000 Leuven Belgium Fax: +32-16-344419 [email protected]
Please see related article from Canto et al. p. 582.
postprocedural pain in four patients (6 %) and stricture in one patient (2 %). Two serious adverse events were reported and required hospitalization: one suspected perforation (minute sub-diaphragmatic air) and one postprocedural bradycardia. Buried glands during follow-up were noted in 7 % of patients. What does this study add to our knowledge of treatment for dysplastic Barrett’s esophagus? First, the safety data appear to be very favorable, especially given that 48 % of the patients had a history of upper gastrointestinal bleeding or were at risk of bleeding, including one patient with esophageal varices. No bleeding occurred after CO2 cryotherapy. Therefore, there might be a place for this technique in patients who are at a higher risk of bleeding or when RFA is contraindicated in patients with varices. Second, the majority of patients underwent a rescue treatment for failed endoluminal therapy. These are the first results to show that CO2 cryotherapy may be useful in patients who are refractory to other treatments. However, it has to be emphasized that 1) it is not clear from the study how proton pump inhibitor intake had been controlled during previous RFA treatment and 2) three treatments of RFA would not have been considered a failure in the EURO-II, AIM dysplasia, or SURF trials, where a maximum of five RFA sessions was permitted [4 – 6]. Third, the study confirms that meticulous follow-up after treatment of patients with degenerated Barrett’s esophagus is mandatory to ensure a good oncological outcome. In the Canto study, the risk of dysplasia in recurrent intestinal metaplasia was as high as 40 %. This is much higher than what is reported for APC and RFA, but may very well be due to the selection of patients with refractory disease in 68 % of the cohort. A variety of methods for ablation of Barrett’s esophagus has been assessed over past decades. The ideal ablation tool should be safe, easy to apply, and have excellent long term outcomes for
Bisschops Raf. What is the ideal ablation therapy for Barrett’s esophagus? … Endoscopy 2015; 47: 579–581
Downloaded by: Rutgers University. Copyrighted material.
What is the ideal ablation therapy for Barrett’s esophagus?
Editorial
sustained endoscopic and histological remission of all intestinal metaplasia. A perfect tool with a 100 % remission rate and 0 % complication rate does not exist. In the era of evidence-based medicine, a literature search reveals clearly that the best scientific data and systematic assessment of an ablation technique are only available for RFA [4 – 11]. Indeed, the technique has been assessed from the bench [12, 13] and feasibility studies [7] to wellconducted randomized controlled trials and prospectively controlled multicenter trials, showing high efficacy and safety for ablation of flat high grade dysplasia [6], low grade dysplasia [5], and, recently, for ablation of residual Barrett’s mucosa after endoscopic resection of visible lesions [4, 6]. The company behind the RFA technique has set a new benchmark against which the efficacy and safety of future promising techniques must now be assessed. However, the study by Canto et al. exemplifies the shortcomings of the manufacturers in terms of device testing. For a long time, companies have been bombarding endoscopists with new CE-labelled or FDA-approved devices, exposing patients to techniques that have not been comprehensively assessed in a clinical study. The fact that long term data are the result of a retrospective analysis from a single centre, and that the study combined dosimetry assessment with clinical outcome, merely illustrate Dr Canto’s merit in gathering and analyzing the data in order to overcome the shortcomings of companies that failed to properly investigate this new, possibly promising, device. To answer the question of the best ablation tool for Barrett’s esophagus, only one randomized controlled trial has compared two different techniques [14]. Stepwise radical endoscopic resection has been compared with staging endoscopic resection of visible lesions followed by RFA. Both techniques had a comparable outcome in terms of complete removal of dysplasia and Barrett’s esophagus; however, stepwise endoscopic resection was technically more challenging and resulted in significantly more stenoses and, as a consequence, a higher number of interventions compared with RFA. For other ablation methods, there are currently no comparative data available to make a final conclusion on whether one ablation device is better than another. However, PDT has shown insufficient efficacy for complete remission of intestinal metaplasia and was associated with an unacceptable rate of complications, mainly stenosis and phototoxicity. In addition, there is a significant cost associated with PDT and it is no longer widely used [15]. Recently, a randomized controlled trial showed a significant reduction of recurrent metachronous disease after argon plasma coagulation (APC) of residual Barrett’s mucosa in patients after endoscopic resection for high grade dysplasia and early mucosal cancer [2]. After a mean of 4 APC sessions, complete removal of Barrett’s esophagus was achieved in 26 /33 patients (79 %). The study by Canto et al. [3] suggests a similar efficacy for CO2 cryotherapy but provides a longer follow-up period. Although the device cost of APC and CO2 cryotherapy may be lower compared with RFA, other factors need to be taken into account, such as operator dependency of the technique and number of treatment sessions. In the study by Canto et al., the goal of each treatment session was to freeze all visible columnar mucosa and perform focal or circumferential ablation in patients with a Barrett’s segment length of up to 8 cm. Although 68 % of patients had previously undergone other ablation treatments, the median number of sessions for Barrett’s segments of 3 – 8 cm was 4, increasing to 7 sessions for segments > 8 cm. This is in contrast to RFA data where a median of 2 – 3 treatments were required for complete
remission [6, 8, 10]. Even for long Barrett’s segments, complete remission was achieved in 83 % of patients after a median of three RFA ablation sessions [11]. Similarly, it seems that APC as a spotby-spot ablation technique would be too time-consuming in long-segment Barrett’s esophagus. In addition, CO2 cryotherapy, and in particular APC, are very operator dependent both for energy settings and delivery. This may explain the variable results for APC in the literature [16]. To date, good efficacy data have been provided mainly by single-center or single-operator studies, and results need to be confirmed in multicenter prospective trials. Considering the simplicity of the RFA technique, the fact that energy delivery is operator independent, and the excellent long term clinical results, it appears that, at this time, RFA will be hard to beat as the preferred ablation tool for long Barrett’s segments. Even with the publication of studies assessing the effect of new ablation devices, the jury is still out as to which device is preferable for focal ablation of residual Barrett’s esophagus or short Barrett’s segments. Only studies with a head-to-head comparison, assessing hard clinical end points and cost effectiveness, will provide a definitive answer to this question. Competing interests: Professor Bisschops is a consultant for Covidien and has received research support from ERBE.
Acknowledgment !
Professor Bisschops is supported by a grant from the Research Foundation – Flanders (FWO).
References 1 Pech O, Bollschweiler E, Manner H et al. Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett’s esophagus at two high-volume centers. Ann Surg 2011; 254: 67 – 72 2 Manner H, Rabenstein T, Pech O et al. Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term followup study of argon plasma coagulation vs. surveillance (APE study). Endoscopy 2014; 46: 6 – 12 3 Canto M, Shin E, Khashab M et al. Safety and efficacy of carbon dioxide cryotherapy for treatment of neoplastic Barrett’s esophagus. Endoscopy 2015; 47: 582 – 591 4 Phoa KN, Pouw RE, Bisschops R et al. Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II). Gut 2015: DOI 10.1136/gutjnl-2015-309298 (in press) 5 Phoa KN, van Vilsteren FG, Weusten BL et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and lowgrade dysplasia: a randomized clinical trial. JAMA 2014; 311: 1209 – 1217 6 Shaheen NJ, Sharma P, Overholt BF et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360: 2277 – 2288 7 Fleischer DE, Sharma VK. Endoscopic ablation of Barrett’s esophagus using the Halo system. Dig Dis 2008; 26: 280 – 284 8 Pouw RE, Wirths K, Eisendrath P et al. Efficacy of radiofrequency ablation combined with endoscopic resection for Barrett’s oesophagus with early neoplasia. Clin Gastroenterol Hepatol 2010; 8: 23 – 29 9 Bulsiewicz WJ, Kim HP, Dellon ES et al. Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett’s esophagus. Clin Gastroenterol Hepatol 2012; 11: 636 – 642 10 Phoa KN, Pouw RE, van Vilsteren FG et al. Remission of Barrett’s esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study. Gastroenterology 2013; 145: 96 – 104
Bisschops Raf. What is the ideal ablation therapy for Barrett’s esophagus? … Endoscopy 2015; 47: 579–581
Downloaded by: Rutgers University. Copyrighted material.
580
Editorial 14 van Vilsteren FG, Pouw RE, Seewald S et al. Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett’s oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. Gut 2011; 60: 765 – 773 15 Overholt BF, Panjehpour M, Halberg DL. Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: longterm results. Gastrointest Endosc 2003; 58: 183 – 188 16 Kahaleh M, Van Laethem JL, Nagy N et al. Long-term follow-up and factors predictive of recurrence in Barrett’s esophagus treated by argon plasma coagulation and acid suppression. Endoscopy 2002; 34: 950 – 955
Downloaded by: Rutgers University. Copyrighted material.
11 Alvarez Herrero L, van Vilsteren FG, Pouw RE et al. Endoscopic radiofrequency ablation combined with endoscopic resection for early neoplasia in Barrett’s esophagus longer than 10 cm. Gastrointest Endosc 2011; 73: 682 – 690 12 Herrero LA, van Vilsteren FG, Visser M et al. Simultaneous use of endoscopic resection and radiofrequency ablation is not safe in an esophageal porcine model. Dis Esophagus 2015; 28: 25 – 31 13 Schölvinck DW, Alvarez Herrero L, Visser M et al. Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model. Dis Esophagus 2014: DOI 10.1111/dote.12225 (in press)
581
Bisschops Raf. What is the ideal ablation therapy for Barrett’s esophagus? … Endoscopy 2015; 47: 579–581
