Endoscopy 2022; 54(03): 229-240
DOI: 10.1055/a-1521-6318
Original article

Incidence and outcomes of poor healing and poor squamous regeneration after radiofrequency ablation therapy for early Barrett’s neoplasia

Sanne N. van Munster*
1   Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
2   Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
1   Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
3   Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
,
Esther A. Nieuwenhuis
2   Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
Lorenza Alvarez Herrero
1   Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
,
Auke Bogte
3   Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
,
Alaa Alkhalaf
4   Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
,
Boudewijn E. Schenk
4   Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
,
Erik J. Schoon
5   Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
,
Wouter L. Curvers
5   Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
,
Arjun D. Koch
6   Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
,
6   Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
,
Pieter J. F. de Jonge
6   Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
,
Thjon J. Tang
7   Department of Gastroenterology and Hepatology, IJsselland Hospital, Cappelle a/d IJssel, the Netherlands
,
Wouter B. Nagengast
8   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
,
Frans T. M. Peters
8   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
,
Jessie Westerhof
8   Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen University, Groningen, the Netherlands
,
Martin H. M. G. Houben
9   Department of Gastroenterology and Hepatology, Haga Hospital, Den Haag, the Netherlands
,
Jacques J. G. H. M. Bergman
2   Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
Roos E. Pouw
2   Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands
,
Bas L. A. M. Weusten
1   Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
3   Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
› Author Affiliations
Trial Registration: Netherlands National Trial Register (http://www.trialregister.nl) Registration number (trial ID): NL7039 Type of study: Retrospective, multicenter study


Abstract

Background Endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most patients with Barrett’s esophagus (BE). However, some patients experience poor healing and/or poor squamous regeneration. We evaluated incidence and treatment outcomes of poor healing and poor squamous regeneration.

Methods We included all patients treated with RFA for early BE neoplasia from a nationwide Dutch registry based on a joint treatment protocol. Poor healing (active inflammatory changes or visible ulcerations ≥ 3 months post-RFA), poor squamous regeneration (< 50 % squamous regeneration), and treatment success (complete eradication of BE [CE-BE]) were evaluated.

Results 1386 patients (median BE C2M5) underwent RFA with baseline low grade dysplasia (27 %), high grade dysplasia (30 %), or early cancer (43 %). In 134 patients with poor healing (10 %), additional time and acid suppression resulted in complete esophageal healing, and 67/134 (50 %) had normal squamous regeneration with 97 % CE-BE. Overall, 74 patients had poor squamous regeneration (5 %). Compared with patients with normal regeneration, patients with poor squamous regeneration had a higher risk for treatment failure (64 % vs. 2 %, relative risk [RR] 27 [95 % confidence interval [CI] 18–40]) and progression to advanced disease (15 % vs. < 1 %, RR 30 [95 %CI 12–81]). Higher body mass index, longer BE segment, reflux esophagitis, and < 50 % squamous regeneration after baseline endoscopic resection were independently associated with poor squamous regeneration in multivariable logistic regression.

Conclusions In half of the patients with poor healing, additional time and acid suppression led to normal squamous regeneration and excellent treatment outcomes. In patients with poor squamous regeneration, however, the risk for treatment failure and progression to advanced disease was significantly increased.

* Co-first authors.


Supplementary material



Publication History

Received: 03 February 2021

Accepted after revision: 01 June 2021

Accepted Manuscript online:
01 June 2021

Article published online:
04 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Shaheen NJ, Falk GW, Iyer PG. et al. ACG Clinical Guideline: Diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016; 111: 30-50
  • 2 Weusten B, Bisschops R, Coron E. et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 2017; 49: 191-198
  • 3 Phoa KN, van Vilsteren FGI, Weusten BLAM. et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low grade dysplasia. JAMA 2014; 311: 1209
  • 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 2016; 65: 555-562
  • 5 Shaheen NJ, Sharma P, Overholt BF. et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360: 2277-2288
  • 6 Pouw RE, Wirths K, Eisendrath P. et al. Efficacy of radiofrequency ablation combined with endoscopic resection for Barrett’s esophagus with early neoplasia. Clin Gastroenterol Hepatol 2010; 8: 23-29
  • 7 van Vilsteren FGI, Alvarez Herrero L, Pouw RE. et al. Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett’s esophagus with early neoplasia: a prospective multicenter study. Endoscopy 2013; 45: 516-525
  • 8 Nederlandse Vereniging van Maag-darm-leverartsen. Richtlijn Barrett-Oesofagus. 2018 http://www.mdl.nl/richtlijnen2?noCache=214;1484584659
  • 9 van Munster S, Nieuwenhuis E, Weusten BLAM. et al. Long-term outcomes after endoscopic treatment for Barrett’s neoplasia with radiofrequency ablation ± endoscopic resection: results from the national Dutch database in a 10-year period. Gut 2021; DOI: 10.1136/gutjnl-2020-322615.
  • 10 Sengupta N, Ketwaroo GA, Bak DM. et al. Salvage cryotherapy after failed radiofrequency ablation for Barrett’s esophagus-related dysplasia is safe and effective. Gastrointest Endosc 2015; 82: 443-448
  • 11 Weusten BLAM, Bergman JJGHM. Cryoablation for managing Barrett’s esophagus refractory to radiofrequency ablation? Don’t embrace the cold too soon! . Gastrointest Endosc 2015; 82: 449-451
  • 12 Timmer MR, Brankley SM, Gorospe EC. et al. Prediction of response to endoscopic therapy of Barrett’s dysplasia by using genetic biomarkers. Gastrointest Endosc 2014; 80: 984-991
  • 13 Shaheen NJ, Richter JE. Barrett’s oesophagus. Lancet 2009; 373: 850-861
  • 14 Akiyama J, Marcus SN, Triadafilopoulos G. Effective intra-esophageal acid control is associated with improved radiofrequency ablation outcomes in Barrett’s esophagus. Dig Dis Sci 2012; 57: 2625-2632
  • 15 Krishnan K, Pandolfino JE, Kahrilas PJ. et al. Increased risk for persistent intestinal metaplasia in patients with Barrett’s esophagus and uncontrolled reflux exposure before radiofrequency ablation. Gastroenterology 2012; 143: 576-581
  • 16 Kruger L, Gonzalez LM, Pridgen TA. et al. Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair. Am J Physiol Gastrointest Liver Physiol 2017; 313: G180-G191
  • 17 Becq A, Camus M, Rahmi G. et al. Emerging indications of endoscopic radiofrequency ablation. United Eur Gastroenterol J 2015; 3: 313-324
  • 18 Trunzo JA, McGee MF, Poulose BK. et al. A feasibility and dosimetric evaluation of endoscopic radiofrequency ablation for human colonic and rectal epithelium in a treat and resect trial. Surg Endosc 2011; 25: 491-496
  • 19 May A, Gossner L, Pech O. et al. Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett’s oesophagus: acute-phase and intermediate results of a new treatment approach. Eur J Gastroenterol Hepatol 2002; 14: 1085-1091
  • 20 Ell C, May A, Pech O. et al. Curative endoscopic resection of early esophageal adenocarcinomas (Barrett’s cancer). Gastrointest Endosc 2007; 65: 3-10
  • 21 Pech O, Behrens A, May A. et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett’s oesophagus. Gut 2008; 57: 1200-1206
  • 22 van Munster SN, Nieuwenhuis EA, Weusten BLAM. et al. Endoscopic resection without subsequent ablation therapy for early Barrett’s neoplasia: endoscopic findings and long-term mortality. J Gastrointest Surg 2021; 25: 67-76