Challenges in Endoscopic Therapy of Dysplastic Barrett’s Esophagus
- 12 Downloads
Purpose of review
Barrett’s esophagus (BE) is the only known measurable factor associated with esophageal adenocarcinoma. The development of endoscopic eradication therapy (EET) has transformed the way BE is managed. Given the fairly recent development of EET, its role in BE is still evolving.
This paper discusses the challenges that endoscopists face at the preprocedural, intraprocedural, and postprocedural stages of BE management. These include challenges in risk stratification, dysplasia detection, ablation methods and dosimetry, choice of resection technique, and management of refractory disease.
Despite the advances in EET in BE, there remain challenges that this review focuses on. Future research into these challenges will optimize ablation techniques and strategies in the future.
KeywordsAblation Radiofrequency Endoscopy Cryotherapy Acid control Pain
Conception and design (AJT, AC)
Analysis and interpretation of the data (AJT, AC)
Drafting of the article (AJT, AC)
Critical revision of the article for important intellectual content (AJT, AC)
Final approval of the article (AJT, AC)
Compliance with Ethical Standards
Conflict of Interest
Arvind Trindade reports personal fees as a consultant from Pentax Medical and CSA Medical.
Aurada Cholapranee declares no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance
- 7.Standards of Practice Committee et al. Endoscopic eradication therapy for patients with Barrett’s esophagus-associated dysplasia and intramucosal cancer. Gastrointest Endosc. 87, 907–931.e9 (2018).Google Scholar
- 8.•• Shaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of Gastroenterology. ACG Clinical Guideline. Diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111:30–50; quiz 51 The American College of Gastroenterology provides recommendations for clinical practice in identifying and managing patients with Barrett’s esophagus (BE) in 2016. Although many of their suggestions are based on weak evidence, it provides an useful algorithm of care for BE patients based on expert opinion.Google Scholar
- 15.Heeren PAM, et al. Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus. Anticancer Res. 2004;24:2579–83.Google Scholar
- 17.Altaf K, Xiong J-J, la Iglesia, D. De, Hickey, L. & Kaul, A. Meta-analysis of biomarkers predicting risk of malignant progression in Barrett’s oesophagus. Br J Surg. 2017;104:493–502.Google Scholar
- 18.• Kerkhof M, et al. Grading of dysplasia in Barrett’s oesophagus: substantial interobserver variation between general and gastrointestinal pathologists. Histopathology. 2007;50:920–7 This prospective multicenter study of 920 patients with endoscopically identified BE demonstrated that there was significant variability among pathologists (both experts and non-experts) when interpreting nondysplastic or low-grade dysplasia (LGD) via biopsies in BE patients.CrossRefGoogle Scholar
- 21.• Duits LC, et al. Patients with Barrett’s esophagus and confirmed persistent low-grade dysplasia are at increased risk for progression to neoplasia. Gastroenterology. 2017;152:993–1001.e1 This retrospective study of 255 patients with a primary diagnosis of LGD demonstrated that interobserver variability for LGD is high, a problem that makes it difficult to determine the appropriate management for these patients. This study concluded that as the number of pathologists (up to three pathologists in the study) who agreed on a diagnosis of LGD increased the risk of developing high-grade dysplasia (HGD) and adenocarcioma (EAC) increased.CrossRefGoogle Scholar
- 22.• Wani S, Rubenstein JH, Vieth M, Bergman J. Diagnosis and management of low-grade dysplasia in Barrett’s esophagus: expert review from the clinical practice updates Committee of the American Gastroenterological Association. Gastroenterology. 2016;151:822–35 The diagnosis and management of BE patients with LGD has been the most difficult and controversial for endoscopists. This clinical update offers expert opinion and a review of the best clinical practice guidelines for this particular patient population as decided in 2016.CrossRefGoogle Scholar
- 24.Sami SS, et al. High definition versus standard definition white light endoscopy for detecting dysplasia in patients with Barrett’s esophagus. Dis Esophagus Off J Int Soc Dis Esophagus. 28:742–9.Google Scholar
- 26.•• ASGE Technology Committee, et al. ASGE Technology Committee systematic review and meta-analysis assessing the ASGE preservation and incorporation of valuable endoscopic innovations thresholds for adopting real-time imaging-assisted endoscopic targeted biopsy during endoscopic surveillance. Gastrointest Endosc. 2016;83:684–98.e7 This meta-analysis looked at the sensitivity and specificity of various advanced imaging technologies available for endoscopic real-time imaging of BE including chromoendoscopy with acetic acid , electronic chromoendoscopy using narrow-band imaging, and endoscopic confocal laser endomicroscopy for detection of dysplasia. This study found that each of these imaging methods met acceptable performance thresholds defined by the ASGE and are reasonable modalities to help guide targeted biopsies to detect dysplasia in BE patients.CrossRefGoogle Scholar
- 27.• Alshelleh M, et al. Incremental yield of dysplasia detection in Barrett’s esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol. Gastrointest Endosc. 2018;88:35–42 This retrospective study looked at the efficacy of volumetric laser endomicroscopy (VLE) as a surveillance strategy for management of dysplastic BE in comparison with random biopsies or random biopsies as per Seattle protocol. This study found that VLE with and without laser markings led to higher detection rates of dysplasia and neoplasia compared to random biopsies.CrossRefGoogle Scholar
- 30.Johanson JF, Frakes J, Eisen D, EndoCDx Collaborative Group. Computer-assisted analysis of abrasive transepithelial brush biopsies increases the effectiveness of esophageal screening: a multicenter prospective clinical trial by the EndoCDx Collaborative Group. Dig Dis Sci. 2011;56:767–72.CrossRefGoogle Scholar
- 36.•• Shaheen NJ, et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med. 2009;360:2277–88 This multicenter randomized control trial looked at 127 patients with dysplastic Barrett’s esophagus who received either RFA or sham procedure. The study demonstrated that RFA was both a safe and effective treatment for intestinal metaplasia (IM) as well as dysplastic BE.CrossRefGoogle Scholar
- 37.van Vilsteren FGI, Pouw RE, Seewald S, Alvarez Herrero L, Sondermeijer CMT, Visser M, 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;60:765–73.CrossRefGoogle Scholar
- 39.Tomizawa Y, Konda VJA, Coronel E, Chapman CG, Siddiqui UD. Efficacy, durability, and safety of complete endoscopic mucosal resection of Barrett esophagus: a systematic review and meta-analysis. J Clin Gastroenterol. 2018;52:210–6.Google Scholar
- 41.ASGE Standards of Practice Committee et al. Management of antithrombotic agents for endoscopic procedures Gastrointest Endosc 70, 1060–1070 (2009).Google Scholar
- 43.Namasivayam V, Wang KK, Prasad GA. Endoscopic mucosal resection in the management of esophageal neoplasia: current status and future directions. Clin Gastroenterol Hepatol. 2010;8:743–54; quiz e96.Google Scholar
- 45.•• Terheggen G, et al. A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia. Gut. 2017;66:783–93 This randomised controlled trial compared the safety and efficacy of endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD). While this study showed that ESD achieved higher rates of complete resection, this had no overall clinical relevance. Compared to EMR, ESD was more time-consuming, technically difficult, and associated with more severe adverse events.CrossRefGoogle Scholar
- 51.• Orman ES, Li NAN, Shaheen NJ. Efficacy and durability of radiofrequency ablation for barrett’s esophagus: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11:1245–55 This meta-analysis of 18 studies and 3802 patients looked at the efficacy of RFA. It demonstrated that RFA is associated with a high proportion of CE-D and CE-IM (91% and 78% respectively) with a low rate of recurrent disease as well as adverse events.CrossRefGoogle Scholar
- 58.Künzli HT, Schölvinck DW, Meijer SL, Seldenrijk KA, Bergman JGHM, Weusten BLAM. Efficacy of the CryoBalloon focal ablation system for the eradication of dysplastic Barrett’s esophagus islands. Endoscopy. 2017;49:169–75.Google Scholar
- 59.Canto MI, Shaheen NJ, Almario JA, Voltaggio L, Montgomery E, Lightdale CJ. Multifocal nitrous oxide cryoballoon ablation with or without EMR for treatment of neoplastic Barrett’s esophagus (with video). Gastrointest Endosc. 2018;88:438–446.e2. https://doi.org/10.1016/j.gie.2018.03.024.CrossRefGoogle Scholar
- 64.•• Pouw RE, Bergman JJ. Safety signal for the simple double ablation regimen when using the Barrx 360 express radiofrequency ablation balloon catheter. Gastroenterology. 2017;153:614 This is a letter to the editors commenting on the interim findings of an ongoing randomized controlled multicenter trial looking at the efficacy and safety of RFA balloon catheter ablation using a standard regimen (2 × 10 J/cm2 with cleaning) versus two simplified regimens a) 2 × 10J/cm2 without cleaning and b) 1 × 10 J/cm2. Their interim findings showed unexpectedly high rates of stricturing (17%) in the 2 × 10 J/cm2 group without cleaning compared with the other two treatment groups.Google Scholar
- 65.•• Pouw RE, et al. Simplified versus standard regimen for focal radiofrequency ablation of dysplastic Barrett’s oesophagus: a multicentre randomised controlled trial. Lancet Gastroenterol Hepatol. 2018. https://doi.org/10.1016/S2468-1253(18)30157-2 A simplified RFA regimen of 3 × 15 J/cm2 without cleaning has been shown to be as effective as the standard regimen of 2 × 15 J/cm2 with cleaning; however, it has been showed to be associated with higher stricturing rates. This randomized non-inferiority study looks at a new lower radiofrequency energy regimen of 3 × 12J/cm2 without cleaning versus the standard regimen for focal treatments. The results of this study demonstrated that the lower energy simplified version was noninferior to the standard regimen with no increase in adverse events or stricturing.
- 73.•• Solomon SS, et al. Liquid nitrogen spray cryotherapy is associated with less postprocedural pain than radiofrequency ablation in barrett’s esophagus: a multicenter prospective study. J Clin Gastroenterol. 2018. https://doi.org/10.1097/MCG.0000000000000999 This multicenter prospective study compared focal RFA with liquid nitrogen spray cryotherapy and found that RFA was associated with five times greater odds of pain immediately following the procedure as well as 48 hours postprocedure compared to cryotherapy.
- 74.• van Munster SN, et al. Focal cryoballoon versus radiofrequency ablation of dysplastic Barrett’s esophagus: impact on treatment response and postprocedural pain. Gastrointest Endosc. 2018. https://doi.org/10.1016/j.gie.2018.06.015 This multicenter cohort study looked at the efficacy as well as the degree of postprocedural pain in focal cryoballoon therapy versus RFA. This study found no difference in efficacy for treatment of short-segment BE. However, cryotherapy was associated with less reported pain as well as fewer analgesic use compared with RFA.
- 76.Pech O, Behrens A, May A, Nachbar L, Gossner L, Rabenstein T, 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;57:1200–6.CrossRefGoogle Scholar
- 82.• Visrodia K, et al. Cryotherapy for persistent Barrett’s esophagus after radiofrequency ablation: a systematic review and meta-analysis. Gastrointest Endosc. 2018;87:1396–1404.e1 This meta-analysis of 11 studies and 148 patients looked at the efficacy of cryoablation as salvage therapy in patients with persistent BE despite prior initial RFA treatment. The study found that cryotherapy successfully achieved CE-D and CE-IM (76% and 46% respectively) in this patient population.CrossRefGoogle Scholar
- 84.•• Komanduri S, et al. recurrence of Barrett’s esophagus is rare following endoscopic eradication therapy coupled with effective reflux control. Am J Gastroenterol. 2017;112:556–66 This 2017 study found that concurrent use of PPI with RFA was associated with a lower number of required RFA sessions to achieve CE-IM as well as lower disease recurrence rates following eradiation therapy.CrossRefGoogle Scholar
- 85.• Krishnan K, et al. Increased risk for persistent intestinal metaplasia in patients with Barrett’s esophagus and uncontrolled reflux exposure before radiofrequency ablation. Gastroenterology. 2012;143:576–81 This study demonstrated that ongoing mild reflux despite twice a day PPI therapy before initiation of RFA was associated with persistent IM after BE ablation. The study also showed an association between the size of the hiatal hernia and length of BE with persistent IM after RFA.CrossRefGoogle Scholar