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Original article Clinical endoscopy: Editorial| Volume 92, ISSUE 3, P551-553, September 2020

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Successful endoscopic treatment of Barrett’s dysplasia is not just about the destination; it is about the journey

      Abbreviation:

      RFA (radiofrequency ablation)
      In the current edition of this journal, Lipman et al
      • Lipman G.
      • Markar S.
      • Gupta A.
      • et al.
      Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus.
      addressed 2 topics that influence outcomes for endoscopic treatment of Barrett’s neoplasia, namely, center volume and learning curve.
      Looking at complete eradication of dysplasia and intestinal metaplasia after endoscopic treatment with radiofrequency ablation (RFA), which did not show significant differences between low-volume, medium-volume, and high-volume centers, the authors conclude that their data do not support centralization of endoscopic treatment for Barrett’s dysplasia to only high-volume centers. Furthermore, the data suggest that 18 supervised cases of endoscopic ablation may be required to reach competency in endoscopic treatment of Barrett’s dysplasia.
      • Lipman G.
      • Markar S.
      • Gupta A.
      • et al.
      Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus.
      In Amsterdam, we have always been strong advocates for centralization of endoscopic treatment of Barrett’s dysplasia. Centers that treat patients with Barrett’s dysplasia and early cancer should, in our opinion, have had adequate training in endoscopic imaging, endoscopic resection, and ablation. Furthermore, these centers should have access to experts in pathology with experience in diagnosing Barrett’s dysplasia and assessing endoscopic resection specimens. Also, these centers should practice endoscopic treatment on a regular basis with at least 10 new patients per year. These recommendations are also incorporated in the guideline of the European Society of Gastrointestinal Endoscopy.
      • Weusten B.
      • Bisschops R.
      • Coron E.
      • et al.
      Endoscopic management of Barrett's esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.
      After reading the article by Lipman et al,
      • Lipman G.
      • Markar S.
      • Gupta A.
      • et al.
      Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus.
      we are concerned that the article focused only on a limited number of outcomes to assess adequacy of endoscopic treatment of Barrett’s dysplasia. Furthermore, we question whether the methods and data that were used will lead to recommendations that can be put into clinical practice.
      The guidelines from the European Society of Gastrointestinal Endoscopy and the British Society of Gastroenterology
      • Fitzgerald R.C.
      • di Pietro M.
      • Ragunath K.
      • et al.
      British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.
      advise a minimum of 30 supervised cases of endoscopic resection and 30 cases of endoscopic ablation for an endoscopist to acquire competence in technical skills, management pathways, and adverse events. Although there is some evidence for this recommendation for endoscopic resection,
      • Haidry R.J.
      • Lipman G.
      • Banks M.R.
      • et al.
      Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry.
      ,
      • Van Vilsteren F.G.I.
      • Pouw R.E.
      • Herrero L.
      • et al.
      Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications even within a structured training program.
      evidence for RFA is lacking. Therefore, the aim of the authors to establish the learning curve for endoscopic eradication therapy with RFA was interesting. However, we doubt whether the analyses that were performed could indeed answer this question.
      Treatment of patients with Barrett’s dysplasia is a multistep process, which starts with endoscopic imaging. Endoscopic detection of Barrett’s-related neoplasia is challenging and requires proper training.
      • Bergman J.J.G.H.M.
      • de Groof A.J.
      • Pech O.
      • et al.
      An interactive web-based educational tool improves detection and delineation of Barrett’s esophagus-related neoplasia.
      Any lesion that is suspected of harboring cancer should be recognized and removed by endoscopic resection. A missed cancer that is inadvertently treated with RFA may lead to incomplete treatment, resulting in progression that remains undetected during the treatment course, or to recurrent cancer if cancer cells are buried beneath neosquamous epithelium. This occurrence may place the patient outside the window of opportunity for curative endoscopic treatment.
      The second step is then to endoscopically resect any suggestive lesions, which should be done safely and radically. If a lesion is not completely resected and residual cancer is left in situ and treated with RFA at a later stage, again, this may lead to inadequate treatment and may result in recurrence at a later stage. Furthermore, histologic assessment of resection specimens to assess the presence of poor prognostic histologic risk factors, such as lymphovascular invasion, deep submucosal invasion, and poor differentiation of nonradical resection at the deep resection margin, is of the utmost importance to distinguish patients who are eligible for curative endoscopic management from who that require esophagectomy.
      • Van der Wel M.H.
      • Jansen M.
      • Vieth M.
      • et al.
      What makes an expert Barrett’s histopathologist?.
      Only after meticulous imaging and, if necessary, endoscopic resection, as was the case in 53% of patients in this study, can RFA be performed to eradicate all Barrett’s mucosa. In this whole process, RFA is technically the least challenging part. Therefore, looking at eradication rates for intestinal metaplasia and dysplasia, and basing the conclusion on the need for centralization of endoscopic treatment of Barrett’s neoplasia on only this parameter, we may miss other key outcomes relevant to good clinical care.
      Endpoints that might give more insight into actual RFA learning curves could be the proportion of Barrett’s adequately ablated during a single RFA treatment, the Barrett’s esophagus surface regression after a single RFA, and adverse events such as bleeding and perforation, although the latter 2 are very uncommon.
      Another concern with the outcomes of the risk-adjusted cumulative sum control plots that found a significant change-point for outcomes at 12 cases for eradication of dysplasia and 18 cases for eradication of intestinal metaplasia, is the fact that these data were only available per center, not per endoscopist. As the authors address in their discussion, for practical application, a minimum number of cases one should perform with supervision should be based on data that reflect the learning curve of an endoscopist, not of a center. Furthermore, an important source of bias influencing the outcomes and learning curves in this study is the likelihood that the endoscopists at the 24 participating centers had different levels of experience at the start of the United Kingdom RFA Registry.
      • Haidry R.J.
      • Butt M.
      • Dunn J.M.
      • et al.
      Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett’s oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.
      Furthermore, as the authors point out, operators in the medium-volume and high-volume centers may have been trainees.
      We are not informed about the level of proficiency in endoscopic imaging and treatment of Barrett’s dysplasia at baseline, nor do we know whether all endoscopists had the same level of training in RFA before they started treating patients, or whether they had any supervision during their first cases. Endoscopists who participated in one of the available structured endoscopic resection and RFA training programs with theoretic lectures, hands-on training in animal models, and supervised cases in patients will logically have a different learning curve than endoscopists who did not receive such dedicated training.
      As mentioned before, current guidelines define expert centers as centers with a minimum of 10 new Barrett’s dysplasia cases per year.
      • Weusten B.
      • Bisschops R.
      • Coron E.
      • et al.
      Endoscopic management of Barrett's esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.
      ,
      • Fitzgerald R.C.
      • di Pietro M.
      • Ragunath K.
      • et al.
      British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.
      In their study, the authors looked at the impact of center caseload on patient outcomes.
      • Lipman G.
      • Markar S.
      • Gupta A.
      • et al.
      Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus.
      For this, they compared rates of complete eradication of intestinal metaplasia and dysplasia at 12 months after treatment, in low-volume, medium-volume, and high-volume centers. There was no significant difference in rates of eradication at 12 months among the centers, but there were lower recurrence rates in high-volume than in low-volume centers. On the basis of these findings, the authors conclude that their data do not support further centralization of endoscopic treatment for Barrett’s dysplasia to only high-volume centers. However, the effects of centralization of care cannot, in our opinion, be assessed in this analysis, which did not adjust for potential confounding effects.
      As we mentioned before, ablation of subtle lesions that should have been removed by endoscopic resection, or incomplete endoscopic resection, can lead to recurrence of neoplasia during follow-up. Therefore, more information on these recurrent cases that were found in low-volume centers would have been interesting, to assess whether these patients could still be curatively treated endoscopically. Paying attention only to the successful eradication of dysplasia and intestinal metaplasia at 12 months would likely miss relevant neoplasia that recurs during follow-up.
      Centers were divided into low-volume (<50 cases), medium-volume (50–100 cases), and high-volume (>100 cases). This division unfortunately does not give us any information on how many cases are treated at each center yearly, nor does it allow easy comparison with other centers with a certain yearly caseload. Furthermore, a source of selection bias to the detriment of high-volume centers is the fact that these centers, being more experienced, probably treated more “difficult” patients. Different studies have demonstrated that response to RFA treatment and risk of recurrence are likely less favorable in patients with multifocal dysplasia, esophagitis, narrowed esophagus, and long Barrett’s segment.
      • van Vilsteren F.G.
      • Alvarez Herrero L.
      • Pouw R.E.
      • et al.
      Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett's esophagus with early neoplasia: a prospective multicenter study.
      ,
      • Tan M.C.
      • Kanthasamy K.A.
      • Yeh A.G.
      • et al.
      Factors associated with recurrence of Barrett's esophagus after radiofrequency ablation.
      Although the baseline characteristics as shown in Table 2 of Lipman et al
      • Lipman G.
      • Markar S.
      • Gupta A.
      • et al.
      Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus.
      do not significantly differ among the low-volume, medium- volume, and high-volume centers, we cannot exclude that the medium-volume and high-volume centers treated more patients with multifocal dysplasia, more widespread endoscopic resection, severe reflux disease, and also longer Barrett’s segments because the table does not provide any (interquartile) ranges.
      Although the authors conclude that their data do not support further centralization of services to high-volume centers, we believe that the outcomes of the study are subject to bias and that looking at eradication of intestinal metaplasia and dysplasia at 12 months is not sufficient to enable strong conclusions to be drawn. This endpoint is reached by way of a journey including imaging, endoscopic resection, and adequate histologic assessment. Any inadequate treatment of neoplastic lesions missed during imaging, or lesions that were incompletely resected, can lead to recurrences after 12 months. Centralization of care should not be interpreted as concentration in high-volume centers but as treatment performed in high-quality centers. Besides a minimum annual case load, this includes treatment by 1 to 2 dedicated endoscopists after sufficient training in endoscopic imaging, endoscopic resection, and ablation, and a pathologist with sufficient experience in the diagnosis of Barrett’s esophagus neoplasia.

      Disclosure

      Dr Bergman is a consultant for, and the recipient of financial support for research from, Covidien/Medtronic, Cook Medical, and Boston Scientific, and the recipient of financal support for research from Olympus Endoscopy, Erbe Medical, C2 Therapeutic, and Ninepoint Medical. The other authors disclosed no financial relationships.

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