Does radiofrequency ablation affect endoscopic submucosal dissection in Barrett’s esophagus?

Endoscopic submucosal dissection (ESD) has become the salvage treatment of choice after the failure of ablation therapies because it can completely remove the remaining neoplastic tissue and provide tissue for examination for hidden malignancy. Although resection prior to ablative therapy is currently the standard of care for Barrett’s esophagus (BE) neoplasia, as suggested by recent guidelines, the use of ESD after ablation has not been well described [1]. Risk factors for complications of ESD are known to include prior injury to the mucosa, and common clinical practice in Japan has been to avoid biopsy prior to ESD for squamous dysplasia. It makes sense to investigate the past use of radiofrequency ablation (RFA) as a potential risk factor for ESD of BE.

“Knowledge of the degree of submucosal fibrosis prior to ESD could lead to the use of alternative therapies if this could be determined by noninvasive methods.”

In the study by Mesureur et al. [2] published in this issue of Endoscopy, the uncommon need for ESD after ablation is illustrated by the small number (n = 56) of patients collected from 16 referral centers over a period of 8 years. This represented less than 2% of the patients treated for BE from 15 of the centers, which is far less than the 23% of patients who have residual intestinal mucosal after RFA as established in a randomized trial [3]. Most patients respond to additional ablative therapy, which is the clinical practice unless endoscopically apparent lesions are observed. This study enrolled patients who clearly could be anticipated to have residual neoplastic tissue after RFA, with 77% having received a mucosal resection prior to RFA and 27 (48%) having had a prior diagnosis of esophageal adenocarcinoma.

Nonetheless, this is an important clinical problem for most endoscopists as this residual BE is felt to represent an increased risk of neoplastic progression despite often lacking evidence of dysplasia on histology. In fact, it appears that factors that increase the risk of progression to cancer are similar to those that predict resistance to ablation therapy [4], namely, age, residual BE after ablation, and histological evidence of cancer prior to ablation. These residual areas of BE contain genomic evidence of neoplastic transformation and likely require excision if ablative therapies have been unsuccessful.

Much of our information regarding the safety and efficacy of ESD comes from Asia, where resection is the primary therapy and ablation is not commonly performed for dysplastic squamous tissue. This limits the ability to translate this large experience with esophageal ESD into Western practice. Mesureur et al. investigated the effect of RFA in this BE cohort and found that there were more complications (one muscular tear and seven strictures) after ablation but there was still a high rate (89% en bloc resection) of successful completion [2]. The investigators also included patients who had other fibrosis-producing therapies during treatment, including argon plasma coagulation and endoscopic mucosal resection, which can often provoke significantly greater fibrosis than RFA. However, ablative procedures such as RFA do not usually produce significant fibrosis by themselves and some, such as cryotherapy, may produce less as judged by rates of esophageal stricture. Spray cryotherapy has also been found to be effective in treating BE, with a stricture rate of only 3% in a retrospective cohort study [5].

Mesureur et al. have nicely shown that a history of RFA does not appear to affect the ability to perform a successful ESD in patients with BE. However, an important question remains about patients who undergo RFA and develop submucosal fibrosis: are they at increased risk of complications and poor outcomes from ESD? Studies from Japan have classified the degree of submucosal fibrosis as F0–F2, F0 being no fibrosis, F1 moderate fibrosis, and F2 extensive fibrosis. It has been shown that F2 fibrosis is associated with more complications such as perforation and bleeding, as well as incomplete or failed ESD, in multiple areas of the gastrointestinal tract [6] [7] [8]. It will be important to determine whether ablation-induced fibrosis (both mild and extensive) leads to worse outcomes of ESD for BE. In addition, it would be valuable to know whether the forms of ablative therapy produce different rates of submucosal fibrosis or whether this is simply the result of more aggressive ablation in terms of quantity of energy applied or number of applications. It has become common practice to use the higher energy settings and increase the number of applications in areas of BE that remain after initial RFA.

These questions may be more difficult to answer given the small number of patients who actually require ESD, which would currently be the only method available to assess submucosal fibrosis, although other forms of esophageal testing such as compliance balloons (Endoflip; Medtronic, Minneapolis, Minnesota, USA) might be useful in assessing distensibility as a surrogate marker of submucosal fibrosis or utilizing high resolution cross-sectional imaging with optical coherence tomography for direct observation of the fibrosis. Knowledge of the degree of submucosal fibrosis prior to ESD could lead to the use of alternative therapies if this could be determined by noninvasive methods.

The ability to predict ease of ESD will become more important in the future as third space endoscopy continues to be disseminated into widespread clinical use and is no longer concentrated in tertiary referral centers. The significant rate of complications found in the Mesureur et al. study (14%) will undoubtedly be higher in practices with less expertise in ESD compared with these experts [2]. Clearly there is a substantial learning curve with ESD and being able to exclude patients with more difficult lesions would be quite valuable for many endoscopists and provide better direction for shared decision making with the patient. This study suggests that a history of RFA should not preclude the ability to resect BE. However, the question of whether RFA can produce substantial submucosal fibrosis in some cases and whether this finding influences outcomes of ESD in BE will need to be answered.

Publication History

Article published online:
17 July 2024

• References

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