New data on an old weapon: is argon plasma coagulation adequate treatment for dysplastic Barrett’s esophagus?Referring to Wronska E et al. p. 123–132
Endoscopic eradication therapy in Barrett’s esophagus (BE) has come full circle. Early proof of principle studies utilized heater probes and multipolar electrocoagulation demonstrated that destruction of the epithelium, combined with rigorous acid suppression, resulted in the repopulation of the treated area with squamous epithelium that appeared histologically indistinguishable from native squamous epithelium . While this phenomenon was widely recognized, endoscopic treatment of BE in this manner was tedious, especially for long Barrett’s segments, and was largely confined to tertiary care centers with a special interest in the disease. The development of photodynamic therapy did little to increase the popularity of endoscopic therapy for BE, as special lasers were required and expensive photosensitizing agents had to be administered in order to achieve results, which were often underwhelming .
The advent of radiofrequency ablation (RFA) broadened the availability of endoscopic eradication therapy for BE  . The devices are relatively easy to use, the power generator is small, and the technique is effective in inducing complete eradication of intestinal metaplasia in the vast majority of treated patients in most studies. But the catheters are expensive, and the use of the equipment is largely dedicated to BE, with less versatility than some other thermal methods.
“…I do believe that APC represents a reasonable choice as primary therapy for endoscopic eradication therapy of dysplastic BE, especially in experienced hands, and in settings where resource availability is such that RFA is not economically feasible.”
On this background, in this issue of Endoscopy, Wronska et al. present the results of their randomized controlled trial of a well-established technology, argon plasma coagulation (APC), for the treatment of BE with low-grade dysplasia . This remarkable single-center study randomized patients with BE and low-grade dysplasia to one of three arms: 1) high-energy APC (90 W)/high-dose proton pump inhibitor (PPI; 120 mg omeprazole daily); 2) high-energy APC/low-dose PPI (40 mg omeprazole daily); or 3) low-energy APC (60 W)/high-dose PPI. These three arms allowed the investigators to independently assess the impact of both the energy used in APC, as well as the PPI dose during treatment. A tribute to persistence, this study enrolled patients over 12 years (!), and followed them after ablation for a median of 9 years. In addition to this long follow-up, other strengths of the study include its low loss to follow-up (6 %), expert pathological review, and a rigorous blinding regimen. Weaknesses include the lack of a standardized treatment schedule (many patients in the study received a single treatment), and the lack of a stated systematic biopsy protocol. The latter is especially important when assessing the impact of energy settings in APC, since incompletely treated dysplastic BE might result in subsquamous dysplastic tissue, which is not visible endoscopically, and can only be detected through a rigorous systematic biopsy protocol .
The results of this trial are, in some respects, reassuring. Neither PPI dosage nor APC energy setting seemed to impact the efficacy of the treatment. Perhaps unsurprisingly, post-procedural chest pain was more common in those treated with higher energy APC. Otherwise, no differences were noted between the arms. The treatment appeared effective, in that no patient in the trial progressed to high-grade dysplasia or esophageal adenocarcinoma, and 93 % of the patients at the end of follow-up of the trial had no BE.
As we enter the second decade of broadly available endoscopic eradication therapy for dysplastic BE, many questions remain unresolved. Despite a proliferation of new tools and techniques for eradication, there is a paucity of head-to-head comparisons of ablation modalities. Therefore, the simple question of which ablative technique is best remains unanswered. Similarly, while we believe that rigorous acid suppression during and after ablation is key to success, we do not know how much is enough. This question has gained special relevance with the increased focus on putative PPI side effects – many patients wish to be on the lowest effective dose of these medications, and this dose remains to be defined .
The results of this trial join a heterogeneous literature on the use of APC for endoscopic eradication therapy. Some trials suggest modest efficacy and/or higher recurrence rates    , while other studies suggest efficacy similar to that of RFA  . APC has other appealing features, such as broad availability, utility for multiple different disease states, and lower costs when compared with some rival technologies.
So how should we think about positioning APC in our armamentarium for BE endoscopic eradication therapy? The problem with “point-and-shoot” technologies such as APC and spray cryotherapy is that they do not guarantee even distribution of energy over the entirety of the Barrett’s mucosa. With any such technology, for a single application, there will be a “ground zero,” which gets the highest density of energy, and decreasing energy effect as you move away from that ground zero location. Overtreating ground zero might induce transmural necrosis, pleural effusions, and even perforation. Undertreatment, conversely, risks incomplete eradication of intestinal metaplasia. The skill of the endoscopist in “painting” the area to be treated decides the degree to which the energy is spread, and this skill is variable. Even in patients with apparent complete eradication of intestinal metaplasia, the specter of residual subsquamous disease exists. For this reason, in general, I think “point-and-shoot” technologies are most effective for patients with a small burden of BE disease, and/or widely scattered islands. In such cases, the mandate to assure uniform distribution over the surface area is less demanding on the endoscopist – “ground zero” is often large enough to encompass the area to be treated. Practically, I often use APC as a secondary therapy in a multimodality approach, after I have applied RFA, and am faced in the subsequent endoscopy with scattered islands or small tongues of residual columnar tissue. In that setting, APC is both an effective and cost-effective approach to allow the patient to achieve complete eradication of intestinal metaplasia.
However, I do believe that APC represents a reasonable choice as primary therapy for endoscopic eradication therapy of dysplastic BE, especially in experienced hands, and in settings where resource availability is such that RFA is not economically feasible. It is likely that technological advancements in APC will facilitate the safe treatment of larger areas of BE with more even energy distribution  , to allow uniform eradication of disease without overtreatment. If so, APC may become as attractive or more attractive than RFA as a primary therapy for endoscopic eradication therapy in BE.
30 July 2020 (online)
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- 1 Sampliner RE, Fennerty B, Garewal HS. Reversal of Barrett’s esophagus with acid suppression and multipolar electrocoagulation: preliminary results. Gastrointest Endosc 1996; 44: 532-535
- 2 Overholt BF, Lightdale CJ, Wang K. et al. International, multicenter, partially blinded, randomised study of the efficacy of photodynamic therapy (PDT) using porfimer sodium (POR) for the ablation of high-grade dysplasia (HGD) in Barrett’s esophagus (BE): results of a 24 month follow-up. Gastroenterology 2003; 124 (Suppl. 01) A20 DOI: 10.1016/S0016-5085(03)80098-7.
- 3 Ganz RA, Overholt BF, Sharma VK. et al. Circumferential ablation of Barrett’s esophagus that contains high-grade dysplasia: a U.S. multicenter registry. Gastrointest Endosc 2008; 68: 35-40
- 4 Shaheen NJ, Sharma P, Overholt BF. et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360: 2277-2288
- 5 Wronska E, Polkowski M, Orlowska J. et al. Argon plasma coagulation for Barrett’s esophagus with low-grade dysplasia: a randomized trial with long-term follow-up on the impact of power setting and proton pump inhibitor dose. Endoscopy 2021; 123-132
- 6 Mashimo H. Subsquamous intestinal metaplasia after ablation of Barrett’s esophagus: frequency and importance. Curr Opin Gastroenterol 2013; 29: 454-459
- 7 Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology 2017; 153: 35-48
- 8 Sie C, Bright T, Schoeman M. et al. Argon plasma coagulation ablation versus endoscopic surveillance of Barrett’s esophagus: late outcomes from two randomized trials. Endoscopy 2013; 45: 859-865
- 9 Sharma P, Wani S, Weston AP. et al. A randomised controlled trial of ablation of Barrett’s oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results. Gut 2006; 55: 1233-1239
- 10 Dulai GS, Jensen DM, Cortina G. et al. Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett’s esophagus. Gastrointest Endosc 2005; 61: 232-240
- 11 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
- 12 Schulz H, Miehlke S, Antos D. et al. Ablation of Barrett’s epithelium by endoscopic argon plasma coagulation in combination with high-dose omeprazole. Gastrointest Endosc 2000; 51: 659-663
- 13 Peerally MF, Bhandari P, Ragunath K. et al. Radiofrequency ablation compared with argon plasma coagulation after endoscopic resection of high-grade dysplasia or stage T1 adenocarcinoma in Barrett’s esophagus: a randomized pilot study (BRIDE). Gastrointest Endosc 2019; 89: 680-689
- 14 Estifan E, Cavanagh Y, Grossman MA. Hybrid argon plasma coagulation for treatment of gastric intestinal metaplasia. Cureus 2020; 12: e7427
- 15 Manner H, May A, Kouti I. et al. Efficacy and safety of hybrid-APC for the ablation of Barrett’s esophagus. Surg Endosc 2016; 30: 1364-1370