Barrett’s esophagus in 2016: From pathophysiology to treatment

Table 1 Comparison of endoscopic surveillance recommendations for Barrett’s esophagus in currently available guidelines

Guidelines	NDBE	IND	LGD	HDG
BOB CAT[90]	Not recommended1	≤ 12 mo	6-12 mo	Not recommended
ACPG[57]	< 3 cm 3-5 yr	≤ 6 mo	6 mo	Not recommended
	≥ 3 cm 2-3 yr
BSG[58]	< 3 cm 3-5 yr	≤ 6 mo	6 mo	Not recommended
	≥ 3 cm 2-3 yr
ASGE[100]	3-5 yr	No specific time frame	12 mo2	3 mo3
ACP[101]	3-5 yr	Not recommended	No specific time frame	No specific time frame
AGA[59]	3-5 yr	Not recommended	6-12 mo	3 mo3

¹If undertaken, surveillance should be directed at high-risk groups (i.e., composite risk factors including but not limited to 50 years of age or older, white race, male sex, central obesity, the length of the segment, and the symptom duration, frequency and severity), unless the life expectancy ≤ 5 yr;

²Six months to confirm LGD;

³In the absence of eradication therapy. BOB CAT: Benign Barrett’s and Cancer Taskforce; ACPG: Australian Clinical Practice Guidelines; BSG: British Society for Gastroenterology; ASGE: American Society for Gastrointestinal Endoscopy; ACP: American College of Physicians; AGA: American Gastroenterological Association; NDBE: Non-dysplastic Barrett’s esophagus; IND: Indefinite for dysplasia; LGD: Low-grade dysplasia; HGD: High-grade dysplasia.

Table 2 Recommendations for endoscopic eradication therapy in Barrett’s esophagus

Guidelines	NDBE	LGD	HGD/intramucosal EAC
ACG[118]	Not recommended	Not recommended	Endoscopic ablation or surgical esophagectomy
AGA[59]	RFA (± EMR) for select individuals at risk for progression	RFA is a therapeutic option	Endoscopic therapy with RFA, PDT or EMR EMR in BE dysplasia with a visible mucosal irregularity Before proceeding with esophagectomy, patients with HGD or intramucosal EAC should be referred for evaluation by surgical specialized centres
BAD CAT[120]	-	-	Endoscopic treatment should be preferred over endoscopic surveillance or surgery for the management of most patients with HGD/intramucosal EAC RFA is currently the best available ablation technique for the treatment of flat HGD and for the eradication of residual BE after focal EMR In the HGD endoscopic resection of all visible abnormalities, cap and snare and band ligation with resection are equally effective
ASGE (2012)[100]	Consider endoscopic ablation in select cases	Consider endoscopic resection or ablation	Consider endoscopic resection or RFA ablation. Consider EUS for local staging and lymphadenopathy Consider surgical consultation
BSG[58]	Not recommended	Not routinely recommended	Endoscopic therapy preferred over esophagectomy
ASGE (2013)[123]	-	-	EMR is indicated for nodular BE and T1a EAC and may be used for flat BE with HGD ESD can be used in similar situations but is preferred to EMR for large areas of dysplasia or T1b EAC (i.e., confined to the submucosa) Ablation techniques may be used alone or in combination with mucosal resection techniques
BOB CAT[90]	If the lesion is visible, endoscopic resection for diagnosis is then appropriate ablative therapy		-
	Not recommended	Lower risk: Intense surveillance. Higher risk: Ablative therapy with follow-up

ACG: American College of Gastroenterology; AGA: American Gastroenterology Association; BAD CAT: Barrett’s Dysplasia and Cancer Taskforce; ASGE: American Society for Gastrointestinal Endoscopy; BSG: British Society for Gastroenterology; BOB CAT: Benign Barrett’s and Cancer Taskforce; RFA: Radiofrequency ablation; EMR: Endoscopic mucosal resection; PDT: Photodynamic therapy; EUS: Endoscopic ultrasound; ESD: Endoscopic submucosal dissection; BE: Barrett’s esophagus; NDBE: Non-dysplastic Barrett’s esophagus; LGD: Low-grade dysplasia; HGD: High-grade dysplasia; EAC: Esophageal adenocarcinoma.

Table 3 Ablation therapy in Barrett’s esophagus

Ablationmodalities	Description of the technique	Outcome	Ref.
RFA	RFA uses a balloon-based circumferential array of closely spaced electrodes to deliver radiofrequency energy to the esophageal mucosa. With this technique, the mucosa is ablated to the submucosal level. A smaller, endoscope-mounted, radiofrequency catheter ablation device could be used for the focal ablation of metaplasia that could remain after treatment with the circumferential system. A follow-up endoscopy is at 3 mo when any remaining metaplasia is ablated, with a further follow-up endoscopy at 1 yr	A landmark large, multicentre, randomized trial showed that RFA can eliminate HGD, reducing the risk of EAC compared with a sham procedure. Overall, the eradication rates for HGD range from 79% to 90% and from 69% and 97% for NDBE/LGD patients RFA is safer and easier to administer, and it causes fewer major complications, particularly stricture formation, than PDT	[133,145]
APC	APC produces a flow of ionized argon plasma that generates a high-frequency monopolar current to the BE surface under direct vision	Different eradication rates for NDBE and LGD in the short term ranged from 36% to 100% for NDBE and rates of recurrence between 62% and 100% for LGD patients	[133]
PDT	PDT is based on the injection of a light sensitizing drug (e.g., porfimer sodium) into the patient and then the exposure of a portion of the esophagus to light of a specific wavelength, which would lead to dysplasia cell death. Once the photosensitizer is activated by the light, it generates oxygen free radicals that result in cytotoxicity to the mucosal cells	The eradication rates for HGD range from 77% to 100%, and those for NDBE/LGD range from 50%-100% of patients The limitations include the cost of the intravenous agent, the prolonged period (weeks) of photosensitivity following exposure, and an appreciable post-treatment stricture rate	[133]
CRY	CRY is a non-contact method of cryotherapy that involves an endoscopically directed spray of liquid nitrogen at -196 °C directly onto the Barrett’s mucosa The advantage is a lack of contact with mucosa and hence can be applied to irregularity, which would make the application of contact therapies such as RFA challenging	The rates of complete eradication are approximately 68%-97% for HGD and 57% for NDBE The current literature is inadequate to assess the ability of CRY to achieve sustained reversion of the metaplastic mucosa to normal-appearing squamous epithelium in subjects at any stage of BE. Further longitudinal studies are needed	[133,156]
MPEC	MPEC uses an endoscopic multipolar electrical probe, which is used to control gastrointestinal haemorrhage that applies electrical energy at 50 W so that all BE surfaces are treated	Complete eradication in 65%-100% of NDBE. This technique is very much operator dependent and causes dysphagia as the most common side effect	[133]

RFA: Radiofrequency ablation; APC: Argon plasma coagulation; PDT: Photodynamic therapy; CRY: Cryoablation; MPEC: Multipolar electrocoagulation; EAC: Esophageal adenocarcinoma; BE: Barrett’s esophagus; IM: Intestinal metaplasia; NDBE: Non-dysplastic Barrett’s esophagus; LGD: Low-grade dysplasia; HGD: High-grade dysplasia.