Our search aimed to update the current data on to the diagnosis, therapy, and follow-up of patients with GERD and BE.
Diagnosis of BE
The diagnosis of BE is established by histopathology of endoscopic biopsies obtained from the esophagus and esophagogastric junction (EGJ), using the novel Chandrasoma classification [
1]: The normal lining of the esophagus and the proximal stomach are stratified squamous and oxyntic mucosa, respectively [
1]. Owing to the failure of the antireflux mechanism within the lower end of the esophagus, reflux occurs and stimulates the metaplasia of the squamous lined mucosa [
1,
2]. Thereafter, the columnar lined esophagus (CLE) develops and is interposed between the squamous lining of the esophagus and the oxyntic mucosa of the proximal stomach, i. e., this condition is termed the squamo-oxyntic gap (SOG) and represents the morphologic proof of GERD [
1].
According to the Chandrasoma classification, CLE includes cardiac mucosa (CM: mucus-cell-only epithelium), oxyntocardiac mucosa (OCM: mixture of mucus and parietal cells within the subfoveolar region of the glands), nondysplastic BE (cardiac mucosa with goblet cells; intestinal metaplasia: IM), LGD, HGD, and cancer ([
1,
3]; Fig.
2). Over time, further dysfunction of the antireflux mechanism aggravates the reflux and increases the length of the CLE, i. e., the length of the SOG. BE affects 20–30% of individuals with symptoms of GERD [
2]. The diagnosis of LGD, HGD, and early cancer should be confirmed by an expert pathologist (second opinion; [
4,
5]).
Management of dysplastic BE
The interdisciplinary expert panel meeting recommended RFA ± ER for T1a cancer, HGD, and LGD [
3]. An accurate baseline diagnosis is of profound importance for the disease management [
3]. Recent studies have confirmed these recommendations.
Duits et al. [
4] retrospectively examined the effect of RFA for elimination of BE with LGD in 255 patients after 42 months (range: 25–61; 3–5 years of follow-up; SURF trial data). During the follow-up, 18% of the patients (45/255) progressed to esophageal cancer.
The study showed the vital importance of accurate baseline histopathology for the assessment of risk for disease progression after the RFA therapy. As such, the odds for progression increased 8–13-fold, and 22–38-fold, when baseline LGD (prior to RFA) was assessed by each of the pathologists or reconfirmed by all of them, respectively [
4].
Guthikonda et al. [
6] conducted a retrospective analysis of 306 patients who underwent RFA for the elimination of dysplastic BE between March 2006 and June 2015. At the first follow-up endoscopy (<1 year) after RFA elimination, BE and dysplasia were assessed in 85 and 88.9% of cases, respectively. In all, 218 patients continued with follow-up to assess disease recurrence. During a mean time to recurrence of 1.88 years, 24% (
n = 52) of the patients developed recurrence of IM, this translates to an incidence of 9.6% per year for IM after RFA. Recurrences were assessed in biopsy samples obtained from the esophagus, cardia, and both in 63%, 33%, and 4% of cases, respectively. Following repeated RFA, 58% (
n = 30) of those with recurrence were free from IM. Those positive for IM were enrolled in additional follow-up RFAs. During the study, four patients developed cancer. Risk factors for progression and development of cancer included baseline HGD and longer CLE segments.
Cameron et al. [
7] retrospectively examined the recurrence rate following one to six RFA ± endoscopic mucosa resection (EMR) sessions in 137 individuals for the treatment of BE low- (25%), high-grade (54%), and intramucosal adenocarcinoma (21%; AIM dysplasia trial). Elimination of dysplasia and intestinal metaplasia was achieved in 88%, 92%, 100%, and in 69%, 74%, and 81% of patients after 1, 2, and 3 years, respectively. Thus, Kaplan–Meier estimates were 58%, 88%, and 95% and 41%, 72%, and 82% for dysplastic and nondysplastic BE after 1, 2, and 3 years, respectively. Dysplasia (HGD or LGD) was the most advanced stage of recurrence, and none of the patients progressed to or developed cancer. In all, 80% of the recurrences were assessed in biopsy samples obtained from the EGJ [
7].
A recent meta-analysis examined the efficacy of RFA ±EMR for the management of dysplastic and nondysplastic BE.
Luigiano et al. [
8] confirmed that 1–3 years after RFA dysplastic and nondysplastic BE were eliminated in 60–100% and 60–90% of the cases, respectively. Furthermore, RFA was demonstrated to be superior to surveillance for the management of LGD. The cumulative 3‑year risk of LGD to progress to HGD and cancer was 33% and 2.9% in the RFA ± EMR treatment group vs. surveillance, respectively [
8].
Following RFA ± EMR, the reported elimination rates for HGD and IM were 70–100% and 60–96%, respectively [
8].
In their meta-analysis, Fujii-Lau et al. [
9] included 39 out of 3311 studies and examined the rate of recurrence of IM and dysplasia after RFA ± EMR for the management of nondysplastic and dysplastic BE or early intramucosal cancer. The authors also compared the efficacy of RFA ± EMR (RFA) vs. stepwise endoscopic treatment (SRER) for the management of dysplastic BE.
The pooled incidence for any recurrence, recurrence of IM, and dysplasia was 7.5/100 patient years (PY), 4.8/100 PY, and 2.0/100 PY, respectively. The recurrence rate differed between those who underwent SRER vs. RFA ± EMR. The overall recurrence rate and the IM recurrence rate were increased after RFA ± EMR vs. stepwise treatment: 8.6/100 PY vs. 4.9/100 PY and 5.8/100 PY vs. 3.3/100 PY for stepwise vs. RFA ± EMR treatment, respectively [
9].
The authors could not find a uniform typical risk profile for recurrent disease that was shared by all studies. However, factors fostering recurrence of BE after endoscopic treatment include esophagitis, presence of hiatal hernia and increased hernia size, CLE length, number of treatment sessions required to achieve IM-negative CLE, age, non-Caucasian background, smoking, decreased body mass index (25.3 vs. 29.8 for recurrence vs. no recurrence, respectively), and residual acidic reflux [
9].
In their meta-analysis, Qumseya et al. [
10] compared the efficacy of RFA vs. surveillance to prevent progression to HGD and cancer in patients with LGD BE. The final analysis included 19 out of 2029 cited studies. Calculations with fixed-effects models showed that RFA caused an 86% reduction in the risk of progression, when compared with surveillance. Including the data of 2746 patients, the random-effects models showed that the cumulative progression rate was 12.6% vs. 1.7% for surveillance vs. RFA, respectively. Finally, the number of RFAs required to prevent one case of HGD or cancer was 9.2; thus, fewer than ten RFAs prevents one case of HGD or cancer in patients with LGD. Therefore, the data of the study by Qumseya et al. [
10] reconfirm the recommendation of the recent expert panel meeting [
3].
Antireflux surgery for BE
The role of antireflux surgery and dietary aspects for the management of GERD and BE remains to be examined.
Conceptually, BE results from the impaired function or loss of function of the antireflux mechanism within the lower end of the esophagus. As a consequence, reflux occurs and fosters the development of GERD and BE [
1]. Thus, it seems justified to consider the impact of treating the cause of the disease, e. g., repair of the antireflux mechanism (i. e., lower esophageal sphincter, diastasis of the musculature of the cura of the diaphragm, and formation of hiatal hernia). Medical therapy alters the acidity of the reflux, but does not alter the amount of reflux per se [
11‐
13]. By contrast, Knight et al. [
11] and Skrobic et al. [
12] demonstrated that functional, effective antireflux surgery fosters the regression of BE and improves the efficacy of RFA in BE segments >4.0 cm [
11,
12]. Thus, the recent data support antireflux surgery for symptomatic GERD and BE before, during, or after RFA [
3,
13]. Esophageal manometry and reflux monitoring are recommended for an accurate diagnosis [
2,
3,
11,
12].
Recent data showed that regular consumption of food and beverages rich in sugars and sweeteners positively correlates with obesity and GERD [
14,
15]. New data published in 2017 extended this notion to BE and cancer. Li et al. found a positive correlation between a sugar-rich diet and the development of BE [
16] and cancer [
17]. Sugar-rich nutrition increased the incidence of BE and cancer by 70–79% [
16] and 51–58% [
17], respectively. Thus, nutrition seems to be of relevance in the development of GERD, BE, and cancer [
14‐
17].