Esophagectomy or endoscopic eradication therapy, either using endoscopic resection or radiofrequency ablation, cryoablation, or a combination of resection and ablation, aims not only to completely eliminate Barrett’s esophagus (BE) dysplasia and early neoplasia but also a complete eradication of intestinal metaplasia (CEIM). We review the existing evidence and propose management strategies that would be applicable to the everyday care of patients with BE after they have received endoscopic or surgical eradication. CEIM is a key initial outcome that requires, at present, validation by endoscopic and histologic assessments. Because of the possibilities for biopsy sampling errors and persistence of buried metaplasia, patients receiving endoscopic therapy or esophagectomy for dysplastic BE should be kept in surveillance until definitive long-term, prospective data become available.
KeywordsBarrett’s esophagus, dysplasia, endoscopic eradication therapy, esophagectomy, GERD, ablation, resection
Endoscopic eradication therapy (EET), either using endoscopic resection (ER) or radiofrequency ablation (RFA), cryoablation, or a combination of resection and ablation, aims not only to completely eliminate Barrett’s esophagus (BE) dysplasia and early neoplasia but also a complete eradication of intestinal metaplasia (CEIM) . EET is mostly applied in patients with high-grade dysplasia (HGD) and intramucosal cancer (IMC) and increasingly in patients with BE and low-grade dysplasia (LGD). In general, a successful EET is based on the ability to accurately diagnose the disease burden and extent, remove the responsible endoscopically recognizable lesion or lesions, successfully treat surrounding BE epithelium, and effectively survey for recurrent intestinal metaplasia (IM), dysplasia, or malignancy after the initial effective therapy.
Most studies on EET of BE with advanced histopathology have shown a real, albeit small, risk of cancer progression. In a recent US multicenter study, 2- and 3-year follow-ups found that 5 of 119 patients (4.2%) progressed with two patients progressing to cancer. In this study, the rate of esophageal adenocarcinoma (EAC) was 1 per 181 patient-years (0.55% per patient-years) with no cancer-related morbidity or mortality, while the annual rate of any neoplastic progression was 1 per 73 patient-years (1.37% per patient-years). Therefore, lifelong intensive surveillance is mandatory in patients treated with EET, but the exact surveillance intervals have not been well established . Hence, although EET reduces the risk of progression to invasive cancer, it does not completely eliminate it. Broad and detailed discussion of all available alternative therapies, including esophagectomy, as well as a commitment to lifelong treatment of gastroesophageal acid reflux disease (GERD) and endoscopic surveillance are essential and they are best managed in multidisciplinary and experienced referral centers.
In a similar fashion, esophagectomy aims at complete removal of early neoplasia and the entire BE length. The premise of these approaches is the complete elimination of the risk of EAC occurrence and mortality during the lifetime of the patient ( Fig. 15.1 ). Several studies suggest an enhanced patient survival if early esophageal neoplasia is detected by endoscopic surveillance as compared with symptomatic detection. However, the rates and predictors of BE recurrence after CEIM have not been well defined.
The purpose of this chapter is to review the existing evidence and propose management strategies that would be applicable to the everyday care of patients with BE after they have received endoscopic or surgical eradication. It is important to note that CEIM is a key initial outcome that requires, at present, validation by endoscopic and histologic assessments ( Fig. 15.2 ). Advanced imaging methods, such as narrow band imaging (NBI; Olympus), Fuji intelligent color enhancement (FICE), or i-scan (Pentax), confocal laser endomicroscopy, endocytoscopy, and optical coherence tomography (OCT), are increasingly utilized in the assessment of patients with BE and they are poised to be the methods of choice in the determination of CEIM .
A key issue is the durability of the treatment effect and the longer term outcomes of therapy. Because durability of treatment effect is a determinant of the cost effectiveness of the intervention and because subjects with recurrent BE after EET are at continued risk for developing EAC, it is vital to know whether the neo-squamous epithelium present after EET is durable. Hence, the posttreatment surveillance and the risk for recurrence of BE and EAC after EET or surgery start with the determination of CEIM, usually 3 months postintervention. In the context of this posttreatment endoscopy, it is important not only to carefully assess the neo-squamous epithelium by white light and advanced imaging, but also to obtain careful random and directed biopsies to evaluate for overt or buried metaplasia or dysplasia . Compared to conventional random biopsies, the use of Wide Area Transepithelial Sampling with 3D computer-assisted analysis (WATS-3D) promises to enhance the yield for intestinal metaplasia and dysplasia by up to 60% . In addition, acid suppressive therapy, using proton pump inhibitors (PPIs) and preferably adjusted using ambulatory pH monitoring, is mandatory. Alternatively, antireflux surgery may be required to control esophageal pH and symptoms of GERD, if any.
Surveillance and Risk for Recurrence After Ablation
Recent evidence supports the use of RFA as an effective and safe therapeutic modality for patients with dysplastic BE, but in all prospective cohort studies, repeated RFA treatments were needed during follow-up surveillance ( Fig. 15.3 ).
The US RFA registry is a nationwide registry of BE patients who have been receiving RFA and was aimed to determine rates and factors that would predict recurrence of IM. In a recent study of that cohort, 85% of patients achieved CEIM. After an average of 2.4 years, IM recurred in 20% and was nondysplastic or indefinite for dysplasia in 86%. The average length of recurrent BE was 0.6 cm. They also noted that the yearly recurrence rate was worse with higher pretreatment histology, increasing age, BE length, and non-Caucasian race .
Another single-center retrospective study evaluated the recurrence and progression rates of patients who had completed RFA for dysplastic BE or intramucosal carcinoma (IMC). The cohort consisted of 231 patients who had achieved CEIM and underwent subsequent surveillance for a median observation time of 397 days. BE recurred at a rate of 5.2% per year, while disease progression occurred in 1.9% per year. The authors found no clinical characteristics to be associated with disease recurrence . These studies suggest that patients who are undergoing RFA for dysplastic BE should be retained in endoscopic surveillance after CEIM ( Fig. 15.4 ).
Cryoablation is another endoscopic technique that applies cold nitrogen or carbon dioxide gas to freeze the BE surface. In a retrospective, nonrandomized study of 60 patients with dysplastic BE, 97% had complete eradication of HGD, 87% had complete eradication of all dysplasia, and 57% had CEIM. Buried metaplasia was found in 3%. However, the study had short follow-up of 10.5 months . In another smaller study, 32 patients with BE and HGD were treated with cryoablation. At 2 years of follow-up, 100% had complete eradication of HGD and 84% had CEIM. HGD recurred in 19%; those patients were treated with repeat cryotherapy or argon plasma coagulation and were HGD free on follow-up ranging 24–57 months. One patient progressed to adenocarcinoma, but after cryotherapy downgraded to HGD .