Barrett’s esophagus (BE) is more common in developed countries. Endoscopic therapy is an effective treatment method in management of dysplastic BE. Ablation by thermal energy, freezing, or photochemical injury completely eradicates dysplasia and specialized intestinal metaplasia resulting in neosquamation of esophagus. Among the ablative modalities, radiofrequency ablation (RFA) is the most studied with safe, effective, and durable long-term outcomes. Cryotherapy, argon plasma coagulation, and photodynamic therapy can be offered in select patients when RFA is unavailable, has failed, or is contraindicated. Future research on natural disease progression, biomarkers, advanced imaging, and application of endoscopic techniques will lead to better clinical outcomes for BE-associated neoplasia.
Key points
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Ablative therapy aims at elimination of Barrett’s esophagus (BE) by the induction of superficial tissue necrosis by thermal energy, freezing, or photochemical injury.
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Radiofrequency ablation (RFA) is the most studied method with safe, effective, and durable long-term treatment outcomes.
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Two types of RFA are performed, circumferential ablation (c-RFA) and focal ablation (f-RFA).
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RFA is effective either alone or in combination with endoscopic resection for high-grade dysplasia (HGD).
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The role of RFA in low-grade dysplasia (LGD) is still debated, but it can be offered as an alternate treatment in select patients.
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Cryotherapy, argon plasma coagulation (APC), and photodynamic therapy (PDT) can be offered in select patients when RFA is unavailable, has failed, or is contraindicated.
Introduction
BE is an acquired condition characterized by a change of the normal esophageal squamous epithelium to columnar epithelium containing goblet cells ( Boxes 1 and 2 , Table 1 ). This metaplastic change can progress to LGD and HGD, the latter having a 5% to 10% per patient-year risk of developing esophageal adenocarcinoma (EAC). On the other hand, the risk of EAC in the general population with nondysplastic BE is only 0.1%– to 0.3% per year. BE is more common in developed countries, affecting 1% to 2% of the general population, and has a strong association with male gender, white race, and gastroesophageal reflux disease. The incidence of EAC has increased more than 5-fold over the past decades. Ablation by thermal energy, freezing, or photochemical injury achieves complete eradication of dysplasia (CE-D) and complete eradication of specialized intestinal metaplasia (IM) resulting in squamous reepithelialization of esophagus. Endoscopic ablative therapies aim to eradicate dysplasia and IM to prevent the development of EAC. This article focuses on the most published ablative therapies, which are RFA, PDT, and cryoablation.
Endoscope and equipment
RFA energy generator console
HALO 360 sizing balloon
HALO 360 balloon ablation catheter
HALO cap
Gauze
1% N -acetylcysteine solution
Spray catheter
Savary spring-tipped guidewire of 0.025 or 0.035 in diameter, minimum of 260 cm length; Nitinol-based guidewire (Tracer Metro [Cook Endoscopy, Cook Medical Endoscopy Inc, Winston Salem, NC] or equivalent)
Endoscope and equipment
RFA energy generator console
HALO 90 ablation device
Gauze
1% N -acetyl cysteine solution
Spray catheter
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Introduction
BE is an acquired condition characterized by a change of the normal esophageal squamous epithelium to columnar epithelium containing goblet cells ( Boxes 1 and 2 , Table 1 ). This metaplastic change can progress to LGD and HGD, the latter having a 5% to 10% per patient-year risk of developing esophageal adenocarcinoma (EAC). On the other hand, the risk of EAC in the general population with nondysplastic BE is only 0.1%– to 0.3% per year. BE is more common in developed countries, affecting 1% to 2% of the general population, and has a strong association with male gender, white race, and gastroesophageal reflux disease. The incidence of EAC has increased more than 5-fold over the past decades. Ablation by thermal energy, freezing, or photochemical injury achieves complete eradication of dysplasia (CE-D) and complete eradication of specialized intestinal metaplasia (IM) resulting in squamous reepithelialization of esophagus. Endoscopic ablative therapies aim to eradicate dysplasia and IM to prevent the development of EAC. This article focuses on the most published ablative therapies, which are RFA, PDT, and cryoablation.
Endoscope and equipment
RFA energy generator console
HALO 360 sizing balloon
HALO 360 balloon ablation catheter
HALO cap
Gauze
1% N -acetylcysteine solution
Spray catheter
Savary spring-tipped guidewire of 0.025 or 0.035 in diameter, minimum of 260 cm length; Nitinol-based guidewire (Tracer Metro [Cook Endoscopy, Cook Medical Endoscopy Inc, Winston Salem, NC] or equivalent)
Endoscope and equipment
RFA energy generator console
HALO 90 ablation device
Gauze
1% N -acetyl cysteine solution
Spray catheter
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Principles of mucosal ablation in Barrett’s esophagus
Ablative therapy aims at elimination of BE by the induction of superficial tissue necrosis by thermal energy, freezing, or photochemical injury. Healing ensues in an acid-suppressed state, and the damaged tissue is then replaced by normal squamous mucosa. This reepithelialization, characterized by neosquamous epithelium, remains the main goal of therapy. The exact mechanism that leads to reepithelialization is still not clear. It is theorized that squamous regeneration seems to occur from neighboring squamous cells and bone-marrow-derived stem cells. Immunohistology and fluorescent in situ hybridization (FISH) studies of this epithelium show loss of preexisting ontogenetic alterations suggesting a low risk for malignant progression. However, ablative treatment approach is limited to superficial flat mucosal tissue, does not provide a tissue specimen for histologic staging or assessment, and therefore is distinct from endoscopic resection techniques. The ablative techniques used in the eradication of BE have been classified as (1) thermal: RFA, APC, laser, and multipolar electrocoagulation (the latter 2 being infrequently used) and (2) nonthermal: cryoablation and PDT.
Radiofrequency ablation
RFA is a safe and effective endoscopic treatment modality for BE. The technique is based on using a bipolar electrode array and a generator that delivers a fixed amount of thermal radiofrequency energy that results in uniform tissue dissipation to a depth of 0.5 mm. The electrode array is available on 2 main delivery device platforms: (1) HALO 360 circumferential also called Barrx 360 Balloon catheter and (2) HALO 90 focal or Barrx 90 Focal catheter (Covidien Barrx, Sunnyvale, CA, USA) ( Fig. 1 ). Furthermore, 3 modifications of the focal device are available for select patients: Barrx 60 RFA Focal Catheter, Barrx Ultra Long RFA Focal Catheter, and Barrx Channel RFA Endoscopic Catheter.
Selection of patients for RFA requires a multidisciplinary approach consisting of the endoscopist, gastrointestinal (GI) pathologist, and the surgeon. Accurate endoscopic pretreatment staging is essential to ensure optimal long-term outcomes. Endoscopic inspection should be performed with high-definition white light. The extent of BE segment should be defined using the Prague C & M classification including the length of the circumferential segment (C) and the maximal extent (M) of the BE segment ( Fig. 2 ). Other imaging modalities that might help in delineating BE are narrow band imaging, standard chromoendoscopy, autofluorescence imaging, and confocal laser endoscopy. Although these methods have not been proven to be superior to white light endoscopy to detect dysplasia, all these techniques might aid in directed or targeted biopsies of suspicious areas. Targeted biopsies are obtained from visible abnormalities, followed by 4-quadrant biopsies of every 1 to 2 cm of the BE segment (Seattle protocol). Nodular lesions or focal visible lesions should be resected and are best staged by doing an endoscopic mucosal resection (EMR) before performing RFA therapy as described by Kaul V and Kothari S, elsewhere in this issue. Before performing RFA, a second, dedicated GI pathologist must confirm the presence of dysplasia on biopsies or resected specimens.
Technique of radiofrequency ablation
Preoperative Planning
Patients undergo standard esophagoduodenoscopy preprocedure preparation with specific note of sedation and procedural risks. Special attention should be exercised when treating patients with morbid obesity, anatomic variants such as short neck, cervical osteophytes, cricopharyngeal hypertrophy, and prior history of surgery involving the GI tract, radiation, or documentation of previous strictures. No antibiotics are required before any of the ablative therapies. It is desirable to minimize or stop antiplatelet and anticoagulation therapy before the procedure. Procedures are routinely performed on an outpatient basis using conscious sedation delivered by the endoscopists or by the anesthesia department (ie, monitored anesthesia care). The patient is placed in the left lateral decubitus position and prepared in the same manner as for a routine upper endoscopy.
Circumferential Ablation
c-RFA is done in patients in whom the segment of BE is longer than 2 cm and is circumferential ( Box 1 ). The steps include:
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Endoscopy with inspection and recording the landmarks : Measurements are taken to map the extent of the BE showing (a) the Z-line, which is the top of cylindrical epithelium or top of intestinal metaplasia (TIM), (b) the proximal contiguous area of BE (M), as well as (c) the proximal level at which the BE is circumferential (C) and the top of the gastric folds. The top of the gastric folds corresponds to the gastroesophageal junction. Careful inspection should be made to evaluate for hiatal hernia and to rule out prior ulceration, strictures, previous scarring from EMR, or residual nodularity because these may compromise any balloon c-RFA. If strictures are noted, esophageal dilatation should be performed 2 to 3 weeks before ablation. Ideally, before performing RFA, the esophageal mucosa is washed with N -acetylcysteine to clear any excess mucus.
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Sizing : After adequate inspection, recording landmarks, a guidewire is passed into the gastric antrum and then the endoscope removed. The sizing balloon is attached to the control unit and then calibrated externally to rule out any leaks ( Fig. 3 ). The balloon is then introduced over the guidewire into the body of the esophagus placing it 3 cm proximal to the TIM measurement. Serial measurements are taken at 1-cm intervals, starting proximally and proceeding distally by inflating the device. A technician or nurse then records the displayed measurements. The smallest diameter treatment balloon suggested throughout the sizing is chosen as the appropriate ablation catheter.
Fig. 3
Sizing balloon for c-RFA.
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Selecting appropriate ablation device : After sizing, the balloon catheter is removed, keeping the guidewire in place. The smallest diameter treatment balloon suggested throughout the sizing is chosen as the appropriate ablation device and attached to the generator. Balloon catheters are available in several diameters: 18, 22, 25, 28, 31, and 34 mm.
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First ablation pass : The HALO 360 catheter consisting of a 3-cm electrode array encircling a 4-cm-long balloon is then passed over the guidewire into the esophagus ( Fig. 4 ). The endoscope is intubated alongside the catheter to visualize the proximal end of the balloon, which is then positioned 1 cm proximal to the TIM. The balloon is automatically inflated first, and then energy is delivered by using the foot pedals attached to the control unit. The uniform energy has a density of 12 J/cm 2 and power of 40 W/cm 2 ablating to a depth of 700 to 1000 μm over 3 cm of array. After a second of ablation, the balloon automatically deflates and the circumferential burn is visible. Depending on the length of the segment, an additional 3 cm of c-RFA is performed such that there is minimal overlap (<1 cm) with the previously ablated segment.
