The goals for treatment of BE are (1) to decrease or eliminate gastroduodenal reflux into the esophagus, primarily to improve the associated symptoms of GERD and potentially to limit progression or cause regression of BE and (2) to directly eliminate Barrett metaplasia and dysplasia (via resection or ablation), thereby decreasing the risk for development of esophageal adenocarcinoma. The methods by which to achieve these goals are continuously evolving and in certain clinical scenarios, still remain somewhat controversial.
There are several ways to reduce and eliminate gastroduodenal reflux. Medical therapy, in the form of proton pump inhibitors, has been shown to be very effective for neutralizing gastric acid and controlling acid reflux symptoms. In addition, there are several studies that have shown that medical therapy can cause modest regression of BE. Regression is often defined in several ways, including decrease in the length of BE, down-grading of Barrett dysplasia, and complete elimination of IM. The regression rates have been reported to be from 19% to 41% depending on the definition of regression. Practitioners should be aware, however, that there can be progression of BE while on medical therapy. Reported rates of progression to dysplasia range from 1.8% up to 31%. Similarly, rates of progression from BE to esophageal adenocarcinoma have been reported to be from 1.6% to 7.4% while on medical therapy. Therefore, acid and symptom control with proton pump inhibitors alone should be used in conjunction with endoscopic surveillance to monitor for regression or progression of disease.
Antireflux surgery has been offered to patients who have failed medical treatment, usually defined as breakthrough symptoms, or progression or continuation of esophageal damage due to reflux. The technical details of the various types of antireflux operations are discussed in detail in other chapters. Laparoscopic Nissen fundoplication is the most common operation performed, but all operations described for the treatment of GERD may be used in patients with BE.
The use of antireflux surgery to change the natural history of BE is controversial. While there are no randomized controlled trials that show superiority of laparoscopic antireflux surgery over medical therapy for causing regression of BE or preventing the development of esophageal adenocarcinoma, there are some retrospective studies that suggest there may be a benefit of surgery.8 In a recent review of the literature, we found that on average, 11.1% of patients who underwent medical therapy progressed to dysplasia compared to only 3.4% of patients who had antireflux surgery.9 Similarly, 4.1% of patients undergoing medical therapy for BE progressed to adenocarcinoma compared to only 0.7% of patients who had antireflux surgery. Although these are selective case studies and few were established to compare medical and surgical therapy, the trends do suggest a possible benefit from antireflux surgery. Despite the improved symptomatic responses to surgery compared to medical therapy and the apparent decreased rates of regression of BE and progression to adenocarcinoma, the regression is still incomplete and progression to adenocarcinoma still occurs.10 Therefore, surveillance endoscopy should still remain as an important component of treatment for BE after antireflux surgery (Table 41-2).
Table 41-2Medication Versus Laparoscopic Antireflux Surgery for Be ||Download (.pdf) Table 41-2Medication Versus Laparoscopic Antireflux Surgery for Be
|PUBLICATION ||NUMBER OF PATIENTS ||FOLLOW-UP (YEARS) ||ADENOCARCINOMA ||DYSPLASIA ||REGRESSION |
|Medical therapy |
|Hillman 2004 ||279 ||4.7 ||7 ||5 ||NA |
|Cooper 2006 ||188 ||5.1 ||3 ||6 ||NA |
|Nguyen 2009 ||231 ||7.6 ||17 ||53 ||NA |
|Heath 2007 ||82 ||0.9 ||6 ||9 ||34 |
|Horwhat 2007 ||67 ||3.8 ||2 ||21 ||13 |
|Total ||847 ||4.4 ||35 (4.1%) ||94 (11.1%) ||47 (31.5%) |
|Hofstetter 2001 ||79 ||5.0 ||0 ||4 ||16 |
|Bowers 2002 ||64 ||4.6 ||0 ||1 ||31 |
|Mabrut 2003 ||13 ||3.8 ||0 ||0 ||6 |
|Oelschlager 2003 ||90 ||2.6 ||1 ||3 ||30 |
|Desai 2003 ||50 ||3.1 ||0 ||1 ||9 |
|O'Riordan 2004 ||57 ||3.8 ||2 ||2 ||14 |
|Abbas 2004 ||33 ||1.5 ||1 ||2 ||13 |
|Zaninotto 2005 ||35 ||2.3 ||0 ||0 ||6 |
|Ozmen 2006 ||37 ||1.6 ||0 ||1 ||6 |
|Biertho 2007 ||70 ||4.2 ||0 ||3 ||23 |
|Biertho 2009 ||23 ||4.5 ||0 ||0 ||14 |
|Total ||551 ||3.4 ||4 (0.7%) ||17 (3.4%) ||168 (30.5%) |
Elimination of Barrett Metaplasia and Dysplasia
Once dysplasia develops, the risk of cancer increases exponentially, therefore, more aggressive treatments are recommended. Not very long ago, esophagectomy was recommended as the only treatment of choice in patients with BE and HGD and still appears in the Society of Thoracic Surgeons guidelines.11 In the last decade, however, advanced endoscopic tools have been developed that can provide less invasive ways to adequately treat BE and have made esophagectomy rarely necessary.
Endoscopic ablation therapy for BE was first reported in 1992. Laser therapy was studied early on, yet remains largely experimental, given its ineffectiveness in treating large areas of disease, associated perforation rate, and need for multiple treatments to achieve elimination. Multipolar electrocoagulation (MPEC) involves application of a 50-watt probe to an area of metaplasia until a coagulum forms. Studies have shown high success rates for eliminating nondysplastic BE ranging from 89% to 100%, but also have associated high complication rates. Dysphagia occurred in approximately 19% of patients and odynophagia occurred in approximately 16% of patients undergoing MPEC. For this reason, MPEC is not routinely used for treatment of BE.12 Argon plasma coagulation (APC) is a cauterization tool that uses ionized argon gas to transmit a constant current to a superficial layer of mucosa. Results have shown 89% to 100% elimination of Barrett mucosa, but also a high 3% to 11% recurrence rate after treatment. This is thought to be due to the relatively low depth (2–3 mm) of treatment. Although the penetration depth prevents complications such as perforations from occurring, there have been reports of “buried dysplasia/neoplasia.” Given better alternative endoscopic ablation technologies on the market, APC is not frequently performed.12 Photodynamic therapy (PDT) involves administration of a systemic light-sensitizing agent (porfimer sodium or 5-aminolevulinic acid) followed by endoscopic application of diffusing fiber optics against the target tissue to create necrosis. PDT has been compared with APC in a randomized trial. The result showed only 50% complete eradication of BE compared to 97% for APC.13 In addition, a higher stricture rate was seen with PDT ranging from 30% overall to 50% after receiving two treatments12 (Fig. 41-2).
Multipolar electrocoagulation (A) and photodynamic therapy (B) devices.
Radiofrequency ablation (RFA) has been shown to be an effective method to destroy dysplastic Barrett's epithelium, and is currently the most common method to do so. A randomized controlled multicenter clinical trial recently showed that ablation can both reduce progression and permanently eliminate Barrett's metaplasia.14 In this study, there was 90.5% complete eradication of dysplasia in patients with LGD compared to 22.7% of patients who had a sham procedure. For patients with HGD, 81% of patients had complete eradication compared to 19.0% in the sham group. Patients who had RFA also had less disease progression (3.6% vs. 16.3%) and fewer cancers (1.2% vs. 9.3%) compared to sham procedures. It is also a relatively safe procedure with one multicenter prospective study that reported no strictures 2.5 years after having focal ablation.15 Although there is an apparent high success rate, several limitations exist. Large surface areas of BE and circumferential BE are difficult to treat with RFA compared with focal BE because of the potential for postablation strictures. In addition, some reports have suggested that Barrett tissue that is deeper than the treatment depth of RFA may become “buried” and overgrown with normal squamous epithelium, thus harboring a deeper focus of dysplastic cells that cannot be accessed with surveillance biopsies. Although this is rare and has not been seen as commonly compared to APC, it is still a concern with this treatment modality (Fig. 41-3).
Cryoablation is a newer technology originally introduced in 1997, which has undergone some recent refinements that holds some promise for ablation of Barrett tissue. This technique involves using liquid nitrogen to freeze the tissue resulting in intracellular destruction while preserving the extracellular matrix, and may allow for deeper, submucosal ablation. A recent study showed 97% complete eradication of HGD, 87% had eradication of all dysplasia, and 57% complete resolution of BE.16 Randomized clinical trials are currently in progress to evaluate its efficacy compared to other ablative therapies.
Endoscopic Ablation for Nondysplastic BE
Ablation as an alternative for surveillance may be considered for nondysplastic BE. This practice is controversial, but the argument often used is the same one that is used for polypectomy for colonic adenomas—it is a lesion that has some propensity for progressing to cancer; therefore, if the lesion can be safely eradicated, then the risk of cancer can be modified. A multicenter cohort study that followed patients with a diagnosis of nondysplastic BE found that 0.5% per patient-year progressed to esophageal adenocarcinoma.17 Given the relatively low risk of complications related to RFA and the potential sampling error related to surveillance, ablation may be presented as a reasonable alternative to surveillance.15 In addition, several studies have reported complete clinical response (no residual IM) with RFA for nondysplastic BE.18
Endoscopic Mucosal Resection
Endoscopic mucosal resection (EMR) is a technique that provides both diagnostic and therapeutic benefits for patients with BE. The EMR technique is described in detail in Chapter 173. By taking full mucosal resections of esophageal mucosa, depth and extent of metaplasia and dysplasia can be accurately assessed. This is a clear benefit over ablative therapies in which histopathologic specimens are not obtainable. In patients who undergo EMR for HGD or early cancer, depth of invasion and surgical staging can be performed. In patients who have early-stage esophageal cancer that is confined to the mucosa, EMR has been shown to be an acceptable curative tool, given the low rate of lymph node metastases in these lesions. EMR does bear the risk of causing strictures in up to 50% of patients in addition to causing bleeding or perforation. Therefore, patients with long-segment BE (>3 cm in length) or multifocal BE spanning across a larger distance are typically not amenable to EMR, given the very high likelihood of developing strictures.
EMR in conjunction with RFA has been shown to have excellent results while maintaining a lower complication profile. EMR with RFA was shown to completely eliminate BE with HGD or intramucosal adenocarcinoma in excess of 94% of patients.12 A recent multicenter trial demonstrated complete eradication of BE in 96% of patients who underwent EMR with RFA, but had only a stricture rate of 14% compared to a stricture rate of 88% for patients who underwent widespread EMR for eradication of BE.19 This high success rate in combination with accurate histopathologic staging of BE has made EMR followed by RFA the primary method of treatment in patients who have HGD or intramucosal adenocarcinoma (Fig. 41-4).
Endoscopic mucosal resection.
With improvement in endoscopic therapies such as EMR for BE, there became fewer indications for surgical resection. The presence of esophageal adenocarcinoma with invasion beyond the mucosa is currently an indication for esophagectomy, with or without neoadjuvant or adjuvant therapy depending on final staging. For patients without invasive cancer, esophagectomy is becoming reserved for patients with specific characteristics of BE, who are also physically able to tolerate this potentially highly morbid procedure. There are several techniques for performing esophagectomy and that are discussed in other chapters. We will discuss specific scenarios when esophagectomy may be indicated for BE.