Surgical Management of B a r re t t ’s Es o p h a g u s Christian G. Peyre,
MD,
Thomas J. Watson,
MD*
KEYWORDS Barrett’s esophagus Antireflux surgery Esophagectomy Nissen fundoplication Intramucosal adenocarcinoma KEY POINTS Antireflux surgery is a safe and effective treatment option to control gastroesophageal reflux disease in patients with Barrett’s esophagus. Antireflux surgery prevents reflux of acid and nonacid gastric content, and can induce regression in some cases of Barrett’s metaplasia or dysplasia. Antireflux has not been proved to be superior to medical therapy in preventing the progression of Barrett’s esophagus to esophageal adenocarcinoma. Esophagectomy has been supplanted by endoscopic therapies as the ideal treatment option for most patients with high-grade dysplasia or focal intramucosal adenocarcinoma. Esophagectomy may be the preferred treatment option in a minority of select cases with multifocal dysplasia, high-risk tumor characteristics, an esophagus otherwise not worth salvaging, or because of patient preference.
INTRODUCTION
Gastroesophageal reflux disease (GERD) is the major risk factor for the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).1,2 The treatment of BE is focused primarily on controlling reflux, most commonly with antisecretory medication to abolish gastric acid production.3 In patients with dysplastic BE or early esophageal neoplasia, endoscopic therapies, including various forms of ablation and resection, have become the primary treatment options to eradicate the pathologic mucosa.4 Adjunctive medical or surgical antireflux therapies are necessary to control ongoing reflux, in an effort to reduce the recurrence of esophageal metaplasia, dysplasia, or neoplasia. Although medical therapy is the most commonly used treatment modality for BE, antireflux surgery is a safe and effective alternative and should be considered in all
Disclosure: The authors have no disclosures. Division of Thoracic and Foregut Surgery, Department of Surgery, University of Rochester School of Medicine and Dentistry, University of Rochester Medical Center, 601 Elmwood Avenue, Box Surgery, Rochester, NY 14642, USA * Corresponding author. E-mail address:
[email protected] Gastroenterol Clin N Am 44 (2015) 459–471 http://dx.doi.org/10.1016/j.gtc.2015.02.013 gastro.theclinics.com 0889-8553/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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Box 1 Relative indications for esophagectomy in patients with high-grade dysplasia or intramucosal adenocarcinoma Tumor characteristics with a significant risk of lymph node metastasis Poorly differentiated tumors Positive deep margin after endoscopic resection Lymphovascular invasion Invasion beyond the muscularis mucosa Dysplastic or neoplastic Barrett’s esophagus, which is difficult to eradicate Ultra-long segment Barrett’s esophagus Diffusely nodular esophagus with multifocal high-grade dysplasia or intramucosal adenocarcinoma Long or large intramucosal adenocarcinomas Failed eradication of disease following endoscopic therapy Patient unwilling or unable to comply with the required repeat endoscopies and long-term surveillance Esophagus not worth salvage Recalcitrant stricture End-stage motility disorder
patients to control underlying GERD. In select cases, such as individuals with end-stage esophageal motility disorders, recalcitrant strictures, or long-segment BE (LSBE) with multifocal high-grade dysplasia (HGD) or intra-mucosal adenocarcinoma (IMC), esophagectomy should be considered in the treatment paradigm (Box 1). This article reviews the role of antireflux surgery in the management of nondysplastic and dysplastic BE, and highlights the evolution of esophagectomy in the treatment of patients with HGD or early esophageal neoplasia. GOALS OF THERAPY FOR BARRETT’S ESOPHAGUS
Although most patients treated for GERD without BE can be managed successfully with medical therapy alone, those patients identified with BE are at increased risk for the development of EAC and may require a more intense treatment regimen.5 Such patients should (1) undergo a detailed endoscopic examination, with multiple biopsies per established protocols, to rule out dysplasia or early neoplasia; (2) be treated aggressively for reflux to prevent further mucosal injury; and (3) be enrolled in an ongoing endoscopic surveillance program for early detection of progression of disease. The ideal treatment of BE should control troublesome reflux symptoms, result in healing of mucosal injury, induce regression of Barrett’s epithelium to normal squamous mucosa, and prevent progression of BE to EAC, all with few side effects. LIMITATIONS OF MEDICAL THERAPY IN PATIENTS WITH BARRETT’S ESOPHAGUS
Long-term, continuous control of reflux is critical in patients with BE to allow healing of the esophageal mucosa and to prevent progression of disease. Patients with GERD and BE compared with those without BE, however, have increased amounts of acid
Surgical Management of Barrett’s Esophagus
and bile reflux, and a higher prevalence of incompetent lower esophageal sphincters, hiatal hernias, and impaired esophageal motility.6,7 Consequently, control of GERD in patients with BE is much more challenging than in patients with GERD without BE.8,9 Although the primary treatment end point in patients with GERD is symptom control, it has been shown in patients with BE that control of reflux symptoms does not equate to control of gastric pH or esophageal acid exposure.10,11 Greater than 50% of patients with BE have pathologic levels of esophageal acid exposure despite relief of symptoms.12 To maintain tight control of acid production, strict adherence to daily, and often twice daily, proton pump inhibitor (PPI) is necessary, making patient compliance a challenge. Additionally, antisecretory medications are directed at abolishment of acid production alone; they are ineffective at controlling the reflux of biliopancreatic substrates and nonacid gastric contents (eg, pepsin) that can contribute to ongoing mucosal injury.13,14
BENEFITS OF ANTIREFLUX SURGERY
Antireflux surgery is a safe and effective alternative to medical therapy for patients with BE. Surgery corrects an incompetent lower esophageal sphincter and concomitant hiatal hernia, preventing the reflux of acid, bile, and other nonacid substrates. Complete reflux control can lead to healing and regression of Barrett’s mucosa, and may reduce the risk of progression to cancer. Surgery also eliminates the concern for patient compliance with medical therapy, and may reduce the cost of treatment compared with life-long antisecretory therapy.15 Approach to Antireflux Surgery for Barrett’s Esophagus
Beginning with Rudolph Nissen’s transabdominal open “gastroplication,” first described in 1956 and modified for laparoscopy by Dallemagne in 1991, modern antireflux surgery has undergone a tremendous evolution over the past half century.16 Surgery can be accomplished via open transabdominal or transthoracic approaches, but laparoscopic fundoplication has become the gold standard for surgical management of GERD because of decreased morbidity, quicker recovery, improved cosmesis, and superior patient satisfaction over open surgery. Most patients with GERD are candidates for laparoscopic antireflux surgery, although in a select group open surgery may be required because of extensive abdominal adhesions from previous surgery or other patient factors. The technique of constructing the fundoplication has also evolved over time. The original fundic wrap described by Nissen was approximately 6 cm long and was associated with significant postoperative dysphagia.17 The modern Nissen technique consists of a short (1.5–2 cm) floppy wrap over a large (56–60F catheter) bougie, affording excellent reflux control but with a lower risk of postoperative dysphagia.18,19 If esophageal motility is significantly impaired, a partial fundoplication may be better suited than a 360-degree Nissen wrap to prevent dysphagia. The efficacy of a partial fundoplication in patients with BE is questionable, however, with some studies suggesting decreased long-term control of reflux compared with a complete Nissen fundoplication.20,21 Other less used surgical techniques have been described as well, including near-total or subtotal gastrectomy with Roux-en-y reconstruction, or duodenal switch with biliopancreatic diversion. Perioperative risks and long-term gastrointestinal side effects may be increased with these more complex operations, and the data are less robust to support such interventions.22 As a result, this discussion focuses on the results of fundoplication.
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Outcomes of Antireflux Surgery in Patients with Barrett’s Esophagus
Success following antireflux surgery can be assessed in several different domains.23 Primary end points include symptom relief, normalization of esophageal acid exposure, prevention of dysplasia or neoplasia, and regression of metaplasia or dysplasia. Most data are derived from cohort analyses from high-volume esophageal surgery centers, although there are limited publications comparing medical and surgical therapies. Safety of antireflux surgery for Barrett’s esophagus
Laparoscopic antireflux surgery is safe with low morbidity and mortality. A recent review of the American College of Surgeons National Surgical Quality Improvement Program database, examining more than 7500 laparoscopic antireflux surgeries performed across the United States, revealed the 30-day operative mortality to be only 0.3%, and morbidity 3.8%.24 As expected, mortality increased with age, but was only 0.8% for patients older than 70 years. Control of gastroesophageal reflux disease symptoms
The primary focus of the treatment of GERD is the control of troublesome symptoms, most commonly “typical” heartburn and regurgitation. Studies assessing short-term outcomes of laparoscopic Nissen fundoplication (LNF) have revealed excellent control of such typical GERD symptoms. In one study looking at 100 consecutive patients treated with LNF, including 37 patients with BE, 87% of patients considered themselves “cured” and another 11% had significantly improved symptoms at a median follow-up of 2 years.19 When focusing on patients with BE treated with antireflux surgery, similar results for the control of symptoms have been seen. In a cohort of 85 patients followed for a median of 5 years, 77% of patients considered themselves “cured,” and an additional 22% had significant improvement of symptoms, following antireflux surgery.25 Similarly, a series of 59 patients followed for a median of 59 months revealed that 90% of patients undergoing antireflux surgery had no or only minor postoperative symptoms.26 “Minor” symptoms were defined as not interfering with quality of life or requiring medication. A third study of 215 patients followed for a median of 8 years after antireflux surgery demonstrated that 86% of patients had control of heartburn and regurgitation.27 As these studies demonstrate, laparoscopic antireflux surgery results in excellent control of GERD symptoms in most patients with BE. Control of esophageal acid exposure: postoperative pH monitoring
Antireflux surgery has been shown to control the reflux of gastric acid into the esophagus, and to normalize esophageal acid exposure, in most patients treated for GERD.28 Because patients with BE represent a challenging patient population with severe reflux disease, control of esophageal acid exposure may not be as effective as in patients with GERD without BE. In a study of 53 patients with BE examined with preoperative and postoperative esophageal pH monitoring (at a median followup of 40 months after surgery), a significant reduction in distal esophageal acid exposure as measured by percent time pH less than 4 was seen (27.9% vs 4.0%; P