Chapter 15. Gastroesophageal Reflux Disease and Hiatal Hernia (Including Paraesophageal)

Definition

Gastroesophageal reflux disease (GERD) is a chronic disorder related to the retrograde flow of gastric contents into the esophagus, resulting in a spectrum of symptoms with or without tissue injury.1 Classic GERD symptoms in the absence of esophageal mucosal complications are the hallmarks of nonerosive reflux disease (NERD). Patients with NERD account for up to 70% of those with GERD in the community.2 Antireflux surgery is the only effective and long-term therapy. Although various endoscopic approaches to treat GERD have been introduced, none of them has been able to achieve an efficacy equivalent to antireflux surgery.3,4

Symptoms

Heartburn (ascending retrosternal burning) and regurgitation are typical GERD symptoms. Epidemiologic studies have demonstrated that heartburn occurs monthly in as many as 40–50% of the Western population. The occurrence of heartburn at night and its effect on quality of life have recently been highlighted by a Gallup poll conducted by the American Gastroenterologic Society (Table 15-1).5 Regurgitation of gastric contents often occurs when the patient is supine or with increases in intra-abdominal pressure, and may result in atypical symptoms, including cough, globus sensation, hoarseness, throat clearing, asthma, aspiration pneumonia, and pulmonary fibrosis. Dysphagia is a typical symptom of GERD and can be divided into (1) an oropharyngeal etiology, which is characterized by difficulty transferring food out of the mouth into the esophagus, and (2) esophageal etiology, which is characterized by the sensation of food sticking in the lower chest. Dysphagia can be a sign of underlying malignancy and should be aggressively investigated with upper endoscopy. Chest pain can be caused by GERD; however, it is very important to exclude a cardiac etiology. DeMeester and colleagues reported that nearly 50% of patients with severe noncardiac chest pain had a positive 24-hour pH study implicating GERD as the underlying etiology.6 Chest pain precipitated by meals, occurring at night while supine, nonradiating, responsive to antacid medication, or accompanied by other symptoms such as dysphagia and/or regurgitation should trigger an evaluation for an esophageal cause. Additionally, it should be noted that the distinction between heartburn and chest pain can be difficult to make, and the perception of these symptoms is highly variable between patients.7,8

The antireflux mechanism includes four important components: (1) lower esophageal sphincter (LES); (2) crural diaphragm; (3) esophageal peristalsis; and (4) stomach (the reservoir).

Lower Esophageal Sphincter

The gastroesophageal junction (GEJ) is a complex arrangement of specialized muscles composed of both intrinsic (LES) and extrinsic (crural diaphragm) contractile elements. The LES, which can be identified as a high-pressure zone located at the GEJ, creates the barrier between the esophagus and stomach that normally prevents reflux. LES relaxation occurs in two situations: (1) immediately following a swallow, when it momentarily relaxes to allow passage of food into the stomach, and (2) when the fundus is distended with gas, it is eliminated to allow venting of the gas (a belch)—transient LES relaxation (TLESR). For an LES to be effective, it must possess three characteristics: an adequate (1) total length, (2) intra-abdominal length, and (3) resting pressure (Table 15-2).9 Therefore, a defective LES is identified by one or more of the following characteristics: (1) a high-pressure zone with an average pressure of less than 6 mm Hg, (2) an average overall length of 2 cm or less, and (3) an average length exposed to the positive pressure environment of the abdomen (intra-abdominal length) of 1 cm or less. The most common cause of a permanently defective LES is an inadequate abdominal length, secondary to the high prevalence of a hiatal hernia in patients with GERD.9 A TLESR is an LES relaxation that occurs without a swallow and accounts for the physiologic reflux and “venting” of the stomach, particularly in the postprandial state. Frequent and prolonged TLESR can be associated with the development of GERD, and this may explain the etiology of disease observed in the 40% of patients with a manometrically normal sphincter. A transient loss of the LES can also occur due to a functional problem of the gastric reservoir and delayed emptying.10 In this setting, if excessive air and food are swallowed, there are gastric distention and an increase in intra-gastric pressure with shortening of the LES (Fig. 15-1). This process continues until a critical LES length is reached and eventually the pressure drops precipitously and reflux occurs. This “transient sphincter” shortening occurs in the initial stages of GERD and is the mechanism for the early complaint of excessive postprandial reflux. This process is associated with the common complaints of belching and bloating in patients with GERD. To compound matters, there is an increased frequency of swallowing (air and saliva) observed in GERD patients because the ingestion of saliva (pH 7) serves to neutralize the acidic fluid (pH 1) in the esophagus.11 Therefore, GERD may begin in the stomach, secondary to gastric distention due to overeating and a high-fat diet, which delays gastric emptying. Further, a close relationship between the geometry of the cardia and one's propensity to reflux in the face of a given intragastric pressure has been established.10 Greater gastric distension, as reflected by an increasing intragastric pressure, is necessary to “open” the sphincter in patients with an intact angle of His compared to those with hiatal hernia (Fig. 15-2).12 These data elucidate why the presence of a hiatal hernia is often associated with GERD and explain the loss of the flap valve mechanism (intragastric portion of LES). In addition, in the presence of a hiatal hernia the intrinsic portion of the LES is no longer aided by the crural diaphragm (extrinsic LES).

Esophageal Peristalsis

Esophageal peristalsis is an extremely important component of the antireflux mechanism and serves to clear physiologic reflux and thus reduces contact time between the esophageal epithelium and gastric fluid. Ineffective esophageal motility can result in an abnormal esophageal exposure to gastric juice even in individuals with a mechanically effective LES and normal gastric function.13 However, ineffective motility is more often seen in patients with a mechanically defective LES, where distal esophageal body function deteriorates as a direct result of repetitive inflammation; this effect further prolongs the esophageal exposure to gastric juice, which creates a vicious cycle leading to more severe disease. Diener and colleagues reported that 40–50% of patients with GERD had abnormal esophageal peristalsis.13 In these patients, esophageal clearance time was prolonged, and gastric fluid was in contact with the esophageal mucosa for a longer period of time and traveled more proximally when compared to GERD patients with intact esophageal motility. Therefore, these patients were prone to having more severe mucosal injury and extraesophageal symptoms such as cough.14,15 To highlight these points, it is established that patients with mixed connective tissue diseases such as scleroderma commonly have an aperistaltic esophagus and absent LES, which results in the most severe form of GERD.16

Crural Diaphragm

The crural diaphragm provides an extrinsic component to the gastroesophageal barrier. Mittal and colleagues demonstrated a direct correlation between intraluminal pressure of the GEJ and integrated electrical activity of the crural diaphragm.17 Additionally, normal pressure of the GEJ from manometric tracings has been shown to range from 15 ± 11 mm Hg at the end of expiration to 40 ± 13 mm Hg at the end of inspiration mainly as a result of the diaphragmatic contribution.18 This pinchcock action of the diaphragm is particularly important as a protection mechanism against reflux induced by sudden increases in intra-abdominal pressure.19 This mechanism is obviously disrupted by the presence of a hiatal hernia where the intrinsic LES has “migrated” proximal to the diaphragmatic pinch.

Stomach

Impaired function of the stomach such as abnormal gastric emptying may contribute to GERD by increasing intragastric pressure, distension, and LES unrolling.20 This may occur in patients with a large hiatal hernia, in which the herniated stomach in the chest does not empty appropriately, gastric outlet obstruction either from malignancy or peptic ulcer disease, and diabetic gastroparesis.

The complications of GERD result from the damage inflicted by gastric juice on the esophageal mucosa, pharyngeal or respiratory epithelium, and the mucosal changes caused by their subsequent repair and fibrosis. These complications can be categorized into three groups: (1) mucosal complications such as esophagitis or stricture; (2) extraesophageal or respiratory complications such as laryngitis, pneumonia, asthma, and pulmonary fibrosis; and (3) metaplastic and neoplastic complications such as Barrett's esophagus and adenocarcinoma. The prevalence and severity of GERD-related complications are positively correlated with the degree of LES dysfunction and impaired esophageal motility (Table 15-3).21

Mucosal Complications

Mucosal complications such as esophagitis and stricture can occur in the presence of two predisposing factors: (1) a mechanically defective LES and (2) an increased esophageal exposure to the gastric fluid with a pH less than 4 and greater than 7 (Fig. 15-3).21 The components of the refluxed gastric fluid can include acid and pepsin as well as biliary and pancreatic secretions that travel from the duodenum into the stomach.22,23 Although acid and activated pepsin are the key ingredients of the gastric juice that leads to esophagitis, it has been established that the most severe epithelial injury occurs during exposure to bile salts combined with acid and pepsin.24 Previous experimental studies have shown that gastric or duodenal juice alone causes minimal or little damage to the esophageal mucosa, but the combination of duodenal juice and gastric juice is highly noxious. Previous study to directly measure esophageal bilirubin exposure as a marker of duodenogastroesophageal reflux has shown that 58% of patients with GERD have increased esophageal exposure to duodenal juice and that this exposure occurs most commonly when the esophageal pH is between 4 and 7 (Fig. 15-4).25 Within this pH range, there is formation of nonpolarized, soluble bile acids, which can diffuse through the cell membrane and cause damage to the mucosal cells. Additionally, this type of exposure correlates with the development of Barrett's esophagus (Fig. 15-5).25 The fact that the combination of gastric and duodenal juice is more noxious to the esophageal mucosa than gastric juice alone may provide an explanation for the observation that 25% of patients with reflux esophagitis develop recurrent and/or progressive mucosal damage despite medical therapy.21 Clinically, there is poor correlation between the symptom of heartburn and the endoscopic finding of esophagitis.26 The reflux of acidic gastric juice combined with duodenal contents can irritate nerve endings close to the luminal surface and cause severe heartburn in the absence of endoscopically detectable erosions; bile salts inhibit pepsin and acid inactivates trypsin, and the patient exhibits little or no gross evidence of esophagitis. By contrast, the reflux of alkaline gastric juice may occur without symptoms because of the absence of hydrogen ions but cause endoscopically evident esophagitis secondary to bile-activated trypsin exposure to the esophageal epithelium. This is supported by recent clinical studies that demonstrated that the presence of alkaline reflux is associated with the development of mucosal injury.25,27 In addition, several studies using either prolonged ambulatory aspiration techniques28 or spectrophotometric bilirubin measurement29 have shown that patients with GERD have more concentrated bile acid exposure to the esophageal mucosa than normal subjects, commonly in the supine position during sleep and in the upright position during the postprandial period. Furthermore, reflux of both acid and pancreaticobiliary juice is the most prevalent pattern of exposure and present in 100% of complicated Barrett's patients, 89% of uncomplicated Barrett's patients, 79% of patients with esophagitis, and 50% of patients with NERD.30,31 These findings support that the reflux of duodenal juice containing bile acids is common in patients with GERD and that proton pump inhibitor (PPI) therapy cannot prevent mucosal damage due to bile acids.

Esophageal stricture (circumferential scarring) formation and/or shortening (axial scarring) can be associated with severe esophagitis or Barrett's esophagus. Scarring occurs at the site of maximal inflammatory injury (ie, squamocolumnar junction). Thought by some to be a protective mechanism, the metaplastic columnar epithelium advances proximally into the area of inflammation leading to “protection” of that given length of esophagus; the proximal migration of the squamocolumnar junction leads to more proximal stricture formation within the esophagus. The presence of stricture can be an indicator of GERD even if there is no evidence of esophagitis or Barrett's esophagus. However, in patients with normal acid exposure, the stricture may be due to malignancy or a drug-induced chemical injury.32 Biopsy should be obtained to exclude malignancy. A short esophagus should be suspected when there is a hiatal hernia of greater than 5 cm that does not reduce in the upright position on esophogram.

Extraesophageal or Pulmonary Complications

It has been increasingly recognized that a significant proportion of patients with GERD have laryngeal or respiratory symptoms such as cough, recurrent pneumonia, asthma, and progressive pulmonary fibrosis, sometimes in conjunction with typical GERD symptoms such as heartburn and regurgitation.33 In addition, a strong association between GERD and the development of lung disease such as asthma and idiopathic pulmonary fibrosis has been established. Previous studies have demonstrated that up to 50% of asthmatics have either endoscopic evidence of esophagitis or increased esophageal acid exposure on 24-hour ambulatory pH monitoring,34,35 and that 87% of patients with idiopathic pulmonary fibrosis36 and 90.9% with cystic fibrosis37 have documented GERD based on esophageal pH monitoring.

Two mechanisms have been proposed as the pathogenesis of reflux-induced respiratory symptoms: (1) aspiration of gastric contents and (2) vagally mediated bronchoconstriction. Recent clinical studies have demonstrated a strong correlation between idiopathic pulmonary fibrosis and hiatal hernia and a high association between GERD and pulmonary disease such as asthma.33 Pathological acid exposure in the proximal esophagus is often identified in patients with respiratory symptoms and GERD. Scintigraphic studies have demonstrated aspiration of ingested radioisotope in patients with GERD and respiratory symptoms.38 Simultaneous tracheal and esophageal pH monitoring has demonstrated the presence of concomitant acidification both in the trachea and the esophagus in patients with asthma.39 Animal studies have shown an increased airway resistance after the instillation of hydrochloric acid into the trachea.40 Additionally, it is well known that bronchoconstriction occurs following the acid exposure in the distal esophagus.41 This can be explained by the common embryologic origin of the trachea and esophagus and their shared vagal innervation.

It is difficult to document that respiratory symptoms and/or injury are caused the underlining GERD as both are very prevalent. In a substantial number of patients with reflux-induced respiratory symptoms, GERD is often silent and is only uncovered when investigation is initiated. A high index of suspicion is required, especially in patients with poorly controlled adult-onset asthma in spite of appropriate bronchodilator therapy. Objective esophageal testing should be performed to document evidence of GERD and to attempt to correlate extraesophageal symptoms with reflux events. Upper endoscopy may reveal the presence of esophagitis or Barrett's esophagus. Manometry may demonstrate a hypotensive LES or some degree of impaired esophageal motility. Traditionally, the diagnosis of reflux-induced respiratory symptoms has been made using ambulatory dual probe pH monitoring; one probe is positioned within the distal esophagus and the other at a proximal location such as the trachea, pharynx, or proximal esophagus. Although ambulatory esophageal pH monitoring allows a direct correlation between esophageal acidification and respiratory symptoms, the chronological relationship between reflux events and bronchoconstriction is complex. The sensitivity of this approach is poor as much of the acid exposure is neutralized proximally after mixing with saliva. Multichannel intraluminal impedance-pH (MII-pH) has been introduced as a promising tool to evaluate the extension of reflux and its symptom correlation regardless of the composition of refluxate (liquid, gas, mixed, alkaline, acidic), especially in patients with atypical symptoms. Although several studies have shown that combined 24-hour MII-pH has a high yield for detection of GERD with atypical symptoms,27 the clinical utility of MII-pH is still being investigated.

Once GERD is suspected or thought to be responsible for respiratory symptoms, the treatment options may be either the trial of high-dose PPI therapy (BID or TID dosing) or antireflux surgery. A 3–6 months trial of high-dose PPI therapy may suggest that GERD is partly or completely responsible for the development of respiratory symptoms. However, the persistence of symptoms despite the maximal PPI therapy does not necessarily rule out the possible contribution of GERD. The algorithm depicted in Fig. 15-6 is made based on the outcome of dual-probe 24-hour pH monitoring and esophageal manometry in patients with respiratory symptoms and does not include impedance. Previous studies have demonstrated that acid suppressive therapy with PPI improves asthma symptoms and/or peak expiratory flow rates in up to 73% of asthmatics with GERD, although fewer than 15% can be expected to have objective improvements in their pulmonary function parameters.4,42,43 Most studies were conducted with a relatively short course of acid suppressive therapy (<3 months). This time period may have been sufficient for symptomatic improvement but insufficient for recovery of pulmonary function. Given the fact that acid suppressive therapy can only reduce the acidity of the gastric fluid but does not reduce the total number of reflux events, the conflicting results regarding medical therapy in asthmatics may be secondary to the continued exposure of the aerodigestive tract by caustic nonacid gastric juice. This is supported by the literature indicating that antireflux surgery improves respiratory symptoms in nearly 90% of children and 70% of adults with asthma and GERD.35,44 Additionally, improvements in pulmonary function were observed in around one-third of patients. A randomized controlled trial to compare surgical treatment with medical treatment for asthmatics with GERD demonstrated that fundoplication is the most effective approach to improve asthma symptoms and clinical course, although there was a minimal effect on pulmonary function, pulmonary medication requirement, or survival.35 On the other hand, a potential benefit of antireflux surgery is to stabilize or delay the progression of end-stage lung disease such as idiopathic pulmonary fibrosis.45

Metaplastic (Barrett's Esophagus) and Neoplastic (Adenocarcinoma) Complications

Barrett's esophagus (BE) is defined as a columnar lined segment of esophagus of any length visible on endoscopy with a biopsy showing intestinal metaplasia with the presence of goblet cells (Fig. 15-7). Despite this classification, it is common to make the distinction between short-segment BE (<3 cm) and long-segment BE (≥3cm). Both short- and long-segment BE are considered pathologic and premalignant. The prevalence of BE in the general population has been reported to be 1–25%.46–50 BE represents an end-stage form of GERD and carries a 30- to 50-fold increased risk of developing esophageal adenocarcinoma via the metaplasia-dysplasia-carcinoma sequence compared to people without BE.51 The incidence of esophageal adenocarcinoma in patient with known BE may be as high as 0.5% per year.52–54 BE is currently classified into four broad categories: (1) BE without dysplasia, (2) indefinite for dysplasia, (3) low-grade dysplasia (LGD), and (4) high-grade dysphagia (HGD). Recent studies have identified a high prevalence of biopsy-proven intestinal metaplasia at an endoscopically normal appearing GEJ, which is termed cardia intestinal metaplasia (CIM). The significance and natural history of CIM remains unknown. However, CIM is currently considered a separate entity from BE, although the pathogenesis of CIM has been shown to be similar to reflux-induced BE.55 Factors associated with the development of BE include abnormal bile reflux, hiatal hernia larger than 4 cm, a defective LES, and esophageal motility disorder.56

Pathophysiology of Barrett's Metaplasia

The pathogenesis of BE begins with injury to the squamous epithelium of the distal esophagus, secondary to the repeated distension of the stomach with large volume fatty meals that result in effacement of the LES and exposure of the distal esophageal squamous epithelium to caustic gastric juice.10 Continuous inflammatory injury in this area of the lower esophagus can cause permanent loss of the musculature of the LES, resulting in a mechanically defective LES. With further loss of the gastroesophageal barrier function, esophageal exposure worsens with resultant injury to progressively greater lengths of the squamous mucosa. Endoscopically, this injury can be observed as erosive esophagitis. The resulting columnar metaplasia that develops in a previous squamous-lined esophagus appears as a layer of mucus secreting columnar cells termed cardiac mucosa, which is a highly specific mucosa that arises to replace injured squamous epithelium and is believed to be an adaptive response to better tolerate exposure to gastric juice.57 Eventually, cardiac mucosa can remain without changing, form parietal cells, or develop goblet cells to become intestinalized cardiac mucosa in the divergent differentiation pathways.58

Screening and Surveillance

Although patients with the highest likelihood of BE are older (>50 years of age) Caucasian men with chronic reflux symptom,59 screening for BE remains controversial because of the inability to predict who has BE prior to endoscopy, the lack of evidence-based criteria, the invasiveness and expense of standard sedated endoscopy, and the increasing documentation of a subgroup of patients with BE who lack reflux symptoms.60 Surveillance endoscopy also remains controversial because of the lack of randomized trials supporting its value.60 However, previous retrospective studies have demonstrated that survival is statistically enhanced if cancer is detected by endoscopic surveillance rather than presenting with symptoms of obstruction.61,62 Surveillance endoscopy should be performed in patients with documented BE and those who have reflux symptoms controlled with antisecretory therapy or antireflux surgery. The Seattle Protocol (biopsies with jumbo forceps in four quadrants, along every centimeter of metaplastic epithelium with extra biopsies taken from suspicious areas) has been widely accepted. It should be noted that these surveillance biopsies sample only a small fraction of the esophageal epithelium (possibility for sampling error) but are the only method available for recognizing dysplasia.63 In patients with BE without dysplasia, we perform surveillance endoscopy every 3 years. The finding of low-grade dysplasia (LGD) requires a follow-up endoscopy within 6 months to ensure that more advanced disease is not present. If the 6-month surveillance is negative for high-grade dysplasia (HGD) or adenocarcinoma, yearly endoscopy is performed until no dysplasia is present on two consecutive annual endoscopies. The presence of HGD in flat mucosa should be confirmed by two experienced gastrointestinal pathologists and a subsequent endoscopy is performed within 3 months to reduce the chances of sampling error. Nodules within a field of HGD should undergo endoscopic resection to rule out malignancy. Patients with confirmed HGD should be counseled regarding the treatment options, including intensive surveillance, ablation therapies, and esophagectomy. Because the risk for the development of invasive cancer is 50% within 3 years of diagnosis, HGD is considered the threshold for therapeutic intervention. Patients with LGD or no dysplasia can also be a candidate for therapeutic intervention if they have excessive fear of the development of cancer or a significant family history of BE and esophageal cancer. In our practice, patients with nondysplastic BE who undergo antireflux surgery are also offered ablation of the involved segment of the esophagus.

Management of Dysplastic Be

Given the fact that HGD has a high rate of progression to cancer and the prevalence of occult cancer in esophagectomy specimens of patients with a preoperative diagnosis of only HGD has been reported to be 38–73%,64–66 esophagectomy has been recommended as a standard of care for HGD. However, esophagectomy is associated with significant mortality and morbidity even in experienced centers.67–69 Additionally, esophagectomy may be unnecessary in the treatment of HGD because lymph node metastasis is unlikely (<5%).70–72 In the recently updated guidelines by the American College of Gastroenterology, the authors state that “esophagectomy is no longer the necessary treatment response to HGD.”60 Several endoscopic ablation therapies such as photodynamic therapy,73 radiofrequency ablation therapy,74 and cryotherapy,75,76 and endoscopic resection techniques such as endoscopic mucosal resection77 and submucosal dissection78 have been introduced. When considering these endoscopic therapies, the accurate clinical staging is critical to prevent an inappropriate endoscopic therapy on a patient with a high risk of invasive or metastatic disease (Table 15-4).79 Currently, radiofrequency ablation therapy has been most commonly used since the results of a multicenter, sham-controlled trial was reported (Fig. 15-8).80 In this trial, 127 patients with dysplastic BE were randomly assigned to treatment with radiofrequency ablation or a sham procedure. In patients with LGD, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (p < .001). In patients with HGD, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19% of those in the control group (p < .001). The rate of complications such as stricture and bleeding was 6%. This study demonstrated the safety and high efficacy of radiofrequency ablation therapy for dysplastic BE. Theoretically, antireflux surgery potentially prevents the progression to dysplasia and adenocarcinoma.81 However, there have been no prospective randomized controlled studies documenting this supposition. Given the fact that BE results from GERD, antireflux surgery should be considered once BE is successfully treated.

The purpose of esophageal objective testing is to determine if the patients' symptoms are due to gastroesophageal reflux events and to define the severity of GERD and esophageal motility that will impact on the selection of the type of surgical therapy. The esophageal objective testing includes barium esophagram, upper endoscopy, esophageal manometry, esophageal pH monitoring, and MII-pH. Gastric emptying studies may be considered in patients with suspicious symptoms such as bloating and nausea.

Barium Esophagram

The barium esophagram is a test that is used to evaluate the entire anatomy of esophagus, including the esophageal body and both sphincters. This test is used to document the presence and size of a hiatal hernia, stricture severity and location, diverticula, esophageal emptying, and the presence of gastroesophageal reflux, both spontaneously and induced by provocative maneuvers. Esophageal motility can be assessed to some extent but is not the mainstay. Although the finding of reflux during the barium esophagram is thought by some to be a reliable indicator for GERD, the absence of roentgenographic evidence of reflux does not exclude disease.

Upper Endoscopy

Upper endoscopy is performed to examine the mucosa from the esophagus to the second portion of duodenum and biopsies can be obtained if necessary. Although only 40–60% of patients with GERD have endoscopic evidence of esophagitis, upper endoscopy has an excellent specificity for this diagnosis when erosions are present. Upper endoscopy may identify unexpected findings such as BE, malignancy, a large hiatal hernia, eosinophilic esophagitis, and Zenker's diverticulum. The location of the diaphragmatic crura, the anatomic GEJ, and the squamocolumnar junction should be recorded.

Esophagitis is one of indicators of the presence of GERD. The severity of esophagitis is most commonly described by the Los Angeles classification82; LA grade A is defined by the presence of one or more mucosal breaks that are less than or equal to 5 mm in length. LA grade B is defined by the presence of one or more mucosal breaks that are longer than 5 mm. LA grade C represents a more advanced stage where one or more mucosal breaks are continuous between the tops of two or more mucosal folds, but that involve less than 75% of the esophageal lumen circumference. LA grade D classifies one or more mucosal breaks bridging the tops of folds and involving at least 75% of the esophageal lumen circumference. Nonerosive esophagitis is difficult to reliably recognize endoscopically and its presence may be confirmed based on the microscopic findings of mucosal infiltration with polymorphonuclear leukocytes (PMNs), lymphocytes, eosinophils, and the recently described balloon cells.83,84 The extension of the relatively high mucosal papillae and hyperplasia of the basal zone are further evidence of mucosal injury. However, these microscopic findings do not prove the presence of increased exposure to gastric juice as they can occur from other forms of injury.85

Barrett's esophagus is suspected endoscopically when the squamocolumnar junction is located proximal to the anatomic GEJ, and the characteristic appearance of a “salmon pink color” mucosa is encountered in the lower esophagus. Multiple random biopsies should be performed, and the diagnosis of BE must be confirmed by the microscopic findings of columnar epithelium with intestinalization. To standardize the endoscopic findings of BE, the Prague classification system of circumferential (C) and maximal length (M) has been proposed (Fig. 15-9).86 This system identifies the landmarks of the squamocolumnar junction, the GEJ, the extent of circumferential columnar lining, and the most proximal extension of the columnar mucosa excluding islands to determine the length of BE. However, proximal islands of columnar lining and ultrashort BE (<1 cm) are not included in this system. The presence of BE is diagnostic of GERD. Particular attention must be paid to the squamocolumnar junction, where a mass, ulcer, nodularity, or inflammatory tissue should be considered suspicious for malignancy and requires biopsy. Nodules encountered in a field of BE should be removed with endoscopic resection for histologic examination and deep staging.

Abnormalities of the gastroesophageal flap valve (gastric portion of the LES) can be visualized by retroflexion of the endoscope. Hill and colleagues graded the appearance of the gastroesophageal valve from I to IV according to the degree of unfolding or deterioration of the normal valve architecture (Fig. 15-10).87 The appearance of the valve correlates with the presence of increased esophageal acid exposure, occurring predominantly in patients with grades III and IV valves. Grade IV valve is compatible with a hiatal hernia. A hiatal hernia is endoscopically confirmed by the finding of a pouch lined with gastric rugal folds residing 2 cm or more proximal to the margins of the diaphragmatic crura. The presence of hiatal hernia is often associated with an increased esophageal exposure to gastric juice. When a paraesophageal hernia (PEH) is found, a gastric ulcer (Cameron ulcer) or gastritis within the hernia should be excluded. Patients who present with anemia and a PEH with Cameron's ulcers should also have colonoscopy to rule out blood loss from a colon cancer.

Ambulatory pH Monitoring

Fuchs and colleagues demonstrated that 24-hour esophageal pH monitoring had a very high sensitivity and specificity (96%), as well as positive and negative predictive values (96%), with an overall accuracy of 96%.19 Since this study was reported, 24-hour esophageal pH monitoring has been a gold standard for the diagnosis of GERD. It is particularly important that preoperative pH testing be performed off medication in patients being considered for antireflux surgery to evaluate the symptom correlation with reflux events and the severity of the disease. Antisecretory medications should be discontinued 10–14 days prior to the study. An abnormal pH score with good symptom correlation has been shown to be the most important predictor of a successful outcome following antireflux surgery.

Despite being the most reliable technique for quantifying acid exposure in the distal esophagus, catheter-based 24-hour ambulatory pH monitoring has significant methodological limitations. The nasally passed pH electrode is uncomfortable and can lead patients to minimize or avoid reflux-provoking stimuli such as diet and physical activity, thus potentially resulting in a false-negative result. In addition, esophageal shortening during deglutition results in movement of the pH sensor closer to LES, thus potentially leading to a false-positive result.6,88 In addition, patients with atrophic gastritis may be achlorhydric and have nonacid reflux that is not detected with pH testing. The recent development of a wireless pH capsule that can be implanted in the esophagus and transmit pH data to an external receiver has significantly changed patient tolerability and capability of performing extended recording periods of 2–4 days.8,89 In addition, extended pH monitoring using wireless technology may improve the detection of reflux and increase the sensitivity of pH testing. Several studies have demonstrated that increasing the recording period from 24 to 48 hours results in an improvement in sensitivity of pH monitoring by 10–26%.7,8 Several studies have also consistently demonstrated higher acid exposure values on day 2 compared to day 1 with the wireless pH capsule.10 The pH probe should be correctly placed 5 cm (the capsule is placed 6 cm proximal to the LES or endoscopically measured anatomic GEJ) above the proximal border of the LES. This location minimizes potential noise from proximal stomach acid exposure, at the expense of decreased sensitivity.

Results of 24-hour pH monitoring are expressed in the form of a DeMeester score.12 Six variables are measured and factored in to this composite score:

• The total number of reflux events
• The percentage of total time spent in an acid environment with a pH less than 4
• The percentage of upright time spent in an acid environment with a pH less than 4
• The percentage of supine time spent in an acid environment with a pH less than 4
• The duration of the longest reflux episode
• The number of reflux episodes lasting more than 5 minutes.

The first four of these factors evaluate the frequency and severity of reflux, and the last two assess the ability of the esophagus to clear acid. Normal values for these six components were determined from 50 asymptomatic control subjects. The mean values for esophageal acid exposure and 95th percentile results are shown in Table 15-5.12

Combined Multichannel Intraluminal Impedance-pH Monitoring

Combined multichannel intraluminal impedance-pH (MII-pH) detects the intraesophageal bolus movement on the basis of a change in the resistance to electric current across adjacent electrode pairs positioned in a serial manner along a catheter. Multiple electrodes positioned along the axial length of the impedance catheter can determine the proximal extent of a reflux event. Air has a high impedance, whereas liquid has a greater conductivity and a lower impedance (Fig. 15-11). Based on this, it is capable of differentiating antegrade (swallow) from retrograde (reflux) bolus transit regardless of the composition of reflux (ie, liquid, gas, mixed) (Fig. 15-12). A pH monitor incorporated into the impedance catheter allows for simultaneous detection of both acid and nonacid contents. The configuration of impedance catheters can be modified depending on what type of reflux is targeted (ie, laryngopharyngeal reflux). MII-pH is a transnasal catheter-based system and the recording has been limited to 24 hours. As a result of the ability to detect, localize, and classify reflux events as acid, weakly acid, or nonacid, MII-pH has been posited as the future standard for reflux detection and monitoring, especially in patients with persistent typical and/or atypical GERD symptoms despite PPI therapy.27,33 However, the clinical utility of MII-pH is still being investigated.25

Assessment of Esophageal Body and Les Function

Esophageal Manometry

Esophageal manometry is the most accurate method to assess the coordination and pressure of the lower esophageal sphincter (LES) and the esophageal body. Patients with GERD may have manometric findings of a defective LES or impaired esophageal motility. Manometry is an important component in the preoperative workup of patients who are candidates for antireflux surgery. First, this form of testing excludes achalasia that may be occasionally misdiagnosed as GERD. Second, esophageal manometry characterizes the esophageal motility, and this information will be used to determine the surgical approach (Nissen or partial fundoplication). Finally, manometry enables measurement of the precise location of the LES for accurate pH probe placement.

Esophageal manometry used to be performed using water-perfused catheters with lateral side holes attached to transducers outside the body. Usually a train of five pressure transducers are bound together with the transducers placed at 5 cm intervals from the tip and oriented radially at 72 degrees from each other around the circumference of the catheter. The recent introduction and clinical application of high-resolution manometry (HRM) has made esophageal manometry simple, fast, and accurate. The basic concept of HRM is that by vastly increasing the number of pressure recording sensors and decreasing the spacing between them, one can monitor intraluminal pressure without spatial gaps between recording sites or temporal gaps between sampling times. Consequently, the morphology of the gastroesophageal junction pressure and esophageal peristalsis can be dynamically monitored in real time and a consistent fashion with normal respiration and with minimal movement-related artifact. HRM is performed using a solid-state manometric assembly with 36 circumferential sensors spaced at 1 cm intervals (O.D. 4.2 mm) (Sierra Scientific Instruments Inc., Los Angeles, CA). This catheter allows each of the 36 pressure sensing elements to detect pressure over a length of 2.5 mm in each of 12 radially dispersed regions. The vast amount of data generated by these sensors is then processed and presented in traditional linear plots or as a visually enhanced spatiotemporal tracing that is readily interpreted. This enhanced spatial resolution allows real-time monitoring of contractile activity over the entire esophageal length and can be coupled with impedance measurement so as to determine whether pressure readings and bolus movement correlate (Fig. 15-13).

An incompetent LES is defined based on the comparison study between 50 healthy volunteers and patients with symptomatic GERD. An LES is considered defective by having one or more of the following characteristics: an average LES pressure of less than 6 mm Hg, an average length exposed to the positive-pressure environment in the abdomen (intra-abdominal length) of 1 cm or less, and an average overall sphincter length of 2 cm or less. Achalasia is defined by the manometric findings of a hypertensive, nonrelaxing LES with esophageal aperistalsis (100% failed or simultaneous contractions). Ineffective esophageal motility is defined by manometric findings of either failed peristalsis of greater than 30% or mean wave pressure of less than 30 mm Hg. Nutcracker esophagus is defined by peristaltic contractions that exceed 180 mm Hg within the smooth muscle portion of the esophagus. Diffuse esophageal spasm is defined by greater than 20% simultaneous contractions. Depending on the integrity of esophageal peristalsis, the antireflux procedure can be tailored to include either a “floppy” Nissen fundoplication or partial fundoplication. In our practice, patients with ineffective or failed peristalsis undergo a Dor partial fundoplication.

Gastric Emptying

Delayed gastric emptying causes bloating, dyspepsia, postprandial nausea, and abdominal distension. Previous studies have demonstrated that GERD is associated with delayed gastric emptying in approximately 40% of patients, but the precise role of gastric emptying in the pathogenesis of GERD is unclear.90 It has been established that fundoplication improves gastric emptying by reducing the storage capacity of the fundus.91–93 However, persistent delayed gastric emptying can cause an unsatisfactory outcome after antireflux surgery as fundoplication itself can lead to bloating. Therefore, a gastric emptying study should be considered for candidates of antireflux surgery with suspicious symptoms such as nausea, vomiting, and bloating. The gastric emptying study is performed with a radionuclide-labeled meal. Emptying of solids and liquid can be assessed simultaneously by having both phases marked with different tracers. After ingestion of a labeled standard meal, gamma counter images of the stomach are obtained at 5- to 15-minute intervals for 1.5–2 hours. After collection of decay, the counts in the gastric area are plotted as a percentage of the total counts at the beginning of the imaging. The gastric emptying half-time (T1/2) is defined as the time required for 50% of the meal to exit the stomach. Patients with a T1/2 more than 90 minutes are considered to have delayed gastric emptying. It has been suggested that patients with a T1/2 of more than twice the upper limit of normal (T1/2 >180 minutes) undergo pyloroplasty at the time of fundoplication.91 However, the management of patients with a T1/2 between the upper limit of normal and twice the upper limit of normal (90–180 minutes) remains controversial.94 Postoperative bloating can be treated by reoperation and pyloroplasty, endoscopic dilation of the pylorus, or endoscopic botulinum toxin injection.

History of the Evolution of Antireflux Surgery

The first case of successful antireflux surgery was reported by Rudolph Nissen in 1956.95 In this case, Nissen enveloped the lower esophagus with the gastric fundus over a large intraesophageal dilator. Subsequently, Nissen and Rossetti suggested that only the anterior wall of the stomach be wrapped around the lower esophagus.96 Subsequently, the procedure has been modified in many ways. To avoid postoperative “gas bloat” syndrome, the partial anterior and posterior fundoplication techniques, in which the fundus encircles 270 degrees of the esophageal circumference, were developed and reported by Jacques Dor in 196241 and by Andre Toupet in 1963,43 respectively. Donahue et al first described the “floppy” Nissen technique, in which the fundoplication was performed over a large-diameter esophageal dilator.97 Then DeMeester et al further modified the operation by using a large dilator, limited the length of the fundoplication (2 cm), and completely mobilized the gastric fundus by division of the short gastric vessels.98 Since the first description of successful laparoscopic Nissen fundoplication by Dallemagne et al in 1991, the laparoscopic approach has been widely accepted.42 Several randomized trials have established that the laparoscopic approach achieves equivalent results with regard to subjective and objective resolution of GERD, with less postoperative pain, a shorter recovery period, and lower complication rate.99

Patient Selection for Surgery

Most patients have a relatively benign form of GERD that is responsive to life style and dietary modifications and medical therapy, and do not need surgical treatment. The mainstay of therapy for GERD is medical management. PPI therapy is highly effective, resulting in relief of symptoms and healing of esophagitis in more than 80% of patients.44 However, most patients require lifelong treatment and discontinuation of therapy results in symptomatic relapse within 6 months in approximately 90% of patients with esophagitis and 75% of patients with NERD.55 Additionally, it should be noted that PPI therapy does not reduce the esophageal injury associated with alkaline reflux and never addresses the mechanical incompetence of the barrier such as a defective LES and a hiatal hernia. A structurally defective LES is the most important factor predicting failure of medical therapy. Although the presence of a failed LES and esophagitis has been the primary indications for surgical treatment, antireflux surgery should be considered in any symptomatic patients with a documented GERD by pH testing or MII-pH regardless of presence of esophagitis and/or a defective LES. This is particularly true in patients who have PPI-responsive symptoms or persistent symptoms despite maximal PPI therapy. It is important to note that a good response to PPI therapy is a good indicator of the excellent outcome following antireflux surgery.

Young patients, especially women, with documented GERD are also excellent candidates for surgical treatment. They usually require lifelong medical therapy to control their GERD symptoms. The cost-effectiveness of surgical versus medical therapy in patients with GERD remains controversial.51,59,100 Recent studies have suggested that long-term usage of PPI potentially causes impaired calcium absorption and osteoporosis, which may be associated with an increased risk of fractures.57 This is particularly important for women.82 Patients with esophageal stricture are excellent candidates for surgical treatment.101,102 Esophageal stricture is often associated with a structurally defective LES and impaired esophageal contractility. Before proceeding with antireflux surgery, malignancy and a drug-related etiology of the stricture should be excluded, and the stricture should be dilated enough to resolve dysphagia. Esophageal manometry is then performed to evaluate the esophageal motility prior to laparoscopic fundoplication.

Patients with BE commonly have a severe structural defect of the LES and impaired esophageal motility.56 The presence of BE indicates the presence of GERD. In addition, BE may progress to adenocarcinoma. Antireflux surgery may prevent the development of adenocarcinoma, although there has been no prospective study performed that supports this supposition because of an extremely low incidence of adenocarcinoma arising from BE and the resultant inability to adequately power a comparison trial. BE should be first treated, followed by antireflux surgery. If BE with high-grade dysplasia and/or intramucosal carcinoma is found on biopsy specimens, an esophageal resection should be considered.

Patients with extraesophageal symptoms such as cough, aspiration, asthma, and progressive pulmonary fibrosis can also be good candidates for antireflux surgery. Before proceeding to surgical treatment, it is extremely important to document the correlation between reflux events and symptoms. Laryngopharyngeal reflux, a variant of GERD, may be associated with the development of extraesophageal symptoms.83 Because the clinical presentation of laryngopharyngeal reflux is nonspecific and there has been no way to detect laryngeal events, it has been extremely difficult to demonstrate causality in the clinical setting. MII-pH could be an effective tool to make a diagnosis of laryngopharyngeal reflux.

Principles of Surgical Therapy

The primary goal of antireflux surgery is to safely restore the structurally defective gastroesophageal valve, to prevent its shortening with gastric distention while preserving the patient's ability to swallow normally. To achieve this goal, several principles regarding the reconstruction of the valve should be considered. First, the operation should restore the adequate pressure and length of the distal esophageal sphincter to prevent reflux from the stomach. The effect is to augment sphincter characteristics and prevent unfolding of the valve in response to gastric distention. In normal swallowing, a vagally mediated relaxation of the distal esophageal sphincter and the gastric fundus occurs.85 To achieve adequate relaxation of the sphincter, only the gastric fundus should be used to create the fundoplication. The fundoplication should be placed around the distal esophagus and not the proximal stomach because it does not relax well with swallowing and has poor peristalsis. A deep groove on the surface of the fundoplication indicates that the repair is too tight and there should be no hesitation to take the repair down and begin over. Intraoperative injury to the vagal nerves should be avoided because it may cause the failure of sphincter relaxation with deglutition as well as delayed gastric emptying. Second, the fundoplication should not increase the resistance of the relaxed sphincter to a level that exceeds the peristaltic pressure of the esophageal body. Therefore, preoperative esophageal manometry is important to evaluate the esophageal motility. A Nissen fundoplication should be no longer than 3 cm and created over a 60F bougie. After a circumferential mediastinal esophageal mobilization resulting in 3 cm of tension-free intra-abdominal esophageal length, a posterior crural closure is performed to enable easy passage of the esophageal dilator. If adequate esophageal length cannot be achieved secondary to shortening of the esophagus, wedge gastroplasty as a lengthening procedure should be considered. Finally, an intraoperative endoscopic evaluation of the created valve is valuable to confirm the hallmarks of a successful fundoplication (Fig. 15-14). It should be noted that the initial fundoplication has the best chance to achieve the successful outcome.

Procedure Selection

A laparoscopic approach has been widely accepted, and the laparoscopic Nissen fundoplication is the procedure of choice for a primary antireflux surgery in the majority of patients with good esophageal motility and normal esophageal length. Previous prospective studies and randomized controlled studies have shown that the Nissen fundoplication is an effective antireflux surgery with minimal side effects, which provides long-lasting relief of reflux symptoms in over 90% of patients. Patients with a severe esophageal motility disorder defined by greater than 50% failed swallows, low peristaltic pressure, or an aperistaltic esophagus are best treated with a partial fundoplication to avoid the excessive outflow resistance.

Laparoscopic Nissen Fundoplication

The laparoscopic Nissen fundoplication is the most commonly performed antireflux procedure in the United States. The key points of this approach are the following:

• Preservation of both vagal nerves
• Complete mobilization of the gastric fundus by dividing the short gastric and posterior gastric vessels
• Extensive mediastinal dissection to obtain 3 cm length of tension-free intra-abdominal esophagus
• Creation of a large retroesophageal space
• Posterior crural closure
• Creation of a 2.5-cm “floppy” fundoplication around over a 60F bougie

The patient is placed supine and in a split-legged position, and the surgeon stands between the legs. A five-port technique is used: four 5-mm and one 12-mm ports are used. A 5-mm, 30-degree laparoscope is introduced through the 5-mm port placed in the left upper quadrant. All secondary ports should be placed under laparoscopic visualization. The second port (12 mm), which is used for the surgeon's right hand instruments, is placed 12 cm from the tip of the xiphoid process and 2 cm below the left costal margin. The third port (5 mm), which serves as the primary port site for the assistant, is placed within the left anterior axillary line along the costal margin. The fourth port (5 mm) is created immediately to the left of the xiphoid process for placement of the Nathanson liver retractor (Cook Medical, Bloomington, IN) that is used to expose the hiatal opening and gastrohepatic omentum. The fifth port (5 mm), which is for the surgeon's left hand instruments, is placed inferior to the right costal margin immediately to the right of the falciform ligament (Fig. 15-15).

The first step in the hiatal dissection is opening the gastrohepatic omentum and then extending to the right and left crura to expose the esophagus circumferentially at the hiatus. In up to 12% of patients, an accessory left hepatic artery, originating from the left gastric artery, will accompany the hepatic vagal branch. This vessel should be preserved or, when necessary, divided between clips. The relationship between the division of hepatic vagal branch and the dysfunction of gallbladder has been suggested. However, the benefit of preservation of the hepatic vagal branch remains controversial.86,103 The gastrophrenic attachments over the anterior aspect of the left crus are divided, and this dissection is further extended so as to mobilize the angle of His and divide the highest short gastric vessels (Fig. 15-16). The phrenoesophageal ligament is then opened at the right crus, and the dissection between the crus and esophagus is carried anteriorly (Fig. 15-17). During this maneuver, both anterior and posterior vagus nerves should be identified and preserved (Fig. 15-18). The hiatal dissection is then carried posteriorly until the union of the right and left crura is identified and the beginning of the posterior esophageal window is created (Fig. 15-19). Although the necessity of dividing the short gastric vessels remains controversial,104,105 several studies have suggested that incomplete mobilization of the fundus can cause postoperative dysphagia.106 Division of the short gastric vessels begins along the greater curvature of the stomach, at the level of the lower pole of the spleen (Fig. 15-20). After division of short gastric vessels, the posterior stomach is exposed, and the posterior pancreaticogastric fold and posterior gastric vessels are divided to achieve further mobilization of the fundus and expose the base of the left crus (Fig. 15-21). A posterior esophageal window is then completely established from the right side, and a Penrose drain is inserted behind the esophagus and the ends secured together anterior to the esophagus with several clips. The Penrose drain facilitates retraction of the esophagus during the mediastinal dissection (Fig. 15-22).

An extensive mediastinal dissection of the esophagus is performed circumferentially until at least 3.0 cm of distal esophagus remains within the abdomen in a tension-free fashion (Fig. 15-23). Attention must be paid to preserve both vagus nerves. If an adequate length of intra-abdominal esophagus cannot be obtained even after extensive mediastinal dissection, a lengthening procedure such as a stapled-wedge Collis gastroplasty should be considered.107 During the mediastinal dissection, attention should be paid to avoid injury of both vagus nerves and mediastinal pleura (Fig. 15-24). If the pleural cavity is accidentally opened, tension pneumothorax can be prevented by transabdominal insertion of a 14F red rubber catheter into the affected pleural space. At the end of the procedure, the pleural space is evacuated with a Valsalva maneuver and the catheter is removed. At the completion of mediastinal dissection, the diaphragmatic crura are approximated using interrupted 0 nonabsorbable suture. The closure should be snug, but not tight, around the esophagus and enable facile passage of the bougie (Fig. 15-25).

The fundus of the stomach is brought through the posterior esophageal window. By grasping the greater curvature of the fundus on either side of the esophagus, a “shoeshine maneuver” is performed to ensure that there is a proper orientation of the fundus without twisting or torsion (Fig. 15-26). At this point, an esophageal dilator (60F) is inserted and guided along the lesser curvature of the stomach under laparoscopic visualization. A 2.5-cm fundoplication is then performed around the end of esophagus with 0 nonabsorbable sutures that incorporate the right and left limbs of the fundoplication along the greater curvature. At this point, an instrument is advanced through the fundoplication toward the diaphragm to ensure the fundoplication is not too tight. Eventually, the fundoplication is secured with 3 nonabsorbable, unpledgeted sutures. Sutures should incorporate a full thickness of the stomach and partial thickness of the anterior esophageal wall, with care taken to avoid placement into the anterior vagus nerve (Fig. 15-27). The dilator is then removed and the intraoperative upper endoscopy is performed to confirm the proper orientation of the valve.

Laparoscopic Partial Fundoplication

Partial fundoplication is indicated in patients with impaired esophageal motility. The Dor and Toupet antireflux procedures consist of partial anterior and posterior fundoplication, respectively. Most of the key points are common with those listed for a Nissen fundoplication. The difference between a complete and a partial fundoplication is the structure of a newly created valve; a “nipple” valve in a complete fundoplication versus a “flap” valve in a partial fundoplication.

Dor Fundoplication

After mobilization of the distal esophagus and GEJ and hiatal closure, a 60F Bougie is placed as described in the section on Nissen fundoplication. The initial suture of the Dor fundoplication incorporates the greater curvature side of the gastric fundus 2 cm distal to the GEJ, lateral wall of the esophagus 2 cm proximal to the GEJ, and base of the left crus to re-create the angle of His. Re-creation of the angle of His is an essential element of the Dor fundoplication. The greater curvature is then sutured to the arch of the diaphragm toward the apex of the crura, bringing the anterior fundus over the anterior wall of the distal esophagus with seven interrupted 0 nonabsorbable sutures. This repair is carried over to the right crus to the 9 o'clock position. At completion, the fundoplication should appear smooth without creases indicating the absence of tension.

Toupet Fundoplication

In an identical fashion to the Nissen fundoplication, the gastric fundus is passed behind the esophagus through the retroesophageal space after hiatal closure and placement of an esophageal dilator. The right side of the fundus is sutured to the right margin of the esophagus with four nonabsorbable sutures, and the most distal suture is placed to the lesser curvature of the stomach immediately distal to the GEJ. The right posterior aspect of the fundus is sutured to the right side of the proximal preaortic fascia. A similar line of sutures secures the left limb of the fundoplication to the esophagus. The posterior aspect of the gastric fundus on left is sutured to the base of the left crus.

Outcome of Antireflux Surgery

The goal of surgical treatment for GERD is to relieve the symptoms by restoring a mechanically defective gastroesophageal barrier. This goal should be achieved without inducing postoperative complications such as dysphagia and gas bloat syndrome. Temporary dysphagia due to postoperative tissue edema of the wrap is common and generally resolves within 3 months without requiring any intervention such as dilation. However, persistent dysphagia beyond 3 months has been reported in up to 10% of patients. Bloating and hyperflatulence are also common after antireflux surgery because patients with GERD tend to swallow excessive air with saliva in order to neutralized acid refluxate. Scheduled administration of Simethicone is effective to reduce gas in the GI tract, improving the symptoms. In addition, it is important to prevent constipation so as to not worsen bloating. Another common side effect after antireflux surgery is the inability to vomit, but this is rarely clinically relevant. It is critical to control perioperative nausea so as to prevent retching with subsequent disruption of the repair.

Studies of long-term outcome following laparoscopic fundoplication have demonstrated relief of typical GERD symptoms such as heartburn, regurgitation, and dysphagia in more than 90% of patients at the follow-up interval of 2–3 years and 80–90% of patients at 5 years or more.98,108–110 Laparoscopic fundoplication results in a significant increase in LES pressure and length, generally restoring these values to normal. Postoperative pH studies indicate that more than 90% of patients normalize acid exposure to the esophagus. A randomized study with 11-year follow-up demonstrated that the open and laparoscopic approaches for the Nissen fundoplication have similar long-term subjective symptomatic outcome despite the significantly higher incidence of incisional hernia and endoscopically defective valves in the open group; from these data, the authors defined the laparoscopic approach as the procedure of choice in surgical management of GERD.111 There is a less predictable outcome of atypical symptoms such as cough, asthma, and laryngitis after antireflux surgery, being relieved in only two-thirds of patients probably because the documentation of correlation between reflux events and atypical symptoms has been difficult.112–114 This could be addressed with the introduction of a reliable esophageal objective testing tool such as MII-pH.

Quality-of-life analyses have become an important part of surgical outcome assessment, especially for the surgical treatment of benign disease such as GERD. Currently, both global and disease-specific questionnaires have been used to quantify quality of life before and after surgical intervention.115 Most studies have utilized the Short Form 36 (SF-36) instrument that is rapidly administered and well-validated. The GERD Health-Related Quality of Life Scale (GERD-HRQL), which is a disease-specific questionnaire, is also commonly used to address symptom severity in GERD. Fernando et al compared quality of life after antireflux surgery with that of nonoperative management for severe GERD, and showed that both SF 36 and GERD-HRQL were significantly superior in patients who underwent laparoscopic fundoplication compared with those who had medical treatment. They indicated that laparoscopic fundoplication should be considered for patients who are dissatisfied with medical treatment.116

Reoperation for Failed Antireflux Repairs

With the increased number of antireflux surgeries being performed, the reoperation for a failed repair has been more frequent. Previous studies have shown that the failure rates for open fundoplication range from 9 to 30%,98,117,118 whereas those for laparoscopic approach range from 2 to 17%.119,120 Many patients with mild recurrent symptoms can be managed with nonoperative therapy. It has been estimated that between 3 and 6% of antireflux surgeries will require reoperation.121 With the advance of minimally invasive surgical technique, more reoperations are being performed using a laparoscopic approach. However, the success rate for redo surgery does not equal to that of the initial antireflux surgery. Little et al reported that 84% of patients undergoing the first redo antireflux surgery achieved a satisfactory result, but only 42% of patients with three or more previous reoperations had a satisfactory result.118 Although a recent systematic review of reoperations showed that recurrent reflux and dysphagia were the most frequent indications for redo antireflux surgery,122 the etiology of recurrent symptoms varies considerably and patients with any persistent symptoms should be evaluated with objective testing. It is extremely important to identify the etiology of symptoms in order to choose an appropriate treatment option. Evaluation includes the repeat of esophageal objective testing such as upper endoscopy, barium swallow, manometry, pH monitoring, MII-pH, and gastric emptying. Based on radiographic findings, several patterns of recurrence have been reported (Fig. 15-28).123 Herniation and disruption of the fundoplication were the most common causes of failure.122 Additionally, inadequately treated short esophagus often contributed to repair herniation.124

There are several options for reconstructive antireflux surgery, including redo Nissen or partial fundoplication, Roux-en Y esophagojejunostomy, and esophagectomy. In redo fundoplication, it is essential to completely take down the previous repair in order to reestablish the normal anatomy, identify the “true” GEJ by medializing the gastroesophageal fat pat, preserve both vagus nerves, recognize a short esophagus, repair the crura, and re-create the proper fundoplication. The results of redo antireflux surgery are not as good as those of the primary antireflux surgery. However, good-to-excellent results can be achieved in more than 80% of patients using minimally invasive techniques at an experienced center.125,126

History

In 1919, Soresi published the first report on the surgical treatment of hiatal hernia.127 In 1950, Sweet described the transthoracic approach to hiatal hernia repair and 2 years later reported a series of 111 patients.128 Allison established the relationship between hiatal hernia and gastroesophageal reflux and proposed surgical options to correct the defect, namely returning the stomach to the abdomen and repairing the diaphragmatic hiatus.129 Subsequently, Barrett,130 Hiebert and Sir Belsey,131 and Hill et al132 set the stage for the importance of reestablishing the cardiophrenic angle in correcting reflux symptoms. In 1967, Belsey and Skinner presented data on 1063 patients with hiatal hernia.133 The work was the first to distinguish between a sliding hiatal hernia and a paraesophageal hernia (PEH). Since then, further evaluation and subclassification of hiatal hernias has occurred. From this work, the overriding consensus for the next several decades was that PEH required surgical repair so as to prevent strangulation, gastric necrosis, and patient death.

Categories of Hiatal Hernia

There are four types of hiatal hernia. Type I, sliding hiatal hernias, account for nearly 95% of all hiatal hernias.134,135 The combination of hiatal enlargement, lengthening of the phrenoesophageal ligament, and increased intra-abdominal pressure allows the GEJ to become intrathoracic. Sliding hiatal hernias may be more likely to progress in patients who are obese, pregnant, or have a chronic cough. Because the GEJ is displaced from its normal anatomic position, there is concurrent dysfunction of the LES manifesting as decreased resting pressure. This causes a loss of the angle of His, thus distorting the esophageal flap valve.87

The other three types of hiatal hernias are broadly classified as paraesophageal. Compared with a type I hernia, which has no hernia sac, all PEHs are covered circumferentially by a layer of peritoneum that forms a true hernia sac. Type II PEH is the least common.136 Type II hernias are characterized by preservation of the GEJ at its normal anatomic position within in the abdomen. The phrenoesophageal ligament is preserved, but the esophageal hiatus is enlarged and the fundus of the stomach is in the thoracic cavity. When there is proximal displacement of the GEJ and at least 30% of the stomach above the diaphragm, this is classified as a type III PEH, the most common type of PEH. When there is herniation of other organs into the thoracic cavity along with the stomach, this is termed a type IV PEH. Colon, small bowel, pancreas, spleen, omentum, and liver can migrate into the true anterior or posterior hernia sac. In addition to obstruction of the stomach, colon, or small bowel, there is the potential for compromised blood flow to the organs that are displaced intrathoracically.137 The most common complaints associated with PEH are related to mechanical issues caused by the location of the fundus above the diaphragm while the GEJ is fixed in its proper anatomic position in the abdomen. These include chest pain or pressure, obstruction, incarceration, possible strangulation, and pulmonary dysfunction commonly associated with chronic aspiration. Additionally, about 40% of patients with a PEH have chronic anemia that may be the result of either mucosal venous engorgement or a Cameron ulcer.138

Hiatal hernias, including PEHs, occur most commonly in women. In the largest published series on treatment of PEH, 75% of patients were female.139 About half of all patients presenting with PEH are older than 70, possibly because of loss of elasticity and muscle weakening. This loss of muscle tone around the diaphragmatic opening allows it to become dilated more easily. The gastric cardia then pushes into the opening and may or may not return to its normal anatomic position, thus further dilating the hiatus. Women may be affected more frequently than men because of changes during pregnancy. Other etiologies that cause increases in intra-abdominal pressures (obesity, constipation, and abdominal ascites) are also implicated.

Peh and Short Esophagus

Short esophagus is defined as less than 2.5 cm of tension-free intra-abdominal esophagus. Three types of esophageal shortening have been identified.140 The first is the apparent short esophagus, which is longitudinal compression of the esophagus in the mediastinum, but maintenance of normal esophageal length. The other two types are truly shortened esophagus and are classified as reducible and nonreducible. A reducible short esophagus is foreshortened, but with extensive mediastinal mobilization 2.5 cm of intra-abdominal esophagus can be obtained. In patients with a nonreducible short esophagus, extensive mediastinal mobilization fails to produce sufficient length and an esophageal lengthening procedure must be considered. The ability to accurately identify a nonreducible short esophagus is critical to accomplish a tension-free PEH repair that results in a low risk of recurrence. The incidence of short esophagus in patients undergoing antireflux surgery is 3–10%, 140,141 while a higher incidence has been noted in patients with PEH, which is commonly identified as a risk factor for short esophagus.142–144 Diagnosis of a short esophagus is made intraoperatively.

Preoperative Evaluation

At the time of evaluation, a detailed history and physical examination are important. While symptoms of reflux and dysphagia occur in 40–70% of patients, other symptoms are also commonly experienced. In the largest series to date, regurgitation, dyspnea, chest pain, or abdominal pain was also seen in 40–70% of patients.139 If a patient presents with acute-onset, severe abdominal pain with vomiting, the physician needs to be mindful of the possibility of gastric volvulus, especially in patients with a known history of PEH. In these cases, urgency is essential as timely diagnosis and emergent operative intervention can mean the difference between reduction of the hernia and repair and subtotal gastrectomy or death.

Esophogram

A barium esophogram will delineate how much stomach is herniated through the hiatus, and will determine whether there is organoaxial rotation of the stomach, which in conjunction with complaints of intermittent abdominal pain may be a harbinger of pending volvulus and either incarceration or strangulation necessitating elective repair on an urgent basis. Contrast examinations are also very important in the evaluation of recurrent PEH and may lend insight into the cause of the recurrence and assist in identifying complexities that may be encountered at the time of surgery.

Endoscopy

Endoscopy enables examination of the mucosa to evaluate for esophagitis, BE, stricture, or malignancy. Endoscopy may also estimate the size of the hiatus. In cases where there is concern for incarceration or strangulation, flexible endoscopy is a valuable diagnostic test of mucosal viability and enables gastric decompression.

Manometry and pH Testing

Most patients who have a PEH have poor esophageal motility. However, up to 80% may demonstrate improvement following surgical repair of the hiatal hernia.145 The use of pH probe testing is not necessary; it can be difficult to get accurate results, and the results do not change the management algorithm. Esophageal manometry will determine whether there is normal esophageal body function and enable tailoring of the antireflux procedure.

Gastric Emptying Study

Gastric emptying studies are not obtained unless the patient is presenting with a recurrence of a PEH that will require reoperation. For patients who have previously undergone surgical repair of the PEH, a gastric emptying study is important to determine if the vagus nerves have been injured, as this may alter the surgical approach.

Operative Approach

Surgery for PEH is reconstructive in nature with two primary goals: restore the normal anatomy by returning the GEJ and stomach to the abdomen and correct the condition that contributed to the development of the anatomic problem, namely GERD. Surgeons can either choose a transthoracic, transabdominal, or laparoscopic approach to repair a PEH.146–148 The best approach is a point of considerable debate and the different approaches to PEH repair have not been compared in a prospective, randomized trial. Laparoscopic repair significantly decreases postoperative complications and is the procedure of choice in most centers. The tenants of surgical repair include sac excision with complete reduction of the hernia from the mediastinum, establish tension-free esophageal length, repair the diaphragmatic crura, and perform an antireflux procedure.

Transthoracic Approach

A left posterolateral thoracotomy is performed with a planned entry at the seventh interspace. The inferior pulmonary ligament is incised to the level of the inferior pulmonary vein and the mediastinal pleura overlying the esophagus is opened. The esophagus is circumferentially mobilized from the carina toward the diaphragm. The hernia sac is then dissected free of surrounding structures until the crura are identified. The sac is then incised just above the crural fibers to avoid loss of the peritoneal covering of the crura. The esophagus and stomach are then dissected away from the crura. When the right crus is identified, the gastrohepatic ligament is divided to the level of the left gastric artery. The stomach is mobilized beginning with the highest short gastric vessels. Once the fundus is restored to its normal anatomic position, the crural approximation stitches are placed, but not tied. During mobilization of the anterior esophageal fat pad, the vagus nerves need to be identified and protected. Mobilization of the fat pad enables identification of GEJ to determine if there is appropriate intra-abdominal esophageal length. A fundoplication is then performed as described in section on Nissen fundoplication. The fundoplication is placed into the abdominal cavity and crural sutures are tied.

Laparoscopic Approach

The hernia sac is gently reduced. This is accomplished by grasping the sac just inside the diaphragmatic crura at the 12 o'clock position (Fig. 15-29). The sac is incised providing access to the fibroareolar plane within the posterior mediastinum. Dissection in the correct plane is generally free of hemorrhage and provides excellent visualization of the pleura, esophagus, and vagus nerves. The borders of the dissection are the pleura laterally, the pericardium anteriorly, and the aorta posteriorly. Circumferential mobilization facilitates reduction of the entire hernia sac into the abdomen, thus returning the stomach to its normal anatomic position. The gastrohepatic ligament is divided and this provides access to the posterior aspect of the sac from the right side. Short gastric vessels are completely divided and the gastroesophageal fat pad is fully mobilized to allow visualization of the GEJ (Fig. 15-30). Anterior and posterior vagus nerves are identified and preserved. The GEJ is evaluated to determine that there is an adequate length of intra-abdominal esophagus (Fig. 15-31). If aggressive esophageal mobilization fails to produce an appropriate length of esophagus, an esophageal lengthening procedure is performed using a stapled wedge gastroplasty.149 (Fig. 15-32). An antireflux procedure is routinely performed (Fig. 15-33). The crura are reapproximated using nonabsorbable 0-suture. Bioprosthetic mesh is used selectively to buttress the hiatal closure.

Outcomes—Transthoracic Approach

The University of Michigan retrospectively reported their 25-year experience with open transthoracic repair of PEH.146 In their series, 240 patients underwent PEH repair via a left thoracotomy, and 96% had a Collis-Nissen gastroplasty performed as part of the repair. At a median follow-up of 28 months, 86% of patients were satisfied with the results of the PEH repair, despite radiographic recurrence in 12% of patients. Maziak and colleagues followed 94 patients who underwent transthoracic PEH repair.150 The majority of the patients underwent a Collis gastroplasty with a Belsey fundoplication. With a median follow-up of 72 months, anatomic recurrence was identified in 2%, postoperative morbidity in 19%, and mortality in 2%. More than 90% of the patients had good-to-excellent symptom resolution.

Outcomes—Laparoscopic Approach

Surgical repair of PEH is a complex operation and the minimally invasive approach requires advanced laparoscopic expertise. Very early experience of small, retrospective case reports was that these reports were able to demonstrate feasibility with good outcomes over a short follow-up.151 The initial enthusiasm for laparoscopic repair of giant PEH waned as further reports were unable to reproduce the early results and were associated with high failure rates.152–154 Recurrence rates as high as 40% with mortality rates of up to 5%, both considerably higher than those for either open transthoracic or transabdominal repairs, were reported. However, over the past decade there has been a considerable evolution of the technique, and the feasibility and safety of the laparoscopic approach have been well established.139,155 Operative mortality following laparoscopic PEH repair is now extremely low (0–2%) but is higher in patients older than 80 and in those requiring urgent repair.139,156 Laparoscopic repair of PEH produces equivalent long-term outcomes to open approaches when all the surgical principles of the open technique are meticulously followed. At the University of Pittsburgh we have reported on 662 patients over the past 10 years who have undergone laparoscopic repair of PEH with low rates of radiographic recurrence (15.7%) and reoperations (3.2%). In the subset of these patients with a minimum follow-up of 5 years and a median of over 6 years, these results are durable and show unchanged rates of recurrence or reoperation.157 Interestingly, we have found that radiographic recurrence was not associated with symptom recurrence and reflux-related quality-of-life scores indicated good-to-excellent results in 86.7% of patients. Additionally, laparoscopic repair significantly decreased postoperative complications, as well as length of intensive care unit stay, length of hospital stay, time to oral intake, and pain medication use.158,159

The routine use of mesh to reinforce the esophageal hiatus after laparoscopic repair decreases recurrence rates. In the only prospective randomized study on the use of mesh in laparoscopic repair of PEH, the recurrence rate in patients who did not have mesh was 42% as compared with a recurrence rate of only 9% when mesh was used, with only 6-month follow-up.160 Furthermore, while a number of studies have shown safe and effective use of mesh,161–163 reinforcement with mesh may increase the incidence of complications. A recent paper by Stadlhuber and associates reports that complications from mesh reinforcement of the esophageal hiatus may be underreported.164

Conclusion: PEH are most commonly diagnosed in people older than 70 years. With the population aging, surgical repair of PEH may become more common in the future. A detailed history is important because PEH produces either gastrointestinal or pulmonary symptoms, such as shortness of breath. Over 90% of people who undergo PEH repair have a significant improvement in symptoms that are long lasting. While open repairs using transthoracic and transabdominal approaches have resulted in low complication rates and mortality, the laparoscopic repair, in experienced hands, results in excellent outcomes and is safe.