Three basic defense systems exist to prevent pathologic GER and minimize the effects of physiologic reflux. They are anatomic reflux barriers, esophageal luminal clearance mechanisms, and intrinsic tissue resistance to esophageal mucosal damage. Orlando⁴¹ has suggested that these defenses are hierarchically arranged according to their significance and potential impact. Anatomic barriers are the first line of defense and physically limit both reflux episode frequency and material amount. The second tier of defenses acts to reduce the duration of contact between the deleterious components of the refluxate and the esophageal mucosa. The third level of defense is more theoretical and pertains to the esophageal epithelium itself. It has been proposed that histochemical and cytoprotective elements exist that can curtail acid or other toxin-mediated tissue destruction.

The most critical anatomic reflux barrier is the LES. Esophageal contraction waves are noted to slow immediately above the LES segment. In primates, the LES is not a true sphincter, but a region of relative high pressure in the distal esophagus at or just above the esophagogastric junction (EGJ). In adults, it measures 3 to 5 cm in length. A circumscribed area of thickened smooth muscle in this location can be found, but a distinct valve-like entity, as at the pylorus or anus, is not identifiable. In normal individuals, manometry demonstrates pressures between 15 and 30 mm Hg within the LES segment, separating lower-pressure zones above and below. Above the LES, the esophageal pressure is normally 5 mm Hg less than atmospheric pressure; below it (gastric), 5 mm Hg greater than atmospheric pressure. Fundamentally, LES integrity depends on (a) its overall length (dP/dT), (b) its external pressure environment relative to body compartment (intra-abdominal positive pressure versus intrathoracic negative pressure), and (c) its abdominal length, a synthesis of these characteristics.

The LES remains contracted at rest owing to intrinsic myogenic activity, and it normally relaxes with the approach of a primary peristaltic wave. Once food passes through the LES,
the LES returns to its contracted state, achieving a closing pressure that is about twice its resting value. Lower esophageal pressure relaxation also occurs with secondary peristalsis. Holloway and coworkers²² have shown that postprandial gastric distention leads to transient LES relaxation, whereby gas is vented from the stomach. According to Mittal and coinvestigators,³⁸ physiologic and pathologic GER occurs principally during these vagally mediated and non–swallow-induced relaxations. Longer reflux events and increased episode frequency dominate in the development of GERD. Ultimately, Dodds and colleagues¹² have ascribed these GERD-inherent alterations to (a) attenuated LES tone, (b) intra-abdominal pressure spikes that overcome the LES (stress reflux), or (c) increased transient LES relaxations. This mechanistic account, however, considers little beyond sphincter impairment in the multifactorial etiology of GERD.

Equally integral to the barrier defenses are the other components of the diaphragmatic apparatus. Encircled by the right crus of the diaphragm, the LES is mechanically buttressed. On inspiration and other states of increased intra-abdominal pressure, the hiatal–crural complex contracts, amplifying LES closure strength. Also, the pincer-like arrangement of the crural fibers creates an oblique entry for the esophagus as it meets the stomach. This configuration, termed the angle of His, augments LES pressure more indirectly. Because of this acute angle, a distended stomach’s walls compress the esophagus, reciprocally applying force to the LES from outside the esophageal wall. The phrenoesophageal ligament provides further scaffold-like support to the LES. This membranous continuation of the endothoracic fascia and peritoneum circumferentially envelops the distal esophagus within its diaphragmatic canal. It anchors the distal esophagus in the abdomen, maximizing LES abdominal length. Finally, the redundant nature of the mucosal folds within the gastric cardia acts like a sponge and soaks up the refluxate, limiting its total overall volume.

In addition to an anatomic barrier defense, the esophagus defends against caustic refluxed agents by clearing them from its lumen. The bulk of refluxate volume is cleared by a combination of gravity and esophageal peristalsis. In terms of gravity, a patient’s posture, whether upright or supine, warrants consideration. In nocturnal reflux, the effects of gravity’s force are difficult to realize; in recumbency, little benefit is derived. Similarly, the patient who remains upright following meals may minimize the consequences of reflex-induced LES relaxations. More essential to effective luminal clearance is normal esophageal motility and preserved motor function. An intact peristaltic pump clears the esophagus of refluxed irritants much as a coordinated peristaltic wave propels a food bolus from the cervical esophagus through to the stomach. Although the propulsive contractions following deglutition are initiated quite differently, reactive peristalsis that empties a reflux-filled esophagus ultimately relies on the same end network of striated and smooth muscle. Proper esophageal body motor activity is critical, therefore, for clearance by peristalsis to succeed. Failed peristalsis and diminished muscular strength, moreover, can arise secondary to reflux-mediated injury. A vicious, perpetual cycle includes mucosal inflammation leading to submucosal and mural thickening, loss of myogenic tone, compromised luminal clearance, stasis of refluxed material, and a reinvigoration of this cascade through further tissue damage. Furthermore, Kahrilas and Shi²⁸ and others have demonstrated GERD-associated motor disturbances. Patients with GERD have lower-amplitude peristaltic contractions, more frequent aperistaltic contractions, and more overall failed contractions with swallowing than would be expected in nonpathologic GER.

Salivary and other esophageal gland secretions provide further means of clearance through chemical neutralization. Although produced in quantities nearing 1 L per day, these glandular fluids do not mechanically wash out or dilute refluxed matter to any significant degree. Rather, their bicarbonate-rich composition enables neutralization of refluxed stomach acid, according to Helm and coworkers.²⁰ While contributing minimally to bolus clearance, these secretions are factors in the effective clearance of luminal acid.

The inherent resistance of the esophageal mucosa to tissue destruction constitutes the final line of defense against GER. Although defects in physical barrier defenses have been emphasized historically, it is now increasingly evident that the regressive slide from GER to GERD can occur without failures in anatomic structure. Monitoring of esophageal pH by Schlesinger and colleagues⁵⁰ has revealed that normal acid contact times can be found in a significant proportion of patients with histologically proven erosive and nonerosive esophagitis. In healthy subjects, Schindlbeck and associates⁴⁹ have shown daily cumulative acid contact times of 1 to 2 hours. Explanations for esophagitis in the setting of normal acid contact times are limited. Theorized increased rates of gastric acid and pepsin production in GERD patients have been disproved. The alternative explanation offered by Orlando⁴¹ and other investigators is that impaired tissue resistance accounts for reflux-associated disease and normal acid contact times. A multidimensional schema has been established, detailing cellular and biochemical protection at the level of the esophageal endothelium. Cell membrane and intercellular junctions limiting the diffusion of HCl are being characterized, proton-blocking glycoconjugates have been isolated, and tissue-specific buffering machinery with upregulation of epithelial carbonic anhydrase and transmembrane Na/H and Cl/HCO₃ exchangers has been found. Susceptibility to breaks in tissue resistance has been shown to be greater in cigarette smokers, alcohol users, and consumers of hot or hypertonic solutions as well as with advancing age.

Although independent reference is frequently made to the causal relationship between hiatal hernia and GERD, such separate discussion is unwarranted. As Hiebert²¹ has observed, at least half of patients with hiatal hernia do not have symptomatic GER, and not every patient with severe GERD has a concomitant hiatal hernia. The altered anatomy that defines hiatal hernia also defines critical lapses in antireflux barrier and luminal clearance defenses. The functional hiatal–crural unit disassembles. Lost is the pincer grasp by the right crus on the region of the LES. The angle of His becomes flattened and obtuse, minimizing the counterpressure phenomenon that occurs with gastric distention. In the most common forms of hiatal hernia, the gastroesophageal junction is displaced into the chest, whereby the antireflux positive pressure in the abdomen is replaced with the proreflux negative pressure characteristics in the thorax. The herniated gastric portion becomes functionally obstructed at its distal extent because of diaphragmatic impingement against the stomach’s body. This retained pouch becomes a reservoir for secretions and swallowed air, effectively maintaining a source of refluxate volumes from which individual GER episodes are essentially guaranteed. Luminal clearance is also affected because of esophageal foreshortening in a long-standing hiatal hernia.
Esophageal stripping waves become weakened and attenuated in hiatal hernia with degradation of coordinated peristalsis. The herniated portion of the stomach fails to empty completely or clear thoroughly. Interestingly, Sloan and Kahrilas⁵² have shown that fundoplication, even outside the context of hiatal hernia, improves gastric emptying through sacrifice of the fundic reservoir. Finally, the laxity of the mucosal folds of the cardia is diminished in hiatal hernia, relinquishing trapped gastric juice for its potential increased backflow across the LES.

Clinical manifestations of GERD are divided into two subsets. Patients are grouped according to their presenting symptoms: typical or esophageal GERD, as opposed to atypical or extraesophageal GERD. Typical GERD symptoms include heartburn, regurgitation, and dysphagia. Heartburn is classically characterized as a burning sensation in the epigastrium or substernal area. Patients with regurgitation complain of a sudden bitter or acid taste that develops following eating, commonly at night once supine in bed. Dysphagia is best recognized as a complication of GERD in the setting of an inflammation-induced esophageal stricture or problems with esophageal peristalsis. Atypical symptoms include sore throat, cough, nonallergic asthma with wheezing, dysphonia, and chest pain. These extraesophageal difficulties likely relate to reflux that damages the laryngopharyngeal apparatus and, as suggested by Wetscher and colleagues⁶³ and other investigators, affects the respiratory tract in a complex and only preliminarily understood manner.

Distinguishing between these subpopulations is more essential than perhaps was first realized. The correlation between typical symptoms and increased esophageal acid exposure is certainly stronger than the pathophysiologic link between atypical symptoms and acid reflux. More importantly, atypical symptoms are much less reliably relieved through antireflux surgery than their typical counterparts. The explanation for this difference is likely multifactorial. Overall, the chronicity of the injury pattern may be the most important factor. Extraesophageal manifestations of GERD likely develop gradually and consequently may prove less reversible. Acutely reducing or even removing the insult completely with fundoplication may have little impact on the more permanent changes that have occurred in reflux-related respiratory disease.

Determining that GER is the underlying cause of a patient’s symptoms is not only the most critical element in proper patient selection, it also is central to the diagnostic testing and evaluation of the patient considered for antireflux surgery. Every patient being considered for antireflux surgery undergoes preoperative testing. Although response to proton pump inhibitor (PPI) therapy has definite clinical implications, amelioration of symptoms with PPI treatment does not confirm the diagnosis of GERD. All of these preoperative studies are designed to prove a correlation between symptoms and reflux-mediated disease. Again, establishing this causal relationship, not merely its association, maximizes the chances before the operating room that antireflux surgery will help the patient. This concept is even more important in the laparoscopic era, in which the threshold for surgical referral is markedly lower. Complementing this increased tendency for referral is the knowledge that the GERD patient now presents sooner with an earlier form of the disease and rarely with any significant degree of disease progression. Of course, meticulous intraoperative technique and judgment followed by detailed postoperative care and instruction are integral to a successful surgical outcome. It is this preoperative attitude and assessment, however, that deserves the most emphasis and demands the most skill. At minimum, three preoperative tests are routinely undertaken on all patients: (a) 24-hour continuous esophageal pH monitoring, (b) esophageal manometry, and (c) anatomic imaging by barium swallow, esophagogastroscopy, or both.

Monitoring of pH objectively qualifies the existence of pathologic esophageal acid exposure. A summary 24-hour pH score is computed based on the number of reflux episodes per day, those episodes lasting longer than 5 minutes, and the total time that esophageal pH drops below 4.0. The patient-activated event marker, or a record tracking patient complaints alongside continuous pH measurements, also supports reflux–symptom correlation. Realizing that most patients with typical symptoms, especially in the setting of confirmed erosive esophagitis or clear improvement with PPI therapy, will have an abnormal 24-hour pH score, pH testing also quantifies the degree and pattern of reflux disease. As characterized by Fein¹⁶ and Fein and coinvestigators,¹⁷ failure of medical therapy is more common, and GERD-related strictures, ulcers, and other complications are higher with nocturnal or bipositional reflux. Furthermore, it has been established that a structurally normal LES may function abnormally. A characteristic pattern of reflux is seen in this situation: namely, multiple short reflux episodes following meals and while upright. Interpretation of these patterns may provide added insight into the GERD syndrome beyond an abnormal 24-hour score.

The LES and intrinsic esophageal tone (effective luminal clearance) constitute the chief anatomic defenses limiting the duration and potential impact of refluxed gastric juice. Esophageal manometry provides information relevant to the status of these barriers. Pressure transducers positioned at standard intervals along the length of the esophagus record in real time the propagation of a peristaltic wave with swallowing. A significant correlation between esophageal motor dysfunction and GERD has been established by Rakic and associates,⁴⁵ among others. Absent or disordered peristalsis can significantly complicate the surgical treatment of GERD. Undetected poor peristaltic function can not only undermine the relief potentially garnered through fundoplication but also frequently exacerbate a patient’s overall difficulties. LES pressure <10 mm Hg anticipates the theoretical salutary effect that reinforcement of the LES should have. LES incompetence, however, may have little influence on GERD or antireflux surgery. Many believe that in GERD, normal transient receptive relaxation of the LES occurs too frequently and independent of an initiated peristaltic wave. Others contend that GERD arises because of stress reflux in which sudden spikes in intra-abdominal pressure force acid back across the sphincter irrespective of its integrity. Regardless, as defined by Costantini and colleagues,⁹ the association between low LES tone and medical nonresponders has important implications for GERD therapy in general and surgical therapy in particular. Manometry also assists in localizing the LES, a key factor in determining overall esophageal length. Esophageal manometry is not essential, therefore, to document a lax LES; manometry principally identifies insufficient esophageal
propulsive function that can be caused by long-standing reflux. Preserved peristaltic pressure is needed to propel a bolus of food through the fixed and static obstruction caused by the fundoplication itself; a partial fundoplication may be more appropriate if normal esophageal motility has been lost to any degree.

Barium esophagram and upper endoscopy provide nonfunctional information that also should be integrated in the overall surgical evaluation of the patient with GERD. The knowledge gained through these investigations extends beyond anatomy or “road mapping.” The possibility of a foreshortened esophagus, a significant cause of reherniation and fundoplication failure, is best suggested by findings evident through imaging. A large hiatal hernia (>5 cm) and esophageal stricture are two findings that can herald the existence of a short esophagus. Although a shortened esophagus can be inferred through the manometric localization of the LES, a large hiatal hernia that fails to reduce in the upright position on video esophagram is considerably more indicative of this phenomenon. The patient with long-standing GERD, whether refractory to medical therapy or not, and certainly patients with GERD-associated dysphagia, should undergo endoscopy with biopsy. Mucosal injury is best detected through direct visualization. Endoscopic biopsy of any mucosal irregularity is indicated and can reveal Barrett’s metaplasia, which needs to be monitored even after fundoplication. This is particularly noteworthy given the symptomatic improvement that should follow fundoplication; the impetus for routine surveillance may be lost, from both the patient’s and physician’s standpoint. The discovery of Barrett’s dysplasia, even low-grade, warrants careful consideration. It may be imprudent to manipulate the EGJ surgically, even minimally, with the prospect of a definitive extirpative procedure fairly soon thereafter.

Symptomatic and documented GER that persists despite maximal medical therapy (specifically high-dose, usually twice-daily PPI therapy) is recognized as the most common indication for surgical intervention. As DeVault and Castell¹¹ have pointed out, however, medical intractability is quite a rare phenomenon in current practice. Before the introduction of PPIs, the medical treatment of GERD was suboptimal. Treatment failures with diet modification, weight loss, alkali-based agents, neutralizing antacids, and histamine receptor antagonists (H2 blockers) were common. Historically, nonresponders represented most of those referred for antireflux procedures, irrespective of approach. GERD-related symptomatology refractory to high-dose PPI therapy, as Spechler⁵⁴ argues, should raise essential doubts concerning the very etiology of these symptoms. In fact, a well-established correlation has been drawn by Campos and coworkers^5,6 regarding the effectiveness of PPI therapy and that of antireflux surgery: there is a strong positive predictive value between the response to PPI treatment and the success of fundoplication. This parallel pattern of therapeutic success should and will change practice patterns eventually. The present candidate pool for antireflux surgery is composed less of PPI failures than, primarily, those patients who fail to comply with PPI treatment. Medication expense and the need to follow closely a frequently inflexible dosing schedule are often cited as the chief causes of noncompliance. Many GERD patients are young and unwilling or unable to adhere to long-term if not lifelong medical therapy programs.

The medically optimized patient who develops GERD-related esophageal injury or complications is also appropriately referred for surgery. Endoscopically detected severe esophagitis, mucosal ulceration, or stricture formation should all be recognized as disease progression. Recurrent aspiration with chemical pneumonitis and chronic laryngopharyngeal irritation due to reflux are also indications to proceed with antireflux surgery.

Although GERD-induced epithelial injury leading to metaplasia is a reproducible sequence of events, the ability of surgery to interrupt or delay this pathologic cascade remains dubious. Evidence would suggest that once triggered, this degradation continues without the possibility for interruption. Repeatedly, it has been shown that antireflux surgery cannot prevent dysplastic change. Accepting that GERD surgery has little impact on the natural history of Barrett’s esophagus, it seems prudent to view Barrett’s not only as a controversial indication for antireflux surgery but also, in the absence of symptoms or other complications, not an indication for surgical intervention.

Antireflux surgery has had two main challenges it has needed to overcome in order to be accepted according to Hagen and Peters.¹⁸ As initially performed, the standard fundoplication was a lengthy, tight wrap that overly compensated for a hypotensive LES. The result was dysphagia and gas bloating. Rossetti and Allgower⁴⁶ (as well as Negre⁴⁰ and Donahue¹³ and their colleagues and others) all recognized that reinforcement of the LES could be accomplished with a shorter and looser fundoplication, preserving the capacity to swallow normally the majority of food types and to belch. The second hurdle that faced antireflux surgeons was the perioperative morbidity (and mortality) associated with historical antireflux surgery. Hospital stays were typically longer than 1 week, with 2-month disabilities from work. Minimal access fundoplication has radically if not completely reversed these negative events. Ultimately, although the medical management of GERD is less invasive in design, it has potentially much more complexity in practice. GERD treated medically requires long-term (chronic) therapy, may have unforeseen side effects, and ultimately may be too one-dimensional in its concept.

Operative therapy for GERD incorporates a multitude of surgical decision-making skills. There is no standard antireflux procedure against which all other procedures can be compared; no single operation can repair every GERD-related abnormality or treat every patient with GERD. Important factors that need to be integrated in a comprehensive surgical plan include (a) operative approach (transabdominal, transthoracic, laparoscopic, even thoracoscopic); (b) degree of fundic wrapping—complete (total) or partial; and (c) adjunctive procedures—esophageal lengthening techniques (by gastroplasty), pyloroplasty, and the occasional gastropexy (by gastrostomy tube insertion).

Every antireflux procedure initiates with the same three basic goals. The principal steps of the operative procedure are ordered as to reflect these essential endpoints. First, thorough esophageal mobilization is necessary to restore at least 2.5 cm (optimally, 3 to 5 cm) of intra-abdominal esophageal length. Second, the invariably widened esophageal hiatus must be closed.
Third, the lower esophageal high-pressure zone must be reestablished. The fundic wrap recreates an acute angle of His and in turn refashions normal orientation for the gastric sling and clasp fibers, foundations for LES tone and cardial competence. The wrap secondarily calibrates the esophagogastric orifice. Omission of or compromise in any of these steps will negatively affect the final result.

Finally, every attempt should be made to minimize potential complicating forces before surgical intervention. Weight reduction, both as an inherent counterreflux measure and postoperative decrease in tissue strain, must be encouraged. Optimization of pulmonary function—whether through smoking cessation, treatment of bronchospasm, or reduction in airway obstruction—is necessary. Liberal use of antiemetics, restricted use of anticholinergics, and avoidance of narcotic-induced constipation are important concepts in the immediate postoperative period.

In 1951, Allison¹ described the first procedure designed specifically to treat GERD. Although this was unsuccessful, the essential concepts governing antireflux surgery were defined. In 1955, Rudolf Nissen folded the gastric fundus on itself to envelop the distal esophagus in a 49-year-old woman with chronic GERD. This technique, developed by Nissen serendipitously almost 20 years before, proved successful and was published in 1956. Now referred to as a Nissen fundoplication, this procedure has undergone considerable modification and refinement. Total fundoplication, meaning a 360-degree wrap, can be accomplished through the abdomen, the left chest, and using the laparoscope.