Although the symptoms of heartburn and acid regurgitation are highly specific for GERD, they are imperfect and other non-GERD diagnoses need to be considered. A significant number of symptomatic patients without erosive disease are found not have excessive reflux suggestive that their esophagus is hypersensitive. The best way to validate the diagnosis in a patient with a negative endoscopic examination is ambulatory esophageal pH monitoring, that is performed either using a trans-nasal catheter (impedance/pH), or wirelessly, by placing the Bravo pH probe (Fig. 7.1) [2]. These tools quantify esophageal acid exposure and are invaluable in establishing the diagnosis of GERD and, further, assessing its magnitude, occurrence in the upright or supine position, and relating acid reflux events to symptoms. If the pH/impedance study is negative, other possibilities, particularly achalasia, esophageal spasm, or gastroparesis, need to be considered. Yet, even if the pH/impedance study is positive, overlap syndromes may occur. For example, in a recent study, pathologic acid reflux was found in 44% of patients with esophageal dysmotility/achalasia and 73% of patients with gastroparesis [3].

It is also useful to examine the impact of GERD on the patients’ quality of life (GERD-HRQL) by asking the patient to fill out standardized, disease-specific questionnaires. This way, the decision to proceed with potentially beneficial yet invasive interventions, endoscopic or surgical, can be adequately balanced against their respective risks [4]. Ideally, these GERD-HRQL assessments should be done at baseline as well as during a trial of PPI therapy. In a patient using PPIs, it is useful to ask what happens if these drugs are transiently discontinued. Under such circumstances, bone fide patients with GERD quickly develop heartburn and acid regurgitation (or other more atypical symptoms) while patients with other diagnoses tend to tolerate PPI abstinence for quite some time. The latter group of patients should not be considered as good candidates for invasive procedures but instead be evaluated further to define the underlying reason for their symptoms.

Another important question to be addressed is the presence of regurgitation, or “volume” reflux, particularly while patients are on PPI therapy. Its presence suggests more severe, mostly supine GERD, but also a higher likelihood of underlying hiatal hernia, complicated disease (i.e. Barrett’s esophagus) and respiratory manifestations. Regurgitation is a key point in the discussion of pursuing endoscopic and surgical therapies for GERD [5].

The presence, type and dimensions of hiatal herniation play a pivotal role in further decision-making (Fig. 7.2). Classic para-esophageal hernias readily disqualify from endoscopic intervention. The same is true for mixed hernias that are typically large enough and fixed to lend themselves to a successful endoscopic repair. On the other hand properly assessed sliding hernias that are <3 cm in length could be amenable to transoral fundoplication (TF). Available evidence thus far has questioned the feasibility and efficacy of the other endoscopic modalities if the hiatal length exceeds 2 cm.

There are several ways to assess for hiatal hernia. Traditionally, barium esophagography has been used, but it has a sensitivity of only 34% and cannot be definitively diagnostic for GERD. If a hiatal hernia is found, it is likely to be contributing to the symptoms and should be repaired surgically. CT scanning is increasingly used, since it provides important information on the structures surrounding the hernia, a better definition of the diaphragmatic defect size and esophageal wall thickening and rigidity, all elements that are important in tissue mobilization. Novel methods for in vivo measurement of esophageal hiatal surface area using MDCT multi-planar reconstruction have been introduced [6]. The presence of fluid levels within the esophagus or the hiatal hernia on CT imaging implies more severe disease with impaired motility and esophageal clearance and should raise suspicion for achalasia. High-resolution esophageal manometry (HRM) provides a reliable assessment of the length of the hiatal hernia under physiologic conditions and highlights the relationship between the lower esophageal sphincter (LES) and the crural diaphragm and the spatial dynamics of the esophago-gastric junction (EGJ) at rest and upon swallowing (Fig. 7.3) [7].

In order to provide useful information, endoscopy requires attention to the GEJ at various levels of air distention, forward and retrograde viewing and a meticulous detailing of the mucosa. If the distance of the GEJ from the incisors does not vary significantly with insufflation one can expect wall fibrosis and esophageal foreshortening both messengers of a challenging surgical repair. Fluid pooling, stricture formation or tissue nodularity imply atony and complicated disease and are expected to be associated with suboptimal endoscopic or surgical outcomes (Fig. 7.4).

Retroflexed views of the cardia during endoscopy are essential not only to confirm the type and size of the hernia but also to assess the GEJ using the Hill classification, a grading system that is easy to learn and has been used and validated for over 20 years (Fig. 7.5) [8]. In controls without GERD, there is a prominent tissue fold of tissue along the lesser curvature of the stomach that closely apposes to the endoscope (Hill Grade I). Less commonly, in Hill Grade II, the fold is present but there are times of opening and closing around the endoscope. In contrast, in patients with GERD the fold is not prominent and there is inadequate grip of the endoscope by the GEJ tissues (Hill Grade III) and a sliding hiatal hernia may be present (Fig. 7.6). Patients with GERD and hiatal hernia have essentially no fold and the lumen of the esophagus remains open, allowing the squamous esophageal epithelium, proximal to the GEJ, to be seen from below (Hill Grade IV). In the original study of this classification, the sensitivity and specificity of an abnormal cardia (Hill Grades III and IV) in predicting reflux was 91%, with a positive predictive value of 95%, and a negative predictive value of 87%.

Both these elements need to be examined in every patient with GERD. Esophageal structure is best assessed by endoscopy, first to exclude other conditions (i.e. other forms of esophagitis or cancer), and to carefully define mucosal integrity, ruling out dysplastic Barrett’s esophagus that will require attention prior to any endoscopic or surgical therapy for GERD being applied (Fig. 7.7) [9]. Most EART studies have excluded patients with Barrett’s esophagus, hence the efficacy of these procedures in such patients is not well established. In contrast, we have better efficacy data on Barrett’s esophagus patients undergoing anti-reflux surgery. Moreover, patients with long segment Barrett’s esophagus tend to have large sliding hiatal hernias in need for operative hernia repair and anti-reflux surgery.

Functional assessment mainly aims to exclude achalasia or other forms of severe peristaltic failure that would impede the placement of a magnetic sphincter (LINX) or a 360° fundoplication and may favor instead a partial 270° (Toupet) fundoplication or a Collis gastroplasty. It is debatable to what degree ineffective esophageal peristalsis and other lesser disorders of function detected by HRM serve as contraindications to surgery or endoscopic management. As a general rule, the creation of a tight anti-reflux barrier may aggravate dysphagia and difficulties with throat clearance and any invasive option needs to be carefully examined and individualized.

Complete non-response to PPI therapy is a warning against either endoscopic or surgical intervention for GERD. This is different than PPI-refractory disease, where patients exhibit some (partial) response to pharmacologic therapy. This latter group of patients constitutes the majority of patients referred for invasive therapies. Perception modulators, such as the SSRI citalopram, can reduce esophageal hypersensitivity not limited to acid, as well as other add-on therapies, such as prokinetics, inhibitors of transient lower sphincter relaxations or alginates also play an important therapeutic role. Another group of patients, those who respond well to PPI therapy but do not wish to continue them long-term fearful of adverse events. Such patients may have lesser endoscopic burden of disease that makes them better candidates for any invasive therapies. There are very limited data in patients who have previously undergone either endoscopic or surgical therapies for GERD and present with refractory symptoms. Radiofrequency therapy of GEJ (Stretta) can be performed repeatedly or in a patient post anti-reflux surgery but not after magnetic sphincter implantation, but there is no published data on its efficacy. In a patient presenting with recurrent GERD after anti-reflux surgery, the degree of wrap displacement, if any, plays an essential role in decision-making (Fig. 7.8). If present, there is no role for EART and surgical repair is the only option [10]. Revisional anti-reflux surgery is always more challenging to perform and its outcomes are considered less robust than those of the initial intervention. The use of mesh to close large hiatal defects that contributed to prior failure remains controversial and needs to be individualized. Finally, patients with prior esophageal injury or those with complicated disease (i.e., long peptic strictures) that are resistant to medical therapy lone or in combination with temporary endoscopic stenting, may require esophagectomy instead of EART or anti-reflux surgery.

Patients with morbid obesity have been excluded from EART trials and data on efficacy and safety are scant. In general, if a patient with GERD is a candidate for anti-obesity surgery, the performance of Roux-en-Y bypass is the best surgical option. Sleeve gastrectomy is less likely to be associated with complete control of GERD symptoms, but if such symptoms occur postoperatively, radiofrequency therapy of EGJ is feasible and effective [11]. Regardless of the choice of invasive therapy, endoscopic or surgical, peri-operative morbidity is high in obese patients and needs to be considered and balanced against the anticipated gains.