Modern Esophageal Function Testing and Gastroesophageal Reflux Disease in Morbidly Obese Patients

Due to a dramatic increase within the last decades, overweight and obesity represent a global disease burden estimated to cause 3.4 million deaths per year [1]. The relationship between obesity and deteriorating health status is already well established and bases among other factors on rising prevalence of type 2 diabetes and metabolic syndrome in obese patients [2]. Importantly, bariatric surgery is regarded to be the best long-term solution in terms of long-term weight loss and remission of type 2 diabetes, when compared with conservative strategies [3]. Currently, sleeve gastrectomy (SG) is the leading bariatric procedure in the USA and western world [4]. Recently presented long-term data show a high incidence of hiatal hernia, gastroesophageal reflux disease (GERD), and Barrett’s esophagus in patients after SG [5]. As a consequence, some authors even suggest that preexisting GERD should be a relative contraindication to SG. Furthermore, long-term data of one anastomosis gastric bypass and its consequences on biliary reflux due to a preexisting defect antireflux mechanism are still impatiently awaited.

Importantly, data on preoperative GERD status in patients undergoing bariatric surgery are more than scarce and offer only a low evidence level. Limitations include small sample sizes, selection of only symptomatic or asymptomatic patients prior to surgery and diagnosis of GERD based only on symptom perception, or even lacking cornerstones of objective testing [6‐9]. Moreover, modern diagnosis of true GERD was recently redefined offering a broad spectrum of tools from symptom assessment, endoscopy, and ambulatory pH monitoring to esophageal function testing (EFT) ( [10]. EFT may reveal esophageal dysmotility, rather frequently observed after bariatric surgery, that potentially mimics or interferes with GERD [11, 12]. Concordantly, EFT has also been revolutionized with the development of high-resolution manometry (HRM), a fundamental technological advance in modern medicine. Moreover, implementation of novel metrics and their widespread clinical use led to an algorithm classifying esophageal dysmotility, namely, the Chicago Classification (CC) [13].

Therefore, this study was designed to rigorously assess prevalence and characteristics of esophageal motility disorders and (borderline) GERD in morbidly obese patients planned for primary bariatric surgery.

Between April 2014 and December 2016, consecutive morbidly obese (BMI ≥ 35 kg/m²) patients were offered to undergo HRM and ambulatory 24-h pH impedance monitoring at our tertiary academic center. Medical history and symptoms were assessed in a face-to-face interview with study participants being off proton pump inhibitor (PPI) for at least 10 days. In addition, esophagogastroduodenoscopy (EGD) was performed as well off PPI to determine the presence of hiatal hernia, Barrett’s esophagus, and GERD, classified according to the Los Angeles (LA) classification [14]. All patients underwent informed consent, and the institutional review board approved the study protocol. Data were collected prospectively.

This is the first study evaluating a large cohort of morbidly obese patients by means of high-resolution manometry and modern gastroesophageal reflux testing. We could demonstrate that prevalence of esophageal motility disorders, classified by the Chicago algorithm, was 34%, dominated by the presence of OO and a novel hypercontractile disorder nicknamed JE. True GERD was noted in 35.4% of participants, whereas borderline GERD was observed in another 40.8%.

HRM has revolutionized modern medicine with the implementation of an hierarchical algorithm that classifies abnormality and facilitates evaluation of patients with symptoms of esophageal motility disorders and GERD [13]. Similar to studies using conventional manometry, HRM revealed a high rate of esophageal motility disorders in morbidly obese patients [6, 17]. Interestingly, OO diagnosed in 18.4% of our cohort may cause chest pain and interfere with symptoms of GERD [18]. Comparatively, functional OO with intact peristalsis was observed in only 0.016% among 1000 consecutive HRM studies [19]. The association between high glucose and cholesterols levels, caused by high fat and sugar intake in morbidly obese patients, and the integrated relaxation pressure as well as an increased intraabdominal pressure, may offer an explanation for this difference in prevalence [20]. Nevertheless, therapeutic consequences and impact of bariatric surgery on the evolution of OO still remain unclear [21].

Importantly, JE, a novel hypercontractile disorder related to dysphagia and noncardiac chest pain, was observed in 7.5% of our population. Concordantly, prior trials have also observed hypercontractile disorders using conventional manometry in obesity [6, 7]. The pathophysiological mechanism seems to include a high gastroesophageal gradient, resulting in high-pressure esophageal contractions managing the functional barrier [22]. This may also be the reason for only 2% of patients diagnosed with ineffective esophageal motility in our cohort. Nevertheless, in contrast to nutcracker-like phenotypes of hypercontractility, JE is not observed in healthy controls. Moreover, longitudinal observations revealed that up to 25% of patients with JE subsequently progressed to achalasia [23]. Therefore, a therapeutic approach like peroral endoscopic myotomy is regarded as suitable treatment in these individuals [24]. Confirmatory, our group emphasized that JE is of progressive clinical nature and may even mimic GERD by responding to PPI therapy [15, 25]. It is obvious that these facts influence bariatric strategies or even limit postoperative outcomes after surgery. Moreover, overlapping comorbidities may be misleading in identifying the underlying mechanism for symptoms after interventions. Interestingly, none of our patients with JE experienced dysphagia, whereas symptomatic response to esophageal motility disorders was also rather low. These findings go in line with observations that autonomic and sensory ganglia are susceptible to consequences of obesity like increased immune cell entry causing damage and dysregulation of sensory pathways [26].

Importantly, symptom perception is an essential alarm response to increased gastroesophageal reflux in GERD, which definitely influences the choice of surgical procedure. Interestingly, preoperative high-quality data on GERD in morbidly obese are still scarce and controversial. Fisher et al. investigated 30 morbidly obese patients and revealed that individuals with a pathologic acid exposure in the distal esophagus had a significantly higher body mass index [27]. In contrast, Lundell et al. did not observe any weight-related correlations with reflux variables in the massively obese patients [28]. So far, studies lack objective testing or diagnosis of GERD on the basis of symptoms or the presence of esophagitis, conditions that are also observed in healthy controls [6, 7]. Recently, the Lyon Consensus proposed a modern approach for diagnosis of GERD [10]. Our data indicate that true GERD was met in 35.4%, which is difficult to compare with the previous studies that diagnose GERD solely based on peptic esophagitis or symptoms [7, 17]. From a pathophysiological point of view, structural defectiveness of the LES was noted only in 8% of our cohort, whereas diabetes was significantly associated with GERD. Therefore, peripheral neuronal disorders in type 2 diabetes seem to aggravate high gastroesophageal pressure gradients and increased transient sphincter relaxation in morbid obesity and lead to the development of GERD [22, 29].

Importantly, borderline GERD was noticed in another 40.8% of our population and affected nearly half of our asymptomatic patients. Taken together, 76.2% had at least borderline evidence of GERD with 4.8% of individuals presenting with Barrett’s esophagus, which is alarming as the current data illustrate that a large percentage of de novo GERD after sleeve gastrectomy, one of the leading bariatric procedures worldwide, derives from silent preoperative reflux [30]. Based on this, adverse long-term data revealing considerable conversion rates due to GERD-related complications seem understandable [5].

Although data were collected prospectively, analysis of parameters was conducted retrospectively; thus, potential selection bias was minimized by consecutive inclusion of patients. The number of participants and the rigorous objective evaluation according to the international gold standard represent the strength of this trial.

In conclusion, we were able to demonstrate that modern preoperative esophageal function and reflux testing resulted in a high rate of novel esophageal motility disorders and GERD-associated conditions. Further longitudinal studies are needed to delineate the course of JE in obesity and risk factors for adverse outcomes following bariatric surgery.