Silent Gastroesophageal Reflux Disease in Patients with Morbid Obesity Prior to Primary Metabolic Surgery

Adverse life style behavior and obesity represent demanding challenges in modern medicine. By 2030, 1 in 2 adults is projected to have obesity, whereas 1 in 4 adults will even have severe obesity, which is likely to become the most common body mass index (BMI) category among women [1]. As a consequence, related chronic diseases will affect general health status and increase the socioeconomic burden [2].

As far as weight loss and remission rates of type II diabetes and metabolic syndrome are concerned, metabolic surgery is more effective when compared with non-surgical options and was therefore implemented as an effective strategy fighting obesity [3].

Currently, various primary operations are performed throughout the world with sleeve gastrectomy (SG) being the predominant procedure [4]. Importantly, long-term follow-up after SG revealed a high incidence of gastroesophageal reflux disease (GERD) and Barrett’s esophagus, a premalignant condition caused by reflux of gastric contents [5]. Undetected preoperative silent GERD may attribute to these outcomes [6]. Thus, SG is controversial in patients with pre-existing pathologic reflux.

However, diagnosis of GERD prior to metabolic surgery is more than challenging as symptoms are misleading or even missing on the one side, whereas esophagitis, detected by endoscopic means, may also be present in healthy controls on the other side [7, 8]. As a consequence, GERD may remain undiscovered in asymptomatic individuals.

The Lyon consensus, a novel approach that integrates objective tools to modernize diagnosis of GERD, differentiates between no, borderline, or conclusive evidence for pathologic reflux [9]. Recently, first data applying the Lyon consensus revealed a high prevalence of GERD and motility disorders in the population with morbid obesity [10]. Unfortunately, data of asymptomatic patients with morbid obesity classified by the Lyon consensus have yet to be published.

This study was designed to evaluate the prevalence and phenotypes of GERD and motility disorders in a large cohort of asymptomatic patients with morbid obesity prior to primary metabolic surgery.

Consecutive asymptomatic patients with morbid obesity (BMI ≥ 35 kg/m²), planned for primary metabolic surgery, were included in this study between 2014 and 2019 at our tertiary academic center. Patients were assigned for objective testing for GERD according to the Lyon consensus including ambulatory 24-h pH impedance monitoring and high-resolution manometry (HRM). Esophagogastroduodenoscopy (EGD) was performed to determine presence of hiatal hernia and esophagitis, classified according to the Los Angeles (LA) classification [11]. Hiatal hernia was diagnosed when greater than 2 cm in axial span. Small hiatal hernias were measured between 2 and 4 cm, whereas large hiatal hernias were considered to be larger than 4 cm. Medical history as well as baseline characteristics and a validated GERD-health–related quality of life questionnaire were assessed in face-to-face interviews at the day of esophageal function testing following a standardized documentation [12]. Patients were declared asymptomatic in case of absence of typical and atypical GERD-related symptoms and a scoreless GERD-HRQL [9]. All participants were free of anti-secretory medication during objective testing. Only patients with completed objective testing were included and presented in this trial. Esophageal function testing is routine practice for patients undergoing evaluation for anti-reflux surgery at our institution. The local institutional review board approved the study protocol and informed consent was obtained from all patients. Data were collected prospectively.

This is the first study investigating a large sample of asymptomatic patients with morbid obesity prior to primary metabolic surgery following a modern concept of GERD. According to the Lyon consensus, 31.1% of our patients were diagnosed with GERD, whereas another 44.1% fulfilled the criteria for borderline GERD. Reflux was facilitated by a structurally defective sphincter. Furthermore, esophageal motility disorders, mainly presenting as novel spastic or obstructive phenotypes, were observed in 35.6% of asymptomatic individuals.

Metabolic surgery and the development of postoperative, even complicated, GERD are intensively discussed in literature. Currently, SG is the most frequently performed metabolic procedure worldwide but was recently associated with some limitations concerning GERD [4]. We investigated our first SG patients and noted a high rate of postoperative GERD and de novo hiatal hernia 10 years after SG [5]. Pathologic reflux was observed in 57% of the unconverted cohort and even a rate of 14% of Barrett’s metaplasia, a premalignant condition. Furthermore, symptomatic GERD was one of the major reasons for conversion in this study. Confirmatory, these findings were reproduced in other centers and significantly impact on quality of life after metabolic surgery [14]. From a pathophysiological point of view, Quero et al. revealed several mechanisms that may facilitate pathologic reflux after SG [15]. They evaluated 23 patients by means of magnetic resonance imaging and HRM before and after surgery and realized that LES length was reduced after SG, aggravating our findings, where even 36.2% of asymptomatic patients had a structurally defective LES prior to surgery. Moreover, disruption of the esophagogastric junction and small gastric capacity were associated with the risk of postoperative GERD leading to concepts of novel sphincter augmentation devices being implemented for these patients [16]. Therefore, it seems reasonable that preoperative assessment of LES function could help us tailor our surgical decision-making to prevent additional damage to an already injured sphincter. Although literature is controversial on this issue, it seems that structural defects play an important role in the pathogenesis of GERD [17].

As a consequence, SG may be questioned in individuals with pre-existing sphincter defects or evidence of GERD, which confronts us with several limitations [18]. First and foremost, GERD patients may present asymptomatic like our selected population. Furthermore, silent preoperative reflux seems to play a crucial role in the development of postoperative GERD. Borbély et al. evaluated 116 patients with symptoms of GERD after SG and reported that 66% of patients with preoperative silent GERD became symptomatic after interventions [6]. Furthermore, preoperative objective testing for GERD and LES assessment is not mandatory, which leads to a symptom- or endoscopic-based diagnosis of GERD. Unfortunately, the Diamond trial revealed that symptom-based diagnosis of GERD lacks sensitivity and specificity, even in an expert setting, where it does not exceed 70% [19]. Moreover, esophagitis was observed in up to 11.2% of young healthy volunteers during endoscopy [20]. Due to these issues, the Lyon consensus established objective elements of reflux testing to define borders of abnormality. Importantly, according to the Lyon consensus, 31.1% of our population were diagnosed with GERD, whereas another 44.1% had (borderline) GERD. This results in 75.2% of asymptomatic individuals with morbid obesity being affected by some form of GERD prior to metabolic surgery. This is difficult to compare as objective data prior to metabolic surgery are rare. There is only one trial that identifies patients with GERD using the Lyon consensus in the predominantly symptomatic population with morbid obesity [10]. Within this study, 35.4% of individuals presented with GERD and another 40.8% with (borderline) GERD, which is comparable to our data. Nevertheless, we have to point out that we only included asymptomatic patients, which again highlights the controversial issue of symptom and endoscopic-orientated selection of surgical strategy. Lower quality data, biased by the limitations of endoscopic diagnosis without histopathology of GERD, report prevalence rates of silent GERD starting from 11.6% in the general population [21]. But again, the presence of low-grade esophagitis may be misleading.

Although variations of BMI did not influence the presence of GERD in our cohort of morbidly obese, several facts explain the high prevalence of GERD. Obesity has been established as an important risk factor for occurrence of GERD but central obesity seems to be a better prediction marker when compared with BMI [22, 23]. High pressure gradients registered in the population with morbid obesity explain a hiatal hernia rate of 32.2% and facilitate reflux via a defective sphincter in 36.2% of our participants. Additionally, obesity may lead to central and peripheral neuronal damage and increase the sensory threshold leading to diminished symptom perception [24].

Importantly, high-resolution manometry modernized our understanding of esophageal disorders. Our group noted motility disorders in 35.6% of study participants which is similar to a recent study in the general population of morbid obese prior to bariatric surgery [10]. Interestingly, JE, a novel hypercontractile disorder noted in 7.9% of asymptomatic individuals within this trial, is defined by the Chicago classification not to be present in controls and represents a clear hypercontractile abnormality. Recently, JE was associated with a progressive clinical nature with 25% of individuals even developing achalasia in short-term follow-up [25]. Therefore, aggressive treatment with tailored peroral endoscopic myotomy (POEM) is offered to individuals with JE [26]. However, the underlying mechanism in the asymptomatic morbidly obese and therapeutic consequences are not defined, yet. It is obvious that the majority of our patients with JE experienced concomitant EGJOO. This could be caused by high fat and carbohydrate intake or even an increased intraabdominal pressure [27]. From a pathophysiological point of view, EGJOO may be responsible for the development of JE in our cohort, as overfilling of laparoscopic adjustable gastric bands, simulating an outflow obstruction, was observed to induce repetitive hypercontractile esophageal contractions in a study of 20 patients [28]. This is in line with the finding that EGJOO was noted in 17.5% of our population, which is significantly more frequent when compared with a prevalence of 4% that was observed in a trial including non-obese [29]. However, only longitudinal trials will reveal if alarm symptoms like dysphagia or non-cardiac chest pain will develop over time or are just masked by an increased sensory threshold analogous to GERD. Hypothetically, reduction of intraabdominal pressure accomplished by successful metabolic surgery may also lead to normalization via a reduction of the intraabdominal pressure. As far as esophageal motility disorders are concerned, asymptomatic patients with morbid obesity seem to be associated with a higher prevalence when compared with non-obese controls. Nevertheless, the clinical significance remains unclear.

Due to the retrospective nature of the study design, potential selection bias cannot be ruled out. However, we compensated this limitation by consecutively including patients, prospective data collection, and objective evaluation.

This is the first study using a modern approach to diagnose GERD in asymptomatic patients with morbid obesity prior to primary metabolic surgery. We revealed that GERD was common even in asymptomatic individuals with morbid obesity. Esophageal motility disorders were found in 35.6% with the current need of longitudinal trials to delineate therapeutic implications.