Importance of Esophageal Manometry and pH Monitoring in the Evaluation of Patients with Refractory Gastroesophageal Reflux Disease: A Multicenter Study

Introduction

Symptoms such as heartburn, dysphagia, regurgitation, and chest pain may be caused by many different diseases such as gastroesophageal reflux disease (GERD), achalasia, and other motility disorders and malignancy. ¹ Many patients who present with these symptoms are frequently treated with acid-reducing medications on the assumption that GERD is causing the symptoms. In the presence of partial or absent response to therapy, patients are assumed to have refractory GERD, ² and they are often referred for laparoscopic antireflux surgery (LARS), without further diagnostic evaluation.

We hypothesized that in some of these patients the heartburn is not secondary to reflux, but rather to stasis and fermentation of food in the presence of achalasia. Therefore, this study aims to demonstrate that esophageal manometry and pH monitoring are essential to establish the proper diagnosis before any type of surgery is considered.

Patients and Methods

We performed a retrospective review of data from prospectively maintained databases in two quaternary care centers, the University of Chicago Medical Center (USA) and the University of Milan Medical Center (Italy). Between July 2008 and July 2015, 524 patients whose final diagnosis was achalasia were referred to these centers. Symptomatic evaluation with Eckardt score (ES), barium swallow, endoscopy, manometry, and pH monitoring was performed in all patients.

Results

Five hundred twenty-four patients, whose final diagnosis was achalasia, were referred to our centers. One hundred fifty-two of these patients (29%) were referred for LARS on the assumption that they had refractory GERD. Seventy-five patients were male (49.3%), and the mean age was 50 years. All 152 patients had been previously treated with acid-reducing medications for an average of 29.3 months.

Fourteen patients (9.2%) reported partial relief of symptoms, whereas the remaining 138 (90.8%) had no relief of symptoms. One patient (0.7%) had already undergone a laparoscopic Nissen fundoplication before referral to our center.

Esophageal manometry revealed achalasia in all patients. According to the Chicago classification, 9.5% of patients had type 1, 49.2% had type 2, and 6.4% had type 3 achalasia. In 34.9% of patients, a conventional esophageal manometry was performed, which showed a nonrelaxing LES and absent peristalsis. The mean ES was 6.3.

In 87% of patients, the barium swallow showed typical findings of achalasia, with dilation of the esophageal body, slow emptying of barium, and narrowing of the gastroesophageal junction (bird's beak appearance). The endoscopy showed fungal esophagitis in 8% of patients.

Three patients (2%) had an abnormal reflux score on pH monitoring, but analysis of the tracings showed that it was due to stasis and fermentation of retained food secondary to delayed esophageal clearance, a phenomenon called pseudo-reflux.^4,5 All patients underwent laparoscopic Heller myotomy (LHM) and Dor fundoplication. Laparotomy was performed in two patients (1.3%): one for bleeding and the other because of severe intraperitoneal adhesions. Only one patient required pneumatic dilation after LHM and improved with an ES of 1, 12 months after the procedure. At a median follow-up of 40 months, all patients were doing well with a mean ES of 0.5.

Discussion

The results of this study showed that (1) one-third of patients with achalasia were thought to have refractory GERD because the heartburn had not resolved with medical therapy and (2) patients thought to have refractory GERD must be carefully evaluated before referral for an antireflux operation to rule out achalasia or other esophageal motility disorders.

Our data confirm the importance of a complete work-up, including esophageal manometry and pH monitoring in any patient considered for LARS. In fact, even though several studies demonstrated that reflux-related symptoms have low sensitivity and specificity,^6,7 many physicians still believe that a diagnosis of GERD can be established by a symptomatic evaluation only. Furthermore, when symptoms persist despite treatment with acid-reducing medications, patients are labeled as having refractory GERD. ⁸

In a study by Herregods et al., 106 patients, unresponsive to proton pump inhibitors (PPI) treatment, were studied with esophageal manometry and pH monitoring. Only 65.1% of these patients were diagnosed with GERD, whereas the remaining 34.9% were diagnosed with other conditions, such as functional heartburn, rumination, achalasia, and other esophageal motility disorders. ⁹ Similarly, a larger study by Triadafilopoulos and colleagues on 275 patients with poor response to PPIs demonstrated that in about 35% of patients, the multimodality evaluation, including esophageal manometry and pH monitoring, excluded GERD. Among these patients, 7 (2.5%) had achalasia and 16 (5.8%) had other esophageal motility disorders. ¹⁰ Interestingly, in the same study was shown that in the context of “nonreflux” diagnoses, such as achalasia, some patients had an abnormal pH monitoring score, confirming the importance of the esophageal manometry to rule out motility disorders, and the need to analyze the tracing to distinguish between real and false reflux.^4,5

Likewise, our study provides the evidence that in patients with refractory GERD, further investigation, including esophageal manometry and pH monitoring, is essential to define the proper diagnosis and plan a correct therapeutic approach. Unfortunately, in many cases, these tests are not performed and patients are treated with acid-reducing medication for a long period of time or even referred for LARS.

Today PPIs are among the most frequently prescribed drugs worldwide and, in addition, many of them are available over the counter, allowing their use in the absence of clinical supervision. PPIs are preferred to other acid-reducing medications because they are the most effective on symptoms, and heartburn is usually relieved in the majority of patients.

Unfortunately, long-term treatment with PPIs is costly and associated with important side effects. ¹¹ A study by Shaheen et al., who analyzed the healthcare costs for gastrointestinal and liver diseases, reported that in 2004 the sales of PPIs in the United States reached 10 billion dollars. ¹² A proper work-up for patients with GERD-related symptoms could dramatically reduce this expense. Furthermore, long-term treatment with PPI has been shown to expose patients to several complications, such as Clostridium difficile infection, community-acquired pneumonia, hip fracture, vitamin B₁₂ deficiency, and hypomagnesemia. In addition, their use has been recently associated with increased risk of myocardial infarction (in the general population, in patients with unstable coronary syndromes, and in patients with clopidogrel treatment)^13–16 and with chronic kidney disease. ¹⁷ Consequently, along with an erroneous treatment, these patients are unnecessarily exposed to all the side effects previously described. Even worse, some surgeons perform antireflux surgery on the basis of symptomatic evaluation only, as shown by the patient in our study who underwent a laparoscopic Nissen fundoplication before being referred to our center. This patient required a second operation with take down of the Nissen and performance of an LHM with Dor fundoplication.

Even though this study has some limitations, such as its retrospective nature, we feel that it stresses the importance of a complete work-up in addition to the symptomatic evaluation.

Conclusions

Typical symptoms of GERD may be present in one-third of patients with achalasia. A thorough work-up that includes esophageal manometry and pH monitoring in patients with refractory GERD is essential to plan medical treatment and before any referral to surgery.