Gastric inlet patches in the cervical esophagus: what they are, what they cause, and how they can be treated

Gastric inlet patches (GIPs) comprise islands of heterotopic gastric columnar epithelium in the cervical esophagus. They are often found incidentally at upper endoscopy and have a reported prevalence of 1% to 12%.^,  Factors associated with a higher detection rate of GIPs are the awareness of the endoscopist in finding this mucosal alteration as well as the use of modern endoscopes (high-definition endoscopes and the additional application of virtual chromoendoscopy). The histologic appearance of GIPs is related to, but not identical with, the mucosa of the gastric cardia, fundus, corpus, or antrum. In most studies, particularly a mixed type mucosa has been found; however, several studies identified predominantly parietal cells, and in other studies mainly mucus-producing cells were seen.

The most commonly held theory concerning the origin of an esophageal GIP is the misplacement or sequestration of endoderm from the gastric anlage in the developing esophagus. This process is thought to occur at the 4-week embryonic stage, when the primitive stomach lies in the neck region. Nicholson suggested that local differentiation or metaplasia of existing pluripotential cells might result in heterotopic gastric mucosa. However, it has also been hypothesized that inlet patches may develop in a multistep process from occluded esophageal glands in the proximal esophagus leading to esophageal retention cysts, which may finally burst and result in focal areas of heterotopic gastric mucosa. Of interest is the finding that GIPs are often associated with Barrett’s esophagus in the distal esophagus. Five of the 10 patients with symptomatic GIPs as reported in the study by Dunn et al showed Barrett’s metaplasia in the distal esophagus. This association would favor both the stem cell theory and the cyst theory.

Given that around 10% of all human beings worldwide have to be classified as GIP carriers, it is remarkable that only a very few of them become symptomatic. The diagnosis of GIP is usually made by chance during upper-GI endoscopy performed for other reasons. Nevertheless, in some cases, GIPs can cause local mucosal alterations (eg, strictures, ulcers, fistula, neoplasia) that cause symptoms like pain or dysphagia.

The question of whether symptoms like globus sensations, chronic cough, laryngitis, or other oropharyngeal symptoms are indeed related to GIPs without further abnormalities has been a matter of debate. Most of these symptoms have also been attributed to extraesophageal manifestations of GERD. However, globus can also be of nonsomatic origin. And indeed, behavioral or psychotropic drug therapy has been successfully given to some of these patients. Hence, there is no clearly defined pathophysiologic association between GIPs and globus. Most likely, it is as always: there are several sides to every story, and the truth usually lies somewhere in the middle.

Histologically, GIPs are often characterized by cardiac epithelium and less often by oxyntic corpus mucosa. If the latter is found, acid would be the cause of symptoms, and therapy with proton pump inhibitors (PPIs) would be effective, which is rarely the case. In contrast, cardiac epithelium produces mucus. The mucus itself may often not be perceived at all, but occasionally globus sensations are experienced (“lump in the throat”). Hence, in these patients, PPI therapy will be ineffective, and ablation of the heterotopic cardiac epithelium appears to be the better approach to treat this condition.

Most GIPs are found with no attributable symptoms. In the current issue of Gastrointestinal Endoscopy, Dunn et al present evidence that radiofrequency ablation (RFA) may relieve the symptoms of globus sensation or sore throat. GIPs in 10 symptomatic patients were treated. After a median of 2 RFA sessions, 8 of the 10 patients experienced complete endoscopic and histologic remission of their GIPs. Moreover, globus, sore throat, and cough improved significantly, with complete resolution of symptoms in 7 of the 8 patients and complete eradication of GIP. Although the number of patients was rather small, the results in this study stand in line with those in other reports (several cohort studies and 1 sham-controlled trial) showing that when GIP and oropharyngeal symptoms coexist, ablation of the heterotopic mucosa leads to resolution of the symptoms in a remarkable number of patients. Table 1 gives an overview of published GIP carriers experiencing atypical/oropharyngeal symptoms (eg, globus sensations, sore throat) treated by an ablative therapy.^{,  ,  ,}  A response to therapy was documented in more than 80% of patients. Knowing the significant concomitant psychologic strains in these patients resulting from many failed therapy approaches (eg, psychotherapy, extensive PPI trials, speech therapies), we think that globus or sore throat implies a clear indication for endoscopic ablation without any other prior measures such as empirical PPI treatment. This holds true for both children and adults, especially because not a single adverse event was reported or observed by all authors. Furthermore, the observed response lasts even in the long term of several years, and, if relapses are observed, they are often associated with recurrent or residual GIPs, which can be treated a second time. So far, studies of ablation of GIP have reported the use of endoscopic argon plasma coagulation (APC). APC is broadly available and effective. To enable better visualization and demarcation of GIPs, we recommend the application of narrow-band imaging or similar techniques. Furthermore, a transparent cap is very helpful, particularly during ablation, to enlarge the space in a narrow area close to the upper esophageal sphincter. However, one of the major limitations of APC is the potential risk of creating strictures. To avoid this side effect, the use of RFA applying a through-the-scope device has been reported as a valuable alternative by Dunn et al. We agree with the authors and suggest that RFA should be performed particularly for larger GIPs involving more than a third of the circumference. On the basis of our own sparse and unpublished experience, hybrid APC (so far not available in the United States) might be a further alternative in treating larger GIPs without causing strictures.

Although pathogenic mechanisms are still not fully understood, there is growing evidence that GIPs can be associated with symptoms such as globus sensations and the persistent feeling of a sore throat. Owing to the ineffectiveness of nonendoscopic treatment approaches in contrast to the 80% success rate of endoscopic ablative therapies, we recommend that practitioners closely look for GIPs in symptomatic patients and, when they are detected, ablate the heterotopic mucosa with APC or RFA, depending on the size. If these techniques are performed by experienced endoscopists using the proper methods, the side effects appear negligible.