What Parameters Are Relevant for the Histological Diagnosis of Gastroesophageal Reflux Disease without Barrett’s Mucosa?
Michael ViethU PeitzJoachim LabenzMichael KuligEmma NauclérD JaspersenW. Meyer‐SabellekStefan N. WillichTore LindPeter MalfertheinerM. Stolte
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<i>Background/Aims:</i> There are still ongoing controversies as to which histological parameters allow the diagnosis of gastroesophageal reflux disease (GERD). The aim of the present analysis was to relate histological changes of the esophageal squamous epithelium to different severities of GERD. <i>Methods:</i> Data were obtained from patients participating in the ProGERD study, who had either erosive reflux disease (ERD, n = 3,245) or non-erosive reflux disease (NERD, n = 2,970). 1,475 patients fulfilled our requirement of having complete biopsy data from two sites (2 cm above the z-line and at the z-line). Changes in the squamous epithelium were assessed by measuring the thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness and counting interepithelial inflammatory cells. <i>Results:</i> The most useful parameters for histological assessment of GERD (given as means, 2 cm above the z-line and at the z-line, respectively) were elongation of the papillae: NERD 40.7 and 48.9%; ERD 46.1 and 54.9% and basal cell hyperplasia: NERD 12.7 and 17.9%; ERD 15.7 and 23.0%. The occurrence of intraepithelial lymphocytic infiltrates, however, is dependent on the severity of GERD, and they are more common than neutrophilic and eosinophilic granulocytes. <i>Conclusion:</i> This study shows that both NERD and ERD can be diagnosed histologically if biopsies are obtained from the distal esophagus or from the z-line. Intraepithelial inflammatory cells are rare and show a high specificity, but very low sensitivity.Keywords:
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Non-erosive reflux disease (NERD) has assumed increasing prominence in studies of gastroesophageal reflux disease (GERD), but it remains a challenge to define NERD precisely and to define its place in the investigation and treatment of GERD. Most simply, NERD may be defined as GERD in an individual who has no evidence of erosions at endoscopy. Unfortunately, the characteristic symptoms of GERD – heartburn and regurgitation – are insufficient to identify all GERD patients and, hence, the diagnosis of NERD is hampered by the lack of clear criteria for the symptomatic diagnosis of GERD. The diagnosis of NERD is hampered further by limited interobserver agreement on the endoscopic diagnosis of erosive esophagitis and by the fact that endoscopy is often performed soon after patients have discontinued therapy. Improvements in endoscopic technology will increase the likelihood of identifying small erosions or other reflux-related lesions; however, this will increase the proportion of patients considered to have erosive esophagitis without defining precisely what constitutes NERD. It is important to recognize that NERD is but one manifestation of GERD and that it, like other manifestations of GERD, is associated with a marked diminution in patients’ quality of life. However, this recognition apart, there seems to be little practical benefit or understanding to be gained in clinical practice or clinical research from considering NERD as a distinct entity or from studying NERD patients in isolation. Advances in understanding the pathogenesis of GERD and its symptoms may be better served by categorizing GERD with respect to the spectrum of its histologic, functional, endoscopic and symptomatic manifestations rather than by studying NERD, a manifestation that is characterized solely by the absence of esophageal erosions.
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Gastroesophageal reflux disease (GERD) is one of the most common gastroenterological diseases. For a long time, GERD was considered as a continuum of various pathological conditions based on the degree of dysfunction of the lower esophageal sphincter, from non‑erosive GERD (NERD) and reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma. Currently, the views on the GERD pathophysiology have significantly changed. To date, it is believed that various presentations of GERD represent its individual phenotypes with unique predisposing cofactors and pathophysiology outside this paradigm. Different GERD phenotypes include NERD, reflux esophageal hypersensitivity, functional heartburn, low and high degree reflux esophagitis, Barrett’s esophagus, regurgitation‑dominant GERD, extra‑esophageal GERD, and reflux chest pain syndrome. Due to the fact that not all GERD phenotypes are the same, clinical management of GERD patients should be carried out differentially, depending on the unique pathophysiological features of each phenotype. The time has come to apply a personalized approach to the management of patients with various GERD phenotypes, which will undoubtedly improve the results of treatment of this heterogeneous and extremely widespread pathology in the future.
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Background/Aims In Korea, there are no available multicenter data concerning the prevalence of or diagnostic approaches for non-responsive gastroesophageal reflux disease (GERD) which does not respond to practical dose of proton pump inhibitor (PPI) in Korea. The purpose of this study is to evaluate the prevalence and the symptom pattern of non-responsive GERD. Methods A total of 12 hospitals who were members of a Korean GERD research group joined this study. We used the composite score (CS) as a reflux symptom scale which is a standardized questionnaire based on the frequency and severity of typical symptoms of GERD. We defined "non-responsive GERD" as follows: a subject with the erosive reflux disease (ERD) whose CS was not decreased by at least 50% after standard-dose PPIs for 8 weeks or a subject with non-erosive reflux disease (NERD) whose CS was not decreased by at least 50% after half-dose PPIs for 4 weeks. Results A total of 234 subjects were analyzed. Among them, 87 and 147 were confirmed to have ERD and NERD, respectively. The prevalence of non-responsive GERD was 26.9% (63/234). The rates of non-responsive GERD were not different between the ERD and NERD groups (25.3% vs. 27.9%, respectively, p=0.664). There were no differences between the non-responsive GERD and responsive GERD groups for sex (p=0.659), age (p=0.134), or BMI (p=0.209). However, the initial CS for epigastric pain and fullness were higher in the non-responsive GERD group (p=0.044, p=0.014, respectively). Conclusions In conclusion, this multicenter Korean study showed that the rate of non-responsive GERD was substantially high up to 26%. In addition, the patients with the non-responsive GERD frequently showed dyspeptic symptoms such as epigastric pain and fullness.
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The evaluation of the success of therapy for gastroesophageal reflux disease (GERD) has thus far been primarily on the basis of the endoscopic evaluation of the ability of drugs to heal esophageal mucosal breaks and to a lesser extent on their ability to decrease the diverse symptoms of acid reflux. However, because most patients with GERD have no visible esophageal lesions using conventional endoscopic methods, this paradigm requires serious reconsideration. As patients with nonerosive reflux disease (NERD) are just as symptomatic as patients with erosions and are no easier to treat the use of endoscopic end points alone, as criteria for determining healing and efficacy of therapy requires reassessment. In addition, the symptoms of GERD are now appreciated to be broad-based, including many extraesophageal symptoms that contribute to the marked reduction in quality of life for GERD patients. For this reason, and because endoscopic criteria cannot be applied to evaluating therapy in NERD, the success of GERD therapy should be judged primarily in terms of diminishment of GERD-related symptoms--a return to the traditional way that patients judge therapeutic success. To objectively determine the success of therapy in GERD, multisymptom GERD questionnaires have been developed. The most promising are those that reflect the numerous types of GERD symptoms, are patient-administered, quantitative, responsive, and have been validated in both NERD and erosive GERD patients. The ReQuest instrument is especially attractive as it records the entire range of GERD symptoms on a daily basis (including also their frequency and intensity) and is responsive to changes with time and with therapy. Symptom-based evaluative tools should greatly aid the objective evaluation of GERD symptoms, monitor precisely how patients respond to therapy and thereby lead to improvements in GERD management.
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In Japan prevalence of GERD is still low as compared to Western countries. Although it is almost certain that the number of GERD patients will not increase by increasing patients who will receive eradication in Western countries, it may be the case in Japan, because most of the H. pylori-infected subjects in Japan have a considerable level of mucosal atrophy, that can be improved after eradication of H. pylori. Indeed, prevalence of H. pylori in Japanese patients with GERD is reported to be approximately 30-40%, suggesting protective role of H. pylori infection in the development of GERD. The disease entity of Non-erosive GERD (NERD) is receiving great attention recently, but effective rate of PPI for NERD is reported to be 60%, suggesting that a considerable number of non-GERD patients are included in patients diagnosed as having NERD. Thus, an effort for improving both sensitivity and specificity of the diagnosing method for NERD is required. In any event, it should be kept in mind that pathophysiology of GERD is quite different between Western and Japanese patients.
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