Stuart Spechler M.D.

Spechler, S. J. (2018). “Cardiac Metaplasia: Follow, Treat, or Ignore?” Dig Dis Sci 63(8): 2052-2058.

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Over the past two decades, evidence has accumulated to challenge the traditional view that cardiac mucosa, which is comprised exclusively of mucus glands, is the normal lining of the most proximal portion of the stomach (the gastric cardia). There is now considerable evidence to suggest that cardiac mucosa develops as a GERD-induced, squamous-to-columnar esophageal metaplasia in some, if not all, cases. Although cardiac mucosa lacks the goblet cells commonly required for a histologic diagnosis of intestinal metaplasia, cardiac mucosa has many molecular features of an intestinal-type mucosa, and appears to be the precursor of intestinal metaplasia with goblet cells. In apparently normal individuals, cardiac mucosa is commonly found in a narrow band, less than 3 mm in extent, on the columnar side of the squamo-columnar junction at the end of the esophagus. A greater extent of cardiac mucosa can be found in GERD patients, and the magnitude of that extent appears to be an index of GERD severity. Presently, the risk of adenocarcinoma imposed by cardiac mucosa is not clear, but appears to be far less than that of intestinal metaplasis with goblet cells. The British Society of Gastroenterology accepts an esophagus lined by cardiac mucosa as a “Barrett’s esophagus”. However, if one defines Barrett’s esophagus as a metaplasia that predisposes to cancer, then only intestinal metaplasia clearly fulfills that criterion at this time. Well-designed, prospective studies are needed to establish the malignant potential of cardiac mucosa.

Dellon, E. S., C. A. Liacouras, J. Molina-Infante, G. T. Furuta, J. M. Spergel, N. Zevit, S. J. Spechler . . . and A. J. Bredenoord (2018). “Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference.” Gastroenterology Jul 12. [Epub ahead of print].

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BACKGROUND AND AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE in order to develop updated international consensus criteria for EoE diagnosis. METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries utilized on-line communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences. RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement. CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm(2)) on esophageal biopsy, and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.

Spechler, S. J. (2018). “Speculation as to why the Frequency of Eosinophilic Esophagitis Is Increasing.” Curr Gastroenterol Rep 20(6): 26.

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PURPOSE OF REVIEW: The frequency of eosinophilic esophagitis (EoE), an immune/antigen-mediated disorder first described in 1993, has been increasing rapidly. The purpose of this review is to consider hypotheses proposed to explain this increase and to speculate on their validity. RECENT FINDINGS: The hygiene hypothesis attributes the rise of EoE to modern hygienic conditions resulting in fewer childhood infections with microbes that might have protected against allergy development. Microbial dysbiosis, a change in the microbiome’s composition and diversity caused by a modern affluent lifestyle, also might contribute to allergic conditions. Environmental factors including modern chemicals contaminating crops, livestock treated with hormones and antibiotics, food additives and processing changes, and pollutants in the air and water conceivably might predispose to EoE. One intriguing hypothesis attributes increasing EoE to increasing use of acid-suppressive medications like proton pump inhibitors, which might prevent peptic digestion of food allergens, increase gastric permeability, and alter the microbiome to favor food allergy development. In a recent pediatric case-control study, use of acid suppressants in infancy was by far the single strongest risk factor identified for later development of EoE. It remains unclear which, if any, of the above factors underlies the rising frequency of EoE. These factors need not be mutually exclusive, and the cause of EoE may well be multifactorial.

Yadlapati, R., M. F. Vaezi, M. F. Vela, S. J. Spechler, N. J. Shaheen, J. Richter, B. E. Lacy, D. Katzka, P. O. Katz, P. J. Kahrilas, C. P. Gyawali, L. Gerson, R. Fass, D. O. Castell, J. Craft, L. Hillman and J. E. Pandolfino (2018). “Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel.” Am J Gastroenterol. Apr 24. [Epub ahead of print].

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BACKGROUND: The aim of this study was to assess expert gastroenterologists’ opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. METHODS: Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. RESULTS: Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: H2RA for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association. CONCLUSION: For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies are preferred for all other scenarios.

Wang, J., J. Y. Park, R. Huang, R. F. Souza, S. J. Spechler and E. Cheng (2018). “Obtaining adequate lamina propria for subepithelial fibrosis evaluation in pediatric eosinophilic esophagitis.” Gastrointest Endosc 87(5): 1207-1214.e1203.

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BACKGROUND AND AIMS: Subepithelial fibrosis in eosinophilic esophagitis (EoE) can be detected only in esophageal biopsy specimens with adequate amounts of lamina propria (LP). We investigated how often pediatric esophageal biopsy specimens contain adequate LP, and whether esophageal eosinophilia influences the acquisition rates. METHODS: We evaluated 284 esophageal biopsy specimens from 39 patients with EoE, and 87 biopsy specimens from 32 patients without esophageal eosinophilia or other esophageal abnormalities for the presence of adequate LP and fibrosis. RESULTS: On a per biopsy specimen basis, there was no significant difference in the rate of procuring adequate amounts of LP between patients with EoE and patients without esophageal eosinophilia (43% vs 31%, P = .14). Eighty-five percent of patients with EoE had fibrosis. Fibrosis in patients with EoE was patchy and more likely to be detected in the middle or distal esophagus (odds ratio, 19.93; 95% confidence interval, 4.12-91.52). Among patients with fibrosis, the probability of its detection reached >95% with 7 middle-distal esophageal biopsy specimens. Most children with newly diagnosed EoE already had subepithelial fibrosis despite exhibiting only inflammatory endoscopic features. CONCLUSIONS: Most individual esophageal biopsy specimens in children are inadequate for assessing subepithelial fibrosis, and the rates of procuring adequate LP per biopsy specimen are similar in patients with and without EoE. To reliably detect fibrosis in patients with EoE, at least 7 biopsy specimens should be taken from the middle-distal esophagus. The finding of fibrosis in children with newly diagnosed EoE and only inflammatory endoscopic features suggests that fibrosis can occur early in this disease.