Vani J.A. Konda M.D.

Spechler, S. J., V. Konda and R. Souza (2018). “Can Eosinophilic Esophagitis Cause Achalasia and Other Esophageal Motility Disorders?” Am J Gastroenterol Oct 12. [Epub ahead of print].

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Eosinophilic esophagitis (EoE), a disorder identified by its esophageal mucosal features, often is associated with esophageal motility abnormalities, which are manifestations of esophageal muscle dysfunction. Those motility abnormalities sometimes normalize with treatments that reduce esophageal eosinophilia, suggesting that eosinophils can cause reversible esophageal motility disturbances, perhaps by releasing myoactive and neuroactive eosinophil products. Although achalasia uncommonly is associated with EoE as currently defined, most achalasia patients have evidence of an abnormal accumulation of eosinophils and/or their degranulation products in the esophageal muscularis propria, a location inaccessible to routine endoscopic evaluation. Achalasia is an idiopathic condition resulting from destruction of neurons in the myenteric plexus of the esophagus, and degranulating eosinophils release toxic proteins capable of destroying those neurons, thereby causing the irreversible motility abnormalities of achalasia. This report reviews data on the association of esophageal eosinophilia with achalasia and other esophageal motility abnormalities. Based on this review, we propose that EoE, like eosinophilic gastroenteritis, might have mucosal-predominant and muscle-predominant forms with different clinical manifestations. A muscle-predominant form of EoE could underlie a variety of reversible and irreversible esophageal motility disorders, including achalasia. The concept that esophageal motility abnormalities might develop from a muscle-predominant form of EoE warrants serious consideration and further investigation.

Konda, V. J. A. and R. F. Souza (2018). “Biomarkers of Barrett’s Esophagus: From the Laboratory to Clinical Practice.” Dig Dis Sci 63(8): 2070-2080.

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The currently recommended approach to managing cancer risk for patients with Barrett’s esophagus is endoscopic surveillance including a biopsy protocol to sample the esophageal tissue randomly to detect dysplasia. However, there are numerous limitations in this practice that rely on the histopathological grading of dysplasia alone to make clinical decisions. The availability of in silico models demonstrating the potential cost-effectiveness of biomarker-based stratification has increased interest in finding a clinically relevant “Barrett’s biomarker.” The success of endoscopic eradication therapy in preventing neoplastic progression of dysplastic Barrett’s esophagus has promoted the desire to stratify non-dysplastic Barrett’s esophagus to those with “high risk” that may benefit from endotherapy. Furthermore, on the other end of the spectrum, there is interest in searching for a “low risk” marker that may identify those that would not likely benefit from endoscopy screening or surveillance. This review highlights recent data from the genomics (r)evolution revealing new genetic biomarkers of susceptibility to the development of Barrett’s esophagus and novel pathways for its neoplastic progression, addresses the development of new modes of tissue sampling and imaging to detect early neoplasia in Barrett’s esophagus, and discusses current progress in moving biomarkers from the laboratory into clinical practice in the era of precision medicine.

Konda, V. J. A. and R. F. Souza (2018). “Biomarkers of Barrett’s Esophagus: From the Laboratory to Clinical Practice.” Dig Dis Sci. Apr 30. [Epub ahead of print].

Full text of this article.

The currently recommended approach to managing cancer risk for patients with Barrett’s esophagus is endoscopic surveillance including a biopsy protocol to sample the esophageal tissue randomly to detect dysplasia. However, there are numerous limitations in this practice that rely on the histopathological grading of dysplasia alone to make clinical decisions. The availability of in silico models demonstrating the potential cost-effectiveness of biomarker-based stratification has increased interest in finding a clinically relevant “Barrett’s biomarker.” The success of endoscopic eradication therapy in preventing neoplastic progression of dysplastic Barrett’s esophagus has promoted the desire to stratify non-dysplastic Barrett’s esophagus to those with “high risk” that may benefit from endotherapy. Furthermore, on the other end of the spectrum, there is interest in searching for a “low risk” marker that may identify those that would not likely benefit from endoscopy screening or surveillance. This review highlights recent data from the genomics (r)evolution revealing new genetic biomarkers of susceptibility to the development of Barrett’s esophagus and novel pathways for its neoplastic progression, addresses the development of new modes of tissue sampling and imaging to detect early neoplasia in Barrett’s esophagus, and discusses current progress in moving biomarkers from the laboratory into clinical practice in the era of precision medicine.

Odiase, E., A. Schwartz, R. F. Souza, S. J. Spechler, J. Martin and V. Konda (2018). “New Eosinophilic Esophagitis Concepts Call for Change in Proton Pump Inhibitor Management Before Diagnostic Endoscopy.” Gastroenterology. Mar 3. [Epub ahead of print].

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Irrespective of the stimulus, acid secretion by the gastric parietal cells ultimately involves H+, K+-ATPase, the enzyme that pumps hydrogen ions (protons) out of the cell and into the gastric lumen in exchange for potassium ions. Proton pump inhibitors (PPIs) bind irreversibly to H+, K+-ATPase, thereby disabling the enzyme and profoundly decreasing gastric acid secretion. It is well-established and widely appreciated that PPIs are remarkably effective agents for treating diseases mediated by gastric acid such as gastroesophageal reflux disease (GERD) and peptic ulcer disease. Far less well-known are the numerous potential anti-inflammatory effects that have been described for PPIs, including their inhibitory influence on inflammatory cells and on proinflammatory cytokine production by endothelial and epithelial cells.These anti-inflammatory PPI effects, which are independent of their effects on gastric acid secretion, might enable PPIs to heal inflammatory disorders of the upper gastrointestinal tract other than GERD and peptic ulceration. Nevertheless, physicians generally have regarded a symptomatic response to PPI therapy as de facto evidence of acid peptic disease. Physicians often prescribe PPIs empirically for patients who have symptoms that might be acid related (eg, heartburn, dyspepsia), withholding diagnostic endoscopy for those whose symptoms persist despite PPI therapy. For patients who experience partial symptom relief, the PPIs are not stopped routinely before endoscopy, and physicians generally are aware that this practice creates ≥2 potential problems: (1) PPIs can mask endoscopic evidence of early gastric cancers, and (2) PPIs can eliminate endoscopic evidence of reflux esophagitis. Although there are well-documented cases of PPIs obliterating endoscopic evidence of early gastric cancer by healing associated ulcerations,4 this phenomenon seems to be very uncommon in Western countries in which the incidence of gastric cancer is low. It is less clear why endoscopists evaluating patients with GERD symptoms so readily accept the strong possibility that PPIs will eliminate evidence of reflux esophagitis at diagnostic endoscopy. The endoscopic demonstration of reflux esophagitis for patients with GERD at baseline (off antireflux therapy) has important therapeutic implications. PPI treatment is required indefinitely for patients with severe reflux esophagitis, whereas PPI treatment might be tapered, stopped, or not needed at all for patients with no reflux esophagitis at baseline. For patients who undergo endoscopy while taking PPIs, no meaningful assessment can be made regarding the baseline presence of reflux esophagitis. (Excerpt from text, p.1; no abstract available.)

Gupta, N., V. Konda and U. D. Siddiqui (2018). “Gastric cardia lesion with abnormal volumetric laser endomicroscopy imaging result.” Gastrointest Endosc Feb; 87(2): 610-612.

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A 71-year-old man with a history of epigastric pain and dyspepsia had previously been found to have Barrett’s esophagus (BE) with low-grade dysplasia. He presented to our institution for repeated EGD to thoroughly assess the Barrett’s segment. EGD showed short-segment BE with a 2-cm area of nodular, polypoid-appearing mucosa on the gastric cardia side of the gastroesophageal junction (A). The area was examined by high-definition white-light endoscopy (WLE) and narrow-band imaging (NBI) with near focus (A). Volumetric laser endomicroscopy (VLE) was also used (NVisionVLE, NinePoint Medical, Cambridge, Mass) and showed suggestive features including irregular surface (blue arrow) and atypical glands (red circle) in the area corresponding to the nodular mucosa (B). Further assessment with EUS did not reveal any obvious lesions. The lesion seen on WLE and NBI was nonspecific; however, the suggestive VLE features raised concern about malignancy, so EMR was performed of the polypoid mucosa and associated abnormal VLE area. Four hemostatic clips were placed at the site of resection because of bleeding (C). Dysplasia suspected on the basis of VLE was confirmed by a final pathologic examination, which showed cellular atypia consistent with high-grade dysplasia/intramucosal carcinoma arising from BE (D) and clear resection margins. A 3-month surveillance EGD found a small nodular area of gastric foveolar hyperplasia but no dysplasia. [Excerpt from text of this image study.]