Biljana Jovov1,2, Craig C Reed3,4, Nicholas J Shaheen1,5, Amy Pruitt1,6, Kathleen Ferrell1,7, Geraldine S Orlando1,8, Zorka Djukic1,9, Roy C Orlando1,8. 1. Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. 2. , 405 Legends Way, Chapel Hill, NC, 27516, USA. 3. Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. Craig.Reed@unchealth.unc.edu. 4. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, 101 Manning Drive, Chapel Hill, NC, 27514, USA. Craig.Reed@unchealth.unc.edu. 5. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, CB#7080, 130 Mason Farm Rd, Suite 4150, Chapel Hill, NC, 27599-7080, USA. 6. , 1500 Mayruth Dr. Apt. 1, Durham, NC, 27713, USA. 7. Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC, 27599, USA. 8. University of North Carolina School of Medicine, 340 Triple Creek Drive, Efland, NC, 27248, USA. 9. , 3811 Westcrest St., Durham, NC, 27707, USA.
Abstract
BACKGROUND: Approximately, 20% of patients with heartburn and normal endoscopic findings do not symptomatically improve on proton pump inhibitor (PPI) therapy making diagnosis and treatment uncertain. A biomarker distinguishing PPI-responsive from PPI-refractory heartburn is desirable. AIMS: We performed a pilot study assessing whether carboxy(C)-terminal fragments (CTFs) of e-cadherin in esophageal biopsies or amino(N)-terminal fragments (NTFs) of e-cadherin in serum could serve this purpose. METHODS: Twenty-nine patients with endoscopy-negative heartburn had esophageal biopsies for CTFs on Western blot and blood for serum NTFs on ELISA. All patients received dexlansoprazole 30 mg daily for 4 weeks, and heartburn was assessed by daily diary entry. Post-treatment blood samples were obtained for serum NTFs. A control group without GERD symptoms (n = 6) had biopsies for CTFs and a second control group (n = 20) blood serum for serum NTFs. RESULTS: Twenty-seven of 29 patients (93.1%) with endoscopy-negative heartburn, but 0 of 6 controls, were positive for CTFs. All patients and controls had measureable serum NTFs, but mean NTFs were significantly higher in those with PPI-responsive heartburn compared to those with PPI-refractory heartburn and controls. Following treatment, 24 of 29 (82.8) patients had relief of heartburn, which associated with a decline in mean NTFs compared to controls. NTFs in PPI-refractory patients (n = 5) were similar to controls before and after PPI therapy. CONCLUSIONS: When heartburn responds to PPI, elevated serum NTFs decline to normal. These data suggest that cleaved products of e-cadherin may serve as biomarkers of NERD. Further data are needed to assess and confirm this concept.
BACKGROUND: Approximately, 20% of patients with heartburn and normal endoscopic findings do not symptomatically improve on proton pump inhibitor (PPI) therapy making diagnosis and treatment uncertain. A biomarker distinguishing PPI-responsive from PPI-refractory heartburn is desirable. AIMS: We performed a pilot study assessing whether carboxy(C)-terminal fragments (CTFs) of e-cadherin in esophageal biopsies or amino(N)-terminal fragments (NTFs) of e-cadherin in serum could serve this purpose. METHODS: Twenty-nine patients with endoscopy-negative heartburn had esophageal biopsies for CTFs on Western blot and blood for serum NTFs on ELISA. All patients received dexlansoprazole 30 mg daily for 4 weeks, and heartburn was assessed by daily diary entry. Post-treatment blood samples were obtained for serum NTFs. A control group without GERD symptoms (n = 6) had biopsies for CTFs and a second control group (n = 20) blood serum for serum NTFs. RESULTS: Twenty-seven of 29 patients (93.1%) with endoscopy-negative heartburn, but 0 of 6 controls, were positive for CTFs. All patients and controls had measureable serum NTFs, but mean NTFs were significantly higher in those with PPI-responsive heartburn compared to those with PPI-refractory heartburn and controls. Following treatment, 24 of 29 (82.8) patients had relief of heartburn, which associated with a decline in mean NTFs compared to controls. NTFs in PPI-refractory patients (n = 5) were similar to controls before and after PPI therapy. CONCLUSIONS: When heartburn responds to PPI, elevated serum NTFs decline to normal. These data suggest that cleaved products of e-cadherin may serve as biomarkers of NERD. Further data are needed to assess and confirm this concept.
Authors: Biljana Jovov; Jianwen Que; Nelia A Tobey; Zorka Djukic; Brigid L M Hogan; Roy C Orlando Journal: Am J Gastroenterol Date: 2011-03-29 Impact factor: 10.864
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