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Tu1545 Diagnostic Utility of Volumetric LASER Endo-Microscopy (VLE) Surveillance in Patients With Barrett's Esophagus in Routine Clinical Practice
Abstracts
Tu1545 Diagnostic Utility of Volumetric LASER Endo-Microscopy (VLE) Surveillance in Patients With Barrett’s Esophagus in Routine Clinical Practice Hari P. Sayana1, Utpal Mondal*1, Gurtej Malhi1, David N. Henkes2, Hendrikus Vanderveldt1, Laura Rosenkranz1, Sandeep Patel1 1 Advanced Endoscopy, University of Texas Health Science Center, San Antonio, San Antonio, TX; 2Pathology, CHRISTUS Santa Rosa - City Centre, San Antonio, TX Background: Esophageal adenocarcinoma (EAC) is one of the most rapidly increasing cancers with poor 5-year survival worldwide. Barrett’s esophagus (BE) is a premalignant condition for the development of EAC. Current endoscopic surveillance strategy is fraught with sampling errors. Volumetric Laser Endo-microscopy (VLE) is a novel second generation Optical Coherence Tomography (OCT) imaging technology that elicits 3D volumetric cross-sectional and longitudinal images of the distal esophagus with resolution less than 10 microns. Various studies have reported diagnostic criteria to recognize high-risk lesions such as High-grade dysplasia (HGD) and Intra-mucosal cancer (IMC). It’s diagnostic utility in routine clinical practice is currently unknown. Methods: Charts of all patients enrolled in BE surveillance between July and November 2014 at our Institution were reviewed. Patients of age 18 years and above with Barrett’s esophagus with or without dysplasia agreed to undergo VLE scanning prior to biopsy, endoscopic mucosal resection (EMR) and/or Radio frequency ablation (RFA). VLE scans were obtained after recognition of endoscopic landmarks and mapping of BE segment with high quality white light endoscopy. Based on VLE images, high-risk lesions with atypical intra-mucosal glands and ducts were identified and targeted biopsies were obtained using standard keyhole biopsy technique followed by random biopsies per Seattle protocol. Results: Fifteen patients with BE who met the inclusion criteria were included in the analysis. Mean age was 67+/- 17 years with 79% males (nZ11). 10/15 patients were undergoing surveillance during RFA ablation. Of these, 1 had IMC, 6 had HGD and 3 had LGD. 10 patients underwent prior RFA ablation, with 5 having complete eradication of BE (CEBE) with neo-squamous epithelium. Of the remaining 5/15 patients, 4 were referred for RFA ablation (2 had with HGD, 1 with LGD, 1 non dysplastic BE) and the other with IMC s/p EMR.A total 19 lesions with single or cluster of atypical glands and/or ducts were identified on VLE scans. 17/19 lesions were biopsied using keyhole biopsy technique. Of the 17 biopsies, 4 revealed BE with dysplasia (1 HGD, 3 LGD), 5 non-dysplastic BE, 4 no BE, and 4 with oxynto-cardia type gastric mucosa. Compared to random biopsy sampling, VLE targeted biopsies identified 3 new lesions with dysplasia, which were missed on random biopsy protocol. On the other hand, two new dysplastic lesions were diagnosed on random biopsies that were seen on VLE imaging at the same level however, missed on VLE targeted biopsy. Conclusion: VLE is a useful imaging tool to identify high-risk lesions within Barrett’s esophagus. However, prospectively validated criteria for diagnosis of dysplasia/IMC, optimal spatial orientation and targeted biopsy techniques for tissue acquisition are needed to increase the yield of VLE based approach.
Tu1546 Diagnosis and Management of Barrett’s Esophagus: a Retrospective Study Comparing the Approach of Community and Tertairy Centre Physicians Erin Rayner-Hartley, Oliver Takach*, Cherry E. Galorport, Robert A. Enns University of British Columbia, Burnaby, BC, Canada Aims: Specialized endoscopic evaluation for patients with Barrett’s Esophagus (BE) is well supported, however no studies have shown that centers with expertise provide better quality care for BE with high-grade dysplasia or early adenocarcinoma. In this study, the investigators aimed to evaluate the management and clinical course for patients treated in a community practice versus a specialized BE center. Methods: A retrospective analysis of referrals from the community to our specialized center for evaluation of BE at St Paul’s Hospital Division of Gastroenterology between January 2007 and February 2014 was performed. Subjects were patients referred for BE and dysplasia and subsequently re-evaluated by endoscopy. The pathology and endoscopy reports from the community and our center were reviewed. Inclusion criteria: R 19 years old, pathologic diagnosis of BE or dysplasia in the community. Exclusion criteria: incomplete pathology data or incomplete endoscopy reports from the community physicians. Results: 77 total patients were reviewed. The staging of 28.9% of patients referred from the community was changed from the initial pathological diagnosis. 18.4% of these patients were upstaged. Using the Fischer Exact test, we showed that in our specialized center, endoscopic impressions correlated significantly with pathology results (p!0.0001). Conclusions: The staging of esophageal pathology was changed in a significant proportion of patients referred from the community to our specialized BE center. Our endoscopic impressions correlated well with pathology results. This study supports the early referral of patients with BE to a center of expertise, in order to optimize diagnosis and management.
Tu1547 The Use of Immunohistochemistry (CDx2, MUC2, H2AX, p53) in Patients With Barrett’s Esophagus - the Stratification and the Risk Assessment Jan Gregar*1, Pavla Luzna2, Vlastimil Procházka1, Jiri Ehrmann2, Premysl Falt3, Stepan Suchanek4, Josef Srovnal5
AB504 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 5S : 2015
1
Department of Internal Medicine II, Gastro-enterology and Hepatology, University Hospital Olomouc, Czech Republic, Olomouc, Czech Republic; 2 Department of histology and embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic; 3 Digestive Diseases Centre, Vítkovice Hospital, Ostrava, Czech Republic; 4 Department of Gastroenterology, Internal clinic, Military University Hospital, Prague, Czech Republic; 5Institute of Molecular and Translational Medicine IMTM, Olomouc, Czech Republic Backround: Barrett’s esophagus (BE) is premalignant condition. Sequence of histological changes in the esophagus from intestinal metaplasia (IM) through low-grade dysplasia (LG) up to high-grade dysplasia (HG) and adenocarcinoma is typical for BE. Endoscopy and histopathology assessment is “gold standard” for diagnosis and surveillance. But immunohistochemistry can be helpful for stratification and assessment of risk of dysplasia or malignancy. Methods: The aim of the study was to investigate the role and the diagnostic potential of the immunohistochemistry in the disease progression. BE was inspected by endoscopy ( narrow band imaging and zoom) and biopsies from all suspicious lesions were obtained for histopathological assessment (50 patients, diagnosed in the last 3 years). 25 patients with nondysplastic BE and 25 patients with low-grade dysplazie BE (LG, low-grade intraepithelial neoplasia). Bioptic samples (50 patients) were used for indirect immunohistochemical labelling and analysis of expression of proteins playing an important role during BE progression (CDX2, MUC2, H2AX and p53). Expression of selected proteins was assesed semiquantitatively by “histoscore” (H score), which is the result of intensity of staining (0 Z negative, 1 Z weakly visible intensity, 2 Z ligh brown intensity, 3 Z dark brown intensity of staining) multiplied by percentage of positive cells. Results: Immunohistochemical detection of expression of selected proteins showed the rising histoscore of all selected proteins in BE with LG dysplasia against non-dysplastic IM BE: CDX (16.7% vs. 33.3%), MUC2 (6.3% vs. 36.4%), H2AX 25.9% vs. 44.4% and p53 75.0% vs. 89.6%). Statistical significance was found inCDX, MUC2 and H2AX proteins. Conclusions: Immunohistochemistry of selected proteins showed that they could be helpfull markers of disease progression which may help to select patients with risk of dysplastic changes in BE.Supported by Grant - Czech Ministry of Health: NT 13585-3/2012 and NT 13636-4/2012
Tu1548 Defective Barrier Function in Neosquamous Epithelium: a Risk Factor for Recurrent Barrett’s Esophagus: a BETRNet Pilot Project Thomas Runge*1, Nicholas J. Shaheen1,2, Roy C. Orlando1,2 1 Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC; 2Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC Background: After radiofrequency ablation (RFA) of Barrett’s esophagus (BE), the epithelium reverts to neosquamous epithelium (NSE). However, NSE shows characteristics of defective barrier function (increased paracellular permeability and dilated intercellular spaces) similar to those seen in gastroesophageal reflux disease (GERD). These defects which may reflect exposure of NSE to refluxed acid, and may be a risk factor for recurrence of BE. Since defective barrier function in GERD involves cleavage of the junctional protein e-cadherin, we considered the possibility that a similar phenomenon also occurs in NSE. Aim: To determine whether NSE after RFA contains c-terminal fragments (CTFs) of e-cadherin, indicating cleavage of this junctional protein. Also, to determine whether the serum of patients with NSE contains elevated levels of N-terminal fragments (NTFs) of e-cadherin and, if so, whether the cause for the elevated NTFs reflected ongoing exposure of NSE to pathologic levels of refluxed gastric acid. Methods: Fifteen individuals with NSE after successful RFA were enrolled in this prospective pilot study. Participants were at least 3 months post-RFA of long segment (R3cm) BE and all were taking proton pump inhibitors. Endoscopic biopsies of NSE were obtained for Western blot to assess the presence of CTFs of e-cadherin. Blood samples were simultaneously obtained for determination by ELISA assay of the quantity of NTFs of e-cadherin in serum. Participants were also offered 24hr esophageal pH monitoring to document the degree of esophageal acid exposure and CTF and NTF results compared to prior data obtained from GERD and healthy subjects. Results: Western blots were available for 14/15 patients. This revealed 35-kd CTFs of e-cadherin in 100% of 14 NSE samples. [Note: 35-kd CTFs are absent in esophageal epithelium of healthy subjects.] Mean serum NTFs for NSE patients were slightly higher (67.7 pg/ml) than that in serum of healthy subjects (65.3 pg/ml), a difference that was not statistically significant. Only two subjects agreed to esophageal pH monitoring - one had a dramatically elevated acid-contact time of 24.3% (normal !4%) in association with an elevated level of NTFs and the other had normal acid-contact time (1.5%) in association with a normal level of NTFs. Conclusions: Biopsies of NSE exhibit (35kd) CTFs of e-cadherin on Western blot, a finding consistent with defective barrier function and similar to that present in distal esophageal epithelium in GERD. However, serum NTFs in those with NSE, unlike GERD,are not elevated above NTFs of healthy subjects. This difference may relate to RFA-induced damage to local capillaries, prohibiting NTFs from reaching the bloodstream. Further work will assess whether the presence of pathologic acid exposure determines e-cadherin fragments in blood and tissue.
www.giejournal.org
Tu1545 Diagnostic Utility of Volumetric LASER Endo-Microscopy (VLE) Surveillance in Patients With Barrett’s Esophagus in Routine Clinical Practice Hari P. Sayana1, Utpal Mondal*1, Gurtej Malhi1, David N. Henkes2, Hendrikus Vanderveldt1, Laura Rosenkranz1, Sandeep Patel1 1 Advanced Endoscopy, University of Texas Health Science Center, San Antonio, San Antonio, TX; 2Pathology, CHRISTUS Santa Rosa - City Centre, San Antonio, TX Background: Esophageal adenocarcinoma (EAC) is one of the most rapidly increasing cancers with poor 5-year survival worldwide. Barrett’s esophagus (BE) is a premalignant condition for the development of EAC. Current endoscopic surveillance strategy is fraught with sampling errors. Volumetric Laser Endo-microscopy (VLE) is a novel second generation Optical Coherence Tomography (OCT) imaging technology that elicits 3D volumetric cross-sectional and longitudinal images of the distal esophagus with resolution less than 10 microns. Various studies have reported diagnostic criteria to recognize high-risk lesions such as High-grade dysplasia (HGD) and Intra-mucosal cancer (IMC). It’s diagnostic utility in routine clinical practice is currently unknown. Methods: Charts of all patients enrolled in BE surveillance between July and November 2014 at our Institution were reviewed. Patients of age 18 years and above with Barrett’s esophagus with or without dysplasia agreed to undergo VLE scanning prior to biopsy, endoscopic mucosal resection (EMR) and/or Radio frequency ablation (RFA). VLE scans were obtained after recognition of endoscopic landmarks and mapping of BE segment with high quality white light endoscopy. Based on VLE images, high-risk lesions with atypical intra-mucosal glands and ducts were identified and targeted biopsies were obtained using standard keyhole biopsy technique followed by random biopsies per Seattle protocol. Results: Fifteen patients with BE who met the inclusion criteria were included in the analysis. Mean age was 67+/- 17 years with 79% males (nZ11). 10/15 patients were undergoing surveillance during RFA ablation. Of these, 1 had IMC, 6 had HGD and 3 had LGD. 10 patients underwent prior RFA ablation, with 5 having complete eradication of BE (CEBE) with neo-squamous epithelium. Of the remaining 5/15 patients, 4 were referred for RFA ablation (2 had with HGD, 1 with LGD, 1 non dysplastic BE) and the other with IMC s/p EMR.A total 19 lesions with single or cluster of atypical glands and/or ducts were identified on VLE scans. 17/19 lesions were biopsied using keyhole biopsy technique. Of the 17 biopsies, 4 revealed BE with dysplasia (1 HGD, 3 LGD), 5 non-dysplastic BE, 4 no BE, and 4 with oxynto-cardia type gastric mucosa. Compared to random biopsy sampling, VLE targeted biopsies identified 3 new lesions with dysplasia, which were missed on random biopsy protocol. On the other hand, two new dysplastic lesions were diagnosed on random biopsies that were seen on VLE imaging at the same level however, missed on VLE targeted biopsy. Conclusion: VLE is a useful imaging tool to identify high-risk lesions within Barrett’s esophagus. However, prospectively validated criteria for diagnosis of dysplasia/IMC, optimal spatial orientation and targeted biopsy techniques for tissue acquisition are needed to increase the yield of VLE based approach.
Tu1546 Diagnosis and Management of Barrett’s Esophagus: a Retrospective Study Comparing the Approach of Community and Tertairy Centre Physicians Erin Rayner-Hartley, Oliver Takach*, Cherry E. Galorport, Robert A. Enns University of British Columbia, Burnaby, BC, Canada Aims: Specialized endoscopic evaluation for patients with Barrett’s Esophagus (BE) is well supported, however no studies have shown that centers with expertise provide better quality care for BE with high-grade dysplasia or early adenocarcinoma. In this study, the investigators aimed to evaluate the management and clinical course for patients treated in a community practice versus a specialized BE center. Methods: A retrospective analysis of referrals from the community to our specialized center for evaluation of BE at St Paul’s Hospital Division of Gastroenterology between January 2007 and February 2014 was performed. Subjects were patients referred for BE and dysplasia and subsequently re-evaluated by endoscopy. The pathology and endoscopy reports from the community and our center were reviewed. Inclusion criteria: R 19 years old, pathologic diagnosis of BE or dysplasia in the community. Exclusion criteria: incomplete pathology data or incomplete endoscopy reports from the community physicians. Results: 77 total patients were reviewed. The staging of 28.9% of patients referred from the community was changed from the initial pathological diagnosis. 18.4% of these patients were upstaged. Using the Fischer Exact test, we showed that in our specialized center, endoscopic impressions correlated significantly with pathology results (p!0.0001). Conclusions: The staging of esophageal pathology was changed in a significant proportion of patients referred from the community to our specialized BE center. Our endoscopic impressions correlated well with pathology results. This study supports the early referral of patients with BE to a center of expertise, in order to optimize diagnosis and management.
Tu1547 The Use of Immunohistochemistry (CDx2, MUC2, H2AX, p53) in Patients With Barrett’s Esophagus - the Stratification and the Risk Assessment Jan Gregar*1, Pavla Luzna2, Vlastimil Procházka1, Jiri Ehrmann2, Premysl Falt3, Stepan Suchanek4, Josef Srovnal5
AB504 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 5S : 2015
1
Department of Internal Medicine II, Gastro-enterology and Hepatology, University Hospital Olomouc, Czech Republic, Olomouc, Czech Republic; 2 Department of histology and embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic; 3 Digestive Diseases Centre, Vítkovice Hospital, Ostrava, Czech Republic; 4 Department of Gastroenterology, Internal clinic, Military University Hospital, Prague, Czech Republic; 5Institute of Molecular and Translational Medicine IMTM, Olomouc, Czech Republic Backround: Barrett’s esophagus (BE) is premalignant condition. Sequence of histological changes in the esophagus from intestinal metaplasia (IM) through low-grade dysplasia (LG) up to high-grade dysplasia (HG) and adenocarcinoma is typical for BE. Endoscopy and histopathology assessment is “gold standard” for diagnosis and surveillance. But immunohistochemistry can be helpful for stratification and assessment of risk of dysplasia or malignancy. Methods: The aim of the study was to investigate the role and the diagnostic potential of the immunohistochemistry in the disease progression. BE was inspected by endoscopy ( narrow band imaging and zoom) and biopsies from all suspicious lesions were obtained for histopathological assessment (50 patients, diagnosed in the last 3 years). 25 patients with nondysplastic BE and 25 patients with low-grade dysplazie BE (LG, low-grade intraepithelial neoplasia). Bioptic samples (50 patients) were used for indirect immunohistochemical labelling and analysis of expression of proteins playing an important role during BE progression (CDX2, MUC2, H2AX and p53). Expression of selected proteins was assesed semiquantitatively by “histoscore” (H score), which is the result of intensity of staining (0 Z negative, 1 Z weakly visible intensity, 2 Z ligh brown intensity, 3 Z dark brown intensity of staining) multiplied by percentage of positive cells. Results: Immunohistochemical detection of expression of selected proteins showed the rising histoscore of all selected proteins in BE with LG dysplasia against non-dysplastic IM BE: CDX (16.7% vs. 33.3%), MUC2 (6.3% vs. 36.4%), H2AX 25.9% vs. 44.4% and p53 75.0% vs. 89.6%). Statistical significance was found inCDX, MUC2 and H2AX proteins. Conclusions: Immunohistochemistry of selected proteins showed that they could be helpfull markers of disease progression which may help to select patients with risk of dysplastic changes in BE.Supported by Grant - Czech Ministry of Health: NT 13585-3/2012 and NT 13636-4/2012
Tu1548 Defective Barrier Function in Neosquamous Epithelium: a Risk Factor for Recurrent Barrett’s Esophagus: a BETRNet Pilot Project Thomas Runge*1, Nicholas J. Shaheen1,2, Roy C. Orlando1,2 1 Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC; 2Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC Background: After radiofrequency ablation (RFA) of Barrett’s esophagus (BE), the epithelium reverts to neosquamous epithelium (NSE). However, NSE shows characteristics of defective barrier function (increased paracellular permeability and dilated intercellular spaces) similar to those seen in gastroesophageal reflux disease (GERD). These defects which may reflect exposure of NSE to refluxed acid, and may be a risk factor for recurrence of BE. Since defective barrier function in GERD involves cleavage of the junctional protein e-cadherin, we considered the possibility that a similar phenomenon also occurs in NSE. Aim: To determine whether NSE after RFA contains c-terminal fragments (CTFs) of e-cadherin, indicating cleavage of this junctional protein. Also, to determine whether the serum of patients with NSE contains elevated levels of N-terminal fragments (NTFs) of e-cadherin and, if so, whether the cause for the elevated NTFs reflected ongoing exposure of NSE to pathologic levels of refluxed gastric acid. Methods: Fifteen individuals with NSE after successful RFA were enrolled in this prospective pilot study. Participants were at least 3 months post-RFA of long segment (R3cm) BE and all were taking proton pump inhibitors. Endoscopic biopsies of NSE were obtained for Western blot to assess the presence of CTFs of e-cadherin. Blood samples were simultaneously obtained for determination by ELISA assay of the quantity of NTFs of e-cadherin in serum. Participants were also offered 24hr esophageal pH monitoring to document the degree of esophageal acid exposure and CTF and NTF results compared to prior data obtained from GERD and healthy subjects. Results: Western blots were available for 14/15 patients. This revealed 35-kd CTFs of e-cadherin in 100% of 14 NSE samples. [Note: 35-kd CTFs are absent in esophageal epithelium of healthy subjects.] Mean serum NTFs for NSE patients were slightly higher (67.7 pg/ml) than that in serum of healthy subjects (65.3 pg/ml), a difference that was not statistically significant. Only two subjects agreed to esophageal pH monitoring - one had a dramatically elevated acid-contact time of 24.3% (normal !4%) in association with an elevated level of NTFs and the other had normal acid-contact time (1.5%) in association with a normal level of NTFs. Conclusions: Biopsies of NSE exhibit (35kd) CTFs of e-cadherin on Western blot, a finding consistent with defective barrier function and similar to that present in distal esophageal epithelium in GERD. However, serum NTFs in those with NSE, unlike GERD,are not elevated above NTFs of healthy subjects. This difference may relate to RFA-induced damage to local capillaries, prohibiting NTFs from reaching the bloodstream. Further work will assess whether the presence of pathologic acid exposure determines e-cadherin fragments in blood and tissue.
www.giejournal.org