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Tu1097 HALO Radiofrequency Ablation for High Grade Dysplasia and Early Mucosal Neoplasia Arising in Barrett's Oesophagus: Interim Results Form the UK HALO Radiofrequency Ablation Registry
Tu1097
The BARRx HALO 90 Used as a Stand Alone Device to Treat Non Dysplastic Short Segment Barrett's Esophagus (Ssbe) Michael M. Kline, Alexander K. Han, Victor T. Yu
HALO Radiofrequency Ablation for High Grade Dysplasia and Early Mucosal Neoplasia Arising in Barrett's Oesophagus: Interim Results Form the UK HALO Radiofrequency Ablation Registry Rehan J. Haidry, Jason M. Dunn, Matthew R. Banks, Mohammed A. Butt, Abhinav Gupta, Grant Fullarton, Howard Smart, Ian D. Penman, Massimiliano di Pietro, Robert P. Willert, Hugh Barr, Pradeep Bhandari, Charles Gordon, Praful Patel, Philip C. Boger, Neil Kapoor, Lesley Ann Smith, Brinder S. Mahon, Marco Novelli, Matthew Burnell, Laurence Lovat
Background: Barrx Medical Inc.offers two radiofrequency devices to the medical community, the Halo 360 and Halo 90. Several studies have reported the use of the Halo 360 to treat metaplasic/dysplasic Barrett's esophagus, followed if necessary by the Halo 90 to “touch up” remaining abnormal tissue. Presently there are no reported studies using the Barrx 90 as a stand alone device to treat non dysplastic SSBE. Both long segment and SSBE are considered premalignant conditions and SSBE is approximately 5 times more frequent than long segment. Aim: This is a pilot study to determine if the Halo 90 device, used alone, can successfully ablate non dysplastic SSBE at 1 year. Methods: . Twenty four patients with endoscopic SSBE confirmed as non dyplastic by histology were enrolled after signing informed consents. . Each patient was initially treated with Halo 90 radiofrequency ablation (RFA) using standard technique. . A second endoscopy was performed 2 months after the initial treatment and Halo 90 RFA was repeated, if necessary, as determined by the endoscopist. . A final endoscopy was performed at 1 year where four quadrant biopsies were obtained every 2 cm from visualized possible SSBE. If no abnormal tissue was visualized, four quadrant biopsies were obtained from the Z line. Results: 1.Four patients had persistent SSBE at 1 year (16.6%). 2.The overall decrease in visible length of possible SSBE at 1 year for all 24 patients was 1.25cm (57%). Four patients (16%) had an increase in visible columnar length. Three (13%) had no change in visible length. Seventeen (71%) had a decrease in visible columnar length and 11 of these had no visible columnar epithelium at 1 year. 3.The four patients with persistent SSBE had metaplasia noted in a single biopsy specimen. 4.Three of these 4 patients had a decrease in CM and 1 had stable CM at 1 year. 5.No subcutaneous metaplasia was noted and no patient developed dysplasia. Also see table Conclusions: 1.SSBE was successfully eradicated in the majority of patients after 1 or 2 treatments with the Halo 90 as a stand alone device 1 year after the initial treatment. 2.Complications were infrequent and easily treated. 3.No “buried Barrett's was noted and no patient developed advanced disease. 4.Longer term studies are needed to determine if Halo 90 can provide long term cure for SSBE. Results
Introduction: Barrett's oesophagus (BE) is the pre-cursor to oesophageal adenocarcinmoa (OAC). High grade dysplasia (HGD) & early mucosal neoplasia in BE have traditionally been treated with surgery often with a high mortality and morbidity. Recently there has been a shift toward minimally invasive endotherapy with endoscopic mucosal resection (EMR) & Radiofrequency ablation (RFA). The UK RFA registry was founded in 2008 to audit outcomes of patients under going RFA for HGD and early cancer in BE. Design: Prospective multicenter registry from 14 UK centers to audit RFA outcomes in patients with HGD and early neoplasia in BE. Intervention Prior to RFA, if patients had visible lesions these were removed by EMR. Patients then underwent RFA every 3 months until all visible BE was ablated or cancer developed. Biopsies were taken at the end of this protocol. If BE or dysplasia recurred, they were ablated at the endoscopist's discretion. Outcomes: Primary outcomes were clearance for HGD (CR-HGD), all dysplasia (CR-D) and a BE (CR-BE) at protocol end biopsy. Long term durability for CR-D for those with favorable outcomes at end of protocol was assessed. Results: 369 patients have been recruited to the registry (77% with HGD & 23% with intramucosal cancer). Mean age is 68.6 years (40-90) with 81% male. 216 (59%) have completed protocol with median of 2 ablations & mean of 2.4 (26). A mean 1.4 circumferential & 1.2 focal ablations were performed. Mean length BE segment ablated was 5.8 cm (1-20). Average time to protocol end was 11.3 months (IQR 8-14.3). CR-HGD was achieved in 83% patients at end of protocol biopsy. CR-D was 76% & CR-BE 50%. CR-D was more likely in shorter segment BE (<5cm) (82% vs 54%, p<0.0001, Fisher's exact test). Baseline histology had no influence on outcome. EMR prior to RFA made no impact on CR-D whereas patients who required rescue therapy with EMR for nodular lesions arising during RFA protocol were significantly less likely to achieve CR-D (52% vs 79%, P=0.002, fishers exact test). 3.7% patients progressed to invasive cancer at protocol end. Complications included 1 perforation in over 500 ablations and 1% incidence of superficial tears with sizing balloon. 37 patients have at least 12 months or more follow up after successful completion of protocol (range 12-42), median 16.2 months. Durability in these is excellent with 95% dysplasia free at most recent biopsy. Conclusion: This is the largest series to date of patients undergoing RFA from 14 UK centers. End of protocol CRD is satisfactory at 76% and successful eradication appears to be durable. Patients with short segment BE are likely to respond better. Those who require EMR for new lesions arising after starting RFA are less likely to achieve CR-D. Our data represent real life outcomes of integrating minimally invasive endotherapy into demanding endoscopy service commitments. Tu1098
* median ** Prague CM Barrett's Classification system *** one patient had a distal esophageal ulcer following RFA which healed in 1 month. One patient had an asymptomatic minor stricture noted at the 1 year endoscopy which resolved with treatment.
Validation of a Novel Prognostic DNA FISH Biomarker Assay in a Random Barrett Esophagus Cohort: Preliminary Results From a Phase IV Long Term Prospective Follow up Study Alifiya Pacha, Mike Visser, Fiebo J. ten Kate, Marcel G. Dijkgraaf, Rosalie C. MallantHent, Anton H. Naber, Arnoud H. van Oijen, Bert C. Baak, Pieter Scholten, Clarisse Bohmer, Jacques J. Bergman, Kausilia K. Krishnadath
Tu1096 Infrared Spectroscopy Detects Barrett's Mucosa Biopsy Specimens Ex-Vivo Rehan J. Haidry, Laurence Lovat, Matthew R. Banks, Mohammed A. Butt, Abhinav Gupta, Marco Novelli, Tomasz Kosciolek, Amandine Maréchal, Peter Rich
BACKGROUND: Ploidy changes and loss of the tumor suppressor genes p16 and p53 have been known as promising predictors for progression of Barrett esophagus. By using a DNA FISH marker set consisting of probes specific for chromosome 7 and 17 for determining ploidy status, and the locus specific probes for p53 and p16 to assess losses of these genes, we recently showed that this marker set has a high prognostic value (HR 10) in an academic cohort of BE surveillance patients. AIM: To validate our biomarker assay by determining the frequency and predictive value after prospective follow up in a community based random cohort of BE patients. METHOD: Between 2006-2011, all BE surveillance patients from 6 community hospitals were included and prospectively followed. BE patients with LGD, HGD/EAC or progression within half year, or previously treated for BE were excluded. At index endoscopy (t=0) all patients underwent upper GI endoscopy following ACG guidelines, while brush cytology was performed for the FISH analysis. Hereafter, patients prospectively underwent routine surveillance.Endpoints of the study were histological progression of ND into LGD, HGD or EAC, or a follow up of at least 60 months. All dysplastic/EAC cases were re-evaluated by expert pathologists. Patients were marker positive, if the FISH assay showed loss of p16 and/or p53 and/or anueploidy as determined in the index cytology specimen. HIstological and FISH analysis were performed blinded by independent investigators. RESULTS: A total of 266 BE patients were included and evaluated using the DNA FISH assay. Presently, 170 patients have reached an average follow up of 48 months. Of this group the mean age is 64 (range 32-88), 81% (218/266) is male. The maximum Barrett segment length is 1.16 cm (range:1-3cm. At t=0, the FISH assay tested positive in 48/170 (28%) cases. Ten patients of these 170 BE patients showed histological progression, of which all were marker positive. Eight patients progressed from ND to LGD while two patients progressed from ND to HGD. Using Kaplan Meier curves to evaluate progression free survival, a highly significant difference was observed between the two groups (log-rank test,p-value 0.02,figure 1). Cox regression analysis revealed a HR of 9 (p-value 0.002) to progress in case of a positive test as compared to other variables (Table 1). CONCLUSION: From our preliminary data we can already conclude that in this prospective follow up study our FISH marker assay proves to have high prognostic value to predict progression in BE patients. Combined with the results from our previous study cohort, we propose that this DNA FISH biomarker assay can be used to increase the cost efficacy of Barrett surveillance patients. Table1: Multivariate Analysis using Cox regression Model
INTRODUCTION: Oesophageal cancer arises (OAC) in Barrettt's oesopahgus (BE) and carries a poor prognosis. High grade dysplasia (HGD) and early mucosal neoplasia arising in BE can now be treated successfully with minimally invasive endotherapy. Fourier transform infrared spectroscopy (FTIR) can detect specific molecules from their unique vibrational absorption spectra in complex materials such as human tissue. There is growing literature on it's medical diagnostic uses in the mid-infrared (MID-IR) range of 1800-900cm-1. AIM: To use ex-vivo MID-IR absorption spectra of biopsy specimens to distinguish normal squamous oesophagus from BE mucosa without needing histological analysis METHODS: 98 biopsy specimens were obtained from 21 patients undergoing endoscopy for BE surveillance at a tertiary centre over a 3 months. 30 were from squamous epithelium, at least 2cm above the squamocolumnar junction and remainder from visible BE mucosa. At each site a biopsy was taken for mid-IR spectral analysis. A matched biopsy was taken from the same site for histopathological grading. FTIR spectra were recorded on biopsies at room temperature with a Bruker IFS 66/S spectrometer fitted with a liquid nitrogen-cooled MCT-B detector and an Attenuated Total Reflection silicon microprism. For each spectrum 1000 interferograms (approx. 2 minutes accumulation time) were averaged before Fourier transformation. Spectra were converted to second derivatives to remove baseline artefacts and improve signal resolution. An automated programme was used to quantify specific characteristic features and normalise them relative to intensities of the protein amide II band in the same spectrum. The results were used to calculate their correlation with presence of glandular mucosa in BE. RESULTS: Normal squamous mucosa and BE could be differentiated with a sensitivity of 82% and specificity of 96% by analsying variations in the 1180-1000 cm-1 region of second derivative of spectra. The bands in this region responsible for the observed differences arise from variations in levels of glycogen or a related material within the tissues. BE tissue appear to have at least 50% lower concentrations compared to the squamous epithelium. CONCLUSIONS: FTIR spectroscopy can accurately differentiate between the columnar mucosa of BE and normal squamous oesophagus. Further work is underway to examine the accuracy of this technique in differentiating different states of dysplasia from nondysplastic BE. IR spectroscopy provides a fast and effective means of detecting BE ex-vivo and presents an exciting avenue of future research with a view to incorporating IR spectral analysis into existing technologies to capture real time spectral data at endoscopy to help guide endotherapy to these high risk patients.
S-745
AGA Abstracts
AGA Abstracts
Tu1095
The BARRx HALO 90 Used as a Stand Alone Device to Treat Non Dysplastic Short Segment Barrett's Esophagus (Ssbe) Michael M. Kline, Alexander K. Han, Victor T. Yu
HALO Radiofrequency Ablation for High Grade Dysplasia and Early Mucosal Neoplasia Arising in Barrett's Oesophagus: Interim Results Form the UK HALO Radiofrequency Ablation Registry Rehan J. Haidry, Jason M. Dunn, Matthew R. Banks, Mohammed A. Butt, Abhinav Gupta, Grant Fullarton, Howard Smart, Ian D. Penman, Massimiliano di Pietro, Robert P. Willert, Hugh Barr, Pradeep Bhandari, Charles Gordon, Praful Patel, Philip C. Boger, Neil Kapoor, Lesley Ann Smith, Brinder S. Mahon, Marco Novelli, Matthew Burnell, Laurence Lovat
Background: Barrx Medical Inc.offers two radiofrequency devices to the medical community, the Halo 360 and Halo 90. Several studies have reported the use of the Halo 360 to treat metaplasic/dysplasic Barrett's esophagus, followed if necessary by the Halo 90 to “touch up” remaining abnormal tissue. Presently there are no reported studies using the Barrx 90 as a stand alone device to treat non dysplastic SSBE. Both long segment and SSBE are considered premalignant conditions and SSBE is approximately 5 times more frequent than long segment. Aim: This is a pilot study to determine if the Halo 90 device, used alone, can successfully ablate non dysplastic SSBE at 1 year. Methods: . Twenty four patients with endoscopic SSBE confirmed as non dyplastic by histology were enrolled after signing informed consents. . Each patient was initially treated with Halo 90 radiofrequency ablation (RFA) using standard technique. . A second endoscopy was performed 2 months after the initial treatment and Halo 90 RFA was repeated, if necessary, as determined by the endoscopist. . A final endoscopy was performed at 1 year where four quadrant biopsies were obtained every 2 cm from visualized possible SSBE. If no abnormal tissue was visualized, four quadrant biopsies were obtained from the Z line. Results: 1.Four patients had persistent SSBE at 1 year (16.6%). 2.The overall decrease in visible length of possible SSBE at 1 year for all 24 patients was 1.25cm (57%). Four patients (16%) had an increase in visible columnar length. Three (13%) had no change in visible length. Seventeen (71%) had a decrease in visible columnar length and 11 of these had no visible columnar epithelium at 1 year. 3.The four patients with persistent SSBE had metaplasia noted in a single biopsy specimen. 4.Three of these 4 patients had a decrease in CM and 1 had stable CM at 1 year. 5.No subcutaneous metaplasia was noted and no patient developed dysplasia. Also see table Conclusions: 1.SSBE was successfully eradicated in the majority of patients after 1 or 2 treatments with the Halo 90 as a stand alone device 1 year after the initial treatment. 2.Complications were infrequent and easily treated. 3.No “buried Barrett's was noted and no patient developed advanced disease. 4.Longer term studies are needed to determine if Halo 90 can provide long term cure for SSBE. Results
Introduction: Barrett's oesophagus (BE) is the pre-cursor to oesophageal adenocarcinmoa (OAC). High grade dysplasia (HGD) & early mucosal neoplasia in BE have traditionally been treated with surgery often with a high mortality and morbidity. Recently there has been a shift toward minimally invasive endotherapy with endoscopic mucosal resection (EMR) & Radiofrequency ablation (RFA). The UK RFA registry was founded in 2008 to audit outcomes of patients under going RFA for HGD and early cancer in BE. Design: Prospective multicenter registry from 14 UK centers to audit RFA outcomes in patients with HGD and early neoplasia in BE. Intervention Prior to RFA, if patients had visible lesions these were removed by EMR. Patients then underwent RFA every 3 months until all visible BE was ablated or cancer developed. Biopsies were taken at the end of this protocol. If BE or dysplasia recurred, they were ablated at the endoscopist's discretion. Outcomes: Primary outcomes were clearance for HGD (CR-HGD), all dysplasia (CR-D) and a BE (CR-BE) at protocol end biopsy. Long term durability for CR-D for those with favorable outcomes at end of protocol was assessed. Results: 369 patients have been recruited to the registry (77% with HGD & 23% with intramucosal cancer). Mean age is 68.6 years (40-90) with 81% male. 216 (59%) have completed protocol with median of 2 ablations & mean of 2.4 (26). A mean 1.4 circumferential & 1.2 focal ablations were performed. Mean length BE segment ablated was 5.8 cm (1-20). Average time to protocol end was 11.3 months (IQR 8-14.3). CR-HGD was achieved in 83% patients at end of protocol biopsy. CR-D was 76% & CR-BE 50%. CR-D was more likely in shorter segment BE (<5cm) (82% vs 54%, p<0.0001, Fisher's exact test). Baseline histology had no influence on outcome. EMR prior to RFA made no impact on CR-D whereas patients who required rescue therapy with EMR for nodular lesions arising during RFA protocol were significantly less likely to achieve CR-D (52% vs 79%, P=0.002, fishers exact test). 3.7% patients progressed to invasive cancer at protocol end. Complications included 1 perforation in over 500 ablations and 1% incidence of superficial tears with sizing balloon. 37 patients have at least 12 months or more follow up after successful completion of protocol (range 12-42), median 16.2 months. Durability in these is excellent with 95% dysplasia free at most recent biopsy. Conclusion: This is the largest series to date of patients undergoing RFA from 14 UK centers. End of protocol CRD is satisfactory at 76% and successful eradication appears to be durable. Patients with short segment BE are likely to respond better. Those who require EMR for new lesions arising after starting RFA are less likely to achieve CR-D. Our data represent real life outcomes of integrating minimally invasive endotherapy into demanding endoscopy service commitments. Tu1098
* median ** Prague CM Barrett's Classification system *** one patient had a distal esophageal ulcer following RFA which healed in 1 month. One patient had an asymptomatic minor stricture noted at the 1 year endoscopy which resolved with treatment.
Validation of a Novel Prognostic DNA FISH Biomarker Assay in a Random Barrett Esophagus Cohort: Preliminary Results From a Phase IV Long Term Prospective Follow up Study Alifiya Pacha, Mike Visser, Fiebo J. ten Kate, Marcel G. Dijkgraaf, Rosalie C. MallantHent, Anton H. Naber, Arnoud H. van Oijen, Bert C. Baak, Pieter Scholten, Clarisse Bohmer, Jacques J. Bergman, Kausilia K. Krishnadath
Tu1096 Infrared Spectroscopy Detects Barrett's Mucosa Biopsy Specimens Ex-Vivo Rehan J. Haidry, Laurence Lovat, Matthew R. Banks, Mohammed A. Butt, Abhinav Gupta, Marco Novelli, Tomasz Kosciolek, Amandine Maréchal, Peter Rich
BACKGROUND: Ploidy changes and loss of the tumor suppressor genes p16 and p53 have been known as promising predictors for progression of Barrett esophagus. By using a DNA FISH marker set consisting of probes specific for chromosome 7 and 17 for determining ploidy status, and the locus specific probes for p53 and p16 to assess losses of these genes, we recently showed that this marker set has a high prognostic value (HR 10) in an academic cohort of BE surveillance patients. AIM: To validate our biomarker assay by determining the frequency and predictive value after prospective follow up in a community based random cohort of BE patients. METHOD: Between 2006-2011, all BE surveillance patients from 6 community hospitals were included and prospectively followed. BE patients with LGD, HGD/EAC or progression within half year, or previously treated for BE were excluded. At index endoscopy (t=0) all patients underwent upper GI endoscopy following ACG guidelines, while brush cytology was performed for the FISH analysis. Hereafter, patients prospectively underwent routine surveillance.Endpoints of the study were histological progression of ND into LGD, HGD or EAC, or a follow up of at least 60 months. All dysplastic/EAC cases were re-evaluated by expert pathologists. Patients were marker positive, if the FISH assay showed loss of p16 and/or p53 and/or anueploidy as determined in the index cytology specimen. HIstological and FISH analysis were performed blinded by independent investigators. RESULTS: A total of 266 BE patients were included and evaluated using the DNA FISH assay. Presently, 170 patients have reached an average follow up of 48 months. Of this group the mean age is 64 (range 32-88), 81% (218/266) is male. The maximum Barrett segment length is 1.16 cm (range:1-3cm. At t=0, the FISH assay tested positive in 48/170 (28%) cases. Ten patients of these 170 BE patients showed histological progression, of which all were marker positive. Eight patients progressed from ND to LGD while two patients progressed from ND to HGD. Using Kaplan Meier curves to evaluate progression free survival, a highly significant difference was observed between the two groups (log-rank test,p-value 0.02,figure 1). Cox regression analysis revealed a HR of 9 (p-value 0.002) to progress in case of a positive test as compared to other variables (Table 1). CONCLUSION: From our preliminary data we can already conclude that in this prospective follow up study our FISH marker assay proves to have high prognostic value to predict progression in BE patients. Combined with the results from our previous study cohort, we propose that this DNA FISH biomarker assay can be used to increase the cost efficacy of Barrett surveillance patients. Table1: Multivariate Analysis using Cox regression Model
INTRODUCTION: Oesophageal cancer arises (OAC) in Barrettt's oesopahgus (BE) and carries a poor prognosis. High grade dysplasia (HGD) and early mucosal neoplasia arising in BE can now be treated successfully with minimally invasive endotherapy. Fourier transform infrared spectroscopy (FTIR) can detect specific molecules from their unique vibrational absorption spectra in complex materials such as human tissue. There is growing literature on it's medical diagnostic uses in the mid-infrared (MID-IR) range of 1800-900cm-1. AIM: To use ex-vivo MID-IR absorption spectra of biopsy specimens to distinguish normal squamous oesophagus from BE mucosa without needing histological analysis METHODS: 98 biopsy specimens were obtained from 21 patients undergoing endoscopy for BE surveillance at a tertiary centre over a 3 months. 30 were from squamous epithelium, at least 2cm above the squamocolumnar junction and remainder from visible BE mucosa. At each site a biopsy was taken for mid-IR spectral analysis. A matched biopsy was taken from the same site for histopathological grading. FTIR spectra were recorded on biopsies at room temperature with a Bruker IFS 66/S spectrometer fitted with a liquid nitrogen-cooled MCT-B detector and an Attenuated Total Reflection silicon microprism. For each spectrum 1000 interferograms (approx. 2 minutes accumulation time) were averaged before Fourier transformation. Spectra were converted to second derivatives to remove baseline artefacts and improve signal resolution. An automated programme was used to quantify specific characteristic features and normalise them relative to intensities of the protein amide II band in the same spectrum. The results were used to calculate their correlation with presence of glandular mucosa in BE. RESULTS: Normal squamous mucosa and BE could be differentiated with a sensitivity of 82% and specificity of 96% by analsying variations in the 1180-1000 cm-1 region of second derivative of spectra. The bands in this region responsible for the observed differences arise from variations in levels of glycogen or a related material within the tissues. BE tissue appear to have at least 50% lower concentrations compared to the squamous epithelium. CONCLUSIONS: FTIR spectroscopy can accurately differentiate between the columnar mucosa of BE and normal squamous oesophagus. Further work is underway to examine the accuracy of this technique in differentiating different states of dysplasia from nondysplastic BE. IR spectroscopy provides a fast and effective means of detecting BE ex-vivo and presents an exciting avenue of future research with a view to incorporating IR spectral analysis into existing technologies to capture real time spectral data at endoscopy to help guide endotherapy to these high risk patients.
S-745
AGA Abstracts
AGA Abstracts
Tu1095