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Clinical and Biomarker Predictors of Response to Radiofrequency Ablation in Barrett's Esophagus
Abstracts
(1.2%). Conclusion: ESD for esophageal tumor provided lower complication rate and higher rate of successful en bloc resection, indicating that ESD with a Flex knife is useful and safe for esophageal tumor.
W1325 Four-Year Open-Label Follow-Up of a Randomized, Placebo-Controlled Trial of Endoscopic Gastroplication (Endocinch) for the Treatment of Gastro-Esophageal Reflux Disease (GERD) ´ J. Smout, Matthijs P. Schwartz Rieneke Schreinemakers, Andre Introduction and Aim: In recent years, developments in endotherapy for GERD have been promising. However, reported outcomes vary and long-term results are often lacking. We aimed to evaluate the long-term effect of endoscopic gastroplication for chronic GERD. Methods: After the 3-month randomized trial period and subsequent crossing over, a total of 50 patients received active treatment (3 gastroplications), and were included in the open-label prospective follow-up. Retreatment was optional in the first year. Assessments were done at baseline, 3 months after (re) treatment and yearly, using questionnaires that included: proton pump inhibitor (PPI) use, symptoms, quality of life (QoL), adverse events and other reflux treatments. Results: 47 of the 50 patients were followed for a median of 48 (38-52) months. No serious adverse events occurred. 3 months after the first treatment, 70% had a R50% reduction in PPI use. Heartburn and regurgitation scores improved with 41% and 37% (both p!0.00). 5 QoL subscales (physical health, role and social function, general health, pain perception) significantly improved. 22 (44%) patients were retreated after a median of 4 (3-8) months, with a mean of 1.4 plications. At the end of follow-up, improvement of symptom scores and QoL persisted (both p!0.00). The number of patients with a R50% reduction in PPI use dropped to 19 (40%). 47% indicated that their GERD had improved (30%), or cured (17%). 64% were treatment failures (O50% PPI use or other reflux treatment; Fig 1). Conclusion: In a 4-year period, a gradually declining subset of GERD patients benefit from a long-term effect of endoscopic gastroplication. Moreover, a high proportion was retreated.
length resected was a significant independent predictor for more dilations performed. Conclusions: A variable rate of esophageal strictures occurred post-EMR for BE with HGD or CA with the highest rates after circumferential-EMR. Younger age and larger circumference resected were predictors for post-EMR strictures. Longer length resected was found to predict more dilations needed. Although endoscopic dilation therapy was effective in relieving symptoms of dysphagia, preventive measures are desired for post-EMR strictures, especially for circumferential-EMR. Results
Mean # Resections # EMR Taken Sessions(Range) 100% 21/73 Circumference (28.8%) Removed O50%, !100% 18/73 Circumference (24.7%) Removed !50% 34/73 Circumference (46.6%) Removed Overall 73/73 (100%)
Mean % Circumference Removed (Range)
Mean Time Mean of Follow-Up Length in days Resected # Post- Mean # in cm EMR Dilations (Range) Strictures(Range)
7.1 (4-14)
100 (100)
3.8 (1-8) 16/21 (76.2%)
2.9 (1-9) 166.6
3.8 (1-6)
73.6 (67-80%)
3.6 (2-7)
2.8 (1-8)
44.1 (25-50)
3.6 (1-10) 3/32 (9.4%)z
2.0 (2)
192.5
4.3
67.4%
3.6
2.7
161.1
4/16 2.2 (1-3) (25.0%)y
23/69 (33.3%)
90.8
yExcluded: 1 pt lost to follow-up, 1 pt referred to surgery for findings of submucosal cancer on EMR specimen zExcluded: 2 pts lost to follow-up
W1327 Clinical and Biomarker Predictors of Response to Radiofrequency Ablation in Barrett’s Esophagus Ganapathy A. Prasad, Kevin C. Halling, Shannon M. Brankley, Navtej Buttar, Louis-Michel Wong Kee Song, Kelly T. Dunagan, Lori S. Lutzke, Lynn S. Borkenhagen, Kenneth K. Wang
W1326 Frequency and Risk Factors of Esophageal Stricture After Endoscopic Mucosal Resection (EMR) for Barrett’s Esophagus (BE) with High-Grade Dysplasia (HGD) or Adenocarcinoma (CA) Roy Yen, Alexander A. Dekovich, Yang K. Chen, Raj J. Shah, Brian C. Brauer, Daniel A. Ringold, Norio Fukami Background: EMR for BE with HGD or CA is an accepted diagnostic and therapeutic modality. While stricture is a known complication of EMR, the rate and predictors of post-EMR strictures (pES) and response of strictures to dilation are not well defined. Methods: Analysis was performed of prospectively collected data of pts who underwent EMR for BE with HGD or CA between 5/1/05 and 10/31/08. Dilation of pES was performed for symptoms of dysphagia to solids. The following data was collected: age, gender, ethnicity, number of (#) resected specimens taken, % circumference resected, length resected, occurrence of pES, and # dilations. Proportions were compared by chi-square. Prediction of dichotomous outcomes and continuous outcomes by independent variables was calculated by logistic and linear regression respectively. Results: 57 pts underwent 73 EMR sessions. 21/73 (29%) of treatment sessions were circumferential-EMR (C-EMR) with 100% circumference removed in 2 stages. 52/73 (71%) of treatment sessions were noncircumferential EMR (NC-EMR) with !100% circumference removed. Of 52 NCEMR sessions, 34 sessions had !50% circumference removed and 18 had O50% circumference removed (See Table). C-EMR had a significantly higher rate of pES than O50% NC-EMR and !50% NC-EMR (76% vs 25% vs 9%, p!.001). All patients with pES responded to endoscopic dilation therapy. Younger age and larger circumference resected were significant independent predictors of pES. Longer
AB342 GASTROINTESTINAL ENDOSCOPY Volume 69, No. 5 : 2009
Background: Radiofrequency ablation (RFA) is a promising technique effective for the treatment of dysplasia in BE. Failure rates for the elimination of dysplasia range from 10% to 20%. Predictors of response are yet to be defined. We aimed to characterize clinical and biomarker factors of response in a tertiary care referral center. Methods: We prospectively followed all patients treated with RFA over the last 3 years. We defined failure of RFA as the presence of dysplasia on biopsies taken at the first endoscopy after completion of RFA treatments as performed in the randomized trial (initial Halo 360 ablation with 12 Joules followed by Halo 90 ablation with 12 joules for elimination of all visible BE). Demographic and clinical data were extracted from a prospectively maintained database. Biomarker predictors were assessed using fluorescence in-situ hybridization (FISH) performed on cytology specimens obtained before ablation using previously defined standard methods. Loci assessed included: gains of 8q24.12-q24.13 (C-MYC), 17q11.2-q12 (HER-2), and 20q13.2 and loss of 9p21 (site of p16 gene). Cells were also assessed for multiple gains of loci. Univariate and multivariate logistic regression was performed to assess predictors of response. Results: 62 patients (mean age 63y, 89% male) were included. 37 (60%) were treated for HGD/Carcinoma, and the remainder were treated for LGD or no dysplasia. Mean BE length was 5.9 cm (SD 3.5). 82% were treated with Halo 360 followed by Halo 90 and 18% by Halo 90 alone. 19 patients (31%) met criteria for non-response. Biomarker data was available on 24 patients. On univariate analysis, older age, increasing length of the BE segment, presence of nodularity (requiring EMR) and HGD were predictors of poor response. Results of multivariable analysis confirmed length of the BE segment and nodularity as independent predictors of poor response. Patients with P16 allelic loss showed a numerically lower rate of response (35%) compared to those with intact P16 (55%) (pZ0.10). Gains at protooncogene loci did not appear to influence response to RF ablation. This is similar to prior findings of predictors of response to PDT. Conclusions: Patients with longer BE segments, HGD and nodularity needing EMR are less likely to respond to RF ablation. The role of P16 allelic loss (which may decrease odds of response to RF ablation) needs further study. Results of multivariable analysis Variable
Odds Ratio (95% CI)
p value
Age Gender Length of BE segment Nodularity
0.94 4.39 0.79 0.42
0.09 0.11 0.02 0.04
(0.87, (0.71, (0.64, (0.10,
1.01) 31.96) 0.95) 0.96)
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(1.2%). Conclusion: ESD for esophageal tumor provided lower complication rate and higher rate of successful en bloc resection, indicating that ESD with a Flex knife is useful and safe for esophageal tumor.
W1325 Four-Year Open-Label Follow-Up of a Randomized, Placebo-Controlled Trial of Endoscopic Gastroplication (Endocinch) for the Treatment of Gastro-Esophageal Reflux Disease (GERD) ´ J. Smout, Matthijs P. Schwartz Rieneke Schreinemakers, Andre Introduction and Aim: In recent years, developments in endotherapy for GERD have been promising. However, reported outcomes vary and long-term results are often lacking. We aimed to evaluate the long-term effect of endoscopic gastroplication for chronic GERD. Methods: After the 3-month randomized trial period and subsequent crossing over, a total of 50 patients received active treatment (3 gastroplications), and were included in the open-label prospective follow-up. Retreatment was optional in the first year. Assessments were done at baseline, 3 months after (re) treatment and yearly, using questionnaires that included: proton pump inhibitor (PPI) use, symptoms, quality of life (QoL), adverse events and other reflux treatments. Results: 47 of the 50 patients were followed for a median of 48 (38-52) months. No serious adverse events occurred. 3 months after the first treatment, 70% had a R50% reduction in PPI use. Heartburn and regurgitation scores improved with 41% and 37% (both p!0.00). 5 QoL subscales (physical health, role and social function, general health, pain perception) significantly improved. 22 (44%) patients were retreated after a median of 4 (3-8) months, with a mean of 1.4 plications. At the end of follow-up, improvement of symptom scores and QoL persisted (both p!0.00). The number of patients with a R50% reduction in PPI use dropped to 19 (40%). 47% indicated that their GERD had improved (30%), or cured (17%). 64% were treatment failures (O50% PPI use or other reflux treatment; Fig 1). Conclusion: In a 4-year period, a gradually declining subset of GERD patients benefit from a long-term effect of endoscopic gastroplication. Moreover, a high proportion was retreated.
length resected was a significant independent predictor for more dilations performed. Conclusions: A variable rate of esophageal strictures occurred post-EMR for BE with HGD or CA with the highest rates after circumferential-EMR. Younger age and larger circumference resected were predictors for post-EMR strictures. Longer length resected was found to predict more dilations needed. Although endoscopic dilation therapy was effective in relieving symptoms of dysphagia, preventive measures are desired for post-EMR strictures, especially for circumferential-EMR. Results
Mean # Resections # EMR Taken Sessions(Range) 100% 21/73 Circumference (28.8%) Removed O50%, !100% 18/73 Circumference (24.7%) Removed !50% 34/73 Circumference (46.6%) Removed Overall 73/73 (100%)
Mean % Circumference Removed (Range)
Mean Time Mean of Follow-Up Length in days Resected # Post- Mean # in cm EMR Dilations (Range) Strictures(Range)
7.1 (4-14)
100 (100)
3.8 (1-8) 16/21 (76.2%)
2.9 (1-9) 166.6
3.8 (1-6)
73.6 (67-80%)
3.6 (2-7)
2.8 (1-8)
44.1 (25-50)
3.6 (1-10) 3/32 (9.4%)z
2.0 (2)
192.5
4.3
67.4%
3.6
2.7
161.1
4/16 2.2 (1-3) (25.0%)y
23/69 (33.3%)
90.8
yExcluded: 1 pt lost to follow-up, 1 pt referred to surgery for findings of submucosal cancer on EMR specimen zExcluded: 2 pts lost to follow-up
W1327 Clinical and Biomarker Predictors of Response to Radiofrequency Ablation in Barrett’s Esophagus Ganapathy A. Prasad, Kevin C. Halling, Shannon M. Brankley, Navtej Buttar, Louis-Michel Wong Kee Song, Kelly T. Dunagan, Lori S. Lutzke, Lynn S. Borkenhagen, Kenneth K. Wang
W1326 Frequency and Risk Factors of Esophageal Stricture After Endoscopic Mucosal Resection (EMR) for Barrett’s Esophagus (BE) with High-Grade Dysplasia (HGD) or Adenocarcinoma (CA) Roy Yen, Alexander A. Dekovich, Yang K. Chen, Raj J. Shah, Brian C. Brauer, Daniel A. Ringold, Norio Fukami Background: EMR for BE with HGD or CA is an accepted diagnostic and therapeutic modality. While stricture is a known complication of EMR, the rate and predictors of post-EMR strictures (pES) and response of strictures to dilation are not well defined. Methods: Analysis was performed of prospectively collected data of pts who underwent EMR for BE with HGD or CA between 5/1/05 and 10/31/08. Dilation of pES was performed for symptoms of dysphagia to solids. The following data was collected: age, gender, ethnicity, number of (#) resected specimens taken, % circumference resected, length resected, occurrence of pES, and # dilations. Proportions were compared by chi-square. Prediction of dichotomous outcomes and continuous outcomes by independent variables was calculated by logistic and linear regression respectively. Results: 57 pts underwent 73 EMR sessions. 21/73 (29%) of treatment sessions were circumferential-EMR (C-EMR) with 100% circumference removed in 2 stages. 52/73 (71%) of treatment sessions were noncircumferential EMR (NC-EMR) with !100% circumference removed. Of 52 NCEMR sessions, 34 sessions had !50% circumference removed and 18 had O50% circumference removed (See Table). C-EMR had a significantly higher rate of pES than O50% NC-EMR and !50% NC-EMR (76% vs 25% vs 9%, p!.001). All patients with pES responded to endoscopic dilation therapy. Younger age and larger circumference resected were significant independent predictors of pES. Longer
AB342 GASTROINTESTINAL ENDOSCOPY Volume 69, No. 5 : 2009
Background: Radiofrequency ablation (RFA) is a promising technique effective for the treatment of dysplasia in BE. Failure rates for the elimination of dysplasia range from 10% to 20%. Predictors of response are yet to be defined. We aimed to characterize clinical and biomarker factors of response in a tertiary care referral center. Methods: We prospectively followed all patients treated with RFA over the last 3 years. We defined failure of RFA as the presence of dysplasia on biopsies taken at the first endoscopy after completion of RFA treatments as performed in the randomized trial (initial Halo 360 ablation with 12 Joules followed by Halo 90 ablation with 12 joules for elimination of all visible BE). Demographic and clinical data were extracted from a prospectively maintained database. Biomarker predictors were assessed using fluorescence in-situ hybridization (FISH) performed on cytology specimens obtained before ablation using previously defined standard methods. Loci assessed included: gains of 8q24.12-q24.13 (C-MYC), 17q11.2-q12 (HER-2), and 20q13.2 and loss of 9p21 (site of p16 gene). Cells were also assessed for multiple gains of loci. Univariate and multivariate logistic regression was performed to assess predictors of response. Results: 62 patients (mean age 63y, 89% male) were included. 37 (60%) were treated for HGD/Carcinoma, and the remainder were treated for LGD or no dysplasia. Mean BE length was 5.9 cm (SD 3.5). 82% were treated with Halo 360 followed by Halo 90 and 18% by Halo 90 alone. 19 patients (31%) met criteria for non-response. Biomarker data was available on 24 patients. On univariate analysis, older age, increasing length of the BE segment, presence of nodularity (requiring EMR) and HGD were predictors of poor response. Results of multivariable analysis confirmed length of the BE segment and nodularity as independent predictors of poor response. Patients with P16 allelic loss showed a numerically lower rate of response (35%) compared to those with intact P16 (55%) (pZ0.10). Gains at protooncogene loci did not appear to influence response to RF ablation. This is similar to prior findings of predictors of response to PDT. Conclusions: Patients with longer BE segments, HGD and nodularity needing EMR are less likely to respond to RF ablation. The role of P16 allelic loss (which may decrease odds of response to RF ablation) needs further study. Results of multivariable analysis Variable
Odds Ratio (95% CI)
p value
Age Gender Length of BE segment Nodularity
0.94 4.39 0.79 0.42
0.09 0.11 0.02 0.04
(0.87, (0.71, (0.64, (0.10,
1.01) 31.96) 0.95) 0.96)
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