What s New in the Management of Esophageal Disease Philip O. Katz, MD Chairman, Division of Gastroenterology Einstein Medical Center Philadelphia Clinical Professor of Medicine Jefferson Medical College Philadelphia, PA Disclosure of Conflicts of Interest Philip O. Katz, MD, FACG, has affiliations with Takeda Pharmaceuticals (Honoraria); Ironwood Pharmaceuticals, Inc., Pfizer Consumer Health (Consultant). 1
Comparative Effectiveness of Novel Techniques for Barrett s Esophagus Screening in the Community: A Prospective Randomized Trial Gastrointest Endosc 2014; 79 (5S) [Abstract 160] AB113-114 Comparative Effectiveness of Novel Techniques for Barrett s Esophagus Screening in the Community: A Prospective Randomized Trial (cont d) Screening for Barrett s controversial Cost is major reason Transnasal EGD is less expensive (no sedation, etc.) Patients randomized to TNE or sedated EGD 2
Comparative Effectiveness of Novel Techniques for Barrett s Esophagus Screening in the Community: A Prospective Randomized Trial (cont d) Results: Each completed at same rate Sedated better tolerated, shorter esophagus evaluation time Biopsy success better with sedated EGD Findings overall similar Conclusion: TNE feasible for screening A FISH Biomarker Panel for the Prediction of High-grade Dysplasia and Adenocarcinoma in Non- Dysplastic Barrett s Esophagus: Results from a Long-term Prospective Cohort Study Gastrointest Endosc 2014; 79 (5S) [Abstract 164] AB115-116 3
A FISH Biomarker Panel for the Prediction of High-grade Dysplasia and Adenocarcinoma in Non-Dysplastic Barrett s Esophagus: Results from a Long-term Prospective Cohort Study (cont d) Stratifying risk for Barrett s difficult Biomarkers are still under investigation Prospective study in 428 non-dysplastic patients P16, 53 Her-2/neu, 20 q and MYC aneuploidy -16, aneuploidy double risk for HGD/EAC Increase risk to 2%/year Conclusion: Markers may be useful but still not mainstream 4
Esophageal Brush Biopsy with Computer-assisted Tissue Analysis Increases Detection of Barrett s Esophagus and Dysplasia in a Multi-site Community-based Setting Gastrointest Endosc 2014; 79 (5S) [Abstract 371] AB294 Esophageal Brush Biopsy with Computerassisted Tissue Analysis Increases Detection of Barrett s Esophagus and Dysplasia in a Multi-site Community-based Setting (cont d) Standard biopsy protocol for Barrett s maligned Wide area transepithelial sampling (WATS 3D ) can improve detection of dysphagia 2559 patients EGD plus WATS 3D GERD, possible or proven BE Overall 377 cases of BE (15.1%) Dysplasia detection 10 cases of dysplasia and only EAC missed by biopsy Conclusion: Adding WATS 3D increases yield 5
Inter-observer Agreement Among Pathologists Using Wide Area Transepithelial Sampling of Barrett s Esophagus with Computer-assisted Analysis Gastrointest Endosc 2014; 79 (5S) [Abstract 165] AB116 Inter-observer Agreement Among Pathologists Using Wide Area Transepithelial Sampling of Barrett s Esophagus with Computer-assisted Analysis (cont d) Overall (95% CI) HGD/EAC (95% CI) IND/LGD (95% CI) NDBE (95% CI) 0.86 (0.75-0.97) 0.95 (0.88-0.99) 0.74 (0.61-0.85) 0.88 (90.81-0.94) 6
Modifiable Risk Factors Predict Recurrence of Barrett s Esophagus After Successful Radiofrequency Ablation Gastrointest Endosc 2014; 79 (5S) [Abstract 163] AB115 Modifiable Risk Factors Predict Recurrence of Barrett s Esophagus After Successful Radiofrequency Ablation (cont d) All (n=180) Recurrence (n=20) No Recurrence (n=160) p-value Age mean years + SD 68 + 10 63 + 10 69 + 10 0.01 White n (%) 171 (98) 20 (100) 151 (98) 0.52 Male n (%) 132 (73) 13 (65) 119 (74) 0.37 BMI mean + SD 30 + 5.7 31 + 8.5 29 + 5.3 0.62 Current Alcohol n (%) 81 (45) 4 (20) 77 (48) 0.02 Current Tobacco n (%) 27 (15) 8 (40) 19 (12) 0.0009 Current NSAID n (%) 86 (48) 6 (30) 80 (50) 0.09 Anti-reflux Surgery n (%) 8 94) 0 (0) 8 (5) 0.31 Hiatal Hernia n (%) 161 (89) 18 (90) 143 (89) 0.93 Prague C mean cm + SD 1.2 + 2.3 1.7 + 2.8 1.1 + 2.2 0.36 Prague M mean cm + SD 4.4 + 3.0 5.5 + 2.9 4.2 + 2.9 0.051 Days Treatment mean + SD 171 + 166 170 + 131 171 + 170 0.58 Days Surveillance mean + SD 863 + 520 1032 + 608 842 + 506 0.17 7
Modifiable Risk Factors Predict Recurrence of Barrett s Esophagus After Successful Radiofrequency Ablation (cont d) All (n=180) Recurrence (n=20) No Recurrence (n=160) p-value Worst Treatment Histology NDBE 5 (3) 1 (5) 4 (3) LGD 56 (31) 6 (30) 50 (31) HGD 102 (57) 12 (60) 90 (56) EAC, non-invasive 17 (9) 1 (5) 16 (10) Modifiable Risk Factors Predict Recurrence of Barrett s Esophagus After Successful Radiofrequency Ablation (cont d) Table 2: Odds Ratio from Logistic Regression Predicting Recurrence Unadjusted OR [95% Cl] Adjusted * OR [95%CI] Current Alcohol 0.26 [0.08, 0.85] 0.30 [0.09, 0.99] Current Tobacco 5.02 [1.76, 14.30] 4.76 [1.49, 15.22] 8
The Yield of Early Follow-up Endoscopy in Patients with Initial Nondysplastic or Low-grade Dysplasia Barrett s Esophagus Gastrointest Endosc 2014; 79 (5S) [Abstract 162] AB114-115 The Yield of Early Follow-up Endoscopy in Patients with Initial Nondysplastic or Low-grade Dysplasia Barrett s Esophagus (cont d) Missed HGD or EAC in 2.2% (4 patients) on initial EGD Long segment All white men 9
Surveillance Endoscopy is Associated with Improved Outcomes of Esophageal Adenocarcinoma (EA) Detected in Patients with Barrett s Esophagus (BE) Gastroenterology 2014; 146 (S1) [Abstract 709] S123 Surveillance Endoscopy is Associated with Improved Outcomes of Esophageal Adenocarcinoma (EA) Detected in Patients with Barrett s Esophagus (BE) (cont d) Surveillance for Barrett s debated to efficacy VA database 29,504 cases of BE, 433 EAC All men, 86% white, mean age 67 192 diagnosed on surveillance EGD/241 diagnostic Surveillance cases earlier stage (OR 2.94, 1.87-4.64) Surveillance decreased mortality (HR 0.51, 0.38-0.60) 10
Prevalence and Characteristics of Esophagitis and Barrett s Esophagus in Population Subjects Without Gastroesophageal Reflux Symptoms: Results From a Large Randomized Controlled Study Gastroenterology 2014; 146 (S1) [Abstract 105] S28-29 Prevalence and Characteristics of Esophagitis and Barrett s Esophagus in Population Subjects Without Gastroesophageal Reflux Symptoms: Results From a Large Randomized Controlled Study (cont d) Esophagitis Prevalence Grade A Grade B Grade C BE Prevalence Mean (SD) length Diaphragmatic hernia present (%) Mean (SD) size (cm) Symptomatic GER Group (69) Asymptomatic GER Group (140) Comparison p value 22 (31.9%) 8 12 2 40 (28.5%) 21 17 2 0.78 6 (8.7%) 3.5 (2.4) I (1.4%) 44 (63.7%) 3.6 (2.1) 11 (7.9%) 2.6 (1.4) 2 (1.4%) 0.49 0.62 79 (56.4%) 2.6 (0.9) 026 0.001* 11
Prevalence and Characteristics of Esophagitis and Barrett s Esophagus in Population Subjects Without Gastroesophageal Reflux Symptoms: Results From a Large Randomized Controlled Study (cont d) Group 1: No Esophageal Injury + (142) Group 2: Symptomatic GER Group with Esophageal Injury or Metaplasia + (23) Group 3: Asymptomatic GER Group with Esophageal Injury or Metaplasia + (44) Comparison of Group 1 vs. Group 2 & 3 p value Age (SD) 70 (9) 73 (9) 69 (9) 0.91 0.89 Male proportion (%) 55 (38.7%) 12 (52.2%) 29 (65.9%) 0.004* 0.15 WHR Mean (SD) 0.89 (0.1) 0.91 (0.09) 0.95 (0.09) 0.013* 0.15 BMI Mean (SD) 29.2 (10.7) 30.8 (6.0) 29.5 (5.1) 0.62 0.33 Smoker (>30 PY) (%) Excess Alcohol Use (%) 20 (14.1%) 2 (13.1%) 6 (13.6%) 0.89 0.94 10 (8.7%) 3 (13.1%) 11 (25.0%) 0.014* 0.23 Comparison of Group 2 vs. Group 3 p value + Esophageal injury includes presence of BE or esophagitis LA criteria Grade A, B, C Excess alcohol consumption classified as greater than 2 alcoholic beverages per day * p<0.05 considered significant Gaviscon Double Action (Antacid + Alginate) Versus Equivalent Antacid for Postprandial Acid Reflux: A Double-blind Crossover Study in GERD Patients Gastroenterology 2014; 146 (S1) [Abstract 103] S27-28 12
Gaviscon Double Action (Antacid + Alginate) Versus Equivalent Antacid for Postprandial Acid Reflux: A Double-blind Crossover Study in GERD Patients (cont d) Proximal extent of reflux Reflux events, Gaviscon Acid, n=34* n (%) Total, n=144 n (%) Reflux Events, Antacid Acid, n=78 n (%) Total, n=169 n (%) LES + 5 cm 5 (15%) 18 (13%) 7 (%) 19 (11%) LES + 7 cm 9 (27%) 24 (17%) 13 (7%) 35 (21%) LES + 9 cm 18* (53%) 76 (53%) 47 (60%) 85 (50%) LES + 15 cm 1 (3%) 8 (6%) 4 (5%) 6 (4%) LES + 17 cm 1* (3%) 18 (13%) 7 ((%) 24 (14%) * P<0.05 vs antacid, Student s T=test or Kruskal-Wallis 13
Long-term Efficacy of PPI Therapy in Patients with PPI-responsive Esophageal Eosinophilia: An International Multicenter Study Gastroenterology 2014; 146 (S1) [Abstract 58] S17 Long-term Efficacy of PPI Therapy in Patients with PPI-responsive Esophageal Eosinophilia: An International Multicenter Study (cont d) 40 PPI-REE patients PPI equivalent to OME 20, 40/day or 40 BID to remission Taper based on symptoms EGD, biopsy @ 12 months (or more) 14
Long-term Efficacy of PPI Therapy in Patients with PPI-responsive Esophageal Eosinophilia: An International Multicenter Study (cont d) Initial dose 18 (high) 22 (40) Maintenance 19 (40 Ome) 22 (20 Ome) 26/40 remained in remission Most recurrence distal and resolved with increased dose Two New Budesonide Formulations Are Highly Efficient for Treatment of Active Eosinophilic Esophagitis: Results From a Randomized, Doubleblind, Double-dummy, Placebocontrolled Multicenter Trial Gastroenterology 2014; 146 (S1) [Abstract 55] S16 15
Two New Budesonide Formulations Are Highly Efficient for Treatment of Active Eosinophilic Esophagitis: Results From a Randomized, Double-blind, Doubledummy, Placebo-controlled Multicenter Trial (cont d) Steroids are commonly used in EoE Optimal dose and delivery system are not known Budesonide effervescent tablet (2 x 1 mg/d) and viscous suspension (2 x 2 mg/d) Dysphagia improved in both groups Tolerated well Presence of Basal Cell Hyperplasia and Dilation of Intercellular Spaces and Their Association with Baseline Impedance Values in Patients with Positive Symptom Association Despite Normal Acid Exposure Further Supports Their Role in Symptoms Generation In NERD Gastroenterology 2014; 146 (S1) [Abstract 17] S6 16
Presence of Basal Cell Hyperplasia and Dilation of Intercellular Spaces and Their Association with Baseline Impedance Values in Patients with Positive Symptom Association Despite Normal Acid Exposure Further Supports Their Role in Symptoms Generation In NERD (cont d) Grade 0-1 BCH PE DIS Neu/Eos B1 at 3 cm 2300 (840-4225) B1 at 5 cm 2100 (560-3300) B1 at 3 cm 2415 (560-4225) B1 at 5 cm 2282 (640-3300) B1 at 3 cm 2930 (880-4225) B1 at 5 cm 2850 (560-3540) B1 at 3 cm 2200 (560-4225) B1 at 5 cm 2080 (580-4060) Per-oral Endoscopic Myotomy for Achalasia: Outcomes of a Large Prospective Series Gastrointest Endosc 2014; 79 (5S) [Abstract 731] AB166 17
Per-oral Endoscopic Myotomy for Achalasia: Outcomes of a Large Prospective Series (cont d) POEM is new treatment for achalasia Place not known as technique expertise, results evolving 119 patients underwent POEM; 81 classic 38 vigorous (Type III) Successful POEM in 95%, 6 aborted Follow up 12-24 months GERD 46%, EE 25%, 14 complained of heartburn Conclusion: POEM feasible but NOT in all, successful mostly GERD common by tests Questions? 18