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Snare Tip Soft Coagulation Leaves Clean Margins After Resection
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
August 2024 – ICYMI
Gastroenterology
April 2024
Shah I, et al. Disparities in Colorectal Cancer Screening Among Asian American Populations and Strategies to Address These Disparities. Gastroenterology. 2024 Apr;166(4):549-552. doi: 10.1053/j.gastro.2024.02.009. PMID: 38521575.
Shiha MG, et al. Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis. Gastroenterology. 2024 Apr;166(4):620-630. doi: 10.1053/j.gastro.2023.12.023. Epub 2024 Jan 2. PMID: 38176661.
Goltstein LCMJ, et al. Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Apr;166(4):690-703. doi: 10.1053/j.gastro.2023.12.020. Epub 2023 Dec 28. PMID: 38158089.
May 2024
Robertson DJ, et al. Colonoscopy vs the Fecal Immunochemical Test: Which is Best? Gastroenterology. 2024 May;166(5):758-771. doi: 10.1053/j.gastro.2023.12.027. Epub 2024 Feb 9. PMID: 38342196.
Mårild K, et al. Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study. Gastroenterology. 2024 May;166(5):802-814.e18. doi: 10.1053/j.gastro.2024.01.018. Epub 2024 Feb 6. PMID: 38331202.
June 2024
Trivedi PJ, et al. Immunopathogenesis of Primary Biliary Cholangitis, Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Themes and Concepts. Gastroenterology. 2024 Jun;166(6):995-1019. doi: 10.1053/j.gastro.2024.01.049. Epub 2024 Feb 10. PMID: 38342195.
Rubenstein JH, et al. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett’s Esophagus and Related Neoplasia. Gastroenterology. 2024 Jun;166(6):1020-1055. doi: 10.1053/j.gastro.2024.03.019. PMID: 38763697.
Ridtitid W, et al. Endoscopic Gallbladder Stenting to Prevent Recurrent Cholecystitis in Deferred Cholecystectomy: A Randomized Trial. Gastroenterology. 2024 Jun;166(6):1145-1155. doi: 10.1053/j.gastro.2024.02.007. Epub 2024 Feb 14. PMID: 38360274.
Clinical Gastroenterology and Hepatology
April 2024
Berwald G, et al. The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy. Clin Gastroenterol Hepatol. 2024 Apr;22(4):878-885.e2. doi: 10.1016/j.cgh.2023.09.016. Epub 2023 Sep 22. PMID: 37743036.
Hashash JG, et al. AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication. Clin Gastroenterol Hepatol. 2024 Apr;22(4):705-707. doi: 10.1016/j.cgh.2023.11.002. Epub 2023 Nov 7. PMID: 37944573.
Sharma R, et al. Statins Are Associated With a Decreased Risk of Severe Liver Disease in Individuals With Noncirrhotic Chronic Liver Disease. Clin Gastroenterol Hepatol. 2024 Apr;22(4):749-759.e19. doi: 10.1016/j.cgh.2023.04.017. Epub 2023 Apr 28. PMID: 37121528.
May 2024
Overbeek KA, et al; PrescrAIP Study Group. Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment. Clin Gastroenterol Hepatol. 2024 May;22(5):994-1004.e10. doi: 10.1016/j.cgh.2023.12.010. Epub 2024 Jan 5. Erratum in: Clin Gastroenterol Hepatol. 2024 Jun 1:S1542-3565(24)00446-4. doi: 10.1016/j.cgh.2024.05.005. PMID: 38184096.
Jairath V, et al. ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse. Clin Gastroenterol Hepatol. 2024 May;22(5):1077-1086.e13. doi: 10.1016/j.cgh.2023.10.029. Epub 2023 Nov 10. PMID: 37951560.
Gunby SA, et al. Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in Women. Clin Gastroenterol Hepatol. 2024 May;22(5):1108-1116. doi: 10.1016/j.cgh.2023.11.036. Epub 2023 Dec 19. PMID: 38122959; PMCID: PMC11045313.
June 2024
Krause AJ, et al. Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1200-1209.e1. doi: 10.1016/j.cgh.2024.01.021. Epub 2024 Feb 2. PMID: 38309491; PMCID: PMC11128352.
Peng X, et al. Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1210-1216. doi: 10.1016/j.cgh.2024.01.022. Epub 2024 Feb 1. PMID: 38309492.
Kedia S, et al. Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1295-1306.e7. doi: 10.1016/j.cgh.2024.01.013. Epub 2024 Jan 24. PMID: 38278200.
Techniques and Innovations in Gastrointestinal Endoscopy
Ogura T, et al. Step-Up Strategy for Endoscopic Hemostasis Using PuraStat After Endoscopic Sphincterotomy Bleeding (STOP Trial). Tech Innov Gastrointest Endosc. 2024 March 16. doi: 10.1016/j.tige.2024.03.005.
Nakai Y, et al. Cyst Detection Rate: A Quality Indicator in the Era of Pancreatic Screening Endoscopic Ultrasonography. Tech Innov Gastrointest Endosc. 2024 May. doi: 10.1016/j.tige.2024.04.001.
Gastro Hep Advances
Kimura Y, et al. Early Sonographic Improvement Predicts Clinical Remission and Mucosal Healing With Molecular-Targeted Drugs in Ulcerative Colitis. Gastro Hep Adv. 2024 April 22. doi: 10.1016/j.gastha.2024.04.007.
Hunaut T, et al. Long-Term Neoplastic Risk Associated With Colorectal Strictures in Crohn’s Disease: A Multicenter Study. Gastro Hep Adv. 2024 May 15. doi: 10.1016/j.gastha.2024.05.003.
Gastroenterology
April 2024
Shah I, et al. Disparities in Colorectal Cancer Screening Among Asian American Populations and Strategies to Address These Disparities. Gastroenterology. 2024 Apr;166(4):549-552. doi: 10.1053/j.gastro.2024.02.009. PMID: 38521575.
Shiha MG, et al. Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis. Gastroenterology. 2024 Apr;166(4):620-630. doi: 10.1053/j.gastro.2023.12.023. Epub 2024 Jan 2. PMID: 38176661.
Goltstein LCMJ, et al. Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Apr;166(4):690-703. doi: 10.1053/j.gastro.2023.12.020. Epub 2023 Dec 28. PMID: 38158089.
May 2024
Robertson DJ, et al. Colonoscopy vs the Fecal Immunochemical Test: Which is Best? Gastroenterology. 2024 May;166(5):758-771. doi: 10.1053/j.gastro.2023.12.027. Epub 2024 Feb 9. PMID: 38342196.
Mårild K, et al. Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study. Gastroenterology. 2024 May;166(5):802-814.e18. doi: 10.1053/j.gastro.2024.01.018. Epub 2024 Feb 6. PMID: 38331202.
June 2024
Trivedi PJ, et al. Immunopathogenesis of Primary Biliary Cholangitis, Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Themes and Concepts. Gastroenterology. 2024 Jun;166(6):995-1019. doi: 10.1053/j.gastro.2024.01.049. Epub 2024 Feb 10. PMID: 38342195.
Rubenstein JH, et al. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett’s Esophagus and Related Neoplasia. Gastroenterology. 2024 Jun;166(6):1020-1055. doi: 10.1053/j.gastro.2024.03.019. PMID: 38763697.
Ridtitid W, et al. Endoscopic Gallbladder Stenting to Prevent Recurrent Cholecystitis in Deferred Cholecystectomy: A Randomized Trial. Gastroenterology. 2024 Jun;166(6):1145-1155. doi: 10.1053/j.gastro.2024.02.007. Epub 2024 Feb 14. PMID: 38360274.
Clinical Gastroenterology and Hepatology
April 2024
Berwald G, et al. The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy. Clin Gastroenterol Hepatol. 2024 Apr;22(4):878-885.e2. doi: 10.1016/j.cgh.2023.09.016. Epub 2023 Sep 22. PMID: 37743036.
Hashash JG, et al. AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication. Clin Gastroenterol Hepatol. 2024 Apr;22(4):705-707. doi: 10.1016/j.cgh.2023.11.002. Epub 2023 Nov 7. PMID: 37944573.
Sharma R, et al. Statins Are Associated With a Decreased Risk of Severe Liver Disease in Individuals With Noncirrhotic Chronic Liver Disease. Clin Gastroenterol Hepatol. 2024 Apr;22(4):749-759.e19. doi: 10.1016/j.cgh.2023.04.017. Epub 2023 Apr 28. PMID: 37121528.
May 2024
Overbeek KA, et al; PrescrAIP Study Group. Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment. Clin Gastroenterol Hepatol. 2024 May;22(5):994-1004.e10. doi: 10.1016/j.cgh.2023.12.010. Epub 2024 Jan 5. Erratum in: Clin Gastroenterol Hepatol. 2024 Jun 1:S1542-3565(24)00446-4. doi: 10.1016/j.cgh.2024.05.005. PMID: 38184096.
Jairath V, et al. ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse. Clin Gastroenterol Hepatol. 2024 May;22(5):1077-1086.e13. doi: 10.1016/j.cgh.2023.10.029. Epub 2023 Nov 10. PMID: 37951560.
Gunby SA, et al. Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in Women. Clin Gastroenterol Hepatol. 2024 May;22(5):1108-1116. doi: 10.1016/j.cgh.2023.11.036. Epub 2023 Dec 19. PMID: 38122959; PMCID: PMC11045313.
June 2024
Krause AJ, et al. Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1200-1209.e1. doi: 10.1016/j.cgh.2024.01.021. Epub 2024 Feb 2. PMID: 38309491; PMCID: PMC11128352.
Peng X, et al. Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1210-1216. doi: 10.1016/j.cgh.2024.01.022. Epub 2024 Feb 1. PMID: 38309492.
Kedia S, et al. Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1295-1306.e7. doi: 10.1016/j.cgh.2024.01.013. Epub 2024 Jan 24. PMID: 38278200.
Techniques and Innovations in Gastrointestinal Endoscopy
Ogura T, et al. Step-Up Strategy for Endoscopic Hemostasis Using PuraStat After Endoscopic Sphincterotomy Bleeding (STOP Trial). Tech Innov Gastrointest Endosc. 2024 March 16. doi: 10.1016/j.tige.2024.03.005.
Nakai Y, et al. Cyst Detection Rate: A Quality Indicator in the Era of Pancreatic Screening Endoscopic Ultrasonography. Tech Innov Gastrointest Endosc. 2024 May. doi: 10.1016/j.tige.2024.04.001.
Gastro Hep Advances
Kimura Y, et al. Early Sonographic Improvement Predicts Clinical Remission and Mucosal Healing With Molecular-Targeted Drugs in Ulcerative Colitis. Gastro Hep Adv. 2024 April 22. doi: 10.1016/j.gastha.2024.04.007.
Hunaut T, et al. Long-Term Neoplastic Risk Associated With Colorectal Strictures in Crohn’s Disease: A Multicenter Study. Gastro Hep Adv. 2024 May 15. doi: 10.1016/j.gastha.2024.05.003.
Gastroenterology
April 2024
Shah I, et al. Disparities in Colorectal Cancer Screening Among Asian American Populations and Strategies to Address These Disparities. Gastroenterology. 2024 Apr;166(4):549-552. doi: 10.1053/j.gastro.2024.02.009. PMID: 38521575.
Shiha MG, et al. Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis. Gastroenterology. 2024 Apr;166(4):620-630. doi: 10.1053/j.gastro.2023.12.023. Epub 2024 Jan 2. PMID: 38176661.
Goltstein LCMJ, et al. Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Apr;166(4):690-703. doi: 10.1053/j.gastro.2023.12.020. Epub 2023 Dec 28. PMID: 38158089.
May 2024
Robertson DJ, et al. Colonoscopy vs the Fecal Immunochemical Test: Which is Best? Gastroenterology. 2024 May;166(5):758-771. doi: 10.1053/j.gastro.2023.12.027. Epub 2024 Feb 9. PMID: 38342196.
Mårild K, et al. Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study. Gastroenterology. 2024 May;166(5):802-814.e18. doi: 10.1053/j.gastro.2024.01.018. Epub 2024 Feb 6. PMID: 38331202.
June 2024
Trivedi PJ, et al. Immunopathogenesis of Primary Biliary Cholangitis, Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Themes and Concepts. Gastroenterology. 2024 Jun;166(6):995-1019. doi: 10.1053/j.gastro.2024.01.049. Epub 2024 Feb 10. PMID: 38342195.
Rubenstein JH, et al. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett’s Esophagus and Related Neoplasia. Gastroenterology. 2024 Jun;166(6):1020-1055. doi: 10.1053/j.gastro.2024.03.019. PMID: 38763697.
Ridtitid W, et al. Endoscopic Gallbladder Stenting to Prevent Recurrent Cholecystitis in Deferred Cholecystectomy: A Randomized Trial. Gastroenterology. 2024 Jun;166(6):1145-1155. doi: 10.1053/j.gastro.2024.02.007. Epub 2024 Feb 14. PMID: 38360274.
Clinical Gastroenterology and Hepatology
April 2024
Berwald G, et al. The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy. Clin Gastroenterol Hepatol. 2024 Apr;22(4):878-885.e2. doi: 10.1016/j.cgh.2023.09.016. Epub 2023 Sep 22. PMID: 37743036.
Hashash JG, et al. AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication. Clin Gastroenterol Hepatol. 2024 Apr;22(4):705-707. doi: 10.1016/j.cgh.2023.11.002. Epub 2023 Nov 7. PMID: 37944573.
Sharma R, et al. Statins Are Associated With a Decreased Risk of Severe Liver Disease in Individuals With Noncirrhotic Chronic Liver Disease. Clin Gastroenterol Hepatol. 2024 Apr;22(4):749-759.e19. doi: 10.1016/j.cgh.2023.04.017. Epub 2023 Apr 28. PMID: 37121528.
May 2024
Overbeek KA, et al; PrescrAIP Study Group. Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment. Clin Gastroenterol Hepatol. 2024 May;22(5):994-1004.e10. doi: 10.1016/j.cgh.2023.12.010. Epub 2024 Jan 5. Erratum in: Clin Gastroenterol Hepatol. 2024 Jun 1:S1542-3565(24)00446-4. doi: 10.1016/j.cgh.2024.05.005. PMID: 38184096.
Jairath V, et al. ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse. Clin Gastroenterol Hepatol. 2024 May;22(5):1077-1086.e13. doi: 10.1016/j.cgh.2023.10.029. Epub 2023 Nov 10. PMID: 37951560.
Gunby SA, et al. Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in Women. Clin Gastroenterol Hepatol. 2024 May;22(5):1108-1116. doi: 10.1016/j.cgh.2023.11.036. Epub 2023 Dec 19. PMID: 38122959; PMCID: PMC11045313.
June 2024
Krause AJ, et al. Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1200-1209.e1. doi: 10.1016/j.cgh.2024.01.021. Epub 2024 Feb 2. PMID: 38309491; PMCID: PMC11128352.
Peng X, et al. Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1210-1216. doi: 10.1016/j.cgh.2024.01.022. Epub 2024 Feb 1. PMID: 38309492.
Kedia S, et al. Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial. Clin Gastroenterol Hepatol. 2024 Jun;22(6):1295-1306.e7. doi: 10.1016/j.cgh.2024.01.013. Epub 2024 Jan 24. PMID: 38278200.
Techniques and Innovations in Gastrointestinal Endoscopy
Ogura T, et al. Step-Up Strategy for Endoscopic Hemostasis Using PuraStat After Endoscopic Sphincterotomy Bleeding (STOP Trial). Tech Innov Gastrointest Endosc. 2024 March 16. doi: 10.1016/j.tige.2024.03.005.
Nakai Y, et al. Cyst Detection Rate: A Quality Indicator in the Era of Pancreatic Screening Endoscopic Ultrasonography. Tech Innov Gastrointest Endosc. 2024 May. doi: 10.1016/j.tige.2024.04.001.
Gastro Hep Advances
Kimura Y, et al. Early Sonographic Improvement Predicts Clinical Remission and Mucosal Healing With Molecular-Targeted Drugs in Ulcerative Colitis. Gastro Hep Adv. 2024 April 22. doi: 10.1016/j.gastha.2024.04.007.
Hunaut T, et al. Long-Term Neoplastic Risk Associated With Colorectal Strictures in Crohn’s Disease: A Multicenter Study. Gastro Hep Adv. 2024 May 15. doi: 10.1016/j.gastha.2024.05.003.
Advanced Tissue Resection in Gastroenterology: Indications, Role, and Outcomes
Endoscopists are often faced with unique challenges in the management and resection of various gastrointestinal tract lesions. These challenges could be lesion-related, endoscopist-related, or practice-related (see Table 1). (ATR). Not only does this organ-sparing approach offer a less invasive alternative to surgery, but it has also proved to have outcomes comparable to those of surgical standard of practice in specific scenarios. 
When Do You Refer to an Advanced Endoscopist?
One of the most critical steps in caring for patients with complex lesions is the ability to accurately determine whether a referral to an advanced endoscopist is warranted. The initial assessment of a lesion should always involve a careful assessment that risk stratifies the lesion depending on the location, size, neoplastic potential, and the feasibility of standard endoscopic resection compared to the need for surgical input.
A practical example in the case of colonic polyps is highlighted by the American Gastroenterology Association (AGA) guidelines recommending the referral of patients with polyps’ size ≥ 20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site to an endoscopic referral center.1 In the case of subepithelial lesions without endoscopic characteristics of benign etiology (i.e., lipomas, pancreatic rests, etc.), the threshold for referral to advanced endoscopists for further diagnostic testing by means of endoscopic ultrasonography or for therapeutic ATR should be lower.
Endoscopic tissue resection follows a spectrum, which often involves deeper layers of the gastrointestinal tract (GIT) as we progress along this spectrum (see Figure 1). 
ATR, a term encompassing a variety of endoscopic techniques ranging from endoscopic mucosal resection to full thickness resection, has gained traction over the last years given the ability to effectively remove various lesions in a precise time and cost-effective manner while maintaining the integrity of the GIT and avoiding major surgery. The indications for ATR vary depending on the technique, but generally include the presence of large or poorly positioned lesions, particularly in high-risk areas of the GIT such as the esophagus and small intestine, lesions extending beyond the mucosal layer or originating from deeper layers, and when en bloc resection of select lesions is necessary.
For providers referring patients for ATR, we recommend a few important endoscopic pearls when caring for these patients.
1) Biopsy the lesion if there is concern for malignancy — While some studies have noted increased fibrosis during endoscopic submucosal dissection (ESD) and some guidelines recommend against biopsies pre ESD, we believe that when there is high pretest probability for malignancy, a biopsy should be obtained. This should involve the area that is most concerning for malignancy (at the margin or center).2
2) While marking a lesion with tattoo is helpful for surgical planning and for lesions difficult to locate endoscopically, we stress the importance of placing tattoos 3 to 5 centimeters distal to the lesion and avoiding tattooing the lesion itself, which has been shown to induce fibrosis and can make resection challenging. Based on an international Delphi consensus, expert recommendations on when and how to endoscopically tattoo a lesion can be instrumental in adequately localizing the lesion, allowing for endoscopic resection, and preventing unnecessary surgeries.3
3) If you encounter a lesion that you are not sure can be resected safely and efficaciously, we recommend against attempting resection that may result in partial resection. This can also induce fibrosis and scarring and limit future attempts at resection.
Endoscopic Mucosal Resection (EMR)
EMR is currently utilized for curative treatment of a wide array of GIT lesions limited to the mucosal layer, whether metaplastic, dysplastic, or even in cases with early mucosal cancer, where the risk of submucosal and lymphatic invasion is minimal.4 This makes EMR a versatile and proven therapy, often serving as the first-line treatment for many GIT lesions.
EMR has various techniques that could be categorized into suction or non-suction (lift and cut) techniques. In the suction technique, devices like multiband mucosectomy (MBM) are commonly used, especially in nodular Barrett’s dysplasia, forming a pseudopolyp for subsequent resection. The procedure is characterized by its safety, efficacy, and cost-effectiveness, contributing to its widespread adoption in clinical practice. In the lift and cut approach, a submucosal injection is utilized to separate the muscularis propria from the lesion, thereby reducing the risk of perforation. Different solutions, such as normal saline, hypertonic saline, 50% dextrose, or proprietary submucosal injection solutions, are employed for submucosal injection.5
The non-suction technique using a snare to resect polyps after injection is more often used in colonic and small intestinal EMR. Resection can be done via thermal energy in the form of cut or coagulation; however, there is rising data on the use of piecemeal cold snare resection for select flat polyps of the colon.6 There is also promising data on the role of underwater EMR, a common technique employed for colonic lesions, particularly if the lesion does not lift well with submucosal injection.7
Adverse events associated with EMR include bleeding (7%-8%) and perforation (0.9%-2%).8-9 Adequate submucosal fluid injection is crucial to prevent perforations. However, the main limitation of EMR is the piecemeal nature of resections for lesions larger than 20 mm, leading to compromised histopathologic evaluation for complete excision, especially in cases with superficial submucosal invasion (SMI). This can result in residual or recurrent tissue, reportedly 8% to 20%.10 Despite this limitation, EMR remains a reliable strategy, and recurrent lesions are generally manageable through repeat sessions. The importance of EMR as a therapeutic modality lies in its role in addressing lesions with favorable characteristics, where the risk of SMI is low.
Endoscopic Submucosal Dissection (ESD)
ESD is an evolving technique that can be utilized for submucosal lesions of the GIT, lesions not amenable to EMR due to submucosal fibrosis, when en bloc removal of a lesion is needed for accurate histopathological diagnosis, and when other techniques fail.11-12
ESD was only recently adopted in the United States, requires specialized training, and usually is a lengthier procedure than EMR.13 Compared to EMR, it has higher en bloc resection rates and lower recurrence rates, making it curative for lesions with superficial SMI and favorable histologic features.4,14 The safety profile of ESD appears favorable, with most of the adverse events managed successfully by endoscopic methods. Major complications include intraoperative and delayed perforation, intraoperative and delayed bleeding, aspiration pneumonia, thromboembolism, and stricture formation in the case of circumferential lesions.15
Despite being technically challenging, ESD may provide a cost-effective long-term solution by avoiding surgery, reducing the need for additional interventions by minimizing recurrence rates. Given the technical complexity of ESD, particularly the submucosal dissection portion, techniques such as hybrid ESD developed. Hybrid ESD combines snaring with circumferential mucosal incision and partial submucosal dissection. Although it promises shorter procedure times, reduced complication rates like perforation, and similar recurrence rates compared to traditional ESD, studies have shown lower success rates in en bloc resection.16-17
Both EMR and ESD are considered complementary strategies, and the choice between them should be dictated by lesion characteristics, patient preferences, and local expertise.
Submucosal Tunneling Endoscopic Resection (STER)
STER has emerged as a well-established technique for the endoscopic resection of GI subepithelial tumors (SETs) originating from the muscularis propria layer. The standard STER procedure involves a series of steps including submucosal elevation proximal to the SET, mucosotomy, creation of a submucosal tunnel, dissection of the SET within the tunnel, enucleation from the deep muscle layer, and subsequent specimen retrieval followed by mucosal closure.
This technique is typically recommended for SETs smaller than 3.5 cm, particularly those located in the mid or distal esophagus, cardia, or along the greater curvature of the gastric body.18 However, STER may pose technical challenges for larger SETs or lesions in anatomically difficult locations, where surgical resection is recommended instead.19 Notably, recent large-scale meta-analyses have showcased the favorable complete resection and en bloc resection rates of STER in treating GI SETs.20
Endoscopic Full Thickness Resection (EFTR)
EFTR has emerged as a valuable technique in the endoscopic management of gastrointestinal lesions, particularly SETs and lesions not amenable to EMR or ESD due to fibrosis. EFTR involves the resection of all layers of the GIT from mucosa to serosa, and therefore is well-suited for SETs arising from the muscularis propria (MP).20
EFTR entails two main concepts: tissue resection and complete defect closure. Conventional EFTR consists of several steps, which include mucosal and submucosal pre-cutting, circumferential incision, and dissection through the MP or serosa. This results in a full thickness defect, for which closure of the wall defect is achieved using standard endoscopic clips or a combination of clips and endoloops or endoscopic suturing.21 For lesions less than 2 cm, EFTR can be performed in a single step using a cap-mounted full thickness resection device (FTRD). This results in deployment of over-the-scope clip over the target lesion followed by snaring the lesions above the clip.21
Location of the SET generally dictates the specific modality of ATR. For example, esophageal SETs may be more amenable to STER given that the lesion typically runs parallel with the lumen of the tubular esophagus, which allows for easier dissection without the need of full or partial retroflexion. While gastric SETs can be resected with STER, it may be challenging and more effectively addressed with EFTR, particularly when the entire lesion can be grasped into the full-thickness resection device.22 Limited data exists for duodenal EFTR, and colorectal SETs closure is particularly challenging.
Conclusion
It is key to emphasize that ATR cannot be safely established in practice without the incorporation of a multidisciplinary team (surgeons, radiologists, etc.), specialized tools, and trained personnel. This requires dedicated endoscopic rooms, careful patient selection, and a comprehensive approach to patient care before, during, and after these procedures.
Moreover, it is important to note that some patients may require post-procedure hospitalization for observation to ensure no early complications are encountered. Optimal surveillance strategies after ATR rely heavily on the potential for residual or recurrent disease, underlying pathology, and the expertise of the advanced endoscopist. As the field continues to evolve, ongoing research and technological advances of devices will further enhance the efficacy and safety of ATR in gastroenterology.
Dr. Madi (@MahMadi90) is based in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri. Dr. Rengarajan (@ArvindRenga) and Dr. Bazarbashi (@AhmadBazarbashi) are based in the Division of Gastroenterology, Washington University in St. Louis. The authors have no conflicts of interest to disclose, and no funding was required for this project.
References
1. Copland AP, et al. AGA Clinical Practice Update on appropriate and tailored polypectomy: Expert review. Clin Gastroenterol Hepatol. 2024 Mar. doi: 10.1016/j.cgh.2023.10.012.
2. Lee SP, et al. Effect of preceding biopsy on the results of endoscopic submucosal dissection for colorectal laterally spreading tumor. Dig Dis Sci. 2019 Oct. doi: 10.1007/s10620-019-05625-3.
3. Medina-Prado L, et al. When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Clin Gastroenterol Hepatol. 2021 May. doi: 10.1016/j.cgh.2021.01.024.
4. Rashid MU, et al. EMR and ESD: Indications, techniques and results. Surg Oncol. 2022 Aug. doi: 10.1016/j.suronc.2022.101742.
5. Castro R, et al. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb. doi: 10.3748/wjg.v25.i7.777.
6. Rex DK. Best practices for resection of diminutive and small polyps in the colorectum. Gastrointest Endosc Clin N Am. 2019 Oct. doi: 10.1016/j.giec.2019.06.004.
7. Lv XH, et al. Underwater EMR for nonpedunculated colorectal lesions. Gastrointest Endosc. 2023 Apr. doi: 10.1016/j.gie.2022.10.044.
8. Fujiya M, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar. doi: 10.1016/j.gie.2014.07.034.
9. Kandel P, Wallace MB. Colorectal endoscopic mucosal resection (EMR). Best Pract Res Clin Gastroenterol. 2017 Aug. doi: 10.1016/j.bpg.2017.05.006.
10. Kemper G, et al; ENDOCARE Study Group. Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis. Surg Endosc. 2021 Oct. doi: 10.1007/s00464-021-08574-z.
11. Goto O, et al. Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors). Gastrointest Endosc Clin N Am. 2014 Apr. doi: 10.1016/j.giec.2013.11.006.
12. Wang K, et al. Endoscopic full-thickness resection, indication, methods and perspectives. Dig Endosc. 2023 Jan. doi: 10.1111/den.14474.
13. Herreros de Tejada A. ESD training: A challenging path to excellence. World J Gastrointest Endosc. 2014 Apr 16. doi: 10.4253/wjge.v6.i4.112.
14. Chiba H, et al. Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions. Endosc Int Open. 2017 Jul. doi: 10.1055/s-0043-110567.
15. Mannath J, Ragunath K. Endoscopic mucosal resection: who and how? Therap Adv Gastroenterol. 2011 Sep. doi: 10.1177/1756283X10388683.
16. Wang XY, et al. Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum? BMC Gastroenterol. 2021 May. doi: 10.1186/s12876-021-01766-w.
17. McCarty TR, et al. Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis. Endoscopy. 2021 Oct. doi: 10.1055/a-1266-1855.
18. Jain D, et al. Submucosal tunneling endoscopic resection of upper gastrointestinal tract tumors arising from muscularis propria. Ann Gastroenterol. 2017 Feb. doi: 10.20524/aog.2017.0128.
19. Lv XH, et al. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors: a systematic review and meta-analysis. Surg Endosc. 2017 Jan. doi: 10.1007/s00464-016-4978-7.
20. Cao B, et al. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan. doi: 10.17235/reed.2020.6989/2020.
21. Cai M, et al. Endoscopic full-thickness resection (EFTR) for gastrointestinal subepithelial tumors. Gastrointest Endosc Clin N Am. 2016 Apr. doi: 10.1016/j.giec.2015.12.013.
22. Brigic A, et al. A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions. Surg Endosc. 2013 Oct. doi: 10.1007/s00464-013-2946-z.
Endoscopists are often faced with unique challenges in the management and resection of various gastrointestinal tract lesions. These challenges could be lesion-related, endoscopist-related, or practice-related (see Table 1). (ATR). Not only does this organ-sparing approach offer a less invasive alternative to surgery, but it has also proved to have outcomes comparable to those of surgical standard of practice in specific scenarios.
When Do You Refer to an Advanced Endoscopist?
One of the most critical steps in caring for patients with complex lesions is the ability to accurately determine whether a referral to an advanced endoscopist is warranted. The initial assessment of a lesion should always involve a careful assessment that risk stratifies the lesion depending on the location, size, neoplastic potential, and the feasibility of standard endoscopic resection compared to the need for surgical input.
A practical example in the case of colonic polyps is highlighted by the American Gastroenterology Association (AGA) guidelines recommending the referral of patients with polyps’ size ≥ 20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site to an endoscopic referral center.1 In the case of subepithelial lesions without endoscopic characteristics of benign etiology (i.e., lipomas, pancreatic rests, etc.), the threshold for referral to advanced endoscopists for further diagnostic testing by means of endoscopic ultrasonography or for therapeutic ATR should be lower.
Endoscopic tissue resection follows a spectrum, which often involves deeper layers of the gastrointestinal tract (GIT) as we progress along this spectrum (see Figure 1).
ATR, a term encompassing a variety of endoscopic techniques ranging from endoscopic mucosal resection to full thickness resection, has gained traction over the last years given the ability to effectively remove various lesions in a precise time and cost-effective manner while maintaining the integrity of the GIT and avoiding major surgery. The indications for ATR vary depending on the technique, but generally include the presence of large or poorly positioned lesions, particularly in high-risk areas of the GIT such as the esophagus and small intestine, lesions extending beyond the mucosal layer or originating from deeper layers, and when en bloc resection of select lesions is necessary.
For providers referring patients for ATR, we recommend a few important endoscopic pearls when caring for these patients.
1) Biopsy the lesion if there is concern for malignancy — While some studies have noted increased fibrosis during endoscopic submucosal dissection (ESD) and some guidelines recommend against biopsies pre ESD, we believe that when there is high pretest probability for malignancy, a biopsy should be obtained. This should involve the area that is most concerning for malignancy (at the margin or center).2
2) While marking a lesion with tattoo is helpful for surgical planning and for lesions difficult to locate endoscopically, we stress the importance of placing tattoos 3 to 5 centimeters distal to the lesion and avoiding tattooing the lesion itself, which has been shown to induce fibrosis and can make resection challenging. Based on an international Delphi consensus, expert recommendations on when and how to endoscopically tattoo a lesion can be instrumental in adequately localizing the lesion, allowing for endoscopic resection, and preventing unnecessary surgeries.3
3) If you encounter a lesion that you are not sure can be resected safely and efficaciously, we recommend against attempting resection that may result in partial resection. This can also induce fibrosis and scarring and limit future attempts at resection.
Endoscopic Mucosal Resection (EMR)
EMR is currently utilized for curative treatment of a wide array of GIT lesions limited to the mucosal layer, whether metaplastic, dysplastic, or even in cases with early mucosal cancer, where the risk of submucosal and lymphatic invasion is minimal.4 This makes EMR a versatile and proven therapy, often serving as the first-line treatment for many GIT lesions.
EMR has various techniques that could be categorized into suction or non-suction (lift and cut) techniques. In the suction technique, devices like multiband mucosectomy (MBM) are commonly used, especially in nodular Barrett’s dysplasia, forming a pseudopolyp for subsequent resection. The procedure is characterized by its safety, efficacy, and cost-effectiveness, contributing to its widespread adoption in clinical practice. In the lift and cut approach, a submucosal injection is utilized to separate the muscularis propria from the lesion, thereby reducing the risk of perforation. Different solutions, such as normal saline, hypertonic saline, 50% dextrose, or proprietary submucosal injection solutions, are employed for submucosal injection.5
The non-suction technique using a snare to resect polyps after injection is more often used in colonic and small intestinal EMR. Resection can be done via thermal energy in the form of cut or coagulation; however, there is rising data on the use of piecemeal cold snare resection for select flat polyps of the colon.6 There is also promising data on the role of underwater EMR, a common technique employed for colonic lesions, particularly if the lesion does not lift well with submucosal injection.7
Adverse events associated with EMR include bleeding (7%-8%) and perforation (0.9%-2%).8-9 Adequate submucosal fluid injection is crucial to prevent perforations. However, the main limitation of EMR is the piecemeal nature of resections for lesions larger than 20 mm, leading to compromised histopathologic evaluation for complete excision, especially in cases with superficial submucosal invasion (SMI). This can result in residual or recurrent tissue, reportedly 8% to 20%.10 Despite this limitation, EMR remains a reliable strategy, and recurrent lesions are generally manageable through repeat sessions. The importance of EMR as a therapeutic modality lies in its role in addressing lesions with favorable characteristics, where the risk of SMI is low.
Endoscopic Submucosal Dissection (ESD)
ESD is an evolving technique that can be utilized for submucosal lesions of the GIT, lesions not amenable to EMR due to submucosal fibrosis, when en bloc removal of a lesion is needed for accurate histopathological diagnosis, and when other techniques fail.11-12
ESD was only recently adopted in the United States, requires specialized training, and usually is a lengthier procedure than EMR.13 Compared to EMR, it has higher en bloc resection rates and lower recurrence rates, making it curative for lesions with superficial SMI and favorable histologic features.4,14 The safety profile of ESD appears favorable, with most of the adverse events managed successfully by endoscopic methods. Major complications include intraoperative and delayed perforation, intraoperative and delayed bleeding, aspiration pneumonia, thromboembolism, and stricture formation in the case of circumferential lesions.15
Despite being technically challenging, ESD may provide a cost-effective long-term solution by avoiding surgery, reducing the need for additional interventions by minimizing recurrence rates. Given the technical complexity of ESD, particularly the submucosal dissection portion, techniques such as hybrid ESD developed. Hybrid ESD combines snaring with circumferential mucosal incision and partial submucosal dissection. Although it promises shorter procedure times, reduced complication rates like perforation, and similar recurrence rates compared to traditional ESD, studies have shown lower success rates in en bloc resection.16-17
Both EMR and ESD are considered complementary strategies, and the choice between them should be dictated by lesion characteristics, patient preferences, and local expertise.
Submucosal Tunneling Endoscopic Resection (STER)
STER has emerged as a well-established technique for the endoscopic resection of GI subepithelial tumors (SETs) originating from the muscularis propria layer. The standard STER procedure involves a series of steps including submucosal elevation proximal to the SET, mucosotomy, creation of a submucosal tunnel, dissection of the SET within the tunnel, enucleation from the deep muscle layer, and subsequent specimen retrieval followed by mucosal closure.
This technique is typically recommended for SETs smaller than 3.5 cm, particularly those located in the mid or distal esophagus, cardia, or along the greater curvature of the gastric body.18 However, STER may pose technical challenges for larger SETs or lesions in anatomically difficult locations, where surgical resection is recommended instead.19 Notably, recent large-scale meta-analyses have showcased the favorable complete resection and en bloc resection rates of STER in treating GI SETs.20
Endoscopic Full Thickness Resection (EFTR)
EFTR has emerged as a valuable technique in the endoscopic management of gastrointestinal lesions, particularly SETs and lesions not amenable to EMR or ESD due to fibrosis. EFTR involves the resection of all layers of the GIT from mucosa to serosa, and therefore is well-suited for SETs arising from the muscularis propria (MP).20
EFTR entails two main concepts: tissue resection and complete defect closure. Conventional EFTR consists of several steps, which include mucosal and submucosal pre-cutting, circumferential incision, and dissection through the MP or serosa. This results in a full thickness defect, for which closure of the wall defect is achieved using standard endoscopic clips or a combination of clips and endoloops or endoscopic suturing.21 For lesions less than 2 cm, EFTR can be performed in a single step using a cap-mounted full thickness resection device (FTRD). This results in deployment of over-the-scope clip over the target lesion followed by snaring the lesions above the clip.21
Location of the SET generally dictates the specific modality of ATR. For example, esophageal SETs may be more amenable to STER given that the lesion typically runs parallel with the lumen of the tubular esophagus, which allows for easier dissection without the need of full or partial retroflexion. While gastric SETs can be resected with STER, it may be challenging and more effectively addressed with EFTR, particularly when the entire lesion can be grasped into the full-thickness resection device.22 Limited data exists for duodenal EFTR, and colorectal SETs closure is particularly challenging.
Conclusion
It is key to emphasize that ATR cannot be safely established in practice without the incorporation of a multidisciplinary team (surgeons, radiologists, etc.), specialized tools, and trained personnel. This requires dedicated endoscopic rooms, careful patient selection, and a comprehensive approach to patient care before, during, and after these procedures.
Moreover, it is important to note that some patients may require post-procedure hospitalization for observation to ensure no early complications are encountered. Optimal surveillance strategies after ATR rely heavily on the potential for residual or recurrent disease, underlying pathology, and the expertise of the advanced endoscopist. As the field continues to evolve, ongoing research and technological advances of devices will further enhance the efficacy and safety of ATR in gastroenterology.
Dr. Madi (@MahMadi90) is based in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri. Dr. Rengarajan (@ArvindRenga) and Dr. Bazarbashi (@AhmadBazarbashi) are based in the Division of Gastroenterology, Washington University in St. Louis. The authors have no conflicts of interest to disclose, and no funding was required for this project.
References
1. Copland AP, et al. AGA Clinical Practice Update on appropriate and tailored polypectomy: Expert review. Clin Gastroenterol Hepatol. 2024 Mar. doi: 10.1016/j.cgh.2023.10.012.
2. Lee SP, et al. Effect of preceding biopsy on the results of endoscopic submucosal dissection for colorectal laterally spreading tumor. Dig Dis Sci. 2019 Oct. doi: 10.1007/s10620-019-05625-3.
3. Medina-Prado L, et al. When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Clin Gastroenterol Hepatol. 2021 May. doi: 10.1016/j.cgh.2021.01.024.
4. Rashid MU, et al. EMR and ESD: Indications, techniques and results. Surg Oncol. 2022 Aug. doi: 10.1016/j.suronc.2022.101742.
5. Castro R, et al. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb. doi: 10.3748/wjg.v25.i7.777.
6. Rex DK. Best practices for resection of diminutive and small polyps in the colorectum. Gastrointest Endosc Clin N Am. 2019 Oct. doi: 10.1016/j.giec.2019.06.004.
7. Lv XH, et al. Underwater EMR for nonpedunculated colorectal lesions. Gastrointest Endosc. 2023 Apr. doi: 10.1016/j.gie.2022.10.044.
8. Fujiya M, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar. doi: 10.1016/j.gie.2014.07.034.
9. Kandel P, Wallace MB. Colorectal endoscopic mucosal resection (EMR). Best Pract Res Clin Gastroenterol. 2017 Aug. doi: 10.1016/j.bpg.2017.05.006.
10. Kemper G, et al; ENDOCARE Study Group. Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis. Surg Endosc. 2021 Oct. doi: 10.1007/s00464-021-08574-z.
11. Goto O, et al. Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors). Gastrointest Endosc Clin N Am. 2014 Apr. doi: 10.1016/j.giec.2013.11.006.
12. Wang K, et al. Endoscopic full-thickness resection, indication, methods and perspectives. Dig Endosc. 2023 Jan. doi: 10.1111/den.14474.
13. Herreros de Tejada A. ESD training: A challenging path to excellence. World J Gastrointest Endosc. 2014 Apr 16. doi: 10.4253/wjge.v6.i4.112.
14. Chiba H, et al. Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions. Endosc Int Open. 2017 Jul. doi: 10.1055/s-0043-110567.
15. Mannath J, Ragunath K. Endoscopic mucosal resection: who and how? Therap Adv Gastroenterol. 2011 Sep. doi: 10.1177/1756283X10388683.
16. Wang XY, et al. Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum? BMC Gastroenterol. 2021 May. doi: 10.1186/s12876-021-01766-w.
17. McCarty TR, et al. Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis. Endoscopy. 2021 Oct. doi: 10.1055/a-1266-1855.
18. Jain D, et al. Submucosal tunneling endoscopic resection of upper gastrointestinal tract tumors arising from muscularis propria. Ann Gastroenterol. 2017 Feb. doi: 10.20524/aog.2017.0128.
19. Lv XH, et al. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors: a systematic review and meta-analysis. Surg Endosc. 2017 Jan. doi: 10.1007/s00464-016-4978-7.
20. Cao B, et al. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan. doi: 10.17235/reed.2020.6989/2020.
21. Cai M, et al. Endoscopic full-thickness resection (EFTR) for gastrointestinal subepithelial tumors. Gastrointest Endosc Clin N Am. 2016 Apr. doi: 10.1016/j.giec.2015.12.013.
22. Brigic A, et al. A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions. Surg Endosc. 2013 Oct. doi: 10.1007/s00464-013-2946-z.
Endoscopists are often faced with unique challenges in the management and resection of various gastrointestinal tract lesions. These challenges could be lesion-related, endoscopist-related, or practice-related (see Table 1). (ATR). Not only does this organ-sparing approach offer a less invasive alternative to surgery, but it has also proved to have outcomes comparable to those of surgical standard of practice in specific scenarios.
When Do You Refer to an Advanced Endoscopist?
One of the most critical steps in caring for patients with complex lesions is the ability to accurately determine whether a referral to an advanced endoscopist is warranted. The initial assessment of a lesion should always involve a careful assessment that risk stratifies the lesion depending on the location, size, neoplastic potential, and the feasibility of standard endoscopic resection compared to the need for surgical input.
A practical example in the case of colonic polyps is highlighted by the American Gastroenterology Association (AGA) guidelines recommending the referral of patients with polyps’ size ≥ 20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site to an endoscopic referral center.1 In the case of subepithelial lesions without endoscopic characteristics of benign etiology (i.e., lipomas, pancreatic rests, etc.), the threshold for referral to advanced endoscopists for further diagnostic testing by means of endoscopic ultrasonography or for therapeutic ATR should be lower.
Endoscopic tissue resection follows a spectrum, which often involves deeper layers of the gastrointestinal tract (GIT) as we progress along this spectrum (see Figure 1).
ATR, a term encompassing a variety of endoscopic techniques ranging from endoscopic mucosal resection to full thickness resection, has gained traction over the last years given the ability to effectively remove various lesions in a precise time and cost-effective manner while maintaining the integrity of the GIT and avoiding major surgery. The indications for ATR vary depending on the technique, but generally include the presence of large or poorly positioned lesions, particularly in high-risk areas of the GIT such as the esophagus and small intestine, lesions extending beyond the mucosal layer or originating from deeper layers, and when en bloc resection of select lesions is necessary.
For providers referring patients for ATR, we recommend a few important endoscopic pearls when caring for these patients.
1) Biopsy the lesion if there is concern for malignancy — While some studies have noted increased fibrosis during endoscopic submucosal dissection (ESD) and some guidelines recommend against biopsies pre ESD, we believe that when there is high pretest probability for malignancy, a biopsy should be obtained. This should involve the area that is most concerning for malignancy (at the margin or center).2
2) While marking a lesion with tattoo is helpful for surgical planning and for lesions difficult to locate endoscopically, we stress the importance of placing tattoos 3 to 5 centimeters distal to the lesion and avoiding tattooing the lesion itself, which has been shown to induce fibrosis and can make resection challenging. Based on an international Delphi consensus, expert recommendations on when and how to endoscopically tattoo a lesion can be instrumental in adequately localizing the lesion, allowing for endoscopic resection, and preventing unnecessary surgeries.3
3) If you encounter a lesion that you are not sure can be resected safely and efficaciously, we recommend against attempting resection that may result in partial resection. This can also induce fibrosis and scarring and limit future attempts at resection.
Endoscopic Mucosal Resection (EMR)
EMR is currently utilized for curative treatment of a wide array of GIT lesions limited to the mucosal layer, whether metaplastic, dysplastic, or even in cases with early mucosal cancer, where the risk of submucosal and lymphatic invasion is minimal.4 This makes EMR a versatile and proven therapy, often serving as the first-line treatment for many GIT lesions.
EMR has various techniques that could be categorized into suction or non-suction (lift and cut) techniques. In the suction technique, devices like multiband mucosectomy (MBM) are commonly used, especially in nodular Barrett’s dysplasia, forming a pseudopolyp for subsequent resection. The procedure is characterized by its safety, efficacy, and cost-effectiveness, contributing to its widespread adoption in clinical practice. In the lift and cut approach, a submucosal injection is utilized to separate the muscularis propria from the lesion, thereby reducing the risk of perforation. Different solutions, such as normal saline, hypertonic saline, 50% dextrose, or proprietary submucosal injection solutions, are employed for submucosal injection.5
The non-suction technique using a snare to resect polyps after injection is more often used in colonic and small intestinal EMR. Resection can be done via thermal energy in the form of cut or coagulation; however, there is rising data on the use of piecemeal cold snare resection for select flat polyps of the colon.6 There is also promising data on the role of underwater EMR, a common technique employed for colonic lesions, particularly if the lesion does not lift well with submucosal injection.7
Adverse events associated with EMR include bleeding (7%-8%) and perforation (0.9%-2%).8-9 Adequate submucosal fluid injection is crucial to prevent perforations. However, the main limitation of EMR is the piecemeal nature of resections for lesions larger than 20 mm, leading to compromised histopathologic evaluation for complete excision, especially in cases with superficial submucosal invasion (SMI). This can result in residual or recurrent tissue, reportedly 8% to 20%.10 Despite this limitation, EMR remains a reliable strategy, and recurrent lesions are generally manageable through repeat sessions. The importance of EMR as a therapeutic modality lies in its role in addressing lesions with favorable characteristics, where the risk of SMI is low.
Endoscopic Submucosal Dissection (ESD)
ESD is an evolving technique that can be utilized for submucosal lesions of the GIT, lesions not amenable to EMR due to submucosal fibrosis, when en bloc removal of a lesion is needed for accurate histopathological diagnosis, and when other techniques fail.11-12
ESD was only recently adopted in the United States, requires specialized training, and usually is a lengthier procedure than EMR.13 Compared to EMR, it has higher en bloc resection rates and lower recurrence rates, making it curative for lesions with superficial SMI and favorable histologic features.4,14 The safety profile of ESD appears favorable, with most of the adverse events managed successfully by endoscopic methods. Major complications include intraoperative and delayed perforation, intraoperative and delayed bleeding, aspiration pneumonia, thromboembolism, and stricture formation in the case of circumferential lesions.15
Despite being technically challenging, ESD may provide a cost-effective long-term solution by avoiding surgery, reducing the need for additional interventions by minimizing recurrence rates. Given the technical complexity of ESD, particularly the submucosal dissection portion, techniques such as hybrid ESD developed. Hybrid ESD combines snaring with circumferential mucosal incision and partial submucosal dissection. Although it promises shorter procedure times, reduced complication rates like perforation, and similar recurrence rates compared to traditional ESD, studies have shown lower success rates in en bloc resection.16-17
Both EMR and ESD are considered complementary strategies, and the choice between them should be dictated by lesion characteristics, patient preferences, and local expertise.
Submucosal Tunneling Endoscopic Resection (STER)
STER has emerged as a well-established technique for the endoscopic resection of GI subepithelial tumors (SETs) originating from the muscularis propria layer. The standard STER procedure involves a series of steps including submucosal elevation proximal to the SET, mucosotomy, creation of a submucosal tunnel, dissection of the SET within the tunnel, enucleation from the deep muscle layer, and subsequent specimen retrieval followed by mucosal closure.
This technique is typically recommended for SETs smaller than 3.5 cm, particularly those located in the mid or distal esophagus, cardia, or along the greater curvature of the gastric body.18 However, STER may pose technical challenges for larger SETs or lesions in anatomically difficult locations, where surgical resection is recommended instead.19 Notably, recent large-scale meta-analyses have showcased the favorable complete resection and en bloc resection rates of STER in treating GI SETs.20
Endoscopic Full Thickness Resection (EFTR)
EFTR has emerged as a valuable technique in the endoscopic management of gastrointestinal lesions, particularly SETs and lesions not amenable to EMR or ESD due to fibrosis. EFTR involves the resection of all layers of the GIT from mucosa to serosa, and therefore is well-suited for SETs arising from the muscularis propria (MP).20
EFTR entails two main concepts: tissue resection and complete defect closure. Conventional EFTR consists of several steps, which include mucosal and submucosal pre-cutting, circumferential incision, and dissection through the MP or serosa. This results in a full thickness defect, for which closure of the wall defect is achieved using standard endoscopic clips or a combination of clips and endoloops or endoscopic suturing.21 For lesions less than 2 cm, EFTR can be performed in a single step using a cap-mounted full thickness resection device (FTRD). This results in deployment of over-the-scope clip over the target lesion followed by snaring the lesions above the clip.21
Location of the SET generally dictates the specific modality of ATR. For example, esophageal SETs may be more amenable to STER given that the lesion typically runs parallel with the lumen of the tubular esophagus, which allows for easier dissection without the need of full or partial retroflexion. While gastric SETs can be resected with STER, it may be challenging and more effectively addressed with EFTR, particularly when the entire lesion can be grasped into the full-thickness resection device.22 Limited data exists for duodenal EFTR, and colorectal SETs closure is particularly challenging.
Conclusion
It is key to emphasize that ATR cannot be safely established in practice without the incorporation of a multidisciplinary team (surgeons, radiologists, etc.), specialized tools, and trained personnel. This requires dedicated endoscopic rooms, careful patient selection, and a comprehensive approach to patient care before, during, and after these procedures.
Moreover, it is important to note that some patients may require post-procedure hospitalization for observation to ensure no early complications are encountered. Optimal surveillance strategies after ATR rely heavily on the potential for residual or recurrent disease, underlying pathology, and the expertise of the advanced endoscopist. As the field continues to evolve, ongoing research and technological advances of devices will further enhance the efficacy and safety of ATR in gastroenterology.
Dr. Madi (@MahMadi90) is based in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri. Dr. Rengarajan (@ArvindRenga) and Dr. Bazarbashi (@AhmadBazarbashi) are based in the Division of Gastroenterology, Washington University in St. Louis. The authors have no conflicts of interest to disclose, and no funding was required for this project.
References
1. Copland AP, et al. AGA Clinical Practice Update on appropriate and tailored polypectomy: Expert review. Clin Gastroenterol Hepatol. 2024 Mar. doi: 10.1016/j.cgh.2023.10.012.
2. Lee SP, et al. Effect of preceding biopsy on the results of endoscopic submucosal dissection for colorectal laterally spreading tumor. Dig Dis Sci. 2019 Oct. doi: 10.1007/s10620-019-05625-3.
3. Medina-Prado L, et al. When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Clin Gastroenterol Hepatol. 2021 May. doi: 10.1016/j.cgh.2021.01.024.
4. Rashid MU, et al. EMR and ESD: Indications, techniques and results. Surg Oncol. 2022 Aug. doi: 10.1016/j.suronc.2022.101742.
5. Castro R, et al. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb. doi: 10.3748/wjg.v25.i7.777.
6. Rex DK. Best practices for resection of diminutive and small polyps in the colorectum. Gastrointest Endosc Clin N Am. 2019 Oct. doi: 10.1016/j.giec.2019.06.004.
7. Lv XH, et al. Underwater EMR for nonpedunculated colorectal lesions. Gastrointest Endosc. 2023 Apr. doi: 10.1016/j.gie.2022.10.044.
8. Fujiya M, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar. doi: 10.1016/j.gie.2014.07.034.
9. Kandel P, Wallace MB. Colorectal endoscopic mucosal resection (EMR). Best Pract Res Clin Gastroenterol. 2017 Aug. doi: 10.1016/j.bpg.2017.05.006.
10. Kemper G, et al; ENDOCARE Study Group. Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis. Surg Endosc. 2021 Oct. doi: 10.1007/s00464-021-08574-z.
11. Goto O, et al. Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors). Gastrointest Endosc Clin N Am. 2014 Apr. doi: 10.1016/j.giec.2013.11.006.
12. Wang K, et al. Endoscopic full-thickness resection, indication, methods and perspectives. Dig Endosc. 2023 Jan. doi: 10.1111/den.14474.
13. Herreros de Tejada A. ESD training: A challenging path to excellence. World J Gastrointest Endosc. 2014 Apr 16. doi: 10.4253/wjge.v6.i4.112.
14. Chiba H, et al. Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions. Endosc Int Open. 2017 Jul. doi: 10.1055/s-0043-110567.
15. Mannath J, Ragunath K. Endoscopic mucosal resection: who and how? Therap Adv Gastroenterol. 2011 Sep. doi: 10.1177/1756283X10388683.
16. Wang XY, et al. Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum? BMC Gastroenterol. 2021 May. doi: 10.1186/s12876-021-01766-w.
17. McCarty TR, et al. Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis. Endoscopy. 2021 Oct. doi: 10.1055/a-1266-1855.
18. Jain D, et al. Submucosal tunneling endoscopic resection of upper gastrointestinal tract tumors arising from muscularis propria. Ann Gastroenterol. 2017 Feb. doi: 10.20524/aog.2017.0128.
19. Lv XH, et al. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors: a systematic review and meta-analysis. Surg Endosc. 2017 Jan. doi: 10.1007/s00464-016-4978-7.
20. Cao B, et al. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan. doi: 10.17235/reed.2020.6989/2020.
21. Cai M, et al. Endoscopic full-thickness resection (EFTR) for gastrointestinal subepithelial tumors. Gastrointest Endosc Clin N Am. 2016 Apr. doi: 10.1016/j.giec.2015.12.013.
22. Brigic A, et al. A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions. Surg Endosc. 2013 Oct. doi: 10.1007/s00464-013-2946-z.
Which GI Side Effects Should GLP-1 Prescribers Worry About?
Several recent studies have sought to expound upon what role, if any, GLP-1 RAs may have in increasing the risk for specific gastrointestinal (GI) adverse events.
Herein is a summary of the most current information on this topic, as well as my best guidance for clinicians on integrating it into the clinical care of their patients.
Aspiration Risks
Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide are among the class of medications known as GLP-1 RAs. These medications all work by mimicking the action of hormonal incretins, which are released postprandially. Incretins affect the pancreatic glucose-dependent release of insulin, inhibit release of glucagon, stimulate satiety, and reduce gastric emptying. This last effect has raised concerns that patients taking GLP-1 RAs might be at an elevated risk for endoscopy-related aspiration.
In June 2023, the American Society of Anesthesiologists released recommendations asking providers to consider holding back GLP-1 RAs in patients with scheduled elective procedures.
In August 2023, five national GI societies — the American Gastroenterological Association, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition — issued their own joint statement on the issue.
In the absence of sufficient evidence, these groups suggested that healthcare providers “exercise best practices when performing endoscopy on these patients on GLP-1 [RAs].” They called for more data and encouraged key stakeholders to work together to develop the necessary evidence to provide guidance for these patients prior to elective endoscopy. A rapid clinical update issued by the American Gastroenterological Association in 2024 was consistent with these earlier multisociety recommendations.
Two studies presented at 2024’s Digestive Disease Week provided additional reassurance that concerns about aspiration with these medications were perhaps unwarranted.
The first (since published in The American Journal of Gastroenterology ) was a case-control study of 16,295 patients undergoing upper endoscopy, among whom 306 were taking GLP-1 RAs. It showed a higher rate of solid gastric residue among those taking GLP-1 RAs compared with controls (14% vs 4%, respectively). Patients who had prolonged fasting and clear liquids for concurrent colonoscopy had lower residue rates (2% vs 11%, respectively). However, there were no recorded incidents of procedural complications or aspiration.
The second was a retrospective cohort study using TriNetX, a federated cloud-based network pulling millions of data points from multiple US healthcare organizations. It found that the incidence of aspiration pneumonitis and emergent intubation during or immediately after esophagogastroduodenoscopy and colonoscopy among those taking GLP-1 RAs was not increased compared with those not taking these medications.
These were followed in June 2024 by a systematic review and meta-analysis published by Hiramoto and colleagues, which included 15 studies. The researchers showed a 36-minute prolongation for solid-food emptying and no delay in liquid emptying for patients taking GLP-1 RAs vs controls. The authors concluded that the minimal delay in solid-food emptying would be offset by standard preprocedural fasting periods.
There is concern that patients with complicated type 2 diabetes may have a bit more of a risk for aspiration. However, this was not supported by an analysis from Barlowe and colleagues, who used a national claims database to identify 15,119 patients with type 2 diabetes on GLP-1 RAs. They found no increased events of pulmonary complications (ie, aspiration, pneumonia, respiratory failure) within 14 days following esophagogastroduodenoscopy. Additional evidence suggests that the risk for aspiration in these patients seems to be offset by prolonged fasting and intake of clear liquids.
Although physicians clearly need to use clinical judgment when performing endoscopic procedures on these patients, the emerging evidence on safety has been encouraging.
Association With GI Adverse Events
A recent retrospective analysis of real-world data from 10,328 new users of GLP-1 RAs with diabetes/obesity reported that the most common GI adverse events in this cohort were abdominal pain (57.6%), constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%).
Notably, dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than did semaglutide and exenatide. Compared with semaglutide, dulaglutide and liraglutide had slightly higher odds of abdominal pain, gastroparesis, and nausea and vomiting. There were no significant differences between the GLP-1 RAs in the risk for GI bleeding or pancreatitis.
A 2023 report in JAMA observed that the risk for bowel obstruction is also elevated among patients using these agents for weight loss. Possible reasons for this are currently unknown.
Studies are needed to analyze possible variations in safety profiles between GLP-1 RAs to better guide selection of these drugs, particularly in patients with GI risk factors. Furthermore, the causal relationship between GLP-1 RAs with other concomitant medications requires further investigation.
Although relatively infrequent, the risk for GI adverse events should be given special consideration by providers when prescribing them for weight loss, because the risk/benefit ratios may be different from those in patients with diabetes.
A Lack of Hepatic Concerns
GLP-1 RAs have demonstrated a significant impact on body weight and glycemic control, as well as beneficial effects on clinical, biochemical, and histologic markers in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). These favorable changes are evident by reductions in the hepatic cytolysis markers (ie, aspartate aminotransferase and alanine aminotransferase).
GLP-1 RAs may provide a protective function by reducing the accumulation of hepatic triglycerides and expression of several collagen genes. Some preclinical data suggest a risk reduction for progression to hepatocellular carcinoma, and animal studies indicate that complete suppression of hepatic carcinogenesis is achieved with liraglutide.
The most recent assessment of risk reduction for MASLD progression comes from a Scandinavian cohort analysis of national registries. In looking at 91,479 patients using GLP-1 RAs, investigators demonstrated this treatment was associated with a significant reduction in the composite primary endpoint of hepatocellular carcinoma, as well as both compensated and decompensated cirrhosis.
Given the various favorable hepatic effects of GLP-1 RAs, it is likely that the composite benefit on MASLD is multifactorial. The current literature is clear that it is safe to use these agents across the spectrum of MASLD with or without fibrosis, although it must be noted that GLP-1 RAs are not approved by the Food and Drug Administration for this indication.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
Several recent studies have sought to expound upon what role, if any, GLP-1 RAs may have in increasing the risk for specific gastrointestinal (GI) adverse events.
Herein is a summary of the most current information on this topic, as well as my best guidance for clinicians on integrating it into the clinical care of their patients.
Aspiration Risks
Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide are among the class of medications known as GLP-1 RAs. These medications all work by mimicking the action of hormonal incretins, which are released postprandially. Incretins affect the pancreatic glucose-dependent release of insulin, inhibit release of glucagon, stimulate satiety, and reduce gastric emptying. This last effect has raised concerns that patients taking GLP-1 RAs might be at an elevated risk for endoscopy-related aspiration.
In June 2023, the American Society of Anesthesiologists released recommendations asking providers to consider holding back GLP-1 RAs in patients with scheduled elective procedures.
In August 2023, five national GI societies — the American Gastroenterological Association, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition — issued their own joint statement on the issue.
In the absence of sufficient evidence, these groups suggested that healthcare providers “exercise best practices when performing endoscopy on these patients on GLP-1 [RAs].” They called for more data and encouraged key stakeholders to work together to develop the necessary evidence to provide guidance for these patients prior to elective endoscopy. A rapid clinical update issued by the American Gastroenterological Association in 2024 was consistent with these earlier multisociety recommendations.
Two studies presented at 2024’s Digestive Disease Week provided additional reassurance that concerns about aspiration with these medications were perhaps unwarranted.
The first (since published in The American Journal of Gastroenterology ) was a case-control study of 16,295 patients undergoing upper endoscopy, among whom 306 were taking GLP-1 RAs. It showed a higher rate of solid gastric residue among those taking GLP-1 RAs compared with controls (14% vs 4%, respectively). Patients who had prolonged fasting and clear liquids for concurrent colonoscopy had lower residue rates (2% vs 11%, respectively). However, there were no recorded incidents of procedural complications or aspiration.
The second was a retrospective cohort study using TriNetX, a federated cloud-based network pulling millions of data points from multiple US healthcare organizations. It found that the incidence of aspiration pneumonitis and emergent intubation during or immediately after esophagogastroduodenoscopy and colonoscopy among those taking GLP-1 RAs was not increased compared with those not taking these medications.
These were followed in June 2024 by a systematic review and meta-analysis published by Hiramoto and colleagues, which included 15 studies. The researchers showed a 36-minute prolongation for solid-food emptying and no delay in liquid emptying for patients taking GLP-1 RAs vs controls. The authors concluded that the minimal delay in solid-food emptying would be offset by standard preprocedural fasting periods.
There is concern that patients with complicated type 2 diabetes may have a bit more of a risk for aspiration. However, this was not supported by an analysis from Barlowe and colleagues, who used a national claims database to identify 15,119 patients with type 2 diabetes on GLP-1 RAs. They found no increased events of pulmonary complications (ie, aspiration, pneumonia, respiratory failure) within 14 days following esophagogastroduodenoscopy. Additional evidence suggests that the risk for aspiration in these patients seems to be offset by prolonged fasting and intake of clear liquids.
Although physicians clearly need to use clinical judgment when performing endoscopic procedures on these patients, the emerging evidence on safety has been encouraging.
Association With GI Adverse Events
A recent retrospective analysis of real-world data from 10,328 new users of GLP-1 RAs with diabetes/obesity reported that the most common GI adverse events in this cohort were abdominal pain (57.6%), constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%).
Notably, dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than did semaglutide and exenatide. Compared with semaglutide, dulaglutide and liraglutide had slightly higher odds of abdominal pain, gastroparesis, and nausea and vomiting. There were no significant differences between the GLP-1 RAs in the risk for GI bleeding or pancreatitis.
A 2023 report in JAMA observed that the risk for bowel obstruction is also elevated among patients using these agents for weight loss. Possible reasons for this are currently unknown.
Studies are needed to analyze possible variations in safety profiles between GLP-1 RAs to better guide selection of these drugs, particularly in patients with GI risk factors. Furthermore, the causal relationship between GLP-1 RAs with other concomitant medications requires further investigation.
Although relatively infrequent, the risk for GI adverse events should be given special consideration by providers when prescribing them for weight loss, because the risk/benefit ratios may be different from those in patients with diabetes.
A Lack of Hepatic Concerns
GLP-1 RAs have demonstrated a significant impact on body weight and glycemic control, as well as beneficial effects on clinical, biochemical, and histologic markers in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). These favorable changes are evident by reductions in the hepatic cytolysis markers (ie, aspartate aminotransferase and alanine aminotransferase).
GLP-1 RAs may provide a protective function by reducing the accumulation of hepatic triglycerides and expression of several collagen genes. Some preclinical data suggest a risk reduction for progression to hepatocellular carcinoma, and animal studies indicate that complete suppression of hepatic carcinogenesis is achieved with liraglutide.
The most recent assessment of risk reduction for MASLD progression comes from a Scandinavian cohort analysis of national registries. In looking at 91,479 patients using GLP-1 RAs, investigators demonstrated this treatment was associated with a significant reduction in the composite primary endpoint of hepatocellular carcinoma, as well as both compensated and decompensated cirrhosis.
Given the various favorable hepatic effects of GLP-1 RAs, it is likely that the composite benefit on MASLD is multifactorial. The current literature is clear that it is safe to use these agents across the spectrum of MASLD with or without fibrosis, although it must be noted that GLP-1 RAs are not approved by the Food and Drug Administration for this indication.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
Several recent studies have sought to expound upon what role, if any, GLP-1 RAs may have in increasing the risk for specific gastrointestinal (GI) adverse events.
Herein is a summary of the most current information on this topic, as well as my best guidance for clinicians on integrating it into the clinical care of their patients.
Aspiration Risks
Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide are among the class of medications known as GLP-1 RAs. These medications all work by mimicking the action of hormonal incretins, which are released postprandially. Incretins affect the pancreatic glucose-dependent release of insulin, inhibit release of glucagon, stimulate satiety, and reduce gastric emptying. This last effect has raised concerns that patients taking GLP-1 RAs might be at an elevated risk for endoscopy-related aspiration.
In June 2023, the American Society of Anesthesiologists released recommendations asking providers to consider holding back GLP-1 RAs in patients with scheduled elective procedures.
In August 2023, five national GI societies — the American Gastroenterological Association, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition — issued their own joint statement on the issue.
In the absence of sufficient evidence, these groups suggested that healthcare providers “exercise best practices when performing endoscopy on these patients on GLP-1 [RAs].” They called for more data and encouraged key stakeholders to work together to develop the necessary evidence to provide guidance for these patients prior to elective endoscopy. A rapid clinical update issued by the American Gastroenterological Association in 2024 was consistent with these earlier multisociety recommendations.
Two studies presented at 2024’s Digestive Disease Week provided additional reassurance that concerns about aspiration with these medications were perhaps unwarranted.
The first (since published in The American Journal of Gastroenterology ) was a case-control study of 16,295 patients undergoing upper endoscopy, among whom 306 were taking GLP-1 RAs. It showed a higher rate of solid gastric residue among those taking GLP-1 RAs compared with controls (14% vs 4%, respectively). Patients who had prolonged fasting and clear liquids for concurrent colonoscopy had lower residue rates (2% vs 11%, respectively). However, there were no recorded incidents of procedural complications or aspiration.
The second was a retrospective cohort study using TriNetX, a federated cloud-based network pulling millions of data points from multiple US healthcare organizations. It found that the incidence of aspiration pneumonitis and emergent intubation during or immediately after esophagogastroduodenoscopy and colonoscopy among those taking GLP-1 RAs was not increased compared with those not taking these medications.
These were followed in June 2024 by a systematic review and meta-analysis published by Hiramoto and colleagues, which included 15 studies. The researchers showed a 36-minute prolongation for solid-food emptying and no delay in liquid emptying for patients taking GLP-1 RAs vs controls. The authors concluded that the minimal delay in solid-food emptying would be offset by standard preprocedural fasting periods.
There is concern that patients with complicated type 2 diabetes may have a bit more of a risk for aspiration. However, this was not supported by an analysis from Barlowe and colleagues, who used a national claims database to identify 15,119 patients with type 2 diabetes on GLP-1 RAs. They found no increased events of pulmonary complications (ie, aspiration, pneumonia, respiratory failure) within 14 days following esophagogastroduodenoscopy. Additional evidence suggests that the risk for aspiration in these patients seems to be offset by prolonged fasting and intake of clear liquids.
Although physicians clearly need to use clinical judgment when performing endoscopic procedures on these patients, the emerging evidence on safety has been encouraging.
Association With GI Adverse Events
A recent retrospective analysis of real-world data from 10,328 new users of GLP-1 RAs with diabetes/obesity reported that the most common GI adverse events in this cohort were abdominal pain (57.6%), constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%).
Notably, dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than did semaglutide and exenatide. Compared with semaglutide, dulaglutide and liraglutide had slightly higher odds of abdominal pain, gastroparesis, and nausea and vomiting. There were no significant differences between the GLP-1 RAs in the risk for GI bleeding or pancreatitis.
A 2023 report in JAMA observed that the risk for bowel obstruction is also elevated among patients using these agents for weight loss. Possible reasons for this are currently unknown.
Studies are needed to analyze possible variations in safety profiles between GLP-1 RAs to better guide selection of these drugs, particularly in patients with GI risk factors. Furthermore, the causal relationship between GLP-1 RAs with other concomitant medications requires further investigation.
Although relatively infrequent, the risk for GI adverse events should be given special consideration by providers when prescribing them for weight loss, because the risk/benefit ratios may be different from those in patients with diabetes.
A Lack of Hepatic Concerns
GLP-1 RAs have demonstrated a significant impact on body weight and glycemic control, as well as beneficial effects on clinical, biochemical, and histologic markers in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). These favorable changes are evident by reductions in the hepatic cytolysis markers (ie, aspartate aminotransferase and alanine aminotransferase).
GLP-1 RAs may provide a protective function by reducing the accumulation of hepatic triglycerides and expression of several collagen genes. Some preclinical data suggest a risk reduction for progression to hepatocellular carcinoma, and animal studies indicate that complete suppression of hepatic carcinogenesis is achieved with liraglutide.
The most recent assessment of risk reduction for MASLD progression comes from a Scandinavian cohort analysis of national registries. In looking at 91,479 patients using GLP-1 RAs, investigators demonstrated this treatment was associated with a significant reduction in the composite primary endpoint of hepatocellular carcinoma, as well as both compensated and decompensated cirrhosis.
Given the various favorable hepatic effects of GLP-1 RAs, it is likely that the composite benefit on MASLD is multifactorial. The current literature is clear that it is safe to use these agents across the spectrum of MASLD with or without fibrosis, although it must be noted that GLP-1 RAs are not approved by the Food and Drug Administration for this indication.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He disclosed ties with ISOTHRIVE and Johnson & Johnson.
A version of this article appeared on Medscape.com.
GLP-1 Receptor Agonists in Endoscopy
Dear colleagues,
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are revolutionizing the field of obesity management and are now common medication in patients presenting for endoscopy. With their effect on gastric emptying, the American Society of Anesthesiologists has recommended cessation of such agents prior to endoscopy. However, is this necessary in patients who have been on a clear liquid diet in preparation for a colonoscopy or who are undergoing moderate sedation? Additionally, there are risks to holding GLP-1 RAs, especially for those taking them for glycemic control.
In this issue of Perspectives, Dr. Thomas Hickey and Dr. Ryan Pouliot discuss the nuances of pre-procedure cessation from an anesthesiologist’s perspective. Dr. Jana Al Hashash provides a gastroenterologist’s view, also highlighting the current paucity of evidence guiding management strategies. We hope these pieces will help your discussions in managing GLP-1 RAs prior to endoscopy in your own practice. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Connecticut, and chief of endoscopy at West Haven (Connecticut) VA Medical Center. He is an associate editor for GI & Hepatology News.
GLP-1 Receptor Agonists in Endoscopy
BY THOMAS R. HICKEY, MD; RYAN C. POULIOT, MD
In response to the recent dramatic increase in GLP-1 receptor agonist (GLP-1RA) prescribing and at the urging of its membership, the American Society of Anesthesiologists issued guidance on the preoperative management of these medications. The big takeaways were recommendations that patients on daily dosing should hold their dose on the day of a procedure, and that patients on weekly dosing should hold their dose a week prior.
The ASA guidance recognizes the sparse available evidence base and makes its recommendations in the spirit of patient safety, presuming that a more conservative approach will mitigate risk of rare but potentially devastating pulmonary aspiration, until prospective evidence informs the ideal approach. Until that approach is defined, whether more or less conservative, it is expected that anesthesiologists will adhere to their professional society’s recommendations.
Meanwhile, the American Gastroenterological Association Institute Rapid Clinical Practice Update (CPU) makes little distinction in the management of the endoscopy patient on GLP-1RA. A key refrain throughout the CPU is that there is no actionable data to justify the harms that may come to patients from stopping these medications (e.g., withdrawal of benefit to glycemic control and cardiovascular health) and in delaying or canceling procedures, which could lead to further stress on an overburdened workforce and add complexity to periprocedural processes.
Anesthesiologists should rightly consider themselves leaders in patient safety. As such, when a serious safety concern emerges they should be compelled to caution despite the possibility of other harms, until their concerns are mitigated by robust clinical evidence. Thankfully these questions are quite amenable to research, and prospective trials are already reporting compelling data that residual gastric contents, clearly a risk factor for aspiration, are increased in GLP-1RA groups compared to controls. This is evident even while following recommended fasting times and abstinences from these medications, and adjusting for confounders (e.g., age, diabetes, body mass index).1,2 It logically follows that large studies are likely to find an increased aspiration risk in GLP-1RA populations. Indeed, this increased risk has already been identified in a large retrospective study of endoscopy patients.3 These findings support the ASA’s caution. Additional data indicate that standard fasting guidelines in this patient population may be inadequate.4
The ASA guidance does not differentiate between patients undergoing surgery in the operating room and procedures in the endoscopy suite. Part of our task is to provide perspective on whether GLP-1RA management deserves different treatment for endoscopy patients. We can only speculate pending further data. For example, a prolonged fasting period including a full day of clears, with or without a bowel prep, intuitively protects against pulmonary aspiration. However, this is unlikely to mitigate an anesthesiologist’s concern that administration of propofol, frequently to a state of general anesthesia with an unsecured airway and resulting in a patient devoid of airway protection reflexes, is an inherently higher risk scenario for aspiration compared to surgery in the operating room with a secured airway. We also expect prospective trials will confirm retrospective findings that both propofol and procedures including upper endoscopy confer a higher risk for aspiration compared with conscious sedation and colonoscopy.3
We suggest a reasonable approach based on society guidance and existing evidence, pending additional data. Endoscopists and anesthesiologists should continue this important conversation with a specific focus on risks and benefits in order to decrease conflict and achieve consensus. If anesthesia care is desired, the patient instructions should be updated to reflect ASA guidance. Special attention should be paid to the “gray area,” for example those who did not hold the GLP-1 agonist as recommended.
This category of patients can be considered on a case-by-case basis by the anesthesiologist, proceduralist, and patient, with a range of options including: proceeding with endoscopist-directed sedation, proceeding with anesthesiology-administered conscious sedation, rescheduling the procedure, and proceeding with general anesthesia with rapid-sequence intubation. In addition to patient factors (e.g., GI symptoms, urgency of procedure), this consideration would vary based on local resources (e.g., presence or absence of anesthesia support staff, emergency airway equipment, nursing staff to comfort recovering patients after general endotracheal anesthesia), and aspiration risk inherent to the procedure (e.g., upper and or combination upper and lower endoscopy vs colonoscopy alone). Proficiency and availability of point-of-care ultrasound are rapidly increasing; adoption of a pre-procedure gastric ultrasound to assess for solids, thick liquids, or large volume of clear liquids may provide a less nuanced, more objective means to address this question.
While the question of periprocedural management of these medications has generated intense interest among anesthesiologists and endoscopists alike, it is worth noting the net positive health effects these drugs are likely to have on our patients, including improved glycemic control, significant weight loss, and decreased cardiovascular risk. We are eager to see whether these benefits translate into an overall improvement in periprocedural outcomes, including in our endoscopy patients.
Dr. Hickey is assistant professor of anesthesiology at the Yale University School of Medicine, New Haven, Connecticut, and the VA Connecticut Healthcare System. Dr. Pouliot is assistant professor of anesthesiology at the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, and Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
References
1. Sherwin M et al. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: A prospective observational study in volunteers without obesity recently started on semaglutide. Can J Anaesth. 2023 Aug. doi:10.1007/s12630-023-02549-5.
2. Wu F et al. Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: A historical cohort study. Can J Anaesth. 2024 Mar 14. doi:10.1007/s12630-024-02719-z.
3. Yeo YH et al. Increased risk of aspiration pneumonia associated with endoscopic procedures among patients with glucagon-like peptide 1 receptor agonist use. Gastroenterology. 2024 Mar 27. doi:10.1053/j.gastro.2024.03.015.
4. Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg. 2024 Mar 6. doi:10.1001/jamasurg.2024.0111.
The Impact of GLP-1 Receptor Agonists On Endoscopy
BY JANA G. AL HASHASH, MD, MSc, AGAF
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been approved for the treatment of type 2 diabetes mellitus since 2005. They have become more widely used over the last couple of years for weight loss in individuals who suffer from adiposity-based chronic disease.
The remarkable positive effects that GLP-1 RAs have had on weight loss as well as other medical conditions such as heart disease, hypertension, metabolic dysfunction–associated steatotic liver disease, among many others, have gained these drugs more traction. Even in situations when insurance companies deny coverage of GLP-1 RAs, many patients have been resorting to other routes to obtain these medications, commonly by purchasing them from online compounding pharmacies.
As such, more and more of our patients who present to endoscopy suites across the country are on one of the available GLP-1 RAs. This has necessitated endoscopists and anesthesiologists to become more familiar with the impact of GLP-1 RAs on patients undergoing endoscopic procedures.
Similar to narcotics, GLP-1 RAs affect gastrointestinal motility and delay gastric emptying. Common side effects of patients receiving GLP-1 RAs include nausea, vomiting, and increased satiety. Patients on GLP-1 RAs for weight loss may also have other contributing risk factors for gastroparesis such as diabetes mellitus which may further delay gastric emptying.
For endoscopists, our goals are to achieve the highest quality examination in the safest way possible. As such, being on a GLP-1 RAs could compromise both goals; but to date, the exact impact of these drugs on exam quality and patient safety is yet to be determined.
Studies have shown that patients on GLP-1 RAs have increased gastric residue on upper endoscopy compared with patients not on GLP-1 RAs. The effect of this increased residue on aspiration risk and clinically meaningful patient outcomes is being investigated, and the available published data are conflicting. Additionally, other published cases have shown that GLP-1 RAs are associated with increased solid gastric residue but not liquids, and that symptoms of dyspepsia and abdominal bloating are associated with an increased probability of residual gastric content.
Given the valid concern for increased gastric content residue, anesthesia specialists became more strict about which GLP-1 RA users they would agree to sedate, which ones they would intubate, and which procedures they would cancel. As one would imagine, cancellation and intubation rates have been increasing, and these have affected the schedules of patients, their families, and physicians.
The concern with GLP-1 RAs does not only apply to upper endoscopies, but also impacts colonoscopies. In addition to the concerns of aspiration and pneumonia, studies have shown that the use of GLP-1 RAs may be associated with a lower quality of bowel preparation and higher need for repeat colonoscopy. A study, which I believe is critical, showed that patients on GLP-1 RAs who were scheduled for upper endoscopy and colonoscopy were found to have less gastric residue and less risk of complications when compared with patients who were only having an upper endoscopy. This study sets the stage for a modified prep for patients on GLP-1 RAs prior to their procedures, since patients who received a modified/extended liquid diet on the day prior to their procedure (those preparing for a colonoscopy), had a protective effect against retained gastric content.
Clearly, there is a knowledge gap and a need for guidance. In our recently published AGA Rapid CPU, we advised an individualized approach to managing patients on GLP-1 RAs in the pre-endoscopic setting. Factors to consider are the indication for the GLP-1 RAs, the dose being used, duration of use, and indication and urgency of the procedure, as well as the presence of symptoms in the preoperative area (i.e., do patients have any nausea, vomiting, dyspepsia, etc.). Also an important factor is the facility in which the endoscopy will be taking place, as certain centers have the capacity to act fast and prevent complications or address them in a timely manner while other centers may not be prepared.
We proposed that a modified liquid diet be considered in patients prior to their endoscopies by advising patients to adhere to a clear liquid diet the day before the procedure, as this may help decrease gastric residue and be the safest and best approach for patients on GLP-1 RAs. Of course, it is important to note that more prospective studies are needed to inform clinical practice, and until then, we will have to individualize our approach and continue to put patient safety first.
Dr. Al Hashash is a gastroenterologist and associate professor of medicine at Mayo Clinic, Jacksonville, Florida.
Dear colleagues,
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are revolutionizing the field of obesity management and are now common medication in patients presenting for endoscopy. With their effect on gastric emptying, the American Society of Anesthesiologists has recommended cessation of such agents prior to endoscopy. However, is this necessary in patients who have been on a clear liquid diet in preparation for a colonoscopy or who are undergoing moderate sedation? Additionally, there are risks to holding GLP-1 RAs, especially for those taking them for glycemic control.
In this issue of Perspectives, Dr. Thomas Hickey and Dr. Ryan Pouliot discuss the nuances of pre-procedure cessation from an anesthesiologist’s perspective. Dr. Jana Al Hashash provides a gastroenterologist’s view, also highlighting the current paucity of evidence guiding management strategies. We hope these pieces will help your discussions in managing GLP-1 RAs prior to endoscopy in your own practice. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Connecticut, and chief of endoscopy at West Haven (Connecticut) VA Medical Center. He is an associate editor for GI & Hepatology News.
GLP-1 Receptor Agonists in Endoscopy
BY THOMAS R. HICKEY, MD; RYAN C. POULIOT, MD
In response to the recent dramatic increase in GLP-1 receptor agonist (GLP-1RA) prescribing and at the urging of its membership, the American Society of Anesthesiologists issued guidance on the preoperative management of these medications. The big takeaways were recommendations that patients on daily dosing should hold their dose on the day of a procedure, and that patients on weekly dosing should hold their dose a week prior.
The ASA guidance recognizes the sparse available evidence base and makes its recommendations in the spirit of patient safety, presuming that a more conservative approach will mitigate risk of rare but potentially devastating pulmonary aspiration, until prospective evidence informs the ideal approach. Until that approach is defined, whether more or less conservative, it is expected that anesthesiologists will adhere to their professional society’s recommendations.
Meanwhile, the American Gastroenterological Association Institute Rapid Clinical Practice Update (CPU) makes little distinction in the management of the endoscopy patient on GLP-1RA. A key refrain throughout the CPU is that there is no actionable data to justify the harms that may come to patients from stopping these medications (e.g., withdrawal of benefit to glycemic control and cardiovascular health) and in delaying or canceling procedures, which could lead to further stress on an overburdened workforce and add complexity to periprocedural processes.
Anesthesiologists should rightly consider themselves leaders in patient safety. As such, when a serious safety concern emerges they should be compelled to caution despite the possibility of other harms, until their concerns are mitigated by robust clinical evidence. Thankfully these questions are quite amenable to research, and prospective trials are already reporting compelling data that residual gastric contents, clearly a risk factor for aspiration, are increased in GLP-1RA groups compared to controls. This is evident even while following recommended fasting times and abstinences from these medications, and adjusting for confounders (e.g., age, diabetes, body mass index).1,2 It logically follows that large studies are likely to find an increased aspiration risk in GLP-1RA populations. Indeed, this increased risk has already been identified in a large retrospective study of endoscopy patients.3 These findings support the ASA’s caution. Additional data indicate that standard fasting guidelines in this patient population may be inadequate.4
The ASA guidance does not differentiate between patients undergoing surgery in the operating room and procedures in the endoscopy suite. Part of our task is to provide perspective on whether GLP-1RA management deserves different treatment for endoscopy patients. We can only speculate pending further data. For example, a prolonged fasting period including a full day of clears, with or without a bowel prep, intuitively protects against pulmonary aspiration. However, this is unlikely to mitigate an anesthesiologist’s concern that administration of propofol, frequently to a state of general anesthesia with an unsecured airway and resulting in a patient devoid of airway protection reflexes, is an inherently higher risk scenario for aspiration compared to surgery in the operating room with a secured airway. We also expect prospective trials will confirm retrospective findings that both propofol and procedures including upper endoscopy confer a higher risk for aspiration compared with conscious sedation and colonoscopy.3
We suggest a reasonable approach based on society guidance and existing evidence, pending additional data. Endoscopists and anesthesiologists should continue this important conversation with a specific focus on risks and benefits in order to decrease conflict and achieve consensus. If anesthesia care is desired, the patient instructions should be updated to reflect ASA guidance. Special attention should be paid to the “gray area,” for example those who did not hold the GLP-1 agonist as recommended.
This category of patients can be considered on a case-by-case basis by the anesthesiologist, proceduralist, and patient, with a range of options including: proceeding with endoscopist-directed sedation, proceeding with anesthesiology-administered conscious sedation, rescheduling the procedure, and proceeding with general anesthesia with rapid-sequence intubation. In addition to patient factors (e.g., GI symptoms, urgency of procedure), this consideration would vary based on local resources (e.g., presence or absence of anesthesia support staff, emergency airway equipment, nursing staff to comfort recovering patients after general endotracheal anesthesia), and aspiration risk inherent to the procedure (e.g., upper and or combination upper and lower endoscopy vs colonoscopy alone). Proficiency and availability of point-of-care ultrasound are rapidly increasing; adoption of a pre-procedure gastric ultrasound to assess for solids, thick liquids, or large volume of clear liquids may provide a less nuanced, more objective means to address this question.
While the question of periprocedural management of these medications has generated intense interest among anesthesiologists and endoscopists alike, it is worth noting the net positive health effects these drugs are likely to have on our patients, including improved glycemic control, significant weight loss, and decreased cardiovascular risk. We are eager to see whether these benefits translate into an overall improvement in periprocedural outcomes, including in our endoscopy patients.
Dr. Hickey is assistant professor of anesthesiology at the Yale University School of Medicine, New Haven, Connecticut, and the VA Connecticut Healthcare System. Dr. Pouliot is assistant professor of anesthesiology at the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, and Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
References
1. Sherwin M et al. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: A prospective observational study in volunteers without obesity recently started on semaglutide. Can J Anaesth. 2023 Aug. doi:10.1007/s12630-023-02549-5.
2. Wu F et al. Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: A historical cohort study. Can J Anaesth. 2024 Mar 14. doi:10.1007/s12630-024-02719-z.
3. Yeo YH et al. Increased risk of aspiration pneumonia associated with endoscopic procedures among patients with glucagon-like peptide 1 receptor agonist use. Gastroenterology. 2024 Mar 27. doi:10.1053/j.gastro.2024.03.015.
4. Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg. 2024 Mar 6. doi:10.1001/jamasurg.2024.0111.
The Impact of GLP-1 Receptor Agonists On Endoscopy
BY JANA G. AL HASHASH, MD, MSc, AGAF
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been approved for the treatment of type 2 diabetes mellitus since 2005. They have become more widely used over the last couple of years for weight loss in individuals who suffer from adiposity-based chronic disease.
The remarkable positive effects that GLP-1 RAs have had on weight loss as well as other medical conditions such as heart disease, hypertension, metabolic dysfunction–associated steatotic liver disease, among many others, have gained these drugs more traction. Even in situations when insurance companies deny coverage of GLP-1 RAs, many patients have been resorting to other routes to obtain these medications, commonly by purchasing them from online compounding pharmacies.
As such, more and more of our patients who present to endoscopy suites across the country are on one of the available GLP-1 RAs. This has necessitated endoscopists and anesthesiologists to become more familiar with the impact of GLP-1 RAs on patients undergoing endoscopic procedures.
Similar to narcotics, GLP-1 RAs affect gastrointestinal motility and delay gastric emptying. Common side effects of patients receiving GLP-1 RAs include nausea, vomiting, and increased satiety. Patients on GLP-1 RAs for weight loss may also have other contributing risk factors for gastroparesis such as diabetes mellitus which may further delay gastric emptying.
For endoscopists, our goals are to achieve the highest quality examination in the safest way possible. As such, being on a GLP-1 RAs could compromise both goals; but to date, the exact impact of these drugs on exam quality and patient safety is yet to be determined.
Studies have shown that patients on GLP-1 RAs have increased gastric residue on upper endoscopy compared with patients not on GLP-1 RAs. The effect of this increased residue on aspiration risk and clinically meaningful patient outcomes is being investigated, and the available published data are conflicting. Additionally, other published cases have shown that GLP-1 RAs are associated with increased solid gastric residue but not liquids, and that symptoms of dyspepsia and abdominal bloating are associated with an increased probability of residual gastric content.
Given the valid concern for increased gastric content residue, anesthesia specialists became more strict about which GLP-1 RA users they would agree to sedate, which ones they would intubate, and which procedures they would cancel. As one would imagine, cancellation and intubation rates have been increasing, and these have affected the schedules of patients, their families, and physicians.
The concern with GLP-1 RAs does not only apply to upper endoscopies, but also impacts colonoscopies. In addition to the concerns of aspiration and pneumonia, studies have shown that the use of GLP-1 RAs may be associated with a lower quality of bowel preparation and higher need for repeat colonoscopy. A study, which I believe is critical, showed that patients on GLP-1 RAs who were scheduled for upper endoscopy and colonoscopy were found to have less gastric residue and less risk of complications when compared with patients who were only having an upper endoscopy. This study sets the stage for a modified prep for patients on GLP-1 RAs prior to their procedures, since patients who received a modified/extended liquid diet on the day prior to their procedure (those preparing for a colonoscopy), had a protective effect against retained gastric content.
Clearly, there is a knowledge gap and a need for guidance. In our recently published AGA Rapid CPU, we advised an individualized approach to managing patients on GLP-1 RAs in the pre-endoscopic setting. Factors to consider are the indication for the GLP-1 RAs, the dose being used, duration of use, and indication and urgency of the procedure, as well as the presence of symptoms in the preoperative area (i.e., do patients have any nausea, vomiting, dyspepsia, etc.). Also an important factor is the facility in which the endoscopy will be taking place, as certain centers have the capacity to act fast and prevent complications or address them in a timely manner while other centers may not be prepared.
We proposed that a modified liquid diet be considered in patients prior to their endoscopies by advising patients to adhere to a clear liquid diet the day before the procedure, as this may help decrease gastric residue and be the safest and best approach for patients on GLP-1 RAs. Of course, it is important to note that more prospective studies are needed to inform clinical practice, and until then, we will have to individualize our approach and continue to put patient safety first.
Dr. Al Hashash is a gastroenterologist and associate professor of medicine at Mayo Clinic, Jacksonville, Florida.
Dear colleagues,
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are revolutionizing the field of obesity management and are now common medication in patients presenting for endoscopy. With their effect on gastric emptying, the American Society of Anesthesiologists has recommended cessation of such agents prior to endoscopy. However, is this necessary in patients who have been on a clear liquid diet in preparation for a colonoscopy or who are undergoing moderate sedation? Additionally, there are risks to holding GLP-1 RAs, especially for those taking them for glycemic control.
In this issue of Perspectives, Dr. Thomas Hickey and Dr. Ryan Pouliot discuss the nuances of pre-procedure cessation from an anesthesiologist’s perspective. Dr. Jana Al Hashash provides a gastroenterologist’s view, also highlighting the current paucity of evidence guiding management strategies. We hope these pieces will help your discussions in managing GLP-1 RAs prior to endoscopy in your own practice. We welcome your thoughts on this issue on X @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Connecticut, and chief of endoscopy at West Haven (Connecticut) VA Medical Center. He is an associate editor for GI & Hepatology News.
GLP-1 Receptor Agonists in Endoscopy
BY THOMAS R. HICKEY, MD; RYAN C. POULIOT, MD
In response to the recent dramatic increase in GLP-1 receptor agonist (GLP-1RA) prescribing and at the urging of its membership, the American Society of Anesthesiologists issued guidance on the preoperative management of these medications. The big takeaways were recommendations that patients on daily dosing should hold their dose on the day of a procedure, and that patients on weekly dosing should hold their dose a week prior.
The ASA guidance recognizes the sparse available evidence base and makes its recommendations in the spirit of patient safety, presuming that a more conservative approach will mitigate risk of rare but potentially devastating pulmonary aspiration, until prospective evidence informs the ideal approach. Until that approach is defined, whether more or less conservative, it is expected that anesthesiologists will adhere to their professional society’s recommendations.
Meanwhile, the American Gastroenterological Association Institute Rapid Clinical Practice Update (CPU) makes little distinction in the management of the endoscopy patient on GLP-1RA. A key refrain throughout the CPU is that there is no actionable data to justify the harms that may come to patients from stopping these medications (e.g., withdrawal of benefit to glycemic control and cardiovascular health) and in delaying or canceling procedures, which could lead to further stress on an overburdened workforce and add complexity to periprocedural processes.
Anesthesiologists should rightly consider themselves leaders in patient safety. As such, when a serious safety concern emerges they should be compelled to caution despite the possibility of other harms, until their concerns are mitigated by robust clinical evidence. Thankfully these questions are quite amenable to research, and prospective trials are already reporting compelling data that residual gastric contents, clearly a risk factor for aspiration, are increased in GLP-1RA groups compared to controls. This is evident even while following recommended fasting times and abstinences from these medications, and adjusting for confounders (e.g., age, diabetes, body mass index).1,2 It logically follows that large studies are likely to find an increased aspiration risk in GLP-1RA populations. Indeed, this increased risk has already been identified in a large retrospective study of endoscopy patients.3 These findings support the ASA’s caution. Additional data indicate that standard fasting guidelines in this patient population may be inadequate.4
The ASA guidance does not differentiate between patients undergoing surgery in the operating room and procedures in the endoscopy suite. Part of our task is to provide perspective on whether GLP-1RA management deserves different treatment for endoscopy patients. We can only speculate pending further data. For example, a prolonged fasting period including a full day of clears, with or without a bowel prep, intuitively protects against pulmonary aspiration. However, this is unlikely to mitigate an anesthesiologist’s concern that administration of propofol, frequently to a state of general anesthesia with an unsecured airway and resulting in a patient devoid of airway protection reflexes, is an inherently higher risk scenario for aspiration compared to surgery in the operating room with a secured airway. We also expect prospective trials will confirm retrospective findings that both propofol and procedures including upper endoscopy confer a higher risk for aspiration compared with conscious sedation and colonoscopy.3
We suggest a reasonable approach based on society guidance and existing evidence, pending additional data. Endoscopists and anesthesiologists should continue this important conversation with a specific focus on risks and benefits in order to decrease conflict and achieve consensus. If anesthesia care is desired, the patient instructions should be updated to reflect ASA guidance. Special attention should be paid to the “gray area,” for example those who did not hold the GLP-1 agonist as recommended.
This category of patients can be considered on a case-by-case basis by the anesthesiologist, proceduralist, and patient, with a range of options including: proceeding with endoscopist-directed sedation, proceeding with anesthesiology-administered conscious sedation, rescheduling the procedure, and proceeding with general anesthesia with rapid-sequence intubation. In addition to patient factors (e.g., GI symptoms, urgency of procedure), this consideration would vary based on local resources (e.g., presence or absence of anesthesia support staff, emergency airway equipment, nursing staff to comfort recovering patients after general endotracheal anesthesia), and aspiration risk inherent to the procedure (e.g., upper and or combination upper and lower endoscopy vs colonoscopy alone). Proficiency and availability of point-of-care ultrasound are rapidly increasing; adoption of a pre-procedure gastric ultrasound to assess for solids, thick liquids, or large volume of clear liquids may provide a less nuanced, more objective means to address this question.
While the question of periprocedural management of these medications has generated intense interest among anesthesiologists and endoscopists alike, it is worth noting the net positive health effects these drugs are likely to have on our patients, including improved glycemic control, significant weight loss, and decreased cardiovascular risk. We are eager to see whether these benefits translate into an overall improvement in periprocedural outcomes, including in our endoscopy patients.
Dr. Hickey is assistant professor of anesthesiology at the Yale University School of Medicine, New Haven, Connecticut, and the VA Connecticut Healthcare System. Dr. Pouliot is assistant professor of anesthesiology at the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, and Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
References
1. Sherwin M et al. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: A prospective observational study in volunteers without obesity recently started on semaglutide. Can J Anaesth. 2023 Aug. doi:10.1007/s12630-023-02549-5.
2. Wu F et al. Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: A historical cohort study. Can J Anaesth. 2024 Mar 14. doi:10.1007/s12630-024-02719-z.
3. Yeo YH et al. Increased risk of aspiration pneumonia associated with endoscopic procedures among patients with glucagon-like peptide 1 receptor agonist use. Gastroenterology. 2024 Mar 27. doi:10.1053/j.gastro.2024.03.015.
4. Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg. 2024 Mar 6. doi:10.1001/jamasurg.2024.0111.
The Impact of GLP-1 Receptor Agonists On Endoscopy
BY JANA G. AL HASHASH, MD, MSc, AGAF
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been approved for the treatment of type 2 diabetes mellitus since 2005. They have become more widely used over the last couple of years for weight loss in individuals who suffer from adiposity-based chronic disease.
The remarkable positive effects that GLP-1 RAs have had on weight loss as well as other medical conditions such as heart disease, hypertension, metabolic dysfunction–associated steatotic liver disease, among many others, have gained these drugs more traction. Even in situations when insurance companies deny coverage of GLP-1 RAs, many patients have been resorting to other routes to obtain these medications, commonly by purchasing them from online compounding pharmacies.
As such, more and more of our patients who present to endoscopy suites across the country are on one of the available GLP-1 RAs. This has necessitated endoscopists and anesthesiologists to become more familiar with the impact of GLP-1 RAs on patients undergoing endoscopic procedures.
Similar to narcotics, GLP-1 RAs affect gastrointestinal motility and delay gastric emptying. Common side effects of patients receiving GLP-1 RAs include nausea, vomiting, and increased satiety. Patients on GLP-1 RAs for weight loss may also have other contributing risk factors for gastroparesis such as diabetes mellitus which may further delay gastric emptying.
For endoscopists, our goals are to achieve the highest quality examination in the safest way possible. As such, being on a GLP-1 RAs could compromise both goals; but to date, the exact impact of these drugs on exam quality and patient safety is yet to be determined.
Studies have shown that patients on GLP-1 RAs have increased gastric residue on upper endoscopy compared with patients not on GLP-1 RAs. The effect of this increased residue on aspiration risk and clinically meaningful patient outcomes is being investigated, and the available published data are conflicting. Additionally, other published cases have shown that GLP-1 RAs are associated with increased solid gastric residue but not liquids, and that symptoms of dyspepsia and abdominal bloating are associated with an increased probability of residual gastric content.
Given the valid concern for increased gastric content residue, anesthesia specialists became more strict about which GLP-1 RA users they would agree to sedate, which ones they would intubate, and which procedures they would cancel. As one would imagine, cancellation and intubation rates have been increasing, and these have affected the schedules of patients, their families, and physicians.
The concern with GLP-1 RAs does not only apply to upper endoscopies, but also impacts colonoscopies. In addition to the concerns of aspiration and pneumonia, studies have shown that the use of GLP-1 RAs may be associated with a lower quality of bowel preparation and higher need for repeat colonoscopy. A study, which I believe is critical, showed that patients on GLP-1 RAs who were scheduled for upper endoscopy and colonoscopy were found to have less gastric residue and less risk of complications when compared with patients who were only having an upper endoscopy. This study sets the stage for a modified prep for patients on GLP-1 RAs prior to their procedures, since patients who received a modified/extended liquid diet on the day prior to their procedure (those preparing for a colonoscopy), had a protective effect against retained gastric content.
Clearly, there is a knowledge gap and a need for guidance. In our recently published AGA Rapid CPU, we advised an individualized approach to managing patients on GLP-1 RAs in the pre-endoscopic setting. Factors to consider are the indication for the GLP-1 RAs, the dose being used, duration of use, and indication and urgency of the procedure, as well as the presence of symptoms in the preoperative area (i.e., do patients have any nausea, vomiting, dyspepsia, etc.). Also an important factor is the facility in which the endoscopy will be taking place, as certain centers have the capacity to act fast and prevent complications or address them in a timely manner while other centers may not be prepared.
We proposed that a modified liquid diet be considered in patients prior to their endoscopies by advising patients to adhere to a clear liquid diet the day before the procedure, as this may help decrease gastric residue and be the safest and best approach for patients on GLP-1 RAs. Of course, it is important to note that more prospective studies are needed to inform clinical practice, and until then, we will have to individualize our approach and continue to put patient safety first.
Dr. Al Hashash is a gastroenterologist and associate professor of medicine at Mayo Clinic, Jacksonville, Florida.
Autonomous AI Outperforms Humans in Optical Diagnosis of Colorectal Polyps
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
FROM GASTROENTEROLOGY
Gastroenterology Data Trends 2024
In this issue:
- Eosinophilic Gastrointestinal Diseases: Beyond EoE
Nirmala Gonsalves, MD, AGAF, FACG - The Changing Face of IBD: Beyond the Western World
Gilaad G. Kaplan, MD, MPH, AGAF; Paulo Kotze, MD, MS, PhD; Siew C. Ng, MBBS, PhD, AGAF - Role of Non-invasive Biomarkers in the Evaluation and Management of MASLD
Julia J. Wattacheril, MD, MPH - The Emerging Role of Liquid Biopsy in the Diagnosis and Management of CRC
David Lieberman, MD, AGAF - Cannabinoids and Digestive Disorders
Jami A. Kinnucan, MD, AGAF, FACG - AI and Machine Learning in IBD: Promising Applications and Remaining Challenges
Shirley Cohen-Mekelburg, MD, MS - Simulation-Based Training in Endoscopy: Benefits and Challenges
Richa Shukla, MD - Fluid Management in Acute Pancreatitis
Jorge D. Machicado, MD, MPH
In this issue:
- Eosinophilic Gastrointestinal Diseases: Beyond EoE
Nirmala Gonsalves, MD, AGAF, FACG - The Changing Face of IBD: Beyond the Western World
Gilaad G. Kaplan, MD, MPH, AGAF; Paulo Kotze, MD, MS, PhD; Siew C. Ng, MBBS, PhD, AGAF - Role of Non-invasive Biomarkers in the Evaluation and Management of MASLD
Julia J. Wattacheril, MD, MPH - The Emerging Role of Liquid Biopsy in the Diagnosis and Management of CRC
David Lieberman, MD, AGAF - Cannabinoids and Digestive Disorders
Jami A. Kinnucan, MD, AGAF, FACG - AI and Machine Learning in IBD: Promising Applications and Remaining Challenges
Shirley Cohen-Mekelburg, MD, MS - Simulation-Based Training in Endoscopy: Benefits and Challenges
Richa Shukla, MD - Fluid Management in Acute Pancreatitis
Jorge D. Machicado, MD, MPH
In this issue:
- Eosinophilic Gastrointestinal Diseases: Beyond EoE
Nirmala Gonsalves, MD, AGAF, FACG - The Changing Face of IBD: Beyond the Western World
Gilaad G. Kaplan, MD, MPH, AGAF; Paulo Kotze, MD, MS, PhD; Siew C. Ng, MBBS, PhD, AGAF - Role of Non-invasive Biomarkers in the Evaluation and Management of MASLD
Julia J. Wattacheril, MD, MPH - The Emerging Role of Liquid Biopsy in the Diagnosis and Management of CRC
David Lieberman, MD, AGAF - Cannabinoids and Digestive Disorders
Jami A. Kinnucan, MD, AGAF, FACG - AI and Machine Learning in IBD: Promising Applications and Remaining Challenges
Shirley Cohen-Mekelburg, MD, MS - Simulation-Based Training in Endoscopy: Benefits and Challenges
Richa Shukla, MD - Fluid Management in Acute Pancreatitis
Jorge D. Machicado, MD, MPH
Simulation-Based Training in Endoscopy: Benefits and Challenges
- Hayden EM, Khatri A, Kelly HR, Yager PH, Salazar GM. Mannequinbased telesimulation: increasing access to simulation-based education. Acad Emerg Med. 2018;25(2):144-147. doi:10.1111/acem.13299
- Khan R, Scaffidi MA, Grover SC, Gimpaya N, Walsh CM. Simulation in endoscopy: practical educational strategies to improve learning. World J Gastrointest Endosc. 2019;11(3):209-218. doi:10.4253/wjge.v11.i3.209
- Bhushan S, Anandasabapathy S, Shukla R. Use of augmented reality and virtual reality technologies in endoscopic training. Clin Gastroenterol Hepatol. 2018;16(11):1688-1691. doi:10.1016/j.cgh.2018.08.021
- Bienstock J, Heuer A. A review on the evolution of simulationbased training to help build a safer future. Medicine (Baltimore). 2022;101(25):e29503. doi:10.1097/MD.0000000000029503
- Emergen Research. Global augmented and virtual reality in healthcare market size to reach USD 20.76 billion in 2032. GlobeNewswire. Published October 12, 2023. Accessed January 5, 2024. https://www.globenewswire.com/news-release/2023/10/12/2759433/0/en/GlobalAugmented-and-Virtual-Reality-in-Healthcare-Market-Size-to-ReachUSD-20-76-Billion-in-2032-Emergen-Research.html
- Hippe DS, Umoren RA, McGee A, Bucher SL, Bresnahan BW. A targeted systematic review of cost analyses for implementation of simulation-based education in healthcare. SAGE Open Med. 2020;8:2050312120913451. doi:10.1177/2050312120913451
- Hayden EM, Khatri A, Kelly HR, Yager PH, Salazar GM. Mannequinbased telesimulation: increasing access to simulation-based education. Acad Emerg Med. 2018;25(2):144-147. doi:10.1111/acem.13299
- Khan R, Scaffidi MA, Grover SC, Gimpaya N, Walsh CM. Simulation in endoscopy: practical educational strategies to improve learning. World J Gastrointest Endosc. 2019;11(3):209-218. doi:10.4253/wjge.v11.i3.209
- Bhushan S, Anandasabapathy S, Shukla R. Use of augmented reality and virtual reality technologies in endoscopic training. Clin Gastroenterol Hepatol. 2018;16(11):1688-1691. doi:10.1016/j.cgh.2018.08.021
- Bienstock J, Heuer A. A review on the evolution of simulationbased training to help build a safer future. Medicine (Baltimore). 2022;101(25):e29503. doi:10.1097/MD.0000000000029503
- Emergen Research. Global augmented and virtual reality in healthcare market size to reach USD 20.76 billion in 2032. GlobeNewswire. Published October 12, 2023. Accessed January 5, 2024. https://www.globenewswire.com/news-release/2023/10/12/2759433/0/en/GlobalAugmented-and-Virtual-Reality-in-Healthcare-Market-Size-to-ReachUSD-20-76-Billion-in-2032-Emergen-Research.html
- Hippe DS, Umoren RA, McGee A, Bucher SL, Bresnahan BW. A targeted systematic review of cost analyses for implementation of simulation-based education in healthcare. SAGE Open Med. 2020;8:2050312120913451. doi:10.1177/2050312120913451
- Hayden EM, Khatri A, Kelly HR, Yager PH, Salazar GM. Mannequinbased telesimulation: increasing access to simulation-based education. Acad Emerg Med. 2018;25(2):144-147. doi:10.1111/acem.13299
- Khan R, Scaffidi MA, Grover SC, Gimpaya N, Walsh CM. Simulation in endoscopy: practical educational strategies to improve learning. World J Gastrointest Endosc. 2019;11(3):209-218. doi:10.4253/wjge.v11.i3.209
- Bhushan S, Anandasabapathy S, Shukla R. Use of augmented reality and virtual reality technologies in endoscopic training. Clin Gastroenterol Hepatol. 2018;16(11):1688-1691. doi:10.1016/j.cgh.2018.08.021
- Bienstock J, Heuer A. A review on the evolution of simulationbased training to help build a safer future. Medicine (Baltimore). 2022;101(25):e29503. doi:10.1097/MD.0000000000029503
- Emergen Research. Global augmented and virtual reality in healthcare market size to reach USD 20.76 billion in 2032. GlobeNewswire. Published October 12, 2023. Accessed January 5, 2024. https://www.globenewswire.com/news-release/2023/10/12/2759433/0/en/GlobalAugmented-and-Virtual-Reality-in-Healthcare-Market-Size-to-ReachUSD-20-76-Billion-in-2032-Emergen-Research.html
- Hippe DS, Umoren RA, McGee A, Bucher SL, Bresnahan BW. A targeted systematic review of cost analyses for implementation of simulation-based education in healthcare. SAGE Open Med. 2020;8:2050312120913451. doi:10.1177/2050312120913451
Green Initiative Reduces Endoscopic Waste During Colonoscopies
WASHINGTON — As part of a quality improvement initiative, , according to a study presented at Digestive Disease Week® (DDW).
After discussing environmentally conscious practices during regular meetings, the odds of gastroenterologists using a single tool — either biopsy forceps or a snare — compared with multiple disposable tools was three times higher.
“The burden of waste is massive, with GI being the third-largest waste generator in healthcare. The number of procedures is increasing, which just means more waste, and we have to look at ways to reduce it,” said lead author Prateek Harne, MD, a gastroenterology fellow at the University of Texas Health Science Center.
Overall, the healthcare industry generates 8.5% of U.S. greenhouse emissions, with more than 70% coming from used instruments and supplies, he said. GI endoscopy generates 85,000 metric tons of carbon dioxide waste annually. That waste stems from high case volumes, patient travel, the decontamination process, and single-use devices.
After seeing the waste at his institution, Dr. Harne wondered how to reduce single-use device and nonrenewable waste, particularly the tools used during polypectomies. He and colleagues decided to focus on single-tool use and collected data about the tools used during screening colonoscopies for 8 weeks before an intervention.
As part of the intervention, Dr. Harne and colleagues discussed green endoscopy initiatives supported by North American gastrointestinal societies during a journal club meeting with gastroenterology faculty. They also discussed potential strategies to reduce waste in day-to-day practice during a monthly business meeting, particularly focused on being mindful of using tools during polypectomies. The meetings occurred 3 days apart.
Then Dr. Harne and colleagues collected data regarding tool use during screening colonoscopies, looking at the number and type of instruments used. Before the meetings, 210 patients underwent colonoscopies, including 34% that required no intervention, 32% that required one tool, and 33% that required multiple tools.
After the meetings, 112 patients underwent colonoscopies, including 34% that required no tools, 49% that used one tool, and 17% that used multiple tools. This represented a 17% increase in the use of one tool (P < .01) and a 16% decrease in the use of multiple tools (P < .01). The odds of using a single tool compared with multiple tools was 2.98, and there was a statistically significant increase in uptake of snare for polypectomy.
The study was limited by being at a single center, having a small sample size, and using a short-term assessment. At the same time, the findings show potential for a low-cost solution through open discussion with gastroenterologists.
“Sir Isaac Newton had two holes for two different sized cats in his home, but all of his cats ended up using the bigger hole,” Dr. Harne said in his conclusion. “Maybe we can do the same for polypectomies and use only the tools that we need.”
In an interview, Dr. Harne noted he spoke with the janitorial staff at his institution to learn more about endoscopy unit waste, including how much is recycled, how much is incinerated, and who handles the waste. He recognized the work being done in Europe to understand and reduce endoscopic waste and hopes U.S. groups begin to implement more measures.
“Gastroenterologists and their teams need to be more cognizant of the impact we have on the environment,” Dr. Harne said. “As our study shows, if providers are aware that they can and should use fewer tools to get the same results, it can lead to a statistically significant impact, just with a friendly reminder to reduce use.”
After the presentation, Dr. Harne discussed other shifts with conference attendees, such as not opening or unwrapping tools until needed during a procedure.
“Small changes could have big impacts. Everything that we do in QI [quality improvement] is meant to help patients and the environment,” said Amanda Krouse, MD, a research fellow at the University of California, San Diego, who was a moderator of the DDW session on GI fellow–directed QI projects.
In an interview, Alana Persaud, MD, an endoscopy fellow at Geisinger Medical Center in Danville, Pennsylvania, also a moderator of the session, said: “Ultimately, the medical services we’re providing are for the longevity of our patients, but at the same time, we don’t want it to be to the detriment of the environment, so paying attention to green endoscopy when we can preserve and use more discretion with our devices is worth it so we can all thrive together.”
Dr. Harne did not have any disclosures.
WASHINGTON — As part of a quality improvement initiative, , according to a study presented at Digestive Disease Week® (DDW).
After discussing environmentally conscious practices during regular meetings, the odds of gastroenterologists using a single tool — either biopsy forceps or a snare — compared with multiple disposable tools was three times higher.
“The burden of waste is massive, with GI being the third-largest waste generator in healthcare. The number of procedures is increasing, which just means more waste, and we have to look at ways to reduce it,” said lead author Prateek Harne, MD, a gastroenterology fellow at the University of Texas Health Science Center.
Overall, the healthcare industry generates 8.5% of U.S. greenhouse emissions, with more than 70% coming from used instruments and supplies, he said. GI endoscopy generates 85,000 metric tons of carbon dioxide waste annually. That waste stems from high case volumes, patient travel, the decontamination process, and single-use devices.
After seeing the waste at his institution, Dr. Harne wondered how to reduce single-use device and nonrenewable waste, particularly the tools used during polypectomies. He and colleagues decided to focus on single-tool use and collected data about the tools used during screening colonoscopies for 8 weeks before an intervention.
As part of the intervention, Dr. Harne and colleagues discussed green endoscopy initiatives supported by North American gastrointestinal societies during a journal club meeting with gastroenterology faculty. They also discussed potential strategies to reduce waste in day-to-day practice during a monthly business meeting, particularly focused on being mindful of using tools during polypectomies. The meetings occurred 3 days apart.
Then Dr. Harne and colleagues collected data regarding tool use during screening colonoscopies, looking at the number and type of instruments used. Before the meetings, 210 patients underwent colonoscopies, including 34% that required no intervention, 32% that required one tool, and 33% that required multiple tools.
After the meetings, 112 patients underwent colonoscopies, including 34% that required no tools, 49% that used one tool, and 17% that used multiple tools. This represented a 17% increase in the use of one tool (P < .01) and a 16% decrease in the use of multiple tools (P < .01). The odds of using a single tool compared with multiple tools was 2.98, and there was a statistically significant increase in uptake of snare for polypectomy.
The study was limited by being at a single center, having a small sample size, and using a short-term assessment. At the same time, the findings show potential for a low-cost solution through open discussion with gastroenterologists.
“Sir Isaac Newton had two holes for two different sized cats in his home, but all of his cats ended up using the bigger hole,” Dr. Harne said in his conclusion. “Maybe we can do the same for polypectomies and use only the tools that we need.”
In an interview, Dr. Harne noted he spoke with the janitorial staff at his institution to learn more about endoscopy unit waste, including how much is recycled, how much is incinerated, and who handles the waste. He recognized the work being done in Europe to understand and reduce endoscopic waste and hopes U.S. groups begin to implement more measures.
“Gastroenterologists and their teams need to be more cognizant of the impact we have on the environment,” Dr. Harne said. “As our study shows, if providers are aware that they can and should use fewer tools to get the same results, it can lead to a statistically significant impact, just with a friendly reminder to reduce use.”
After the presentation, Dr. Harne discussed other shifts with conference attendees, such as not opening or unwrapping tools until needed during a procedure.
“Small changes could have big impacts. Everything that we do in QI [quality improvement] is meant to help patients and the environment,” said Amanda Krouse, MD, a research fellow at the University of California, San Diego, who was a moderator of the DDW session on GI fellow–directed QI projects.
In an interview, Alana Persaud, MD, an endoscopy fellow at Geisinger Medical Center in Danville, Pennsylvania, also a moderator of the session, said: “Ultimately, the medical services we’re providing are for the longevity of our patients, but at the same time, we don’t want it to be to the detriment of the environment, so paying attention to green endoscopy when we can preserve and use more discretion with our devices is worth it so we can all thrive together.”
Dr. Harne did not have any disclosures.
WASHINGTON — As part of a quality improvement initiative, , according to a study presented at Digestive Disease Week® (DDW).
After discussing environmentally conscious practices during regular meetings, the odds of gastroenterologists using a single tool — either biopsy forceps or a snare — compared with multiple disposable tools was three times higher.
“The burden of waste is massive, with GI being the third-largest waste generator in healthcare. The number of procedures is increasing, which just means more waste, and we have to look at ways to reduce it,” said lead author Prateek Harne, MD, a gastroenterology fellow at the University of Texas Health Science Center.
Overall, the healthcare industry generates 8.5% of U.S. greenhouse emissions, with more than 70% coming from used instruments and supplies, he said. GI endoscopy generates 85,000 metric tons of carbon dioxide waste annually. That waste stems from high case volumes, patient travel, the decontamination process, and single-use devices.
After seeing the waste at his institution, Dr. Harne wondered how to reduce single-use device and nonrenewable waste, particularly the tools used during polypectomies. He and colleagues decided to focus on single-tool use and collected data about the tools used during screening colonoscopies for 8 weeks before an intervention.
As part of the intervention, Dr. Harne and colleagues discussed green endoscopy initiatives supported by North American gastrointestinal societies during a journal club meeting with gastroenterology faculty. They also discussed potential strategies to reduce waste in day-to-day practice during a monthly business meeting, particularly focused on being mindful of using tools during polypectomies. The meetings occurred 3 days apart.
Then Dr. Harne and colleagues collected data regarding tool use during screening colonoscopies, looking at the number and type of instruments used. Before the meetings, 210 patients underwent colonoscopies, including 34% that required no intervention, 32% that required one tool, and 33% that required multiple tools.
After the meetings, 112 patients underwent colonoscopies, including 34% that required no tools, 49% that used one tool, and 17% that used multiple tools. This represented a 17% increase in the use of one tool (P < .01) and a 16% decrease in the use of multiple tools (P < .01). The odds of using a single tool compared with multiple tools was 2.98, and there was a statistically significant increase in uptake of snare for polypectomy.
The study was limited by being at a single center, having a small sample size, and using a short-term assessment. At the same time, the findings show potential for a low-cost solution through open discussion with gastroenterologists.
“Sir Isaac Newton had two holes for two different sized cats in his home, but all of his cats ended up using the bigger hole,” Dr. Harne said in his conclusion. “Maybe we can do the same for polypectomies and use only the tools that we need.”
In an interview, Dr. Harne noted he spoke with the janitorial staff at his institution to learn more about endoscopy unit waste, including how much is recycled, how much is incinerated, and who handles the waste. He recognized the work being done in Europe to understand and reduce endoscopic waste and hopes U.S. groups begin to implement more measures.
“Gastroenterologists and their teams need to be more cognizant of the impact we have on the environment,” Dr. Harne said. “As our study shows, if providers are aware that they can and should use fewer tools to get the same results, it can lead to a statistically significant impact, just with a friendly reminder to reduce use.”
After the presentation, Dr. Harne discussed other shifts with conference attendees, such as not opening or unwrapping tools until needed during a procedure.
“Small changes could have big impacts. Everything that we do in QI [quality improvement] is meant to help patients and the environment,” said Amanda Krouse, MD, a research fellow at the University of California, San Diego, who was a moderator of the DDW session on GI fellow–directed QI projects.
In an interview, Alana Persaud, MD, an endoscopy fellow at Geisinger Medical Center in Danville, Pennsylvania, also a moderator of the session, said: “Ultimately, the medical services we’re providing are for the longevity of our patients, but at the same time, we don’t want it to be to the detriment of the environment, so paying attention to green endoscopy when we can preserve and use more discretion with our devices is worth it so we can all thrive together.”
Dr. Harne did not have any disclosures.
FROM DDW 2024
Endoscopic Management of Barrett’s Esophagus
Introduction
Barrett’s esophagus (BE) is characterized by the replacement of squamous epithelium by columnar metaplasia of the distal esophagus (>1 cm length). It is a precancerous condition, with 3%-5% of patients with BE developing esophageal adenocarcinoma (EAC) in their lifetime. EAC is one of the cancers with high morbidity and mortality (5-year survival < 20%), and its incidence has been on the rise. Studies examining the natural history of BE have demonstrated that the progression happens through a metaplasia-dysplasia-neoplasia sequence. Therefore, early detection of BE and timely management to prevent progression to EAC is crucial.
Grades of Dysplasia
The current gold standard for the diagnosis of BE neoplasia includes a high-quality endoscopic evaluation and biopsies. Biopsies should be obtained from any visible lesions (nodules, ulcers) followed by a random 4-quadrant fashion (Seattle protocol) interval of the entire length of the BE segment. It is essential to pay attention to the results of the biopsy that have been obtained since it will not only determine the surveillance interval but is crucial in planning any necessary endoscopic therapy. The possible results of the biopsy and its implications are:
- No intestinal metaplasia (IM): This would rule out Barrett’s esophagus and no further surveillance would be necessary. A recent population-based study of over 1 million patients showed a 55% and 61% reduced risk of upper gastrointestinal (UGI) cancer and deaths respectively after a negative endoscopy.1
- Intestinal metaplasia with no dysplasia (non-dysplastic BE): Biopsies confirm presence of intestinal metaplasia in the biopsies without any evidence of dysplasia. While the rate of progression to EAC is low (0.07%-0.25%), it is not absent and thus surveillance would be indicated. Current guidelines suggest repeating an endoscopy with biopsy in 5 years if the length of BE is < 3 cm or 3 years if length of BE ≥ 3 cm.2
- Indeterminate for dysplasia (BE-IND): Biopsies confirm IM but are not able to definitively rule out dysplasia. This can be seen in about 4%-8% of the biopsies obtained. The progression rates to EAC are reported to be comparable or lower to low-grade dysplasia (LGD), so the current recommendation is to intensify acid reduction therapy and repeat endoscopy in 6 months. If repeat endoscopy downgrades to non-dysplastic, then can follow surveillance according to NDBE protocol; otherwise recommend continuing surveillance every 12 months.
- Low-grade dysplasia (BE-LGD): Biopsies confirm IM but also show tightly packed overlapping basal nuclei with hyperchromasia and irregular contours, basal stratification of nuclei, and diminished goblet and columnar cell mucus. There is significant inter-observer variability reported,3 and thus the slides must be reviewed by a second pathologist with experience in BE to confirm the findings. Once confirmed, based on risk factors such as presence of multifocal LGD, persistence of LGD, presence of visible lesions, etc., the patient can be offered Barrett’s endoscopic therapy (BET) or undergo continued surveillance. The decision of pursuing one or the other would be dependent on patient preference and shared decision-making between the patient and the provider.
- High-grade dysplasia (BE-HGD): Biopsies confirm IM with cells showing greater degree of cytologic and architectural alterations of dysplasia than LGD but without overt neoplastic features. Over 40% of the patients would progress to EAC and thus the current recommendations would be to recommend BET in these patients.4
- Esophageal adenocarcinoma (EAC): Biopsies demonstrate neoplasia. If the neoplastic changes are limited to the mucosa (T1a) on endoscopic ultrasound or cross-sectional imaging, then BET is suggested. If there is involvement of submucosa, then depending on the depth of invasion, absence of high-risk features (poor differentiation, lymphovascular invasion), BET can be considered as an alternative to esophagectomy.
Lesion Detection on Endoscopy
Data from large population-based studies with at least 3 years of follow-up reported that 58%-66% of EAC detected during endoscopy were diagnosed within 1 year of an index Barrett’s esophagus screening endoscopy, or post-endoscopy Barrett’s neoplasia, and were considered likely to have been missed during index endoscopy.5 This underscores the importance of careful and systematic endoscopic examination during an upper endoscopy.
Studies have also demonstrated that longer examination time was associated with significantly higher detection of HGD/EAC.6,7 Careful examination of the tubular esophagus and gastroesophageal junction (GEJ) should be performed in forward and retroflexed views looking for any subtle areas of nodularity, loop distortion, variability in vascular patterns, mucosal changes concerning for dysplasia or neoplasia. Use of high-definition white light endoscopy (HD-WLE) and virtual chromoendoscopy techniques such as narrow banding imaging (NBI) or blue laser imaging (BLI) are currently recommended in the guidelines.2 Spray chromoendoscopy using acetic acid can also be utilized. Another exciting development is the use of artificial intelligence (AI) in detecting and diagnosing BE associated lesions and neoplasia.
Barrett’s Endoscopic Therapy (BET)
Patients with visible lesions, dysplasia, or early EAC are candidates for BET (Table 1). 
BET involves resective and ablative modalities. The resective modalities include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) and are the modalities of choice for nodular or raised lesions.
EMR involves endoscopic resection of abnormal mucosa using either lift-assisted technique or multi-band ligation (Figure 1). 
ESD, on the other hand, involves submucosal dissection and perimeter resection of the lesion, thus providing the advantage of an en-bloc resection. In a recent randomized controlled trial (RCT) of 40 patients undergoing ESD vs EMR for HGD/EAC, ESD was better for curative resection (R0) (58%) compared with EMR (12%); however, the remission rates at 3 months were comparable with two perforations reported in the ESD group while there were no complications in the EMR group.8
There is an apparent learning curve when it comes to these advanced techniques, and with more experience, we are seeing comparable results for both these modalities. However, given the complexity and time required for the procedure, current practices typically involve preserving ESD for lesions > 2 cm, those having a likelihood of cancer in the superficial submucosa, or those that EMR cannot remove due to underlying fibrosis or post-EMR recurrence.
The ablative modalities include radiofrequency ablation (RFA), cryotherapy, and hybrid argon plasma coagulation (hybrid APC). These modalities are used for flat lesions, and as therapy following endoscopic resection of nodular lesions to treat residual flat segment of BE. RFA, one of the earliest introduced endoscopic modalities, involves applying directed and controlled heat energy to ablate lesions. Current devices allow circumferential or focal application of RFA. It is a safe and effective modality with good complete eradication of IM (CE-IM) (71%-93%) and complete eradication of dysplasia (CE-D) (91%-100%) rates. These results have been sustained even at 2 years, with the most recent long-term data from a registry study showing a relapse rate of 6% for dysplasia and 19% for IM after 8 years, suggesting durability of this treatment.9
Cryotherapy involves the application of liquid nitrogen or rapidly expanding CO2 to the abnormal mucosa, leading to the rapid freezing and thawing that leads to the death of the cells. Cryogen can be applied as a spray or using a balloon with the spray nozzle in the center. This modality can be used to treat focal lesions and/or larger segments. While it has not been systematically compared with RFA, rates of CE-IM up to 81% and CE-D up to 97% are reported. Hybrid APC involves the use of submucosal saline injection to provide a protective cushion before APC is applied. It has CE-IM rate of 69% and CE-D rate of 67%-86%.10 In a recent RCT of 101 patients randomized to RFA or hybrid APC, CE-IM rates were similar (RFA:74.2% vs hAPC: 82.9%).11
Recently, another technique called radiofrequency vapor ablation (RFVA) is being evaluated, which involves ablating BE segment using vapor at 100° C generated with an RF electrode. A proof-of-concept study of 15 patients showed median squamous conversion of 55% (IQR 33-74) and 98% (IQR 56-99) for 1- and 3-second applications, respectively, with no reported adverse events.12
Barrett’s Refractory to Endoscopic Therapy
Failure of BET is defined as persistent columnar lined epithelium (intestinal metaplasia) with inadequate response, after adequate attempts at endoscopic ablation therapy (after resection) with at least four ablation sessions.13 If encountered, special attention must be given to check compliance with proton pump inhibitors (PPIs), previous incomplete resection, and presence of large hiatal hernia. If CE-IM is not achieved after multiple sessions, change of ablative modality is typically considered. In addition, careful examination for visible lesions should be performed and even if a small one is noted, this should be first resected prior to application of any ablative therapy.
Currently there are no guideline recommendations regarding the preference of one endoscopic modality over another or consideration of potential endoscopic or surgical fundoplication. These modalities primarily rely on technologies available at an institution and the preference of a provider based on their training and experience. Most studies indicate 1-3 sessions (~ 3 months apart) of ablative treatment before achieving CE-IM.
Success and Adverse Events of BET
In a recent real-world study of over 27,000 patients with dysplastic BE, 5295 underwent BET. Analysis showed that patients with HGD/EAC who had BET had a significantly lower 3-year mortality (HGD: RR, 0.59; 95%CI, 0.49-0.71; EAC: RR, 0.53; 95% CI, 0.44-0.65) compared with those who did not undergo BET. Esophageal strictures were the most common adverse event and were noted in 6.5%, followed by chest pain (1.8%), upper GI bleeding (0.47%), and esophageal perforation (0.2%).14
In general, adverse events can be divided into immediate and delayed adverse events. Immediate adverse events typically involve bleeding and perforation that can occur during or shortly after the procedure. These are reported at higher rates with resective modalities compared with ablative therapies. Standard endoscopic techniques involving coagulation grasper or clips can be used to achieve hemostasis. Endoscopic suturing devices offer the ability to contain any perforation. The need for surgical intervention is small and limited to adverse events not detected during the procedure.
Delayed adverse events such as stricture and stenosis are higher for resective modalities (up to 30%), especially when involving more significant than 75% of the esophageal circumference. Post-procedural pain/dysphagia is most common after ablative therapies. Dysphagia reported after any endoscopic therapy should be promptly evaluated, and sequential dilation until the goal esophageal lumen is achieved should be performed every 2-4 weeks.
Recurrences and Surveillance After BET
What is established is that recurrences can occur and may be subtle, therefore detailed endoscopic surveillance is required. In a prospective study, recurrence rates of 15%-16% for IM and 3%-5% for any dysplasia were reported, with the majority being in the first 2 years after achieving CE-IM.15 A systematic review of 21 studies looking at the location of recurrences suggested that the majority (56%) occur in the distal esophagus. Of those that occur in the esophagus, about 80% of them were in the distal 2 cm of the esophagus and only 50% of the recurrences were visible recurrences, thus reiterating the importance of meticulous examination and systematic biopsies.16
On the contrary, a recent single-center study of 217 patients who had achieved CE-IM with 5.5 years of follow-up demonstrated a 26% and 8% recurrence of IM and dysplasia, respectively. One hundred percent of the recurrence in the esophagus was reported as visible.17 Therefore, follow-up endoscopy surveillance protocol after CE-IM should still involve meticulous examination, biopsy of visible lesions, and systematic biopsies for non-visible lesions from the original BE segment, similar to those patients who have not needed BET.
Current guidelines based on expert consensus and evidence recommend surveillance after CE-IM based on original most advanced histology:2
1. LGD: 1 year, 3 years, and every 2 years after that.
2. HGD/EAC: 3 months, 6 months, 12 months, and annually after that.
There is no clear guideline on when to stop surveillance since the longest available follow-up is around 10 years, and recurrences are still detected. A potential surveillance endpoint may be based on age and comorbidities, especially those that would preclude a patient from being a candidate for BET.
When Should a Patient Be Referred?
BE patients with visible lesions and/or dysplastic changes in the biopsy who would require BET should be considered for referral to high-volume centers. Studies have shown higher success for CE-IM and lower rates of adverse events and recurrences in these patients managed at expert centers. The presence of a multidisciplinary team involving pathologists, surgeons, and oncologists is critical and offers a timely opportunity in case of need for a high-risk patient.
Conclusion
BE is a precursor to EAC, with rising incidence and poor 5-year survival. Endoscopic diagnosis is the gold standard and requires a high-quality examination and biopsies. Based on histopathology, a systematic surveillance and BET plan should be performed to achieve CE-IM in patients with dysplasia. Once CE-IM is achieved, regular surveillance should be performed with careful attention to recurrences and complications from the BET modalities.
Dr. Srinivasan and Dr. Sharma are based at the University of Kansas Medical Center, Kansas City, Kansas, and the Kansas City Veterans Affairs Medical Center, Kansas City, Missouri. Dr. Srinivasan has no relevant disclosures. Dr. Sharma disclosed research grants from ERBE, Ironwood Pharmaceuticals, Olympus, and Medtronic. He has served as a consultant for Takeda, Samsung Bioepis, Olympus, and Lumendi, and reports other funding from Medtronic, Fujifilm Medical Systems USA, and Salix.
References
1. Holmberg D, et al. Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease. Gastroenterology. 2022;162(2):431-438.e4.
2. Shaheen NJ, et al. Diagnosis and management of Barrett’s esophagus: An updated ACG guideline. Am J Gastroenterol. 2022 Apr;117(4):559-587.
3. Pech O, et al. Inter-observer variability in the diagnosis of low-grade dysplasia in pathologists: A comparison between experienced and inexperienced pathologists. Gastrointest Endosc. 2006 Apr;63(5):AB130.
4. Krishnamoorthi R, et al. Factors associated with progression of Barrett’s esophagus: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1046-1055.e8.
5. Visrodia K, et al. Magnitude of missed esophageal adenocarcinoma after Barrett’s esophagus diagnosis: A systematic review and meta-analysis. Gastroenterology. 2016 Mar;150(3):599-607.e7; quiz e14-5.
6. Perisetti A, Sharma P. Tips for improving the identification of neoplastic visible lesions in Barrett’s esophagus. Gastrointest Endosc. 2023 Feb;97(2):248-250.
7. Gupta N, et al. Longer inspection time is associated with increased detection of high-grade dysplasia and esophageal adenocarcinoma in Barrett’s esophagus. Gastrointest Endosc. 2012 Sep;76(3):531-538.
8. Terheggen G, et al. A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia. Gut. 2017 May;66(5):783-793.
9. Wolfson P, et al. Endoscopic eradication therapy for Barrett’s esophagus-related neoplasia: A final 10-year report from the UK National HALO Radiofrequency Ablation Registry. Gastrointest Endosc. 2022 Aug;96(2):223-233.
10. Rösch T, et al. 1151 Multicenter feasibility study of combined injection and argon plasma coagulation (hybrid-APC) in the ablation therapy of neoplastic Barrett esophagus. Gastrointest Endosc. 2017;85(5):AB154.
11. Knabe M, et al. Radiofrequency ablation versus hybrid argon plasma coagulation in Barrett’s esophagus: A prospective randomised trial. Surg Endosc. 2023;37(10):7803-7811.
12. Van Munster SN, et al. Radiofrequency vapor ablation for Barrett’s esophagus: Feasibility, safety, and proof of concept in a stepwise study with in vitro, animal, and the first in-human application. Endoscopy. 2021 Nov;53(11):1162-1168.
13. Emura F, et al. Rio de Janeiro global consensus on landmarks, definitions, and classifications in Barrett’s esophagus: World Endoscopy Organization Delphi study. Gastroenterology. 2022 Jul;163(1):84-96.e2.
14. Singh RR, et al. Real-world evidence of safety and effectiveness of Barrett’s endoscopic therapy. Gastrointest Endosc. 2023 Aug;98(2):155-161.e1.
15. Wani S, et al. Recurrence Is rare following complete eradication of intestinal metaplasia in patients with Barrett’s esophagus and peaks at 18 months. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2609-2617.e2.
16. Duvvuri A, et al. Mo1273 Location and pattern of recurrences in patients with Barrett’s esophagus after endoscopic therapy: A systematic review and critical analysis of the published literature. Gastrointest Endosc. 2020;91(6):AB410-1.
17. He T, et al. Location and appearance of dysplastic Barrett’s esophagus recurrence after endoscopic eradication therapy: No additional yield from random biopsy sampling neosquamous mucosa. Gastrointest Endosc. 2023 Nov;98(5):722-732.
Introduction
Barrett’s esophagus (BE) is characterized by the replacement of squamous epithelium by columnar metaplasia of the distal esophagus (>1 cm length). It is a precancerous condition, with 3%-5% of patients with BE developing esophageal adenocarcinoma (EAC) in their lifetime. EAC is one of the cancers with high morbidity and mortality (5-year survival < 20%), and its incidence has been on the rise. Studies examining the natural history of BE have demonstrated that the progression happens through a metaplasia-dysplasia-neoplasia sequence. Therefore, early detection of BE and timely management to prevent progression to EAC is crucial.
Grades of Dysplasia
The current gold standard for the diagnosis of BE neoplasia includes a high-quality endoscopic evaluation and biopsies. Biopsies should be obtained from any visible lesions (nodules, ulcers) followed by a random 4-quadrant fashion (Seattle protocol) interval of the entire length of the BE segment. It is essential to pay attention to the results of the biopsy that have been obtained since it will not only determine the surveillance interval but is crucial in planning any necessary endoscopic therapy. The possible results of the biopsy and its implications are:
- No intestinal metaplasia (IM): This would rule out Barrett’s esophagus and no further surveillance would be necessary. A recent population-based study of over 1 million patients showed a 55% and 61% reduced risk of upper gastrointestinal (UGI) cancer and deaths respectively after a negative endoscopy.1
- Intestinal metaplasia with no dysplasia (non-dysplastic BE): Biopsies confirm presence of intestinal metaplasia in the biopsies without any evidence of dysplasia. While the rate of progression to EAC is low (0.07%-0.25%), it is not absent and thus surveillance would be indicated. Current guidelines suggest repeating an endoscopy with biopsy in 5 years if the length of BE is < 3 cm or 3 years if length of BE ≥ 3 cm.2
- Indeterminate for dysplasia (BE-IND): Biopsies confirm IM but are not able to definitively rule out dysplasia. This can be seen in about 4%-8% of the biopsies obtained. The progression rates to EAC are reported to be comparable or lower to low-grade dysplasia (LGD), so the current recommendation is to intensify acid reduction therapy and repeat endoscopy in 6 months. If repeat endoscopy downgrades to non-dysplastic, then can follow surveillance according to NDBE protocol; otherwise recommend continuing surveillance every 12 months.
- Low-grade dysplasia (BE-LGD): Biopsies confirm IM but also show tightly packed overlapping basal nuclei with hyperchromasia and irregular contours, basal stratification of nuclei, and diminished goblet and columnar cell mucus. There is significant inter-observer variability reported,3 and thus the slides must be reviewed by a second pathologist with experience in BE to confirm the findings. Once confirmed, based on risk factors such as presence of multifocal LGD, persistence of LGD, presence of visible lesions, etc., the patient can be offered Barrett’s endoscopic therapy (BET) or undergo continued surveillance. The decision of pursuing one or the other would be dependent on patient preference and shared decision-making between the patient and the provider.
- High-grade dysplasia (BE-HGD): Biopsies confirm IM with cells showing greater degree of cytologic and architectural alterations of dysplasia than LGD but without overt neoplastic features. Over 40% of the patients would progress to EAC and thus the current recommendations would be to recommend BET in these patients.4
- Esophageal adenocarcinoma (EAC): Biopsies demonstrate neoplasia. If the neoplastic changes are limited to the mucosa (T1a) on endoscopic ultrasound or cross-sectional imaging, then BET is suggested. If there is involvement of submucosa, then depending on the depth of invasion, absence of high-risk features (poor differentiation, lymphovascular invasion), BET can be considered as an alternative to esophagectomy.
Lesion Detection on Endoscopy
Data from large population-based studies with at least 3 years of follow-up reported that 58%-66% of EAC detected during endoscopy were diagnosed within 1 year of an index Barrett’s esophagus screening endoscopy, or post-endoscopy Barrett’s neoplasia, and were considered likely to have been missed during index endoscopy.5 This underscores the importance of careful and systematic endoscopic examination during an upper endoscopy.
Studies have also demonstrated that longer examination time was associated with significantly higher detection of HGD/EAC.6,7 Careful examination of the tubular esophagus and gastroesophageal junction (GEJ) should be performed in forward and retroflexed views looking for any subtle areas of nodularity, loop distortion, variability in vascular patterns, mucosal changes concerning for dysplasia or neoplasia. Use of high-definition white light endoscopy (HD-WLE) and virtual chromoendoscopy techniques such as narrow banding imaging (NBI) or blue laser imaging (BLI) are currently recommended in the guidelines.2 Spray chromoendoscopy using acetic acid can also be utilized. Another exciting development is the use of artificial intelligence (AI) in detecting and diagnosing BE associated lesions and neoplasia.
Barrett’s Endoscopic Therapy (BET)
Patients with visible lesions, dysplasia, or early EAC are candidates for BET (Table 1).
BET involves resective and ablative modalities. The resective modalities include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) and are the modalities of choice for nodular or raised lesions.
EMR involves endoscopic resection of abnormal mucosa using either lift-assisted technique or multi-band ligation (Figure 1).
ESD, on the other hand, involves submucosal dissection and perimeter resection of the lesion, thus providing the advantage of an en-bloc resection. In a recent randomized controlled trial (RCT) of 40 patients undergoing ESD vs EMR for HGD/EAC, ESD was better for curative resection (R0) (58%) compared with EMR (12%); however, the remission rates at 3 months were comparable with two perforations reported in the ESD group while there were no complications in the EMR group.8
There is an apparent learning curve when it comes to these advanced techniques, and with more experience, we are seeing comparable results for both these modalities. However, given the complexity and time required for the procedure, current practices typically involve preserving ESD for lesions > 2 cm, those having a likelihood of cancer in the superficial submucosa, or those that EMR cannot remove due to underlying fibrosis or post-EMR recurrence.
The ablative modalities include radiofrequency ablation (RFA), cryotherapy, and hybrid argon plasma coagulation (hybrid APC). These modalities are used for flat lesions, and as therapy following endoscopic resection of nodular lesions to treat residual flat segment of BE. RFA, one of the earliest introduced endoscopic modalities, involves applying directed and controlled heat energy to ablate lesions. Current devices allow circumferential or focal application of RFA. It is a safe and effective modality with good complete eradication of IM (CE-IM) (71%-93%) and complete eradication of dysplasia (CE-D) (91%-100%) rates. These results have been sustained even at 2 years, with the most recent long-term data from a registry study showing a relapse rate of 6% for dysplasia and 19% for IM after 8 years, suggesting durability of this treatment.9
Cryotherapy involves the application of liquid nitrogen or rapidly expanding CO2 to the abnormal mucosa, leading to the rapid freezing and thawing that leads to the death of the cells. Cryogen can be applied as a spray or using a balloon with the spray nozzle in the center. This modality can be used to treat focal lesions and/or larger segments. While it has not been systematically compared with RFA, rates of CE-IM up to 81% and CE-D up to 97% are reported. Hybrid APC involves the use of submucosal saline injection to provide a protective cushion before APC is applied. It has CE-IM rate of 69% and CE-D rate of 67%-86%.10 In a recent RCT of 101 patients randomized to RFA or hybrid APC, CE-IM rates were similar (RFA:74.2% vs hAPC: 82.9%).11
Recently, another technique called radiofrequency vapor ablation (RFVA) is being evaluated, which involves ablating BE segment using vapor at 100° C generated with an RF electrode. A proof-of-concept study of 15 patients showed median squamous conversion of 55% (IQR 33-74) and 98% (IQR 56-99) for 1- and 3-second applications, respectively, with no reported adverse events.12
Barrett’s Refractory to Endoscopic Therapy
Failure of BET is defined as persistent columnar lined epithelium (intestinal metaplasia) with inadequate response, after adequate attempts at endoscopic ablation therapy (after resection) with at least four ablation sessions.13 If encountered, special attention must be given to check compliance with proton pump inhibitors (PPIs), previous incomplete resection, and presence of large hiatal hernia. If CE-IM is not achieved after multiple sessions, change of ablative modality is typically considered. In addition, careful examination for visible lesions should be performed and even if a small one is noted, this should be first resected prior to application of any ablative therapy.
Currently there are no guideline recommendations regarding the preference of one endoscopic modality over another or consideration of potential endoscopic or surgical fundoplication. These modalities primarily rely on technologies available at an institution and the preference of a provider based on their training and experience. Most studies indicate 1-3 sessions (~ 3 months apart) of ablative treatment before achieving CE-IM.
Success and Adverse Events of BET
In a recent real-world study of over 27,000 patients with dysplastic BE, 5295 underwent BET. Analysis showed that patients with HGD/EAC who had BET had a significantly lower 3-year mortality (HGD: RR, 0.59; 95%CI, 0.49-0.71; EAC: RR, 0.53; 95% CI, 0.44-0.65) compared with those who did not undergo BET. Esophageal strictures were the most common adverse event and were noted in 6.5%, followed by chest pain (1.8%), upper GI bleeding (0.47%), and esophageal perforation (0.2%).14
In general, adverse events can be divided into immediate and delayed adverse events. Immediate adverse events typically involve bleeding and perforation that can occur during or shortly after the procedure. These are reported at higher rates with resective modalities compared with ablative therapies. Standard endoscopic techniques involving coagulation grasper or clips can be used to achieve hemostasis. Endoscopic suturing devices offer the ability to contain any perforation. The need for surgical intervention is small and limited to adverse events not detected during the procedure.
Delayed adverse events such as stricture and stenosis are higher for resective modalities (up to 30%), especially when involving more significant than 75% of the esophageal circumference. Post-procedural pain/dysphagia is most common after ablative therapies. Dysphagia reported after any endoscopic therapy should be promptly evaluated, and sequential dilation until the goal esophageal lumen is achieved should be performed every 2-4 weeks.
Recurrences and Surveillance After BET
What is established is that recurrences can occur and may be subtle, therefore detailed endoscopic surveillance is required. In a prospective study, recurrence rates of 15%-16% for IM and 3%-5% for any dysplasia were reported, with the majority being in the first 2 years after achieving CE-IM.15 A systematic review of 21 studies looking at the location of recurrences suggested that the majority (56%) occur in the distal esophagus. Of those that occur in the esophagus, about 80% of them were in the distal 2 cm of the esophagus and only 50% of the recurrences were visible recurrences, thus reiterating the importance of meticulous examination and systematic biopsies.16
On the contrary, a recent single-center study of 217 patients who had achieved CE-IM with 5.5 years of follow-up demonstrated a 26% and 8% recurrence of IM and dysplasia, respectively. One hundred percent of the recurrence in the esophagus was reported as visible.17 Therefore, follow-up endoscopy surveillance protocol after CE-IM should still involve meticulous examination, biopsy of visible lesions, and systematic biopsies for non-visible lesions from the original BE segment, similar to those patients who have not needed BET.
Current guidelines based on expert consensus and evidence recommend surveillance after CE-IM based on original most advanced histology:2
1. LGD: 1 year, 3 years, and every 2 years after that.
2. HGD/EAC: 3 months, 6 months, 12 months, and annually after that.
There is no clear guideline on when to stop surveillance since the longest available follow-up is around 10 years, and recurrences are still detected. A potential surveillance endpoint may be based on age and comorbidities, especially those that would preclude a patient from being a candidate for BET.
When Should a Patient Be Referred?
BE patients with visible lesions and/or dysplastic changes in the biopsy who would require BET should be considered for referral to high-volume centers. Studies have shown higher success for CE-IM and lower rates of adverse events and recurrences in these patients managed at expert centers. The presence of a multidisciplinary team involving pathologists, surgeons, and oncologists is critical and offers a timely opportunity in case of need for a high-risk patient.
Conclusion
BE is a precursor to EAC, with rising incidence and poor 5-year survival. Endoscopic diagnosis is the gold standard and requires a high-quality examination and biopsies. Based on histopathology, a systematic surveillance and BET plan should be performed to achieve CE-IM in patients with dysplasia. Once CE-IM is achieved, regular surveillance should be performed with careful attention to recurrences and complications from the BET modalities.
Dr. Srinivasan and Dr. Sharma are based at the University of Kansas Medical Center, Kansas City, Kansas, and the Kansas City Veterans Affairs Medical Center, Kansas City, Missouri. Dr. Srinivasan has no relevant disclosures. Dr. Sharma disclosed research grants from ERBE, Ironwood Pharmaceuticals, Olympus, and Medtronic. He has served as a consultant for Takeda, Samsung Bioepis, Olympus, and Lumendi, and reports other funding from Medtronic, Fujifilm Medical Systems USA, and Salix.
References
1. Holmberg D, et al. Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease. Gastroenterology. 2022;162(2):431-438.e4.
2. Shaheen NJ, et al. Diagnosis and management of Barrett’s esophagus: An updated ACG guideline. Am J Gastroenterol. 2022 Apr;117(4):559-587.
3. Pech O, et al. Inter-observer variability in the diagnosis of low-grade dysplasia in pathologists: A comparison between experienced and inexperienced pathologists. Gastrointest Endosc. 2006 Apr;63(5):AB130.
4. Krishnamoorthi R, et al. Factors associated with progression of Barrett’s esophagus: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1046-1055.e8.
5. Visrodia K, et al. Magnitude of missed esophageal adenocarcinoma after Barrett’s esophagus diagnosis: A systematic review and meta-analysis. Gastroenterology. 2016 Mar;150(3):599-607.e7; quiz e14-5.
6. Perisetti A, Sharma P. Tips for improving the identification of neoplastic visible lesions in Barrett’s esophagus. Gastrointest Endosc. 2023 Feb;97(2):248-250.
7. Gupta N, et al. Longer inspection time is associated with increased detection of high-grade dysplasia and esophageal adenocarcinoma in Barrett’s esophagus. Gastrointest Endosc. 2012 Sep;76(3):531-538.
8. Terheggen G, et al. A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia. Gut. 2017 May;66(5):783-793.
9. Wolfson P, et al. Endoscopic eradication therapy for Barrett’s esophagus-related neoplasia: A final 10-year report from the UK National HALO Radiofrequency Ablation Registry. Gastrointest Endosc. 2022 Aug;96(2):223-233.
10. Rösch T, et al. 1151 Multicenter feasibility study of combined injection and argon plasma coagulation (hybrid-APC) in the ablation therapy of neoplastic Barrett esophagus. Gastrointest Endosc. 2017;85(5):AB154.
11. Knabe M, et al. Radiofrequency ablation versus hybrid argon plasma coagulation in Barrett’s esophagus: A prospective randomised trial. Surg Endosc. 2023;37(10):7803-7811.
12. Van Munster SN, et al. Radiofrequency vapor ablation for Barrett’s esophagus: Feasibility, safety, and proof of concept in a stepwise study with in vitro, animal, and the first in-human application. Endoscopy. 2021 Nov;53(11):1162-1168.
13. Emura F, et al. Rio de Janeiro global consensus on landmarks, definitions, and classifications in Barrett’s esophagus: World Endoscopy Organization Delphi study. Gastroenterology. 2022 Jul;163(1):84-96.e2.
14. Singh RR, et al. Real-world evidence of safety and effectiveness of Barrett’s endoscopic therapy. Gastrointest Endosc. 2023 Aug;98(2):155-161.e1.
15. Wani S, et al. Recurrence Is rare following complete eradication of intestinal metaplasia in patients with Barrett’s esophagus and peaks at 18 months. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2609-2617.e2.
16. Duvvuri A, et al. Mo1273 Location and pattern of recurrences in patients with Barrett’s esophagus after endoscopic therapy: A systematic review and critical analysis of the published literature. Gastrointest Endosc. 2020;91(6):AB410-1.
17. He T, et al. Location and appearance of dysplastic Barrett’s esophagus recurrence after endoscopic eradication therapy: No additional yield from random biopsy sampling neosquamous mucosa. Gastrointest Endosc. 2023 Nov;98(5):722-732.
Introduction
Barrett’s esophagus (BE) is characterized by the replacement of squamous epithelium by columnar metaplasia of the distal esophagus (>1 cm length). It is a precancerous condition, with 3%-5% of patients with BE developing esophageal adenocarcinoma (EAC) in their lifetime. EAC is one of the cancers with high morbidity and mortality (5-year survival < 20%), and its incidence has been on the rise. Studies examining the natural history of BE have demonstrated that the progression happens through a metaplasia-dysplasia-neoplasia sequence. Therefore, early detection of BE and timely management to prevent progression to EAC is crucial.
Grades of Dysplasia
The current gold standard for the diagnosis of BE neoplasia includes a high-quality endoscopic evaluation and biopsies. Biopsies should be obtained from any visible lesions (nodules, ulcers) followed by a random 4-quadrant fashion (Seattle protocol) interval of the entire length of the BE segment. It is essential to pay attention to the results of the biopsy that have been obtained since it will not only determine the surveillance interval but is crucial in planning any necessary endoscopic therapy. The possible results of the biopsy and its implications are:
- No intestinal metaplasia (IM): This would rule out Barrett’s esophagus and no further surveillance would be necessary. A recent population-based study of over 1 million patients showed a 55% and 61% reduced risk of upper gastrointestinal (UGI) cancer and deaths respectively after a negative endoscopy.1
- Intestinal metaplasia with no dysplasia (non-dysplastic BE): Biopsies confirm presence of intestinal metaplasia in the biopsies without any evidence of dysplasia. While the rate of progression to EAC is low (0.07%-0.25%), it is not absent and thus surveillance would be indicated. Current guidelines suggest repeating an endoscopy with biopsy in 5 years if the length of BE is < 3 cm or 3 years if length of BE ≥ 3 cm.2
- Indeterminate for dysplasia (BE-IND): Biopsies confirm IM but are not able to definitively rule out dysplasia. This can be seen in about 4%-8% of the biopsies obtained. The progression rates to EAC are reported to be comparable or lower to low-grade dysplasia (LGD), so the current recommendation is to intensify acid reduction therapy and repeat endoscopy in 6 months. If repeat endoscopy downgrades to non-dysplastic, then can follow surveillance according to NDBE protocol; otherwise recommend continuing surveillance every 12 months.
- Low-grade dysplasia (BE-LGD): Biopsies confirm IM but also show tightly packed overlapping basal nuclei with hyperchromasia and irregular contours, basal stratification of nuclei, and diminished goblet and columnar cell mucus. There is significant inter-observer variability reported,3 and thus the slides must be reviewed by a second pathologist with experience in BE to confirm the findings. Once confirmed, based on risk factors such as presence of multifocal LGD, persistence of LGD, presence of visible lesions, etc., the patient can be offered Barrett’s endoscopic therapy (BET) or undergo continued surveillance. The decision of pursuing one or the other would be dependent on patient preference and shared decision-making between the patient and the provider.
- High-grade dysplasia (BE-HGD): Biopsies confirm IM with cells showing greater degree of cytologic and architectural alterations of dysplasia than LGD but without overt neoplastic features. Over 40% of the patients would progress to EAC and thus the current recommendations would be to recommend BET in these patients.4
- Esophageal adenocarcinoma (EAC): Biopsies demonstrate neoplasia. If the neoplastic changes are limited to the mucosa (T1a) on endoscopic ultrasound or cross-sectional imaging, then BET is suggested. If there is involvement of submucosa, then depending on the depth of invasion, absence of high-risk features (poor differentiation, lymphovascular invasion), BET can be considered as an alternative to esophagectomy.
Lesion Detection on Endoscopy
Data from large population-based studies with at least 3 years of follow-up reported that 58%-66% of EAC detected during endoscopy were diagnosed within 1 year of an index Barrett’s esophagus screening endoscopy, or post-endoscopy Barrett’s neoplasia, and were considered likely to have been missed during index endoscopy.5 This underscores the importance of careful and systematic endoscopic examination during an upper endoscopy.
Studies have also demonstrated that longer examination time was associated with significantly higher detection of HGD/EAC.6,7 Careful examination of the tubular esophagus and gastroesophageal junction (GEJ) should be performed in forward and retroflexed views looking for any subtle areas of nodularity, loop distortion, variability in vascular patterns, mucosal changes concerning for dysplasia or neoplasia. Use of high-definition white light endoscopy (HD-WLE) and virtual chromoendoscopy techniques such as narrow banding imaging (NBI) or blue laser imaging (BLI) are currently recommended in the guidelines.2 Spray chromoendoscopy using acetic acid can also be utilized. Another exciting development is the use of artificial intelligence (AI) in detecting and diagnosing BE associated lesions and neoplasia.
Barrett’s Endoscopic Therapy (BET)
Patients with visible lesions, dysplasia, or early EAC are candidates for BET (Table 1).
BET involves resective and ablative modalities. The resective modalities include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) and are the modalities of choice for nodular or raised lesions.
EMR involves endoscopic resection of abnormal mucosa using either lift-assisted technique or multi-band ligation (Figure 1).
ESD, on the other hand, involves submucosal dissection and perimeter resection of the lesion, thus providing the advantage of an en-bloc resection. In a recent randomized controlled trial (RCT) of 40 patients undergoing ESD vs EMR for HGD/EAC, ESD was better for curative resection (R0) (58%) compared with EMR (12%); however, the remission rates at 3 months were comparable with two perforations reported in the ESD group while there were no complications in the EMR group.8
There is an apparent learning curve when it comes to these advanced techniques, and with more experience, we are seeing comparable results for both these modalities. However, given the complexity and time required for the procedure, current practices typically involve preserving ESD for lesions > 2 cm, those having a likelihood of cancer in the superficial submucosa, or those that EMR cannot remove due to underlying fibrosis or post-EMR recurrence.
The ablative modalities include radiofrequency ablation (RFA), cryotherapy, and hybrid argon plasma coagulation (hybrid APC). These modalities are used for flat lesions, and as therapy following endoscopic resection of nodular lesions to treat residual flat segment of BE. RFA, one of the earliest introduced endoscopic modalities, involves applying directed and controlled heat energy to ablate lesions. Current devices allow circumferential or focal application of RFA. It is a safe and effective modality with good complete eradication of IM (CE-IM) (71%-93%) and complete eradication of dysplasia (CE-D) (91%-100%) rates. These results have been sustained even at 2 years, with the most recent long-term data from a registry study showing a relapse rate of 6% for dysplasia and 19% for IM after 8 years, suggesting durability of this treatment.9
Cryotherapy involves the application of liquid nitrogen or rapidly expanding CO2 to the abnormal mucosa, leading to the rapid freezing and thawing that leads to the death of the cells. Cryogen can be applied as a spray or using a balloon with the spray nozzle in the center. This modality can be used to treat focal lesions and/or larger segments. While it has not been systematically compared with RFA, rates of CE-IM up to 81% and CE-D up to 97% are reported. Hybrid APC involves the use of submucosal saline injection to provide a protective cushion before APC is applied. It has CE-IM rate of 69% and CE-D rate of 67%-86%.10 In a recent RCT of 101 patients randomized to RFA or hybrid APC, CE-IM rates were similar (RFA:74.2% vs hAPC: 82.9%).11
Recently, another technique called radiofrequency vapor ablation (RFVA) is being evaluated, which involves ablating BE segment using vapor at 100° C generated with an RF electrode. A proof-of-concept study of 15 patients showed median squamous conversion of 55% (IQR 33-74) and 98% (IQR 56-99) for 1- and 3-second applications, respectively, with no reported adverse events.12
Barrett’s Refractory to Endoscopic Therapy
Failure of BET is defined as persistent columnar lined epithelium (intestinal metaplasia) with inadequate response, after adequate attempts at endoscopic ablation therapy (after resection) with at least four ablation sessions.13 If encountered, special attention must be given to check compliance with proton pump inhibitors (PPIs), previous incomplete resection, and presence of large hiatal hernia. If CE-IM is not achieved after multiple sessions, change of ablative modality is typically considered. In addition, careful examination for visible lesions should be performed and even if a small one is noted, this should be first resected prior to application of any ablative therapy.
Currently there are no guideline recommendations regarding the preference of one endoscopic modality over another or consideration of potential endoscopic or surgical fundoplication. These modalities primarily rely on technologies available at an institution and the preference of a provider based on their training and experience. Most studies indicate 1-3 sessions (~ 3 months apart) of ablative treatment before achieving CE-IM.
Success and Adverse Events of BET
In a recent real-world study of over 27,000 patients with dysplastic BE, 5295 underwent BET. Analysis showed that patients with HGD/EAC who had BET had a significantly lower 3-year mortality (HGD: RR, 0.59; 95%CI, 0.49-0.71; EAC: RR, 0.53; 95% CI, 0.44-0.65) compared with those who did not undergo BET. Esophageal strictures were the most common adverse event and were noted in 6.5%, followed by chest pain (1.8%), upper GI bleeding (0.47%), and esophageal perforation (0.2%).14
In general, adverse events can be divided into immediate and delayed adverse events. Immediate adverse events typically involve bleeding and perforation that can occur during or shortly after the procedure. These are reported at higher rates with resective modalities compared with ablative therapies. Standard endoscopic techniques involving coagulation grasper or clips can be used to achieve hemostasis. Endoscopic suturing devices offer the ability to contain any perforation. The need for surgical intervention is small and limited to adverse events not detected during the procedure.
Delayed adverse events such as stricture and stenosis are higher for resective modalities (up to 30%), especially when involving more significant than 75% of the esophageal circumference. Post-procedural pain/dysphagia is most common after ablative therapies. Dysphagia reported after any endoscopic therapy should be promptly evaluated, and sequential dilation until the goal esophageal lumen is achieved should be performed every 2-4 weeks.
Recurrences and Surveillance After BET
What is established is that recurrences can occur and may be subtle, therefore detailed endoscopic surveillance is required. In a prospective study, recurrence rates of 15%-16% for IM and 3%-5% for any dysplasia were reported, with the majority being in the first 2 years after achieving CE-IM.15 A systematic review of 21 studies looking at the location of recurrences suggested that the majority (56%) occur in the distal esophagus. Of those that occur in the esophagus, about 80% of them were in the distal 2 cm of the esophagus and only 50% of the recurrences were visible recurrences, thus reiterating the importance of meticulous examination and systematic biopsies.16
On the contrary, a recent single-center study of 217 patients who had achieved CE-IM with 5.5 years of follow-up demonstrated a 26% and 8% recurrence of IM and dysplasia, respectively. One hundred percent of the recurrence in the esophagus was reported as visible.17 Therefore, follow-up endoscopy surveillance protocol after CE-IM should still involve meticulous examination, biopsy of visible lesions, and systematic biopsies for non-visible lesions from the original BE segment, similar to those patients who have not needed BET.
Current guidelines based on expert consensus and evidence recommend surveillance after CE-IM based on original most advanced histology:2
1. LGD: 1 year, 3 years, and every 2 years after that.
2. HGD/EAC: 3 months, 6 months, 12 months, and annually after that.
There is no clear guideline on when to stop surveillance since the longest available follow-up is around 10 years, and recurrences are still detected. A potential surveillance endpoint may be based on age and comorbidities, especially those that would preclude a patient from being a candidate for BET.
When Should a Patient Be Referred?
BE patients with visible lesions and/or dysplastic changes in the biopsy who would require BET should be considered for referral to high-volume centers. Studies have shown higher success for CE-IM and lower rates of adverse events and recurrences in these patients managed at expert centers. The presence of a multidisciplinary team involving pathologists, surgeons, and oncologists is critical and offers a timely opportunity in case of need for a high-risk patient.
Conclusion
BE is a precursor to EAC, with rising incidence and poor 5-year survival. Endoscopic diagnosis is the gold standard and requires a high-quality examination and biopsies. Based on histopathology, a systematic surveillance and BET plan should be performed to achieve CE-IM in patients with dysplasia. Once CE-IM is achieved, regular surveillance should be performed with careful attention to recurrences and complications from the BET modalities.
Dr. Srinivasan and Dr. Sharma are based at the University of Kansas Medical Center, Kansas City, Kansas, and the Kansas City Veterans Affairs Medical Center, Kansas City, Missouri. Dr. Srinivasan has no relevant disclosures. Dr. Sharma disclosed research grants from ERBE, Ironwood Pharmaceuticals, Olympus, and Medtronic. He has served as a consultant for Takeda, Samsung Bioepis, Olympus, and Lumendi, and reports other funding from Medtronic, Fujifilm Medical Systems USA, and Salix.
References
1. Holmberg D, et al. Incidence and mortality in upper gastrointestinal cancer after negative endoscopy for gastroesophageal reflux disease. Gastroenterology. 2022;162(2):431-438.e4.
2. Shaheen NJ, et al. Diagnosis and management of Barrett’s esophagus: An updated ACG guideline. Am J Gastroenterol. 2022 Apr;117(4):559-587.
3. Pech O, et al. Inter-observer variability in the diagnosis of low-grade dysplasia in pathologists: A comparison between experienced and inexperienced pathologists. Gastrointest Endosc. 2006 Apr;63(5):AB130.
4. Krishnamoorthi R, et al. Factors associated with progression of Barrett’s esophagus: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1046-1055.e8.
5. Visrodia K, et al. Magnitude of missed esophageal adenocarcinoma after Barrett’s esophagus diagnosis: A systematic review and meta-analysis. Gastroenterology. 2016 Mar;150(3):599-607.e7; quiz e14-5.
6. Perisetti A, Sharma P. Tips for improving the identification of neoplastic visible lesions in Barrett’s esophagus. Gastrointest Endosc. 2023 Feb;97(2):248-250.
7. Gupta N, et al. Longer inspection time is associated with increased detection of high-grade dysplasia and esophageal adenocarcinoma in Barrett’s esophagus. Gastrointest Endosc. 2012 Sep;76(3):531-538.
8. Terheggen G, et al. A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia. Gut. 2017 May;66(5):783-793.
9. Wolfson P, et al. Endoscopic eradication therapy for Barrett’s esophagus-related neoplasia: A final 10-year report from the UK National HALO Radiofrequency Ablation Registry. Gastrointest Endosc. 2022 Aug;96(2):223-233.
10. Rösch T, et al. 1151 Multicenter feasibility study of combined injection and argon plasma coagulation (hybrid-APC) in the ablation therapy of neoplastic Barrett esophagus. Gastrointest Endosc. 2017;85(5):AB154.
11. Knabe M, et al. Radiofrequency ablation versus hybrid argon plasma coagulation in Barrett’s esophagus: A prospective randomised trial. Surg Endosc. 2023;37(10):7803-7811.
12. Van Munster SN, et al. Radiofrequency vapor ablation for Barrett’s esophagus: Feasibility, safety, and proof of concept in a stepwise study with in vitro, animal, and the first in-human application. Endoscopy. 2021 Nov;53(11):1162-1168.
13. Emura F, et al. Rio de Janeiro global consensus on landmarks, definitions, and classifications in Barrett’s esophagus: World Endoscopy Organization Delphi study. Gastroenterology. 2022 Jul;163(1):84-96.e2.
14. Singh RR, et al. Real-world evidence of safety and effectiveness of Barrett’s endoscopic therapy. Gastrointest Endosc. 2023 Aug;98(2):155-161.e1.
15. Wani S, et al. Recurrence Is rare following complete eradication of intestinal metaplasia in patients with Barrett’s esophagus and peaks at 18 months. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2609-2617.e2.
16. Duvvuri A, et al. Mo1273 Location and pattern of recurrences in patients with Barrett’s esophagus after endoscopic therapy: A systematic review and critical analysis of the published literature. Gastrointest Endosc. 2020;91(6):AB410-1.
17. He T, et al. Location and appearance of dysplastic Barrett’s esophagus recurrence after endoscopic eradication therapy: No additional yield from random biopsy sampling neosquamous mucosa. Gastrointest Endosc. 2023 Nov;98(5):722-732.