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Barrett’s Esophagus: No Survival Difference Between Regular and At-Need Surveillance
SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?
Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.
, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week® (DDW) 2025.
At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.
The BOSS Trial
The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.
Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.
The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.
Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.
Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.
“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.
Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.
The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.
Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.
Will BOSS Change Minds?
Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.
However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”
The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.
Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”
Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.
Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.
While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”
The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?
Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.
, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week® (DDW) 2025.
At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.
The BOSS Trial
The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.
Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.
The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.
Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.
Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.
“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.
Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.
The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.
Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.
Will BOSS Change Minds?
Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.
However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”
The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.
Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”
Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.
Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.
While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”
The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?
Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.
, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week® (DDW) 2025.
At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.
The BOSS Trial
The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.
Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.
The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.
Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.
Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.
“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.
Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.
The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.
Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.
Will BOSS Change Minds?
Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.
However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”
The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.
Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”
Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.
Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.
While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”
The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Post-Polypectomy Colorectal Cancers Common Before Follow-Up
SAN DIEGO — , according to new research.
Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.
“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.
“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”
Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.
“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.
In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.
The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.
Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).
Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.
Colonoscopist Skill and Benchmarks
A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).
Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).
“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.
“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.
The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.
They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.
And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”
Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.
She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).
“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”
Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.
Patient Compliance Can’t Be Counted On
In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.
“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.
One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.
This underscores the need for better prevention as well as follow-up strategies, he added.
Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.
A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.
While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.
Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.
The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.
Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.
FIT Tests Potentially a ‘Major Advantage’
“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.
“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.
More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.
“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.
Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”
Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.
“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.
“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”
Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.
“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.
In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.
The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.
Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).
Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.
Colonoscopist Skill and Benchmarks
A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).
Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).
“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.
“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.
The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.
They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.
And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”
Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.
She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).
“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”
Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.
Patient Compliance Can’t Be Counted On
In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.
“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.
One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.
This underscores the need for better prevention as well as follow-up strategies, he added.
Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.
A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.
While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.
Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.
The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.
Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.
FIT Tests Potentially a ‘Major Advantage’
“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.
“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.
More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.
“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.
Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”
Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.
“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.
“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”
Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.
“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.
In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.
The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.
Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).
Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.
Colonoscopist Skill and Benchmarks
A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).
Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).
“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.
“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.
The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.
They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.
And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”
Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.
She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).
“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”
Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.
Patient Compliance Can’t Be Counted On
In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.
“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.
One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.
This underscores the need for better prevention as well as follow-up strategies, he added.
Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.
A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.
While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.
Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.
The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.
Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.
FIT Tests Potentially a ‘Major Advantage’
“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.
“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.
More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.
“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.
Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”
Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Train Advanced Practice Providers in Transnasal Endoscopy?
SAN DIEGO – , a pilot study showed.
“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.
“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.
The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.
The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.
Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.
Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.
TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).
Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.
Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.
Technical success was achieved in all but one patient (96%), and there were no adverse events.
All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.
The average TNE procedure time was 7.3 minutes.
TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.
The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.
“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.
Caveats and Cautionary Notes
Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”
Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.
“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.
“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.
The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.
A version of this article appeared on Medscape.com.
SAN DIEGO – , a pilot study showed.
“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.
“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.
The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.
The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.
Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.
Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.
TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).
Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.
Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.
Technical success was achieved in all but one patient (96%), and there were no adverse events.
All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.
The average TNE procedure time was 7.3 minutes.
TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.
The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.
“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.
Caveats and Cautionary Notes
Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”
Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.
“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.
“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.
The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.
A version of this article appeared on Medscape.com.
SAN DIEGO – , a pilot study showed.
“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.
“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.
The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.
The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.
Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.
Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.
TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).
Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.
Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.
Technical success was achieved in all but one patient (96%), and there were no adverse events.
All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.
The average TNE procedure time was 7.3 minutes.
TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.
The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.
“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.
Caveats and Cautionary Notes
Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”
Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.
“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.
“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.
The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.
A version of this article appeared on Medscape.com.
Precision-Medicine Approach Improves IBD Infliximab Outcomes
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Once-Monthly Efimosfermin Leads to Significant MASH Improvement in Phase 2 Trial
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Endoscopic Procedure Shows Promise in Type 2 Diabetes Care
SAN DIEGO – .
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. “The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,” said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. “It’s nonthermal regeneration, not just ablation. It’s regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,” Abu Dayyeh told GI & Hepatology News.
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities “diabetic duodenopathy.”
Abu Dayyeh likened the duodenum to a “conductor” of the “dysfunctional orchestra” of metabolic disease that includes T2D. “It’s tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.”
Currently, he said, “We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there’s an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.”
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won’t replace medications. “On the contrary, I see it as enhancing and complementing medications,” he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, told GI & Hepatology News, “Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn’t explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.”
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, “The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.”
In fact, such a study is underway. Results of “a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)” are expected in late 2026.
In the meantime, Amanian said about the current findings, “I’d argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.”
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, “the vision of this is to be a 20-minute outpatient procedure eventually,” Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. “They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.”
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.
A version of this article appeared on Medscape.com.
SAN DIEGO – .
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. “The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,” said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. “It’s nonthermal regeneration, not just ablation. It’s regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,” Abu Dayyeh told GI & Hepatology News.
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities “diabetic duodenopathy.”
Abu Dayyeh likened the duodenum to a “conductor” of the “dysfunctional orchestra” of metabolic disease that includes T2D. “It’s tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.”
Currently, he said, “We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there’s an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.”
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won’t replace medications. “On the contrary, I see it as enhancing and complementing medications,” he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, told GI & Hepatology News, “Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn’t explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.”
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, “The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.”
In fact, such a study is underway. Results of “a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)” are expected in late 2026.
In the meantime, Amanian said about the current findings, “I’d argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.”
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, “the vision of this is to be a 20-minute outpatient procedure eventually,” Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. “They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.”
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.
A version of this article appeared on Medscape.com.
SAN DIEGO – .
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. “The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,” said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. “It’s nonthermal regeneration, not just ablation. It’s regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,” Abu Dayyeh told GI & Hepatology News.
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities “diabetic duodenopathy.”
Abu Dayyeh likened the duodenum to a “conductor” of the “dysfunctional orchestra” of metabolic disease that includes T2D. “It’s tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.”
Currently, he said, “We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there’s an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.”
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won’t replace medications. “On the contrary, I see it as enhancing and complementing medications,” he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, told GI & Hepatology News, “Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn’t explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.”
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, “The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.”
In fact, such a study is underway. Results of “a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)” are expected in late 2026.
In the meantime, Amanian said about the current findings, “I’d argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.”
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, “the vision of this is to be a 20-minute outpatient procedure eventually,” Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. “They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.”
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Papilla Sphincterotomy Shows No Risk Reduction in Pancreas Divisum
SAN DIEGO — , suggesting that patients can be spared the intervention, which can carry risks of its own.
“This is a topic that has been debated for decades,” said first author Gregory A. Coté, MD, AGAF, Division Head, professor of medicine, Division of Gastroenterology & Hepatology, Oregon Health & Science University, in Portland, Oregon.
“Many doctors believe the procedure helps and offer it because we have limited options to help our patients, whereas others believe the procedure is harmful and doesn’t help,” he explained in a press briefing for the late-breaking study, presented at Digestive Disease Week (DDW) 2025.
The study’s findings supported the latter argument.
“Patients who underwent ERCP with sphincterotomy were just as likely as those who did not have this procedure to develop acute pancreatitis again,” Coté reported.
While clinical guidelines currently recommend ERCP as treatment for pancreas divisum, “these guidelines are likely to change based on this study,” he said.
Pancreas divisum, occurring in about 7%-10% of people, is an anatomic variation that can represent an obstructive risk factor for acute recurrent pancreatitis.
The common use of ERCP with minor papilla endoscopic sphincterotomy to treat the condition is based on prior retrospective studies showing that in patients who did develop acute pancreatitis, up to 70% with the treatment never developed acute pancreatitis again. However, there have been no studies comparing the use of the treatment with a control group.
Coté and colleagues conducted the multicenter SHARP trial, in which 148 patients with pancreas divisum were enrolled between September 2018 and August 2024 and randomized to receive either ERCP with minor papilla endoscopic sphincterotomy (n = 75) or a sham treatment (n = 73).
The patients, who had a median age of 51 years, had a median of 3 acute pancreatitis episodes prior to randomization.
With a median follow-up of 33.5 months (range, 6-48 months), 34.7% of patients in the ERCP arm experienced an acute pancreatitis incident compared with 43.8% in the sham arm, for a hazard ratio of 0.83 after adjusting for duct size and the number of episodes, which was not a statistically significant difference (P = .27).
A subgroup analysis further showed no indication of a treatment effect based on factors including age, diabetes status, sex, alcohol or tobacco use, or other factors.
“Compared with a sham ERCP group, we found that minor papillotomy did not reduce the risk of acute pancreatitis, incident chronic pancreatitis, endocrine pancreatic insufficiency or diabetes, or pancreas-related pain events,” Coté said.
The findings are particularly important because the treatment itself is associated with some risks, he added.
“Ironically, the problem with this procedure is that it can cause acute pancreatitis in 10%-20% of patients and may instigate other issues later,” such as the development of scarring of the pancreas related to incisions in the procedure.
“No one wants to offer an expensive procedure that has its own risks if it doesn’t help,” Coté said.
Based on the findings, “pancreas divisum anatomy should no longer be considered an indication for ERCP, even for idiopathic acute pancreatitis,” he concluded.
A version of this article appeared on Medscape.com.
SAN DIEGO — , suggesting that patients can be spared the intervention, which can carry risks of its own.
“This is a topic that has been debated for decades,” said first author Gregory A. Coté, MD, AGAF, Division Head, professor of medicine, Division of Gastroenterology & Hepatology, Oregon Health & Science University, in Portland, Oregon.
“Many doctors believe the procedure helps and offer it because we have limited options to help our patients, whereas others believe the procedure is harmful and doesn’t help,” he explained in a press briefing for the late-breaking study, presented at Digestive Disease Week (DDW) 2025.
The study’s findings supported the latter argument.
“Patients who underwent ERCP with sphincterotomy were just as likely as those who did not have this procedure to develop acute pancreatitis again,” Coté reported.
While clinical guidelines currently recommend ERCP as treatment for pancreas divisum, “these guidelines are likely to change based on this study,” he said.
Pancreas divisum, occurring in about 7%-10% of people, is an anatomic variation that can represent an obstructive risk factor for acute recurrent pancreatitis.
The common use of ERCP with minor papilla endoscopic sphincterotomy to treat the condition is based on prior retrospective studies showing that in patients who did develop acute pancreatitis, up to 70% with the treatment never developed acute pancreatitis again. However, there have been no studies comparing the use of the treatment with a control group.
Coté and colleagues conducted the multicenter SHARP trial, in which 148 patients with pancreas divisum were enrolled between September 2018 and August 2024 and randomized to receive either ERCP with minor papilla endoscopic sphincterotomy (n = 75) or a sham treatment (n = 73).
The patients, who had a median age of 51 years, had a median of 3 acute pancreatitis episodes prior to randomization.
With a median follow-up of 33.5 months (range, 6-48 months), 34.7% of patients in the ERCP arm experienced an acute pancreatitis incident compared with 43.8% in the sham arm, for a hazard ratio of 0.83 after adjusting for duct size and the number of episodes, which was not a statistically significant difference (P = .27).
A subgroup analysis further showed no indication of a treatment effect based on factors including age, diabetes status, sex, alcohol or tobacco use, or other factors.
“Compared with a sham ERCP group, we found that minor papillotomy did not reduce the risk of acute pancreatitis, incident chronic pancreatitis, endocrine pancreatic insufficiency or diabetes, or pancreas-related pain events,” Coté said.
The findings are particularly important because the treatment itself is associated with some risks, he added.
“Ironically, the problem with this procedure is that it can cause acute pancreatitis in 10%-20% of patients and may instigate other issues later,” such as the development of scarring of the pancreas related to incisions in the procedure.
“No one wants to offer an expensive procedure that has its own risks if it doesn’t help,” Coté said.
Based on the findings, “pancreas divisum anatomy should no longer be considered an indication for ERCP, even for idiopathic acute pancreatitis,” he concluded.
A version of this article appeared on Medscape.com.
SAN DIEGO — , suggesting that patients can be spared the intervention, which can carry risks of its own.
“This is a topic that has been debated for decades,” said first author Gregory A. Coté, MD, AGAF, Division Head, professor of medicine, Division of Gastroenterology & Hepatology, Oregon Health & Science University, in Portland, Oregon.
“Many doctors believe the procedure helps and offer it because we have limited options to help our patients, whereas others believe the procedure is harmful and doesn’t help,” he explained in a press briefing for the late-breaking study, presented at Digestive Disease Week (DDW) 2025.
The study’s findings supported the latter argument.
“Patients who underwent ERCP with sphincterotomy were just as likely as those who did not have this procedure to develop acute pancreatitis again,” Coté reported.
While clinical guidelines currently recommend ERCP as treatment for pancreas divisum, “these guidelines are likely to change based on this study,” he said.
Pancreas divisum, occurring in about 7%-10% of people, is an anatomic variation that can represent an obstructive risk factor for acute recurrent pancreatitis.
The common use of ERCP with minor papilla endoscopic sphincterotomy to treat the condition is based on prior retrospective studies showing that in patients who did develop acute pancreatitis, up to 70% with the treatment never developed acute pancreatitis again. However, there have been no studies comparing the use of the treatment with a control group.
Coté and colleagues conducted the multicenter SHARP trial, in which 148 patients with pancreas divisum were enrolled between September 2018 and August 2024 and randomized to receive either ERCP with minor papilla endoscopic sphincterotomy (n = 75) or a sham treatment (n = 73).
The patients, who had a median age of 51 years, had a median of 3 acute pancreatitis episodes prior to randomization.
With a median follow-up of 33.5 months (range, 6-48 months), 34.7% of patients in the ERCP arm experienced an acute pancreatitis incident compared with 43.8% in the sham arm, for a hazard ratio of 0.83 after adjusting for duct size and the number of episodes, which was not a statistically significant difference (P = .27).
A subgroup analysis further showed no indication of a treatment effect based on factors including age, diabetes status, sex, alcohol or tobacco use, or other factors.
“Compared with a sham ERCP group, we found that minor papillotomy did not reduce the risk of acute pancreatitis, incident chronic pancreatitis, endocrine pancreatic insufficiency or diabetes, or pancreas-related pain events,” Coté said.
The findings are particularly important because the treatment itself is associated with some risks, he added.
“Ironically, the problem with this procedure is that it can cause acute pancreatitis in 10%-20% of patients and may instigate other issues later,” such as the development of scarring of the pancreas related to incisions in the procedure.
“No one wants to offer an expensive procedure that has its own risks if it doesn’t help,” Coté said.
Based on the findings, “pancreas divisum anatomy should no longer be considered an indication for ERCP, even for idiopathic acute pancreatitis,” he concluded.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Weekend Workout, Regular Exercise Are Equals at Lowering GI Disease Risk
SAN DIEGO — The session started with a question that many in the audience at Digestive Disease Week (DDW) 2025 seemed to relate to: “How many of you find yourself squeezing workouts into a weekend after a hectic work week?”
Although regular exercise three or more times a week is often viewed as preferable, Shiyi Yu, MD, a resident physician in the Department of Gastroenterology at Guangdong Provincial People’s Hospital in Guangzhou, China, had good news for weekend warriors.
Both patterns reduce digestive disease almost equally.
Her study compared weekend warriors with those she called “active regulars” and sedentary folks to see how activity patterns affect digestive disease risks.
Her bottom line: “Your gut does not care about your schedule.”
The researchers analyzed wrist-based accelerometer data from 89,595 participants in the UK Biobank. To categorize participants as active or inactive, they used the World Health Organization 2020 guidelines for physical activity, which recommend at least 150-300 minutes of moderate-intensity aerobic physical activity or at least 75-150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination throughout the week. Median age of participants was 63.3 years and 48.8% were men.
They divided participants into three groups:
- About 43% were weekend warriors who met or exceeded 150 minutes of moderate to vigorous physical activity (MVPA), with 50% or more of total MVPA achieved in 1-2 days.
- About 23% were active regulars who met or exceeded 150 minutes a week but spread over more days.
- About 34% were inactive participants who were active less than 150 minutes a week.
The researchers followed the participants for a median of 7.9 years, looking for the incidence of multiple digestive diseases, identified using the International Classification of Diseases, 10th Revision, codes. These included diverticulosis, constipation, metabolic dysfunction–associated steatotic liver disease, cholelithiasis, and gastroesophageal reflux disease.
,” Yu said. At the threshold ≥ 150 minutes, for instance, hazard ratios for any digestive disease were 0.83 for weekend warriors and 0.79 for active regulars, compared with sedentary participants.
The analysis was repeated using a median threshold ≥ 230.4 minutes of MVPA a week, and the researchers found the same results.
As a validation cohort, the researchers used more than 6,000 participants from the National Institutes of Health’s All of Us Research Program with over 6 months of wrist-based accelerometer data.
A recent meta-epidemiology study found that the weekend warrior pattern offers other health benefits, including reducing the risk for cardiovascular disease mortality, mental disorders, and metabolic syndrome.
A Pleasant Surprise
The digestive disease study’s findings were “a surprise and a pleasant one,” said Aasma Shaukat, MD, MPH, AGAF, professor of medicine and a gastroenterologist at NYU Grossman School of Medicine, New York City.
“We often think if we’re not able to exercise regularly, then there’s no hope for us,” said Shaukat, who moderated the session. “But this implies that even if we have time only during the weekend to engage in physical activity, it still confers benefits in reducing our risk of any GI health disorder, as well as cardiovascular or other health disorders, compared to people inactive at baseline.”
“It gives us flexibility in terms of how we structure our exercise. Obviously, people should try to get into the habit of doing regular activity; it’s more sustainable. But a good alternative, according to this research, is that packing all of that in over the weekend seems to confer benefit. So all is not lost.”
Will this change her conversation with patients moving forward? Absolutely, Shaukat said. She generally recommends physical activity for at least 30 minutes three times a week. Now Shaukat said she can tell patients: “If that’s not possible, take that time out during the weekend for your health”.
This study was funded by grants from the National Natural Science Foundation of China and its Regional Innovation and Development Joint Foundation. Yu and Shaukat reported no disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — The session started with a question that many in the audience at Digestive Disease Week (DDW) 2025 seemed to relate to: “How many of you find yourself squeezing workouts into a weekend after a hectic work week?”
Although regular exercise three or more times a week is often viewed as preferable, Shiyi Yu, MD, a resident physician in the Department of Gastroenterology at Guangdong Provincial People’s Hospital in Guangzhou, China, had good news for weekend warriors.
Both patterns reduce digestive disease almost equally.
Her study compared weekend warriors with those she called “active regulars” and sedentary folks to see how activity patterns affect digestive disease risks.
Her bottom line: “Your gut does not care about your schedule.”
The researchers analyzed wrist-based accelerometer data from 89,595 participants in the UK Biobank. To categorize participants as active or inactive, they used the World Health Organization 2020 guidelines for physical activity, which recommend at least 150-300 minutes of moderate-intensity aerobic physical activity or at least 75-150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination throughout the week. Median age of participants was 63.3 years and 48.8% were men.
They divided participants into three groups:
- About 43% were weekend warriors who met or exceeded 150 minutes of moderate to vigorous physical activity (MVPA), with 50% or more of total MVPA achieved in 1-2 days.
- About 23% were active regulars who met or exceeded 150 minutes a week but spread over more days.
- About 34% were inactive participants who were active less than 150 minutes a week.
The researchers followed the participants for a median of 7.9 years, looking for the incidence of multiple digestive diseases, identified using the International Classification of Diseases, 10th Revision, codes. These included diverticulosis, constipation, metabolic dysfunction–associated steatotic liver disease, cholelithiasis, and gastroesophageal reflux disease.
,” Yu said. At the threshold ≥ 150 minutes, for instance, hazard ratios for any digestive disease were 0.83 for weekend warriors and 0.79 for active regulars, compared with sedentary participants.
The analysis was repeated using a median threshold ≥ 230.4 minutes of MVPA a week, and the researchers found the same results.
As a validation cohort, the researchers used more than 6,000 participants from the National Institutes of Health’s All of Us Research Program with over 6 months of wrist-based accelerometer data.
A recent meta-epidemiology study found that the weekend warrior pattern offers other health benefits, including reducing the risk for cardiovascular disease mortality, mental disorders, and metabolic syndrome.
A Pleasant Surprise
The digestive disease study’s findings were “a surprise and a pleasant one,” said Aasma Shaukat, MD, MPH, AGAF, professor of medicine and a gastroenterologist at NYU Grossman School of Medicine, New York City.
“We often think if we’re not able to exercise regularly, then there’s no hope for us,” said Shaukat, who moderated the session. “But this implies that even if we have time only during the weekend to engage in physical activity, it still confers benefits in reducing our risk of any GI health disorder, as well as cardiovascular or other health disorders, compared to people inactive at baseline.”
“It gives us flexibility in terms of how we structure our exercise. Obviously, people should try to get into the habit of doing regular activity; it’s more sustainable. But a good alternative, according to this research, is that packing all of that in over the weekend seems to confer benefit. So all is not lost.”
Will this change her conversation with patients moving forward? Absolutely, Shaukat said. She generally recommends physical activity for at least 30 minutes three times a week. Now Shaukat said she can tell patients: “If that’s not possible, take that time out during the weekend for your health”.
This study was funded by grants from the National Natural Science Foundation of China and its Regional Innovation and Development Joint Foundation. Yu and Shaukat reported no disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO — The session started with a question that many in the audience at Digestive Disease Week (DDW) 2025 seemed to relate to: “How many of you find yourself squeezing workouts into a weekend after a hectic work week?”
Although regular exercise three or more times a week is often viewed as preferable, Shiyi Yu, MD, a resident physician in the Department of Gastroenterology at Guangdong Provincial People’s Hospital in Guangzhou, China, had good news for weekend warriors.
Both patterns reduce digestive disease almost equally.
Her study compared weekend warriors with those she called “active regulars” and sedentary folks to see how activity patterns affect digestive disease risks.
Her bottom line: “Your gut does not care about your schedule.”
The researchers analyzed wrist-based accelerometer data from 89,595 participants in the UK Biobank. To categorize participants as active or inactive, they used the World Health Organization 2020 guidelines for physical activity, which recommend at least 150-300 minutes of moderate-intensity aerobic physical activity or at least 75-150 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination throughout the week. Median age of participants was 63.3 years and 48.8% were men.
They divided participants into three groups:
- About 43% were weekend warriors who met or exceeded 150 minutes of moderate to vigorous physical activity (MVPA), with 50% or more of total MVPA achieved in 1-2 days.
- About 23% were active regulars who met or exceeded 150 minutes a week but spread over more days.
- About 34% were inactive participants who were active less than 150 minutes a week.
The researchers followed the participants for a median of 7.9 years, looking for the incidence of multiple digestive diseases, identified using the International Classification of Diseases, 10th Revision, codes. These included diverticulosis, constipation, metabolic dysfunction–associated steatotic liver disease, cholelithiasis, and gastroesophageal reflux disease.
,” Yu said. At the threshold ≥ 150 minutes, for instance, hazard ratios for any digestive disease were 0.83 for weekend warriors and 0.79 for active regulars, compared with sedentary participants.
The analysis was repeated using a median threshold ≥ 230.4 minutes of MVPA a week, and the researchers found the same results.
As a validation cohort, the researchers used more than 6,000 participants from the National Institutes of Health’s All of Us Research Program with over 6 months of wrist-based accelerometer data.
A recent meta-epidemiology study found that the weekend warrior pattern offers other health benefits, including reducing the risk for cardiovascular disease mortality, mental disorders, and metabolic syndrome.
A Pleasant Surprise
The digestive disease study’s findings were “a surprise and a pleasant one,” said Aasma Shaukat, MD, MPH, AGAF, professor of medicine and a gastroenterologist at NYU Grossman School of Medicine, New York City.
“We often think if we’re not able to exercise regularly, then there’s no hope for us,” said Shaukat, who moderated the session. “But this implies that even if we have time only during the weekend to engage in physical activity, it still confers benefits in reducing our risk of any GI health disorder, as well as cardiovascular or other health disorders, compared to people inactive at baseline.”
“It gives us flexibility in terms of how we structure our exercise. Obviously, people should try to get into the habit of doing regular activity; it’s more sustainable. But a good alternative, according to this research, is that packing all of that in over the weekend seems to confer benefit. So all is not lost.”
Will this change her conversation with patients moving forward? Absolutely, Shaukat said. She generally recommends physical activity for at least 30 minutes three times a week. Now Shaukat said she can tell patients: “If that’s not possible, take that time out during the weekend for your health”.
This study was funded by grants from the National Natural Science Foundation of China and its Regional Innovation and Development Joint Foundation. Yu and Shaukat reported no disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Do GLP-1s Lower CRC Risk in Patients With Obesity and T2D?
SAN DIEGO — new research showed.
CRC risk was also lower for patients taking GLP-1s than the general population.
“Our findings show we might need to evaluate these therapies beyond their glycemic or weight loss [effects],” said first author Omar Al Ta’ani, MD, of the Allegheny Health Network, Pittsburgh.
This supports future prospective studies examining GLP-1s for CRC reduction, added Ta’ani, who presented the results at Digestive Disease Week (DDW) 2025.
Patients with type 2 diabetes and obesity are known to have a higher risk for CRC, stemming from metabolic risk factors. Whereas prior studies suggested that GLP-1s decrease the risk for CRC compared with other antidiabetic medications, studies looking at the risk for CRC associated with bariatric surgery have had more mixed results, Ta’ani said.
For the comparison, Ta’ani and colleagues conducted a retrospective analysis of the TriNetX database, identifying patients with type 2 diabetes and obesity (body mass index [BMI] > 30) enrolled in the database between 2005 and 2019.
Overall, the study included 94,098 GLP-1 users and 24,969 patients who underwent bariatric surgery. Those with a prior history of CRC were excluded.
Using propensity score matching, patients treated with GLP-1s were matched 1:1 with patients who had bariatric surgery based on wide-ranging factors including age, race, gender, demographics, diseases, medications, personal and family history, and hemoglobin A1c.
After the propensity matching, each group included 21,022 patients. About 64% in each group were women; their median age was 53 years and about 65% were White.
Overall, the results showed that patients on GLP-1s had a significantly lower CRC risk compared with those who had bariatric surgery (adjusted hazard ratio [aHR], 0.29; P < .0001). The lower risk was also observed among those with high obesity (defined as BMI > 35) compared with those who had surgery (aHR, 0.39; P < .0001).
The results were consistent across genders; however, the differences between GLP-1s and bariatric surgery were not observed in the 18- to 45-year-old age group (BMI > 30, P = .0809; BMI > 35, P = .2318).
Compared with the general population, patients on GLP-1s also had a reduced risk for CRC (aHR, 0.28; P < .0001); however, the difference was not observed between the bariatric surgery group and the general population (aHR, 1.11; P = .3).
Among patients with type 2 diabetes with CRC and a BMI > 30, the 5-year mortality rate was lower in the GLP-1 group vs the bariatric surgery group (aHR, 0.42; P < .001).
Speculating on the mechanisms of GLP-1s that could result in a greater reduction in CRC risk, Ta’ani explained that the key pathways linking type 2 diabetes, obesity, and CRC include hyperinsulinemia, chronic inflammation, and impaired immune surveillance.
Studies have shown that GLP-1s may be more effective in addressing the collective pathways, he said. They “may improve insulin resistance and lower systemic inflammation.”
Furthermore, GLP1s “inhibit tumor pathways like Wnt/beta-catenin and PI3K/Akt/mTOR signaling, which promote apoptosis and reduce tumor cell proliferation,” he added.
Bariatric Surgery Findings Questioned
Meanwhile, “bariatric surgery’s impact on CRC remains mixed,” said Ta’ani.
Commenting on the study, Vance L. Albaugh, MD, an assistant professor of metabolic surgery at the Metamor Institute, Pennington Biomedical Research Center, Baton Rouge, Louisiana, noted that prior studies, including a recent meta-analysis, suggest a potential benefit of bariatric surgery in cancer prevention.
“I think the [current study] is interesting, but it’s been pretty [well-reported] that bariatric surgery does decrease cancer incidence, so I find it questionable that this study shows the opposite of what’s in the literature,” Albaugh, an obesity medicine specialist and bariatric surgeon, said in an interview.
Ta’ani acknowledged the study’s important limitations, including that with a retrospective design, causality cannot be firmly established.
And, as noted by an audience member in the session’s Q&A, the study ended in 2019, which was before GLP-1s had taken off as anti-obesity drugs and before US Food and Drug Administration approvals for weight loss.
Participants were matched based on BMI, however, Ta’ani pointed out.
Albaugh agreed that the study ending in 2019 was a notable limitation. However, the relatively long study period — extending from 2005 to 2019 — was a strength.
“It’s nice to have a very long period to capture people who are diagnosed, because it takes a long time to develop CRC,” he said. “To evaluate effects [of more recent drug regimens], you would not be able to have the follow-up they had.”
Other study limitations included the need to adjust for ranges of obesity severity, said Albaugh. “The risk of colorectal cancer is probably much different for someone with a BMI of 60 vs a BMI of 30.”
Ultimately, a key question the study results raise is whether GLP-1 drugs have protective effects above and beyond that of weight loss, he said.
“I think that’s a very exciting question and that’s what I think the researchers’ next work should really focus on.”
Ta’ani had no disclosures to report. Albaugh reported that he had consulted for Novo Nordisk.
A version of this article appeared on Medscape.com.
SAN DIEGO — new research showed.
CRC risk was also lower for patients taking GLP-1s than the general population.
“Our findings show we might need to evaluate these therapies beyond their glycemic or weight loss [effects],” said first author Omar Al Ta’ani, MD, of the Allegheny Health Network, Pittsburgh.
This supports future prospective studies examining GLP-1s for CRC reduction, added Ta’ani, who presented the results at Digestive Disease Week (DDW) 2025.
Patients with type 2 diabetes and obesity are known to have a higher risk for CRC, stemming from metabolic risk factors. Whereas prior studies suggested that GLP-1s decrease the risk for CRC compared with other antidiabetic medications, studies looking at the risk for CRC associated with bariatric surgery have had more mixed results, Ta’ani said.
For the comparison, Ta’ani and colleagues conducted a retrospective analysis of the TriNetX database, identifying patients with type 2 diabetes and obesity (body mass index [BMI] > 30) enrolled in the database between 2005 and 2019.
Overall, the study included 94,098 GLP-1 users and 24,969 patients who underwent bariatric surgery. Those with a prior history of CRC were excluded.
Using propensity score matching, patients treated with GLP-1s were matched 1:1 with patients who had bariatric surgery based on wide-ranging factors including age, race, gender, demographics, diseases, medications, personal and family history, and hemoglobin A1c.
After the propensity matching, each group included 21,022 patients. About 64% in each group were women; their median age was 53 years and about 65% were White.
Overall, the results showed that patients on GLP-1s had a significantly lower CRC risk compared with those who had bariatric surgery (adjusted hazard ratio [aHR], 0.29; P < .0001). The lower risk was also observed among those with high obesity (defined as BMI > 35) compared with those who had surgery (aHR, 0.39; P < .0001).
The results were consistent across genders; however, the differences between GLP-1s and bariatric surgery were not observed in the 18- to 45-year-old age group (BMI > 30, P = .0809; BMI > 35, P = .2318).
Compared with the general population, patients on GLP-1s also had a reduced risk for CRC (aHR, 0.28; P < .0001); however, the difference was not observed between the bariatric surgery group and the general population (aHR, 1.11; P = .3).
Among patients with type 2 diabetes with CRC and a BMI > 30, the 5-year mortality rate was lower in the GLP-1 group vs the bariatric surgery group (aHR, 0.42; P < .001).
Speculating on the mechanisms of GLP-1s that could result in a greater reduction in CRC risk, Ta’ani explained that the key pathways linking type 2 diabetes, obesity, and CRC include hyperinsulinemia, chronic inflammation, and impaired immune surveillance.
Studies have shown that GLP-1s may be more effective in addressing the collective pathways, he said. They “may improve insulin resistance and lower systemic inflammation.”
Furthermore, GLP1s “inhibit tumor pathways like Wnt/beta-catenin and PI3K/Akt/mTOR signaling, which promote apoptosis and reduce tumor cell proliferation,” he added.
Bariatric Surgery Findings Questioned
Meanwhile, “bariatric surgery’s impact on CRC remains mixed,” said Ta’ani.
Commenting on the study, Vance L. Albaugh, MD, an assistant professor of metabolic surgery at the Metamor Institute, Pennington Biomedical Research Center, Baton Rouge, Louisiana, noted that prior studies, including a recent meta-analysis, suggest a potential benefit of bariatric surgery in cancer prevention.
“I think the [current study] is interesting, but it’s been pretty [well-reported] that bariatric surgery does decrease cancer incidence, so I find it questionable that this study shows the opposite of what’s in the literature,” Albaugh, an obesity medicine specialist and bariatric surgeon, said in an interview.
Ta’ani acknowledged the study’s important limitations, including that with a retrospective design, causality cannot be firmly established.
And, as noted by an audience member in the session’s Q&A, the study ended in 2019, which was before GLP-1s had taken off as anti-obesity drugs and before US Food and Drug Administration approvals for weight loss.
Participants were matched based on BMI, however, Ta’ani pointed out.
Albaugh agreed that the study ending in 2019 was a notable limitation. However, the relatively long study period — extending from 2005 to 2019 — was a strength.
“It’s nice to have a very long period to capture people who are diagnosed, because it takes a long time to develop CRC,” he said. “To evaluate effects [of more recent drug regimens], you would not be able to have the follow-up they had.”
Other study limitations included the need to adjust for ranges of obesity severity, said Albaugh. “The risk of colorectal cancer is probably much different for someone with a BMI of 60 vs a BMI of 30.”
Ultimately, a key question the study results raise is whether GLP-1 drugs have protective effects above and beyond that of weight loss, he said.
“I think that’s a very exciting question and that’s what I think the researchers’ next work should really focus on.”
Ta’ani had no disclosures to report. Albaugh reported that he had consulted for Novo Nordisk.
A version of this article appeared on Medscape.com.
SAN DIEGO — new research showed.
CRC risk was also lower for patients taking GLP-1s than the general population.
“Our findings show we might need to evaluate these therapies beyond their glycemic or weight loss [effects],” said first author Omar Al Ta’ani, MD, of the Allegheny Health Network, Pittsburgh.
This supports future prospective studies examining GLP-1s for CRC reduction, added Ta’ani, who presented the results at Digestive Disease Week (DDW) 2025.
Patients with type 2 diabetes and obesity are known to have a higher risk for CRC, stemming from metabolic risk factors. Whereas prior studies suggested that GLP-1s decrease the risk for CRC compared with other antidiabetic medications, studies looking at the risk for CRC associated with bariatric surgery have had more mixed results, Ta’ani said.
For the comparison, Ta’ani and colleagues conducted a retrospective analysis of the TriNetX database, identifying patients with type 2 diabetes and obesity (body mass index [BMI] > 30) enrolled in the database between 2005 and 2019.
Overall, the study included 94,098 GLP-1 users and 24,969 patients who underwent bariatric surgery. Those with a prior history of CRC were excluded.
Using propensity score matching, patients treated with GLP-1s were matched 1:1 with patients who had bariatric surgery based on wide-ranging factors including age, race, gender, demographics, diseases, medications, personal and family history, and hemoglobin A1c.
After the propensity matching, each group included 21,022 patients. About 64% in each group were women; their median age was 53 years and about 65% were White.
Overall, the results showed that patients on GLP-1s had a significantly lower CRC risk compared with those who had bariatric surgery (adjusted hazard ratio [aHR], 0.29; P < .0001). The lower risk was also observed among those with high obesity (defined as BMI > 35) compared with those who had surgery (aHR, 0.39; P < .0001).
The results were consistent across genders; however, the differences between GLP-1s and bariatric surgery were not observed in the 18- to 45-year-old age group (BMI > 30, P = .0809; BMI > 35, P = .2318).
Compared with the general population, patients on GLP-1s also had a reduced risk for CRC (aHR, 0.28; P < .0001); however, the difference was not observed between the bariatric surgery group and the general population (aHR, 1.11; P = .3).
Among patients with type 2 diabetes with CRC and a BMI > 30, the 5-year mortality rate was lower in the GLP-1 group vs the bariatric surgery group (aHR, 0.42; P < .001).
Speculating on the mechanisms of GLP-1s that could result in a greater reduction in CRC risk, Ta’ani explained that the key pathways linking type 2 diabetes, obesity, and CRC include hyperinsulinemia, chronic inflammation, and impaired immune surveillance.
Studies have shown that GLP-1s may be more effective in addressing the collective pathways, he said. They “may improve insulin resistance and lower systemic inflammation.”
Furthermore, GLP1s “inhibit tumor pathways like Wnt/beta-catenin and PI3K/Akt/mTOR signaling, which promote apoptosis and reduce tumor cell proliferation,” he added.
Bariatric Surgery Findings Questioned
Meanwhile, “bariatric surgery’s impact on CRC remains mixed,” said Ta’ani.
Commenting on the study, Vance L. Albaugh, MD, an assistant professor of metabolic surgery at the Metamor Institute, Pennington Biomedical Research Center, Baton Rouge, Louisiana, noted that prior studies, including a recent meta-analysis, suggest a potential benefit of bariatric surgery in cancer prevention.
“I think the [current study] is interesting, but it’s been pretty [well-reported] that bariatric surgery does decrease cancer incidence, so I find it questionable that this study shows the opposite of what’s in the literature,” Albaugh, an obesity medicine specialist and bariatric surgeon, said in an interview.
Ta’ani acknowledged the study’s important limitations, including that with a retrospective design, causality cannot be firmly established.
And, as noted by an audience member in the session’s Q&A, the study ended in 2019, which was before GLP-1s had taken off as anti-obesity drugs and before US Food and Drug Administration approvals for weight loss.
Participants were matched based on BMI, however, Ta’ani pointed out.
Albaugh agreed that the study ending in 2019 was a notable limitation. However, the relatively long study period — extending from 2005 to 2019 — was a strength.
“It’s nice to have a very long period to capture people who are diagnosed, because it takes a long time to develop CRC,” he said. “To evaluate effects [of more recent drug regimens], you would not be able to have the follow-up they had.”
Other study limitations included the need to adjust for ranges of obesity severity, said Albaugh. “The risk of colorectal cancer is probably much different for someone with a BMI of 60 vs a BMI of 30.”
Ultimately, a key question the study results raise is whether GLP-1 drugs have protective effects above and beyond that of weight loss, he said.
“I think that’s a very exciting question and that’s what I think the researchers’ next work should really focus on.”
Ta’ani had no disclosures to report. Albaugh reported that he had consulted for Novo Nordisk.
A version of this article appeared on Medscape.com.
FROM DDW 2025
ctDNA Positivity in Colorectal Cancer Links to Chemotherapy Response
SAN DIEGO — the results of the BESPOKE study showed.
“These findings highlight the value of utilizing ctDNA to select which patients should receive management chemotherapy and which patients can be potentially spared chemotherapy’s physical, emotional, and financial toxicities without compromising their long-term outcomes,” said first author Kim Magee of Natera, a clinical genetic testing company in Austin, Texas.
“ctDNA is emerging as the most powerful and prognostic biomarker in colorectal cancer,” said Magee, who presented the findings at Digestive Disease Week (DDW) 2025.
In stage II CRC, as many as 80% of patients are cured by surgery alone, while only about 5% benefit from chemotherapy. In stage III CRC, about half of patients are cured by surgery alone, while only 20% benefit from chemotherapy, and 30% recur despite chemotherapy, Magee explained.
The inability to pinpoint which patients will most benefit from chemotherapy means “we know we are needlessly treating [many] of these patients,” she said.
ctDNA Offers Insights Into Tumor’s Real-Time Status
Just as cells release fragments (cell-free DNA) into the blood as they regenerate, tumor cells also release fragments — ctDNA — which can represent a biomarker of a cancer’s current state, Magee explained.
Because the DNA fragments have a half-life of only about 2 hours, they represent a key snapshot in real time, “as opposed to imaging, which can take several weeks or months to show changes,” she said.
To determine the effects of ctDNA testing on treatment decisions and asymptomatic recurrence rates, Magee and colleagues analyzed data from the multicenter, prospective study, which used the Signatera (Natera) residual disease test.
The study included 1794 patients with resected stage II-III CRC who were treated with the standard of care between May 2020 and March 2023 who had complete clinical and laboratory data available.
ctDNA was collected 2-6 weeks post surgery and at surveillance months 2, 4, 6, and every 3 months through month 24.
Among the 1166 patients included in a final analysis, 694 (59.5%) patients received adjunctive chemotherapy, and 472 (40.5%) received no chemotherapy.
Among those with stage II CRC, a postoperative MRD positivity rate was 7.54%, while the rate in those with stage III disease was 28.35%.
Overall, 16.1% of patients had a recurrence by the trial end at 24 months.
The results showed that among patients who tested negative for ctDNA, the disease-free survival estimates were highly favorable, at 91.8% for stage II and 87.4% for stage III CRC.
Comparatively, for those who were ctDNA-positive, disease-free survival rates were just 45.9% and 35.5%, respectively, regardless of whether those patients received adjunctive chemotherapy.
At the study’s first ctDNA surveillance timepoint, patients who were ctDNA-positive with stage II and III CRC combined had substantially worse disease-free survival than patients who were ctDNA-negative (HR, 26.4; P < .0001).
Impact of Chemotherapy
Patients who were found to be MRD-positive on ctDNA testing and treated with chemotherapy had a 40.3% 2-year disease-free survival rate compared with just 24.7% among MRD-positive patients who did not receive chemotherapy.
Meanwhile, those who were MRD-negative and treated with chemotherapy had a substantially higher 2-year disease-free survival rate of 89.7% — nearly identical to the 89.5% observed in the no-chemotherapy group.
The findings underscored that “the adjuvant chemotherapy benefits were only observed among those who were ctDNA-positive,” Magee said.
“ctDNA can guide postsurgical treatment decisions by identifying which patients are most likely to benefit from chemotherapy, and in the surveillance setting, ctDNA can predict recurrence — usually ahead of scans,” she added. “This opens the opportunity to intervene and give those patients a second chance at cure.”
On the heels of major recent advances including CT, MRI, and PET-CT, “we believe that ctDNA represents the next major pivotal advancement in monitoring and eventually better understanding cancer diagnostics,” Magee said.
Commenting on the study, William M. Grady, MD, AGAF, medical director of the Fred Hutchinson Cancer Center Gastrointestinal Cancer Prevention Clinic, Seattle, said the BESPOKE trial represents a “well-done” study, adding to research underscoring that “MRD testing is a more accurate prognostic assay than the current standards of CT scan and CEA [carcinoembryonic antigen, a tumor marker] testing.”
However, “a limitation is that this is 2 years of follow-up, [while] 5-year follow-up data would be ideal,” he said in an interview, noting, importantly, that “a small number of patients who have no evidence of disease (NED) at 2 years develop recurrence by 5 years.”
Furthermore, more research demonstrating the outcomes of MRD detection is needed, Grady added.
“A caveat is that studies are still needed showing that if you change your care of patients based on the MRD result, that you improve outcomes,” he said. “These studies are being planned and initiated at this time, from my understanding.”
Oncologists treating patients with CRC are commonly performing MRD assessment with ctDNA assays; however, Grady noted that the practice is still not the standard of care.
Regarding the suggestion of ctDNA representing the next major, pivotal step in cancer monitoring, Grady responded that “I think this is aspirational, and further studies are needed to make this claim.”
However, “it does look like it has the promise to turn out to be true.”
Magee is an employee of Nater. Grady has been on the scientific advisory boards for Guardant Health and Freenome and has consulted for Karius.
A version of this article appeared on Medscape.com.
SAN DIEGO — the results of the BESPOKE study showed.
“These findings highlight the value of utilizing ctDNA to select which patients should receive management chemotherapy and which patients can be potentially spared chemotherapy’s physical, emotional, and financial toxicities without compromising their long-term outcomes,” said first author Kim Magee of Natera, a clinical genetic testing company in Austin, Texas.
“ctDNA is emerging as the most powerful and prognostic biomarker in colorectal cancer,” said Magee, who presented the findings at Digestive Disease Week (DDW) 2025.
In stage II CRC, as many as 80% of patients are cured by surgery alone, while only about 5% benefit from chemotherapy. In stage III CRC, about half of patients are cured by surgery alone, while only 20% benefit from chemotherapy, and 30% recur despite chemotherapy, Magee explained.
The inability to pinpoint which patients will most benefit from chemotherapy means “we know we are needlessly treating [many] of these patients,” she said.
ctDNA Offers Insights Into Tumor’s Real-Time Status
Just as cells release fragments (cell-free DNA) into the blood as they regenerate, tumor cells also release fragments — ctDNA — which can represent a biomarker of a cancer’s current state, Magee explained.
Because the DNA fragments have a half-life of only about 2 hours, they represent a key snapshot in real time, “as opposed to imaging, which can take several weeks or months to show changes,” she said.
To determine the effects of ctDNA testing on treatment decisions and asymptomatic recurrence rates, Magee and colleagues analyzed data from the multicenter, prospective study, which used the Signatera (Natera) residual disease test.
The study included 1794 patients with resected stage II-III CRC who were treated with the standard of care between May 2020 and March 2023 who had complete clinical and laboratory data available.
ctDNA was collected 2-6 weeks post surgery and at surveillance months 2, 4, 6, and every 3 months through month 24.
Among the 1166 patients included in a final analysis, 694 (59.5%) patients received adjunctive chemotherapy, and 472 (40.5%) received no chemotherapy.
Among those with stage II CRC, a postoperative MRD positivity rate was 7.54%, while the rate in those with stage III disease was 28.35%.
Overall, 16.1% of patients had a recurrence by the trial end at 24 months.
The results showed that among patients who tested negative for ctDNA, the disease-free survival estimates were highly favorable, at 91.8% for stage II and 87.4% for stage III CRC.
Comparatively, for those who were ctDNA-positive, disease-free survival rates were just 45.9% and 35.5%, respectively, regardless of whether those patients received adjunctive chemotherapy.
At the study’s first ctDNA surveillance timepoint, patients who were ctDNA-positive with stage II and III CRC combined had substantially worse disease-free survival than patients who were ctDNA-negative (HR, 26.4; P < .0001).
Impact of Chemotherapy
Patients who were found to be MRD-positive on ctDNA testing and treated with chemotherapy had a 40.3% 2-year disease-free survival rate compared with just 24.7% among MRD-positive patients who did not receive chemotherapy.
Meanwhile, those who were MRD-negative and treated with chemotherapy had a substantially higher 2-year disease-free survival rate of 89.7% — nearly identical to the 89.5% observed in the no-chemotherapy group.
The findings underscored that “the adjuvant chemotherapy benefits were only observed among those who were ctDNA-positive,” Magee said.
“ctDNA can guide postsurgical treatment decisions by identifying which patients are most likely to benefit from chemotherapy, and in the surveillance setting, ctDNA can predict recurrence — usually ahead of scans,” she added. “This opens the opportunity to intervene and give those patients a second chance at cure.”
On the heels of major recent advances including CT, MRI, and PET-CT, “we believe that ctDNA represents the next major pivotal advancement in monitoring and eventually better understanding cancer diagnostics,” Magee said.
Commenting on the study, William M. Grady, MD, AGAF, medical director of the Fred Hutchinson Cancer Center Gastrointestinal Cancer Prevention Clinic, Seattle, said the BESPOKE trial represents a “well-done” study, adding to research underscoring that “MRD testing is a more accurate prognostic assay than the current standards of CT scan and CEA [carcinoembryonic antigen, a tumor marker] testing.”
However, “a limitation is that this is 2 years of follow-up, [while] 5-year follow-up data would be ideal,” he said in an interview, noting, importantly, that “a small number of patients who have no evidence of disease (NED) at 2 years develop recurrence by 5 years.”
Furthermore, more research demonstrating the outcomes of MRD detection is needed, Grady added.
“A caveat is that studies are still needed showing that if you change your care of patients based on the MRD result, that you improve outcomes,” he said. “These studies are being planned and initiated at this time, from my understanding.”
Oncologists treating patients with CRC are commonly performing MRD assessment with ctDNA assays; however, Grady noted that the practice is still not the standard of care.
Regarding the suggestion of ctDNA representing the next major, pivotal step in cancer monitoring, Grady responded that “I think this is aspirational, and further studies are needed to make this claim.”
However, “it does look like it has the promise to turn out to be true.”
Magee is an employee of Nater. Grady has been on the scientific advisory boards for Guardant Health and Freenome and has consulted for Karius.
A version of this article appeared on Medscape.com.
SAN DIEGO — the results of the BESPOKE study showed.
“These findings highlight the value of utilizing ctDNA to select which patients should receive management chemotherapy and which patients can be potentially spared chemotherapy’s physical, emotional, and financial toxicities without compromising their long-term outcomes,” said first author Kim Magee of Natera, a clinical genetic testing company in Austin, Texas.
“ctDNA is emerging as the most powerful and prognostic biomarker in colorectal cancer,” said Magee, who presented the findings at Digestive Disease Week (DDW) 2025.
In stage II CRC, as many as 80% of patients are cured by surgery alone, while only about 5% benefit from chemotherapy. In stage III CRC, about half of patients are cured by surgery alone, while only 20% benefit from chemotherapy, and 30% recur despite chemotherapy, Magee explained.
The inability to pinpoint which patients will most benefit from chemotherapy means “we know we are needlessly treating [many] of these patients,” she said.
ctDNA Offers Insights Into Tumor’s Real-Time Status
Just as cells release fragments (cell-free DNA) into the blood as they regenerate, tumor cells also release fragments — ctDNA — which can represent a biomarker of a cancer’s current state, Magee explained.
Because the DNA fragments have a half-life of only about 2 hours, they represent a key snapshot in real time, “as opposed to imaging, which can take several weeks or months to show changes,” she said.
To determine the effects of ctDNA testing on treatment decisions and asymptomatic recurrence rates, Magee and colleagues analyzed data from the multicenter, prospective study, which used the Signatera (Natera) residual disease test.
The study included 1794 patients with resected stage II-III CRC who were treated with the standard of care between May 2020 and March 2023 who had complete clinical and laboratory data available.
ctDNA was collected 2-6 weeks post surgery and at surveillance months 2, 4, 6, and every 3 months through month 24.
Among the 1166 patients included in a final analysis, 694 (59.5%) patients received adjunctive chemotherapy, and 472 (40.5%) received no chemotherapy.
Among those with stage II CRC, a postoperative MRD positivity rate was 7.54%, while the rate in those with stage III disease was 28.35%.
Overall, 16.1% of patients had a recurrence by the trial end at 24 months.
The results showed that among patients who tested negative for ctDNA, the disease-free survival estimates were highly favorable, at 91.8% for stage II and 87.4% for stage III CRC.
Comparatively, for those who were ctDNA-positive, disease-free survival rates were just 45.9% and 35.5%, respectively, regardless of whether those patients received adjunctive chemotherapy.
At the study’s first ctDNA surveillance timepoint, patients who were ctDNA-positive with stage II and III CRC combined had substantially worse disease-free survival than patients who were ctDNA-negative (HR, 26.4; P < .0001).
Impact of Chemotherapy
Patients who were found to be MRD-positive on ctDNA testing and treated with chemotherapy had a 40.3% 2-year disease-free survival rate compared with just 24.7% among MRD-positive patients who did not receive chemotherapy.
Meanwhile, those who were MRD-negative and treated with chemotherapy had a substantially higher 2-year disease-free survival rate of 89.7% — nearly identical to the 89.5% observed in the no-chemotherapy group.
The findings underscored that “the adjuvant chemotherapy benefits were only observed among those who were ctDNA-positive,” Magee said.
“ctDNA can guide postsurgical treatment decisions by identifying which patients are most likely to benefit from chemotherapy, and in the surveillance setting, ctDNA can predict recurrence — usually ahead of scans,” she added. “This opens the opportunity to intervene and give those patients a second chance at cure.”
On the heels of major recent advances including CT, MRI, and PET-CT, “we believe that ctDNA represents the next major pivotal advancement in monitoring and eventually better understanding cancer diagnostics,” Magee said.
Commenting on the study, William M. Grady, MD, AGAF, medical director of the Fred Hutchinson Cancer Center Gastrointestinal Cancer Prevention Clinic, Seattle, said the BESPOKE trial represents a “well-done” study, adding to research underscoring that “MRD testing is a more accurate prognostic assay than the current standards of CT scan and CEA [carcinoembryonic antigen, a tumor marker] testing.”
However, “a limitation is that this is 2 years of follow-up, [while] 5-year follow-up data would be ideal,” he said in an interview, noting, importantly, that “a small number of patients who have no evidence of disease (NED) at 2 years develop recurrence by 5 years.”
Furthermore, more research demonstrating the outcomes of MRD detection is needed, Grady added.
“A caveat is that studies are still needed showing that if you change your care of patients based on the MRD result, that you improve outcomes,” he said. “These studies are being planned and initiated at this time, from my understanding.”
Oncologists treating patients with CRC are commonly performing MRD assessment with ctDNA assays; however, Grady noted that the practice is still not the standard of care.
Regarding the suggestion of ctDNA representing the next major, pivotal step in cancer monitoring, Grady responded that “I think this is aspirational, and further studies are needed to make this claim.”
However, “it does look like it has the promise to turn out to be true.”
Magee is an employee of Nater. Grady has been on the scientific advisory boards for Guardant Health and Freenome and has consulted for Karius.
A version of this article appeared on Medscape.com.
FROM DDW 2025