Conference Coverage

SAN DIEGO – A novel investigational endoscopic procedure targeting the duodenum appears beneficial in improving glycemic parameters in people with type 2 diabetes (T2D).

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 – A novel investigational endoscopic procedure targeting the duodenum appears beneficial in improving glycemic parameters in people with type 2 diabetes (T2D).

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 – A novel investigational endoscopic procedure targeting the duodenum appears beneficial in improving glycemic parameters in people with type 2 diabetes (T2D).

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 treating pancreas divisum, the common use of endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy showed no significant benefit over a sham procedure, 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 — In treating pancreas divisum, the common use of endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy showed no significant benefit over a sham procedure, 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 — In treating pancreas divisum, the common use of endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy showed no significant benefit over a sham procedure, 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 — 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. 

Both activity patterns “showed similar risk reduction with no significant difference,” 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. 

Both activity patterns “showed similar risk reduction with no significant difference,” 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. 

Both activity patterns “showed similar risk reduction with no significant difference,” 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 — Patients with obesity and type 2 diabetes treated with glucagon-like peptide 1 (GLP-1) receptor agonists had significantly reduced rates of colorectal cancer (CRC) risk and associated mortality compared with those undergoing bariatric surgery, 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 — Patients with obesity and type 2 diabetes treated with glucagon-like peptide 1 (GLP-1) receptor agonists had significantly reduced rates of colorectal cancer (CRC) risk and associated mortality compared with those undergoing bariatric surgery, 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 — Patients with obesity and type 2 diabetes treated with glucagon-like peptide 1 (GLP-1) receptor agonists had significantly reduced rates of colorectal cancer (CRC) risk and associated mortality compared with those undergoing bariatric surgery, 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 — Molecular residual disease (MRD) positivity, as detected via circulating tumor (ct) DNA following curative resection, was significantly associated with improved disease-free survival after chemotherapy in patients with stage II or III colorectal cancer (CRC), 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 — Molecular residual disease (MRD) positivity, as detected via circulating tumor (ct) DNA following curative resection, was significantly associated with improved disease-free survival after chemotherapy in patients with stage II or III colorectal cancer (CRC), 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 — Molecular residual disease (MRD) positivity, as detected via circulating tumor (ct) DNA following curative resection, was significantly associated with improved disease-free survival after chemotherapy in patients with stage II or III colorectal cancer (CRC), 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 — Patients with cirrhosis treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors show significant reductions in a range of portal hypertension complications and all-cause mortality compared with those not receiving the drugs, new research shows.

“Our study found that SGLT2 inhibitors were associated with fewer portal hypertension complications and lower mortality, suggesting they may be a valuable addition to cirrhosis management,” first author Abhinav K. Rao, MD, of the Medical University of South Carolina, Charleston, South Carolina, told GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

Portal hypertension, a potentially life-threatening complication of cirrhosis, can be a key driver of additional complications including ascites and gastro-esophageal varices in cirrhosis.

Current treatments such as beta-blockers can prevent some complications, however, more effective therapies are needed.

SGLT2 inhibitors are often used in the treatment of cardiovascular disease as well as metabolic dysfunction–associated steatohepatitis (MASH)–mediated liver disease; research is lacking regarding their effects in portal hypertension in the broader population of people with cirrhosis.

“The therapeutic efficacy of SGLT2 inhibitors might be related to their ability to improve vascular function, making them attractive in portal hypertension,” Rao explained.

To investigate, Rao and colleagues evaluated data on 637,079 patients with cirrhosis in the TriNetX database, which includes patients in the United States from 66 healthcare organizations.

Patients were divided into three subgroups, including those with MASH, alcohol-associated, and other etiologies of cirrhosis.

Using robust 1:1 propensity score matching, patients in each subgroup were stratified as either having or not having been treated with SGLT2 inhibitors, limited to those who initiated the drugs within 1 year of their cirrhosis diagnosis to prevent immortal time bias. Patients were matched on other characteristics.

For the primary outcome of all-cause mortality, with an overall median follow-up of 2 years, patients prescribed SGLT2 inhibitors in the MASH cirrhosis (n = 47,385), alcohol-associated cirrhosis (n = 107,844), and other etiologies of cirrhosis (n = 59,499) groups all had a significantly lower risk for all-cause mortality than those not prescribed SGLT2 inhibitors (P < .05 for all).

 

SGLT2 Inhibitors in MASH Cirrhosis

Specifically looking at the MASH cirrhosis group, Rao described outcomes of the two groups of 3026 patients each who were and were not treated with SGLT2 inhibitors.

The patients had similar rates of esophageal varices (25% in the SGLT2 group and 22% in the no SGLT2 group), ascites (19% in each group), and a similar rate of 19% had hepatic encephalopathy (HE).

About 57% of patients in each treatment group used beta-blockers and 33% used glucagon-like peptide 1 (GLP-1) receptor agonists. Those with a history of liver transplantation, hemodialysis, or transjugular intrahepatic portosystemic shunt placement were excluded.

The secondary outcome results in those patients showed that treatment with SGLT2 inhibitors was associated with significantly reduced risks of developing portal hypertension complications including ascites, HE, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (P < .05 for all).

Esophageal variceal bleeding was also reduced with SGLT-2 inhibitors; however the difference was not statistically significant.

 

Effects Diminished With Beta-Blocker Treatment

In a secondary analysis of patients in the MASH cirrhosis group treated with one type of a nonselective beta-blockers (n = 509) and another nonselective beta-blockers (n = 2561), the beneficial effects of SGLT2 inhibitors on portal hypertension, with the exception of HE and SBP, were found to be somewhat diminished, likely because patients were already benefitting from the beta-blockers, Rao noted.

Other Groups

In outcomes of the non–MASH-related cirrhosis groups, patients prescribed SGLT2 inhibitors also had a reduced risk for specific, as well as any portal hypertension complications (P < .05), Rao noted.

Overall, the findings add to previous studies on SGLT2 inhibitors in MASH and expand on the possible benefits, he said.

“Our findings validate these [previous] results and suggest potential benefits across for patients with other types of liver disease and raise the possibility of a beneficial effect in portal hypertension,” he said.

“Given the marked reduction in portal hypertension complications after SGLT2 inhibitor initiation, the associated survival benefit may not be surprising,” he noted.

“However, we were intrigued by the consistent reduction in portal hypertension complications across all cirrhosis types, especially since SGLT-2 inhibitors are most commonly used in patients with diabetes who have MASH-mediated liver disease.”

 

‘Real World Glimpse’ at SGLT2 Inhibitors; Limitations Need Noting 

Commenting on the study, Rotonya M. Carr, MD, Division Head of Gastroenterology at the University of Washington, Seattle, said the study sheds important light on an issue previously addressed only in smaller cohorts.

“To date, there have only been a few small prospective, retrospective, and case series studies investigating SGTL2 inhibitors in patients with cirrhosis,” she told GI & Hepatology Newsv.

“This retrospective study is a real-world glimpse at how patients with cirrhosis may fare on these drugs — very exciting data.”

Carr cautioned, however, that, in addition to the retrospective study design, limitations included that the study doesn’t provide details on the duration of therapy, preventing an understanding of whether the results represent chronic, sustained use of SGLT2 inhibitors.

“[Therefore], we cannot interpret these results to mean that chronic, sustained use of SGTL2 inh is beneficial, or does not cause harm, in patients with cirrhosis.”

“While these data are provocative, more work needs to be done before we understand the full safety and efficacy of SGTL2 inhibitors for patients with cirrhosis,” Carr added.

“However, these data are very encouraging, and I am optimistic that we will indeed see both SGTL2 inhibitors and GLP-1s among the group of medications we use in the future for the primary management of patients with liver disease.”

The authors had no disclosures to report. Carr’s disclosures included relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO — Patients with cirrhosis treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors show significant reductions in a range of portal hypertension complications and all-cause mortality compared with those not receiving the drugs, new research shows.

“Our study found that SGLT2 inhibitors were associated with fewer portal hypertension complications and lower mortality, suggesting they may be a valuable addition to cirrhosis management,” first author Abhinav K. Rao, MD, of the Medical University of South Carolina, Charleston, South Carolina, told GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

Portal hypertension, a potentially life-threatening complication of cirrhosis, can be a key driver of additional complications including ascites and gastro-esophageal varices in cirrhosis.

Current treatments such as beta-blockers can prevent some complications, however, more effective therapies are needed.

SGLT2 inhibitors are often used in the treatment of cardiovascular disease as well as metabolic dysfunction–associated steatohepatitis (MASH)–mediated liver disease; research is lacking regarding their effects in portal hypertension in the broader population of people with cirrhosis.

“The therapeutic efficacy of SGLT2 inhibitors might be related to their ability to improve vascular function, making them attractive in portal hypertension,” Rao explained.

To investigate, Rao and colleagues evaluated data on 637,079 patients with cirrhosis in the TriNetX database, which includes patients in the United States from 66 healthcare organizations.

Patients were divided into three subgroups, including those with MASH, alcohol-associated, and other etiologies of cirrhosis.

Using robust 1:1 propensity score matching, patients in each subgroup were stratified as either having or not having been treated with SGLT2 inhibitors, limited to those who initiated the drugs within 1 year of their cirrhosis diagnosis to prevent immortal time bias. Patients were matched on other characteristics.

For the primary outcome of all-cause mortality, with an overall median follow-up of 2 years, patients prescribed SGLT2 inhibitors in the MASH cirrhosis (n = 47,385), alcohol-associated cirrhosis (n = 107,844), and other etiologies of cirrhosis (n = 59,499) groups all had a significantly lower risk for all-cause mortality than those not prescribed SGLT2 inhibitors (P < .05 for all).

 

SGLT2 Inhibitors in MASH Cirrhosis

Specifically looking at the MASH cirrhosis group, Rao described outcomes of the two groups of 3026 patients each who were and were not treated with SGLT2 inhibitors.

The patients had similar rates of esophageal varices (25% in the SGLT2 group and 22% in the no SGLT2 group), ascites (19% in each group), and a similar rate of 19% had hepatic encephalopathy (HE).

About 57% of patients in each treatment group used beta-blockers and 33% used glucagon-like peptide 1 (GLP-1) receptor agonists. Those with a history of liver transplantation, hemodialysis, or transjugular intrahepatic portosystemic shunt placement were excluded.

The secondary outcome results in those patients showed that treatment with SGLT2 inhibitors was associated with significantly reduced risks of developing portal hypertension complications including ascites, HE, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (P < .05 for all).

Esophageal variceal bleeding was also reduced with SGLT-2 inhibitors; however the difference was not statistically significant.

 

Effects Diminished With Beta-Blocker Treatment

In a secondary analysis of patients in the MASH cirrhosis group treated with one type of a nonselective beta-blockers (n = 509) and another nonselective beta-blockers (n = 2561), the beneficial effects of SGLT2 inhibitors on portal hypertension, with the exception of HE and SBP, were found to be somewhat diminished, likely because patients were already benefitting from the beta-blockers, Rao noted.

Other Groups

In outcomes of the non–MASH-related cirrhosis groups, patients prescribed SGLT2 inhibitors also had a reduced risk for specific, as well as any portal hypertension complications (P < .05), Rao noted.

Overall, the findings add to previous studies on SGLT2 inhibitors in MASH and expand on the possible benefits, he said.

“Our findings validate these [previous] results and suggest potential benefits across for patients with other types of liver disease and raise the possibility of a beneficial effect in portal hypertension,” he said.

“Given the marked reduction in portal hypertension complications after SGLT2 inhibitor initiation, the associated survival benefit may not be surprising,” he noted.

“However, we were intrigued by the consistent reduction in portal hypertension complications across all cirrhosis types, especially since SGLT-2 inhibitors are most commonly used in patients with diabetes who have MASH-mediated liver disease.”

 

‘Real World Glimpse’ at SGLT2 Inhibitors; Limitations Need Noting 

Commenting on the study, Rotonya M. Carr, MD, Division Head of Gastroenterology at the University of Washington, Seattle, said the study sheds important light on an issue previously addressed only in smaller cohorts.

“To date, there have only been a few small prospective, retrospective, and case series studies investigating SGTL2 inhibitors in patients with cirrhosis,” she told GI & Hepatology Newsv.

“This retrospective study is a real-world glimpse at how patients with cirrhosis may fare on these drugs — very exciting data.”

Carr cautioned, however, that, in addition to the retrospective study design, limitations included that the study doesn’t provide details on the duration of therapy, preventing an understanding of whether the results represent chronic, sustained use of SGLT2 inhibitors.

“[Therefore], we cannot interpret these results to mean that chronic, sustained use of SGTL2 inh is beneficial, or does not cause harm, in patients with cirrhosis.”

“While these data are provocative, more work needs to be done before we understand the full safety and efficacy of SGTL2 inhibitors for patients with cirrhosis,” Carr added.

“However, these data are very encouraging, and I am optimistic that we will indeed see both SGTL2 inhibitors and GLP-1s among the group of medications we use in the future for the primary management of patients with liver disease.”

The authors had no disclosures to report. Carr’s disclosures included relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO — Patients with cirrhosis treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors show significant reductions in a range of portal hypertension complications and all-cause mortality compared with those not receiving the drugs, new research shows.

“Our study found that SGLT2 inhibitors were associated with fewer portal hypertension complications and lower mortality, suggesting they may be a valuable addition to cirrhosis management,” first author Abhinav K. Rao, MD, of the Medical University of South Carolina, Charleston, South Carolina, told GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

Portal hypertension, a potentially life-threatening complication of cirrhosis, can be a key driver of additional complications including ascites and gastro-esophageal varices in cirrhosis.

Current treatments such as beta-blockers can prevent some complications, however, more effective therapies are needed.

SGLT2 inhibitors are often used in the treatment of cardiovascular disease as well as metabolic dysfunction–associated steatohepatitis (MASH)–mediated liver disease; research is lacking regarding their effects in portal hypertension in the broader population of people with cirrhosis.

“The therapeutic efficacy of SGLT2 inhibitors might be related to their ability to improve vascular function, making them attractive in portal hypertension,” Rao explained.

To investigate, Rao and colleagues evaluated data on 637,079 patients with cirrhosis in the TriNetX database, which includes patients in the United States from 66 healthcare organizations.

Patients were divided into three subgroups, including those with MASH, alcohol-associated, and other etiologies of cirrhosis.

Using robust 1:1 propensity score matching, patients in each subgroup were stratified as either having or not having been treated with SGLT2 inhibitors, limited to those who initiated the drugs within 1 year of their cirrhosis diagnosis to prevent immortal time bias. Patients were matched on other characteristics.

For the primary outcome of all-cause mortality, with an overall median follow-up of 2 years, patients prescribed SGLT2 inhibitors in the MASH cirrhosis (n = 47,385), alcohol-associated cirrhosis (n = 107,844), and other etiologies of cirrhosis (n = 59,499) groups all had a significantly lower risk for all-cause mortality than those not prescribed SGLT2 inhibitors (P < .05 for all).

 

SGLT2 Inhibitors in MASH Cirrhosis

Specifically looking at the MASH cirrhosis group, Rao described outcomes of the two groups of 3026 patients each who were and were not treated with SGLT2 inhibitors.

The patients had similar rates of esophageal varices (25% in the SGLT2 group and 22% in the no SGLT2 group), ascites (19% in each group), and a similar rate of 19% had hepatic encephalopathy (HE).

About 57% of patients in each treatment group used beta-blockers and 33% used glucagon-like peptide 1 (GLP-1) receptor agonists. Those with a history of liver transplantation, hemodialysis, or transjugular intrahepatic portosystemic shunt placement were excluded.

The secondary outcome results in those patients showed that treatment with SGLT2 inhibitors was associated with significantly reduced risks of developing portal hypertension complications including ascites, HE, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (P < .05 for all).

Esophageal variceal bleeding was also reduced with SGLT-2 inhibitors; however the difference was not statistically significant.

 

Effects Diminished With Beta-Blocker Treatment

In a secondary analysis of patients in the MASH cirrhosis group treated with one type of a nonselective beta-blockers (n = 509) and another nonselective beta-blockers (n = 2561), the beneficial effects of SGLT2 inhibitors on portal hypertension, with the exception of HE and SBP, were found to be somewhat diminished, likely because patients were already benefitting from the beta-blockers, Rao noted.

Other Groups

In outcomes of the non–MASH-related cirrhosis groups, patients prescribed SGLT2 inhibitors also had a reduced risk for specific, as well as any portal hypertension complications (P < .05), Rao noted.

Overall, the findings add to previous studies on SGLT2 inhibitors in MASH and expand on the possible benefits, he said.

“Our findings validate these [previous] results and suggest potential benefits across for patients with other types of liver disease and raise the possibility of a beneficial effect in portal hypertension,” he said.

“Given the marked reduction in portal hypertension complications after SGLT2 inhibitor initiation, the associated survival benefit may not be surprising,” he noted.

“However, we were intrigued by the consistent reduction in portal hypertension complications across all cirrhosis types, especially since SGLT-2 inhibitors are most commonly used in patients with diabetes who have MASH-mediated liver disease.”

 

‘Real World Glimpse’ at SGLT2 Inhibitors; Limitations Need Noting 

Commenting on the study, Rotonya M. Carr, MD, Division Head of Gastroenterology at the University of Washington, Seattle, said the study sheds important light on an issue previously addressed only in smaller cohorts.

“To date, there have only been a few small prospective, retrospective, and case series studies investigating SGTL2 inhibitors in patients with cirrhosis,” she told GI & Hepatology Newsv.

“This retrospective study is a real-world glimpse at how patients with cirrhosis may fare on these drugs — very exciting data.”

Carr cautioned, however, that, in addition to the retrospective study design, limitations included that the study doesn’t provide details on the duration of therapy, preventing an understanding of whether the results represent chronic, sustained use of SGLT2 inhibitors.

“[Therefore], we cannot interpret these results to mean that chronic, sustained use of SGTL2 inh is beneficial, or does not cause harm, in patients with cirrhosis.”

“While these data are provocative, more work needs to be done before we understand the full safety and efficacy of SGTL2 inhibitors for patients with cirrhosis,” Carr added.

“However, these data are very encouraging, and I am optimistic that we will indeed see both SGTL2 inhibitors and GLP-1s among the group of medications we use in the future for the primary management of patients with liver disease.”

The authors had no disclosures to report. Carr’s disclosures included relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO — An artificial intelligence (AI)–enhanced digital collaborative care model led to rapid, clinically significant, and sustained symptom relief for patients with irritable bowel syndrome (IBS) seen at Cleveland Clinic, Cleveland, Ohio, an observational study found.

Symptom tracking at 4-week intervals showed that “almost everybody got better” regardless of IBS subtype, with relief starting in the first 4 weeks, Stephen Lupe, PsyD, gastrointestinal psychologist and director of Behavioral Medicine, Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic, Cleveland, said in an interview with GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

 

Digital Boost to Collaborative Care Model

The combination of dietary interventions and brain-gut behavioral therapy has demonstrated excellent outcomes for patients with IBS, but patients struggle to access these needed services, Lupe noted. A medical home collaborative care model in which patients get care from a multidisciplinary team has been shown to be a good way to successfully deliver this combination of care.

“When you do collaborative in-person care, people get better quicker,” Lupe said.

However, scaling access to this model remains a challenge. For their study, Cleveland Clinic researchers added an AI-enhanced digital platform, Ayble Health, to the in-person collaborative care model to expand access to disease-management services and evaluated whether it improved clinical outcomes for study’s 171 participants, who were recruited via social media advertisements.

Here’s how the platform works. Once a patient enrolls in Ayble Health, a personalized care plan is recommended based on a virtual visit, screening questionnaire, and baseline survey.

The platform includes brain-gut programs, including guided audio content on mindfulness, hypnosis, meditation, cognitive behavioral therapy, and breathing techniques; personalized nutrition support to find and remove trigger foods, a food barcode scanner, and a comprehensive groceries database; and AI-powered wellness tools to help manage and track symptoms. Lupe worked with Ayble Health to develop the platform’s behavioral health content and care pathways.

Patients may choose to follow any combination of three care pathways: A care team overseen by gastro-psychologists, dietitians, and gastroenterologists; a holistic nutrition program including a personalized elimination diet; and a brain-gut behavioral therapy program with gut-directed hypnosis, cognitive behavioral therapy, and acceptance and commitment therapy. They go at their own pace, can connect with Ayble Health’s virtual care team to help with education and goal setting, and continue to consult their Cleveland Clinic providers as needed for evaluation and treatment.

“The care team is still there. We’ve just augmented it to make sure that as many people as possible get behavioral skills training and dietary support, with monitoring between visits — instead of the traditional, ‘I’ll see you in 6 months approach,” Lupe explained.

 

IBS Symptom Scores Improve

Of the study’s 171 patients, 20 had IBS-diarrhea, 23 had IBS-constipation, 32 had IBS-mixed, and 8 had IBS-unspecified. The remaining 88 patients reported IBS without indication of subtype.

At intake, all patients had active IBS symptoms, with scores ≥ 75 on the IBS symptom severity scale (IBS-SSS). Most patients enrolled in more than one care pathway, and 95% of participants completed at least 4 weeks on their chosen pathways.

Overall, patients saw an average 140-point decrease in IBS-SSS from intake through follow-up lasting up to 42 weeks. A drop in IBS-SSS score ≥ 50 points was considered a clinically meaningful change.

Symptom improvements occurred as early as week 4, were sustained and were uniform across IBS subtypes, suggesting that the AI-enhanced digital collaborative care model has wide utility in patients with IBS, Lupe said.

Patients with the most severe IBS symptoms showed the greatest improvement, but even 50% of those with mild symptoms had clinically meaningful changes in IBS-SSS.

Improvement in IBS symptoms was seen across all care pathways, but the combination of multiple pathways improved outcomes better than a single care pathway alone. The combination of nutrition and brain-gut behavioral therapy demonstrated the greatest reduction in IBS-SSS scores and proportion of patients achieving clinically meaningful results (95%).

The digital comprehensive car model for IBS is now “up and running” at Cleveland Clinic, and the team plans to proactively reach out to patients with gastrointestinal disorders recently seen at their center to alert them to the availability of this tool, Lupe said.

A randomized controlled trial is planned to further validate these observational findings, he added.

 

‘Wave of the Future’

The digital collaborative care model is “innovative, and I think is the wave of the future,” Kyle Staller, MD, MPH, gastroenterologist and director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, Boston, who wasn’t involved in the study, told GI & Hepatology News.

“These digital platforms bundle nondrug options, such as cognitive-behavioral therapy, dietary therapy, hypnotherapy, so patients can choose what suits them, rather than the gastroenterologist hunting down each individual resource, which requires a lot of work,” Staller said.

The study “provides real-world evidence that a deliberative, digital, collaborative care model that houses various types of nondrug IBS treatment under one roof can provide meaningful benefit to patients,” Staller told GI & Hepatology News.

Importantly, he said, “patients chose which option they wanted. At the end of the day, the way that we should be thinking about IBS care is really making sure that we engage the patient with treatment choices,” Staller said.

This study had no specific funding. Three authors had relationships with Ayble Health. Lupe is a scientific advisor for Boomerang Health and paid lecturer for Takeda Pharmaceuticals. Staller disclosed having relationships with Mahana Therapeutics, Ardelyx Inc, Gemelli Biotech, Salix Pharmaceuticals, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — An artificial intelligence (AI)–enhanced digital collaborative care model led to rapid, clinically significant, and sustained symptom relief for patients with irritable bowel syndrome (IBS) seen at Cleveland Clinic, Cleveland, Ohio, an observational study found.

Symptom tracking at 4-week intervals showed that “almost everybody got better” regardless of IBS subtype, with relief starting in the first 4 weeks, Stephen Lupe, PsyD, gastrointestinal psychologist and director of Behavioral Medicine, Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic, Cleveland, said in an interview with GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

 

Digital Boost to Collaborative Care Model

The combination of dietary interventions and brain-gut behavioral therapy has demonstrated excellent outcomes for patients with IBS, but patients struggle to access these needed services, Lupe noted. A medical home collaborative care model in which patients get care from a multidisciplinary team has been shown to be a good way to successfully deliver this combination of care.

“When you do collaborative in-person care, people get better quicker,” Lupe said.

However, scaling access to this model remains a challenge. For their study, Cleveland Clinic researchers added an AI-enhanced digital platform, Ayble Health, to the in-person collaborative care model to expand access to disease-management services and evaluated whether it improved clinical outcomes for study’s 171 participants, who were recruited via social media advertisements.

Here’s how the platform works. Once a patient enrolls in Ayble Health, a personalized care plan is recommended based on a virtual visit, screening questionnaire, and baseline survey.

The platform includes brain-gut programs, including guided audio content on mindfulness, hypnosis, meditation, cognitive behavioral therapy, and breathing techniques; personalized nutrition support to find and remove trigger foods, a food barcode scanner, and a comprehensive groceries database; and AI-powered wellness tools to help manage and track symptoms. Lupe worked with Ayble Health to develop the platform’s behavioral health content and care pathways.

Patients may choose to follow any combination of three care pathways: A care team overseen by gastro-psychologists, dietitians, and gastroenterologists; a holistic nutrition program including a personalized elimination diet; and a brain-gut behavioral therapy program with gut-directed hypnosis, cognitive behavioral therapy, and acceptance and commitment therapy. They go at their own pace, can connect with Ayble Health’s virtual care team to help with education and goal setting, and continue to consult their Cleveland Clinic providers as needed for evaluation and treatment.

“The care team is still there. We’ve just augmented it to make sure that as many people as possible get behavioral skills training and dietary support, with monitoring between visits — instead of the traditional, ‘I’ll see you in 6 months approach,” Lupe explained.

 

IBS Symptom Scores Improve

Of the study’s 171 patients, 20 had IBS-diarrhea, 23 had IBS-constipation, 32 had IBS-mixed, and 8 had IBS-unspecified. The remaining 88 patients reported IBS without indication of subtype.

At intake, all patients had active IBS symptoms, with scores ≥ 75 on the IBS symptom severity scale (IBS-SSS). Most patients enrolled in more than one care pathway, and 95% of participants completed at least 4 weeks on their chosen pathways.

Overall, patients saw an average 140-point decrease in IBS-SSS from intake through follow-up lasting up to 42 weeks. A drop in IBS-SSS score ≥ 50 points was considered a clinically meaningful change.

Symptom improvements occurred as early as week 4, were sustained and were uniform across IBS subtypes, suggesting that the AI-enhanced digital collaborative care model has wide utility in patients with IBS, Lupe said.

Patients with the most severe IBS symptoms showed the greatest improvement, but even 50% of those with mild symptoms had clinically meaningful changes in IBS-SSS.

Improvement in IBS symptoms was seen across all care pathways, but the combination of multiple pathways improved outcomes better than a single care pathway alone. The combination of nutrition and brain-gut behavioral therapy demonstrated the greatest reduction in IBS-SSS scores and proportion of patients achieving clinically meaningful results (95%).

The digital comprehensive car model for IBS is now “up and running” at Cleveland Clinic, and the team plans to proactively reach out to patients with gastrointestinal disorders recently seen at their center to alert them to the availability of this tool, Lupe said.

A randomized controlled trial is planned to further validate these observational findings, he added.

 

‘Wave of the Future’

The digital collaborative care model is “innovative, and I think is the wave of the future,” Kyle Staller, MD, MPH, gastroenterologist and director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, Boston, who wasn’t involved in the study, told GI & Hepatology News.

“These digital platforms bundle nondrug options, such as cognitive-behavioral therapy, dietary therapy, hypnotherapy, so patients can choose what suits them, rather than the gastroenterologist hunting down each individual resource, which requires a lot of work,” Staller said.

The study “provides real-world evidence that a deliberative, digital, collaborative care model that houses various types of nondrug IBS treatment under one roof can provide meaningful benefit to patients,” Staller told GI & Hepatology News.

Importantly, he said, “patients chose which option they wanted. At the end of the day, the way that we should be thinking about IBS care is really making sure that we engage the patient with treatment choices,” Staller said.

This study had no specific funding. Three authors had relationships with Ayble Health. Lupe is a scientific advisor for Boomerang Health and paid lecturer for Takeda Pharmaceuticals. Staller disclosed having relationships with Mahana Therapeutics, Ardelyx Inc, Gemelli Biotech, Salix Pharmaceuticals, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — An artificial intelligence (AI)–enhanced digital collaborative care model led to rapid, clinically significant, and sustained symptom relief for patients with irritable bowel syndrome (IBS) seen at Cleveland Clinic, Cleveland, Ohio, an observational study found.

Symptom tracking at 4-week intervals showed that “almost everybody got better” regardless of IBS subtype, with relief starting in the first 4 weeks, Stephen Lupe, PsyD, gastrointestinal psychologist and director of Behavioral Medicine, Department of Gastroenterology, Hepatology, and Nutrition at Cleveland Clinic, Cleveland, said in an interview with GI & Hepatology News.

The findings were presented at Digestive Disease Week (DDW) 2025.

 

Digital Boost to Collaborative Care Model

The combination of dietary interventions and brain-gut behavioral therapy has demonstrated excellent outcomes for patients with IBS, but patients struggle to access these needed services, Lupe noted. A medical home collaborative care model in which patients get care from a multidisciplinary team has been shown to be a good way to successfully deliver this combination of care.

“When you do collaborative in-person care, people get better quicker,” Lupe said.

However, scaling access to this model remains a challenge. For their study, Cleveland Clinic researchers added an AI-enhanced digital platform, Ayble Health, to the in-person collaborative care model to expand access to disease-management services and evaluated whether it improved clinical outcomes for study’s 171 participants, who were recruited via social media advertisements.

Here’s how the platform works. Once a patient enrolls in Ayble Health, a personalized care plan is recommended based on a virtual visit, screening questionnaire, and baseline survey.

The platform includes brain-gut programs, including guided audio content on mindfulness, hypnosis, meditation, cognitive behavioral therapy, and breathing techniques; personalized nutrition support to find and remove trigger foods, a food barcode scanner, and a comprehensive groceries database; and AI-powered wellness tools to help manage and track symptoms. Lupe worked with Ayble Health to develop the platform’s behavioral health content and care pathways.

Patients may choose to follow any combination of three care pathways: A care team overseen by gastro-psychologists, dietitians, and gastroenterologists; a holistic nutrition program including a personalized elimination diet; and a brain-gut behavioral therapy program with gut-directed hypnosis, cognitive behavioral therapy, and acceptance and commitment therapy. They go at their own pace, can connect with Ayble Health’s virtual care team to help with education and goal setting, and continue to consult their Cleveland Clinic providers as needed for evaluation and treatment.

“The care team is still there. We’ve just augmented it to make sure that as many people as possible get behavioral skills training and dietary support, with monitoring between visits — instead of the traditional, ‘I’ll see you in 6 months approach,” Lupe explained.

 

IBS Symptom Scores Improve

Of the study’s 171 patients, 20 had IBS-diarrhea, 23 had IBS-constipation, 32 had IBS-mixed, and 8 had IBS-unspecified. The remaining 88 patients reported IBS without indication of subtype.

At intake, all patients had active IBS symptoms, with scores ≥ 75 on the IBS symptom severity scale (IBS-SSS). Most patients enrolled in more than one care pathway, and 95% of participants completed at least 4 weeks on their chosen pathways.

Overall, patients saw an average 140-point decrease in IBS-SSS from intake through follow-up lasting up to 42 weeks. A drop in IBS-SSS score ≥ 50 points was considered a clinically meaningful change.

Symptom improvements occurred as early as week 4, were sustained and were uniform across IBS subtypes, suggesting that the AI-enhanced digital collaborative care model has wide utility in patients with IBS, Lupe said.

Patients with the most severe IBS symptoms showed the greatest improvement, but even 50% of those with mild symptoms had clinically meaningful changes in IBS-SSS.

Improvement in IBS symptoms was seen across all care pathways, but the combination of multiple pathways improved outcomes better than a single care pathway alone. The combination of nutrition and brain-gut behavioral therapy demonstrated the greatest reduction in IBS-SSS scores and proportion of patients achieving clinically meaningful results (95%).

The digital comprehensive car model for IBS is now “up and running” at Cleveland Clinic, and the team plans to proactively reach out to patients with gastrointestinal disorders recently seen at their center to alert them to the availability of this tool, Lupe said.

A randomized controlled trial is planned to further validate these observational findings, he added.

 

‘Wave of the Future’

The digital collaborative care model is “innovative, and I think is the wave of the future,” Kyle Staller, MD, MPH, gastroenterologist and director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, Boston, who wasn’t involved in the study, told GI & Hepatology News.

“These digital platforms bundle nondrug options, such as cognitive-behavioral therapy, dietary therapy, hypnotherapy, so patients can choose what suits them, rather than the gastroenterologist hunting down each individual resource, which requires a lot of work,” Staller said.

The study “provides real-world evidence that a deliberative, digital, collaborative care model that houses various types of nondrug IBS treatment under one roof can provide meaningful benefit to patients,” Staller told GI & Hepatology News.

Importantly, he said, “patients chose which option they wanted. At the end of the day, the way that we should be thinking about IBS care is really making sure that we engage the patient with treatment choices,” Staller said.

This study had no specific funding. Three authors had relationships with Ayble Health. Lupe is a scientific advisor for Boomerang Health and paid lecturer for Takeda Pharmaceuticals. Staller disclosed having relationships with Mahana Therapeutics, Ardelyx Inc, Gemelli Biotech, Salix Pharmaceuticals, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients carrying at least one of the four key genes show a significantly increased risk for disease recurrence and mortality in gastric cancer, according to new research that potentially paves the way for precision oncology and improved targeting of therapies.

“About a third of patients with gastric cancer in our study had somatic mutations or variants of uncertain significance in [one of] four key genes,” lead author Ulysses Ribeiro, MD, PhD, a professor of digestive system surgery at the University of São Paulo School of Medicine in São Paulo, Brazil, said in a press briefing for the study, presented at Digestive Disease Week® (DDW) 2025.

“These patients were more likely to have their cancer come back or to die from the disease, even after surgery and the best chemotherapy and immunotherapy regimens,” said Ribeiro. While treatment strategies in gastric cancer have improved in recent years, resistance to multiple drugs continues, and the 5-year overall survival rate remains low — about 36% — underscoring the critical need for targeted therapies.

In an effort to identify genetic alterations that could have prognostic value, Ribeiro and his colleagues used next-generation DNA sequencing to analyze 21 genes in the tumor samples of 87 patients with gastric cancer who had undergone curative surgery and chemotherapy at the Sao Paulo Cancer Institute, São Paulo, Brazil.

Using Cox regression analysis, they found pathogenic variants or variants of uncertain significance in the following four genes: BRCA2, CDH1, RHOA, and TP53. “We found that 33% of patients carried at least one of these four genes,” Ribeiro told GI & Hepatology News.

Individually, each of the four genes with pathogenic variants or variants of uncertain significance had significantly or near-significantly higher risks in a survival analysis vs wild-type or benign variants, including BRCA2 (hazard ratio [HR], 4.33; P = .030); CDH1 (HR, 7.54; P = .004); RHOA (HR, 29.24; P < .001); and TP53 (HR, 2.82; P = .07).

A further multivariate analysis adjusting for key confounders showed that, when combined, carriers of the genes had lower disease-free survival (P = .005) and worse overall survival (P = .009) than those with none of the mutations.

“Individually, all four genes were related to prognosis in our gastric cancer patients, and when combined, the genes had even a higher difference in prognosis, varying from 2 to 28 times higher,” Ribeiro said.

Overall, factors such as having a more advanced tumor, node, metastasis stage, pathological stage, and the presence of a pathogenic mutation or a variant of uncertain significance in the four genes in the model were independently associated with worse disease-free survival.

 

Familiar Genes

Some of these genes are highly familiar. BRCA2 is well-known for its role in increasing the risk for breast and ovarian cancers, and CDH1 is known to be associated with hereditary diffuse gastric cancer, which is the most common hereditary cancer syndrome linked to gastric cancer.

TP53, also known as the “guardian of the genome,” is the most commonly altered gene in human cancers, while RHOA is known to be involved in encoding the GTPase protein RhoA, which is key in the regulation of cell shape, motility, and other essential cellular processes.

“This is the first time that these four genes have been shown to strongly relate to these gastric cancer outcomes,” said Ribeiro. This suggests that there’s more than one pathway by which stomach cancer forms and that some stomach cancers are much more aggressive than others.

He noted that “patients without these high-risk mutations” could be given “less aggressive treatment, in some cases sparing them from unnecessary side effects.”

Speaking during the press briefing, Loren A. Laine, MD, AGAF, who is a professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine in New Haven, Connecticut, and council chair of DDW 2025, agreed that “certainly, if these genetic factors, along with other factors, predict risk, this also has implications in practice with respect to the level of monitoring during the follow-up and determining the need for therapy.”

In addition, “it will be interesting to see how much this adds to other known risk factors, such as pathologic stage,” said Laine.

A strength of this study, “which I think is unique, is that it looks at a Western population,” whereas data on gastric as well as esophageal cancer is heavily biased to Eastern regions like China and East Asia, where the rates are much higher than in the West, Alia Qureshi, MD, an associate professor of esophageal and gastric cancer surgery at Oregon Health & Science University in Portland, Oregon, told GI & Hepatology News.

While noting the limitation of the relatively small sample size, Qureshi said the study is nevertheless “exciting and moving the direction we want to go, specifically towards precision medicine [and] precision oncology.”

The study “builds on existing understanding, especially with regard to TP53 and CDH1, and it points to the opportunity to use this data in a way to direct patient care or possibly therapeutic intervention,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept Pharmaceuticals, Merck, and Pfizer. Qureshi had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients carrying at least one of the four key genes show a significantly increased risk for disease recurrence and mortality in gastric cancer, according to new research that potentially paves the way for precision oncology and improved targeting of therapies.

“About a third of patients with gastric cancer in our study had somatic mutations or variants of uncertain significance in [one of] four key genes,” lead author Ulysses Ribeiro, MD, PhD, a professor of digestive system surgery at the University of São Paulo School of Medicine in São Paulo, Brazil, said in a press briefing for the study, presented at Digestive Disease Week® (DDW) 2025.

“These patients were more likely to have their cancer come back or to die from the disease, even after surgery and the best chemotherapy and immunotherapy regimens,” said Ribeiro. While treatment strategies in gastric cancer have improved in recent years, resistance to multiple drugs continues, and the 5-year overall survival rate remains low — about 36% — underscoring the critical need for targeted therapies.

In an effort to identify genetic alterations that could have prognostic value, Ribeiro and his colleagues used next-generation DNA sequencing to analyze 21 genes in the tumor samples of 87 patients with gastric cancer who had undergone curative surgery and chemotherapy at the Sao Paulo Cancer Institute, São Paulo, Brazil.

Using Cox regression analysis, they found pathogenic variants or variants of uncertain significance in the following four genes: BRCA2, CDH1, RHOA, and TP53. “We found that 33% of patients carried at least one of these four genes,” Ribeiro told GI & Hepatology News.

Individually, each of the four genes with pathogenic variants or variants of uncertain significance had significantly or near-significantly higher risks in a survival analysis vs wild-type or benign variants, including BRCA2 (hazard ratio [HR], 4.33; P = .030); CDH1 (HR, 7.54; P = .004); RHOA (HR, 29.24; P < .001); and TP53 (HR, 2.82; P = .07).

A further multivariate analysis adjusting for key confounders showed that, when combined, carriers of the genes had lower disease-free survival (P = .005) and worse overall survival (P = .009) than those with none of the mutations.

“Individually, all four genes were related to prognosis in our gastric cancer patients, and when combined, the genes had even a higher difference in prognosis, varying from 2 to 28 times higher,” Ribeiro said.

Overall, factors such as having a more advanced tumor, node, metastasis stage, pathological stage, and the presence of a pathogenic mutation or a variant of uncertain significance in the four genes in the model were independently associated with worse disease-free survival.

 

Familiar Genes

Some of these genes are highly familiar. BRCA2 is well-known for its role in increasing the risk for breast and ovarian cancers, and CDH1 is known to be associated with hereditary diffuse gastric cancer, which is the most common hereditary cancer syndrome linked to gastric cancer.

TP53, also known as the “guardian of the genome,” is the most commonly altered gene in human cancers, while RHOA is known to be involved in encoding the GTPase protein RhoA, which is key in the regulation of cell shape, motility, and other essential cellular processes.

“This is the first time that these four genes have been shown to strongly relate to these gastric cancer outcomes,” said Ribeiro. This suggests that there’s more than one pathway by which stomach cancer forms and that some stomach cancers are much more aggressive than others.

He noted that “patients without these high-risk mutations” could be given “less aggressive treatment, in some cases sparing them from unnecessary side effects.”

Speaking during the press briefing, Loren A. Laine, MD, AGAF, who is a professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine in New Haven, Connecticut, and council chair of DDW 2025, agreed that “certainly, if these genetic factors, along with other factors, predict risk, this also has implications in practice with respect to the level of monitoring during the follow-up and determining the need for therapy.”

In addition, “it will be interesting to see how much this adds to other known risk factors, such as pathologic stage,” said Laine.

A strength of this study, “which I think is unique, is that it looks at a Western population,” whereas data on gastric as well as esophageal cancer is heavily biased to Eastern regions like China and East Asia, where the rates are much higher than in the West, Alia Qureshi, MD, an associate professor of esophageal and gastric cancer surgery at Oregon Health & Science University in Portland, Oregon, told GI & Hepatology News.

While noting the limitation of the relatively small sample size, Qureshi said the study is nevertheless “exciting and moving the direction we want to go, specifically towards precision medicine [and] precision oncology.”

The study “builds on existing understanding, especially with regard to TP53 and CDH1, and it points to the opportunity to use this data in a way to direct patient care or possibly therapeutic intervention,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept Pharmaceuticals, Merck, and Pfizer. Qureshi had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients carrying at least one of the four key genes show a significantly increased risk for disease recurrence and mortality in gastric cancer, according to new research that potentially paves the way for precision oncology and improved targeting of therapies.

“About a third of patients with gastric cancer in our study had somatic mutations or variants of uncertain significance in [one of] four key genes,” lead author Ulysses Ribeiro, MD, PhD, a professor of digestive system surgery at the University of São Paulo School of Medicine in São Paulo, Brazil, said in a press briefing for the study, presented at Digestive Disease Week® (DDW) 2025.

“These patients were more likely to have their cancer come back or to die from the disease, even after surgery and the best chemotherapy and immunotherapy regimens,” said Ribeiro. While treatment strategies in gastric cancer have improved in recent years, resistance to multiple drugs continues, and the 5-year overall survival rate remains low — about 36% — underscoring the critical need for targeted therapies.

In an effort to identify genetic alterations that could have prognostic value, Ribeiro and his colleagues used next-generation DNA sequencing to analyze 21 genes in the tumor samples of 87 patients with gastric cancer who had undergone curative surgery and chemotherapy at the Sao Paulo Cancer Institute, São Paulo, Brazil.

Using Cox regression analysis, they found pathogenic variants or variants of uncertain significance in the following four genes: BRCA2, CDH1, RHOA, and TP53. “We found that 33% of patients carried at least one of these four genes,” Ribeiro told GI & Hepatology News.

Individually, each of the four genes with pathogenic variants or variants of uncertain significance had significantly or near-significantly higher risks in a survival analysis vs wild-type or benign variants, including BRCA2 (hazard ratio [HR], 4.33; P = .030); CDH1 (HR, 7.54; P = .004); RHOA (HR, 29.24; P < .001); and TP53 (HR, 2.82; P = .07).

A further multivariate analysis adjusting for key confounders showed that, when combined, carriers of the genes had lower disease-free survival (P = .005) and worse overall survival (P = .009) than those with none of the mutations.

“Individually, all four genes were related to prognosis in our gastric cancer patients, and when combined, the genes had even a higher difference in prognosis, varying from 2 to 28 times higher,” Ribeiro said.

Overall, factors such as having a more advanced tumor, node, metastasis stage, pathological stage, and the presence of a pathogenic mutation or a variant of uncertain significance in the four genes in the model were independently associated with worse disease-free survival.

 

Familiar Genes

Some of these genes are highly familiar. BRCA2 is well-known for its role in increasing the risk for breast and ovarian cancers, and CDH1 is known to be associated with hereditary diffuse gastric cancer, which is the most common hereditary cancer syndrome linked to gastric cancer.

TP53, also known as the “guardian of the genome,” is the most commonly altered gene in human cancers, while RHOA is known to be involved in encoding the GTPase protein RhoA, which is key in the regulation of cell shape, motility, and other essential cellular processes.

“This is the first time that these four genes have been shown to strongly relate to these gastric cancer outcomes,” said Ribeiro. This suggests that there’s more than one pathway by which stomach cancer forms and that some stomach cancers are much more aggressive than others.

He noted that “patients without these high-risk mutations” could be given “less aggressive treatment, in some cases sparing them from unnecessary side effects.”

Speaking during the press briefing, Loren A. Laine, MD, AGAF, who is a professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine in New Haven, Connecticut, and council chair of DDW 2025, agreed that “certainly, if these genetic factors, along with other factors, predict risk, this also has implications in practice with respect to the level of monitoring during the follow-up and determining the need for therapy.”

In addition, “it will be interesting to see how much this adds to other known risk factors, such as pathologic stage,” said Laine.

A strength of this study, “which I think is unique, is that it looks at a Western population,” whereas data on gastric as well as esophageal cancer is heavily biased to Eastern regions like China and East Asia, where the rates are much higher than in the West, Alia Qureshi, MD, an associate professor of esophageal and gastric cancer surgery at Oregon Health & Science University in Portland, Oregon, told GI & Hepatology News.

While noting the limitation of the relatively small sample size, Qureshi said the study is nevertheless “exciting and moving the direction we want to go, specifically towards precision medicine [and] precision oncology.”

The study “builds on existing understanding, especially with regard to TP53 and CDH1, and it points to the opportunity to use this data in a way to direct patient care or possibly therapeutic intervention,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept Pharmaceuticals, Merck, and Pfizer. Qureshi had no disclosures to report.

A version of this article appeared on Medscape.com.