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GI Side Effects of Immune Checkpoint Inhibitors Linked to Colon Adenoma Risk
PHOENIX — — potentially compounding their cancer burden to include a risk for colon cancer, new research showed.
“The cancer population is already at a higher baseline adenoma risk, and our findings show that ICI-mediated diarrhea and colitis compounds this,” said first author Tanvi Gupta, MD, Department of Internal Medicine, The University of Texas Health Science Center, Houston, in presenting the findings at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
“The study supports a risk-stratified approach to surveillance colonoscopy perhaps within 1 year of ICI-mediated diarrhea and colitis, or earlier if risk factors present,” she said.
ICIs, such as PD-1 and PD-L1 inhibitors, have emerged as highly effective front-line treatments for various cancers, however, diarrhea and colitis are among their most notorious off-target adverse effects, believed to be caused by excessive inflammatory activity from the therapy.
Interestingly, prolonged courses of colitis of more than 3 months have in fact been associated with improved long-term outcomes and survival related to the cancer being treated.
However, prolonged inflammation of the intestine is not without key risks, including compromised colonic mucosa, and such complications are particularly concerning considering indications that the colitis can persist for years even after ICIs are discontinued, the authors noted.
With a previous small study from the researchers at MD Anderson suggesting a higher risk for adenomas associated with ICI-mediated diarrhea and colitis within 1 year of diagnosis, Gupta and colleagues investigated the effects in a larger retrospective study, enrolling 248 patients treated for cancer at MD Anderson from 2010 to 2025.
All patients had developed ICI-mediated diarrhea and/or colitis, confirmed by colonoscopy within 90 days of onset, and all underwent a subsequent colonoscopy at any time point.
The patients, who had a median age of about 63.1 years, were 57.9% men and 90.3% White individuals. Of the patients, 43.7% had been treated with either PD-1 or PD-L1 inhibitors, whereas 42.5% received combination therapy including CTLA-4 inhibitors.
Patients’ predominant cancer types were melanoma and genitourinary malignancies. About 65% had cancer stage IV.
They were compared with a group of historical control individuals who had been treated with ICIs but did not develop diarrhea/colitis, and who had normal baseline and follow-up colonoscopies.
Overall, 71, or nearly 30% of the patients, developed adenomas on follow-up colonoscopies at least 6 months later, with more than 50% of the adenomas developing rapidly, within 7.5 months of ICI-mediated diarrhea and colitis onset. Rates subsequently declined over the following 6 years.
Of 210 who developed ICI-mediated diarrhea and colitis and had baseline and 1-year colonoscopies, those with baseline polyps had an increased risk for detection of adenomas on follow-up endoscopy compared with those with no baseline polyps (33.9% vs 15.9%; P = .004).
However, compared with the patients who were treated with ICIs but did not develop diarrhea and colitis (n = 31), those who did develop the side effects had a higher risk of developing adenomas, even if they had no prior history of polyps (n = 139; P = .002).
Likewise, among those with active histological inflammation at baseline, the risk for adenoma development was higher among those with baseline adenomas vs no adenomas (32.6% vs 15.8%; P = .014), but the risk was higher even among those with no baseline polyps but who did have active inflammation compared with those with ICI treatment but none of the gastrointestinal (GI) side effects (P = .003).
Of those who did develop adenomas, tubular adenomas were the most common types of adenomas, increasing from a median of 46.4% of polyps per patient at baseline to 87.5% at a follow-up endoscopy.
And the size of adenomas increased, with the rate of those under 5 mm at baseline of 100% dropping to 83.3% at the follow-up colonoscopy.
Overall, the findings underscore the role of ICI-mediated diarrhea and colitis in adenoma development.
“We know the cancer population is at a higher baseline risk of adenomas, and ICI-mediated diarrhea and colitis compounds this,” Gupta said.
Importantly, the findings indicate that “histological inflammation drives mucosal injury and adenoma development, regardless of baseline polyps.”
Findings Raise Questions of Surveillance
Danny Issa, MD, an interventional endoscopist and assistant professor of medicine of David Geffen School of Medicine at UCLA, who co-moderated the study, noted that, while longer-term studies are needed, “it’s an interesting study and eye-opening for the many patients on these medications now — but we do need more data.”
“The key question raised is are these patients at a higher risk for colon cancer? It’s possible, and it’s important for clinicians to keep that in mind,” he told GI & Hepatology News.
Further commenting, session co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Paramus, New Jersey, noted the alarming context of ICIs already being used for an existing cancer in the first place.
“So they have one type of cancer and now these patients may be at a higher risk for getting adenomas linked to colon cancer, and so an important question is how often to follow-up on these patients,” she said.
The study’s senior author, Yinghong Wang, MD, PhD, a professor and director of the Oncology-GI Toxicity program at MD Anderson, noted that at MD Anderson, “we routinely offer the first surveillance colonoscopy 1 year after the index ICI-mediated diarrhea and colitis.”
“The following surveillance interval will be based on the finding of this first surveillance colonoscopy,” she told GI & Hepatology News.
Wang recommended that others treating ICI-mediated diarrhea and colitis should follow suit, “given the higher incidence and rapid development of colonic adenomas during this time frame.”
Gupta, Wang, and Chokhavatia had no disclosures to report. Issa reported relationships with Boston Scientific and Eli Lilly.
A version of this article appeared on Medscape.com.
PHOENIX — — potentially compounding their cancer burden to include a risk for colon cancer, new research showed.
“The cancer population is already at a higher baseline adenoma risk, and our findings show that ICI-mediated diarrhea and colitis compounds this,” said first author Tanvi Gupta, MD, Department of Internal Medicine, The University of Texas Health Science Center, Houston, in presenting the findings at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
“The study supports a risk-stratified approach to surveillance colonoscopy perhaps within 1 year of ICI-mediated diarrhea and colitis, or earlier if risk factors present,” she said.
ICIs, such as PD-1 and PD-L1 inhibitors, have emerged as highly effective front-line treatments for various cancers, however, diarrhea and colitis are among their most notorious off-target adverse effects, believed to be caused by excessive inflammatory activity from the therapy.
Interestingly, prolonged courses of colitis of more than 3 months have in fact been associated with improved long-term outcomes and survival related to the cancer being treated.
However, prolonged inflammation of the intestine is not without key risks, including compromised colonic mucosa, and such complications are particularly concerning considering indications that the colitis can persist for years even after ICIs are discontinued, the authors noted.
With a previous small study from the researchers at MD Anderson suggesting a higher risk for adenomas associated with ICI-mediated diarrhea and colitis within 1 year of diagnosis, Gupta and colleagues investigated the effects in a larger retrospective study, enrolling 248 patients treated for cancer at MD Anderson from 2010 to 2025.
All patients had developed ICI-mediated diarrhea and/or colitis, confirmed by colonoscopy within 90 days of onset, and all underwent a subsequent colonoscopy at any time point.
The patients, who had a median age of about 63.1 years, were 57.9% men and 90.3% White individuals. Of the patients, 43.7% had been treated with either PD-1 or PD-L1 inhibitors, whereas 42.5% received combination therapy including CTLA-4 inhibitors.
Patients’ predominant cancer types were melanoma and genitourinary malignancies. About 65% had cancer stage IV.
They were compared with a group of historical control individuals who had been treated with ICIs but did not develop diarrhea/colitis, and who had normal baseline and follow-up colonoscopies.
Overall, 71, or nearly 30% of the patients, developed adenomas on follow-up colonoscopies at least 6 months later, with more than 50% of the adenomas developing rapidly, within 7.5 months of ICI-mediated diarrhea and colitis onset. Rates subsequently declined over the following 6 years.
Of 210 who developed ICI-mediated diarrhea and colitis and had baseline and 1-year colonoscopies, those with baseline polyps had an increased risk for detection of adenomas on follow-up endoscopy compared with those with no baseline polyps (33.9% vs 15.9%; P = .004).
However, compared with the patients who were treated with ICIs but did not develop diarrhea and colitis (n = 31), those who did develop the side effects had a higher risk of developing adenomas, even if they had no prior history of polyps (n = 139; P = .002).
Likewise, among those with active histological inflammation at baseline, the risk for adenoma development was higher among those with baseline adenomas vs no adenomas (32.6% vs 15.8%; P = .014), but the risk was higher even among those with no baseline polyps but who did have active inflammation compared with those with ICI treatment but none of the gastrointestinal (GI) side effects (P = .003).
Of those who did develop adenomas, tubular adenomas were the most common types of adenomas, increasing from a median of 46.4% of polyps per patient at baseline to 87.5% at a follow-up endoscopy.
And the size of adenomas increased, with the rate of those under 5 mm at baseline of 100% dropping to 83.3% at the follow-up colonoscopy.
Overall, the findings underscore the role of ICI-mediated diarrhea and colitis in adenoma development.
“We know the cancer population is at a higher baseline risk of adenomas, and ICI-mediated diarrhea and colitis compounds this,” Gupta said.
Importantly, the findings indicate that “histological inflammation drives mucosal injury and adenoma development, regardless of baseline polyps.”
Findings Raise Questions of Surveillance
Danny Issa, MD, an interventional endoscopist and assistant professor of medicine of David Geffen School of Medicine at UCLA, who co-moderated the study, noted that, while longer-term studies are needed, “it’s an interesting study and eye-opening for the many patients on these medications now — but we do need more data.”
“The key question raised is are these patients at a higher risk for colon cancer? It’s possible, and it’s important for clinicians to keep that in mind,” he told GI & Hepatology News.
Further commenting, session co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Paramus, New Jersey, noted the alarming context of ICIs already being used for an existing cancer in the first place.
“So they have one type of cancer and now these patients may be at a higher risk for getting adenomas linked to colon cancer, and so an important question is how often to follow-up on these patients,” she said.
The study’s senior author, Yinghong Wang, MD, PhD, a professor and director of the Oncology-GI Toxicity program at MD Anderson, noted that at MD Anderson, “we routinely offer the first surveillance colonoscopy 1 year after the index ICI-mediated diarrhea and colitis.”
“The following surveillance interval will be based on the finding of this first surveillance colonoscopy,” she told GI & Hepatology News.
Wang recommended that others treating ICI-mediated diarrhea and colitis should follow suit, “given the higher incidence and rapid development of colonic adenomas during this time frame.”
Gupta, Wang, and Chokhavatia had no disclosures to report. Issa reported relationships with Boston Scientific and Eli Lilly.
A version of this article appeared on Medscape.com.
PHOENIX — — potentially compounding their cancer burden to include a risk for colon cancer, new research showed.
“The cancer population is already at a higher baseline adenoma risk, and our findings show that ICI-mediated diarrhea and colitis compounds this,” said first author Tanvi Gupta, MD, Department of Internal Medicine, The University of Texas Health Science Center, Houston, in presenting the findings at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
“The study supports a risk-stratified approach to surveillance colonoscopy perhaps within 1 year of ICI-mediated diarrhea and colitis, or earlier if risk factors present,” she said.
ICIs, such as PD-1 and PD-L1 inhibitors, have emerged as highly effective front-line treatments for various cancers, however, diarrhea and colitis are among their most notorious off-target adverse effects, believed to be caused by excessive inflammatory activity from the therapy.
Interestingly, prolonged courses of colitis of more than 3 months have in fact been associated with improved long-term outcomes and survival related to the cancer being treated.
However, prolonged inflammation of the intestine is not without key risks, including compromised colonic mucosa, and such complications are particularly concerning considering indications that the colitis can persist for years even after ICIs are discontinued, the authors noted.
With a previous small study from the researchers at MD Anderson suggesting a higher risk for adenomas associated with ICI-mediated diarrhea and colitis within 1 year of diagnosis, Gupta and colleagues investigated the effects in a larger retrospective study, enrolling 248 patients treated for cancer at MD Anderson from 2010 to 2025.
All patients had developed ICI-mediated diarrhea and/or colitis, confirmed by colonoscopy within 90 days of onset, and all underwent a subsequent colonoscopy at any time point.
The patients, who had a median age of about 63.1 years, were 57.9% men and 90.3% White individuals. Of the patients, 43.7% had been treated with either PD-1 or PD-L1 inhibitors, whereas 42.5% received combination therapy including CTLA-4 inhibitors.
Patients’ predominant cancer types were melanoma and genitourinary malignancies. About 65% had cancer stage IV.
They were compared with a group of historical control individuals who had been treated with ICIs but did not develop diarrhea/colitis, and who had normal baseline and follow-up colonoscopies.
Overall, 71, or nearly 30% of the patients, developed adenomas on follow-up colonoscopies at least 6 months later, with more than 50% of the adenomas developing rapidly, within 7.5 months of ICI-mediated diarrhea and colitis onset. Rates subsequently declined over the following 6 years.
Of 210 who developed ICI-mediated diarrhea and colitis and had baseline and 1-year colonoscopies, those with baseline polyps had an increased risk for detection of adenomas on follow-up endoscopy compared with those with no baseline polyps (33.9% vs 15.9%; P = .004).
However, compared with the patients who were treated with ICIs but did not develop diarrhea and colitis (n = 31), those who did develop the side effects had a higher risk of developing adenomas, even if they had no prior history of polyps (n = 139; P = .002).
Likewise, among those with active histological inflammation at baseline, the risk for adenoma development was higher among those with baseline adenomas vs no adenomas (32.6% vs 15.8%; P = .014), but the risk was higher even among those with no baseline polyps but who did have active inflammation compared with those with ICI treatment but none of the gastrointestinal (GI) side effects (P = .003).
Of those who did develop adenomas, tubular adenomas were the most common types of adenomas, increasing from a median of 46.4% of polyps per patient at baseline to 87.5% at a follow-up endoscopy.
And the size of adenomas increased, with the rate of those under 5 mm at baseline of 100% dropping to 83.3% at the follow-up colonoscopy.
Overall, the findings underscore the role of ICI-mediated diarrhea and colitis in adenoma development.
“We know the cancer population is at a higher baseline risk of adenomas, and ICI-mediated diarrhea and colitis compounds this,” Gupta said.
Importantly, the findings indicate that “histological inflammation drives mucosal injury and adenoma development, regardless of baseline polyps.”
Findings Raise Questions of Surveillance
Danny Issa, MD, an interventional endoscopist and assistant professor of medicine of David Geffen School of Medicine at UCLA, who co-moderated the study, noted that, while longer-term studies are needed, “it’s an interesting study and eye-opening for the many patients on these medications now — but we do need more data.”
“The key question raised is are these patients at a higher risk for colon cancer? It’s possible, and it’s important for clinicians to keep that in mind,” he told GI & Hepatology News.
Further commenting, session co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Paramus, New Jersey, noted the alarming context of ICIs already being used for an existing cancer in the first place.
“So they have one type of cancer and now these patients may be at a higher risk for getting adenomas linked to colon cancer, and so an important question is how often to follow-up on these patients,” she said.
The study’s senior author, Yinghong Wang, MD, PhD, a professor and director of the Oncology-GI Toxicity program at MD Anderson, noted that at MD Anderson, “we routinely offer the first surveillance colonoscopy 1 year after the index ICI-mediated diarrhea and colitis.”
“The following surveillance interval will be based on the finding of this first surveillance colonoscopy,” she told GI & Hepatology News.
Wang recommended that others treating ICI-mediated diarrhea and colitis should follow suit, “given the higher incidence and rapid development of colonic adenomas during this time frame.”
Gupta, Wang, and Chokhavatia had no disclosures to report. Issa reported relationships with Boston Scientific and Eli Lilly.
A version of this article appeared on Medscape.com.
FROM ACG 2025
Higher Epilepsy Mortality in Posttraumatic Cases, VA Study Finds
The risk of death in patients with posttraumatic epilepsy (PTE) varies dramatically by type of brain injury, with some facing twice the mortality rate as those with other forms of epilepsy, according to a new study of Veterans Health Administration data.
Of 210,182 veterans with epilepsy followed for a median of 6 years, those who developed PTE after diffuse cerebral injury, focal cerebral injury, or skull/facial fractures had 16% to 18% higher mortality rates than veterans with nontraumatic epilepsy (NTE) the study found. Published in Neurology, the analysis was completed by Zulfi Haneef, MBBS, MD, of Baylor College of Medicine Medical Center, and colleagues.
Young patients who developed PTE after extracerebral hemorrhage faced the highest risk — double the mortality rate of those with NTE.
“These numbers are striking considering that the group against which these rates are compared — other causes of epilepsy — itself suffers from a high mortality rate,” Haneef said in an interview with Federal Practitioner. “Our findings argue for risk-stratified follow-up in PTE based on the underlying TBI [traumatic brain injury] mechanism and age at epilepsy onset.”
How Common is PTE?
PTE is defined as “long-term predisposition to developing recurrent and unprovoked seizures caused by a traumatic brain injury,” according to neurologist Edilberto Amorim, MD, of University of California at San Francisco Weill Institute for Neurosciences, who was not involved with the study but is familiar with its findings. “We do not fully understand why some people with a traumatic brain injury develop epilepsy and others do not, but the risk is higher with more severe types of TBI.”
PTE accounts for about 5% of all epilepsy cases, Amorim said. The study cites research linking PTE to mortality risk that’s 1.75 to 2.30 higher than in people without epilepsy.
Haneef said the study aimed to shed light on mortality in PTE. “Although epilepsy and TBI are each linked to higher mortality, it had never been conclusively shown that PTE specifically carries higher mortality than nontraumatic epilepsy,” he said. “We set out to answer that question in a large national veterans cohort and to see whether mortality differs by the type of antecedent TBI.”
Methodology and Findings
Researchers tracked 210,182 veterans diagnosed with epilepsy from 2005 to 2022 through the end of 2024: 28,832 with PTE (mean onset age 52.6 years, 7.4% female, 74.2% White, 16.2% Black) and 181,350 with NTE (mean onset age 60.9 years, 8.5% female, 71.0% White, 21.4% Black).
Patients with PTE were defined as having had documentation of TBI within 5 years previous to receiving an epilepsy diagnosis.
Among those with NTE (median follow-up, 6.0 years), 51.1% died. In the PTE group (median follow-up, 6.4 years), 37.3% died.
After adjustment for differences in age, sex, and comorbidities, the risk of mortality in PTE was slightly higher than in NTE (adjusted hazard ratio [aHR], 1.02); the risk was lower for the concussive TBI subtype (aHR, 0.91, both P < .05). “The underlying injury in concussion
is likely to be less severe compared with structural TBI, which may have led to the lower relative mortality observed,” the authors wrote.
However, risk of mortality in PTE was higher than in NTE for cases with underlying TBI subtypes of skull/facial fracture (aHR, 1.18), diffuse cerebral injury (aHR, 1.17), and focal cerebral injury (aHR, 1.16).
“These injuries are associated with greater structural brain damage and sustained neuroinflammation, which are factors linked to harder-to-treat (drug-resistant) epilepsy, which carries higher mortality,” Haneef said. “They may also coexist with extracranial trauma and medical comorbidity that compound long-term risk.”
Among various age groups, there was a notably higher risk of mortality linked to patients aged 18 to 39 years at onset with extracerebral PTE (aHR, 2.02, vs NTE): “In younger patients, extracerebral bleeds (eg, subdural, epidural, and subarachnoid) may reflect higher-energy trauma and more aggressive secondary cascades, amplifying epilepsy severity and longer lifetime exposure to risk. Mechanistic differences in hemorrhage types across ages may also contribute,” Haneef said.
Perspective on Findings
Amorim said the new research is “very useful,” although it has limitations that are common in large database studies. “A key point that this study highlights is the variability in the impact of TBI type on mortality and the differential risk across different age groups,” he said.
As for the higher risk in younger people, Amorim said this may be related to severity of injury: “Older patients often have TBI after falls, while younger patients are more frequently involved in traffic accidents or victims of violence,” he said
In the big picture, Amorim said, “studies like this highlight the importance of moving beyond a one-size-fits-all approach in epilepsy care. Understanding the nuances of posttraumatic epilepsy—how the type of injury, age, and other factors affect outcomes—can help us personalize treatment and counseling and maybe even guide future research into preventing or mitigating epilepsy after brain injury. New methods to automate review of medical records with higher resolution, such as large language models and natural language processing, may make this type of study with large databases even more comprehensive and impactful.”
Haneef said the findings highlight the importance of recognizing PTE as a higher-risk epilepsy and prioritizing early specialty care, especially after focal/diffuse brain injury or fracture. “Screen proactively for drug resistance and fast-track definitive therapies—surgery and device-based therapies—when indicated,” Haneef said. “Management should also include optimized antiseizure therapy, comorbidity control, and safety counseling, since many deaths may be preventable with coordinated multidisciplinary care.”
Haneef added that clinicians should “pay particular attention to younger PTE patients with extracerebral hemorrhage, who showed the greatest relative mortality.”
He also noted that the US Department of Veterans Affairs has comprehensive Epilepsy Centers of Excellence across the country.
The US Department of Defense (DoD) funded the study. Haneef discloses DoD funding, and another author discloses DoD and VA funding. Other authors have no disclosures.
Amorim discloses funding from DoD, NIH, American Heart Association, Regents of the University of California, Cures Within Reach, Zoll Foundation, and Hellman Foundation.
The risk of death in patients with posttraumatic epilepsy (PTE) varies dramatically by type of brain injury, with some facing twice the mortality rate as those with other forms of epilepsy, according to a new study of Veterans Health Administration data.
Of 210,182 veterans with epilepsy followed for a median of 6 years, those who developed PTE after diffuse cerebral injury, focal cerebral injury, or skull/facial fractures had 16% to 18% higher mortality rates than veterans with nontraumatic epilepsy (NTE) the study found. Published in Neurology, the analysis was completed by Zulfi Haneef, MBBS, MD, of Baylor College of Medicine Medical Center, and colleagues.
Young patients who developed PTE after extracerebral hemorrhage faced the highest risk — double the mortality rate of those with NTE.
“These numbers are striking considering that the group against which these rates are compared — other causes of epilepsy — itself suffers from a high mortality rate,” Haneef said in an interview with Federal Practitioner. “Our findings argue for risk-stratified follow-up in PTE based on the underlying TBI [traumatic brain injury] mechanism and age at epilepsy onset.”
How Common is PTE?
PTE is defined as “long-term predisposition to developing recurrent and unprovoked seizures caused by a traumatic brain injury,” according to neurologist Edilberto Amorim, MD, of University of California at San Francisco Weill Institute for Neurosciences, who was not involved with the study but is familiar with its findings. “We do not fully understand why some people with a traumatic brain injury develop epilepsy and others do not, but the risk is higher with more severe types of TBI.”
PTE accounts for about 5% of all epilepsy cases, Amorim said. The study cites research linking PTE to mortality risk that’s 1.75 to 2.30 higher than in people without epilepsy.
Haneef said the study aimed to shed light on mortality in PTE. “Although epilepsy and TBI are each linked to higher mortality, it had never been conclusively shown that PTE specifically carries higher mortality than nontraumatic epilepsy,” he said. “We set out to answer that question in a large national veterans cohort and to see whether mortality differs by the type of antecedent TBI.”
Methodology and Findings
Researchers tracked 210,182 veterans diagnosed with epilepsy from 2005 to 2022 through the end of 2024: 28,832 with PTE (mean onset age 52.6 years, 7.4% female, 74.2% White, 16.2% Black) and 181,350 with NTE (mean onset age 60.9 years, 8.5% female, 71.0% White, 21.4% Black).
Patients with PTE were defined as having had documentation of TBI within 5 years previous to receiving an epilepsy diagnosis.
Among those with NTE (median follow-up, 6.0 years), 51.1% died. In the PTE group (median follow-up, 6.4 years), 37.3% died.
After adjustment for differences in age, sex, and comorbidities, the risk of mortality in PTE was slightly higher than in NTE (adjusted hazard ratio [aHR], 1.02); the risk was lower for the concussive TBI subtype (aHR, 0.91, both P < .05). “The underlying injury in concussion
is likely to be less severe compared with structural TBI, which may have led to the lower relative mortality observed,” the authors wrote.
However, risk of mortality in PTE was higher than in NTE for cases with underlying TBI subtypes of skull/facial fracture (aHR, 1.18), diffuse cerebral injury (aHR, 1.17), and focal cerebral injury (aHR, 1.16).
“These injuries are associated with greater structural brain damage and sustained neuroinflammation, which are factors linked to harder-to-treat (drug-resistant) epilepsy, which carries higher mortality,” Haneef said. “They may also coexist with extracranial trauma and medical comorbidity that compound long-term risk.”
Among various age groups, there was a notably higher risk of mortality linked to patients aged 18 to 39 years at onset with extracerebral PTE (aHR, 2.02, vs NTE): “In younger patients, extracerebral bleeds (eg, subdural, epidural, and subarachnoid) may reflect higher-energy trauma and more aggressive secondary cascades, amplifying epilepsy severity and longer lifetime exposure to risk. Mechanistic differences in hemorrhage types across ages may also contribute,” Haneef said.
Perspective on Findings
Amorim said the new research is “very useful,” although it has limitations that are common in large database studies. “A key point that this study highlights is the variability in the impact of TBI type on mortality and the differential risk across different age groups,” he said.
As for the higher risk in younger people, Amorim said this may be related to severity of injury: “Older patients often have TBI after falls, while younger patients are more frequently involved in traffic accidents or victims of violence,” he said
In the big picture, Amorim said, “studies like this highlight the importance of moving beyond a one-size-fits-all approach in epilepsy care. Understanding the nuances of posttraumatic epilepsy—how the type of injury, age, and other factors affect outcomes—can help us personalize treatment and counseling and maybe even guide future research into preventing or mitigating epilepsy after brain injury. New methods to automate review of medical records with higher resolution, such as large language models and natural language processing, may make this type of study with large databases even more comprehensive and impactful.”
Haneef said the findings highlight the importance of recognizing PTE as a higher-risk epilepsy and prioritizing early specialty care, especially after focal/diffuse brain injury or fracture. “Screen proactively for drug resistance and fast-track definitive therapies—surgery and device-based therapies—when indicated,” Haneef said. “Management should also include optimized antiseizure therapy, comorbidity control, and safety counseling, since many deaths may be preventable with coordinated multidisciplinary care.”
Haneef added that clinicians should “pay particular attention to younger PTE patients with extracerebral hemorrhage, who showed the greatest relative mortality.”
He also noted that the US Department of Veterans Affairs has comprehensive Epilepsy Centers of Excellence across the country.
The US Department of Defense (DoD) funded the study. Haneef discloses DoD funding, and another author discloses DoD and VA funding. Other authors have no disclosures.
Amorim discloses funding from DoD, NIH, American Heart Association, Regents of the University of California, Cures Within Reach, Zoll Foundation, and Hellman Foundation.
The risk of death in patients with posttraumatic epilepsy (PTE) varies dramatically by type of brain injury, with some facing twice the mortality rate as those with other forms of epilepsy, according to a new study of Veterans Health Administration data.
Of 210,182 veterans with epilepsy followed for a median of 6 years, those who developed PTE after diffuse cerebral injury, focal cerebral injury, or skull/facial fractures had 16% to 18% higher mortality rates than veterans with nontraumatic epilepsy (NTE) the study found. Published in Neurology, the analysis was completed by Zulfi Haneef, MBBS, MD, of Baylor College of Medicine Medical Center, and colleagues.
Young patients who developed PTE after extracerebral hemorrhage faced the highest risk — double the mortality rate of those with NTE.
“These numbers are striking considering that the group against which these rates are compared — other causes of epilepsy — itself suffers from a high mortality rate,” Haneef said in an interview with Federal Practitioner. “Our findings argue for risk-stratified follow-up in PTE based on the underlying TBI [traumatic brain injury] mechanism and age at epilepsy onset.”
How Common is PTE?
PTE is defined as “long-term predisposition to developing recurrent and unprovoked seizures caused by a traumatic brain injury,” according to neurologist Edilberto Amorim, MD, of University of California at San Francisco Weill Institute for Neurosciences, who was not involved with the study but is familiar with its findings. “We do not fully understand why some people with a traumatic brain injury develop epilepsy and others do not, but the risk is higher with more severe types of TBI.”
PTE accounts for about 5% of all epilepsy cases, Amorim said. The study cites research linking PTE to mortality risk that’s 1.75 to 2.30 higher than in people without epilepsy.
Haneef said the study aimed to shed light on mortality in PTE. “Although epilepsy and TBI are each linked to higher mortality, it had never been conclusively shown that PTE specifically carries higher mortality than nontraumatic epilepsy,” he said. “We set out to answer that question in a large national veterans cohort and to see whether mortality differs by the type of antecedent TBI.”
Methodology and Findings
Researchers tracked 210,182 veterans diagnosed with epilepsy from 2005 to 2022 through the end of 2024: 28,832 with PTE (mean onset age 52.6 years, 7.4% female, 74.2% White, 16.2% Black) and 181,350 with NTE (mean onset age 60.9 years, 8.5% female, 71.0% White, 21.4% Black).
Patients with PTE were defined as having had documentation of TBI within 5 years previous to receiving an epilepsy diagnosis.
Among those with NTE (median follow-up, 6.0 years), 51.1% died. In the PTE group (median follow-up, 6.4 years), 37.3% died.
After adjustment for differences in age, sex, and comorbidities, the risk of mortality in PTE was slightly higher than in NTE (adjusted hazard ratio [aHR], 1.02); the risk was lower for the concussive TBI subtype (aHR, 0.91, both P < .05). “The underlying injury in concussion
is likely to be less severe compared with structural TBI, which may have led to the lower relative mortality observed,” the authors wrote.
However, risk of mortality in PTE was higher than in NTE for cases with underlying TBI subtypes of skull/facial fracture (aHR, 1.18), diffuse cerebral injury (aHR, 1.17), and focal cerebral injury (aHR, 1.16).
“These injuries are associated with greater structural brain damage and sustained neuroinflammation, which are factors linked to harder-to-treat (drug-resistant) epilepsy, which carries higher mortality,” Haneef said. “They may also coexist with extracranial trauma and medical comorbidity that compound long-term risk.”
Among various age groups, there was a notably higher risk of mortality linked to patients aged 18 to 39 years at onset with extracerebral PTE (aHR, 2.02, vs NTE): “In younger patients, extracerebral bleeds (eg, subdural, epidural, and subarachnoid) may reflect higher-energy trauma and more aggressive secondary cascades, amplifying epilepsy severity and longer lifetime exposure to risk. Mechanistic differences in hemorrhage types across ages may also contribute,” Haneef said.
Perspective on Findings
Amorim said the new research is “very useful,” although it has limitations that are common in large database studies. “A key point that this study highlights is the variability in the impact of TBI type on mortality and the differential risk across different age groups,” he said.
As for the higher risk in younger people, Amorim said this may be related to severity of injury: “Older patients often have TBI after falls, while younger patients are more frequently involved in traffic accidents or victims of violence,” he said
In the big picture, Amorim said, “studies like this highlight the importance of moving beyond a one-size-fits-all approach in epilepsy care. Understanding the nuances of posttraumatic epilepsy—how the type of injury, age, and other factors affect outcomes—can help us personalize treatment and counseling and maybe even guide future research into preventing or mitigating epilepsy after brain injury. New methods to automate review of medical records with higher resolution, such as large language models and natural language processing, may make this type of study with large databases even more comprehensive and impactful.”
Haneef said the findings highlight the importance of recognizing PTE as a higher-risk epilepsy and prioritizing early specialty care, especially after focal/diffuse brain injury or fracture. “Screen proactively for drug resistance and fast-track definitive therapies—surgery and device-based therapies—when indicated,” Haneef said. “Management should also include optimized antiseizure therapy, comorbidity control, and safety counseling, since many deaths may be preventable with coordinated multidisciplinary care.”
Haneef added that clinicians should “pay particular attention to younger PTE patients with extracerebral hemorrhage, who showed the greatest relative mortality.”
He also noted that the US Department of Veterans Affairs has comprehensive Epilepsy Centers of Excellence across the country.
The US Department of Defense (DoD) funded the study. Haneef discloses DoD funding, and another author discloses DoD and VA funding. Other authors have no disclosures.
Amorim discloses funding from DoD, NIH, American Heart Association, Regents of the University of California, Cures Within Reach, Zoll Foundation, and Hellman Foundation.
Journal Highlights: July-November 2025
Endoscopy
Barkun AN, et al. Canadian Association of Gastroenterology Clinical Practice Guideline for the Endoscopic Management of Nonvariceal Nonpeptic Ulcer Upper Gastrointestinal Bleeding. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.04.041.
Kindel TL, et al. Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2024.10.003.
Roy A, et al. Endohepatology: Evolving Indications, Challenges, Unmet Needs and Opportunities. Gastro Hep Advances. 2025 Oct. doi: 10.1016/j.gastha.2025.100838.
Esophagus
Wani S, et al. AGA Clinical Practice Guideline on Surveillance of Barrett’s Esophagus. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.09.012.
Reed CC, et al. Worsening Disease Severity as Measured by I-SEE Associates With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis Patients. Clin Gastroenterol Hepatol. 2025 Sep. doi: 10.1016/j.cgh.2025.01.015.
Kagzi Y, et al. Safety and Efficacy of Transoral Incisionless Fundoplication for Post–Esophageal Peroral Endoscopic Myotomy Gastroesophageal Reflux Disease With Esophagitis: A Meta-Analysis. Tech Innov Gastrointest Endosc. 2025 Oct. doi:10.1016/j.tige.2025.250953.
Stomach
Staller K, et al. AGA Clinical Practice Guideline on Management of Gastroparesis. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.08.004.
Colon
Bergman D, et al. Cholecystectomy Is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2024.12.032.
Liver
Younossi ZM, et al. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.02.044.
Kabelitz MA, et al. Early Occurrence of Hepatic Encephalopathy Following Transjugular Intrahepatic Portosystemic Shunt Insertion is Linked to Impaired Survival: A Multicenter Cohort Study. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2025.01.024.
Brar G, et al. Association of Cirrhosis Etiology with Outcomes After TIPS: A National Cohort Study. Gastro Hep Advances. 2025 Nov. doi: 10.1016/j.gastha.2025.100850.
IBD
Kucharzik T, et al. Role of Noninvasive Imaging in the Diagnosis and Management of Patients With Suspected and Established Inflammatory Bowel Disease. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.002.
Griffiths BJ, et al. Hypercoagulation After Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study. Clin Gastroenterol Hepatol. 2025 Sep. doi: 10.1016/j.cgh.2024.10.031.
Disorders of Gut-Brain Interaction
Trindade IA, et al. Implications of Shame for Patient-Reported Outcomes in Bowel Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.06.030.
Salwen-Deremer JK, et al. A Practical Guide to Incorporating a Psychologist Into a Gastroenterology Practice. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.05.014.
Misc
Monahan K, et al. In Our Scope of Practice: Genetic Risk Assessment and Testing for Gastrointestinal Cancers and Polyposis in Gastroenterology. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.001.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Endoscopy
Barkun AN, et al. Canadian Association of Gastroenterology Clinical Practice Guideline for the Endoscopic Management of Nonvariceal Nonpeptic Ulcer Upper Gastrointestinal Bleeding. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.04.041.
Kindel TL, et al. Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2024.10.003.
Roy A, et al. Endohepatology: Evolving Indications, Challenges, Unmet Needs and Opportunities. Gastro Hep Advances. 2025 Oct. doi: 10.1016/j.gastha.2025.100838.
Esophagus
Wani S, et al. AGA Clinical Practice Guideline on Surveillance of Barrett’s Esophagus. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.09.012.
Reed CC, et al. Worsening Disease Severity as Measured by I-SEE Associates With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis Patients. Clin Gastroenterol Hepatol. 2025 Sep. doi: 10.1016/j.cgh.2025.01.015.
Kagzi Y, et al. Safety and Efficacy of Transoral Incisionless Fundoplication for Post–Esophageal Peroral Endoscopic Myotomy Gastroesophageal Reflux Disease With Esophagitis: A Meta-Analysis. Tech Innov Gastrointest Endosc. 2025 Oct. doi:10.1016/j.tige.2025.250953.
Stomach
Staller K, et al. AGA Clinical Practice Guideline on Management of Gastroparesis. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.08.004.
Colon
Bergman D, et al. Cholecystectomy Is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2024.12.032.
Liver
Younossi ZM, et al. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.02.044.
Kabelitz MA, et al. Early Occurrence of Hepatic Encephalopathy Following Transjugular Intrahepatic Portosystemic Shunt Insertion is Linked to Impaired Survival: A Multicenter Cohort Study. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2025.01.024.
Brar G, et al. Association of Cirrhosis Etiology with Outcomes After TIPS: A National Cohort Study. Gastro Hep Advances. 2025 Nov. doi: 10.1016/j.gastha.2025.100850.
IBD
Kucharzik T, et al. Role of Noninvasive Imaging in the Diagnosis and Management of Patients With Suspected and Established Inflammatory Bowel Disease. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.002.
Griffiths BJ, et al. Hypercoagulation After Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study. Clin Gastroenterol Hepatol. 2025 Sep. doi: 10.1016/j.cgh.2024.10.031.
Disorders of Gut-Brain Interaction
Trindade IA, et al. Implications of Shame for Patient-Reported Outcomes in Bowel Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.06.030.
Salwen-Deremer JK, et al. A Practical Guide to Incorporating a Psychologist Into a Gastroenterology Practice. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.05.014.
Misc
Monahan K, et al. In Our Scope of Practice: Genetic Risk Assessment and Testing for Gastrointestinal Cancers and Polyposis in Gastroenterology. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.001.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Endoscopy
Barkun AN, et al. Canadian Association of Gastroenterology Clinical Practice Guideline for the Endoscopic Management of Nonvariceal Nonpeptic Ulcer Upper Gastrointestinal Bleeding. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.04.041.
Kindel TL, et al. Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2024.10.003.
Roy A, et al. Endohepatology: Evolving Indications, Challenges, Unmet Needs and Opportunities. Gastro Hep Advances. 2025 Oct. doi: 10.1016/j.gastha.2025.100838.
Esophagus
Wani S, et al. AGA Clinical Practice Guideline on Surveillance of Barrett’s Esophagus. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.09.012.
Reed CC, et al. Worsening Disease Severity as Measured by I-SEE Associates With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis Patients. Clin Gastroenterol Hepatol. 2025 Sep. doi: 10.1016/j.cgh.2025.01.015.
Kagzi Y, et al. Safety and Efficacy of Transoral Incisionless Fundoplication for Post–Esophageal Peroral Endoscopic Myotomy Gastroesophageal Reflux Disease With Esophagitis: A Meta-Analysis. Tech Innov Gastrointest Endosc. 2025 Oct. doi:10.1016/j.tige.2025.250953.
Stomach
Staller K, et al. AGA Clinical Practice Guideline on Management of Gastroparesis. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.08.004.
Colon
Bergman D, et al. Cholecystectomy Is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2024.12.032.
Liver
Younossi ZM, et al. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025 Oct. doi: 10.1053/j.gastro.2025.02.044.
Kabelitz MA, et al. Early Occurrence of Hepatic Encephalopathy Following Transjugular Intrahepatic Portosystemic Shunt Insertion is Linked to Impaired Survival: A Multicenter Cohort Study. Clin Gastroenterol Hepatol. 2025 Nov. doi: 10.1016/j.cgh.2025.01.024.
Brar G, et al. Association of Cirrhosis Etiology with Outcomes After TIPS: A National Cohort Study. Gastro Hep Advances. 2025 Nov. doi: 10.1016/j.gastha.2025.100850.
IBD
Kucharzik T, et al. Role of Noninvasive Imaging in the Diagnosis and Management of Patients With Suspected and Established Inflammatory Bowel Disease. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.002.
Griffiths BJ, et al. Hypercoagulation After Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study. Clin Gastroenterol Hepatol. 2025 Sep. doi: 10.1016/j.cgh.2024.10.031.
Disorders of Gut-Brain Interaction
Trindade IA, et al. Implications of Shame for Patient-Reported Outcomes in Bowel Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.06.030.
Salwen-Deremer JK, et al. A Practical Guide to Incorporating a Psychologist Into a Gastroenterology Practice. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.05.014.
Misc
Monahan K, et al. In Our Scope of Practice: Genetic Risk Assessment and Testing for Gastrointestinal Cancers and Polyposis in Gastroenterology. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.001.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Office-Based Endoscopy Model Offers Way Forward for Outpatient GI
After decades of successful growth, the ambulatory surgery center (ASC) model may be turning a corner, opening up opportunity for office-based endoscopy models, according to a recent practice management editorial published in Clinical Gastroenterology and Hepatology.
Although office endoscopy has been an option, it hasn’t always felt practical or financially viable in the past. However, the paradigm appears to be shifting as ASC-based revenue streams show signs of stress and fail to keep pace with inflation. As healthcare regulatory and economic environments continue to change, gastroenterologists need a new model to support equity, efficiency, and growth in gastrointestinal (GI) care delivery, the authors wrote.
“Through the course of my 40-year career, I’ve been hit with a lot of changes related to regulations, insurance, and the market. You can’t stay entrenched in your old ways. You have to remain pivotable and come up with new strategic positions,” said Lawrence Kosinski, MD, AGAF, lead author and founder of SonarMD and VOCnomics.
During his private practice career, Kosinski built one of the largest GI practices in Illinois, which had seven ASCs and is now part of one of the largest GI groups in the country. Across 30 years of experience with ASCs, Kosinski has watched the reimbursement for professional services decline, as well as for added revenue streams such as pathology and anesthesia.
Looking for a better solution, Kosinski served on the governing board for the American Gastroenterological Association as the councilor for development and growth. During the past 3 years, he has spoken with GI practices and worked with a national anesthesia company — Ambulatory Anesthesia Care — to better understand the office endoscopy setting.
“In the ’90s, all I wanted was to have an ASC because that was in vogue,” he said. “But if you look critically at what has happened to the business of outpatient endoscopy in the past 25 years, you’ll see that professional fees haven’t kept up, and trying to replace that lost revenue is a losing battle.”
Considering Financial Shifts
Since 2001, professional reimbursement for colonoscopies has fallen by more than 40% while ASC revenue has risen, decreasing the percentage of revenue from professional fees (from 34% to 23%) and increasing the facility component (from 44% to 60%), Kosinski and colleagues wrote.
When looking at profit, compression of professional service fees appears even greater, especially with surging costs of anesthesia care due to high demand and provider shortages. Beyond that, about a third of ASCs are owned at least partially by national entities, as of 2024, leading to even lower realization of profit.
“The profit margins have really been crushed, so what is a GI doc to do? Go where there is opportunity,” Kosinski said. “The difference between hospitals and ASCs has been compressed, so what about the office?”
The proposed 2026 Medicare Physician Fee Schedule includes a 14% increase in reimbursement for office-based procedures, including endoscopy, as well as a 7% decrease for facility-based procedures.
In several states — such as Illinois, Oregon, Virginia, Washington, and Wisconsin — health plans are introducing programs to promote the transition of outpatient endoscopy to office settings rather than hospital-based or ASC-based settings due to costs, the authors wrote.
“The decision to start offering office-based endoscopy services was an easy one for our practice, as it provides a way for us to provide patients convenient, easy-to-access endoscopy that is high quality yet much more affordable than hospital-based settings,” said Neil Gupta, MD, managing partner at Midwest Digestive Health & Nutrition in Des Plaines, Illinois.
The practice has used office-based endoscopy for nearly 2 years, Gupta said, performing about 5000 GI endoscopy procedures per year.
“As we all try to find better ways to provide high-quality but affordable care for patients, office-based endoscopy is a great way to help achieve those goals,” he said. “Healthcare professionals and patients should all be asking, ‘What type of site am I getting my GI endoscopy scheduled at — hospital, surgery center, or physician’s office?’”
Regaining Autonomy and Time
Beyond the financial dynamics, , Kosinski and colleagues wrote.
Looking ahead, office-based models can also provide the agility and infrastructure to compete in value-based care models, they wrote. In turn, value-based models can create relevance and resilience in a continually changing healthcare environment.
Without the involvement of ASC managers, investors, or health system partners, physicians retain control of scheduling, clinical protocols, financial decisions, and operational workflows, the authors wrote. This could create better alignment with personal preferences, clinical judgment, and patient needs, they noted.
“GI physicians should no longer feel trapped in a hospital setting where they lack independence and influence over decision-making,” said Rock Rockett, PhD, owner and principal consultant of Rockett Healthcare Strategies, which partners with GI groups nationwide to help with development, accreditation, and payer contracting for office endoscopy.
“GI physicians should also no longer feel trapped in a ‘bad marriage’ with partners in an ASC or partners in a practice who create a difficult work environment,” he said. “The viability of office endoscopy allows them to strike out on their own or set up a new partnership on more equitable terms that are attractive for them.”
Patient safety and quality also appear to be similar or better in office-based settings, based on benchmarking data analyzed so far. Hospital transfers were lower, falls were similar, and patient experience was positive, the authors wrote.
At the same time, Kosinski and colleagues noted the difficulty in shifting to office-based models. Most practices have committed to ASCs, for instance, and adding an office-based room can be challenging. Otherwise, practices already use their available office space and don’t have extra rooms available. In that case, an office endoscopy suite may be best suited for expansion sites, allowing practices to grow into new service areas, they wrote.
“You can’t fight the market. You have to focus on what the market wants and needs,” Kosinski said. “To do that, you have to be able to pivot and change direction, looking for new ways to change your mission. This could be an option to do that.”
Kosinski, Gupta, and Rockett declared having no conflicts of interest other than their current employments.
A version of this article appeared on Medscape.com.
After decades of successful growth, the ambulatory surgery center (ASC) model may be turning a corner, opening up opportunity for office-based endoscopy models, according to a recent practice management editorial published in Clinical Gastroenterology and Hepatology.
Although office endoscopy has been an option, it hasn’t always felt practical or financially viable in the past. However, the paradigm appears to be shifting as ASC-based revenue streams show signs of stress and fail to keep pace with inflation. As healthcare regulatory and economic environments continue to change, gastroenterologists need a new model to support equity, efficiency, and growth in gastrointestinal (GI) care delivery, the authors wrote.
“Through the course of my 40-year career, I’ve been hit with a lot of changes related to regulations, insurance, and the market. You can’t stay entrenched in your old ways. You have to remain pivotable and come up with new strategic positions,” said Lawrence Kosinski, MD, AGAF, lead author and founder of SonarMD and VOCnomics.
During his private practice career, Kosinski built one of the largest GI practices in Illinois, which had seven ASCs and is now part of one of the largest GI groups in the country. Across 30 years of experience with ASCs, Kosinski has watched the reimbursement for professional services decline, as well as for added revenue streams such as pathology and anesthesia.
Looking for a better solution, Kosinski served on the governing board for the American Gastroenterological Association as the councilor for development and growth. During the past 3 years, he has spoken with GI practices and worked with a national anesthesia company — Ambulatory Anesthesia Care — to better understand the office endoscopy setting.
“In the ’90s, all I wanted was to have an ASC because that was in vogue,” he said. “But if you look critically at what has happened to the business of outpatient endoscopy in the past 25 years, you’ll see that professional fees haven’t kept up, and trying to replace that lost revenue is a losing battle.”
Considering Financial Shifts
Since 2001, professional reimbursement for colonoscopies has fallen by more than 40% while ASC revenue has risen, decreasing the percentage of revenue from professional fees (from 34% to 23%) and increasing the facility component (from 44% to 60%), Kosinski and colleagues wrote.
When looking at profit, compression of professional service fees appears even greater, especially with surging costs of anesthesia care due to high demand and provider shortages. Beyond that, about a third of ASCs are owned at least partially by national entities, as of 2024, leading to even lower realization of profit.
“The profit margins have really been crushed, so what is a GI doc to do? Go where there is opportunity,” Kosinski said. “The difference between hospitals and ASCs has been compressed, so what about the office?”
The proposed 2026 Medicare Physician Fee Schedule includes a 14% increase in reimbursement for office-based procedures, including endoscopy, as well as a 7% decrease for facility-based procedures.
In several states — such as Illinois, Oregon, Virginia, Washington, and Wisconsin — health plans are introducing programs to promote the transition of outpatient endoscopy to office settings rather than hospital-based or ASC-based settings due to costs, the authors wrote.
“The decision to start offering office-based endoscopy services was an easy one for our practice, as it provides a way for us to provide patients convenient, easy-to-access endoscopy that is high quality yet much more affordable than hospital-based settings,” said Neil Gupta, MD, managing partner at Midwest Digestive Health & Nutrition in Des Plaines, Illinois.
The practice has used office-based endoscopy for nearly 2 years, Gupta said, performing about 5000 GI endoscopy procedures per year.
“As we all try to find better ways to provide high-quality but affordable care for patients, office-based endoscopy is a great way to help achieve those goals,” he said. “Healthcare professionals and patients should all be asking, ‘What type of site am I getting my GI endoscopy scheduled at — hospital, surgery center, or physician’s office?’”
Regaining Autonomy and Time
Beyond the financial dynamics, , Kosinski and colleagues wrote.
Looking ahead, office-based models can also provide the agility and infrastructure to compete in value-based care models, they wrote. In turn, value-based models can create relevance and resilience in a continually changing healthcare environment.
Without the involvement of ASC managers, investors, or health system partners, physicians retain control of scheduling, clinical protocols, financial decisions, and operational workflows, the authors wrote. This could create better alignment with personal preferences, clinical judgment, and patient needs, they noted.
“GI physicians should no longer feel trapped in a hospital setting where they lack independence and influence over decision-making,” said Rock Rockett, PhD, owner and principal consultant of Rockett Healthcare Strategies, which partners with GI groups nationwide to help with development, accreditation, and payer contracting for office endoscopy.
“GI physicians should also no longer feel trapped in a ‘bad marriage’ with partners in an ASC or partners in a practice who create a difficult work environment,” he said. “The viability of office endoscopy allows them to strike out on their own or set up a new partnership on more equitable terms that are attractive for them.”
Patient safety and quality also appear to be similar or better in office-based settings, based on benchmarking data analyzed so far. Hospital transfers were lower, falls were similar, and patient experience was positive, the authors wrote.
At the same time, Kosinski and colleagues noted the difficulty in shifting to office-based models. Most practices have committed to ASCs, for instance, and adding an office-based room can be challenging. Otherwise, practices already use their available office space and don’t have extra rooms available. In that case, an office endoscopy suite may be best suited for expansion sites, allowing practices to grow into new service areas, they wrote.
“You can’t fight the market. You have to focus on what the market wants and needs,” Kosinski said. “To do that, you have to be able to pivot and change direction, looking for new ways to change your mission. This could be an option to do that.”
Kosinski, Gupta, and Rockett declared having no conflicts of interest other than their current employments.
A version of this article appeared on Medscape.com.
After decades of successful growth, the ambulatory surgery center (ASC) model may be turning a corner, opening up opportunity for office-based endoscopy models, according to a recent practice management editorial published in Clinical Gastroenterology and Hepatology.
Although office endoscopy has been an option, it hasn’t always felt practical or financially viable in the past. However, the paradigm appears to be shifting as ASC-based revenue streams show signs of stress and fail to keep pace with inflation. As healthcare regulatory and economic environments continue to change, gastroenterologists need a new model to support equity, efficiency, and growth in gastrointestinal (GI) care delivery, the authors wrote.
“Through the course of my 40-year career, I’ve been hit with a lot of changes related to regulations, insurance, and the market. You can’t stay entrenched in your old ways. You have to remain pivotable and come up with new strategic positions,” said Lawrence Kosinski, MD, AGAF, lead author and founder of SonarMD and VOCnomics.
During his private practice career, Kosinski built one of the largest GI practices in Illinois, which had seven ASCs and is now part of one of the largest GI groups in the country. Across 30 years of experience with ASCs, Kosinski has watched the reimbursement for professional services decline, as well as for added revenue streams such as pathology and anesthesia.
Looking for a better solution, Kosinski served on the governing board for the American Gastroenterological Association as the councilor for development and growth. During the past 3 years, he has spoken with GI practices and worked with a national anesthesia company — Ambulatory Anesthesia Care — to better understand the office endoscopy setting.
“In the ’90s, all I wanted was to have an ASC because that was in vogue,” he said. “But if you look critically at what has happened to the business of outpatient endoscopy in the past 25 years, you’ll see that professional fees haven’t kept up, and trying to replace that lost revenue is a losing battle.”
Considering Financial Shifts
Since 2001, professional reimbursement for colonoscopies has fallen by more than 40% while ASC revenue has risen, decreasing the percentage of revenue from professional fees (from 34% to 23%) and increasing the facility component (from 44% to 60%), Kosinski and colleagues wrote.
When looking at profit, compression of professional service fees appears even greater, especially with surging costs of anesthesia care due to high demand and provider shortages. Beyond that, about a third of ASCs are owned at least partially by national entities, as of 2024, leading to even lower realization of profit.
“The profit margins have really been crushed, so what is a GI doc to do? Go where there is opportunity,” Kosinski said. “The difference between hospitals and ASCs has been compressed, so what about the office?”
The proposed 2026 Medicare Physician Fee Schedule includes a 14% increase in reimbursement for office-based procedures, including endoscopy, as well as a 7% decrease for facility-based procedures.
In several states — such as Illinois, Oregon, Virginia, Washington, and Wisconsin — health plans are introducing programs to promote the transition of outpatient endoscopy to office settings rather than hospital-based or ASC-based settings due to costs, the authors wrote.
“The decision to start offering office-based endoscopy services was an easy one for our practice, as it provides a way for us to provide patients convenient, easy-to-access endoscopy that is high quality yet much more affordable than hospital-based settings,” said Neil Gupta, MD, managing partner at Midwest Digestive Health & Nutrition in Des Plaines, Illinois.
The practice has used office-based endoscopy for nearly 2 years, Gupta said, performing about 5000 GI endoscopy procedures per year.
“As we all try to find better ways to provide high-quality but affordable care for patients, office-based endoscopy is a great way to help achieve those goals,” he said. “Healthcare professionals and patients should all be asking, ‘What type of site am I getting my GI endoscopy scheduled at — hospital, surgery center, or physician’s office?’”
Regaining Autonomy and Time
Beyond the financial dynamics, , Kosinski and colleagues wrote.
Looking ahead, office-based models can also provide the agility and infrastructure to compete in value-based care models, they wrote. In turn, value-based models can create relevance and resilience in a continually changing healthcare environment.
Without the involvement of ASC managers, investors, or health system partners, physicians retain control of scheduling, clinical protocols, financial decisions, and operational workflows, the authors wrote. This could create better alignment with personal preferences, clinical judgment, and patient needs, they noted.
“GI physicians should no longer feel trapped in a hospital setting where they lack independence and influence over decision-making,” said Rock Rockett, PhD, owner and principal consultant of Rockett Healthcare Strategies, which partners with GI groups nationwide to help with development, accreditation, and payer contracting for office endoscopy.
“GI physicians should also no longer feel trapped in a ‘bad marriage’ with partners in an ASC or partners in a practice who create a difficult work environment,” he said. “The viability of office endoscopy allows them to strike out on their own or set up a new partnership on more equitable terms that are attractive for them.”
Patient safety and quality also appear to be similar or better in office-based settings, based on benchmarking data analyzed so far. Hospital transfers were lower, falls were similar, and patient experience was positive, the authors wrote.
At the same time, Kosinski and colleagues noted the difficulty in shifting to office-based models. Most practices have committed to ASCs, for instance, and adding an office-based room can be challenging. Otherwise, practices already use their available office space and don’t have extra rooms available. In that case, an office endoscopy suite may be best suited for expansion sites, allowing practices to grow into new service areas, they wrote.
“You can’t fight the market. You have to focus on what the market wants and needs,” Kosinski said. “To do that, you have to be able to pivot and change direction, looking for new ways to change your mission. This could be an option to do that.”
Kosinski, Gupta, and Rockett declared having no conflicts of interest other than their current employments.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
New Drug Eases Side Effects of Weight-Loss Meds
, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.
Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.
Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.
In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.
NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.
Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.
In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.
Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.
The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.
“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.
The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.
Decrease Side Effects for Weight-Loss Success
“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, said in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.
The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.
Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told GI & Hepatology News.
The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.
The study was funded by Neurogastrx.
Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.
A version of this article appeared on Medscape.com.
, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.
Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.
Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.
In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.
NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.
Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.
In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.
Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.
The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.
“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.
The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.
Decrease Side Effects for Weight-Loss Success
“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, said in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.
The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.
Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told GI & Hepatology News.
The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.
The study was funded by Neurogastrx.
Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.
A version of this article appeared on Medscape.com.
, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.
Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.
Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.
In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.
NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.
Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.
In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.
Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.
The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.
“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.
The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.
Decrease Side Effects for Weight-Loss Success
“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, said in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.
The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.
Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told GI & Hepatology News.
The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.
The study was funded by Neurogastrx.
Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.
A version of this article appeared on Medscape.com.
Nailing Neoplastic Lesions in Barrett’s Esophagus
, said Prateek Sharma, MD, in a presentation on the management of BE at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
However, clinicians often make mistakes such as failing to remove debris such as saliva and bile from the esophagus prior to assessing a patient, said Sharma, professor of medicine and the Elaine Blaylock Endowed Professor at the University of Kansas School of Medicine and the Cancer Center, Kansas City, Kansas.
More than 90% of neoplasias in patients with BE are found on an index endoscopy or within 6 months, as shown by Sharma and his colleagues in a systematic review, which highlights the importance of a high-quality index endoscopy, he told meeting attendees.
To improve the index endoscopy, Sharma developed a new algorithm called “CLEAN.”
The algorithm is composed of five steps, he said, the first of which is Clear: clear the esophagus of debris, including saliva and bile. Adequate prep is essential to detecting clinically significant lesions in patients with BE, he explained. In a study published in 2024, Sharma and colleagues found adequate cleanliness of the upper gastrointestinal tract was associated with a significantly higher detection rate of clinically significant lesions.
The second step of the algorithm is Learn: pay attention to BE inspection time and learn slow withdrawal strategies.
It’s important not to shortchange inspection time, Sharma emphasized. He cited a previous study in which the percentage of patients with BE who had high-grade dysplasia or esophageal adenocarcinoma during a surveillance endoscopy was 15% with inspection times of 2 minutes or less but jumped to 69% with inspection times of 7 minutes or more.
The third step of CLEAN is Endoscope: conduct a high-definition white-light endoscopy, which should be coupled with the fourth step, Acquire: acquire education on BE-related neoplasia, to learn how to recognize neoplastic lesions, he stressed.
The final step of the algorithm is Neoplasia detection rate (NDR): follow a quality metric to measure NDR.
The algorithm emphasizes a comprehensive approach in conjunction with resection of visible lesions followed by ablation for complete eradication, Sharma told GI & Hepatology News.
After Identification: What’s Next?
If lesions are identified, the next step is resection and/or ablation, Sharma said.
“Resection is typically used for visible lesions, nodules, or masses, while ablation is used to treat the remaining underlying Barrett tissue,” he told GI & Hepatology News. “A combination of both is often necessary to fully treat advanced cases, such as when a nodule is resected and the surrounding area is subsequently ablated.”
“It’s important to understand why we need to resect,” he said.
“Resection removes the lesion” and “provides more accurate histopathology reading and staging of how deep the lesion is,” he explained. Options for resection of cancerous or precancerous lesions in patients with BE include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
The treatment algorithm for BE continues to evolve, Sharma said in his presentation. Currently, evidence supports EMR for most cases, but ESD is based on factors including lesion size ≥ 25-30 mm and potential submucosal invasion, he said.
He cited a study of 1000 adults with early BE who were managed with EMR that showed a 96% curative response after 5 years. Similarly, a review of ESD for early BE neoplasia including 501 patients showed a 75% curative response rate overall and a 93% en bloc resection rate, he noted.
Ablation
In terms of ablation, radiofrequency ablation, hybrid argon plasma coagulation, and the multifocal cryoballoon procedure have shown significant effectiveness, Sharma said.
In a 2020 multicenter, prospective study of 120 adult patients with BE, 76% achieved complete eradication of dysplasia, and 72% achieved complete eradication of intestinal metaplasia. As for safety, data from nine European centers including 154 patients who underwent ablation after resection had an adverse event rate of 6%, said Sharma.
In the Clinic
“It is sometimes difficult to detect subtle nodularity and irregularity that would benefit more from resection therapy/EMR rather than ablation,” said Gyanprakash A. Ketwaroo, MD, associate professor of medicine (digestive diseases) at Yale University, New Haven, Connecticut.
“Lesions can be obscured by esophagitis, peristalsis, or the shape of the [gastroesophageal] GE junction,” he noted. Therefore, careful scope cleaning and inspection with high-definition white light and narrow band imaging are important, he said. “Using a cap on the scope to better distend or manipulate the gastroesophageal junction also helps identify obscured lesions,” he added.
“Any acronym or approach that reminds us to slow down, and examine carefully, is welcome,” Ketwaroo told GI & Hepatology News. The CLEAN algorithm provides a useful summary of some of the key steps all clinicians should incorporate into approaching BE and could be useful for teaching trainees, he added.
Sharma disclosed serving as a consultant for the Olympus Corporation and Exact Sciences and receiving grant support from Fujifilm, Erbe Medical, and Braintree Pharmaceuticals.
A version of this article appeared on Medscape.com.
, said Prateek Sharma, MD, in a presentation on the management of BE at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
However, clinicians often make mistakes such as failing to remove debris such as saliva and bile from the esophagus prior to assessing a patient, said Sharma, professor of medicine and the Elaine Blaylock Endowed Professor at the University of Kansas School of Medicine and the Cancer Center, Kansas City, Kansas.
More than 90% of neoplasias in patients with BE are found on an index endoscopy or within 6 months, as shown by Sharma and his colleagues in a systematic review, which highlights the importance of a high-quality index endoscopy, he told meeting attendees.
To improve the index endoscopy, Sharma developed a new algorithm called “CLEAN.”
The algorithm is composed of five steps, he said, the first of which is Clear: clear the esophagus of debris, including saliva and bile. Adequate prep is essential to detecting clinically significant lesions in patients with BE, he explained. In a study published in 2024, Sharma and colleagues found adequate cleanliness of the upper gastrointestinal tract was associated with a significantly higher detection rate of clinically significant lesions.
The second step of the algorithm is Learn: pay attention to BE inspection time and learn slow withdrawal strategies.
It’s important not to shortchange inspection time, Sharma emphasized. He cited a previous study in which the percentage of patients with BE who had high-grade dysplasia or esophageal adenocarcinoma during a surveillance endoscopy was 15% with inspection times of 2 minutes or less but jumped to 69% with inspection times of 7 minutes or more.
The third step of CLEAN is Endoscope: conduct a high-definition white-light endoscopy, which should be coupled with the fourth step, Acquire: acquire education on BE-related neoplasia, to learn how to recognize neoplastic lesions, he stressed.
The final step of the algorithm is Neoplasia detection rate (NDR): follow a quality metric to measure NDR.
The algorithm emphasizes a comprehensive approach in conjunction with resection of visible lesions followed by ablation for complete eradication, Sharma told GI & Hepatology News.
After Identification: What’s Next?
If lesions are identified, the next step is resection and/or ablation, Sharma said.
“Resection is typically used for visible lesions, nodules, or masses, while ablation is used to treat the remaining underlying Barrett tissue,” he told GI & Hepatology News. “A combination of both is often necessary to fully treat advanced cases, such as when a nodule is resected and the surrounding area is subsequently ablated.”
“It’s important to understand why we need to resect,” he said.
“Resection removes the lesion” and “provides more accurate histopathology reading and staging of how deep the lesion is,” he explained. Options for resection of cancerous or precancerous lesions in patients with BE include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
The treatment algorithm for BE continues to evolve, Sharma said in his presentation. Currently, evidence supports EMR for most cases, but ESD is based on factors including lesion size ≥ 25-30 mm and potential submucosal invasion, he said.
He cited a study of 1000 adults with early BE who were managed with EMR that showed a 96% curative response after 5 years. Similarly, a review of ESD for early BE neoplasia including 501 patients showed a 75% curative response rate overall and a 93% en bloc resection rate, he noted.
Ablation
In terms of ablation, radiofrequency ablation, hybrid argon plasma coagulation, and the multifocal cryoballoon procedure have shown significant effectiveness, Sharma said.
In a 2020 multicenter, prospective study of 120 adult patients with BE, 76% achieved complete eradication of dysplasia, and 72% achieved complete eradication of intestinal metaplasia. As for safety, data from nine European centers including 154 patients who underwent ablation after resection had an adverse event rate of 6%, said Sharma.
In the Clinic
“It is sometimes difficult to detect subtle nodularity and irregularity that would benefit more from resection therapy/EMR rather than ablation,” said Gyanprakash A. Ketwaroo, MD, associate professor of medicine (digestive diseases) at Yale University, New Haven, Connecticut.
“Lesions can be obscured by esophagitis, peristalsis, or the shape of the [gastroesophageal] GE junction,” he noted. Therefore, careful scope cleaning and inspection with high-definition white light and narrow band imaging are important, he said. “Using a cap on the scope to better distend or manipulate the gastroesophageal junction also helps identify obscured lesions,” he added.
“Any acronym or approach that reminds us to slow down, and examine carefully, is welcome,” Ketwaroo told GI & Hepatology News. The CLEAN algorithm provides a useful summary of some of the key steps all clinicians should incorporate into approaching BE and could be useful for teaching trainees, he added.
Sharma disclosed serving as a consultant for the Olympus Corporation and Exact Sciences and receiving grant support from Fujifilm, Erbe Medical, and Braintree Pharmaceuticals.
A version of this article appeared on Medscape.com.
, said Prateek Sharma, MD, in a presentation on the management of BE at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
However, clinicians often make mistakes such as failing to remove debris such as saliva and bile from the esophagus prior to assessing a patient, said Sharma, professor of medicine and the Elaine Blaylock Endowed Professor at the University of Kansas School of Medicine and the Cancer Center, Kansas City, Kansas.
More than 90% of neoplasias in patients with BE are found on an index endoscopy or within 6 months, as shown by Sharma and his colleagues in a systematic review, which highlights the importance of a high-quality index endoscopy, he told meeting attendees.
To improve the index endoscopy, Sharma developed a new algorithm called “CLEAN.”
The algorithm is composed of five steps, he said, the first of which is Clear: clear the esophagus of debris, including saliva and bile. Adequate prep is essential to detecting clinically significant lesions in patients with BE, he explained. In a study published in 2024, Sharma and colleagues found adequate cleanliness of the upper gastrointestinal tract was associated with a significantly higher detection rate of clinically significant lesions.
The second step of the algorithm is Learn: pay attention to BE inspection time and learn slow withdrawal strategies.
It’s important not to shortchange inspection time, Sharma emphasized. He cited a previous study in which the percentage of patients with BE who had high-grade dysplasia or esophageal adenocarcinoma during a surveillance endoscopy was 15% with inspection times of 2 minutes or less but jumped to 69% with inspection times of 7 minutes or more.
The third step of CLEAN is Endoscope: conduct a high-definition white-light endoscopy, which should be coupled with the fourth step, Acquire: acquire education on BE-related neoplasia, to learn how to recognize neoplastic lesions, he stressed.
The final step of the algorithm is Neoplasia detection rate (NDR): follow a quality metric to measure NDR.
The algorithm emphasizes a comprehensive approach in conjunction with resection of visible lesions followed by ablation for complete eradication, Sharma told GI & Hepatology News.
After Identification: What’s Next?
If lesions are identified, the next step is resection and/or ablation, Sharma said.
“Resection is typically used for visible lesions, nodules, or masses, while ablation is used to treat the remaining underlying Barrett tissue,” he told GI & Hepatology News. “A combination of both is often necessary to fully treat advanced cases, such as when a nodule is resected and the surrounding area is subsequently ablated.”
“It’s important to understand why we need to resect,” he said.
“Resection removes the lesion” and “provides more accurate histopathology reading and staging of how deep the lesion is,” he explained. Options for resection of cancerous or precancerous lesions in patients with BE include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
The treatment algorithm for BE continues to evolve, Sharma said in his presentation. Currently, evidence supports EMR for most cases, but ESD is based on factors including lesion size ≥ 25-30 mm and potential submucosal invasion, he said.
He cited a study of 1000 adults with early BE who were managed with EMR that showed a 96% curative response after 5 years. Similarly, a review of ESD for early BE neoplasia including 501 patients showed a 75% curative response rate overall and a 93% en bloc resection rate, he noted.
Ablation
In terms of ablation, radiofrequency ablation, hybrid argon plasma coagulation, and the multifocal cryoballoon procedure have shown significant effectiveness, Sharma said.
In a 2020 multicenter, prospective study of 120 adult patients with BE, 76% achieved complete eradication of dysplasia, and 72% achieved complete eradication of intestinal metaplasia. As for safety, data from nine European centers including 154 patients who underwent ablation after resection had an adverse event rate of 6%, said Sharma.
In the Clinic
“It is sometimes difficult to detect subtle nodularity and irregularity that would benefit more from resection therapy/EMR rather than ablation,” said Gyanprakash A. Ketwaroo, MD, associate professor of medicine (digestive diseases) at Yale University, New Haven, Connecticut.
“Lesions can be obscured by esophagitis, peristalsis, or the shape of the [gastroesophageal] GE junction,” he noted. Therefore, careful scope cleaning and inspection with high-definition white light and narrow band imaging are important, he said. “Using a cap on the scope to better distend or manipulate the gastroesophageal junction also helps identify obscured lesions,” he added.
“Any acronym or approach that reminds us to slow down, and examine carefully, is welcome,” Ketwaroo told GI & Hepatology News. The CLEAN algorithm provides a useful summary of some of the key steps all clinicians should incorporate into approaching BE and could be useful for teaching trainees, he added.
Sharma disclosed serving as a consultant for the Olympus Corporation and Exact Sciences and receiving grant support from Fujifilm, Erbe Medical, and Braintree Pharmaceuticals.
A version of this article appeared on Medscape.com.
FROM ACG 2025
Research Focuses on Mental Health Needs of Women Veterans
The more than 2 million women US veterans are the fastest-growing military population. While research into women veterans has traditionally lagged, more recently studies have begun to focus on their needs impacts of combat and service on women. These studies have found that women veterans preferred tailored solutions focused on women veterans.
A November 2025 study is one of the first to examine the impact of combat on women veterans. It found that those in combat roles had higher levels of depression, posttraumatic stress disorder (PTSD), dissociation, and overall poorer health compared with civilians and noncombat women military personnel. Previous research had found that women veterans had higher rates of lifetime and past-year PTSD (13.4%) compared with female civilians (8.0%), male veterans (7.7%), and male civilians (3.4%). A 2020 US Department of Veterans (VA) study of 4,928,638 men and 448,455 women similarly found that women had nearly twice the rates of depression and anxiety compared with men.
For many veterans, mental health issues may develop or be exacerbated in their return to civilian life. That transition can be especially confusing and isolating for women veterans, according to a 2024 study: “They neither fit in the military due to gendered relations centered on masculinity, or civilian life where they are largely misunderstood as ‘veterans.’ This ‘no woman’s land’ is poorly understood.” Few programs for transitioning veterans have been found effective for women veterans because they’ve been developed for a largely male veteran population. That includes mental health support programs.
Some women may prefer women-only groups, and even that choice may be dependent on their background, service history, socioeconomic level, and other factors. They may feel more comfortable in women-only groups if they’ve experienced MST. Others who have served in combat may choose mixed-gender programs. One study found that some women benefited from being in a mixed-gender group because it enabled them to work on difficulties with men in a safe environment. Other research has found that women veterans with substance use disorders are reluctant to seek help alongside men in the same facilities.
Accessing care may be especially challenging for rural women veterans. However, separate facilities and women-only groups are not always available, particularly in rural areas where there may be very few women veterans. And even if they are available, rural women are often up against barriers that urban women do not face, such as having to travel long distances to get care. Clinicians also may be hard to find in rural areas. Some participants in a 2025 study were hampered not only by a lack of female practitioners, but practitioners who were well trained to understand and treat the unique needs of female veterans: “[It’s] incredibly difficult to find a mental health practitioner that understands a veteran’s unique experience as a woman,” a participant said.
The more than 2 million women US veterans are the fastest-growing military population. While research into women veterans has traditionally lagged, more recently studies have begun to focus on their needs impacts of combat and service on women. These studies have found that women veterans preferred tailored solutions focused on women veterans.
A November 2025 study is one of the first to examine the impact of combat on women veterans. It found that those in combat roles had higher levels of depression, posttraumatic stress disorder (PTSD), dissociation, and overall poorer health compared with civilians and noncombat women military personnel. Previous research had found that women veterans had higher rates of lifetime and past-year PTSD (13.4%) compared with female civilians (8.0%), male veterans (7.7%), and male civilians (3.4%). A 2020 US Department of Veterans (VA) study of 4,928,638 men and 448,455 women similarly found that women had nearly twice the rates of depression and anxiety compared with men.
For many veterans, mental health issues may develop or be exacerbated in their return to civilian life. That transition can be especially confusing and isolating for women veterans, according to a 2024 study: “They neither fit in the military due to gendered relations centered on masculinity, or civilian life where they are largely misunderstood as ‘veterans.’ This ‘no woman’s land’ is poorly understood.” Few programs for transitioning veterans have been found effective for women veterans because they’ve been developed for a largely male veteran population. That includes mental health support programs.
Some women may prefer women-only groups, and even that choice may be dependent on their background, service history, socioeconomic level, and other factors. They may feel more comfortable in women-only groups if they’ve experienced MST. Others who have served in combat may choose mixed-gender programs. One study found that some women benefited from being in a mixed-gender group because it enabled them to work on difficulties with men in a safe environment. Other research has found that women veterans with substance use disorders are reluctant to seek help alongside men in the same facilities.
Accessing care may be especially challenging for rural women veterans. However, separate facilities and women-only groups are not always available, particularly in rural areas where there may be very few women veterans. And even if they are available, rural women are often up against barriers that urban women do not face, such as having to travel long distances to get care. Clinicians also may be hard to find in rural areas. Some participants in a 2025 study were hampered not only by a lack of female practitioners, but practitioners who were well trained to understand and treat the unique needs of female veterans: “[It’s] incredibly difficult to find a mental health practitioner that understands a veteran’s unique experience as a woman,” a participant said.
The more than 2 million women US veterans are the fastest-growing military population. While research into women veterans has traditionally lagged, more recently studies have begun to focus on their needs impacts of combat and service on women. These studies have found that women veterans preferred tailored solutions focused on women veterans.
A November 2025 study is one of the first to examine the impact of combat on women veterans. It found that those in combat roles had higher levels of depression, posttraumatic stress disorder (PTSD), dissociation, and overall poorer health compared with civilians and noncombat women military personnel. Previous research had found that women veterans had higher rates of lifetime and past-year PTSD (13.4%) compared with female civilians (8.0%), male veterans (7.7%), and male civilians (3.4%). A 2020 US Department of Veterans (VA) study of 4,928,638 men and 448,455 women similarly found that women had nearly twice the rates of depression and anxiety compared with men.
For many veterans, mental health issues may develop or be exacerbated in their return to civilian life. That transition can be especially confusing and isolating for women veterans, according to a 2024 study: “They neither fit in the military due to gendered relations centered on masculinity, or civilian life where they are largely misunderstood as ‘veterans.’ This ‘no woman’s land’ is poorly understood.” Few programs for transitioning veterans have been found effective for women veterans because they’ve been developed for a largely male veteran population. That includes mental health support programs.
Some women may prefer women-only groups, and even that choice may be dependent on their background, service history, socioeconomic level, and other factors. They may feel more comfortable in women-only groups if they’ve experienced MST. Others who have served in combat may choose mixed-gender programs. One study found that some women benefited from being in a mixed-gender group because it enabled them to work on difficulties with men in a safe environment. Other research has found that women veterans with substance use disorders are reluctant to seek help alongside men in the same facilities.
Accessing care may be especially challenging for rural women veterans. However, separate facilities and women-only groups are not always available, particularly in rural areas where there may be very few women veterans. And even if they are available, rural women are often up against barriers that urban women do not face, such as having to travel long distances to get care. Clinicians also may be hard to find in rural areas. Some participants in a 2025 study were hampered not only by a lack of female practitioners, but practitioners who were well trained to understand and treat the unique needs of female veterans: “[It’s] incredibly difficult to find a mental health practitioner that understands a veteran’s unique experience as a woman,” a participant said.
Text vs Video Psychotherapy: Which Is Better for Depression?
Text vs Video Psychotherapy: Which Is Better for Depression?
TOPLINE:
Message-based psychotherapy (MBP), which uses asynchronous emails or texts, showed effectiveness comparable with that of video-based psychotherapy (VBP) for the treatment of depression on a commercial digital mental health platform, a new study showed.
METHODOLOGY:
- Investigators conducted a pragmatic sequential multiple-assignment randomized clinical trial from 2022 to 2024 involving 850 adult patients with a diagnosis of depression (mean age, 34 years; 66% women; 60% White, 22% Black and 14% Hispanic).
- Patients were initially randomly assigned to receive weekly MBP (n = 423) or VBP (n = 427), with nonresponders randomly assigned at week 6 to receive combination therapy of MBP plus weekly or monthly VBP. All patients received treatment for up to 12 weeks.
- Primary outcomes included depression severity measured by the 9-item Patient Health Questionnaire (PHQ-9), social functioning measured by the Quality of Life in Neurological Disorders 8-item tool, response to treatment (≥ 50% reduction in PHQ-9 total score or Clinical Global Impressions-Improvement score ≤ 2), and remissions (PHQ-9 score < 5).
- Secondary outcomes were treating disengagement, therapeutic alliance measured on the Working Alliance Inventory-Short Revised, quality of care in the past 4 weeks, and treatment satisfaction.
TAKEAWAY:
- Rates of response (47.5% and 47.2%, respectively) and remission (31.4% and 30.3%, respectively) were not significantly different at week 12 between the MBP and VBP groups or for nonresponders rerandomized to either group.
- There were also no significant differences in depression change scores between the MBP and VBP groups or for nonresponders rerandomized to either group.
- Treatment disengagement by week 5 was significantly higher in the VBP vs MBP group (21.3% vs 13.2%; P = .003); VBP responders had stronger initial therapeutic alliance at week 4 than MBP responders (P < .001).
- No significant differences were observed in the quality of care among those who responded only after the second randomization to MBP or VBP.
IN PRACTICE:
"Findings reinforced MBP as viable alternative to VBP. Broader insurance reimbursement for MBP could improve access to evidence-based care," the investigators wrote.
SOURCE:
The study was led by Michael D. Pullmann, PhD, School of Medicine, University of Washington, Seattle. It was published online on October 30 in JAMA Network Open.
LIMITATIONS:
The absence of a waiting list or a no-treatment control group made it difficult to rule out regression to the mean as an explanation for improvements. Additionally, missing data may have affected the robustness of some findings.
DISCLOSURES:
The research was funded by the National Institute of Mental Health. Several investigators reported having financial ties with various sources. Details are provided in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Message-based psychotherapy (MBP), which uses asynchronous emails or texts, showed effectiveness comparable with that of video-based psychotherapy (VBP) for the treatment of depression on a commercial digital mental health platform, a new study showed.
METHODOLOGY:
- Investigators conducted a pragmatic sequential multiple-assignment randomized clinical trial from 2022 to 2024 involving 850 adult patients with a diagnosis of depression (mean age, 34 years; 66% women; 60% White, 22% Black and 14% Hispanic).
- Patients were initially randomly assigned to receive weekly MBP (n = 423) or VBP (n = 427), with nonresponders randomly assigned at week 6 to receive combination therapy of MBP plus weekly or monthly VBP. All patients received treatment for up to 12 weeks.
- Primary outcomes included depression severity measured by the 9-item Patient Health Questionnaire (PHQ-9), social functioning measured by the Quality of Life in Neurological Disorders 8-item tool, response to treatment (≥ 50% reduction in PHQ-9 total score or Clinical Global Impressions-Improvement score ≤ 2), and remissions (PHQ-9 score < 5).
- Secondary outcomes were treating disengagement, therapeutic alliance measured on the Working Alliance Inventory-Short Revised, quality of care in the past 4 weeks, and treatment satisfaction.
TAKEAWAY:
- Rates of response (47.5% and 47.2%, respectively) and remission (31.4% and 30.3%, respectively) were not significantly different at week 12 between the MBP and VBP groups or for nonresponders rerandomized to either group.
- There were also no significant differences in depression change scores between the MBP and VBP groups or for nonresponders rerandomized to either group.
- Treatment disengagement by week 5 was significantly higher in the VBP vs MBP group (21.3% vs 13.2%; P = .003); VBP responders had stronger initial therapeutic alliance at week 4 than MBP responders (P < .001).
- No significant differences were observed in the quality of care among those who responded only after the second randomization to MBP or VBP.
IN PRACTICE:
"Findings reinforced MBP as viable alternative to VBP. Broader insurance reimbursement for MBP could improve access to evidence-based care," the investigators wrote.
SOURCE:
The study was led by Michael D. Pullmann, PhD, School of Medicine, University of Washington, Seattle. It was published online on October 30 in JAMA Network Open.
LIMITATIONS:
The absence of a waiting list or a no-treatment control group made it difficult to rule out regression to the mean as an explanation for improvements. Additionally, missing data may have affected the robustness of some findings.
DISCLOSURES:
The research was funded by the National Institute of Mental Health. Several investigators reported having financial ties with various sources. Details are provided in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Message-based psychotherapy (MBP), which uses asynchronous emails or texts, showed effectiveness comparable with that of video-based psychotherapy (VBP) for the treatment of depression on a commercial digital mental health platform, a new study showed.
METHODOLOGY:
- Investigators conducted a pragmatic sequential multiple-assignment randomized clinical trial from 2022 to 2024 involving 850 adult patients with a diagnosis of depression (mean age, 34 years; 66% women; 60% White, 22% Black and 14% Hispanic).
- Patients were initially randomly assigned to receive weekly MBP (n = 423) or VBP (n = 427), with nonresponders randomly assigned at week 6 to receive combination therapy of MBP plus weekly or monthly VBP. All patients received treatment for up to 12 weeks.
- Primary outcomes included depression severity measured by the 9-item Patient Health Questionnaire (PHQ-9), social functioning measured by the Quality of Life in Neurological Disorders 8-item tool, response to treatment (≥ 50% reduction in PHQ-9 total score or Clinical Global Impressions-Improvement score ≤ 2), and remissions (PHQ-9 score < 5).
- Secondary outcomes were treating disengagement, therapeutic alliance measured on the Working Alliance Inventory-Short Revised, quality of care in the past 4 weeks, and treatment satisfaction.
TAKEAWAY:
- Rates of response (47.5% and 47.2%, respectively) and remission (31.4% and 30.3%, respectively) were not significantly different at week 12 between the MBP and VBP groups or for nonresponders rerandomized to either group.
- There were also no significant differences in depression change scores between the MBP and VBP groups or for nonresponders rerandomized to either group.
- Treatment disengagement by week 5 was significantly higher in the VBP vs MBP group (21.3% vs 13.2%; P = .003); VBP responders had stronger initial therapeutic alliance at week 4 than MBP responders (P < .001).
- No significant differences were observed in the quality of care among those who responded only after the second randomization to MBP or VBP.
IN PRACTICE:
"Findings reinforced MBP as viable alternative to VBP. Broader insurance reimbursement for MBP could improve access to evidence-based care," the investigators wrote.
SOURCE:
The study was led by Michael D. Pullmann, PhD, School of Medicine, University of Washington, Seattle. It was published online on October 30 in JAMA Network Open.
LIMITATIONS:
The absence of a waiting list or a no-treatment control group made it difficult to rule out regression to the mean as an explanation for improvements. Additionally, missing data may have affected the robustness of some findings.
DISCLOSURES:
The research was funded by the National Institute of Mental Health. Several investigators reported having financial ties with various sources. Details are provided in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Text vs Video Psychotherapy: Which Is Better for Depression?
Text vs Video Psychotherapy: Which Is Better for Depression?
GLP-1s May Improve Colon Cancer Outcomes
Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.
In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.
The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.
The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.
The study was published online in Cancer Investigation.
Effects Beyond Glucose-Lowering
Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.
Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.
To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.
Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).
When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).
Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
Intriguing and Promising — but Further Studies Needed
“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.
“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.
For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.
Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”
Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.
The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.
In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.
This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.
In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.
The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.
The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.
The study was published online in Cancer Investigation.
Effects Beyond Glucose-Lowering
Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.
Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.
To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.
Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).
When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).
Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
Intriguing and Promising — but Further Studies Needed
“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.
“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.
For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.
Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”
Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.
The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.
In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.
This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.
In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.
The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.
The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.
The study was published online in Cancer Investigation.
Effects Beyond Glucose-Lowering
Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.
Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.
To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.
Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).
When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).
Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
Intriguing and Promising — but Further Studies Needed
“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.
“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.
For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.
Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”
Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.
The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.
In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.
This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM CANCER INVESTIGATION
Does This Bacterial Toxin Drive Early CRC Risk?
Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.
According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year.
A Potential Bacterial Connection
What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.
In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation.
These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure.
In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
Bacteria’s Cancer-Causing Properties
The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk.
Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
Colibactin and DNA Damage
Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.
In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions.
The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”
Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause.
Biofilms and Inflammation
Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.
Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.”
Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
Dysbiosis and Diet
Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.
In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment.
Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.
Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads.
Two Types of Bacterial Drivers
There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness.
These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”
E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor.
Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies.
E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.
Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
E coli and Inflammatory Bowel Disease
E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”
Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
Future Directions
Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention.
From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.
In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage.
A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.
Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.
A version of this article first appeared on Medscape.com.
Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.
According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year.
A Potential Bacterial Connection
What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.
In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation.
These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure.
In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
Bacteria’s Cancer-Causing Properties
The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk.
Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
Colibactin and DNA Damage
Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.
In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions.
The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”
Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause.
Biofilms and Inflammation
Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.
Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.”
Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
Dysbiosis and Diet
Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.
In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment.
Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.
Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads.
Two Types of Bacterial Drivers
There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness.
These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”
E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor.
Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies.
E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.
Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
E coli and Inflammatory Bowel Disease
E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”
Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
Future Directions
Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention.
From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.
In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage.
A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.
Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.
A version of this article first appeared on Medscape.com.
Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.
According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year.
A Potential Bacterial Connection
What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.
In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation.
These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure.
In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
Bacteria’s Cancer-Causing Properties
The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk.
Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
Colibactin and DNA Damage
Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.
In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions.
The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”
Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause.
Biofilms and Inflammation
Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.
Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.”
Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
Dysbiosis and Diet
Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.
In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment.
Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.
Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads.
Two Types of Bacterial Drivers
There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness.
These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”
E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor.
Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies.
E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.
Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
E coli and Inflammatory Bowel Disease
E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”
Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
Future Directions
Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention.
From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.
In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage.
A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.
Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.
A version of this article first appeared on Medscape.com.