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Expert Advice for Difficult GERD Cases
PHOENIX – , said Kristle L. Lynch, MD, in a presentation at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
Patients with persistent GERD who have cough and asthma, as well as those with hoarseness, globus, or other ear, nose, and throat concerns, may first undergo workup by other clinicians, said Lynch, who is a professor of clinical medicine and director of the Physiology and Motility Laboratory at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
With these patients, “given the low pretest probability of an acid reflux source, it makes sense to bypass a trial of acid-suppressing medication if symptoms persist and instead move on to consideration of upper endoscopy,” she said.
“If negative for damage or sequelae of reflux, this test is often followed by advanced reflux testing and high-resolution manometry, to help diagnose the cause of reflux and swallowing problems,” she noted.
For patients with heartburn, regurgitation, or noncardiac chest pain (and no other concerning symptoms), moving to an empiric trial of antisecretory therapy before endoscopy can be reasonable, Lynch said. But if symptoms persist, an endoscopy should be done before any advanced pH testing.
Advanced pH Testing Options
Advanced reflux testing options for persistent GERD after an endoscopy include catheter-based pH-impedance testing and wireless pH testing, said Lynch.
“Wireless pH monitoring offers improved patient comfort by eliminating the need for a nasal catheter, allowing individuals to maintain normal daily activities and diet during testing,” Lynch told GI & Hepatology News.
“It also enables extended monitoring periods of up to 96 hours, enhancing the detection of intermittent acid reflux episodes,” she said. “However, unlike pH-impedance catheter-based testing, wireless pH measures only acid exposure and cannot identify nonacid reflux events.”
In addition, the wireless capsule may detach prematurely or cause mild chest discomfort, and its endoscopic placement adds procedural complexity with the need for anesthesia, as well as additional cost, she noted.
Catheter-based pH-impedance testing involves sedation-free catheter placement while the patient is awake, followed by monitoring for 24 hours, and involves assessment of bolus movement in tandem with pH measurements, Lynch said. The catheter monitors levels of acid refluxing into the esophagus and transmits this information to the smartphone-sized computer worn by the patient over the 24-hour period.
Unlike wireless testing, impedance testing allows for adjunctive measures of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic waves (PSPW), the latter of which is shown to predict response to proton pump inhibitor (PPI) therapy in patients with reflux.
Logistics include a concurrent manometry for the lower esophageal sphincter to optimize location, followed by a transnasal placement. Challenges associated with the catheter-based test include potential catheter migration and patient discomfort, she added.
Assessing pH Testing Results
After pH testing of either type, abnormal acid exposure time (AET) when the pH in the lower esophagus is greater than 6% supports a diagnosis of GERD; AET between 4% and 6% is considered borderline GERD; and AET less than 4% is considered normal and outside the bounds of pathologic reflux, as per the Lyon Consensus, Lynch explained.
Treatment for patients meeting the GERD criteria based on AET includes not only diet and lifestyle changes but also potential pharmacologics, including acid suppressants, alginates, gamma-aminobutyric acid agonists, and prokinetics. In some cases, anti-reflux surgery may be considered, such as magnetic sphincter augmentation, transoral incisionless fundoplication, or Roux-en-Y gastric bypass, Lynch said.
But not all heartburn in patients with persistent GERD is acid-related, she said. Functional heartburn and reflux hypersensitivity can be seen in these cases.
Patients not meeting the criteria for GERD on advanced pH testing and diagnosed with reflux hypersensitivity or functional heartburn may be treated with neuromodulators or nonpharmacologic therapies such as hypnosis, diaphragmatic breathing, cognitive-behavioral therapy, or acupuncture, said Lynch in her presentation.
Overall, “advanced pH testing should be assessed within the framework of other investigations and the patient as a whole,” she emphasized.
Challenges in the Clinic
One of the biggest mistakes while diagnosing a patient with persistent GERD symptoms despite PPI therapy is always assuming their symptoms are driven by ongoing pathologic acid exposure, said Michael Kingsley, MD, a gastroenterologist specializing in gastrointestinal motility disorders and a clinical assistant professor of medicine at the University of Pittsburgh, Pittsburgh, in an interview.
He agreed with Lynch that patients with reflux hypersensitivity or functional heartburn are more likely to benefit from interventions other than a PPI, such as a neuromodulator.
But managing GERD in the clinic also requires making time to assess whether patients are taking PPI correctly and to counsel them on lifestyle modifications, he noted.
One of the current biggest challenges in GERD is how best to manage a patient who falls into the inconclusive range of not definitely normal or abnormal on pH testing, Kingsley told GI & Hepatology News.
“As alluded to in this talk, MNBI and PSPW are emerging metrics, both of which require a pH-impedance study (as opposed to a wireless pH study),” he said. “Further elucidating the ideal application and cutoffs of these metrics may provide additional tools for best treating patients who fall into the “inconclusive” range with standard metrics.”
Lynch and Kingsley disclosed no financial conflicts of interest.
A version of this article appeared on Medscape.com .
PHOENIX – , said Kristle L. Lynch, MD, in a presentation at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
Patients with persistent GERD who have cough and asthma, as well as those with hoarseness, globus, or other ear, nose, and throat concerns, may first undergo workup by other clinicians, said Lynch, who is a professor of clinical medicine and director of the Physiology and Motility Laboratory at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
With these patients, “given the low pretest probability of an acid reflux source, it makes sense to bypass a trial of acid-suppressing medication if symptoms persist and instead move on to consideration of upper endoscopy,” she said.
“If negative for damage or sequelae of reflux, this test is often followed by advanced reflux testing and high-resolution manometry, to help diagnose the cause of reflux and swallowing problems,” she noted.
For patients with heartburn, regurgitation, or noncardiac chest pain (and no other concerning symptoms), moving to an empiric trial of antisecretory therapy before endoscopy can be reasonable, Lynch said. But if symptoms persist, an endoscopy should be done before any advanced pH testing.
Advanced pH Testing Options
Advanced reflux testing options for persistent GERD after an endoscopy include catheter-based pH-impedance testing and wireless pH testing, said Lynch.
“Wireless pH monitoring offers improved patient comfort by eliminating the need for a nasal catheter, allowing individuals to maintain normal daily activities and diet during testing,” Lynch told GI & Hepatology News.
“It also enables extended monitoring periods of up to 96 hours, enhancing the detection of intermittent acid reflux episodes,” she said. “However, unlike pH-impedance catheter-based testing, wireless pH measures only acid exposure and cannot identify nonacid reflux events.”
In addition, the wireless capsule may detach prematurely or cause mild chest discomfort, and its endoscopic placement adds procedural complexity with the need for anesthesia, as well as additional cost, she noted.
Catheter-based pH-impedance testing involves sedation-free catheter placement while the patient is awake, followed by monitoring for 24 hours, and involves assessment of bolus movement in tandem with pH measurements, Lynch said. The catheter monitors levels of acid refluxing into the esophagus and transmits this information to the smartphone-sized computer worn by the patient over the 24-hour period.
Unlike wireless testing, impedance testing allows for adjunctive measures of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic waves (PSPW), the latter of which is shown to predict response to proton pump inhibitor (PPI) therapy in patients with reflux.
Logistics include a concurrent manometry for the lower esophageal sphincter to optimize location, followed by a transnasal placement. Challenges associated with the catheter-based test include potential catheter migration and patient discomfort, she added.
Assessing pH Testing Results
After pH testing of either type, abnormal acid exposure time (AET) when the pH in the lower esophagus is greater than 6% supports a diagnosis of GERD; AET between 4% and 6% is considered borderline GERD; and AET less than 4% is considered normal and outside the bounds of pathologic reflux, as per the Lyon Consensus, Lynch explained.
Treatment for patients meeting the GERD criteria based on AET includes not only diet and lifestyle changes but also potential pharmacologics, including acid suppressants, alginates, gamma-aminobutyric acid agonists, and prokinetics. In some cases, anti-reflux surgery may be considered, such as magnetic sphincter augmentation, transoral incisionless fundoplication, or Roux-en-Y gastric bypass, Lynch said.
But not all heartburn in patients with persistent GERD is acid-related, she said. Functional heartburn and reflux hypersensitivity can be seen in these cases.
Patients not meeting the criteria for GERD on advanced pH testing and diagnosed with reflux hypersensitivity or functional heartburn may be treated with neuromodulators or nonpharmacologic therapies such as hypnosis, diaphragmatic breathing, cognitive-behavioral therapy, or acupuncture, said Lynch in her presentation.
Overall, “advanced pH testing should be assessed within the framework of other investigations and the patient as a whole,” she emphasized.
Challenges in the Clinic
One of the biggest mistakes while diagnosing a patient with persistent GERD symptoms despite PPI therapy is always assuming their symptoms are driven by ongoing pathologic acid exposure, said Michael Kingsley, MD, a gastroenterologist specializing in gastrointestinal motility disorders and a clinical assistant professor of medicine at the University of Pittsburgh, Pittsburgh, in an interview.
He agreed with Lynch that patients with reflux hypersensitivity or functional heartburn are more likely to benefit from interventions other than a PPI, such as a neuromodulator.
But managing GERD in the clinic also requires making time to assess whether patients are taking PPI correctly and to counsel them on lifestyle modifications, he noted.
One of the current biggest challenges in GERD is how best to manage a patient who falls into the inconclusive range of not definitely normal or abnormal on pH testing, Kingsley told GI & Hepatology News.
“As alluded to in this talk, MNBI and PSPW are emerging metrics, both of which require a pH-impedance study (as opposed to a wireless pH study),” he said. “Further elucidating the ideal application and cutoffs of these metrics may provide additional tools for best treating patients who fall into the “inconclusive” range with standard metrics.”
Lynch and Kingsley disclosed no financial conflicts of interest.
A version of this article appeared on Medscape.com .
PHOENIX – , said Kristle L. Lynch, MD, in a presentation at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
Patients with persistent GERD who have cough and asthma, as well as those with hoarseness, globus, or other ear, nose, and throat concerns, may first undergo workup by other clinicians, said Lynch, who is a professor of clinical medicine and director of the Physiology and Motility Laboratory at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
With these patients, “given the low pretest probability of an acid reflux source, it makes sense to bypass a trial of acid-suppressing medication if symptoms persist and instead move on to consideration of upper endoscopy,” she said.
“If negative for damage or sequelae of reflux, this test is often followed by advanced reflux testing and high-resolution manometry, to help diagnose the cause of reflux and swallowing problems,” she noted.
For patients with heartburn, regurgitation, or noncardiac chest pain (and no other concerning symptoms), moving to an empiric trial of antisecretory therapy before endoscopy can be reasonable, Lynch said. But if symptoms persist, an endoscopy should be done before any advanced pH testing.
Advanced pH Testing Options
Advanced reflux testing options for persistent GERD after an endoscopy include catheter-based pH-impedance testing and wireless pH testing, said Lynch.
“Wireless pH monitoring offers improved patient comfort by eliminating the need for a nasal catheter, allowing individuals to maintain normal daily activities and diet during testing,” Lynch told GI & Hepatology News.
“It also enables extended monitoring periods of up to 96 hours, enhancing the detection of intermittent acid reflux episodes,” she said. “However, unlike pH-impedance catheter-based testing, wireless pH measures only acid exposure and cannot identify nonacid reflux events.”
In addition, the wireless capsule may detach prematurely or cause mild chest discomfort, and its endoscopic placement adds procedural complexity with the need for anesthesia, as well as additional cost, she noted.
Catheter-based pH-impedance testing involves sedation-free catheter placement while the patient is awake, followed by monitoring for 24 hours, and involves assessment of bolus movement in tandem with pH measurements, Lynch said. The catheter monitors levels of acid refluxing into the esophagus and transmits this information to the smartphone-sized computer worn by the patient over the 24-hour period.
Unlike wireless testing, impedance testing allows for adjunctive measures of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic waves (PSPW), the latter of which is shown to predict response to proton pump inhibitor (PPI) therapy in patients with reflux.
Logistics include a concurrent manometry for the lower esophageal sphincter to optimize location, followed by a transnasal placement. Challenges associated with the catheter-based test include potential catheter migration and patient discomfort, she added.
Assessing pH Testing Results
After pH testing of either type, abnormal acid exposure time (AET) when the pH in the lower esophagus is greater than 6% supports a diagnosis of GERD; AET between 4% and 6% is considered borderline GERD; and AET less than 4% is considered normal and outside the bounds of pathologic reflux, as per the Lyon Consensus, Lynch explained.
Treatment for patients meeting the GERD criteria based on AET includes not only diet and lifestyle changes but also potential pharmacologics, including acid suppressants, alginates, gamma-aminobutyric acid agonists, and prokinetics. In some cases, anti-reflux surgery may be considered, such as magnetic sphincter augmentation, transoral incisionless fundoplication, or Roux-en-Y gastric bypass, Lynch said.
But not all heartburn in patients with persistent GERD is acid-related, she said. Functional heartburn and reflux hypersensitivity can be seen in these cases.
Patients not meeting the criteria for GERD on advanced pH testing and diagnosed with reflux hypersensitivity or functional heartburn may be treated with neuromodulators or nonpharmacologic therapies such as hypnosis, diaphragmatic breathing, cognitive-behavioral therapy, or acupuncture, said Lynch in her presentation.
Overall, “advanced pH testing should be assessed within the framework of other investigations and the patient as a whole,” she emphasized.
Challenges in the Clinic
One of the biggest mistakes while diagnosing a patient with persistent GERD symptoms despite PPI therapy is always assuming their symptoms are driven by ongoing pathologic acid exposure, said Michael Kingsley, MD, a gastroenterologist specializing in gastrointestinal motility disorders and a clinical assistant professor of medicine at the University of Pittsburgh, Pittsburgh, in an interview.
He agreed with Lynch that patients with reflux hypersensitivity or functional heartburn are more likely to benefit from interventions other than a PPI, such as a neuromodulator.
But managing GERD in the clinic also requires making time to assess whether patients are taking PPI correctly and to counsel them on lifestyle modifications, he noted.
One of the current biggest challenges in GERD is how best to manage a patient who falls into the inconclusive range of not definitely normal or abnormal on pH testing, Kingsley told GI & Hepatology News.
“As alluded to in this talk, MNBI and PSPW are emerging metrics, both of which require a pH-impedance study (as opposed to a wireless pH study),” he said. “Further elucidating the ideal application and cutoffs of these metrics may provide additional tools for best treating patients who fall into the “inconclusive” range with standard metrics.”
Lynch and Kingsley disclosed no financial conflicts of interest.
A version of this article appeared on Medscape.com .
FROM ACG 2025
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.
Finding Your Voice in Advocacy
Dear Friends,
Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.
In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.
In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.
Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.
If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Danielle Kiefer ([email protected]), Communications/Managing Editor of TNG.
Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.
Yours truly,
Judy A. Trieu, MD, MPH
Editor-in-Chief
Assistant Professor of Medicine
Interventional Endoscopy, Division of Gastroenterology
Washington University School of Medicine in St. Louis
Dear Friends,
Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.
In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.
In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.
Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.
If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Danielle Kiefer ([email protected]), Communications/Managing Editor of TNG.
Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.
Yours truly,
Judy A. Trieu, MD, MPH
Editor-in-Chief
Assistant Professor of Medicine
Interventional Endoscopy, Division of Gastroenterology
Washington University School of Medicine in St. Louis
Dear Friends,
Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.
In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.
In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.
Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.
If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Danielle Kiefer ([email protected]), Communications/Managing Editor of TNG.
Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.
Yours truly,
Judy A. Trieu, MD, MPH
Editor-in-Chief
Assistant Professor of Medicine
Interventional Endoscopy, Division of Gastroenterology
Washington University School of Medicine in St. Louis
Non-Invasive Blood and Stool CRC Screening Tests: Available Modalities and Their Clinical Application
Introduction
Colorectal cancer (CRC) screening significantly reduces CRC incidence and mortality, but only 65% of eligible individuals report being up-to-date with screening.1 Colonoscopy is the most widely used opportunistic screening method in the United States and is associated with many barriers to uptake. Providing patients a choice of colonoscopy and/or stool-based tests, improves screening adherence in randomized controlled trials.2,3 Non-invasive screening options have expanded from stool occult blood and multi-target DNA tests, to multi-target stool RNA tests, and novel blood-based tests, the latter only U.S. Food and Drug Administration (FDA) approved for patients who refuse colonoscopy and stool-based tests.
Stool Occult Blood Tests
Guaiac-based fecal occult blood testing (gFOBT) significantly reduces CRC mortality by 33%-35% when implemented on an annual or biennial basis.4,5 Fecal immunochemical testing (FIT) has supplanted gFOBT with advantages including independence from dietary restriction and medication-related interference, use of antibodies specific to human globin, and the need for only a single stool sample.
The most common threshold for a positive FIT in the U.S. is ≥ 20 micrograms (μg) of hemoglobin per gram (g) of stool. FIT is approved by the FDA as a qualitative positive or negative result based on a threshold value.6 A meta-analysis summarized test characteristics of commercially available FITs at various detection thresholds.7 The CRC sensitivity and specificity was 75% and 95% for ≥ 20 ug hemoglobin/g stool, and 91% and 90% for 10 ug hemoglobin/g stool, respectively. The sensitivity for advanced adenomas ranged from 25% at 20 μg/g to 40% at a 10 μg/g. Programmatic use of FIT in adults ages ≥ 50 years at 20 ug/g of stool, in cohort and case control studies, has been shown to significantly reduce CRC mortality by 33%-40% and advanced stage CRC by 34%.8,9
Over 57,000 average-risk individuals ages 50–69 years were randomized to biennial FIT or one-time colonoscopy and followed for 10 years.10 CRC mortality and incidence was similar between the groups: 0.22% with FIT vs. 0.24% with colonoscopy and 1.13% with FIT vs. 1.22% with colonoscopy, respectively. Thus, confirming biennial FIT screening is non-inferior to one-time colonoscopy in important CRC-related outcomes.
Multi-Target Stool Tests
Two multitarget stool DNA tests (mt-sDNA) known as Cologuard™ and Cologuard Plus™ have been approved by the FDA. Both tests include a FIT (with a positivity threshold of 20 μg hemoglobin per gram of stool) combined with DNA methylation markers. The test result is qualitative, reported as a positive or negative. Cologuard™ markers include methylated BMP3, NDRG4, and mutant KRAS while Cologuard Plus™ assesses methylated LASS4, LRRC4, and PPP2R5C. The respective mt-sDNA tests were studied in 9989 of 12,776 and 20,176 of 26,758 average-risk individuals undergoing colonoscopy and the results were compared to a commercially available FIT (with a positivity threshold of 20 μg hemoglobin/gram of stool).11,12 In both trials, the sensitivity for CRC and advanced precancerous lesions was higher with the mt-sDNA tests compared to FIT but had a significantly lower specificity for advanced precancerous lesions versus FIT (see Table 1). An age-related decline in specificity was noted in both trials with mt-sDNA, a trend not observed with FIT. This reduction may be attributed to age-related DNA methylation.
Multi-Target Stool RNA Test
A multi-target stool RNA test (mt-sRNA) commercially available as ColoSense™ is FDA-approved. It combines FIT (at a positivity threshold of 20 μg hemoglobin/gram of stool) with RNA-based stool markers. The combined results of the RNA markers, FIT, and smoking status provide a qualitative single test result. In the trial, 8,920 adults aged ≥45 underwent the mt-sRNA test and FIT followed by colonoscopy (13). The mt-sRNA showed higher sensitivity for CRC than FIT (94.4% versus 77.8%) and advanced adenomas (45.9% versus 28.9%) but lower CRC specificity (84.7% vs 94.7%) (Table 1). Unlike mt-sDNA-based tests, mt-sRNA showed consistent performance across age groups, addressing concerns about age-related declines in specificity attributed to DNA methylation.
Blood-Based Tests
In 2014, the first blood-based (BBT) CRC screening test known as Epi proColon™ was FDA but not Centers for Medicare & Medicaid Services (CMS) approved for average-risk adults ≥50 years of age who are offered and refused other U.S Preventive Services Task Force (USPSTF) endorsed CRC screening tests. It is a qualitative test for detection of circulating methylated Septin 9 (mSeptin9). The accuracy of mSeptin9 to detect CRC was assessed in a subset of 7941 asymptomatic average risk adults undergoing screening colonoscopy.14 The sensitivity and specificity for CRC were 48% and 91.5%, respectively. The sensitivity for advanced adenomas was 11.2%. An increase in sensitivity to 63.9% and reduction in specificity to 88.4% for CRC was demonstrated in a sub-analysis of available samples where an additional (third) polymerase chain replicate was performed. Epi proColon™ is not currently reimbursed by Medicare and not endorsed in the latest USPSTF guidelines.
Technologic advancements have improved the detection of circulating tumor markers in the blood. The Shield™ BBT approved by the FDA in 2024 for average risk adults ≥ 45 years integrates three types of cfDNA data (epigenetic changes resulting in the aberrant methylation or fragmentation patterns, and genomic changes resulting in somatic mutations) into a positive or negative test result. In the trial, 22,877 average-risk, asymptomatic individuals ages 45–84 were enrolled and clinical validation was performed in 7,861 of the participants.15 The sensitivity for CRC was 83.1% which decreased to 55% for stage I tumors (see Table 1). CRC specificity was 89.6% and the sensitivity for advanced adenomas and large sessile serrated lesions was 13.2%.
Another BBT SimpleScreen™, which is not yet FDA-approved, analyzed circulating, cell-free DNA methylation patterns in 27,010 evaluable average-risk, asymptomatic adults ages 45–85 years undergoing screening colonoscopy.16 The sensitivity and specificity for CRC was 79.2% and 91.5%, respectively. Similar to Shield, the sensitivity for stage I CRC was low at 57.1%. The sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5% which did not meet the prespecified study criteria.
Effectiveness and Cost Effectiveness
Modeling studies have evaluated novel noninvasive CRC screening tests compared to FIT and colonoscopy.17-20 One compared a hypothetical BBT performed every 3 years that meets the minimum CMS threshold CRC sensitivity and specificity of 74% and 90%, respectively, to other established CRC screening tests beginning at age 45.17 Every 3-year BBT reduced CRC incidence and mortality by 40% and 52%, respectively compared to no screening. However, the reductions were much lower than yearly FIT (72% and 76%, respectively), every 10 year colonoscopy (79% and 81%, respectively), and triennial mt-sDNA (68% and 73%, respectively). The BBT resulted in fewer quality-adjusted life-years per person compared to the alternatives.
Additionally, FIT, colonoscopy, and mt-sDNA were less costly and more effective. Advanced precancerous lesion detection was a key measure for a test’s effectiveness. BBT characteristics would require a CRC sensitivity and specificity of >90% and 90%, respectively, and 80% sensitivity for advanced precancerous lesions at a cost of ≤$120–$140 to be cost-effective compared to FIT at comparable participation rates.
Another analysis simulated colorectal neoplasia progression and compared clinical effectiveness and cost between annual FIT, every 3 year stool mt-sRNA, every 3 year stool mt-sDNA tests, every 3 year stool Shield™; these outcomes were compared to colonoscopy every 10 years and no screening in adults ≥ age 45 over different adherence rates.19 At real-world adherence rates of 60%, colonoscopy prevented most CRC cases and associated deaths. FIT was the most cost-effective strategy at all adherence levels. Between the multi-target stool tests and Shield™, mt-sRNA was the most cost-effective. Compared to FIT, mt-sRNA reduced CRC cases and deaths by 1% and 14%.
The third study evaluated CRC incidence and mortality, quality-adjusted life-years and costs with annual FIT, colonoscopy every 10 years, mt- sDNA tests, mt-sRNA test, and BBTs.20 The latest mt-sDNA (Colguard plus™) and mt-sRNA achieved benefits approaching FIT but the Shield™ test was substantially less effective. The authors hypothesized that if 15% of the population substituted Shield™ for current effective CRC screening strategies, an increase in CRC deaths would occur and require 9-10% of the unscreened population to uptake screening with Shield to avert the increases in CRC deaths due to the substitution effect.
Clinical Implications
The effectiveness of non-invasive screening strategies depends on their diagnostic performance, adherence, and ensuring a timely colonoscopy after a positive test. Two claims-based studies found 47.9% and 49% of patients underwent follow-up colonoscopy within 6 months of an abnormal stool or BBT CRC screening test, respectively.21-22
Conclusions
Non-invasive stool mt-sDNA and mt-sRNA have higher effectiveness than the new BBTs. BBTs can lead to increased CRC mortality if substituted for the FDA and CMS-approved, USPSTF-endorsed, CRC screening modalities. If future BBTs increase their sensitivity for CRC (including early-stage CRC) and advanced precancerous lesions and decrease their cost, they may prove to have similar cost-effectiveness to stool-based tests. Currently, BBTs are not a substitute for colonoscopy or other stool tests and should be offered to patients who refuse other CRC screening modalities. A personalized, risk-adapted approach, paired with improved adherence and follow-up are essential to optimize the population-level impact of CRC screening and ensure equitable, effective cancer prevention.
Dr. Gupta is based at the Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore. Dr. Burke and Dr. Macaron are based at the Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio. Dr. Gupta and Dr. Macaron declared no conflicts of interest in regard to this article. Dr. Burke declared research support from Emtora Biosciences. She is a current consultant for Lumabridge, and has been a consultant for Sebela and Almirall. She also disclosed support from Myriad, Genzyme, Ferring, Merck, Sharp and Dohme, Abbvie, Salix, and Natera.
References
1. Benavidez GA, Sedani AE, Felder TM, Asare M, Rogers CR. Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022). JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae113
2. Galoosian A, Dai H, Croymans D, et al. Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial. JAMA. 2025 Aug 4:e2512049. doi: 10.1001/jama.2025.12049. Epub ahead of print.
3. Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study). Gastroenterology. 2021 Mar;160(4):1097-1105.
4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.
5. Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996 Nov 30;348(9040):1467-71. doi: 10.1016/S0140-6736(96)03430-7. PMID: 8942774.
6. Burke CA, Lieberman D, Feuerstein JD. AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary. Gastroenterology. 2022 Mar;162(3):952-956. doi: 10.1053/j.gastro.2021.09.075. Epub 2022 Jan 28. PMID: 35094786.
7. Imperiale TF, Gruber RN Stump TE, et al. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis. Ann Intern Med 2019; 170(5):319-329
8. Doubeni CA, Corley DA, Jensen CD, et al. Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death. JAMA Netw Open. 2024 Jul 1;7(7):e2423671. doi: 10.1001/jamanetworkopen.2024.23671.
9. Chiu HM, Jen GH, Wang YW, et al. Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers. Gut. 2021 Dec;70(12):2321-2329. doi: 10.1136/gutjnl-2020-322545. Epub 2021 Jan 25.
10. Castells A, Quintero E, Bujanda L, et al; COLONPREV study investigators. Effect of invitation to colonoscopy versus fecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Lancet. 2025;405(10486):1231–1239
11. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297
12. Imperiale TF, Porter K, Zella J, et al. Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):984-993
13. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023 Nov 14;330(18):1760-1768.
14. Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014; 63:317–325.
15. Chung DC, Gray DM 2nd, Singh H, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983.
16. Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025 Jul 1;334(1):56-63.
17. Ladabaum U, Mannalithara A, Weng Y, et al. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening with Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391.
18. van den Puttelaar R, Nascimento de Lima P, Knudsen AB, et al. Effectiveness and cost-effectiveness of colorectal cancer screening with a blood test that meets the Centers for Medicare & Medicaid Services coverage decision. Gastroenterology 2024;167:368–377.
19. Shaukat A, Levin TR, Liang PS. Cost-effectiveness of Novel Noninvasive Screening Tests for Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2025 Jun 23:S1542-3565(25)00525-7. doi: 10.1016/j.cgh.2025.06.006. Epub ahead of print. PMID: 40562290.
20. Ladabaum U, Mannalithara A, Schoen RE, Dominitz JA, Lieberman D. Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Ann Intern Med. 2024 Dec;177(12):1610-1620.
20. Ciemins EL, Mohl JT, Moreno CA, Colangelo F, Smith RA, Barton M. Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e242693. doi: 10.1001/jamanetworkopen.2024.2693.
21. Zaki TA, Zhang NJ, Forbes SP, Raymond VM, Das AK, May FP. Colonoscopic Follow-up After Abnormal Blood-Based Colorectal Cancer Screening Results. Gastroenterology. 2025 Jul 21:S0016-5085(25)05775-0. doi: 10.1053/j.gastro.2025.07.019. Epub ahead of print. PMID: 40744392.
Introduction
Colorectal cancer (CRC) screening significantly reduces CRC incidence and mortality, but only 65% of eligible individuals report being up-to-date with screening.1 Colonoscopy is the most widely used opportunistic screening method in the United States and is associated with many barriers to uptake. Providing patients a choice of colonoscopy and/or stool-based tests, improves screening adherence in randomized controlled trials.2,3 Non-invasive screening options have expanded from stool occult blood and multi-target DNA tests, to multi-target stool RNA tests, and novel blood-based tests, the latter only U.S. Food and Drug Administration (FDA) approved for patients who refuse colonoscopy and stool-based tests.
Stool Occult Blood Tests
Guaiac-based fecal occult blood testing (gFOBT) significantly reduces CRC mortality by 33%-35% when implemented on an annual or biennial basis.4,5 Fecal immunochemical testing (FIT) has supplanted gFOBT with advantages including independence from dietary restriction and medication-related interference, use of antibodies specific to human globin, and the need for only a single stool sample.
The most common threshold for a positive FIT in the U.S. is ≥ 20 micrograms (μg) of hemoglobin per gram (g) of stool. FIT is approved by the FDA as a qualitative positive or negative result based on a threshold value.6 A meta-analysis summarized test characteristics of commercially available FITs at various detection thresholds.7 The CRC sensitivity and specificity was 75% and 95% for ≥ 20 ug hemoglobin/g stool, and 91% and 90% for 10 ug hemoglobin/g stool, respectively. The sensitivity for advanced adenomas ranged from 25% at 20 μg/g to 40% at a 10 μg/g. Programmatic use of FIT in adults ages ≥ 50 years at 20 ug/g of stool, in cohort and case control studies, has been shown to significantly reduce CRC mortality by 33%-40% and advanced stage CRC by 34%.8,9
Over 57,000 average-risk individuals ages 50–69 years were randomized to biennial FIT or one-time colonoscopy and followed for 10 years.10 CRC mortality and incidence was similar between the groups: 0.22% with FIT vs. 0.24% with colonoscopy and 1.13% with FIT vs. 1.22% with colonoscopy, respectively. Thus, confirming biennial FIT screening is non-inferior to one-time colonoscopy in important CRC-related outcomes.
Multi-Target Stool Tests
Two multitarget stool DNA tests (mt-sDNA) known as Cologuard™ and Cologuard Plus™ have been approved by the FDA. Both tests include a FIT (with a positivity threshold of 20 μg hemoglobin per gram of stool) combined with DNA methylation markers. The test result is qualitative, reported as a positive or negative. Cologuard™ markers include methylated BMP3, NDRG4, and mutant KRAS while Cologuard Plus™ assesses methylated LASS4, LRRC4, and PPP2R5C. The respective mt-sDNA tests were studied in 9989 of 12,776 and 20,176 of 26,758 average-risk individuals undergoing colonoscopy and the results were compared to a commercially available FIT (with a positivity threshold of 20 μg hemoglobin/gram of stool).11,12 In both trials, the sensitivity for CRC and advanced precancerous lesions was higher with the mt-sDNA tests compared to FIT but had a significantly lower specificity for advanced precancerous lesions versus FIT (see Table 1). An age-related decline in specificity was noted in both trials with mt-sDNA, a trend not observed with FIT. This reduction may be attributed to age-related DNA methylation.
Multi-Target Stool RNA Test
A multi-target stool RNA test (mt-sRNA) commercially available as ColoSense™ is FDA-approved. It combines FIT (at a positivity threshold of 20 μg hemoglobin/gram of stool) with RNA-based stool markers. The combined results of the RNA markers, FIT, and smoking status provide a qualitative single test result. In the trial, 8,920 adults aged ≥45 underwent the mt-sRNA test and FIT followed by colonoscopy (13). The mt-sRNA showed higher sensitivity for CRC than FIT (94.4% versus 77.8%) and advanced adenomas (45.9% versus 28.9%) but lower CRC specificity (84.7% vs 94.7%) (Table 1). Unlike mt-sDNA-based tests, mt-sRNA showed consistent performance across age groups, addressing concerns about age-related declines in specificity attributed to DNA methylation.
Blood-Based Tests
In 2014, the first blood-based (BBT) CRC screening test known as Epi proColon™ was FDA but not Centers for Medicare & Medicaid Services (CMS) approved for average-risk adults ≥50 years of age who are offered and refused other U.S Preventive Services Task Force (USPSTF) endorsed CRC screening tests. It is a qualitative test for detection of circulating methylated Septin 9 (mSeptin9). The accuracy of mSeptin9 to detect CRC was assessed in a subset of 7941 asymptomatic average risk adults undergoing screening colonoscopy.14 The sensitivity and specificity for CRC were 48% and 91.5%, respectively. The sensitivity for advanced adenomas was 11.2%. An increase in sensitivity to 63.9% and reduction in specificity to 88.4% for CRC was demonstrated in a sub-analysis of available samples where an additional (third) polymerase chain replicate was performed. Epi proColon™ is not currently reimbursed by Medicare and not endorsed in the latest USPSTF guidelines.
Technologic advancements have improved the detection of circulating tumor markers in the blood. The Shield™ BBT approved by the FDA in 2024 for average risk adults ≥ 45 years integrates three types of cfDNA data (epigenetic changes resulting in the aberrant methylation or fragmentation patterns, and genomic changes resulting in somatic mutations) into a positive or negative test result. In the trial, 22,877 average-risk, asymptomatic individuals ages 45–84 were enrolled and clinical validation was performed in 7,861 of the participants.15 The sensitivity for CRC was 83.1% which decreased to 55% for stage I tumors (see Table 1). CRC specificity was 89.6% and the sensitivity for advanced adenomas and large sessile serrated lesions was 13.2%.
Another BBT SimpleScreen™, which is not yet FDA-approved, analyzed circulating, cell-free DNA methylation patterns in 27,010 evaluable average-risk, asymptomatic adults ages 45–85 years undergoing screening colonoscopy.16 The sensitivity and specificity for CRC was 79.2% and 91.5%, respectively. Similar to Shield, the sensitivity for stage I CRC was low at 57.1%. The sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5% which did not meet the prespecified study criteria.
Effectiveness and Cost Effectiveness
Modeling studies have evaluated novel noninvasive CRC screening tests compared to FIT and colonoscopy.17-20 One compared a hypothetical BBT performed every 3 years that meets the minimum CMS threshold CRC sensitivity and specificity of 74% and 90%, respectively, to other established CRC screening tests beginning at age 45.17 Every 3-year BBT reduced CRC incidence and mortality by 40% and 52%, respectively compared to no screening. However, the reductions were much lower than yearly FIT (72% and 76%, respectively), every 10 year colonoscopy (79% and 81%, respectively), and triennial mt-sDNA (68% and 73%, respectively). The BBT resulted in fewer quality-adjusted life-years per person compared to the alternatives.
Additionally, FIT, colonoscopy, and mt-sDNA were less costly and more effective. Advanced precancerous lesion detection was a key measure for a test’s effectiveness. BBT characteristics would require a CRC sensitivity and specificity of >90% and 90%, respectively, and 80% sensitivity for advanced precancerous lesions at a cost of ≤$120–$140 to be cost-effective compared to FIT at comparable participation rates.
Another analysis simulated colorectal neoplasia progression and compared clinical effectiveness and cost between annual FIT, every 3 year stool mt-sRNA, every 3 year stool mt-sDNA tests, every 3 year stool Shield™; these outcomes were compared to colonoscopy every 10 years and no screening in adults ≥ age 45 over different adherence rates.19 At real-world adherence rates of 60%, colonoscopy prevented most CRC cases and associated deaths. FIT was the most cost-effective strategy at all adherence levels. Between the multi-target stool tests and Shield™, mt-sRNA was the most cost-effective. Compared to FIT, mt-sRNA reduced CRC cases and deaths by 1% and 14%.
The third study evaluated CRC incidence and mortality, quality-adjusted life-years and costs with annual FIT, colonoscopy every 10 years, mt- sDNA tests, mt-sRNA test, and BBTs.20 The latest mt-sDNA (Colguard plus™) and mt-sRNA achieved benefits approaching FIT but the Shield™ test was substantially less effective. The authors hypothesized that if 15% of the population substituted Shield™ for current effective CRC screening strategies, an increase in CRC deaths would occur and require 9-10% of the unscreened population to uptake screening with Shield to avert the increases in CRC deaths due to the substitution effect.
Clinical Implications
The effectiveness of non-invasive screening strategies depends on their diagnostic performance, adherence, and ensuring a timely colonoscopy after a positive test. Two claims-based studies found 47.9% and 49% of patients underwent follow-up colonoscopy within 6 months of an abnormal stool or BBT CRC screening test, respectively.21-22
Conclusions
Non-invasive stool mt-sDNA and mt-sRNA have higher effectiveness than the new BBTs. BBTs can lead to increased CRC mortality if substituted for the FDA and CMS-approved, USPSTF-endorsed, CRC screening modalities. If future BBTs increase their sensitivity for CRC (including early-stage CRC) and advanced precancerous lesions and decrease their cost, they may prove to have similar cost-effectiveness to stool-based tests. Currently, BBTs are not a substitute for colonoscopy or other stool tests and should be offered to patients who refuse other CRC screening modalities. A personalized, risk-adapted approach, paired with improved adherence and follow-up are essential to optimize the population-level impact of CRC screening and ensure equitable, effective cancer prevention.
Dr. Gupta is based at the Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore. Dr. Burke and Dr. Macaron are based at the Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio. Dr. Gupta and Dr. Macaron declared no conflicts of interest in regard to this article. Dr. Burke declared research support from Emtora Biosciences. She is a current consultant for Lumabridge, and has been a consultant for Sebela and Almirall. She also disclosed support from Myriad, Genzyme, Ferring, Merck, Sharp and Dohme, Abbvie, Salix, and Natera.
References
1. Benavidez GA, Sedani AE, Felder TM, Asare M, Rogers CR. Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022). JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae113
2. Galoosian A, Dai H, Croymans D, et al. Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial. JAMA. 2025 Aug 4:e2512049. doi: 10.1001/jama.2025.12049. Epub ahead of print.
3. Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study). Gastroenterology. 2021 Mar;160(4):1097-1105.
4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.
5. Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996 Nov 30;348(9040):1467-71. doi: 10.1016/S0140-6736(96)03430-7. PMID: 8942774.
6. Burke CA, Lieberman D, Feuerstein JD. AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary. Gastroenterology. 2022 Mar;162(3):952-956. doi: 10.1053/j.gastro.2021.09.075. Epub 2022 Jan 28. PMID: 35094786.
7. Imperiale TF, Gruber RN Stump TE, et al. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis. Ann Intern Med 2019; 170(5):319-329
8. Doubeni CA, Corley DA, Jensen CD, et al. Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death. JAMA Netw Open. 2024 Jul 1;7(7):e2423671. doi: 10.1001/jamanetworkopen.2024.23671.
9. Chiu HM, Jen GH, Wang YW, et al. Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers. Gut. 2021 Dec;70(12):2321-2329. doi: 10.1136/gutjnl-2020-322545. Epub 2021 Jan 25.
10. Castells A, Quintero E, Bujanda L, et al; COLONPREV study investigators. Effect of invitation to colonoscopy versus fecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Lancet. 2025;405(10486):1231–1239
11. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297
12. Imperiale TF, Porter K, Zella J, et al. Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):984-993
13. Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023 Nov 14;330(18):1760-1768.
14. Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014; 63:317–325.
15. Chung DC, Gray DM 2nd, Singh H, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983.
16. Shaukat A, Burke CA, Chan AT, et al. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025 Jul 1;334(1):56-63.
17. Ladabaum U, Mannalithara A, Weng Y, et al. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening with Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391.
18. van den Puttelaar R, Nascimento de Lima P, Knudsen AB, et al. Effectiveness and cost-effectiveness of colorectal cancer screening with a blood test that meets the Centers for Medicare & Medicaid Services coverage decision. Gastroenterology 2024;167:368–377.
19. Shaukat A, Levin TR, Liang PS. Cost-effectiveness of Novel Noninvasive Screening Tests for Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2025 Jun 23:S1542-3565(25)00525-7. doi: 10.1016/j.cgh.2025.06.006. Epub ahead of print. PMID: 40562290.
20. Ladabaum U, Mannalithara A, Schoen RE, Dominitz JA, Lieberman D. Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Ann Intern Med. 2024 Dec;177(12):1610-1620.
20. Ciemins EL, Mohl JT, Moreno CA, Colangelo F, Smith RA, Barton M. Development of a Follow-Up Measure to Ensure Complete Screening for Colorectal Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e242693. doi: 10.1001/jamanetworkopen.2024.2693.
21. Zaki TA, Zhang NJ, Forbes SP, Raymond VM, Das AK, May FP. Colonoscopic Follow-up After Abnormal Blood-Based Colorectal Cancer Screening Results. Gastroenterology. 2025 Jul 21:S0016-5085(25)05775-0. doi: 10.1053/j.gastro.2025.07.019. Epub ahead of print. PMID: 40744392.
Introduction
Colorectal cancer (CRC) screening significantly reduces CRC incidence and mortality, but only 65% of eligible individuals report being up-to-date with screening.1 Colonoscopy is the most widely used opportunistic screening method in the United States and is associated with many barriers to uptake. Providing patients a choice of colonoscopy and/or stool-based tests, improves screening adherence in randomized controlled trials.2,3 Non-invasive screening options have expanded from stool occult blood and multi-target DNA tests, to multi-target stool RNA tests, and novel blood-based tests, the latter only U.S. Food and Drug Administration (FDA) approved for patients who refuse colonoscopy and stool-based tests.
Stool Occult Blood Tests
Guaiac-based fecal occult blood testing (gFOBT) significantly reduces CRC mortality by 33%-35% when implemented on an annual or biennial basis.4,5 Fecal immunochemical testing (FIT) has supplanted gFOBT with advantages including independence from dietary restriction and medication-related interference, use of antibodies specific to human globin, and the need for only a single stool sample.
The most common threshold for a positive FIT in the U.S. is ≥ 20 micrograms (μg) of hemoglobin per gram (g) of stool. FIT is approved by the FDA as a qualitative positive or negative result based on a threshold value.6 A meta-analysis summarized test characteristics of commercially available FITs at various detection thresholds.7 The CRC sensitivity and specificity was 75% and 95% for ≥ 20 ug hemoglobin/g stool, and 91% and 90% for 10 ug hemoglobin/g stool, respectively. The sensitivity for advanced adenomas ranged from 25% at 20 μg/g to 40% at a 10 μg/g. Programmatic use of FIT in adults ages ≥ 50 years at 20 ug/g of stool, in cohort and case control studies, has been shown to significantly reduce CRC mortality by 33%-40% and advanced stage CRC by 34%.8,9
Over 57,000 average-risk individuals ages 50–69 years were randomized to biennial FIT or one-time colonoscopy and followed for 10 years.10 CRC mortality and incidence was similar between the groups: 0.22% with FIT vs. 0.24% with colonoscopy and 1.13% with FIT vs. 1.22% with colonoscopy, respectively. Thus, confirming biennial FIT screening is non-inferior to one-time colonoscopy in important CRC-related outcomes.
Multi-Target Stool Tests
Two multitarget stool DNA tests (mt-sDNA) known as Cologuard™ and Cologuard Plus™ have been approved by the FDA. Both tests include a FIT (with a positivity threshold of 20 μg hemoglobin per gram of stool) combined with DNA methylation markers. The test result is qualitative, reported as a positive or negative. Cologuard™ markers include methylated BMP3, NDRG4, and mutant KRAS while Cologuard Plus™ assesses methylated LASS4, LRRC4, and PPP2R5C. The respective mt-sDNA tests were studied in 9989 of 12,776 and 20,176 of 26,758 average-risk individuals undergoing colonoscopy and the results were compared to a commercially available FIT (with a positivity threshold of 20 μg hemoglobin/gram of stool).11,12 In both trials, the sensitivity for CRC and advanced precancerous lesions was higher with the mt-sDNA tests compared to FIT but had a significantly lower specificity for advanced precancerous lesions versus FIT (see Table 1). An age-related decline in specificity was noted in both trials with mt-sDNA, a trend not observed with FIT. This reduction may be attributed to age-related DNA methylation.
Multi-Target Stool RNA Test
A multi-target stool RNA test (mt-sRNA) commercially available as ColoSense™ is FDA-approved. It combines FIT (at a positivity threshold of 20 μg hemoglobin/gram of stool) with RNA-based stool markers. The combined results of the RNA markers, FIT, and smoking status provide a qualitative single test result. In the trial, 8,920 adults aged ≥45 underwent the mt-sRNA test and FIT followed by colonoscopy (13). The mt-sRNA showed higher sensitivity for CRC than FIT (94.4% versus 77.8%) and advanced adenomas (45.9% versus 28.9%) but lower CRC specificity (84.7% vs 94.7%) (Table 1). Unlike mt-sDNA-based tests, mt-sRNA showed consistent performance across age groups, addressing concerns about age-related declines in specificity attributed to DNA methylation.
Blood-Based Tests
In 2014, the first blood-based (BBT) CRC screening test known as Epi proColon™ was FDA but not Centers for Medicare & Medicaid Services (CMS) approved for average-risk adults ≥50 years of age who are offered and refused other U.S Preventive Services Task Force (USPSTF) endorsed CRC screening tests. It is a qualitative test for detection of circulating methylated Septin 9 (mSeptin9). The accuracy of mSeptin9 to detect CRC was assessed in a subset of 7941 asymptomatic average risk adults undergoing screening colonoscopy.14 The sensitivity and specificity for CRC were 48% and 91.5%, respectively. The sensitivity for advanced adenomas was 11.2%. An increase in sensitivity to 63.9% and reduction in specificity to 88.4% for CRC was demonstrated in a sub-analysis of available samples where an additional (third) polymerase chain replicate was performed. Epi proColon™ is not currently reimbursed by Medicare and not endorsed in the latest USPSTF guidelines.
Technologic advancements have improved the detection of circulating tumor markers in the blood. The Shield™ BBT approved by the FDA in 2024 for average risk adults ≥ 45 years integrates three types of cfDNA data (epigenetic changes resulting in the aberrant methylation or fragmentation patterns, and genomic changes resulting in somatic mutations) into a positive or negative test result. In the trial, 22,877 average-risk, asymptomatic individuals ages 45–84 were enrolled and clinical validation was performed in 7,861 of the participants.15 The sensitivity for CRC was 83.1% which decreased to 55% for stage I tumors (see Table 1). CRC specificity was 89.6% and the sensitivity for advanced adenomas and large sessile serrated lesions was 13.2%.
Another BBT SimpleScreen™, which is not yet FDA-approved, analyzed circulating, cell-free DNA methylation patterns in 27,010 evaluable average-risk, asymptomatic adults ages 45–85 years undergoing screening colonoscopy.16 The sensitivity and specificity for CRC was 79.2% and 91.5%, respectively. Similar to Shield, the sensitivity for stage I CRC was low at 57.1%. The sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5% which did not meet the prespecified study criteria.
Effectiveness and Cost Effectiveness
Modeling studies have evaluated novel noninvasive CRC screening tests compared to FIT and colonoscopy.17-20 One compared a hypothetical BBT performed every 3 years that meets the minimum CMS threshold CRC sensitivity and specificity of 74% and 90%, respectively, to other established CRC screening tests beginning at age 45.17 Every 3-year BBT reduced CRC incidence and mortality by 40% and 52%, respectively compared to no screening. However, the reductions were much lower than yearly FIT (72% and 76%, respectively), every 10 year colonoscopy (79% and 81%, respectively), and triennial mt-sDNA (68% and 73%, respectively). The BBT resulted in fewer quality-adjusted life-years per person compared to the alternatives.
Additionally, FIT, colonoscopy, and mt-sDNA were less costly and more effective. Advanced precancerous lesion detection was a key measure for a test’s effectiveness. BBT characteristics would require a CRC sensitivity and specificity of >90% and 90%, respectively, and 80% sensitivity for advanced precancerous lesions at a cost of ≤$120–$140 to be cost-effective compared to FIT at comparable participation rates.
Another analysis simulated colorectal neoplasia progression and compared clinical effectiveness and cost between annual FIT, every 3 year stool mt-sRNA, every 3 year stool mt-sDNA tests, every 3 year stool Shield™; these outcomes were compared to colonoscopy every 10 years and no screening in adults ≥ age 45 over different adherence rates.19 At real-world adherence rates of 60%, colonoscopy prevented most CRC cases and associated deaths. FIT was the most cost-effective strategy at all adherence levels. Between the multi-target stool tests and Shield™, mt-sRNA was the most cost-effective. Compared to FIT, mt-sRNA reduced CRC cases and deaths by 1% and 14%.
The third study evaluated CRC incidence and mortality, quality-adjusted life-years and costs with annual FIT, colonoscopy every 10 years, mt- sDNA tests, mt-sRNA test, and BBTs.20 The latest mt-sDNA (Colguard plus™) and mt-sRNA achieved benefits approaching FIT but the Shield™ test was substantially less effective. The authors hypothesized that if 15% of the population substituted Shield™ for current effective CRC screening strategies, an increase in CRC deaths would occur and require 9-10% of the unscreened population to uptake screening with Shield to avert the increases in CRC deaths due to the substitution effect.
Clinical Implications
The effectiveness of non-invasive screening strategies depends on their diagnostic performance, adherence, and ensuring a timely colonoscopy after a positive test. Two claims-based studies found 47.9% and 49% of patients underwent follow-up colonoscopy within 6 months of an abnormal stool or BBT CRC screening test, respectively.21-22
Conclusions
Non-invasive stool mt-sDNA and mt-sRNA have higher effectiveness than the new BBTs. BBTs can lead to increased CRC mortality if substituted for the FDA and CMS-approved, USPSTF-endorsed, CRC screening modalities. If future BBTs increase their sensitivity for CRC (including early-stage CRC) and advanced precancerous lesions and decrease their cost, they may prove to have similar cost-effectiveness to stool-based tests. Currently, BBTs are not a substitute for colonoscopy or other stool tests and should be offered to patients who refuse other CRC screening modalities. A personalized, risk-adapted approach, paired with improved adherence and follow-up are essential to optimize the population-level impact of CRC screening and ensure equitable, effective cancer prevention.
Dr. Gupta is based at the Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore. Dr. Burke and Dr. Macaron are based at the Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio. Dr. Gupta and Dr. Macaron declared no conflicts of interest in regard to this article. Dr. Burke declared research support from Emtora Biosciences. She is a current consultant for Lumabridge, and has been a consultant for Sebela and Almirall. She also disclosed support from Myriad, Genzyme, Ferring, Merck, Sharp and Dohme, Abbvie, Salix, and Natera.
References
1. Benavidez GA, Sedani AE, Felder TM, Asare M, Rogers CR. Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022). JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae113
2. Galoosian A, Dai H, Croymans D, et al. Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial. JAMA. 2025 Aug 4:e2512049. doi: 10.1001/jama.2025.12049. Epub ahead of print.
3. Pilonis ND, Bugajski M, Wieszczy P, et al. Participation in Competing Strategies for Colorectal Cancer Screening: A Randomized Health Services Study (PICCOLINO Study). Gastroenterology. 2021 Mar;160(4):1097-1105.
4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.
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