DDW

SAN DIEGO — A novel generative artificial intelligence (AI) framework known as trajectory flow matching (TFM) can predict the need for red blood cell transfusion and mortality risk in intensive care unit (ICU) patients with acute gastrointestinal (GI) bleeding, researchers reported at Digestive Disease Week^® (DDW) 2025.

Acute GI bleeding is the most common cause of digestive disease–related hospitalization, with an estimated 500,000 hospital admissions annually. It’s known that predicting the need for red blood cell transfusion in the first 24 hours may improve resuscitation and decrease both morbidity and mortality.

However, an existing clinical score known as the Rockall Score does not perform well for predicting mortality, Xi (Nicole) Zhang, an MD-PhD student at McGill University, Montreal, Quebec, Canada, told attendees at DDW. With an area under the curve of 0.65-0.75, better prediction is needed, said Zhang, whose coresearchers included Dennis Shung, MD, MHS, PhD, director of Applied Artificial Intelligence at Yale University School of Medicine, New Haven, Connecticut.

“We’d like to predict multiple outcomes in addition to mortality,” said Zhang, who is also a student at the Mila-Quebec Artificial Intelligence Institute.

As a result, the researchers turned to the TFM approach, applying it to ICU patients with acute GI bleeding to predict both the need for transfusion and in-hospital mortality risk. The all-cause mortality rate is up to 11%, according to a 2020 study by James Y. W. Lau, MD, and colleagues. The rebleeding rate of nonvariceal upper GI bleeds is up to 10.4%. Zhang said the rebleeding rate for variceal upper gastrointestinal bleeding is up to 65%.

The AI method the researchers used outperformed a standard deep learning model at predicting the need for transfusion and estimating mortality risk.

 

Defining the AI Framework

“Probabilistic flow matching is a class of generative artificial intelligence that learns how a simple distribution becomes a more complex distribution with ordinary differential equations,” Zhang told GI & Hepatology News. “For example, if you had a few lines and shapes you could learn how it could become a detailed portrait of a face. In our case, we start with a few blood pressure and heart rate measurements and learn the pattern of blood pressures and heart rates over time, particularly if they reflect clinical deterioration with hemodynamic instability.”

Another way to think about the underlying algorithm, Zhang said, is to think about a river with boats where the river flow determines where the boats end up. “We are trying to direct the boat to the correct dock by adjusting the flow of water in the canal. In this case we are mapping the distribution with the first few data points to the distribution with the entire patient trajectory.”

The information gained, she said, could be helpful in timing endoscopic evaluation or allocating red blood cell products for emergent transfusion.

 

Study Details

The researchers evaluated a cohort of 2602 patients admitted to the ICU, identified from the publicly available MIMIC-III database. They divided the patients into a training set of 2342 patients and an internal validation set of 260 patients. Input variables were severe liver disease comorbidity, administration of vasopressor medications, mean arterial blood pressure, and heart rate over the first 24 hours.

Excluded was hemoglobin, since the point was to test the trajectory of hemodynamic parameters independent of hemoglobin thresholds used to guide red blood cell transfusion.

The outcome measures were administration of packed red blood cell transfusion within 24 hours and all-cause hospital mortality.

The TFM was more accurate than a standard deep learning model in predicting red blood cell transfusion, with an accuracy of 93.6% vs 43.2%; P ≤ .001. It was also more accurate at predicting all-cause in-hospital mortality, with an accuracy of 89.5% vs 42.5%, P = .01.

The researchers concluded that the TFM approach was able to predict the hemodynamic trajectories of patients with acute GI bleeding defined as deviation and outperformed the baseline from the measured mean arterial pressure and heart rate.

 

Expert Perspective

“This is an exciting proof-of-concept study that shows generative AI methods may be applied to complex datasets in order to improve on our current predictive models and improve patient care,” said Jeremy Glissen Brown, MD, MSc, an assistant professor of medicine and a practicing gastroenterologist at Duke University who has published research on the use of AI in clinical practice. He reviewed the study for GI & Hepatology News but was not involved in the research.

“Future work will likely look into the implementation of a version of this model on real-time data.” he said. “We are at an exciting inflection point in predictive models within GI and clinical medicine. Predictive models based on deep learning and generative AI hold the promise of improving how we predict and treat disease states, but the excitement being generated with studies such as this needs to be balanced with the trade-offs inherent to the current paradigm of deep learning and generative models compared to more traditional regression-based models. These include many of the same ‘black box’ explainability questions that have risen in the age of convolutional neural networks as well as some method-specific questions due to the continuous and implicit nature of TFM.”

Elaborating on that, Glissen Brown said: “TFM, like many deep learning techniques, raises concerns about explainability that we’ve long seen with convolutional neural networks — the ‘black box’ problem, where it’s difficult to interpret exactly how and why the model arrives at a particular decision. But TFM also introduces unique challenges due to its continuous and implicit formulation. Since it often learns flows without explicitly defining intermediate representations or steps, it can be harder to trace the logic or pathways it uses to connect inputs to outputs. This makes standard interpretability tools less effective and calls for new techniques tailored to these continuous architectures.”

“This approach could have a real clinical impact,” said Robert Hirten, MD, associate professor of medicine and artificial intelligence, Icahn School of Medicine at Mount Sinai, New York City, who also reviewed the study. “Accurately predicting transfusion needs and mortality risk in real time could support earlier, more targeted interventions for high-risk patients. While these findings still need to be validated in prospective studies, it could enhance ICU decision-making and resource allocation.”

“For the practicing gastroenterologist, we envision this system could help them figure out when to perform endoscopy in a patient admitted with acute gastrointestinal bleeding in the ICU at very high risk of exsanguination,” Zhang told GI & Hepatology News.

The approach, the researchers said, will be useful in identifying unique patient characteristics, make possible the identification of high-risk patients and lead to more personalized medicine.

Hirten, Zhang, and Shung had no disclosures. Glissen Brown reported consulting relationships with Medtronic, OdinVision, Doximity, and Olympus. The National Institutes of Health funded this study.

A version of this article appeared on Medscape.com.

SAN DIEGO — A novel generative artificial intelligence (AI) framework known as trajectory flow matching (TFM) can predict the need for red blood cell transfusion and mortality risk in intensive care unit (ICU) patients with acute gastrointestinal (GI) bleeding, researchers reported at Digestive Disease Week^® (DDW) 2025.

Acute GI bleeding is the most common cause of digestive disease–related hospitalization, with an estimated 500,000 hospital admissions annually. It’s known that predicting the need for red blood cell transfusion in the first 24 hours may improve resuscitation and decrease both morbidity and mortality.

However, an existing clinical score known as the Rockall Score does not perform well for predicting mortality, Xi (Nicole) Zhang, an MD-PhD student at McGill University, Montreal, Quebec, Canada, told attendees at DDW. With an area under the curve of 0.65-0.75, better prediction is needed, said Zhang, whose coresearchers included Dennis Shung, MD, MHS, PhD, director of Applied Artificial Intelligence at Yale University School of Medicine, New Haven, Connecticut.

“We’d like to predict multiple outcomes in addition to mortality,” said Zhang, who is also a student at the Mila-Quebec Artificial Intelligence Institute.

As a result, the researchers turned to the TFM approach, applying it to ICU patients with acute GI bleeding to predict both the need for transfusion and in-hospital mortality risk. The all-cause mortality rate is up to 11%, according to a 2020 study by James Y. W. Lau, MD, and colleagues. The rebleeding rate of nonvariceal upper GI bleeds is up to 10.4%. Zhang said the rebleeding rate for variceal upper gastrointestinal bleeding is up to 65%.

The AI method the researchers used outperformed a standard deep learning model at predicting the need for transfusion and estimating mortality risk.

 

Defining the AI Framework

“Probabilistic flow matching is a class of generative artificial intelligence that learns how a simple distribution becomes a more complex distribution with ordinary differential equations,” Zhang told GI & Hepatology News. “For example, if you had a few lines and shapes you could learn how it could become a detailed portrait of a face. In our case, we start with a few blood pressure and heart rate measurements and learn the pattern of blood pressures and heart rates over time, particularly if they reflect clinical deterioration with hemodynamic instability.”

Another way to think about the underlying algorithm, Zhang said, is to think about a river with boats where the river flow determines where the boats end up. “We are trying to direct the boat to the correct dock by adjusting the flow of water in the canal. In this case we are mapping the distribution with the first few data points to the distribution with the entire patient trajectory.”

The information gained, she said, could be helpful in timing endoscopic evaluation or allocating red blood cell products for emergent transfusion.

 

Study Details

The researchers evaluated a cohort of 2602 patients admitted to the ICU, identified from the publicly available MIMIC-III database. They divided the patients into a training set of 2342 patients and an internal validation set of 260 patients. Input variables were severe liver disease comorbidity, administration of vasopressor medications, mean arterial blood pressure, and heart rate over the first 24 hours.

Excluded was hemoglobin, since the point was to test the trajectory of hemodynamic parameters independent of hemoglobin thresholds used to guide red blood cell transfusion.

The outcome measures were administration of packed red blood cell transfusion within 24 hours and all-cause hospital mortality.

The TFM was more accurate than a standard deep learning model in predicting red blood cell transfusion, with an accuracy of 93.6% vs 43.2%; P ≤ .001. It was also more accurate at predicting all-cause in-hospital mortality, with an accuracy of 89.5% vs 42.5%, P = .01.

The researchers concluded that the TFM approach was able to predict the hemodynamic trajectories of patients with acute GI bleeding defined as deviation and outperformed the baseline from the measured mean arterial pressure and heart rate.

 

Expert Perspective

“This is an exciting proof-of-concept study that shows generative AI methods may be applied to complex datasets in order to improve on our current predictive models and improve patient care,” said Jeremy Glissen Brown, MD, MSc, an assistant professor of medicine and a practicing gastroenterologist at Duke University who has published research on the use of AI in clinical practice. He reviewed the study for GI & Hepatology News but was not involved in the research.

“Future work will likely look into the implementation of a version of this model on real-time data.” he said. “We are at an exciting inflection point in predictive models within GI and clinical medicine. Predictive models based on deep learning and generative AI hold the promise of improving how we predict and treat disease states, but the excitement being generated with studies such as this needs to be balanced with the trade-offs inherent to the current paradigm of deep learning and generative models compared to more traditional regression-based models. These include many of the same ‘black box’ explainability questions that have risen in the age of convolutional neural networks as well as some method-specific questions due to the continuous and implicit nature of TFM.”

Elaborating on that, Glissen Brown said: “TFM, like many deep learning techniques, raises concerns about explainability that we’ve long seen with convolutional neural networks — the ‘black box’ problem, where it’s difficult to interpret exactly how and why the model arrives at a particular decision. But TFM also introduces unique challenges due to its continuous and implicit formulation. Since it often learns flows without explicitly defining intermediate representations or steps, it can be harder to trace the logic or pathways it uses to connect inputs to outputs. This makes standard interpretability tools less effective and calls for new techniques tailored to these continuous architectures.”

“This approach could have a real clinical impact,” said Robert Hirten, MD, associate professor of medicine and artificial intelligence, Icahn School of Medicine at Mount Sinai, New York City, who also reviewed the study. “Accurately predicting transfusion needs and mortality risk in real time could support earlier, more targeted interventions for high-risk patients. While these findings still need to be validated in prospective studies, it could enhance ICU decision-making and resource allocation.”

“For the practicing gastroenterologist, we envision this system could help them figure out when to perform endoscopy in a patient admitted with acute gastrointestinal bleeding in the ICU at very high risk of exsanguination,” Zhang told GI & Hepatology News.

The approach, the researchers said, will be useful in identifying unique patient characteristics, make possible the identification of high-risk patients and lead to more personalized medicine.

Hirten, Zhang, and Shung had no disclosures. Glissen Brown reported consulting relationships with Medtronic, OdinVision, Doximity, and Olympus. The National Institutes of Health funded this study.

A version of this article appeared on Medscape.com.

SAN DIEGO — A novel generative artificial intelligence (AI) framework known as trajectory flow matching (TFM) can predict the need for red blood cell transfusion and mortality risk in intensive care unit (ICU) patients with acute gastrointestinal (GI) bleeding, researchers reported at Digestive Disease Week^® (DDW) 2025.

Acute GI bleeding is the most common cause of digestive disease–related hospitalization, with an estimated 500,000 hospital admissions annually. It’s known that predicting the need for red blood cell transfusion in the first 24 hours may improve resuscitation and decrease both morbidity and mortality.

However, an existing clinical score known as the Rockall Score does not perform well for predicting mortality, Xi (Nicole) Zhang, an MD-PhD student at McGill University, Montreal, Quebec, Canada, told attendees at DDW. With an area under the curve of 0.65-0.75, better prediction is needed, said Zhang, whose coresearchers included Dennis Shung, MD, MHS, PhD, director of Applied Artificial Intelligence at Yale University School of Medicine, New Haven, Connecticut.

“We’d like to predict multiple outcomes in addition to mortality,” said Zhang, who is also a student at the Mila-Quebec Artificial Intelligence Institute.

As a result, the researchers turned to the TFM approach, applying it to ICU patients with acute GI bleeding to predict both the need for transfusion and in-hospital mortality risk. The all-cause mortality rate is up to 11%, according to a 2020 study by James Y. W. Lau, MD, and colleagues. The rebleeding rate of nonvariceal upper GI bleeds is up to 10.4%. Zhang said the rebleeding rate for variceal upper gastrointestinal bleeding is up to 65%.

The AI method the researchers used outperformed a standard deep learning model at predicting the need for transfusion and estimating mortality risk.

 

Defining the AI Framework

“Probabilistic flow matching is a class of generative artificial intelligence that learns how a simple distribution becomes a more complex distribution with ordinary differential equations,” Zhang told GI & Hepatology News. “For example, if you had a few lines and shapes you could learn how it could become a detailed portrait of a face. In our case, we start with a few blood pressure and heart rate measurements and learn the pattern of blood pressures and heart rates over time, particularly if they reflect clinical deterioration with hemodynamic instability.”

Another way to think about the underlying algorithm, Zhang said, is to think about a river with boats where the river flow determines where the boats end up. “We are trying to direct the boat to the correct dock by adjusting the flow of water in the canal. In this case we are mapping the distribution with the first few data points to the distribution with the entire patient trajectory.”

The information gained, she said, could be helpful in timing endoscopic evaluation or allocating red blood cell products for emergent transfusion.

 

Study Details

The researchers evaluated a cohort of 2602 patients admitted to the ICU, identified from the publicly available MIMIC-III database. They divided the patients into a training set of 2342 patients and an internal validation set of 260 patients. Input variables were severe liver disease comorbidity, administration of vasopressor medications, mean arterial blood pressure, and heart rate over the first 24 hours.

Excluded was hemoglobin, since the point was to test the trajectory of hemodynamic parameters independent of hemoglobin thresholds used to guide red blood cell transfusion.

The outcome measures were administration of packed red blood cell transfusion within 24 hours and all-cause hospital mortality.

The TFM was more accurate than a standard deep learning model in predicting red blood cell transfusion, with an accuracy of 93.6% vs 43.2%; P ≤ .001. It was also more accurate at predicting all-cause in-hospital mortality, with an accuracy of 89.5% vs 42.5%, P = .01.

The researchers concluded that the TFM approach was able to predict the hemodynamic trajectories of patients with acute GI bleeding defined as deviation and outperformed the baseline from the measured mean arterial pressure and heart rate.

 

Expert Perspective

“This is an exciting proof-of-concept study that shows generative AI methods may be applied to complex datasets in order to improve on our current predictive models and improve patient care,” said Jeremy Glissen Brown, MD, MSc, an assistant professor of medicine and a practicing gastroenterologist at Duke University who has published research on the use of AI in clinical practice. He reviewed the study for GI & Hepatology News but was not involved in the research.

“Future work will likely look into the implementation of a version of this model on real-time data.” he said. “We are at an exciting inflection point in predictive models within GI and clinical medicine. Predictive models based on deep learning and generative AI hold the promise of improving how we predict and treat disease states, but the excitement being generated with studies such as this needs to be balanced with the trade-offs inherent to the current paradigm of deep learning and generative models compared to more traditional regression-based models. These include many of the same ‘black box’ explainability questions that have risen in the age of convolutional neural networks as well as some method-specific questions due to the continuous and implicit nature of TFM.”

Elaborating on that, Glissen Brown said: “TFM, like many deep learning techniques, raises concerns about explainability that we’ve long seen with convolutional neural networks — the ‘black box’ problem, where it’s difficult to interpret exactly how and why the model arrives at a particular decision. But TFM also introduces unique challenges due to its continuous and implicit formulation. Since it often learns flows without explicitly defining intermediate representations or steps, it can be harder to trace the logic or pathways it uses to connect inputs to outputs. This makes standard interpretability tools less effective and calls for new techniques tailored to these continuous architectures.”

“This approach could have a real clinical impact,” said Robert Hirten, MD, associate professor of medicine and artificial intelligence, Icahn School of Medicine at Mount Sinai, New York City, who also reviewed the study. “Accurately predicting transfusion needs and mortality risk in real time could support earlier, more targeted interventions for high-risk patients. While these findings still need to be validated in prospective studies, it could enhance ICU decision-making and resource allocation.”

“For the practicing gastroenterologist, we envision this system could help them figure out when to perform endoscopy in a patient admitted with acute gastrointestinal bleeding in the ICU at very high risk of exsanguination,” Zhang told GI & Hepatology News.

The approach, the researchers said, will be useful in identifying unique patient characteristics, make possible the identification of high-risk patients and lead to more personalized medicine.

Hirten, Zhang, and Shung had no disclosures. Glissen Brown reported consulting relationships with Medtronic, OdinVision, Doximity, and Olympus. The National Institutes of Health funded this study.

A version of this article appeared on Medscape.com.

SAN DIEGO — Crohn’s disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.

“It’s pretty much accepted that Crohn’s disease does not begin at diagnosis,” said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW)^® 2025.

Although individual blood markers have been associated with the future risk for CD, what’s needed, he said, is to understand which combination of biomarkers are most predictive.

Now, Ungaro and his team have developed a risk score they found accurate in predicting CD onset within 2 years before its onset.

It’s an early version that will likely be further improved and needs additional validation, Ungaro told GI & Hepatology News.

“Once we can accurately identify individuals at risk for developing Crohn’s disease, we can then imagine a number of potential interventions,” Ungaro said.

Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn’t develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.

 

Developing and Testing the Risk Score

To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.

The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.

Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.

Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.

A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).

Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.

The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.

The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.

The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.

The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.

 

A Strong Start

The research represents “an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,” said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.

Currently, physicians treat IBD once it manifests, and it’s difficult to predict who will get CD, he said.

The integrative model’s AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.

Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.

“Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,” he said.

Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told GI & Hepatology News.

A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.

Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.

The PROMISE Consortium is funded by the Helmsley Charitable Trust.

A version of this article appeared on Medscape.com.

SAN DIEGO — Crohn’s disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.

“It’s pretty much accepted that Crohn’s disease does not begin at diagnosis,” said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW)^® 2025.

Although individual blood markers have been associated with the future risk for CD, what’s needed, he said, is to understand which combination of biomarkers are most predictive.

Now, Ungaro and his team have developed a risk score they found accurate in predicting CD onset within 2 years before its onset.

It’s an early version that will likely be further improved and needs additional validation, Ungaro told GI & Hepatology News.

“Once we can accurately identify individuals at risk for developing Crohn’s disease, we can then imagine a number of potential interventions,” Ungaro said.

Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn’t develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.

 

Developing and Testing the Risk Score

To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.

The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.

Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.

Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.

A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).

Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.

The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.

The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.

The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.

The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.

 

A Strong Start

The research represents “an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,” said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.

Currently, physicians treat IBD once it manifests, and it’s difficult to predict who will get CD, he said.

The integrative model’s AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.

Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.

“Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,” he said.

Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told GI & Hepatology News.

A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.

Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.

The PROMISE Consortium is funded by the Helmsley Charitable Trust.

A version of this article appeared on Medscape.com.

SAN DIEGO — Crohn’s disease (CD) has become more common in the United States, and an estimated 1 million Americans have the condition. Still, much is unknown about how to evaluate the individual risk for the disease.

“It’s pretty much accepted that Crohn’s disease does not begin at diagnosis,” said Ryan Ungaro, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, speaking at Digestive Disease Week (DDW)^® 2025.

Although individual blood markers have been associated with the future risk for CD, what’s needed, he said, is to understand which combination of biomarkers are most predictive.

Now, Ungaro and his team have developed a risk score they found accurate in predicting CD onset within 2 years before its onset.

It’s an early version that will likely be further improved and needs additional validation, Ungaro told GI & Hepatology News.

“Once we can accurately identify individuals at risk for developing Crohn’s disease, we can then imagine a number of potential interventions,” Ungaro said.

Approaches would vary depending on how far away the onset is estimated to be. For people who likely wouldn’t develop disease for many years, one intervention might be close monitoring to enable diagnosis in the earliest stages, when treatment works best, he said. Someone at a high risk of developing CD in the next 2 or 3 years, on the other hand, might be offered a pharmaceutical intervention.

 

Developing and Testing the Risk Score

To develop the risk score, Ungaro and colleagues analyzed data of 200 patients with CD and 100 healthy control participants from PREDICTS, a nested case-controlled study of active US military service members. The study is within the larger Department of Defense Serum Repository, which began in 1985 and has more than 62.5 million samples, all stored at −30 °C.

The researchers collected serum samples at four timepoints up to 6 or more years before the diagnosis. They assayed antimicrobial antibodies using the Prometheus Laboratories platform, proteomic markers using the Olink inflammation panel, and anti–granulocyte macrophage colony-stimulating factor autoantibodies using enzyme-linked immunosorbent assay.

Participants (median age, 33 years for both groups) were randomly divided into equally sized training and testing sets. In both the group, 83% of patients were White and about 90% were men.

Time-varying trajectories of marker abundance were estimated for each biomarker. Then, logistic regression modeled disease status as a function of each marker for different timepoints and multivariate modeling was performed via logistic LASSO regression.

A risk score to predict CD onset within 2 years was developed. Prediction models were fit on the testing set and predictive performance evaluated using receiver operating characteristic curves and area under the curve (AUC).

Blood proteins and antibodies have differing associations with CD depending on the time before diagnosis, the researchers found.

The integrative model to predict CD onset within 2 years incorporated 10 biomarkers associated significantly with CD onset.

The AUC for the model was 0.87 (considered good, with 1 indicating perfect discrimination). It produced a specificity of 99% and a positive predictive value of 84%.

The researchers stratified the model scores into quartiles and found the CD incidence within 2 years increased from 2% in the first quartile to 57.7% in the fourth. The relative risk of developing CD in the top quartile individuals vs lower quartile individuals was 10.4.

The serologic and proteomic markers show dynamic changes years before the diagnosis, Ungaro said.

 

A Strong Start

The research represents “an ambitious and exciting frontier for the future of IBD [inflammatory bowel disease] care,” said Victor G. Chedid, MD, MS, consultant and assistant professor of medicine at Mayo Clinic, Rochester, Minnesota, who reviewed the findings but was not involved in the study.

Currently, physicians treat IBD once it manifests, and it’s difficult to predict who will get CD, he said.

The integrative model’s AUC of 0.87 is impressive, and its specificity and positive predictive value levels show it is highly accurate in predicting the onset of CD within 2 years, Chedid added.

Further validation in larger and more diverse population is needed, Chedid said, but he sees the potential for the model to be practical in clinical practice.

“Additionally, the use of blood-based biomarkers makes the model relatively noninvasive and easy to implement in a clinical setting,” he said.

Now, the research goal is to understand the best biomarkers for characterizing the different preclinical phases of CD and to test different interventions in prevention trials, Ungaro told GI & Hepatology News.

A few trials are planned or ongoing, he noted. The trial PIONIR trial will look at the impact of a specific diet on the risk of developing CD, and the INTERCEPT trial aims to develop a blood-based risk score that can identify individuals with a high risk of developing CD within 5 years after initial evaluation.

Ungaro reported being on the advisory board of and/or receiving speaker or consulting fees from AbbVie, Bristol Myer Squibb, Celltrion, ECM Therapeutics, Genentech, Jansen, Eli Lilly, Pfizer, Roivant, Sanofi, and Takeda. Chedid reported having no relevant disclosures.

The PROMISE Consortium is funded by the Helmsley Charitable Trust.

A version of this article appeared on Medscape.com.

SAN DIEGO — With the recently updated recommendations by the US Preventive Services Task Force lowering the age for colorectal cancer screening to 45 instead of 50, an additional 19 million patients now require screening, Asma Khapra, MD, AGAF, a gastroenterologist at Gastro Health in Fairfax, Virginia, told attendees at Digestive Disease Week^® (DDW) 2025.

That change, coupled with the expected shortage of gastroenterologists, means one thing: The current workforce can’t meet patient demand, she said. Private practices in particular face challenges in retaining gastroenterologists, Khapra added.

The private practice model is already declining, she said. The fraction of US gastroenterologists in “fully independent” private practice was about 30% in 2019, Khapra noted. Then, “COVID really changed the landscape even more.” By 2022, “that number has shrunk to 13%.” Meanwhile, 67% are employed gastroenterologists (not in private practice), 7% work in large group practices, and 13% are private equity (PE) backed.

That makes effective retention strategies crucial for private practices, Khapra said. She first addressed the common attractions of private practices, then the challenges, and finally the winning strategies to retain and keep a viable private practice gastroenterology workforce.

 

The Attractions of Private Practice

The reasons for choosing private practice are many, Khapra said, including:

• Autonomy,
• Flexibility,
• Competitive compensation,
• Ownership mindset,
• Partnership paths, and
• Work-life balance including involvement in community and culture.

On the other hand, private practices have unique challenges, including:

• Administrative burdens such as EHR documentation, paperwork, prior authorizations, and staffing issues,
• Financial pressures, including competition with the employment packages offered by hospitals, as reimbursements continue to drop and staffing costs increase,
• Burnout,
• Variety of buy-ins and partnership tracks,
• Limited career development, and
• The strains of aging and endoscopy. “We used to joke in our practice that at any given time, three staff members are in physical therapy due to injuries and disabilities.”
•  

Employing the Iceberg Model

One strategy, Khapra said, is to follow Edward T. Hall’s Iceberg Model of Culture , which focuses on the importance of both visible and invisible elements.

“The key to retention in private practice is to develop a value system where everyone is treated well and respected and compensated fairly,” she said. “That doesn’t mean you split the pie [equally].”

“Visible” elements of the model include the physical environment, policies and practices, symbols and behaviors, she said. While under the surface (“invisible” elements) are shared values, perceptions and attitudes, leadership style, conflict resolution, decision making and unwritten rules.

The key, she said, is to provide physicians an actual voice in decision making and to avoid favouritism, thus avoiding comments such as “Why do the same two people always get the prime scoping blocks?”

Financial transparency is also important, Khapra said. And people want flexibility without it being called special treatment. She provided several practical suggestions to accomplish the invisible Iceberg goals.

For instance, she suggested paying for activities outside the practice that physicians do, such as serving on committees. If the practice can’t afford that, she suggested asking the affiliated hospitals to do so, noting that such an initiative can often build community support.

Paying more attention to early associates than is typical can also benefit the practice, Khapra said. “So much effort is made to recruit them, and then once there, we’re on to the next [recruits].” Instead, she suggested, “pay attention to their needs.”

Providing support to physicians who are injured is also crucial and can foster a community culture, she said. For example, one Gastro Health physician was out for 4 weeks due to complications from surgery. “Everyone jumped in” to help fill the injured physician’s shifts, she said, reassuring the physician that the money would be figured out later. “That’s the culture you want to instill.”

To prevent burnout, another key to retaining physicians, “you have to provide support staff.” And offering good benefits, including parental and maternal leave and disability benefits, is also crucial, Khapra said. Consider practices such as having social dinners, another way to build a sense of community.

Finally, bring in national and local gastroenterologist organizations for discussions, including advocating for fair reimbursement for private practice. Consider working with the Digestive Health Physicians Alliance, which describes itself as the voice of independent gastroenterology, she suggested.

 

More Perspectives

Jami Kinnucan, MD, AGAF, a gastroenterologist and associate professor of medicine at Mayo Clinic, Jacksonville , Florida, spoke about optimizing recruitment of young gastroenterologists and provided perspective on Khapra’s talk.

“I think there’s a lot of overlap” with her topic and retaining private practice gastroenterologists, she said in an interview with GI & Hepatology News. Most important, she said, is having an efficient system in which the administrative flow is left to digital tools or other staff, not physicians. “That will also help to reduce burnout,” she said, and allow physicians to do what they most want to do, which is to focus on providing care to patients.

“People want to feel valued for their work,” she agreed. “People want opportunity for career development, opportunities for growth.”

As gastroenterologists age, flexibility is important, as it in in general for all physicians, Kinnucan said. She suggested schedule flexibility as one way. For instance, “if I tell 10 providers, ‘I need you to see 100 patients this week, but you can do it however you want,’ that promotes flexibility. They might want to see all of them on Monday and Tuesday, for instance. If you give people choice and autonomy, they are more likely to feel like they are part of the decision.”

How do you build a high-functioning team? “You do it by letting them operate autonomously,” and “you let people do the things they are really excited about.” And always, as Khapra said, focus on the invisible elements that are so crucial.

Khapra and Kinnucan had no relevant disclosures. Khapra received no funding for her presentation.

A version of this article appeared on Medscape.com.

SAN DIEGO — With the recently updated recommendations by the US Preventive Services Task Force lowering the age for colorectal cancer screening to 45 instead of 50, an additional 19 million patients now require screening, Asma Khapra, MD, AGAF, a gastroenterologist at Gastro Health in Fairfax, Virginia, told attendees at Digestive Disease Week^® (DDW) 2025.

That change, coupled with the expected shortage of gastroenterologists, means one thing: The current workforce can’t meet patient demand, she said. Private practices in particular face challenges in retaining gastroenterologists, Khapra added.

The private practice model is already declining, she said. The fraction of US gastroenterologists in “fully independent” private practice was about 30% in 2019, Khapra noted. Then, “COVID really changed the landscape even more.” By 2022, “that number has shrunk to 13%.” Meanwhile, 67% are employed gastroenterologists (not in private practice), 7% work in large group practices, and 13% are private equity (PE) backed.

That makes effective retention strategies crucial for private practices, Khapra said. She first addressed the common attractions of private practices, then the challenges, and finally the winning strategies to retain and keep a viable private practice gastroenterology workforce.

 

The Attractions of Private Practice

The reasons for choosing private practice are many, Khapra said, including:

• Autonomy,
• Flexibility,
• Competitive compensation,
• Ownership mindset,
• Partnership paths, and
• Work-life balance including involvement in community and culture.

On the other hand, private practices have unique challenges, including:

• Administrative burdens such as EHR documentation, paperwork, prior authorizations, and staffing issues,
• Financial pressures, including competition with the employment packages offered by hospitals, as reimbursements continue to drop and staffing costs increase,
• Burnout,
• Variety of buy-ins and partnership tracks,
• Limited career development, and
• The strains of aging and endoscopy. “We used to joke in our practice that at any given time, three staff members are in physical therapy due to injuries and disabilities.”
•  

Employing the Iceberg Model

One strategy, Khapra said, is to follow Edward T. Hall’s Iceberg Model of Culture , which focuses on the importance of both visible and invisible elements.

“The key to retention in private practice is to develop a value system where everyone is treated well and respected and compensated fairly,” she said. “That doesn’t mean you split the pie [equally].”

“Visible” elements of the model include the physical environment, policies and practices, symbols and behaviors, she said. While under the surface (“invisible” elements) are shared values, perceptions and attitudes, leadership style, conflict resolution, decision making and unwritten rules.

The key, she said, is to provide physicians an actual voice in decision making and to avoid favouritism, thus avoiding comments such as “Why do the same two people always get the prime scoping blocks?”

Financial transparency is also important, Khapra said. And people want flexibility without it being called special treatment. She provided several practical suggestions to accomplish the invisible Iceberg goals.

For instance, she suggested paying for activities outside the practice that physicians do, such as serving on committees. If the practice can’t afford that, she suggested asking the affiliated hospitals to do so, noting that such an initiative can often build community support.

Paying more attention to early associates than is typical can also benefit the practice, Khapra said. “So much effort is made to recruit them, and then once there, we’re on to the next [recruits].” Instead, she suggested, “pay attention to their needs.”

Providing support to physicians who are injured is also crucial and can foster a community culture, she said. For example, one Gastro Health physician was out for 4 weeks due to complications from surgery. “Everyone jumped in” to help fill the injured physician’s shifts, she said, reassuring the physician that the money would be figured out later. “That’s the culture you want to instill.”

To prevent burnout, another key to retaining physicians, “you have to provide support staff.” And offering good benefits, including parental and maternal leave and disability benefits, is also crucial, Khapra said. Consider practices such as having social dinners, another way to build a sense of community.

Finally, bring in national and local gastroenterologist organizations for discussions, including advocating for fair reimbursement for private practice. Consider working with the Digestive Health Physicians Alliance, which describes itself as the voice of independent gastroenterology, she suggested.

 

More Perspectives

Jami Kinnucan, MD, AGAF, a gastroenterologist and associate professor of medicine at Mayo Clinic, Jacksonville , Florida, spoke about optimizing recruitment of young gastroenterologists and provided perspective on Khapra’s talk.

“I think there’s a lot of overlap” with her topic and retaining private practice gastroenterologists, she said in an interview with GI & Hepatology News. Most important, she said, is having an efficient system in which the administrative flow is left to digital tools or other staff, not physicians. “That will also help to reduce burnout,” she said, and allow physicians to do what they most want to do, which is to focus on providing care to patients.

“People want to feel valued for their work,” she agreed. “People want opportunity for career development, opportunities for growth.”

As gastroenterologists age, flexibility is important, as it in in general for all physicians, Kinnucan said. She suggested schedule flexibility as one way. For instance, “if I tell 10 providers, ‘I need you to see 100 patients this week, but you can do it however you want,’ that promotes flexibility. They might want to see all of them on Monday and Tuesday, for instance. If you give people choice and autonomy, they are more likely to feel like they are part of the decision.”

How do you build a high-functioning team? “You do it by letting them operate autonomously,” and “you let people do the things they are really excited about.” And always, as Khapra said, focus on the invisible elements that are so crucial.

Khapra and Kinnucan had no relevant disclosures. Khapra received no funding for her presentation.

A version of this article appeared on Medscape.com.

SAN DIEGO — With the recently updated recommendations by the US Preventive Services Task Force lowering the age for colorectal cancer screening to 45 instead of 50, an additional 19 million patients now require screening, Asma Khapra, MD, AGAF, a gastroenterologist at Gastro Health in Fairfax, Virginia, told attendees at Digestive Disease Week^® (DDW) 2025.

That change, coupled with the expected shortage of gastroenterologists, means one thing: The current workforce can’t meet patient demand, she said. Private practices in particular face challenges in retaining gastroenterologists, Khapra added.

The private practice model is already declining, she said. The fraction of US gastroenterologists in “fully independent” private practice was about 30% in 2019, Khapra noted. Then, “COVID really changed the landscape even more.” By 2022, “that number has shrunk to 13%.” Meanwhile, 67% are employed gastroenterologists (not in private practice), 7% work in large group practices, and 13% are private equity (PE) backed.

That makes effective retention strategies crucial for private practices, Khapra said. She first addressed the common attractions of private practices, then the challenges, and finally the winning strategies to retain and keep a viable private practice gastroenterology workforce.

 

The Attractions of Private Practice

The reasons for choosing private practice are many, Khapra said, including:

• Autonomy,
• Flexibility,
• Competitive compensation,
• Ownership mindset,
• Partnership paths, and
• Work-life balance including involvement in community and culture.

On the other hand, private practices have unique challenges, including:

• Administrative burdens such as EHR documentation, paperwork, prior authorizations, and staffing issues,
• Financial pressures, including competition with the employment packages offered by hospitals, as reimbursements continue to drop and staffing costs increase,
• Burnout,
• Variety of buy-ins and partnership tracks,
• Limited career development, and
• The strains of aging and endoscopy. “We used to joke in our practice that at any given time, three staff members are in physical therapy due to injuries and disabilities.”
•  

Employing the Iceberg Model

One strategy, Khapra said, is to follow Edward T. Hall’s Iceberg Model of Culture , which focuses on the importance of both visible and invisible elements.

“The key to retention in private practice is to develop a value system where everyone is treated well and respected and compensated fairly,” she said. “That doesn’t mean you split the pie [equally].”

“Visible” elements of the model include the physical environment, policies and practices, symbols and behaviors, she said. While under the surface (“invisible” elements) are shared values, perceptions and attitudes, leadership style, conflict resolution, decision making and unwritten rules.

The key, she said, is to provide physicians an actual voice in decision making and to avoid favouritism, thus avoiding comments such as “Why do the same two people always get the prime scoping blocks?”

Financial transparency is also important, Khapra said. And people want flexibility without it being called special treatment. She provided several practical suggestions to accomplish the invisible Iceberg goals.

For instance, she suggested paying for activities outside the practice that physicians do, such as serving on committees. If the practice can’t afford that, she suggested asking the affiliated hospitals to do so, noting that such an initiative can often build community support.

Paying more attention to early associates than is typical can also benefit the practice, Khapra said. “So much effort is made to recruit them, and then once there, we’re on to the next [recruits].” Instead, she suggested, “pay attention to their needs.”

Providing support to physicians who are injured is also crucial and can foster a community culture, she said. For example, one Gastro Health physician was out for 4 weeks due to complications from surgery. “Everyone jumped in” to help fill the injured physician’s shifts, she said, reassuring the physician that the money would be figured out later. “That’s the culture you want to instill.”

To prevent burnout, another key to retaining physicians, “you have to provide support staff.” And offering good benefits, including parental and maternal leave and disability benefits, is also crucial, Khapra said. Consider practices such as having social dinners, another way to build a sense of community.

Finally, bring in national and local gastroenterologist organizations for discussions, including advocating for fair reimbursement for private practice. Consider working with the Digestive Health Physicians Alliance, which describes itself as the voice of independent gastroenterology, she suggested.

 

More Perspectives

Jami Kinnucan, MD, AGAF, a gastroenterologist and associate professor of medicine at Mayo Clinic, Jacksonville , Florida, spoke about optimizing recruitment of young gastroenterologists and provided perspective on Khapra’s talk.

“I think there’s a lot of overlap” with her topic and retaining private practice gastroenterologists, she said in an interview with GI & Hepatology News. Most important, she said, is having an efficient system in which the administrative flow is left to digital tools or other staff, not physicians. “That will also help to reduce burnout,” she said, and allow physicians to do what they most want to do, which is to focus on providing care to patients.

“People want to feel valued for their work,” she agreed. “People want opportunity for career development, opportunities for growth.”

As gastroenterologists age, flexibility is important, as it in in general for all physicians, Kinnucan said. She suggested schedule flexibility as one way. For instance, “if I tell 10 providers, ‘I need you to see 100 patients this week, but you can do it however you want,’ that promotes flexibility. They might want to see all of them on Monday and Tuesday, for instance. If you give people choice and autonomy, they are more likely to feel like they are part of the decision.”

How do you build a high-functioning team? “You do it by letting them operate autonomously,” and “you let people do the things they are really excited about.” And always, as Khapra said, focus on the invisible elements that are so crucial.

Khapra and Kinnucan had no relevant disclosures. Khapra received no funding for her presentation.

A version of this article appeared on Medscape.com.

SAN DIEGO — A real-time, blood-sensing capsule (PillSense) is a safe and effective diagnostic tool for patients with suspected upper gastrointestinal (GI) bleeding that can aid patient triage, reduce unnecessary procedures, and optimize resource use, a study found.

Notably, patients with negative capsule results had shorter hospital stays and lower acuity markers, and in more than one third of cases, an esophagogastroduodenoscopy (EGD) was avoided altogether without any observed adverse events or readmissions, the study team found.

“Our study shows that this novel capsule that detects blood in the upper GI tract (PillSense) was highly sensitive and specific (> 90%) for detecting recent or active upper GI blood, influenced clinical management in 80% of cases and allowed about one third of patients to be safely discharged from the emergency department, with close outpatient follow-up,” Linda Lee, MD, AGAF, medical director of endoscopy, Brigham and Women’s Hospital and associate professor of medicine, Harvard Medical School, Boston, told GI & Hepatology News.

The study was presented at Digestive Disease Week^® (DDW) 2025.

 

Real-World Insights

EGD is the gold standard for diagnosing suspected upper GI bleeding, but limited access to timely EGD complicates diagnosis and resource allocation.

Approved by the US Food and Drug Administration, PillSense (EnteraSense) is an ingestible capsule with a reusable receiver that provides a rapid, noninvasive method for detecting upper GI bleeding. The capsule analyzes light absorption to identify blood and transmits the result within 10 minutes.

Lee and colleagues evaluated the real-world impact of this point-of-care device on clinical triage and resource allocation, while assessing its safety profile.

They analyzed data on 43 patients (mean age 60 years; 72% men) with clinical suspicion of upper GI bleeding in whom the device was used. The most common symptoms were symptomatic anemia (70%), melena (67%), and hematemesis (33%).

Sixteen PillSense studies (37%) were positive for blood detection, and 27 (63%) were negative.

Compared to patients with a positive capsule results, those without blood detected by the capsule had shorter hospital stays (mean, 3.8 vs 13.4 days, P = .02), lower GBS scores (mean, 7.93 vs 12.81; P = .005), and fewer units of blood transfused (mean, 1.19 vs 10.94; P = .01) and were less apt to be hemodynamically unstable (5 vs 8 patients; P = .03).

Capsule results influenced clinical management in 80% of cases, leading to avoidance of EGD in 37% and prioritization of urgent EGD in 18% (all had active bleeding on EGD).

Capsule use improved resource allocation in 51% of cases. This included 12 patients who were discharged from the ED, six who were assigned an inpatient bed early, and four who underwent expedited colonoscopy as upper GI bleeding was ruled out, they noted.

Among the eight patients who did not undergo EGD, there were no readmissions within 30 days and no adverse events. There were no capsule-related adverse events.

“Clinicians should consider using this novel capsule PillSense as another data point in the management of suspected upper GI bleed,” Lee told GI & Hepatology News.

“This could include in helping to triage patients for safe discharge from the ED or to more urgent endoscopy, to differentiate between upper vs lower GI bleed and to manage ICU patients with possible rebleeding,” Lee said.

 

Important Real-World Evidence

Reached for comment, Shahin Ayazi, MD, esophageal surgeon, Director, Allegheny Health Network Chevalier Jackson Esophageal Research Center, Pittsburgh, Pennsylvania, said this study is important for several reasons.

“Prior investigations have established that PillSense possesses a high negative predictive value for detecting upper GI bleeding and have speculated on its utility in triage, decision-making, and potentially avoiding unnecessary endoscopy. This study is important because it substantiates that speculation with clinical data,” Ayazi, who wasn’t involved in the study, told GI & Hepatology News.

“These findings support the capsule’s practical application in patient stratification and clinical workflow, particularly when diagnostic uncertainty is high and endoscopic resources are limited,” Ayazi noted.

In his experience, PillSense is “highly useful as a triage adjunct in the evaluation of suspected upper GI bleeding. It provides direct and objective evidence as to whether blood is currently present in the stomach,” he said.

“In patients whose presentation is ambiguous or whose clinical scores fall into an intermediate risk zone, this binary result can provide clarity that subjective assessment alone may not achieve. This is particularly relevant in settings where the goal is to perform endoscopy within 24 hours, but the volume of consults exceeds procedural capacity,” Ayazi explained.

“In such scenarios, PillSense enables physicians to stratify patients based on objective evidence of active bleeding, helping to prioritize those who require urgent endoscopy and defer or even avoid endoscopic evaluation in those who do not. The result is a more efficient allocation of endoscopic resources without compromising patient safety,” he added.

Ayazi cautioned that the PillSense capsule should not be used as a replacement for clinical evaluation or established risk stratification protocols.

“It is intended for hemodynamically stable patients and has not been validated in cases of active or massive bleeding. Its diagnostic yield depends on the presence of blood in the stomach at the time of capsule transit; intermittent or proximal bleeding that has ceased may not be detected, introducing the potential for false-negative results,” Ayazi told GI & Hepatology News.

“However, in prior studies, the negative predictive value was high, and in the present study, no adverse outcomes were observed in patients who did not undergo endoscopy following a negative PillSense result,” Ayazi noted.

“It must also be understood that PillSense does not localize the source of bleeding or replace endoscopy in patients with a high likelihood of active hemorrhage. It is not designed to detect bleeding from the lower GI tract or distal small bowel. Rather, it serves as an adjunct that can provide immediate clarity when the need for endoscopy is uncertain, and should be interpreted within the broader context of clinical findings, laboratory data, and established risk stratification tools,” he added.

The study had no specific funding. Lee and Ayazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — A real-time, blood-sensing capsule (PillSense) is a safe and effective diagnostic tool for patients with suspected upper gastrointestinal (GI) bleeding that can aid patient triage, reduce unnecessary procedures, and optimize resource use, a study found.

Notably, patients with negative capsule results had shorter hospital stays and lower acuity markers, and in more than one third of cases, an esophagogastroduodenoscopy (EGD) was avoided altogether without any observed adverse events or readmissions, the study team found.

“Our study shows that this novel capsule that detects blood in the upper GI tract (PillSense) was highly sensitive and specific (> 90%) for detecting recent or active upper GI blood, influenced clinical management in 80% of cases and allowed about one third of patients to be safely discharged from the emergency department, with close outpatient follow-up,” Linda Lee, MD, AGAF, medical director of endoscopy, Brigham and Women’s Hospital and associate professor of medicine, Harvard Medical School, Boston, told GI & Hepatology News.

The study was presented at Digestive Disease Week^® (DDW) 2025.

 

Real-World Insights

EGD is the gold standard for diagnosing suspected upper GI bleeding, but limited access to timely EGD complicates diagnosis and resource allocation.

Approved by the US Food and Drug Administration, PillSense (EnteraSense) is an ingestible capsule with a reusable receiver that provides a rapid, noninvasive method for detecting upper GI bleeding. The capsule analyzes light absorption to identify blood and transmits the result within 10 minutes.

Lee and colleagues evaluated the real-world impact of this point-of-care device on clinical triage and resource allocation, while assessing its safety profile.

They analyzed data on 43 patients (mean age 60 years; 72% men) with clinical suspicion of upper GI bleeding in whom the device was used. The most common symptoms were symptomatic anemia (70%), melena (67%), and hematemesis (33%).

Sixteen PillSense studies (37%) were positive for blood detection, and 27 (63%) were negative.

Compared to patients with a positive capsule results, those without blood detected by the capsule had shorter hospital stays (mean, 3.8 vs 13.4 days, P = .02), lower GBS scores (mean, 7.93 vs 12.81; P = .005), and fewer units of blood transfused (mean, 1.19 vs 10.94; P = .01) and were less apt to be hemodynamically unstable (5 vs 8 patients; P = .03).

Capsule results influenced clinical management in 80% of cases, leading to avoidance of EGD in 37% and prioritization of urgent EGD in 18% (all had active bleeding on EGD).

Capsule use improved resource allocation in 51% of cases. This included 12 patients who were discharged from the ED, six who were assigned an inpatient bed early, and four who underwent expedited colonoscopy as upper GI bleeding was ruled out, they noted.

Among the eight patients who did not undergo EGD, there were no readmissions within 30 days and no adverse events. There were no capsule-related adverse events.

“Clinicians should consider using this novel capsule PillSense as another data point in the management of suspected upper GI bleed,” Lee told GI & Hepatology News.

“This could include in helping to triage patients for safe discharge from the ED or to more urgent endoscopy, to differentiate between upper vs lower GI bleed and to manage ICU patients with possible rebleeding,” Lee said.

 

Important Real-World Evidence

Reached for comment, Shahin Ayazi, MD, esophageal surgeon, Director, Allegheny Health Network Chevalier Jackson Esophageal Research Center, Pittsburgh, Pennsylvania, said this study is important for several reasons.

“Prior investigations have established that PillSense possesses a high negative predictive value for detecting upper GI bleeding and have speculated on its utility in triage, decision-making, and potentially avoiding unnecessary endoscopy. This study is important because it substantiates that speculation with clinical data,” Ayazi, who wasn’t involved in the study, told GI & Hepatology News.

“These findings support the capsule’s practical application in patient stratification and clinical workflow, particularly when diagnostic uncertainty is high and endoscopic resources are limited,” Ayazi noted.

In his experience, PillSense is “highly useful as a triage adjunct in the evaluation of suspected upper GI bleeding. It provides direct and objective evidence as to whether blood is currently present in the stomach,” he said.

“In patients whose presentation is ambiguous or whose clinical scores fall into an intermediate risk zone, this binary result can provide clarity that subjective assessment alone may not achieve. This is particularly relevant in settings where the goal is to perform endoscopy within 24 hours, but the volume of consults exceeds procedural capacity,” Ayazi explained.

“In such scenarios, PillSense enables physicians to stratify patients based on objective evidence of active bleeding, helping to prioritize those who require urgent endoscopy and defer or even avoid endoscopic evaluation in those who do not. The result is a more efficient allocation of endoscopic resources without compromising patient safety,” he added.

Ayazi cautioned that the PillSense capsule should not be used as a replacement for clinical evaluation or established risk stratification protocols.

“It is intended for hemodynamically stable patients and has not been validated in cases of active or massive bleeding. Its diagnostic yield depends on the presence of blood in the stomach at the time of capsule transit; intermittent or proximal bleeding that has ceased may not be detected, introducing the potential for false-negative results,” Ayazi told GI & Hepatology News.

“However, in prior studies, the negative predictive value was high, and in the present study, no adverse outcomes were observed in patients who did not undergo endoscopy following a negative PillSense result,” Ayazi noted.

“It must also be understood that PillSense does not localize the source of bleeding or replace endoscopy in patients with a high likelihood of active hemorrhage. It is not designed to detect bleeding from the lower GI tract or distal small bowel. Rather, it serves as an adjunct that can provide immediate clarity when the need for endoscopy is uncertain, and should be interpreted within the broader context of clinical findings, laboratory data, and established risk stratification tools,” he added.

The study had no specific funding. Lee and Ayazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — A real-time, blood-sensing capsule (PillSense) is a safe and effective diagnostic tool for patients with suspected upper gastrointestinal (GI) bleeding that can aid patient triage, reduce unnecessary procedures, and optimize resource use, a study found.

Notably, patients with negative capsule results had shorter hospital stays and lower acuity markers, and in more than one third of cases, an esophagogastroduodenoscopy (EGD) was avoided altogether without any observed adverse events or readmissions, the study team found.

“Our study shows that this novel capsule that detects blood in the upper GI tract (PillSense) was highly sensitive and specific (> 90%) for detecting recent or active upper GI blood, influenced clinical management in 80% of cases and allowed about one third of patients to be safely discharged from the emergency department, with close outpatient follow-up,” Linda Lee, MD, AGAF, medical director of endoscopy, Brigham and Women’s Hospital and associate professor of medicine, Harvard Medical School, Boston, told GI & Hepatology News.

The study was presented at Digestive Disease Week^® (DDW) 2025.

 

Real-World Insights

EGD is the gold standard for diagnosing suspected upper GI bleeding, but limited access to timely EGD complicates diagnosis and resource allocation.

Approved by the US Food and Drug Administration, PillSense (EnteraSense) is an ingestible capsule with a reusable receiver that provides a rapid, noninvasive method for detecting upper GI bleeding. The capsule analyzes light absorption to identify blood and transmits the result within 10 minutes.

Lee and colleagues evaluated the real-world impact of this point-of-care device on clinical triage and resource allocation, while assessing its safety profile.

They analyzed data on 43 patients (mean age 60 years; 72% men) with clinical suspicion of upper GI bleeding in whom the device was used. The most common symptoms were symptomatic anemia (70%), melena (67%), and hematemesis (33%).

Sixteen PillSense studies (37%) were positive for blood detection, and 27 (63%) were negative.

Compared to patients with a positive capsule results, those without blood detected by the capsule had shorter hospital stays (mean, 3.8 vs 13.4 days, P = .02), lower GBS scores (mean, 7.93 vs 12.81; P = .005), and fewer units of blood transfused (mean, 1.19 vs 10.94; P = .01) and were less apt to be hemodynamically unstable (5 vs 8 patients; P = .03).

Capsule results influenced clinical management in 80% of cases, leading to avoidance of EGD in 37% and prioritization of urgent EGD in 18% (all had active bleeding on EGD).

Capsule use improved resource allocation in 51% of cases. This included 12 patients who were discharged from the ED, six who were assigned an inpatient bed early, and four who underwent expedited colonoscopy as upper GI bleeding was ruled out, they noted.

Among the eight patients who did not undergo EGD, there were no readmissions within 30 days and no adverse events. There were no capsule-related adverse events.

“Clinicians should consider using this novel capsule PillSense as another data point in the management of suspected upper GI bleed,” Lee told GI & Hepatology News.

“This could include in helping to triage patients for safe discharge from the ED or to more urgent endoscopy, to differentiate between upper vs lower GI bleed and to manage ICU patients with possible rebleeding,” Lee said.

 

Important Real-World Evidence

Reached for comment, Shahin Ayazi, MD, esophageal surgeon, Director, Allegheny Health Network Chevalier Jackson Esophageal Research Center, Pittsburgh, Pennsylvania, said this study is important for several reasons.

“Prior investigations have established that PillSense possesses a high negative predictive value for detecting upper GI bleeding and have speculated on its utility in triage, decision-making, and potentially avoiding unnecessary endoscopy. This study is important because it substantiates that speculation with clinical data,” Ayazi, who wasn’t involved in the study, told GI & Hepatology News.

“These findings support the capsule’s practical application in patient stratification and clinical workflow, particularly when diagnostic uncertainty is high and endoscopic resources are limited,” Ayazi noted.

In his experience, PillSense is “highly useful as a triage adjunct in the evaluation of suspected upper GI bleeding. It provides direct and objective evidence as to whether blood is currently present in the stomach,” he said.

“In patients whose presentation is ambiguous or whose clinical scores fall into an intermediate risk zone, this binary result can provide clarity that subjective assessment alone may not achieve. This is particularly relevant in settings where the goal is to perform endoscopy within 24 hours, but the volume of consults exceeds procedural capacity,” Ayazi explained.

“In such scenarios, PillSense enables physicians to stratify patients based on objective evidence of active bleeding, helping to prioritize those who require urgent endoscopy and defer or even avoid endoscopic evaluation in those who do not. The result is a more efficient allocation of endoscopic resources without compromising patient safety,” he added.

Ayazi cautioned that the PillSense capsule should not be used as a replacement for clinical evaluation or established risk stratification protocols.

“It is intended for hemodynamically stable patients and has not been validated in cases of active or massive bleeding. Its diagnostic yield depends on the presence of blood in the stomach at the time of capsule transit; intermittent or proximal bleeding that has ceased may not be detected, introducing the potential for false-negative results,” Ayazi told GI & Hepatology News.

“However, in prior studies, the negative predictive value was high, and in the present study, no adverse outcomes were observed in patients who did not undergo endoscopy following a negative PillSense result,” Ayazi noted.

“It must also be understood that PillSense does not localize the source of bleeding or replace endoscopy in patients with a high likelihood of active hemorrhage. It is not designed to detect bleeding from the lower GI tract or distal small bowel. Rather, it serves as an adjunct that can provide immediate clarity when the need for endoscopy is uncertain, and should be interpreted within the broader context of clinical findings, laboratory data, and established risk stratification tools,” he added.

The study had no specific funding. Lee and Ayazi had no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — In the ever-expanding options for colorectal cancer (CRC) screening, blood tests using precision medicine are becoming more advanced and convenient than ever; however, caveats abound, and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.

Regarding tests, “perfect is not possible,” said William M. Grady, MD, AGAF, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week^® (DDW) 2025.

“We have to remember that that’s the reality of colorectal cancer screening, and we need to meet our patients where they live,” said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).

A big point in their favor is their convenience and higher patient compliance — better tests that don’t get done do not work, he stressed.

He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.

With troubling increases in CRC incidence among younger patients, “that’s a group we’re particularly concerned about,” Grady said.

Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.

Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.

“What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,” he said.

Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).

“The bottom line is that these tests decrease CRC mortality and incidence, and we know there’s a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,” Grady said.

 

Blood-Based Tests: Caveats, Harms?

Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, in Pittsburgh, Pennsylvania, checked off some of the key caveats.

While the overall sensitivity of blood-based tests may look favorable, these tests don’t detect early CRC well,” said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.

Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.

These rates are “similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,” Schoen said. “Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].”

Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.

Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.

He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.

“We have a long way to go to make sure that people who get positive noninvasive tests get followed up,” he said.

In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.

Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.

Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, “the rate of CRC deaths would increase,” Schoen noted.

The findings underscore that “blood testing is unfavorable as a ‘substitution test,’” he added. “In fact, widespread adoption of blood testing could increase CRC morbidity.”

“Is it better than nothing?” he asked. “Yes, but only if performance of a colonoscopy after a positive test is accomplished.”

 

What About FIT?

Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.

Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.

In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.

Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).

“This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,” Tinmouth said.

Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.

“FIT has clear and compelling advantages over colonoscopy,” she said. As well as better compliance among all groups, “it is less costly and also better for the environment [by using fewer resources],” she added.

 

Colonoscopy: ‘Best for First-Line Screening’

Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.

A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.

In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.

Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.

“Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,” she said.

Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study’s appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.

The collective findings underscore that “colonoscopy as a standalone test is uniquely cost-effective,” in the face of costs related to colon cancer treatment.

Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.

Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.

A version of this article appeared on Medscape.com.

SAN DIEGO — In the ever-expanding options for colorectal cancer (CRC) screening, blood tests using precision medicine are becoming more advanced and convenient than ever; however, caveats abound, and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.

Regarding tests, “perfect is not possible,” said William M. Grady, MD, AGAF, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week^® (DDW) 2025.

“We have to remember that that’s the reality of colorectal cancer screening, and we need to meet our patients where they live,” said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).

A big point in their favor is their convenience and higher patient compliance — better tests that don’t get done do not work, he stressed.

He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.

With troubling increases in CRC incidence among younger patients, “that’s a group we’re particularly concerned about,” Grady said.

Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.

Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.

“What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,” he said.

Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).

“The bottom line is that these tests decrease CRC mortality and incidence, and we know there’s a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,” Grady said.

 

Blood-Based Tests: Caveats, Harms?

Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, in Pittsburgh, Pennsylvania, checked off some of the key caveats.

While the overall sensitivity of blood-based tests may look favorable, these tests don’t detect early CRC well,” said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.

Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.

These rates are “similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,” Schoen said. “Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].”

Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.

Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.

He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.

“We have a long way to go to make sure that people who get positive noninvasive tests get followed up,” he said.

In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.

Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.

Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, “the rate of CRC deaths would increase,” Schoen noted.

The findings underscore that “blood testing is unfavorable as a ‘substitution test,’” he added. “In fact, widespread adoption of blood testing could increase CRC morbidity.”

“Is it better than nothing?” he asked. “Yes, but only if performance of a colonoscopy after a positive test is accomplished.”

 

What About FIT?

Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.

Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.

In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.

Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).

“This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,” Tinmouth said.

Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.

“FIT has clear and compelling advantages over colonoscopy,” she said. As well as better compliance among all groups, “it is less costly and also better for the environment [by using fewer resources],” she added.

 

Colonoscopy: ‘Best for First-Line Screening’

Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.

A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.

In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.

Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.

“Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,” she said.

Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study’s appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.

The collective findings underscore that “colonoscopy as a standalone test is uniquely cost-effective,” in the face of costs related to colon cancer treatment.

Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.

Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.

A version of this article appeared on Medscape.com.

SAN DIEGO — In the ever-expanding options for colorectal cancer (CRC) screening, blood tests using precision medicine are becoming more advanced and convenient than ever; however, caveats abound, and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.

Regarding tests, “perfect is not possible,” said William M. Grady, MD, AGAF, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week^® (DDW) 2025.

“We have to remember that that’s the reality of colorectal cancer screening, and we need to meet our patients where they live,” said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).

A big point in their favor is their convenience and higher patient compliance — better tests that don’t get done do not work, he stressed.

He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.

With troubling increases in CRC incidence among younger patients, “that’s a group we’re particularly concerned about,” Grady said.

Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.

Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.

“What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,” he said.

Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).

“The bottom line is that these tests decrease CRC mortality and incidence, and we know there’s a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,” Grady said.

 

Blood-Based Tests: Caveats, Harms?

Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, in Pittsburgh, Pennsylvania, checked off some of the key caveats.

While the overall sensitivity of blood-based tests may look favorable, these tests don’t detect early CRC well,” said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.

Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.

These rates are “similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,” Schoen said. “Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].”

Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.

Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.

He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.

“We have a long way to go to make sure that people who get positive noninvasive tests get followed up,” he said.

In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.

Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.

Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, “the rate of CRC deaths would increase,” Schoen noted.

The findings underscore that “blood testing is unfavorable as a ‘substitution test,’” he added. “In fact, widespread adoption of blood testing could increase CRC morbidity.”

“Is it better than nothing?” he asked. “Yes, but only if performance of a colonoscopy after a positive test is accomplished.”

 

What About FIT?

Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.

Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.

In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.

Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).

“This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,” Tinmouth said.

Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.

“FIT has clear and compelling advantages over colonoscopy,” she said. As well as better compliance among all groups, “it is less costly and also better for the environment [by using fewer resources],” she added.

 

Colonoscopy: ‘Best for First-Line Screening’

Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.

A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.

In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.

Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.

“Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,” she said.

Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study’s appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.

The collective findings underscore that “colonoscopy as a standalone test is uniquely cost-effective,” in the face of costs related to colon cancer treatment.

Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.

Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.

A version of this article appeared on Medscape.com.

SAN DIEGO — The majority of colorectal cancers (CRCs) that emerge following a negative colonoscopy and polypectomy occur prior to recommended surveillance exams, and those cases are more likely to be at an advanced stage, according to new research.

Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.

“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.

“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”

Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.

“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.

In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.

The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.

Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).

Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.

 

Colonoscopist Skill and Benchmarks

A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).

Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).

“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.

“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.

The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.

They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.

And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”

Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.

She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).

“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”

Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.

 

Patient Compliance Can’t Be Counted On 

In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.

“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.

One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.

This underscores the need for better prevention as well as follow-up strategies, he added.

Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.

A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.

While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.

Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.

The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.

Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.

 

FIT Tests Potentially a ‘Major Advantage’

“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.

“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.

More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.

“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.

Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”

Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.

A version of this article appeared on Medscape.com.

SAN DIEGO — The majority of colorectal cancers (CRCs) that emerge following a negative colonoscopy and polypectomy occur prior to recommended surveillance exams, and those cases are more likely to be at an advanced stage, according to new research.

Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.

“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.

“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”

Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.

“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.

In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.

The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.

Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).

Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.

 

Colonoscopist Skill and Benchmarks

A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).

Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).

“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.

“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.

The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.

They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.

And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”

Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.

She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).

“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”

Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.

 

Patient Compliance Can’t Be Counted On 

In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.

“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.

One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.

This underscores the need for better prevention as well as follow-up strategies, he added.

Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.

A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.

While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.

Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.

The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.

Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.

 

FIT Tests Potentially a ‘Major Advantage’

“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.

“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.

More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.

“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.

Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”

Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.

A version of this article appeared on Medscape.com.

SAN DIEGO — The majority of colorectal cancers (CRCs) that emerge following a negative colonoscopy and polypectomy occur prior to recommended surveillance exams, and those cases are more likely to be at an advanced stage, according to new research.

Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.

“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.

“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”

Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.

“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.

In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.

The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.

Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).

Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.

 

Colonoscopist Skill and Benchmarks

A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).

Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).

“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.

“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.

The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.

They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.

And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”

Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.

She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).

“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”

Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.

 

Patient Compliance Can’t Be Counted On 

In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.

“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.

One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.

This underscores the need for better prevention as well as follow-up strategies, he added.

Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.

A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.

While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.

Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.

The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.

Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.

 

FIT Tests Potentially a ‘Major Advantage’

“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.

“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.

More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.

“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.

Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”

Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.

A version of this article appeared on Medscape.com.

SAN DIEGO – Advanced practice providers (APPs) can be trained to perform transnasal endoscopy (TNE) with a single-use ultra-slim gastroscope with only topical anesthesia, a pilot study showed.

“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.

“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.

The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.

The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.

Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.

Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.

TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).

Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.

Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.

Technical success was achieved in all but one patient (96%), and there were no adverse events.

All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.

The average TNE procedure time was 7.3 minutes.

TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.

The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.

“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.

 

Caveats and Cautionary Notes

Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”

Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.

“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.

“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.

The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.

A version of this article appeared on Medscape.com.

SAN DIEGO – Advanced practice providers (APPs) can be trained to perform transnasal endoscopy (TNE) with a single-use ultra-slim gastroscope with only topical anesthesia, a pilot study showed.

“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.

“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.

The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.

The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.

Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.

Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.

TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).

Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.

Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.

Technical success was achieved in all but one patient (96%), and there were no adverse events.

All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.

The average TNE procedure time was 7.3 minutes.

TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.

The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.

“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.

 

Caveats and Cautionary Notes

Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”

Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.

“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.

“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.

The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.

A version of this article appeared on Medscape.com.

SAN DIEGO – Advanced practice providers (APPs) can be trained to perform transnasal endoscopy (TNE) with a single-use ultra-slim gastroscope with only topical anesthesia, a pilot study showed.

“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.

“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.

The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.

The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.

Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.

Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.

TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).

Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.

Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.

Technical success was achieved in all but one patient (96%), and there were no adverse events.

All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.

The average TNE procedure time was 7.3 minutes.

TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.

The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.

“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.

 

Caveats and Cautionary Notes

Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”

Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.

“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.

“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.

The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.

A version of this article appeared on Medscape.com.

SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.

“This is the first study implementing multi-biomarker signatures in informed decisions instead of single biomarker–based trial algorithms [in IBD],” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.

“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.

Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.

In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.

“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.

Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.

To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.

All patients had been assigned the anti-TNF drug infliximab for the first time.

Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.

Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.

The assessments also looked at infliximab and anti-drug antibody levels.

Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.

Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.

The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).

A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.

For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).

Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).

An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.

More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).

“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.

The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.

 

Approach Pioneered in Oncology

Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.

“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.

Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.

The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.” 

 

Benefits in Other IBD Therapies Unclear

Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”

Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”

While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.

“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.

How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.

Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.

“This is the first study implementing multi-biomarker signatures in informed decisions instead of single biomarker–based trial algorithms [in IBD],” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.

“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.

Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.

In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.

“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.

Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.

To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.

All patients had been assigned the anti-TNF drug infliximab for the first time.

Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.

Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.

The assessments also looked at infliximab and anti-drug antibody levels.

Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.

Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.

The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).

A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.

For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).

Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).

An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.

More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).

“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.

The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.

 

Approach Pioneered in Oncology

Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.

“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.

Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.

The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.” 

 

Benefits in Other IBD Therapies Unclear

Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”

Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”

While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.

“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.

How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.

Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.

“This is the first study implementing multi-biomarker signatures in informed decisions instead of single biomarker–based trial algorithms [in IBD],” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.

“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.

Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.

In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.

“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.

Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.

To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.

All patients had been assigned the anti-TNF drug infliximab for the first time.

Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.

Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.

The assessments also looked at infliximab and anti-drug antibody levels.

Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.

Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.

The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).

A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.

For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).

Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).

An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.

More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).

“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.

The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.

 

Approach Pioneered in Oncology

Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.

“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.

Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.

The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.” 

 

Benefits in Other IBD Therapies Unclear

Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”

Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”

While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.

“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.

How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.

Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — Boston Pharmaceuticals’ once-monthly efimosfermin alfa (formerly BOS-580) prescribed for metabolic dysfunction–associated steatohepatitis (MASH) with F2 and F3 fibrosis significantly improved MASH resolution and fibrosis after 24 weeks, according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.

An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.

MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.

The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.

The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.

Primary endpoints were safety and tolerability.

Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.

Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.

 

Positive Results

“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”

After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).

The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.

Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.

Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.

“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.

 

Hopeful Development

“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.

The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.

Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.

Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — Boston Pharmaceuticals’ once-monthly efimosfermin alfa (formerly BOS-580) prescribed for metabolic dysfunction–associated steatohepatitis (MASH) with F2 and F3 fibrosis significantly improved MASH resolution and fibrosis after 24 weeks, according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.

An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.

MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.

The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.

The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.

Primary endpoints were safety and tolerability.

Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.

Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.

 

Positive Results

“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”

After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).

The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.

Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.

Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.

“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.

 

Hopeful Development

“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.

The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.

Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.

Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — Boston Pharmaceuticals’ once-monthly efimosfermin alfa (formerly BOS-580) prescribed for metabolic dysfunction–associated steatohepatitis (MASH) with F2 and F3 fibrosis significantly improved MASH resolution and fibrosis after 24 weeks, according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.

An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.

MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.

The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.

The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.

Primary endpoints were safety and tolerability.

Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.

Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.

 

Positive Results

“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”

After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).

The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.

Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.

Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.

“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.

 

Hopeful Development

“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.

The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.

Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.

Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.

A version of this article appeared on Medscape.com.