David A. Johnson, MD

This transcript has been edited for clarity.

New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we’re still seeing advanced cancer in younger patients who haven’t been screened in time. 

Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, “What can I do now to help myself?” 

Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let’s take a closer look at the results.

 

Exercise’s Risk Reduction Potential

The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep. 

A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. 

Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. 

The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.

Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise. 

The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.

At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% (P = .02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively. 

Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise. 

There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it’s unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group. 

But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.

 

Adjuvant Aspirin in Colon Cancer Subset

That’s a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.

The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). 

PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression. 

Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery. 

Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years (P = .044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction. 

There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160-mg use in the current study is fairly normal, roughly equivalent to two low-dose (81-mg) aspirin tablets. 

Now, it’s worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Services Task Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach. 

 

Two Proactive Actions

These studies highlight 2 interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring. 

Exercise is broadly beneficial and can be recommended immediately. 

For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most. 

These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.

Johnson is a regular contributor to Medscape. He is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He disclosed that he is an adviser for ISOThrive. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we’re still seeing advanced cancer in younger patients who haven’t been screened in time. 

Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, “What can I do now to help myself?” 

Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let’s take a closer look at the results.

 

Exercise’s Risk Reduction Potential

The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep. 

A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. 

Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. 

The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.

Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise. 

The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.

At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% (P = .02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively. 

Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise. 

There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it’s unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group. 

But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.

 

Adjuvant Aspirin in Colon Cancer Subset

That’s a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.

The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). 

PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression. 

Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery. 

Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years (P = .044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction. 

There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160-mg use in the current study is fairly normal, roughly equivalent to two low-dose (81-mg) aspirin tablets. 

Now, it’s worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Services Task Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach. 

 

Two Proactive Actions

These studies highlight 2 interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring. 

Exercise is broadly beneficial and can be recommended immediately. 

For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most. 

These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.

Johnson is a regular contributor to Medscape. He is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He disclosed that he is an adviser for ISOThrive. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we’re still seeing advanced cancer in younger patients who haven’t been screened in time. 

Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, “What can I do now to help myself?” 

Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let’s take a closer look at the results.

 

Exercise’s Risk Reduction Potential

The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep. 

A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. 

Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. 

The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.

Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise. 

The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.

At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% (P = .02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively. 

Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise. 

There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it’s unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group. 

But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.

 

Adjuvant Aspirin in Colon Cancer Subset

That’s a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.

The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). 

PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression. 

Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery. 

Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years (P = .044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction. 

There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160-mg use in the current study is fairly normal, roughly equivalent to two low-dose (81-mg) aspirin tablets. 

Now, it’s worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Services Task Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach. 

 

Two Proactive Actions

These studies highlight 2 interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring. 

Exercise is broadly beneficial and can be recommended immediately. 

For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most. 

These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.

Johnson is a regular contributor to Medscape. He is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He disclosed that he is an adviser for ISOThrive. 

A version of this article appeared on Medscape.com.

Hello. I’m Dr. David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia. 

The American College of Gastroenterology (ACG) recently issued a clinical guideline on the diagnosis and management of gastric premalignant conditions. 

Coincidentally, earlier this year, the ACG and the American Society for Gastrointestinal Endoscopy (ASGE) collaborated to issue recommendations on quality indicators for upper endoscopy. 

In this overview, I’ll focus on gastric premalignant conditions while drawing upon some of the quality indicators from ACG/ASGE. Together, these publications highlight several things that we may be overlooking and clearly need to do better at addressing, given the emerging data in this area.

 

Gastric Premalignant Conditions: Increased Risk for Progression

Gastric premalignant conditions are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. 

The increased risk for progression to gastric adenocarcinoma in the United States is quite striking. It also reveals an important cancer disparity in certain high-risk groups. 

The incidence rates of gastric cancer are two- to 13-fold greater in non-White individuals, particularly among immigrants from high-risk areas. The rates exceed those for esophageal cancer and approach those for colorectal cancer. We have had a dramatic oversight in recognizing the risk for gastric carcinoma in underserved areas. 

Gastric carcinoma is not a good diagnosis. The 5-year survival rate is 36%. Approximately 40% of cases are metastatic at the time of diagnosis; only about 15% are caught at a curable early stage. 

These rates are in far contrast to Asia and areas that do programmatic screening, where the numbers are dramatically reduced. However, in the United States, we’re simply not there yet.

 

Endoscopic Evaluation

There are three phases of endoscopic evaluation for gastric premalignant conditions on which I’d like to focus: pre-endoscopy, intra-endoscopy, and post-endoscopy.

Pre-endoscopy — that is, before you even put in the endoscope — it’s important to assess patients’ potential risk for certain conditions, regardless of the reason for performing the endoscopy. 

Gastric carcinoma is in the top eight leading causes of cancer death in the United States, with the risk being particularly high in Hispanics and Asians. 

According to 2020 data, 40 million people living in the United States were born in another country, with over 70% coming from areas that have a high incidence of gastric carcinoma. 

Accounting for the increased risk in these groups will become even more important. By 2065, it is projected that Asian and Hispanic individuals — the immigrant groups with the highest risk for gastric cancer — will comprise 70% of the US population. Therefore, we need to do a better job on pre-endoscopic assessment if we want to address this major cancer disparity in the United States. 

However, it’s a potentially fixable problem because, in most cases, gastric carcinoma is preceded by a typical asymptomatic precancerous cascade known as the “Correa’s cascade.” It is analogous to what we see in Barrett’s esophagus or even in colorectal neoplasia as it evolves. 

This histologic cascade is important to recognize in patients before they get to the stage of progression. Doing so is highly dependent on the assessment prior to the endoscopy. 

You should also be thinking about high-risk groups before a pre-endoscopy evaluation.

During intra-endoscopy, it’s important to plan your actions while performing the procedure, even if you are not specifically screening for gastric carcinoma. We must be held accountable to established recommendations, standards, and best practices for accurately defining observations, determining appropriate actions, and effectively implementing screening protocols.

A high-quality evaluation of the gastric mucosa is critically important, as an estimated 5%-11% of neoplastic lesions are missed on upper endoscopy completed within 3 years of a gastric cancer diagnosis. With less-experienced endoscopists, the rate of missed neoplastic lesions may be as high as 25%. 

A quality endoscopy begins (as it would in the colon) with mucosal cleaning. This may not be achieved by water alone and requires the use of mucolytic and defoaming agents, such as simethicone or N-acetylcysteine, which can be inordinately helpful. 

Complete mucosal evaluation entails using insufflation to adequately distend the gastric folds.

Atrophic gastritis is observed in a high percentage of patients, and I’m always on the lookout for it when performing endoscopies. One way to identify atrophic gastritis is to look for the loss of gastric folds, which has an approximate sensitivity of 67% and specificity of 85%. The increased visibility of the submucosal venules is another sign of atrophic gastritis, although its sensitivity and specificity are relatively lower at 48% and 87%, respectively. 

Full photo documentation of the gastric mucosa should be included. It is an important part of the intra-endoscopy procedure and also is mentioned as part of the recently published quality indicators for upper endoscopy from ACG/ASGE. 

Recognizing which patients require a biopsy is important. Appropriate biopsy samples should be obtained in patients with recognizable abnormalities. We’re often looking for changes that may be quite subtle. Dysplasia and even adenocarcinoma in the stomach sometimes just cannot be appreciated based on pure endoscopic evaluation.

When it comes to the biopsy protocol, the recommendation is to follow the Sydney system, which was developed in the 1990s. Simply put, this protocol calls for the biopsy samples to be obtained and placed in two separate jars. You look at the greater and lesser curvature of the antrum and the incisura (jar one), and the greater and lesser curvature of the corpus (jar two) in any identified incidental focused biopsy. This is what we do in the colon and the esophagus. 

You should do this after you appropriately clean the mucosa and distend the gastric lumen, ideally using CO2, to avoid the retention of gas. 

Time is another important quality measure. This is similar to the colon, where we see that withdrawal times have increased from 6 minutes to 8-9 minutes. In the stomach, there were initial data about a minimum of 2-3 minutes. However, more recent data in the ACG guideline and the ACG/ASGE quality indicators indicate that detection rates increase after mucosal clearance and dissension when the gastric evaluation is 6-7 minutes. These are numbers we need to pay attention to. The ACG guideline notes that a 2- to 3-minute withdrawal time for upper endoscopy is substandard and not acceptable. If you’re still at that level, then you’re below the standard of care. 

Again, consider time and photo documentation while examining four to six specific areas of both the greater and lesser curvature of the antrum and corpus, and the incisura angularis. It is ideal to use high-definition endoscopy along with the available virtual imaging enhancers. This is the basic requirement for achieving high-quality assessments. 

When it comes to post-endoscopy, it’s essential to talk to your pathologist about using validated instruments of reporting what gastric precancerous lesions involve. There are two different systems: the Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia (OLGIM). Although not routinely used in the United States, they are the best recommendations we have for validated histologic scoring systems.

Your pathologist needs to be up to speed on understanding how to report the extent of intestinal metaplasia (complete, incomplete, and mixed) and identifying the areas of focality or abnormalities. It defines what the subsequent surveillance recommendations should be.

 

Know What’s Required

Let’s review what’s required when it comes to diagnosing and managing gastric premalignant conditions.

First, pre-endoscopy must involve the assessment of risk. Before we put in the endoscope, it’s critical to know, regardless of why the patient is there, who needs to be assessed for gastric premalignant conditions. 

Second, during the intra-endoscopy phase, don’t forget the assessments and documentation. If you’re assessing for gastric intestinal metaplasia, use the Sydney system.

Time is a big component. Withdrawal times are discussed much more frequently now, with the takeaway being that longer is better. Aiming for 6-7 minutes is best, according to recommendations from international endoscopy societies and quality measures from the United States. The ACG guideline says that withdrawal times of 2-3 minutes are not best practice and fall short of standard of care. 

For post-endoscopy, talk to your pathologist to ensure better communication and understanding. Make sure that you have a quality gastrointestinal pathologist interpreting these lesions so patients can either enter surveillance or discontinue surveillance after potentially two exams negative for evidence of progressive change.

To do better, we need to understand these guidelines, which are all applicable now. 

I’m Dr. David Johnson. Thanks for listening. See you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

He has disclosed the relevant financial relationships: Advisor to ISOTHRIVE.

A version of this article first appeared on Medscape.com.

Hello. I’m Dr. David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia. 

The American College of Gastroenterology (ACG) recently issued a clinical guideline on the diagnosis and management of gastric premalignant conditions. 

Coincidentally, earlier this year, the ACG and the American Society for Gastrointestinal Endoscopy (ASGE) collaborated to issue recommendations on quality indicators for upper endoscopy. 

In this overview, I’ll focus on gastric premalignant conditions while drawing upon some of the quality indicators from ACG/ASGE. Together, these publications highlight several things that we may be overlooking and clearly need to do better at addressing, given the emerging data in this area.

 

Gastric Premalignant Conditions: Increased Risk for Progression

Gastric premalignant conditions are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. 

The increased risk for progression to gastric adenocarcinoma in the United States is quite striking. It also reveals an important cancer disparity in certain high-risk groups. 

The incidence rates of gastric cancer are two- to 13-fold greater in non-White individuals, particularly among immigrants from high-risk areas. The rates exceed those for esophageal cancer and approach those for colorectal cancer. We have had a dramatic oversight in recognizing the risk for gastric carcinoma in underserved areas. 

Gastric carcinoma is not a good diagnosis. The 5-year survival rate is 36%. Approximately 40% of cases are metastatic at the time of diagnosis; only about 15% are caught at a curable early stage. 

These rates are in far contrast to Asia and areas that do programmatic screening, where the numbers are dramatically reduced. However, in the United States, we’re simply not there yet.

 

Endoscopic Evaluation

There are three phases of endoscopic evaluation for gastric premalignant conditions on which I’d like to focus: pre-endoscopy, intra-endoscopy, and post-endoscopy.

Pre-endoscopy — that is, before you even put in the endoscope — it’s important to assess patients’ potential risk for certain conditions, regardless of the reason for performing the endoscopy. 

Gastric carcinoma is in the top eight leading causes of cancer death in the United States, with the risk being particularly high in Hispanics and Asians. 

According to 2020 data, 40 million people living in the United States were born in another country, with over 70% coming from areas that have a high incidence of gastric carcinoma. 

Accounting for the increased risk in these groups will become even more important. By 2065, it is projected that Asian and Hispanic individuals — the immigrant groups with the highest risk for gastric cancer — will comprise 70% of the US population. Therefore, we need to do a better job on pre-endoscopic assessment if we want to address this major cancer disparity in the United States. 

However, it’s a potentially fixable problem because, in most cases, gastric carcinoma is preceded by a typical asymptomatic precancerous cascade known as the “Correa’s cascade.” It is analogous to what we see in Barrett’s esophagus or even in colorectal neoplasia as it evolves. 

This histologic cascade is important to recognize in patients before they get to the stage of progression. Doing so is highly dependent on the assessment prior to the endoscopy. 

You should also be thinking about high-risk groups before a pre-endoscopy evaluation.

During intra-endoscopy, it’s important to plan your actions while performing the procedure, even if you are not specifically screening for gastric carcinoma. We must be held accountable to established recommendations, standards, and best practices for accurately defining observations, determining appropriate actions, and effectively implementing screening protocols.

A high-quality evaluation of the gastric mucosa is critically important, as an estimated 5%-11% of neoplastic lesions are missed on upper endoscopy completed within 3 years of a gastric cancer diagnosis. With less-experienced endoscopists, the rate of missed neoplastic lesions may be as high as 25%. 

A quality endoscopy begins (as it would in the colon) with mucosal cleaning. This may not be achieved by water alone and requires the use of mucolytic and defoaming agents, such as simethicone or N-acetylcysteine, which can be inordinately helpful. 

Complete mucosal evaluation entails using insufflation to adequately distend the gastric folds.

Atrophic gastritis is observed in a high percentage of patients, and I’m always on the lookout for it when performing endoscopies. One way to identify atrophic gastritis is to look for the loss of gastric folds, which has an approximate sensitivity of 67% and specificity of 85%. The increased visibility of the submucosal venules is another sign of atrophic gastritis, although its sensitivity and specificity are relatively lower at 48% and 87%, respectively. 

Full photo documentation of the gastric mucosa should be included. It is an important part of the intra-endoscopy procedure and also is mentioned as part of the recently published quality indicators for upper endoscopy from ACG/ASGE. 

Recognizing which patients require a biopsy is important. Appropriate biopsy samples should be obtained in patients with recognizable abnormalities. We’re often looking for changes that may be quite subtle. Dysplasia and even adenocarcinoma in the stomach sometimes just cannot be appreciated based on pure endoscopic evaluation.

When it comes to the biopsy protocol, the recommendation is to follow the Sydney system, which was developed in the 1990s. Simply put, this protocol calls for the biopsy samples to be obtained and placed in two separate jars. You look at the greater and lesser curvature of the antrum and the incisura (jar one), and the greater and lesser curvature of the corpus (jar two) in any identified incidental focused biopsy. This is what we do in the colon and the esophagus. 

You should do this after you appropriately clean the mucosa and distend the gastric lumen, ideally using CO2, to avoid the retention of gas. 

Time is another important quality measure. This is similar to the colon, where we see that withdrawal times have increased from 6 minutes to 8-9 minutes. In the stomach, there were initial data about a minimum of 2-3 minutes. However, more recent data in the ACG guideline and the ACG/ASGE quality indicators indicate that detection rates increase after mucosal clearance and dissension when the gastric evaluation is 6-7 minutes. These are numbers we need to pay attention to. The ACG guideline notes that a 2- to 3-minute withdrawal time for upper endoscopy is substandard and not acceptable. If you’re still at that level, then you’re below the standard of care. 

Again, consider time and photo documentation while examining four to six specific areas of both the greater and lesser curvature of the antrum and corpus, and the incisura angularis. It is ideal to use high-definition endoscopy along with the available virtual imaging enhancers. This is the basic requirement for achieving high-quality assessments. 

When it comes to post-endoscopy, it’s essential to talk to your pathologist about using validated instruments of reporting what gastric precancerous lesions involve. There are two different systems: the Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia (OLGIM). Although not routinely used in the United States, they are the best recommendations we have for validated histologic scoring systems.

Your pathologist needs to be up to speed on understanding how to report the extent of intestinal metaplasia (complete, incomplete, and mixed) and identifying the areas of focality or abnormalities. It defines what the subsequent surveillance recommendations should be.

 

Know What’s Required

Let’s review what’s required when it comes to diagnosing and managing gastric premalignant conditions.

First, pre-endoscopy must involve the assessment of risk. Before we put in the endoscope, it’s critical to know, regardless of why the patient is there, who needs to be assessed for gastric premalignant conditions. 

Second, during the intra-endoscopy phase, don’t forget the assessments and documentation. If you’re assessing for gastric intestinal metaplasia, use the Sydney system.

Time is a big component. Withdrawal times are discussed much more frequently now, with the takeaway being that longer is better. Aiming for 6-7 minutes is best, according to recommendations from international endoscopy societies and quality measures from the United States. The ACG guideline says that withdrawal times of 2-3 minutes are not best practice and fall short of standard of care. 

For post-endoscopy, talk to your pathologist to ensure better communication and understanding. Make sure that you have a quality gastrointestinal pathologist interpreting these lesions so patients can either enter surveillance or discontinue surveillance after potentially two exams negative for evidence of progressive change.

To do better, we need to understand these guidelines, which are all applicable now. 

I’m Dr. David Johnson. Thanks for listening. See you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

He has disclosed the relevant financial relationships: Advisor to ISOTHRIVE.

A version of this article first appeared on Medscape.com.

Hello. I’m Dr. David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia. 

The American College of Gastroenterology (ACG) recently issued a clinical guideline on the diagnosis and management of gastric premalignant conditions. 

Coincidentally, earlier this year, the ACG and the American Society for Gastrointestinal Endoscopy (ASGE) collaborated to issue recommendations on quality indicators for upper endoscopy. 

In this overview, I’ll focus on gastric premalignant conditions while drawing upon some of the quality indicators from ACG/ASGE. Together, these publications highlight several things that we may be overlooking and clearly need to do better at addressing, given the emerging data in this area.

 

Gastric Premalignant Conditions: Increased Risk for Progression

Gastric premalignant conditions are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. 

The increased risk for progression to gastric adenocarcinoma in the United States is quite striking. It also reveals an important cancer disparity in certain high-risk groups. 

The incidence rates of gastric cancer are two- to 13-fold greater in non-White individuals, particularly among immigrants from high-risk areas. The rates exceed those for esophageal cancer and approach those for colorectal cancer. We have had a dramatic oversight in recognizing the risk for gastric carcinoma in underserved areas. 

Gastric carcinoma is not a good diagnosis. The 5-year survival rate is 36%. Approximately 40% of cases are metastatic at the time of diagnosis; only about 15% are caught at a curable early stage. 

These rates are in far contrast to Asia and areas that do programmatic screening, where the numbers are dramatically reduced. However, in the United States, we’re simply not there yet.

 

Endoscopic Evaluation

There are three phases of endoscopic evaluation for gastric premalignant conditions on which I’d like to focus: pre-endoscopy, intra-endoscopy, and post-endoscopy.

Pre-endoscopy — that is, before you even put in the endoscope — it’s important to assess patients’ potential risk for certain conditions, regardless of the reason for performing the endoscopy. 

Gastric carcinoma is in the top eight leading causes of cancer death in the United States, with the risk being particularly high in Hispanics and Asians. 

According to 2020 data, 40 million people living in the United States were born in another country, with over 70% coming from areas that have a high incidence of gastric carcinoma. 

Accounting for the increased risk in these groups will become even more important. By 2065, it is projected that Asian and Hispanic individuals — the immigrant groups with the highest risk for gastric cancer — will comprise 70% of the US population. Therefore, we need to do a better job on pre-endoscopic assessment if we want to address this major cancer disparity in the United States. 

However, it’s a potentially fixable problem because, in most cases, gastric carcinoma is preceded by a typical asymptomatic precancerous cascade known as the “Correa’s cascade.” It is analogous to what we see in Barrett’s esophagus or even in colorectal neoplasia as it evolves. 

This histologic cascade is important to recognize in patients before they get to the stage of progression. Doing so is highly dependent on the assessment prior to the endoscopy. 

You should also be thinking about high-risk groups before a pre-endoscopy evaluation.

During intra-endoscopy, it’s important to plan your actions while performing the procedure, even if you are not specifically screening for gastric carcinoma. We must be held accountable to established recommendations, standards, and best practices for accurately defining observations, determining appropriate actions, and effectively implementing screening protocols.

A high-quality evaluation of the gastric mucosa is critically important, as an estimated 5%-11% of neoplastic lesions are missed on upper endoscopy completed within 3 years of a gastric cancer diagnosis. With less-experienced endoscopists, the rate of missed neoplastic lesions may be as high as 25%. 

A quality endoscopy begins (as it would in the colon) with mucosal cleaning. This may not be achieved by water alone and requires the use of mucolytic and defoaming agents, such as simethicone or N-acetylcysteine, which can be inordinately helpful. 

Complete mucosal evaluation entails using insufflation to adequately distend the gastric folds.

Atrophic gastritis is observed in a high percentage of patients, and I’m always on the lookout for it when performing endoscopies. One way to identify atrophic gastritis is to look for the loss of gastric folds, which has an approximate sensitivity of 67% and specificity of 85%. The increased visibility of the submucosal venules is another sign of atrophic gastritis, although its sensitivity and specificity are relatively lower at 48% and 87%, respectively. 

Full photo documentation of the gastric mucosa should be included. It is an important part of the intra-endoscopy procedure and also is mentioned as part of the recently published quality indicators for upper endoscopy from ACG/ASGE. 

Recognizing which patients require a biopsy is important. Appropriate biopsy samples should be obtained in patients with recognizable abnormalities. We’re often looking for changes that may be quite subtle. Dysplasia and even adenocarcinoma in the stomach sometimes just cannot be appreciated based on pure endoscopic evaluation.

When it comes to the biopsy protocol, the recommendation is to follow the Sydney system, which was developed in the 1990s. Simply put, this protocol calls for the biopsy samples to be obtained and placed in two separate jars. You look at the greater and lesser curvature of the antrum and the incisura (jar one), and the greater and lesser curvature of the corpus (jar two) in any identified incidental focused biopsy. This is what we do in the colon and the esophagus. 

You should do this after you appropriately clean the mucosa and distend the gastric lumen, ideally using CO2, to avoid the retention of gas. 

Time is another important quality measure. This is similar to the colon, where we see that withdrawal times have increased from 6 minutes to 8-9 minutes. In the stomach, there were initial data about a minimum of 2-3 minutes. However, more recent data in the ACG guideline and the ACG/ASGE quality indicators indicate that detection rates increase after mucosal clearance and dissension when the gastric evaluation is 6-7 minutes. These are numbers we need to pay attention to. The ACG guideline notes that a 2- to 3-minute withdrawal time for upper endoscopy is substandard and not acceptable. If you’re still at that level, then you’re below the standard of care. 

Again, consider time and photo documentation while examining four to six specific areas of both the greater and lesser curvature of the antrum and corpus, and the incisura angularis. It is ideal to use high-definition endoscopy along with the available virtual imaging enhancers. This is the basic requirement for achieving high-quality assessments. 

When it comes to post-endoscopy, it’s essential to talk to your pathologist about using validated instruments of reporting what gastric precancerous lesions involve. There are two different systems: the Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia (OLGIM). Although not routinely used in the United States, they are the best recommendations we have for validated histologic scoring systems.

Your pathologist needs to be up to speed on understanding how to report the extent of intestinal metaplasia (complete, incomplete, and mixed) and identifying the areas of focality or abnormalities. It defines what the subsequent surveillance recommendations should be.

 

Know What’s Required

Let’s review what’s required when it comes to diagnosing and managing gastric premalignant conditions.

First, pre-endoscopy must involve the assessment of risk. Before we put in the endoscope, it’s critical to know, regardless of why the patient is there, who needs to be assessed for gastric premalignant conditions. 

Second, during the intra-endoscopy phase, don’t forget the assessments and documentation. If you’re assessing for gastric intestinal metaplasia, use the Sydney system.

Time is a big component. Withdrawal times are discussed much more frequently now, with the takeaway being that longer is better. Aiming for 6-7 minutes is best, according to recommendations from international endoscopy societies and quality measures from the United States. The ACG guideline says that withdrawal times of 2-3 minutes are not best practice and fall short of standard of care. 

For post-endoscopy, talk to your pathologist to ensure better communication and understanding. Make sure that you have a quality gastrointestinal pathologist interpreting these lesions so patients can either enter surveillance or discontinue surveillance after potentially two exams negative for evidence of progressive change.

To do better, we need to understand these guidelines, which are all applicable now. 

I’m Dr. David Johnson. Thanks for listening. See you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

He has disclosed the relevant financial relationships: Advisor to ISOTHRIVE.

A version of this article first appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

A version of this article first appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

A version of this article first appeared on Medscape.com.

I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania. 

In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations. 

 

Performing Capsule Endoscopy in Patients Taking GLP-1s 

We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.

In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.

Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).

Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01). 

We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs. 

 

Barrett Esophagus On the Rise in the Young 

The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).

This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups. 

Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group. 

Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.

Results also showed that 6% of those with young-onset BE had BE-related neoplasia. 

ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE. 

We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors. 

There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker. 

Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.

 

A Novel Biologic for Eosinophilic Esophagitis 

The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).

Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE. 

The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks. 

There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups. 

I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.

 

No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation 

Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.

Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose. 

Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment. 

Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03). 

In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT. 

 

Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis 

Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August. 

Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis. 

Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.

Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.

The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis. 

 

Advantages to Respiratory Syncytial Virus Vaccination in IBD 

Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD. 

Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently. 

Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not. 

Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk. 

For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services. 

This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.

I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.

 

The Impact of Palliative Care Consultations in Decompensated Cirrhosis 

The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.

Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis. 

Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).

The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.

 

Auxora: A Novel Treatment for Acute Pancreatitis 

The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.

There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).

Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure. 

The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.

This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days. 

The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation. 

The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement. 

There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure. 

The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them. 

 

Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.

A version of this article first appeared on Medscape.com.

I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania. 

In this series, I’ll be giving you my top studies presented at ACG 2024, which will be split into two parts. These studies are not presented in any order of priority because I think they all have clinical applications, some of which are more immediate. Where possible, I’ll also provide you with some teaching points that occurred to me when I viewed the data in these presentations. 

 

Repetitive Use Injuries Among Endoscopists 

First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward. 

This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.

Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work. 

Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response. 

Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.

There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day. 

Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength. 

The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this. 

Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.

During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from. 

So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward. 

 

On-Demand Vonoprazan for Heartburn 

The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.

The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand. 

This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.

Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour. 

We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.

 

Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence

The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy. 

Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients. 

This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.

There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12. 

Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19. 

The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone. 

 

Apraglutide’s Efficacy in Short-Bowel Syndrome 

The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.

Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics. 

Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.

Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint. 

Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily. 

From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026. 

This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.

 

Biologics for Treating Immune Checkpoint Inhibitor Colitis

The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients. 

The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well. 

ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.

Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.

The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups. 

There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.

There are two additional teaching points I’d like to convey.

First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.

Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well. 

These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity. 

A version of this article appeared on Medscape.com.

I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania. 

In this series, I’ll be giving you my top studies presented at ACG 2024, which will be split into two parts. These studies are not presented in any order of priority because I think they all have clinical applications, some of which are more immediate. Where possible, I’ll also provide you with some teaching points that occurred to me when I viewed the data in these presentations. 

 

Repetitive Use Injuries Among Endoscopists 

First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward. 

This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.

Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work. 

Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response. 

Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.

There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day. 

Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength. 

The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this. 

Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.

During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from. 

So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward. 

 

On-Demand Vonoprazan for Heartburn 

The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.

The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand. 

This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.

Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour. 

We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.

 

Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence

The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy. 

Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients. 

This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.

There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12. 

Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19. 

The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone. 

 

Apraglutide’s Efficacy in Short-Bowel Syndrome 

The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.

Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics. 

Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.

Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint. 

Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily. 

From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026. 

This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.

 

Biologics for Treating Immune Checkpoint Inhibitor Colitis

The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients. 

The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well. 

ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.

Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.

The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups. 

There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.

There are two additional teaching points I’d like to convey.

First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.

Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well. 

These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity. 

A version of this article appeared on Medscape.com.

I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania. 

In this series, I’ll be giving you my top studies presented at ACG 2024, which will be split into two parts. These studies are not presented in any order of priority because I think they all have clinical applications, some of which are more immediate. Where possible, I’ll also provide you with some teaching points that occurred to me when I viewed the data in these presentations. 

 

Repetitive Use Injuries Among Endoscopists 

First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward. 

This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.

Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work. 

Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response. 

Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.

There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day. 

Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength. 

The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this. 

Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.

During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from. 

So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward. 

 

On-Demand Vonoprazan for Heartburn 

The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.

The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand. 

This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.

Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour. 

We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.

 

Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence

The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy. 

Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients. 

This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.

There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12. 

Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19. 

The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone. 

 

Apraglutide’s Efficacy in Short-Bowel Syndrome 

The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.

Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics. 

Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.

Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint. 

Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily. 

From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026. 

This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.

 

Biologics for Treating Immune Checkpoint Inhibitor Colitis

The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients. 

The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well. 

ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.

Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.

The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups. 

There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.

There are two additional teaching points I’d like to convey.

First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.

Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well. 

These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity. 

A version of this article appeared on Medscape.com.