GI Oncology

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

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

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

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

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

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

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

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

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

 

Familiar Genes

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

 

Familiar Genes

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

 

Familiar Genes

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

SAN DIEGO — A 20-year initiative by Kaiser Permanente Northern California that assessed colorectal cancer (CRC) screening status and offered flexible options for screening has made a huge difference in CRC incidence, deaths, and racial disparities, an analysis showed.

“The program promptly doubled the proportion of people up to date with screening,” reported lead investigator Douglas A. Corley, MD, PhD, AGAF, a research scientist with Kaiser’s Division of Research, at a press briefing held on April 24, ahead of a presentation at the Digestive Disease Week® (DDW) 2025.

Additionally, within about 10 years, cancer rates were cut by a third, deaths were halved for the second most common cause of cancer deaths in the United States, and the differences that had previously been seen by race or ethnicity were largely eliminated, he said.

“Ten years ago, there were big gaps in cancer risk and death, especially among our Black patients. Now, those differences are nearly gone,” Corley said.

 

Closing the Gap

A systematic CRC screening program was implemented across Kaiser Permanente Northern California. The program included proactive outreach to members who were overdue for screening and mailing them fecal immunochemical test (FIT) kits for at-home use.

Corley and colleagues tracked screening status and CRC incidence and mortality annually from 2000 to 2019 among about 1.1 million members aged 50-75 years across 22 medical centers of the integrated healthcare system. The cohort included American Indian or Alaska Native, Asian, Black, Hispanic, Native Hawaiian or Pacific Islander, and White members.

Screening rates via FIT, colonoscopy, or sigmoidoscopy more than doubled after starting the program, from about 37% in the early years to about 80% within a few years, and it stayed that high through 2019, Corley reported. 

“Importantly, these large increases occurred across the whole population with only small differences,” he said. 

For example, about 76% of Hispanic members, 77% of Black members, 82% of White members, and 83% of Asian members were up to date in the later years and through 2019.

“This shows that systematic, comparable outreach can provide a level playing field for completion of preventive care,” Corley said.

After an expected early uptick in CRC incidence due to early detection, incidence later declined and by 2019 had dropped approximately 30% across the groups.

 

Long-Standing Disparities Erased

CRC deaths also fell by about 50% across all groups, with the largest decline among Black members, Corley noted.

Racial and ethnic disparities in both CRC incidence and mortality have long existed, with Black patients in particular experiencing higher risks and worse outcomes, likely from a mixture of risk factors and healthcare utilization, Corley said.

Offering outreach and equal access to screening in the Kaiser program erased those long-standing disparities.

“It’s remarkable that some of these large differences in mortality by race and ethnicity that we saw two decades ago, and which are found throughout the United States, are now similar to small chance variation in the population,” Corley said.

Flexibility was key to getting more people screened, he noted. “It’s about reaching people at their homes and offering a choice to patients. It’s an astonishingly simple concept.”

It’s important to note that these findings stem from a large, integrated healthcare system, which may differ from other settings, although similar outreach strategies have succeeded in safety net clinics and smaller practices, Corley added.

By boosting screening rates to 80%, the health system reached the level that’s essentially been defined in the past as our goal of screening programs, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, New Haven, Connecticut, and chair of this year’s DDW. 

“It shows that if health systems institute programmatic screening for all their covered individuals, they could markedly increase screening, said Laine, who also served as moderator of the press briefing.

“Most importantly, of course, [screening] was associated with a reduction in colorectal cancer incidence and deaths,” he said.

The study had no commercial funding. Corley reported having no relevant conflicts of interest.

Laine’s disclosures included consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer.

A version of this article appeared on Medscape.com.

SAN DIEGO — A 20-year initiative by Kaiser Permanente Northern California that assessed colorectal cancer (CRC) screening status and offered flexible options for screening has made a huge difference in CRC incidence, deaths, and racial disparities, an analysis showed.

“The program promptly doubled the proportion of people up to date with screening,” reported lead investigator Douglas A. Corley, MD, PhD, AGAF, a research scientist with Kaiser’s Division of Research, at a press briefing held on April 24, ahead of a presentation at the Digestive Disease Week® (DDW) 2025.

Additionally, within about 10 years, cancer rates were cut by a third, deaths were halved for the second most common cause of cancer deaths in the United States, and the differences that had previously been seen by race or ethnicity were largely eliminated, he said.

“Ten years ago, there were big gaps in cancer risk and death, especially among our Black patients. Now, those differences are nearly gone,” Corley said.

 

Closing the Gap

A systematic CRC screening program was implemented across Kaiser Permanente Northern California. The program included proactive outreach to members who were overdue for screening and mailing them fecal immunochemical test (FIT) kits for at-home use.

Corley and colleagues tracked screening status and CRC incidence and mortality annually from 2000 to 2019 among about 1.1 million members aged 50-75 years across 22 medical centers of the integrated healthcare system. The cohort included American Indian or Alaska Native, Asian, Black, Hispanic, Native Hawaiian or Pacific Islander, and White members.

Screening rates via FIT, colonoscopy, or sigmoidoscopy more than doubled after starting the program, from about 37% in the early years to about 80% within a few years, and it stayed that high through 2019, Corley reported. 

“Importantly, these large increases occurred across the whole population with only small differences,” he said. 

For example, about 76% of Hispanic members, 77% of Black members, 82% of White members, and 83% of Asian members were up to date in the later years and through 2019.

“This shows that systematic, comparable outreach can provide a level playing field for completion of preventive care,” Corley said.

After an expected early uptick in CRC incidence due to early detection, incidence later declined and by 2019 had dropped approximately 30% across the groups.

 

Long-Standing Disparities Erased

CRC deaths also fell by about 50% across all groups, with the largest decline among Black members, Corley noted.

Racial and ethnic disparities in both CRC incidence and mortality have long existed, with Black patients in particular experiencing higher risks and worse outcomes, likely from a mixture of risk factors and healthcare utilization, Corley said.

Offering outreach and equal access to screening in the Kaiser program erased those long-standing disparities.

“It’s remarkable that some of these large differences in mortality by race and ethnicity that we saw two decades ago, and which are found throughout the United States, are now similar to small chance variation in the population,” Corley said.

Flexibility was key to getting more people screened, he noted. “It’s about reaching people at their homes and offering a choice to patients. It’s an astonishingly simple concept.”

It’s important to note that these findings stem from a large, integrated healthcare system, which may differ from other settings, although similar outreach strategies have succeeded in safety net clinics and smaller practices, Corley added.

By boosting screening rates to 80%, the health system reached the level that’s essentially been defined in the past as our goal of screening programs, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, New Haven, Connecticut, and chair of this year’s DDW. 

“It shows that if health systems institute programmatic screening for all their covered individuals, they could markedly increase screening, said Laine, who also served as moderator of the press briefing.

“Most importantly, of course, [screening] was associated with a reduction in colorectal cancer incidence and deaths,” he said.

The study had no commercial funding. Corley reported having no relevant conflicts of interest.

Laine’s disclosures included consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer.

A version of this article appeared on Medscape.com.

SAN DIEGO — A 20-year initiative by Kaiser Permanente Northern California that assessed colorectal cancer (CRC) screening status and offered flexible options for screening has made a huge difference in CRC incidence, deaths, and racial disparities, an analysis showed.

“The program promptly doubled the proportion of people up to date with screening,” reported lead investigator Douglas A. Corley, MD, PhD, AGAF, a research scientist with Kaiser’s Division of Research, at a press briefing held on April 24, ahead of a presentation at the Digestive Disease Week® (DDW) 2025.

Additionally, within about 10 years, cancer rates were cut by a third, deaths were halved for the second most common cause of cancer deaths in the United States, and the differences that had previously been seen by race or ethnicity were largely eliminated, he said.

“Ten years ago, there were big gaps in cancer risk and death, especially among our Black patients. Now, those differences are nearly gone,” Corley said.

 

Closing the Gap

A systematic CRC screening program was implemented across Kaiser Permanente Northern California. The program included proactive outreach to members who were overdue for screening and mailing them fecal immunochemical test (FIT) kits for at-home use.

Corley and colleagues tracked screening status and CRC incidence and mortality annually from 2000 to 2019 among about 1.1 million members aged 50-75 years across 22 medical centers of the integrated healthcare system. The cohort included American Indian or Alaska Native, Asian, Black, Hispanic, Native Hawaiian or Pacific Islander, and White members.

Screening rates via FIT, colonoscopy, or sigmoidoscopy more than doubled after starting the program, from about 37% in the early years to about 80% within a few years, and it stayed that high through 2019, Corley reported. 

“Importantly, these large increases occurred across the whole population with only small differences,” he said. 

For example, about 76% of Hispanic members, 77% of Black members, 82% of White members, and 83% of Asian members were up to date in the later years and through 2019.

“This shows that systematic, comparable outreach can provide a level playing field for completion of preventive care,” Corley said.

After an expected early uptick in CRC incidence due to early detection, incidence later declined and by 2019 had dropped approximately 30% across the groups.

 

Long-Standing Disparities Erased

CRC deaths also fell by about 50% across all groups, with the largest decline among Black members, Corley noted.

Racial and ethnic disparities in both CRC incidence and mortality have long existed, with Black patients in particular experiencing higher risks and worse outcomes, likely from a mixture of risk factors and healthcare utilization, Corley said.

Offering outreach and equal access to screening in the Kaiser program erased those long-standing disparities.

“It’s remarkable that some of these large differences in mortality by race and ethnicity that we saw two decades ago, and which are found throughout the United States, are now similar to small chance variation in the population,” Corley said.

Flexibility was key to getting more people screened, he noted. “It’s about reaching people at their homes and offering a choice to patients. It’s an astonishingly simple concept.”

It’s important to note that these findings stem from a large, integrated healthcare system, which may differ from other settings, although similar outreach strategies have succeeded in safety net clinics and smaller practices, Corley added.

By boosting screening rates to 80%, the health system reached the level that’s essentially been defined in the past as our goal of screening programs, said Loren Laine, MD, AGAF, professor of medicine (digestive diseases) at Yale School of Medicine, New Haven, Connecticut, and chair of this year’s DDW. 

“It shows that if health systems institute programmatic screening for all their covered individuals, they could markedly increase screening, said Laine, who also served as moderator of the press briefing.

“Most importantly, of course, [screening] was associated with a reduction in colorectal cancer incidence and deaths,” he said.

The study had no commercial funding. Corley reported having no relevant conflicts of interest.

Laine’s disclosures included consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer.

A version of this article appeared on Medscape.com.

An AGA multidisciplinary panel has reached the conclusion that no recommendation can be made for or against the use of computer-aided detection (CADe)–assisted colonoscopy for colorectal cancer (CRC), the third most common cause of cancer mortality in the United States.

The systematic data review is a collaboration between AGA and The BMJ’s MAGIC Rapid Recommendations. The BMJ issued a separate recommendation against CADe shortly after the AGA guideline was published.

Led by Shahnaz S. Sultan, MD, MHSc, AGAF, of the Division of Gastroenterology, Hepatology, and Nutrition at University of Minnesota, Minneapolis, and recently published in Gastroenterology, found only very low certainty of GRADE-based evidence for several critical long-term outcomes, both desirable and undesirable. These included the following: 11 fewer CRCs per 10,000 individuals and two fewer CRC deaths per 10,000 individuals, an increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications.

This technology did, however, yield an 8% (95% CI, 6-10) absolute increase in the adenoma detection rate (ADR) and a 2% (95% CI, 0-4) increase in the detection rate of advanced adenomas and/or sessile serrated lesions. “How this translates into a reduction in CRC incidence or death is where we were uncertain,” Sultan said. “Our best effort at trying to translate the ADR and other endoscopy outcomes to CRC incidence and CRC death relied on the modeling study, which included a lot of assumptions, which also contributed to our overall lower certainty.”

The systematic and meta-analysis included 41 randomized controlled trials with more than 32,108 participants who underwent CADe-assisted colonoscopy. This technology was associated with a higher polyp detection rate than standard colonoscopy: 56.1% vs 47.9% (relative risk [RR], 1.22, 95% CI, 1.15-1.28). It also had a higher ADR: 44.8% vs 37.4% (RR, 1.22; 95% CI, 1.16-1.29).

But although CADe-assisted colonoscopy may increase ADR, it carries a risk for overdiagnosis, as most polyps detected during colonoscopy are diminutive (< 5 mm) and of low malignant potential, the panel noted. Approximately 25% of lesions are missed at colonoscopy. More than 15 million colonoscopies are performed annually in the United States, but studies have demonstrated variable quality of colonoscopies across key quality indicators.

“Artificial intelligence [AI] is revolutionizing medicine and healthcare in the field of GI [gastroenterology], and CADe in colonoscopy has been brought to commercialization,” Sultan told GI & Hepatology News. “Unlike many areas of endoscopic research where we often have a finite number of clinical trial data, CADe-assisted colonoscopy intervention has been studied in over 44 randomized controlled trials and numerous nonrandomized, real-world studies. The question of whether or not to adopt this intervention at a health system or practice level is an important question that was prioritized to be addressed as guidance was needed.”

Commenting on the guideline but not involved in its formulation, Larry S. Kim, MD, MBA, AGAF, a gastroenterologist at South Denver Gastroenterology in Denver, Colorado, said his practice group has used the GI Genius AI system in its affiliated hospitals but has so far chosen not to implement the technology at its endoscopy centers. “At the hospital, our physicians have the ability to utilize the system for select patients or not at all,” he told GI & Hepatology News.

The fact that The BMJ reached a different conclusion based on the same data, evidence-grading system, and microsimulation, Kim added, “highlights the point that when evidence for benefit is uncertain, underlying values are critical.” In declining to make a recommendation, the AGA panel balanced the benefit of improved detection of potentially precancerous adenomas vs increased resource utilization in the face of unclear benefit. “With different priorities, other bodies could reasonably decide to recommend either for or against CADe.”

 

The Future

According to Sultan, gastroenterologists need a better understanding of patient values and preferences and the value placed on increased adenoma detection, which may also lead to more lifetime colonoscopies without reducing the risk for CRC. “We need better intermediate- and long-term data on the impact of adenoma detection on interval cancers and CRC incidence,” she said. “We need data on detection of polyps that are more clinically significant such as those 6-10 mm in size, as well as serrated sessile lesions. We also need to understand at the population or health system level what the impact is on resources, cost, and access.”

Ultimately, the living guideline underscores the trade-off between desirable and undesirable effects and the limitations of current evidence to support a recommendation, but CADe has to improve as an iterative AI application with further validation and better training.

With the anticipated improvement in software accuracy as AI machine learning reads increasing numbers of images, Sultan added, “the next version of the software may perform better, especially for polyps that are more clinically significant or for flat sessile serrated polyps, which are harder to detect. We plan to revisit the question in the next year or two and potentially revise the guideline.”

These guidelines were fully funded by the AGA Institute with no funding from any outside agency or industry.

Sultan is supported by the US Food and Drug Administration. Co-authors Shazia Mehmood Siddique, Dennis L. Shung, and Benjamin Lebwohl are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Theodore R. Levin is supported by the Permanente Medical Group Delivery Science and Applied Research Program. Cesare Hassan is a consultant for Fujifilm and Olympus. Peter S. Liang reported doing research work for Freenome and advisory board work for Guardant Health and Natera.

Kim is the AGA president-elect. He disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

An AGA multidisciplinary panel has reached the conclusion that no recommendation can be made for or against the use of computer-aided detection (CADe)–assisted colonoscopy for colorectal cancer (CRC), the third most common cause of cancer mortality in the United States.

The systematic data review is a collaboration between AGA and The BMJ’s MAGIC Rapid Recommendations. The BMJ issued a separate recommendation against CADe shortly after the AGA guideline was published.

Led by Shahnaz S. Sultan, MD, MHSc, AGAF, of the Division of Gastroenterology, Hepatology, and Nutrition at University of Minnesota, Minneapolis, and recently published in Gastroenterology, found only very low certainty of GRADE-based evidence for several critical long-term outcomes, both desirable and undesirable. These included the following: 11 fewer CRCs per 10,000 individuals and two fewer CRC deaths per 10,000 individuals, an increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications.

This technology did, however, yield an 8% (95% CI, 6-10) absolute increase in the adenoma detection rate (ADR) and a 2% (95% CI, 0-4) increase in the detection rate of advanced adenomas and/or sessile serrated lesions. “How this translates into a reduction in CRC incidence or death is where we were uncertain,” Sultan said. “Our best effort at trying to translate the ADR and other endoscopy outcomes to CRC incidence and CRC death relied on the modeling study, which included a lot of assumptions, which also contributed to our overall lower certainty.”

The systematic and meta-analysis included 41 randomized controlled trials with more than 32,108 participants who underwent CADe-assisted colonoscopy. This technology was associated with a higher polyp detection rate than standard colonoscopy: 56.1% vs 47.9% (relative risk [RR], 1.22, 95% CI, 1.15-1.28). It also had a higher ADR: 44.8% vs 37.4% (RR, 1.22; 95% CI, 1.16-1.29).

But although CADe-assisted colonoscopy may increase ADR, it carries a risk for overdiagnosis, as most polyps detected during colonoscopy are diminutive (< 5 mm) and of low malignant potential, the panel noted. Approximately 25% of lesions are missed at colonoscopy. More than 15 million colonoscopies are performed annually in the United States, but studies have demonstrated variable quality of colonoscopies across key quality indicators.

“Artificial intelligence [AI] is revolutionizing medicine and healthcare in the field of GI [gastroenterology], and CADe in colonoscopy has been brought to commercialization,” Sultan told GI & Hepatology News. “Unlike many areas of endoscopic research where we often have a finite number of clinical trial data, CADe-assisted colonoscopy intervention has been studied in over 44 randomized controlled trials and numerous nonrandomized, real-world studies. The question of whether or not to adopt this intervention at a health system or practice level is an important question that was prioritized to be addressed as guidance was needed.”

Commenting on the guideline but not involved in its formulation, Larry S. Kim, MD, MBA, AGAF, a gastroenterologist at South Denver Gastroenterology in Denver, Colorado, said his practice group has used the GI Genius AI system in its affiliated hospitals but has so far chosen not to implement the technology at its endoscopy centers. “At the hospital, our physicians have the ability to utilize the system for select patients or not at all,” he told GI & Hepatology News.

The fact that The BMJ reached a different conclusion based on the same data, evidence-grading system, and microsimulation, Kim added, “highlights the point that when evidence for benefit is uncertain, underlying values are critical.” In declining to make a recommendation, the AGA panel balanced the benefit of improved detection of potentially precancerous adenomas vs increased resource utilization in the face of unclear benefit. “With different priorities, other bodies could reasonably decide to recommend either for or against CADe.”

 

The Future

According to Sultan, gastroenterologists need a better understanding of patient values and preferences and the value placed on increased adenoma detection, which may also lead to more lifetime colonoscopies without reducing the risk for CRC. “We need better intermediate- and long-term data on the impact of adenoma detection on interval cancers and CRC incidence,” she said. “We need data on detection of polyps that are more clinically significant such as those 6-10 mm in size, as well as serrated sessile lesions. We also need to understand at the population or health system level what the impact is on resources, cost, and access.”

Ultimately, the living guideline underscores the trade-off between desirable and undesirable effects and the limitations of current evidence to support a recommendation, but CADe has to improve as an iterative AI application with further validation and better training.

With the anticipated improvement in software accuracy as AI machine learning reads increasing numbers of images, Sultan added, “the next version of the software may perform better, especially for polyps that are more clinically significant or for flat sessile serrated polyps, which are harder to detect. We plan to revisit the question in the next year or two and potentially revise the guideline.”

These guidelines were fully funded by the AGA Institute with no funding from any outside agency or industry.

Sultan is supported by the US Food and Drug Administration. Co-authors Shazia Mehmood Siddique, Dennis L. Shung, and Benjamin Lebwohl are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Theodore R. Levin is supported by the Permanente Medical Group Delivery Science and Applied Research Program. Cesare Hassan is a consultant for Fujifilm and Olympus. Peter S. Liang reported doing research work for Freenome and advisory board work for Guardant Health and Natera.

Kim is the AGA president-elect. He disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

An AGA multidisciplinary panel has reached the conclusion that no recommendation can be made for or against the use of computer-aided detection (CADe)–assisted colonoscopy for colorectal cancer (CRC), the third most common cause of cancer mortality in the United States.

The systematic data review is a collaboration between AGA and The BMJ’s MAGIC Rapid Recommendations. The BMJ issued a separate recommendation against CADe shortly after the AGA guideline was published.

Led by Shahnaz S. Sultan, MD, MHSc, AGAF, of the Division of Gastroenterology, Hepatology, and Nutrition at University of Minnesota, Minneapolis, and recently published in Gastroenterology, found only very low certainty of GRADE-based evidence for several critical long-term outcomes, both desirable and undesirable. These included the following: 11 fewer CRCs per 10,000 individuals and two fewer CRC deaths per 10,000 individuals, an increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications.

This technology did, however, yield an 8% (95% CI, 6-10) absolute increase in the adenoma detection rate (ADR) and a 2% (95% CI, 0-4) increase in the detection rate of advanced adenomas and/or sessile serrated lesions. “How this translates into a reduction in CRC incidence or death is where we were uncertain,” Sultan said. “Our best effort at trying to translate the ADR and other endoscopy outcomes to CRC incidence and CRC death relied on the modeling study, which included a lot of assumptions, which also contributed to our overall lower certainty.”

The systematic and meta-analysis included 41 randomized controlled trials with more than 32,108 participants who underwent CADe-assisted colonoscopy. This technology was associated with a higher polyp detection rate than standard colonoscopy: 56.1% vs 47.9% (relative risk [RR], 1.22, 95% CI, 1.15-1.28). It also had a higher ADR: 44.8% vs 37.4% (RR, 1.22; 95% CI, 1.16-1.29).

But although CADe-assisted colonoscopy may increase ADR, it carries a risk for overdiagnosis, as most polyps detected during colonoscopy are diminutive (< 5 mm) and of low malignant potential, the panel noted. Approximately 25% of lesions are missed at colonoscopy. More than 15 million colonoscopies are performed annually in the United States, but studies have demonstrated variable quality of colonoscopies across key quality indicators.

“Artificial intelligence [AI] is revolutionizing medicine and healthcare in the field of GI [gastroenterology], and CADe in colonoscopy has been brought to commercialization,” Sultan told GI & Hepatology News. “Unlike many areas of endoscopic research where we often have a finite number of clinical trial data, CADe-assisted colonoscopy intervention has been studied in over 44 randomized controlled trials and numerous nonrandomized, real-world studies. The question of whether or not to adopt this intervention at a health system or practice level is an important question that was prioritized to be addressed as guidance was needed.”

Commenting on the guideline but not involved in its formulation, Larry S. Kim, MD, MBA, AGAF, a gastroenterologist at South Denver Gastroenterology in Denver, Colorado, said his practice group has used the GI Genius AI system in its affiliated hospitals but has so far chosen not to implement the technology at its endoscopy centers. “At the hospital, our physicians have the ability to utilize the system for select patients or not at all,” he told GI & Hepatology News.

The fact that The BMJ reached a different conclusion based on the same data, evidence-grading system, and microsimulation, Kim added, “highlights the point that when evidence for benefit is uncertain, underlying values are critical.” In declining to make a recommendation, the AGA panel balanced the benefit of improved detection of potentially precancerous adenomas vs increased resource utilization in the face of unclear benefit. “With different priorities, other bodies could reasonably decide to recommend either for or against CADe.”

 

The Future

According to Sultan, gastroenterologists need a better understanding of patient values and preferences and the value placed on increased adenoma detection, which may also lead to more lifetime colonoscopies without reducing the risk for CRC. “We need better intermediate- and long-term data on the impact of adenoma detection on interval cancers and CRC incidence,” she said. “We need data on detection of polyps that are more clinically significant such as those 6-10 mm in size, as well as serrated sessile lesions. We also need to understand at the population or health system level what the impact is on resources, cost, and access.”

Ultimately, the living guideline underscores the trade-off between desirable and undesirable effects and the limitations of current evidence to support a recommendation, but CADe has to improve as an iterative AI application with further validation and better training.

With the anticipated improvement in software accuracy as AI machine learning reads increasing numbers of images, Sultan added, “the next version of the software may perform better, especially for polyps that are more clinically significant or for flat sessile serrated polyps, which are harder to detect. We plan to revisit the question in the next year or two and potentially revise the guideline.”

These guidelines were fully funded by the AGA Institute with no funding from any outside agency or industry.

Sultan is supported by the US Food and Drug Administration. Co-authors Shazia Mehmood Siddique, Dennis L. Shung, and Benjamin Lebwohl are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Theodore R. Levin is supported by the Permanente Medical Group Delivery Science and Applied Research Program. Cesare Hassan is a consultant for Fujifilm and Olympus. Peter S. Liang reported doing research work for Freenome and advisory board work for Guardant Health and Natera.

Kim is the AGA president-elect. He disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

Patient navigation was more effective than usual care in increasing follow-up colonoscopy rates after an abnormal stool test result, a new randomized controlled trial revealed.

The intervention led to a significant 13-point increase in follow-up colonoscopy completion at 1 year, compared with usual care (55.1% vs 42.1%), according the study, which was published online in Annals of Internal Medicine.

 

“Patients with an abnormal fecal test results have about a 1 in 20 chance of having colorectal cancer found, and many more will be found to have advanced adenomas that can be removed to prevent cancer,” Gloria Coronado, PhD, of Kaiser Permanente Center for Health Research, Portland, Oregon, and University of Arizona Cancer Center, Tucson, said in an interview.

“It is critical that these patients get a follow-up colonoscopy,” she said. “Patient navigation can accomplish this goal.”

 

‘Highly Effective’ Intervention

Researchers compared the effectiveness of a patient navigation program with that of usual care outreach in increasing follow-up colonoscopy completion after an abnormal stool test. They also developed a risk-prediction model that calculated a patient’s probability of obtaining a follow-up colonoscopy without navigation to determine if the addition of this intervention had a greater impact on those determined to be less likely to follow through.

The study included 967 patients from a community health center in Washington State who received an abnormal fecal test result within the prior month. The mean age of participants was 61 years, approximately 45% were women and 77% were White, and 18% preferred a Spanish-language intervention. In total, 479 patients received the intervention and 488 received usual care.

The intervention was delivered by a patient navigator who mailed introductory letters, sent text messages, and made live phone calls. In the calls, the navigators addressed the topics of barrier assessment and resolution, bowel preparation instruction and reminders, colonoscopy check-in, and understanding colonoscopy results and retesting intervals.

Patients in the usual-care group were contacted by a referral coordinator to schedule a follow-up colonoscopy appointment. If they couldn’t be reached initially, up to two follow-up attempts were made at 30 and 45 days after the referral date.

Patient navigation resulted in a significant 13% increase in follow-up, and those in this group completed a colonoscopy 27 days sooner than those in the usual care group (mean, 229 days vs 256 days).

Contrary to the authors’ expectation, the effectiveness of the intervention did not vary by patients’ predicted likelihood of obtaining a colonoscopy without navigation.

Notably, 20.3% of patients were unreachable or lost to follow-up, and 29.7% did not receive navigation. Among the 479 patients assigned to navigation, 79 (16.5%) declined participation and 56 (11.7%) were never reached.

The study was primarily conducted during the height of the COVID-19 pandemic, which created additional systemic and individual barriers to completing colonoscopies.

Nevertheless, the authors wrote, “our findings suggest that patient navigation is highly effective for patients eligible for colonoscopy.”

“Most patients who were reached were contacted with six or fewer phone attempts,” Coronado noted. “Further efforts are needed to determine how to reach and motivate patients [who did not participate] to get a follow-up colonoscopy.”

Coronado and colleagues are exploring ways to leverage artificial intelligence and virtual approaches to augment patient navigation programs — for example, by using a virtual navigator or low-cost automated tools to provide education to build patient confidence in getting a colonoscopy.

 

‘A Promising Tool’

“Colonoscopy completion after positive stool-based testing is critical to mitigating the impact of colon cancer,” commented Rajiv Bhuta, MD, assistant professor of clinical gastroenterology & hepatology, Lewis Katz School of Medicine, Temple University, Philadelphia, who was not involved in the study. “While prior studies assessing navigation have demonstrated improvements, none were as large enrollment-wise or as generalizable as the current study.”

That said, Bhuta said in an interview that the study could have provided more detail about coordination and communication with local gastrointestinal practices.

“Local ordering and prescribing practices vary and can significantly impact compliance rates. Were colonoscopies completed via an open access pathway or were the patients required to see a gastroenterologist first? How long was the average wait time for colonoscopy once scheduled? What were the local policies on requiring an escort after the procedure?”

He also noted that some aspects of the study — such as access to reduced-cost specialty care and free ride-share services — may limit generalizable to settings without such resources.

He added: “Although patient navigators for cancer treatment have mandated reimbursement, there is no current reimbursement for navigators for abnormal screening tests, another barrier to wide-spread implementation.”

Bhuta said that the dropout rate in the study mirrors that of his own real-world practice, which serves a high-risk, low-resource community. “I would specifically like to see research that provides behavioral insights on why patients respond positively to navigation — whether it is due to reminders, emotional support, or logistical assistance. Is it systemic barriers or patient disinterest or both that drives noncompliance?”

Despite these uncertainties and the need to refine implementation logistics, Bhuta concluded, “this strategy is a promising tool to reduce disparities and improve colorectal cancer outcomes. Clinicians should advocate for or implement structured follow-up systems, particularly in high-risk populations.”

The study was funded by the US National Cancer Institute. Coronado received a grant/contract from Guardant Health. Bhuta declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Patient navigation was more effective than usual care in increasing follow-up colonoscopy rates after an abnormal stool test result, a new randomized controlled trial revealed.

The intervention led to a significant 13-point increase in follow-up colonoscopy completion at 1 year, compared with usual care (55.1% vs 42.1%), according the study, which was published online in Annals of Internal Medicine.

 

“Patients with an abnormal fecal test results have about a 1 in 20 chance of having colorectal cancer found, and many more will be found to have advanced adenomas that can be removed to prevent cancer,” Gloria Coronado, PhD, of Kaiser Permanente Center for Health Research, Portland, Oregon, and University of Arizona Cancer Center, Tucson, said in an interview.

“It is critical that these patients get a follow-up colonoscopy,” she said. “Patient navigation can accomplish this goal.”

 

‘Highly Effective’ Intervention

Researchers compared the effectiveness of a patient navigation program with that of usual care outreach in increasing follow-up colonoscopy completion after an abnormal stool test. They also developed a risk-prediction model that calculated a patient’s probability of obtaining a follow-up colonoscopy without navigation to determine if the addition of this intervention had a greater impact on those determined to be less likely to follow through.

The study included 967 patients from a community health center in Washington State who received an abnormal fecal test result within the prior month. The mean age of participants was 61 years, approximately 45% were women and 77% were White, and 18% preferred a Spanish-language intervention. In total, 479 patients received the intervention and 488 received usual care.

The intervention was delivered by a patient navigator who mailed introductory letters, sent text messages, and made live phone calls. In the calls, the navigators addressed the topics of barrier assessment and resolution, bowel preparation instruction and reminders, colonoscopy check-in, and understanding colonoscopy results and retesting intervals.

Patients in the usual-care group were contacted by a referral coordinator to schedule a follow-up colonoscopy appointment. If they couldn’t be reached initially, up to two follow-up attempts were made at 30 and 45 days after the referral date.

Patient navigation resulted in a significant 13% increase in follow-up, and those in this group completed a colonoscopy 27 days sooner than those in the usual care group (mean, 229 days vs 256 days).

Contrary to the authors’ expectation, the effectiveness of the intervention did not vary by patients’ predicted likelihood of obtaining a colonoscopy without navigation.

Notably, 20.3% of patients were unreachable or lost to follow-up, and 29.7% did not receive navigation. Among the 479 patients assigned to navigation, 79 (16.5%) declined participation and 56 (11.7%) were never reached.

The study was primarily conducted during the height of the COVID-19 pandemic, which created additional systemic and individual barriers to completing colonoscopies.

Nevertheless, the authors wrote, “our findings suggest that patient navigation is highly effective for patients eligible for colonoscopy.”

“Most patients who were reached were contacted with six or fewer phone attempts,” Coronado noted. “Further efforts are needed to determine how to reach and motivate patients [who did not participate] to get a follow-up colonoscopy.”

Coronado and colleagues are exploring ways to leverage artificial intelligence and virtual approaches to augment patient navigation programs — for example, by using a virtual navigator or low-cost automated tools to provide education to build patient confidence in getting a colonoscopy.

 

‘A Promising Tool’

“Colonoscopy completion after positive stool-based testing is critical to mitigating the impact of colon cancer,” commented Rajiv Bhuta, MD, assistant professor of clinical gastroenterology & hepatology, Lewis Katz School of Medicine, Temple University, Philadelphia, who was not involved in the study. “While prior studies assessing navigation have demonstrated improvements, none were as large enrollment-wise or as generalizable as the current study.”

That said, Bhuta said in an interview that the study could have provided more detail about coordination and communication with local gastrointestinal practices.

“Local ordering and prescribing practices vary and can significantly impact compliance rates. Were colonoscopies completed via an open access pathway or were the patients required to see a gastroenterologist first? How long was the average wait time for colonoscopy once scheduled? What were the local policies on requiring an escort after the procedure?”

He also noted that some aspects of the study — such as access to reduced-cost specialty care and free ride-share services — may limit generalizable to settings without such resources.

He added: “Although patient navigators for cancer treatment have mandated reimbursement, there is no current reimbursement for navigators for abnormal screening tests, another barrier to wide-spread implementation.”

Bhuta said that the dropout rate in the study mirrors that of his own real-world practice, which serves a high-risk, low-resource community. “I would specifically like to see research that provides behavioral insights on why patients respond positively to navigation — whether it is due to reminders, emotional support, or logistical assistance. Is it systemic barriers or patient disinterest or both that drives noncompliance?”

Despite these uncertainties and the need to refine implementation logistics, Bhuta concluded, “this strategy is a promising tool to reduce disparities and improve colorectal cancer outcomes. Clinicians should advocate for or implement structured follow-up systems, particularly in high-risk populations.”

The study was funded by the US National Cancer Institute. Coronado received a grant/contract from Guardant Health. Bhuta declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Patient navigation was more effective than usual care in increasing follow-up colonoscopy rates after an abnormal stool test result, a new randomized controlled trial revealed.

The intervention led to a significant 13-point increase in follow-up colonoscopy completion at 1 year, compared with usual care (55.1% vs 42.1%), according the study, which was published online in Annals of Internal Medicine.

 

“Patients with an abnormal fecal test results have about a 1 in 20 chance of having colorectal cancer found, and many more will be found to have advanced adenomas that can be removed to prevent cancer,” Gloria Coronado, PhD, of Kaiser Permanente Center for Health Research, Portland, Oregon, and University of Arizona Cancer Center, Tucson, said in an interview.

“It is critical that these patients get a follow-up colonoscopy,” she said. “Patient navigation can accomplish this goal.”

 

‘Highly Effective’ Intervention

Researchers compared the effectiveness of a patient navigation program with that of usual care outreach in increasing follow-up colonoscopy completion after an abnormal stool test. They also developed a risk-prediction model that calculated a patient’s probability of obtaining a follow-up colonoscopy without navigation to determine if the addition of this intervention had a greater impact on those determined to be less likely to follow through.

The study included 967 patients from a community health center in Washington State who received an abnormal fecal test result within the prior month. The mean age of participants was 61 years, approximately 45% were women and 77% were White, and 18% preferred a Spanish-language intervention. In total, 479 patients received the intervention and 488 received usual care.

The intervention was delivered by a patient navigator who mailed introductory letters, sent text messages, and made live phone calls. In the calls, the navigators addressed the topics of barrier assessment and resolution, bowel preparation instruction and reminders, colonoscopy check-in, and understanding colonoscopy results and retesting intervals.

Patients in the usual-care group were contacted by a referral coordinator to schedule a follow-up colonoscopy appointment. If they couldn’t be reached initially, up to two follow-up attempts were made at 30 and 45 days after the referral date.

Patient navigation resulted in a significant 13% increase in follow-up, and those in this group completed a colonoscopy 27 days sooner than those in the usual care group (mean, 229 days vs 256 days).

Contrary to the authors’ expectation, the effectiveness of the intervention did not vary by patients’ predicted likelihood of obtaining a colonoscopy without navigation.

Notably, 20.3% of patients were unreachable or lost to follow-up, and 29.7% did not receive navigation. Among the 479 patients assigned to navigation, 79 (16.5%) declined participation and 56 (11.7%) were never reached.

The study was primarily conducted during the height of the COVID-19 pandemic, which created additional systemic and individual barriers to completing colonoscopies.

Nevertheless, the authors wrote, “our findings suggest that patient navigation is highly effective for patients eligible for colonoscopy.”

“Most patients who were reached were contacted with six or fewer phone attempts,” Coronado noted. “Further efforts are needed to determine how to reach and motivate patients [who did not participate] to get a follow-up colonoscopy.”

Coronado and colleagues are exploring ways to leverage artificial intelligence and virtual approaches to augment patient navigation programs — for example, by using a virtual navigator or low-cost automated tools to provide education to build patient confidence in getting a colonoscopy.

 

‘A Promising Tool’

“Colonoscopy completion after positive stool-based testing is critical to mitigating the impact of colon cancer,” commented Rajiv Bhuta, MD, assistant professor of clinical gastroenterology & hepatology, Lewis Katz School of Medicine, Temple University, Philadelphia, who was not involved in the study. “While prior studies assessing navigation have demonstrated improvements, none were as large enrollment-wise or as generalizable as the current study.”

That said, Bhuta said in an interview that the study could have provided more detail about coordination and communication with local gastrointestinal practices.

“Local ordering and prescribing practices vary and can significantly impact compliance rates. Were colonoscopies completed via an open access pathway or were the patients required to see a gastroenterologist first? How long was the average wait time for colonoscopy once scheduled? What were the local policies on requiring an escort after the procedure?”

He also noted that some aspects of the study — such as access to reduced-cost specialty care and free ride-share services — may limit generalizable to settings without such resources.

He added: “Although patient navigators for cancer treatment have mandated reimbursement, there is no current reimbursement for navigators for abnormal screening tests, another barrier to wide-spread implementation.”

Bhuta said that the dropout rate in the study mirrors that of his own real-world practice, which serves a high-risk, low-resource community. “I would specifically like to see research that provides behavioral insights on why patients respond positively to navigation — whether it is due to reminders, emotional support, or logistical assistance. Is it systemic barriers or patient disinterest or both that drives noncompliance?”

Despite these uncertainties and the need to refine implementation logistics, Bhuta concluded, “this strategy is a promising tool to reduce disparities and improve colorectal cancer outcomes. Clinicians should advocate for or implement structured follow-up systems, particularly in high-risk populations.”

The study was funded by the US National Cancer Institute. Coronado received a grant/contract from Guardant Health. Bhuta declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Long-term use of statins may delay or deflect the development of hepatocellular carcinoma in adults with chronic liver disease, as well as in the general population, emerging research, including several large cohort studies, suggested.

The most recent study, published in JAMA Internal Medicine, showed a lower incidence of hepatic decompensation among statin users in a registry for adults aged 40 years or older with baseline chronic liver disease.

“Our findings support the idea that statins may offer benefits beyond lipid-lowering in patients with [chronic liver disease], and clinicians may be more confident in prescribing statins when indicated,” even in these patients, said corresponding Co-author Raymond T. Chung, MD, gastroenterology investigator at Mass General Research Institute, Boston, in an interview. 

“While prior studies have suggested an association between statin use and reduced hepatocellular carcinoma risk, our study aimed to build on that evidence by using a large, real-world, hospital-based cohort inclusive of all etiologies of chronic liver disease,” Chung told GI & Hepatology News.

Chung, along with Jonggi Choi, MD, of the University of Ulsan College of Medicine, Seoul, South Korea, and colleagues, reviewed data from the Research Patient Data Registry from 2000 to 2023 for 16,501 participantsaged 40 years or older with baseline chronic liver disease and baseline Fibrosis-4 (FIB-4) scores ≥ 1.3.

The study population had a mean age of 59.7 years, and 40.9% were women. The researchers divided the population into statin users (n = 3610) and nonusers (n = 12,891). Statin use was defined as a cumulative defined daily dose ≥ 30 mg.

The primary outcome was the cumulative incidence of hepatocellular carcinoma and hepatic decompensation.

At 10 years follow-up, statin users showed a significantly reduced incidence of hepatocellular carcinoma vs nonusers (3.8% vs 8.0%; P < .001) as well as a significantly reduced incidence of hepatic decompensation (10.6% vs 19.5%; P < .001).

Incorporating FIB-4 scores, a surrogate marker for liver fibrosis, also showed that statin users were less likely to experience fibrosis progression, offering a potential mechanism of action for the observed reduction in adverse liver outcomes, Chung told GI & Hepatology News.

“Similar trends have been observed in prior observational studies, but our findings now support a real effect of statin use on fibrosis progression,” he said. “However, what strengthened our study was that the association remained consistent across multiple subgroups and sensitivity analyses.”

Another study published in Clinical Gastroenterology and Hepatology showed a reduced risk of developing severe liver disease in a Swedish cohort of noncirrhotic adults with chronic liver disease who used statins (n = 3862) compared with control patients with chronic liver disease (matched 1:1) and who did not use statins (hazard ratio [HR], 0.60). 

In that study, Rajani Sharma, MD, and colleagues found a protective association in both prefibrosis and fibrosis stages at diagnosis, and statin use was associated with reduced rates of progression to both cirrhosis and hepatocellular carcinoma (HR, 0.62 and 0.44, respectively).

 

Exciting and Necessary Research

The research by Choi and colleagues is “exciting,” said Bubu Banini, MD, PhD, an assistant professor in digestive diseases at Yale School of Medicine, New Haven, Connecticut, in an interview.

Liver cancer prevalence has risen over the past few decades in the United States and worldwide, and the 5-year overall survival rate of liver cancer is less than 20%, Banini told GI & Hepatology News.

Clinicians often withhold statins out of fear of liver injury in persons with chronic liver disease; however, a takeaway from this study is that for persons with chronic liver disease who have indications for statin use, the medication should not be withheld, she said.

Of course, prospective studies are needed to replicate the results, Banini added.

The study findings were limited by several factors, including the inability to adjust for all potential confounding variables, lack of data on post-index treatments, and the use of wide, cumulative, defined daily dose categories to ensure statistical power, the researchers noted.

“Moving forward, randomized controlled trials are essential to establish a causal relationship and clarify the molecular and clinical pathways through which statins exert hepatoprotective effects,” Chung added.

Randomized controlled trials are also needed to determine whether statins can actually reduce the risk for hepatocellular carcinoma and hepatic decompensation in patients with chronic liver disease, and cost-effectiveness analyses may be essential for translating this evidence into clinical guidelines, he added.

 

Statins and HCC Risk in the General Population

A large cohort study, published in JAMA Network Open by Mara Sophie Vell, PhD, and colleagues, showed an association between reduced risk for hepatocellular carcinoma and statin use in the general population and in those at increased risk for liver disease.

The study, which included data for individuals aged 37-73 years from the UK Biobank, found a 15% reduced risk for new-onset liver disease and a 28% reduced risk for liver-related death among regular statin users than among nonusers (HR, 0.85 and 0.72, respectively). 

In addition, regular statin users showed a 74% reduced risk (P = .003) of developing hepatocellular carcinoma compared with those not using statins. The researchers identified a particular impact on liver disease risk reduction among men, individuals with diabetes, and patients with high levels of liver scarring at baseline based on the FIB-4 index.

A meta-analysis of 24 studies, previously published in the journal Cancers, showed a significant reduction of 46% in hepatocellular carcinoma risk among statins users compared with nonusers.

The researchers found this risk reduction was significant in subgroups of patients with diabetes, liver cirrhosis, and those on antiviral therapy, and they suggested that the antiangiogenic, immunomodulatory, antiproliferative, and antifibrotic properties of statins may contribute to their potential to reduce tumor growth or hepatocellular carcinoma development.

The meta-analysis authors noted that although most studies have reported a low risk for statin-induced hepatotoxicity, clinicians should proceed with caution in some patients with existing cirrhosis.

“If the patients are diagnosed with decompensated cirrhosis, then statins should be prescribed with caution at low doses,” they wrote.

Advocating statin use solely for chemoprevention may be premature based on observational data, Chung told GI & Hepatology News.

“However, in patients with [chronic liver disease] who already meet indications for statin therapy, the potential added benefit of reducing liver-related complications strengthens the rationale for their use,” he said. Future randomized clinical trials will be key to defining the risk-benefit profile in this context.

The study by Choi and colleagues was supported by the National Institutes of Health.

The study by Sharma and colleagues was supported by the Karolinska Institutet, Stockholm, Sweden, and the Columbia University Irving Medical Center, New York City; researchers were supported by grants from the Swedish Research Council, Center for Innovative Medicine, the Swedish Cancer Society, and the National Institutes of Health.

The study by Vell and colleagues had no outside funding.

The study by Mohaimenul Islam and colleagues was supported by the Ministry of Education and Ministry of Science and Technology, Taiwan.

Chung and Banini had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Long-term use of statins may delay or deflect the development of hepatocellular carcinoma in adults with chronic liver disease, as well as in the general population, emerging research, including several large cohort studies, suggested.

The most recent study, published in JAMA Internal Medicine, showed a lower incidence of hepatic decompensation among statin users in a registry for adults aged 40 years or older with baseline chronic liver disease.

“Our findings support the idea that statins may offer benefits beyond lipid-lowering in patients with [chronic liver disease], and clinicians may be more confident in prescribing statins when indicated,” even in these patients, said corresponding Co-author Raymond T. Chung, MD, gastroenterology investigator at Mass General Research Institute, Boston, in an interview. 

“While prior studies have suggested an association between statin use and reduced hepatocellular carcinoma risk, our study aimed to build on that evidence by using a large, real-world, hospital-based cohort inclusive of all etiologies of chronic liver disease,” Chung told GI & Hepatology News.

Chung, along with Jonggi Choi, MD, of the University of Ulsan College of Medicine, Seoul, South Korea, and colleagues, reviewed data from the Research Patient Data Registry from 2000 to 2023 for 16,501 participantsaged 40 years or older with baseline chronic liver disease and baseline Fibrosis-4 (FIB-4) scores ≥ 1.3.

The study population had a mean age of 59.7 years, and 40.9% were women. The researchers divided the population into statin users (n = 3610) and nonusers (n = 12,891). Statin use was defined as a cumulative defined daily dose ≥ 30 mg.

The primary outcome was the cumulative incidence of hepatocellular carcinoma and hepatic decompensation.

At 10 years follow-up, statin users showed a significantly reduced incidence of hepatocellular carcinoma vs nonusers (3.8% vs 8.0%; P < .001) as well as a significantly reduced incidence of hepatic decompensation (10.6% vs 19.5%; P < .001).

Incorporating FIB-4 scores, a surrogate marker for liver fibrosis, also showed that statin users were less likely to experience fibrosis progression, offering a potential mechanism of action for the observed reduction in adverse liver outcomes, Chung told GI & Hepatology News.

“Similar trends have been observed in prior observational studies, but our findings now support a real effect of statin use on fibrosis progression,” he said. “However, what strengthened our study was that the association remained consistent across multiple subgroups and sensitivity analyses.”

Another study published in Clinical Gastroenterology and Hepatology showed a reduced risk of developing severe liver disease in a Swedish cohort of noncirrhotic adults with chronic liver disease who used statins (n = 3862) compared with control patients with chronic liver disease (matched 1:1) and who did not use statins (hazard ratio [HR], 0.60). 

In that study, Rajani Sharma, MD, and colleagues found a protective association in both prefibrosis and fibrosis stages at diagnosis, and statin use was associated with reduced rates of progression to both cirrhosis and hepatocellular carcinoma (HR, 0.62 and 0.44, respectively).

 

Exciting and Necessary Research

The research by Choi and colleagues is “exciting,” said Bubu Banini, MD, PhD, an assistant professor in digestive diseases at Yale School of Medicine, New Haven, Connecticut, in an interview.

Liver cancer prevalence has risen over the past few decades in the United States and worldwide, and the 5-year overall survival rate of liver cancer is less than 20%, Banini told GI & Hepatology News.

Clinicians often withhold statins out of fear of liver injury in persons with chronic liver disease; however, a takeaway from this study is that for persons with chronic liver disease who have indications for statin use, the medication should not be withheld, she said.

Of course, prospective studies are needed to replicate the results, Banini added.

The study findings were limited by several factors, including the inability to adjust for all potential confounding variables, lack of data on post-index treatments, and the use of wide, cumulative, defined daily dose categories to ensure statistical power, the researchers noted.

“Moving forward, randomized controlled trials are essential to establish a causal relationship and clarify the molecular and clinical pathways through which statins exert hepatoprotective effects,” Chung added.

Randomized controlled trials are also needed to determine whether statins can actually reduce the risk for hepatocellular carcinoma and hepatic decompensation in patients with chronic liver disease, and cost-effectiveness analyses may be essential for translating this evidence into clinical guidelines, he added.

 

Statins and HCC Risk in the General Population

A large cohort study, published in JAMA Network Open by Mara Sophie Vell, PhD, and colleagues, showed an association between reduced risk for hepatocellular carcinoma and statin use in the general population and in those at increased risk for liver disease.

The study, which included data for individuals aged 37-73 years from the UK Biobank, found a 15% reduced risk for new-onset liver disease and a 28% reduced risk for liver-related death among regular statin users than among nonusers (HR, 0.85 and 0.72, respectively). 

In addition, regular statin users showed a 74% reduced risk (P = .003) of developing hepatocellular carcinoma compared with those not using statins. The researchers identified a particular impact on liver disease risk reduction among men, individuals with diabetes, and patients with high levels of liver scarring at baseline based on the FIB-4 index.

A meta-analysis of 24 studies, previously published in the journal Cancers, showed a significant reduction of 46% in hepatocellular carcinoma risk among statins users compared with nonusers.

The researchers found this risk reduction was significant in subgroups of patients with diabetes, liver cirrhosis, and those on antiviral therapy, and they suggested that the antiangiogenic, immunomodulatory, antiproliferative, and antifibrotic properties of statins may contribute to their potential to reduce tumor growth or hepatocellular carcinoma development.

The meta-analysis authors noted that although most studies have reported a low risk for statin-induced hepatotoxicity, clinicians should proceed with caution in some patients with existing cirrhosis.

“If the patients are diagnosed with decompensated cirrhosis, then statins should be prescribed with caution at low doses,” they wrote.

Advocating statin use solely for chemoprevention may be premature based on observational data, Chung told GI & Hepatology News.

“However, in patients with [chronic liver disease] who already meet indications for statin therapy, the potential added benefit of reducing liver-related complications strengthens the rationale for their use,” he said. Future randomized clinical trials will be key to defining the risk-benefit profile in this context.

The study by Choi and colleagues was supported by the National Institutes of Health.

The study by Sharma and colleagues was supported by the Karolinska Institutet, Stockholm, Sweden, and the Columbia University Irving Medical Center, New York City; researchers were supported by grants from the Swedish Research Council, Center for Innovative Medicine, the Swedish Cancer Society, and the National Institutes of Health.

The study by Vell and colleagues had no outside funding.

The study by Mohaimenul Islam and colleagues was supported by the Ministry of Education and Ministry of Science and Technology, Taiwan.

Chung and Banini had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Long-term use of statins may delay or deflect the development of hepatocellular carcinoma in adults with chronic liver disease, as well as in the general population, emerging research, including several large cohort studies, suggested.

The most recent study, published in JAMA Internal Medicine, showed a lower incidence of hepatic decompensation among statin users in a registry for adults aged 40 years or older with baseline chronic liver disease.

“Our findings support the idea that statins may offer benefits beyond lipid-lowering in patients with [chronic liver disease], and clinicians may be more confident in prescribing statins when indicated,” even in these patients, said corresponding Co-author Raymond T. Chung, MD, gastroenterology investigator at Mass General Research Institute, Boston, in an interview. 

“While prior studies have suggested an association between statin use and reduced hepatocellular carcinoma risk, our study aimed to build on that evidence by using a large, real-world, hospital-based cohort inclusive of all etiologies of chronic liver disease,” Chung told GI & Hepatology News.

Chung, along with Jonggi Choi, MD, of the University of Ulsan College of Medicine, Seoul, South Korea, and colleagues, reviewed data from the Research Patient Data Registry from 2000 to 2023 for 16,501 participantsaged 40 years or older with baseline chronic liver disease and baseline Fibrosis-4 (FIB-4) scores ≥ 1.3.

The study population had a mean age of 59.7 years, and 40.9% were women. The researchers divided the population into statin users (n = 3610) and nonusers (n = 12,891). Statin use was defined as a cumulative defined daily dose ≥ 30 mg.

The primary outcome was the cumulative incidence of hepatocellular carcinoma and hepatic decompensation.

At 10 years follow-up, statin users showed a significantly reduced incidence of hepatocellular carcinoma vs nonusers (3.8% vs 8.0%; P < .001) as well as a significantly reduced incidence of hepatic decompensation (10.6% vs 19.5%; P < .001).

Incorporating FIB-4 scores, a surrogate marker for liver fibrosis, also showed that statin users were less likely to experience fibrosis progression, offering a potential mechanism of action for the observed reduction in adverse liver outcomes, Chung told GI & Hepatology News.

“Similar trends have been observed in prior observational studies, but our findings now support a real effect of statin use on fibrosis progression,” he said. “However, what strengthened our study was that the association remained consistent across multiple subgroups and sensitivity analyses.”

Another study published in Clinical Gastroenterology and Hepatology showed a reduced risk of developing severe liver disease in a Swedish cohort of noncirrhotic adults with chronic liver disease who used statins (n = 3862) compared with control patients with chronic liver disease (matched 1:1) and who did not use statins (hazard ratio [HR], 0.60). 

In that study, Rajani Sharma, MD, and colleagues found a protective association in both prefibrosis and fibrosis stages at diagnosis, and statin use was associated with reduced rates of progression to both cirrhosis and hepatocellular carcinoma (HR, 0.62 and 0.44, respectively).

 

Exciting and Necessary Research

The research by Choi and colleagues is “exciting,” said Bubu Banini, MD, PhD, an assistant professor in digestive diseases at Yale School of Medicine, New Haven, Connecticut, in an interview.

Liver cancer prevalence has risen over the past few decades in the United States and worldwide, and the 5-year overall survival rate of liver cancer is less than 20%, Banini told GI & Hepatology News.

Clinicians often withhold statins out of fear of liver injury in persons with chronic liver disease; however, a takeaway from this study is that for persons with chronic liver disease who have indications for statin use, the medication should not be withheld, she said.

Of course, prospective studies are needed to replicate the results, Banini added.

The study findings were limited by several factors, including the inability to adjust for all potential confounding variables, lack of data on post-index treatments, and the use of wide, cumulative, defined daily dose categories to ensure statistical power, the researchers noted.

“Moving forward, randomized controlled trials are essential to establish a causal relationship and clarify the molecular and clinical pathways through which statins exert hepatoprotective effects,” Chung added.

Randomized controlled trials are also needed to determine whether statins can actually reduce the risk for hepatocellular carcinoma and hepatic decompensation in patients with chronic liver disease, and cost-effectiveness analyses may be essential for translating this evidence into clinical guidelines, he added.

 

Statins and HCC Risk in the General Population

A large cohort study, published in JAMA Network Open by Mara Sophie Vell, PhD, and colleagues, showed an association between reduced risk for hepatocellular carcinoma and statin use in the general population and in those at increased risk for liver disease.

The study, which included data for individuals aged 37-73 years from the UK Biobank, found a 15% reduced risk for new-onset liver disease and a 28% reduced risk for liver-related death among regular statin users than among nonusers (HR, 0.85 and 0.72, respectively). 

In addition, regular statin users showed a 74% reduced risk (P = .003) of developing hepatocellular carcinoma compared with those not using statins. The researchers identified a particular impact on liver disease risk reduction among men, individuals with diabetes, and patients with high levels of liver scarring at baseline based on the FIB-4 index.

A meta-analysis of 24 studies, previously published in the journal Cancers, showed a significant reduction of 46% in hepatocellular carcinoma risk among statins users compared with nonusers.

The researchers found this risk reduction was significant in subgroups of patients with diabetes, liver cirrhosis, and those on antiviral therapy, and they suggested that the antiangiogenic, immunomodulatory, antiproliferative, and antifibrotic properties of statins may contribute to their potential to reduce tumor growth or hepatocellular carcinoma development.

The meta-analysis authors noted that although most studies have reported a low risk for statin-induced hepatotoxicity, clinicians should proceed with caution in some patients with existing cirrhosis.

“If the patients are diagnosed with decompensated cirrhosis, then statins should be prescribed with caution at low doses,” they wrote.

Advocating statin use solely for chemoprevention may be premature based on observational data, Chung told GI & Hepatology News.

“However, in patients with [chronic liver disease] who already meet indications for statin therapy, the potential added benefit of reducing liver-related complications strengthens the rationale for their use,” he said. Future randomized clinical trials will be key to defining the risk-benefit profile in this context.

The study by Choi and colleagues was supported by the National Institutes of Health.

The study by Sharma and colleagues was supported by the Karolinska Institutet, Stockholm, Sweden, and the Columbia University Irving Medical Center, New York City; researchers were supported by grants from the Swedish Research Council, Center for Innovative Medicine, the Swedish Cancer Society, and the National Institutes of Health.

The study by Vell and colleagues had no outside funding.

The study by Mohaimenul Islam and colleagues was supported by the Ministry of Education and Ministry of Science and Technology, Taiwan.

Chung and Banini had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Researchers have developed and internally validated a simple score using clinical factors that can help estimate the likelihood of advanced colorectal neoplasia in adults younger than age 45 years.

While colorectal cancer (CRC) incidence has declined overall due to screening, early-onset CRC is on the rise, particularly in individuals younger than 45 years — an age group not currently recommended for CRC screening.

Studies have shown that the risk for early-onset advanced neoplasia varies based on several factors, including sex, race, family history of CRC, smoking, alcohol consumption, diabetes, hyperlipidemia, obesity, and diet.

A score that incorporates some of these factors to identify which younger adults are at higher risk for advanced neoplasia, a precursor to CRC, could support earlier, more targeted screening interventions.

The simple clinical score can be easily calculated by primary care providers in the office, Carole Macaron, MD, lead author of the study and a gastroenterologist at Cleveland Clinic, told GI & Hepatology News. “Patients with a high-risk score would be referred for colorectal cancer screening.”

The study was published in Digestive Diseases and Sciences.

To develop and validate their risk score, Macaron and colleagues did a retrospective cross-sectional analysis of 9446 individuals aged 18-44 years (mean age, 36.8 years; 61% women) who underwent colonoscopy at their center.

Advanced neoplasia was defined as a tubular adenoma ≥ 10 mm or any adenoma with villous features or high-grade dysplasia, sessile serrated polyp ≥ 10 mm, sessile serrated polyp with dysplasia, traditional serrated adenoma, or invasive adenocarcinoma.

The 346 (3.7%) individuals found to have advanced neoplasia served as the case group, and the remainder with normal colonoscopy or non-advanced neoplasia served as controls.

A multivariate logistic regression model identified three independent risk factors significantly associated with advanced neoplasia: Higher body mass index (BMI; P = .0157), former and current tobacco use (P = .0009 and P = .0015, respectively), and having a first-degree relative with CRC < 60 years (P < .0001) or other family history of CRC (P = .0117).

The researchers used these risk factors to develop a risk prediction score to estimate the likelihood of detecting advanced neoplasia, which ranged from a risk of 1.8% for patients with a score of 1 to 22.2% for those with a score of 12. Individuals with a score of ≥ 9 had a 14% or higher risk for advanced neoplasia.

Based on the risk model, the likelihood of detecting advanced neoplasia in an asymptomatic 32-year-old overweight individual, with a history of previous tobacco use and a first-degree relative younger than age 60 with CRC would be 20.3%, Macaron and colleagues noted.

The model demonstrated “moderate” discriminatory power in the validation set (C-statistic: 0.645), indicating that it can effectively differentiate between individuals at a higher and lower risk for advanced neoplasia.

Additionally, the authors are exploring ways to improve the discriminatory power of the score, possibly by including additional risk factors.

Given the score is calculated using easily obtainable risk factors for individuals younger than 45 who are at risk for early-onset colorectal neoplasia, it could help guide individualized screening decisions for those in whom screening is not currently offered, Macaron said. It could also serve as a tool for risk communication and shared decision-making.

Integration into electronic health records or online calculators may enhance its accessibility and clinical utility.

The authors noted that this retrospective study was conducted at a single center caring mainly for White non-Hispanic adults, limiting generalizability to the general population and to other races and ethnicities.

 

Validation in Real-World Setting Needed

“There are no currently accepted advanced colorectal neoplasia risk scores that are used in general practice,” said Steven H. Itzkowitz, MD, AGAF, professor of medicine, oncological sciences, and medical education, Icahn School of Medicine at Mount Sinai in New York City. “If these lesions can be predicted, it would enable these young individuals to undergo screening colonoscopy, which could detect and remove these lesions, thereby preventing CRC.”

Many of the known risk factors (family history, high BMI, or smoking) for CRC development at any age are incorporated within this tool, so it should be feasible to collect these data,” said Itzkowitz, who was not involved with the study.

But he cautioned that accurate and adequate family histories are not always performed. Clinicians also may not have considered combining these factors into an actionable risk score.

“If this score can be externally validated in a real-world setting, it could be a useful addition in our efforts to lower CRC rates among young individuals,” Itzkowitz said.

The study did not receive any funding. Macaron and Itzkowitz reported no competing interests.

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

Researchers have developed and internally validated a simple score using clinical factors that can help estimate the likelihood of advanced colorectal neoplasia in adults younger than age 45 years.

While colorectal cancer (CRC) incidence has declined overall due to screening, early-onset CRC is on the rise, particularly in individuals younger than 45 years — an age group not currently recommended for CRC screening.

Studies have shown that the risk for early-onset advanced neoplasia varies based on several factors, including sex, race, family history of CRC, smoking, alcohol consumption, diabetes, hyperlipidemia, obesity, and diet.

A score that incorporates some of these factors to identify which younger adults are at higher risk for advanced neoplasia, a precursor to CRC, could support earlier, more targeted screening interventions.

The simple clinical score can be easily calculated by primary care providers in the office, Carole Macaron, MD, lead author of the study and a gastroenterologist at Cleveland Clinic, told GI & Hepatology News. “Patients with a high-risk score would be referred for colorectal cancer screening.”

The study was published in Digestive Diseases and Sciences.

To develop and validate their risk score, Macaron and colleagues did a retrospective cross-sectional analysis of 9446 individuals aged 18-44 years (mean age, 36.8 years; 61% women) who underwent colonoscopy at their center.

Advanced neoplasia was defined as a tubular adenoma ≥ 10 mm or any adenoma with villous features or high-grade dysplasia, sessile serrated polyp ≥ 10 mm, sessile serrated polyp with dysplasia, traditional serrated adenoma, or invasive adenocarcinoma.

The 346 (3.7%) individuals found to have advanced neoplasia served as the case group, and the remainder with normal colonoscopy or non-advanced neoplasia served as controls.

A multivariate logistic regression model identified three independent risk factors significantly associated with advanced neoplasia: Higher body mass index (BMI; P = .0157), former and current tobacco use (P = .0009 and P = .0015, respectively), and having a first-degree relative with CRC < 60 years (P < .0001) or other family history of CRC (P = .0117).

The researchers used these risk factors to develop a risk prediction score to estimate the likelihood of detecting advanced neoplasia, which ranged from a risk of 1.8% for patients with a score of 1 to 22.2% for those with a score of 12. Individuals with a score of ≥ 9 had a 14% or higher risk for advanced neoplasia.

Based on the risk model, the likelihood of detecting advanced neoplasia in an asymptomatic 32-year-old overweight individual, with a history of previous tobacco use and a first-degree relative younger than age 60 with CRC would be 20.3%, Macaron and colleagues noted.

The model demonstrated “moderate” discriminatory power in the validation set (C-statistic: 0.645), indicating that it can effectively differentiate between individuals at a higher and lower risk for advanced neoplasia.

Additionally, the authors are exploring ways to improve the discriminatory power of the score, possibly by including additional risk factors.

Given the score is calculated using easily obtainable risk factors for individuals younger than 45 who are at risk for early-onset colorectal neoplasia, it could help guide individualized screening decisions for those in whom screening is not currently offered, Macaron said. It could also serve as a tool for risk communication and shared decision-making.

Integration into electronic health records or online calculators may enhance its accessibility and clinical utility.

The authors noted that this retrospective study was conducted at a single center caring mainly for White non-Hispanic adults, limiting generalizability to the general population and to other races and ethnicities.

 

Validation in Real-World Setting Needed

“There are no currently accepted advanced colorectal neoplasia risk scores that are used in general practice,” said Steven H. Itzkowitz, MD, AGAF, professor of medicine, oncological sciences, and medical education, Icahn School of Medicine at Mount Sinai in New York City. “If these lesions can be predicted, it would enable these young individuals to undergo screening colonoscopy, which could detect and remove these lesions, thereby preventing CRC.”

Many of the known risk factors (family history, high BMI, or smoking) for CRC development at any age are incorporated within this tool, so it should be feasible to collect these data,” said Itzkowitz, who was not involved with the study.

But he cautioned that accurate and adequate family histories are not always performed. Clinicians also may not have considered combining these factors into an actionable risk score.

“If this score can be externally validated in a real-world setting, it could be a useful addition in our efforts to lower CRC rates among young individuals,” Itzkowitz said.

The study did not receive any funding. Macaron and Itzkowitz reported no competing interests.

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

Researchers have developed and internally validated a simple score using clinical factors that can help estimate the likelihood of advanced colorectal neoplasia in adults younger than age 45 years.

While colorectal cancer (CRC) incidence has declined overall due to screening, early-onset CRC is on the rise, particularly in individuals younger than 45 years — an age group not currently recommended for CRC screening.

Studies have shown that the risk for early-onset advanced neoplasia varies based on several factors, including sex, race, family history of CRC, smoking, alcohol consumption, diabetes, hyperlipidemia, obesity, and diet.

A score that incorporates some of these factors to identify which younger adults are at higher risk for advanced neoplasia, a precursor to CRC, could support earlier, more targeted screening interventions.

The simple clinical score can be easily calculated by primary care providers in the office, Carole Macaron, MD, lead author of the study and a gastroenterologist at Cleveland Clinic, told GI & Hepatology News. “Patients with a high-risk score would be referred for colorectal cancer screening.”

The study was published in Digestive Diseases and Sciences.

To develop and validate their risk score, Macaron and colleagues did a retrospective cross-sectional analysis of 9446 individuals aged 18-44 years (mean age, 36.8 years; 61% women) who underwent colonoscopy at their center.

Advanced neoplasia was defined as a tubular adenoma ≥ 10 mm or any adenoma with villous features or high-grade dysplasia, sessile serrated polyp ≥ 10 mm, sessile serrated polyp with dysplasia, traditional serrated adenoma, or invasive adenocarcinoma.

The 346 (3.7%) individuals found to have advanced neoplasia served as the case group, and the remainder with normal colonoscopy or non-advanced neoplasia served as controls.

A multivariate logistic regression model identified three independent risk factors significantly associated with advanced neoplasia: Higher body mass index (BMI; P = .0157), former and current tobacco use (P = .0009 and P = .0015, respectively), and having a first-degree relative with CRC < 60 years (P < .0001) or other family history of CRC (P = .0117).

The researchers used these risk factors to develop a risk prediction score to estimate the likelihood of detecting advanced neoplasia, which ranged from a risk of 1.8% for patients with a score of 1 to 22.2% for those with a score of 12. Individuals with a score of ≥ 9 had a 14% or higher risk for advanced neoplasia.

Based on the risk model, the likelihood of detecting advanced neoplasia in an asymptomatic 32-year-old overweight individual, with a history of previous tobacco use and a first-degree relative younger than age 60 with CRC would be 20.3%, Macaron and colleagues noted.

The model demonstrated “moderate” discriminatory power in the validation set (C-statistic: 0.645), indicating that it can effectively differentiate between individuals at a higher and lower risk for advanced neoplasia.

Additionally, the authors are exploring ways to improve the discriminatory power of the score, possibly by including additional risk factors.

Given the score is calculated using easily obtainable risk factors for individuals younger than 45 who are at risk for early-onset colorectal neoplasia, it could help guide individualized screening decisions for those in whom screening is not currently offered, Macaron said. It could also serve as a tool for risk communication and shared decision-making.

Integration into electronic health records or online calculators may enhance its accessibility and clinical utility.

The authors noted that this retrospective study was conducted at a single center caring mainly for White non-Hispanic adults, limiting generalizability to the general population and to other races and ethnicities.

 

Validation in Real-World Setting Needed

“There are no currently accepted advanced colorectal neoplasia risk scores that are used in general practice,” said Steven H. Itzkowitz, MD, AGAF, professor of medicine, oncological sciences, and medical education, Icahn School of Medicine at Mount Sinai in New York City. “If these lesions can be predicted, it would enable these young individuals to undergo screening colonoscopy, which could detect and remove these lesions, thereby preventing CRC.”

Many of the known risk factors (family history, high BMI, or smoking) for CRC development at any age are incorporated within this tool, so it should be feasible to collect these data,” said Itzkowitz, who was not involved with the study.

But he cautioned that accurate and adequate family histories are not always performed. Clinicians also may not have considered combining these factors into an actionable risk score.

“If this score can be externally validated in a real-world setting, it could be a useful addition in our efforts to lower CRC rates among young individuals,” Itzkowitz said.

The study did not receive any funding. Macaron and Itzkowitz reported no competing interests.

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

In patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy, adjunctive use of wide-area transepithelial sampling with 3D computer-assisted analysis (WATS-3D) increases detection of Barrett’s esophagus (BE) and dysplasia, new research showed. 

Compared with forceps biopsies (FB) alone, the addition of WATS-3D led to confirmation of BE in an additional one fifth of patients, roughly doubled dysplasia diagnoses, and influenced clinical management in the majority of patients. 

“The big take-home point here is that the use of WATS-3D brushing along with conventional biopsies increases the likelihood that intestinal metaplasia will be identified,” first author Nicholas Shaheen, MD, MPH, AGAF, with the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine at Chapel Hill, North Carolina, told GI & Hepatology News. 

“Almost 20% of patients who harbor BE were only identified by WATS-3D and might have otherwise gone undiagnosed had only forceps biopsies been performed,” Shaheen said. 

The study was published in The American Journal of Gastroenterology.

 

Beyond Traditional Biopsies

BE develops as a complication of chronic GERD and is the chief precursor to esophageal adenocarcinoma. Early detection of BE and dysplasia is crucial to enable timely intervention. 

The current gold standard for BE screening involves upper endoscopy with FB following the Seattle protocol, which consists of four-quadrant biopsies from every 1-2 cm of areas of columnar-lined epithelium (CLE) to confirm the presence of intestinal metaplasia. However, this protocol is prone to sampling errors and high false-negative rates, leading to repeat endoscopy, the study team pointed out. 

WATS-3D (CDx Diagnostics) is a complementary technique designed to improve diagnostic yield by using brush biopsy to sample more tissue than routine biopsies.

WATS-3D has been shown to increase detection of dysplasia in patients with BE undergoing surveillance for BE, but less is known about the value of WATS-3D for BE screening in a community-based cohort of patients with GERD. 

To investigate, Shaheen and colleagues studied 23,933 consecutive patients enrolled in a prospective observational registry assessing the utility of WATS-3D in the screening of symptomatic GERD patients for BE. 

Patients had both WATS-3D and FB in the same endoscopic session. No patient had a history of BE, intestinal metaplasia or dysplasia in esophageal mucosa, or esophageal surgery, endoscopic ablation or endoscopic mucosal resection prior to enrollment. 

Overall, 6829 patients (29%) met endoscopic criteria for BE (≥ 1 cm esophageal CLE with accompanying biopsies showing intestinal metaplasia). 

Of these, 2878 (42%) had intestinal metaplasia identified by either FB or WATS-3D, but 19.3% had their BE diagnosis confirmed solely on the basis of WATS-3D findings. 

Among patients who fulfilled the endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and the absolute yield was 18.1%.

Of the 240 (1.0%) patients with dysplasia, 107 (45%) were found solely by WATS-3D.

 

‘Clinically Valuable Adjunct’

Among patients with positive WATS-3D but negative FB results, clinical management changed in 90.7% of cases, mostly involving initiation or modification of surveillance and proton pump inhibitor therapy. 

These results suggest that WATS-3D is a “clinically valuable adjunct” to FB for the diagnosis of BE when used as a screening tool in symptomatic GERD patients and particularly in patients with endoscopic evidence of > 1 cm esophageal columnar-lined epithelium, the study team wrote. 

Adjunctive use of WATS-3D when BE is suspected “may save endoscopies and lead to quicker, more accurate diagnoses,” they added. 

The investigators said a limitation of the study is the lack of central pathology review, potentially leading to diagnostic variability. They also noted that over half of the detected dysplasia cases were crypt dysplasia or indefinite for dysplasia, raising concerns about clinical significance. 

Reached for comment, Philip O. Katz, MD, AGAF, professor of medicine and director of the GI Function Laboratories, Weill Cornell Medicine in New York, said he’s been using WATS for more than a decade as an adjunct to standard biopsy in patients undergoing screening and surveillance for BE and finds it clinically helpful in managing his patients.

This new study provides “further information that WATS added to biopsy that has been traditionally done with the Seattle protocol increases the yield of intestinal metaplasia and likely dysplasia in patients being screened for Barrett’s,” Katz, who wasn’t involved in the study, told GI & Hepatology News.

Funding for the study was provided by CDx Diagnostics. Shaheen and several coauthors disclosed relationships with the company. Katz disclosed relationships (consultant/advisor) for Phathom Pharmaceuticals and Sebella.

A version of this article appeared on Medscape.com.

In patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy, adjunctive use of wide-area transepithelial sampling with 3D computer-assisted analysis (WATS-3D) increases detection of Barrett’s esophagus (BE) and dysplasia, new research showed. 

Compared with forceps biopsies (FB) alone, the addition of WATS-3D led to confirmation of BE in an additional one fifth of patients, roughly doubled dysplasia diagnoses, and influenced clinical management in the majority of patients. 

“The big take-home point here is that the use of WATS-3D brushing along with conventional biopsies increases the likelihood that intestinal metaplasia will be identified,” first author Nicholas Shaheen, MD, MPH, AGAF, with the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine at Chapel Hill, North Carolina, told GI & Hepatology News. 

“Almost 20% of patients who harbor BE were only identified by WATS-3D and might have otherwise gone undiagnosed had only forceps biopsies been performed,” Shaheen said. 

The study was published in The American Journal of Gastroenterology.

 

Beyond Traditional Biopsies

BE develops as a complication of chronic GERD and is the chief precursor to esophageal adenocarcinoma. Early detection of BE and dysplasia is crucial to enable timely intervention. 

The current gold standard for BE screening involves upper endoscopy with FB following the Seattle protocol, which consists of four-quadrant biopsies from every 1-2 cm of areas of columnar-lined epithelium (CLE) to confirm the presence of intestinal metaplasia. However, this protocol is prone to sampling errors and high false-negative rates, leading to repeat endoscopy, the study team pointed out. 

WATS-3D (CDx Diagnostics) is a complementary technique designed to improve diagnostic yield by using brush biopsy to sample more tissue than routine biopsies.

WATS-3D has been shown to increase detection of dysplasia in patients with BE undergoing surveillance for BE, but less is known about the value of WATS-3D for BE screening in a community-based cohort of patients with GERD. 

To investigate, Shaheen and colleagues studied 23,933 consecutive patients enrolled in a prospective observational registry assessing the utility of WATS-3D in the screening of symptomatic GERD patients for BE. 

Patients had both WATS-3D and FB in the same endoscopic session. No patient had a history of BE, intestinal metaplasia or dysplasia in esophageal mucosa, or esophageal surgery, endoscopic ablation or endoscopic mucosal resection prior to enrollment. 

Overall, 6829 patients (29%) met endoscopic criteria for BE (≥ 1 cm esophageal CLE with accompanying biopsies showing intestinal metaplasia). 

Of these, 2878 (42%) had intestinal metaplasia identified by either FB or WATS-3D, but 19.3% had their BE diagnosis confirmed solely on the basis of WATS-3D findings. 

Among patients who fulfilled the endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and the absolute yield was 18.1%.

Of the 240 (1.0%) patients with dysplasia, 107 (45%) were found solely by WATS-3D.

 

‘Clinically Valuable Adjunct’

Among patients with positive WATS-3D but negative FB results, clinical management changed in 90.7% of cases, mostly involving initiation or modification of surveillance and proton pump inhibitor therapy. 

These results suggest that WATS-3D is a “clinically valuable adjunct” to FB for the diagnosis of BE when used as a screening tool in symptomatic GERD patients and particularly in patients with endoscopic evidence of > 1 cm esophageal columnar-lined epithelium, the study team wrote. 

Adjunctive use of WATS-3D when BE is suspected “may save endoscopies and lead to quicker, more accurate diagnoses,” they added. 

The investigators said a limitation of the study is the lack of central pathology review, potentially leading to diagnostic variability. They also noted that over half of the detected dysplasia cases were crypt dysplasia or indefinite for dysplasia, raising concerns about clinical significance. 

Reached for comment, Philip O. Katz, MD, AGAF, professor of medicine and director of the GI Function Laboratories, Weill Cornell Medicine in New York, said he’s been using WATS for more than a decade as an adjunct to standard biopsy in patients undergoing screening and surveillance for BE and finds it clinically helpful in managing his patients.

This new study provides “further information that WATS added to biopsy that has been traditionally done with the Seattle protocol increases the yield of intestinal metaplasia and likely dysplasia in patients being screened for Barrett’s,” Katz, who wasn’t involved in the study, told GI & Hepatology News.

Funding for the study was provided by CDx Diagnostics. Shaheen and several coauthors disclosed relationships with the company. Katz disclosed relationships (consultant/advisor) for Phathom Pharmaceuticals and Sebella.

A version of this article appeared on Medscape.com.

In patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy, adjunctive use of wide-area transepithelial sampling with 3D computer-assisted analysis (WATS-3D) increases detection of Barrett’s esophagus (BE) and dysplasia, new research showed. 

Compared with forceps biopsies (FB) alone, the addition of WATS-3D led to confirmation of BE in an additional one fifth of patients, roughly doubled dysplasia diagnoses, and influenced clinical management in the majority of patients. 

“The big take-home point here is that the use of WATS-3D brushing along with conventional biopsies increases the likelihood that intestinal metaplasia will be identified,” first author Nicholas Shaheen, MD, MPH, AGAF, with the Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine at Chapel Hill, North Carolina, told GI & Hepatology News. 

“Almost 20% of patients who harbor BE were only identified by WATS-3D and might have otherwise gone undiagnosed had only forceps biopsies been performed,” Shaheen said. 

The study was published in The American Journal of Gastroenterology.

 

Beyond Traditional Biopsies

BE develops as a complication of chronic GERD and is the chief precursor to esophageal adenocarcinoma. Early detection of BE and dysplasia is crucial to enable timely intervention. 

The current gold standard for BE screening involves upper endoscopy with FB following the Seattle protocol, which consists of four-quadrant biopsies from every 1-2 cm of areas of columnar-lined epithelium (CLE) to confirm the presence of intestinal metaplasia. However, this protocol is prone to sampling errors and high false-negative rates, leading to repeat endoscopy, the study team pointed out. 

WATS-3D (CDx Diagnostics) is a complementary technique designed to improve diagnostic yield by using brush biopsy to sample more tissue than routine biopsies.

WATS-3D has been shown to increase detection of dysplasia in patients with BE undergoing surveillance for BE, but less is known about the value of WATS-3D for BE screening in a community-based cohort of patients with GERD. 

To investigate, Shaheen and colleagues studied 23,933 consecutive patients enrolled in a prospective observational registry assessing the utility of WATS-3D in the screening of symptomatic GERD patients for BE. 

Patients had both WATS-3D and FB in the same endoscopic session. No patient had a history of BE, intestinal metaplasia or dysplasia in esophageal mucosa, or esophageal surgery, endoscopic ablation or endoscopic mucosal resection prior to enrollment. 

Overall, 6829 patients (29%) met endoscopic criteria for BE (≥ 1 cm esophageal CLE with accompanying biopsies showing intestinal metaplasia). 

Of these, 2878 (42%) had intestinal metaplasia identified by either FB or WATS-3D, but 19.3% had their BE diagnosis confirmed solely on the basis of WATS-3D findings. 

Among patients who fulfilled the endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and the absolute yield was 18.1%.

Of the 240 (1.0%) patients with dysplasia, 107 (45%) were found solely by WATS-3D.

 

‘Clinically Valuable Adjunct’

Among patients with positive WATS-3D but negative FB results, clinical management changed in 90.7% of cases, mostly involving initiation or modification of surveillance and proton pump inhibitor therapy. 

These results suggest that WATS-3D is a “clinically valuable adjunct” to FB for the diagnosis of BE when used as a screening tool in symptomatic GERD patients and particularly in patients with endoscopic evidence of > 1 cm esophageal columnar-lined epithelium, the study team wrote. 

Adjunctive use of WATS-3D when BE is suspected “may save endoscopies and lead to quicker, more accurate diagnoses,” they added. 

The investigators said a limitation of the study is the lack of central pathology review, potentially leading to diagnostic variability. They also noted that over half of the detected dysplasia cases were crypt dysplasia or indefinite for dysplasia, raising concerns about clinical significance. 

Reached for comment, Philip O. Katz, MD, AGAF, professor of medicine and director of the GI Function Laboratories, Weill Cornell Medicine in New York, said he’s been using WATS for more than a decade as an adjunct to standard biopsy in patients undergoing screening and surveillance for BE and finds it clinically helpful in managing his patients.

This new study provides “further information that WATS added to biopsy that has been traditionally done with the Seattle protocol increases the yield of intestinal metaplasia and likely dysplasia in patients being screened for Barrett’s,” Katz, who wasn’t involved in the study, told GI & Hepatology News.

Funding for the study was provided by CDx Diagnostics. Shaheen and several coauthors disclosed relationships with the company. Katz disclosed relationships (consultant/advisor) for Phathom Pharmaceuticals and Sebella.

A version of this article appeared on Medscape.com.

The United States multi-society task force on colorectal cancer (CRC) has updated its 2014 guidance for optimizing the adequacy of bowel preparation for colonoscopy.

The latest consensus recommendations emphasize the importance of verbal and written patient education, refine diet restrictions, update optimal purgative regimens, and advise tracking bowel prep adequacy rates at both the individual endoscopist and unit levels.

“Colorectal cancer remains the second most common cause of cancer death in the United States, and colonoscopy is considered the gold standard for evaluating the colon, including assessing causes of colon-related signs or symptoms and the detection of precancerous lesions. It is well recognized that the adequacy of bowel preparation is essential for optimal colonoscopy performance,” the task force wrote.

 

Choice of Prep, Dosing and Timing, and Dietary Restrictions 

When choosing bowel preparation regimens, the task force recommends considering the individual’s medical history, medications, and, when available, the adequacy of bowel preparation reported from prior colonoscopies. Other considerations include patient preference, associated additional costs to the patient, and ease in obtaining and consuming any purgatives or adjuncts.

In terms of timing and dose, the task force now “suggests that lower-volume bowel preparation regimens, such as those that rely on only 2 liters of fluid compared to the traditional 4L, are acceptable options for individuals considered unlikely to have an inadequate bowel preparation. This assumes that the purgative is taken in a split-dose fashion (half the evening prior to colonoscopy and half the morning of the colonoscopy),” co–lead author Brian C. Jacobson, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, both in Boston, said in an interview.

The task force also states that a same-day bowel preparation regimen for afternoon, but not morning, colonoscopy is a “reasonable alternative to the now-common split-dose regimen,” Jacobson said.

The group did not find one bowel preparation purgative to be better than others, although table 7 in the document details characteristics of commonly used prep regimens including their side effects and contraindications.

Recommendations regarding dietary modifications depend upon the patient’s risk for inadequate bowel prep. For patients at low risk for inadequate bowel prep, the task force recommends limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. Table 5 in the document provides a list of low-residue foods and sample meals.

The task force also suggests the adjunctive use of oral simethicone (≥ 320 mg) to bowel prep as a way to potentially improve visualization, although they acknowledge that further research is needed.

How might these updated consensus recommendations change current clinical practice? 

Jacobson said: “Some physicians may try to identify individuals who will do just as well with a more patient-friendly, easily tolerated bowel preparation regimen, including less stringent dietary restrictions leading up to colonoscopy.” 

He noted that the task force prefers the term “guidance” to “guidelines.”

 

New Quality Benchmark 

The task force recommends documenting bowel prep quality in the endoscopy report after all washing and suctioning have been completed using reliably understood descriptors that communicate the adequacy of the preparation.

They recommend the term “adequate bowel preparation” be used to indicate that standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy.

Additionally, the task force recommends that endoscopy units and individual endoscopists track and aim for ≥ 90% adequacy rates in bowel preparation — up from the 85% benchmark contained in the prior recommendations.

Jacobson told this news organization it’s “currently unknown” how many individual endoscopists and endoscopy units track and meet the 90% benchmark at present.

David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, who wasn’t on the task force, said endoscopy units and providers “need to be accountable and should be tracking this quality metric.”

Johnson noted that bowel prep inadequacy has “intrinsic costs,” impacting lesion detection, CRC incidence, and patient outcomes. Inadequate prep leads to “increased risk for morbidity, mortality, longer appointment and wait times for rescheduling, and negative connotations that may deter patients from returning.”

 

Brian Sullivan, MD, MHS, assistant professor of medicine, division of gastroenterology, Duke University School of Medicine, Durham, North Carolina, who wasn’t on the task force, said the recommendation to target a 90% or higher bowel preparation adequacy rate is “appreciated.”

“This benchmark encourages practices to standardize measurement, tracking, and reporting of preparation quality at both the individual and unit levels. Specifically, it should motivate providers to critically evaluate their interpretation of preparation quality and ensure adequate cleansing before making determinations,” Sullivan said in an interview.

“At the unit level, this metric can identify whether there are opportunities for quality improvement, such as by implementing evidence-based initiatives (provided in the guidance) to enhance outpatient preparation processes,” Sullivan noted.

The task force emphasized that the majority of consensus recommendations focus on individuals at average risk for inadequate bowel prep. Patients at high risk for inadequate bowel prep (eg, diabetes, constipation, opioid use) should receive tailored instructions, including a more extended dietary prep and high-volume purgatives.

 

‘Timely and Important’ Updates

Sullivan said the updated consensus recommendations on optimizing bowel preparation quality for colonoscopy are both “timely and important.” 

“Clear guidance facilitates dissemination and adoption, promoting flexible yet evidence-based approaches that enhance patient and provider satisfaction while potentially improving CRC prevention outcomes. For instance, surveys reveal that some practices still do not utilize split-dose bowel preparation, which is proven to improve preparation quality, particularly for the right-side of the colon. This gap underscores the need for standardized guidance to ensure high-quality colonoscopy and effective CRC screening,” Sullivan said.

He also noted that the inclusion of lower-volume bowel prep regimens and less intensive dietary modifications for selected patients is a “welcome update.”

“These options can improve patient adherence and satisfaction, which are critical not only for the quality of the index exam but also for ensuring patients return for future screenings, thereby supporting long-term CRC prevention efforts,” Sullivan said.

The task force includes representatives from the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy.

The consensus document was published online in the three societies’ respective scientific journals — Gastroenterology, the American Journal of Gastroenterology, and Gastrointestinal Endsocopy.

This research had no financial support. Jacobson is a consultant for Curis and Guardant Health. Sullivan had no disclosures. Johnson is an adviser to ISOThrive and a past president of the American College of Gastroenterology.

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

The United States multi-society task force on colorectal cancer (CRC) has updated its 2014 guidance for optimizing the adequacy of bowel preparation for colonoscopy.

The latest consensus recommendations emphasize the importance of verbal and written patient education, refine diet restrictions, update optimal purgative regimens, and advise tracking bowel prep adequacy rates at both the individual endoscopist and unit levels.

“Colorectal cancer remains the second most common cause of cancer death in the United States, and colonoscopy is considered the gold standard for evaluating the colon, including assessing causes of colon-related signs or symptoms and the detection of precancerous lesions. It is well recognized that the adequacy of bowel preparation is essential for optimal colonoscopy performance,” the task force wrote.

 

Choice of Prep, Dosing and Timing, and Dietary Restrictions 

When choosing bowel preparation regimens, the task force recommends considering the individual’s medical history, medications, and, when available, the adequacy of bowel preparation reported from prior colonoscopies. Other considerations include patient preference, associated additional costs to the patient, and ease in obtaining and consuming any purgatives or adjuncts.

In terms of timing and dose, the task force now “suggests that lower-volume bowel preparation regimens, such as those that rely on only 2 liters of fluid compared to the traditional 4L, are acceptable options for individuals considered unlikely to have an inadequate bowel preparation. This assumes that the purgative is taken in a split-dose fashion (half the evening prior to colonoscopy and half the morning of the colonoscopy),” co–lead author Brian C. Jacobson, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, both in Boston, said in an interview.

The task force also states that a same-day bowel preparation regimen for afternoon, but not morning, colonoscopy is a “reasonable alternative to the now-common split-dose regimen,” Jacobson said.

The group did not find one bowel preparation purgative to be better than others, although table 7 in the document details characteristics of commonly used prep regimens including their side effects and contraindications.

Recommendations regarding dietary modifications depend upon the patient’s risk for inadequate bowel prep. For patients at low risk for inadequate bowel prep, the task force recommends limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. Table 5 in the document provides a list of low-residue foods and sample meals.

The task force also suggests the adjunctive use of oral simethicone (≥ 320 mg) to bowel prep as a way to potentially improve visualization, although they acknowledge that further research is needed.

How might these updated consensus recommendations change current clinical practice? 

Jacobson said: “Some physicians may try to identify individuals who will do just as well with a more patient-friendly, easily tolerated bowel preparation regimen, including less stringent dietary restrictions leading up to colonoscopy.” 

He noted that the task force prefers the term “guidance” to “guidelines.”

 

New Quality Benchmark 

The task force recommends documenting bowel prep quality in the endoscopy report after all washing and suctioning have been completed using reliably understood descriptors that communicate the adequacy of the preparation.

They recommend the term “adequate bowel preparation” be used to indicate that standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy.

Additionally, the task force recommends that endoscopy units and individual endoscopists track and aim for ≥ 90% adequacy rates in bowel preparation — up from the 85% benchmark contained in the prior recommendations.

Jacobson told this news organization it’s “currently unknown” how many individual endoscopists and endoscopy units track and meet the 90% benchmark at present.

David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, who wasn’t on the task force, said endoscopy units and providers “need to be accountable and should be tracking this quality metric.”

Johnson noted that bowel prep inadequacy has “intrinsic costs,” impacting lesion detection, CRC incidence, and patient outcomes. Inadequate prep leads to “increased risk for morbidity, mortality, longer appointment and wait times for rescheduling, and negative connotations that may deter patients from returning.”

 

Brian Sullivan, MD, MHS, assistant professor of medicine, division of gastroenterology, Duke University School of Medicine, Durham, North Carolina, who wasn’t on the task force, said the recommendation to target a 90% or higher bowel preparation adequacy rate is “appreciated.”

“This benchmark encourages practices to standardize measurement, tracking, and reporting of preparation quality at both the individual and unit levels. Specifically, it should motivate providers to critically evaluate their interpretation of preparation quality and ensure adequate cleansing before making determinations,” Sullivan said in an interview.

“At the unit level, this metric can identify whether there are opportunities for quality improvement, such as by implementing evidence-based initiatives (provided in the guidance) to enhance outpatient preparation processes,” Sullivan noted.

The task force emphasized that the majority of consensus recommendations focus on individuals at average risk for inadequate bowel prep. Patients at high risk for inadequate bowel prep (eg, diabetes, constipation, opioid use) should receive tailored instructions, including a more extended dietary prep and high-volume purgatives.

 

‘Timely and Important’ Updates

Sullivan said the updated consensus recommendations on optimizing bowel preparation quality for colonoscopy are both “timely and important.” 

“Clear guidance facilitates dissemination and adoption, promoting flexible yet evidence-based approaches that enhance patient and provider satisfaction while potentially improving CRC prevention outcomes. For instance, surveys reveal that some practices still do not utilize split-dose bowel preparation, which is proven to improve preparation quality, particularly for the right-side of the colon. This gap underscores the need for standardized guidance to ensure high-quality colonoscopy and effective CRC screening,” Sullivan said.

He also noted that the inclusion of lower-volume bowel prep regimens and less intensive dietary modifications for selected patients is a “welcome update.”

“These options can improve patient adherence and satisfaction, which are critical not only for the quality of the index exam but also for ensuring patients return for future screenings, thereby supporting long-term CRC prevention efforts,” Sullivan said.

The task force includes representatives from the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy.

The consensus document was published online in the three societies’ respective scientific journals — Gastroenterology, the American Journal of Gastroenterology, and Gastrointestinal Endsocopy.

This research had no financial support. Jacobson is a consultant for Curis and Guardant Health. Sullivan had no disclosures. Johnson is an adviser to ISOThrive and a past president of the American College of Gastroenterology.

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

The United States multi-society task force on colorectal cancer (CRC) has updated its 2014 guidance for optimizing the adequacy of bowel preparation for colonoscopy.

The latest consensus recommendations emphasize the importance of verbal and written patient education, refine diet restrictions, update optimal purgative regimens, and advise tracking bowel prep adequacy rates at both the individual endoscopist and unit levels.

“Colorectal cancer remains the second most common cause of cancer death in the United States, and colonoscopy is considered the gold standard for evaluating the colon, including assessing causes of colon-related signs or symptoms and the detection of precancerous lesions. It is well recognized that the adequacy of bowel preparation is essential for optimal colonoscopy performance,” the task force wrote.

 

Choice of Prep, Dosing and Timing, and Dietary Restrictions 

When choosing bowel preparation regimens, the task force recommends considering the individual’s medical history, medications, and, when available, the adequacy of bowel preparation reported from prior colonoscopies. Other considerations include patient preference, associated additional costs to the patient, and ease in obtaining and consuming any purgatives or adjuncts.

In terms of timing and dose, the task force now “suggests that lower-volume bowel preparation regimens, such as those that rely on only 2 liters of fluid compared to the traditional 4L, are acceptable options for individuals considered unlikely to have an inadequate bowel preparation. This assumes that the purgative is taken in a split-dose fashion (half the evening prior to colonoscopy and half the morning of the colonoscopy),” co–lead author Brian C. Jacobson, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, both in Boston, said in an interview.

The task force also states that a same-day bowel preparation regimen for afternoon, but not morning, colonoscopy is a “reasonable alternative to the now-common split-dose regimen,” Jacobson said.

The group did not find one bowel preparation purgative to be better than others, although table 7 in the document details characteristics of commonly used prep regimens including their side effects and contraindications.

Recommendations regarding dietary modifications depend upon the patient’s risk for inadequate bowel prep. For patients at low risk for inadequate bowel prep, the task force recommends limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. Table 5 in the document provides a list of low-residue foods and sample meals.

The task force also suggests the adjunctive use of oral simethicone (≥ 320 mg) to bowel prep as a way to potentially improve visualization, although they acknowledge that further research is needed.

How might these updated consensus recommendations change current clinical practice? 

Jacobson said: “Some physicians may try to identify individuals who will do just as well with a more patient-friendly, easily tolerated bowel preparation regimen, including less stringent dietary restrictions leading up to colonoscopy.” 

He noted that the task force prefers the term “guidance” to “guidelines.”

 

New Quality Benchmark 

The task force recommends documenting bowel prep quality in the endoscopy report after all washing and suctioning have been completed using reliably understood descriptors that communicate the adequacy of the preparation.

They recommend the term “adequate bowel preparation” be used to indicate that standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy.

Additionally, the task force recommends that endoscopy units and individual endoscopists track and aim for ≥ 90% adequacy rates in bowel preparation — up from the 85% benchmark contained in the prior recommendations.

Jacobson told this news organization it’s “currently unknown” how many individual endoscopists and endoscopy units track and meet the 90% benchmark at present.

David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, who wasn’t on the task force, said endoscopy units and providers “need to be accountable and should be tracking this quality metric.”

Johnson noted that bowel prep inadequacy has “intrinsic costs,” impacting lesion detection, CRC incidence, and patient outcomes. Inadequate prep leads to “increased risk for morbidity, mortality, longer appointment and wait times for rescheduling, and negative connotations that may deter patients from returning.”

 

Brian Sullivan, MD, MHS, assistant professor of medicine, division of gastroenterology, Duke University School of Medicine, Durham, North Carolina, who wasn’t on the task force, said the recommendation to target a 90% or higher bowel preparation adequacy rate is “appreciated.”

“This benchmark encourages practices to standardize measurement, tracking, and reporting of preparation quality at both the individual and unit levels. Specifically, it should motivate providers to critically evaluate their interpretation of preparation quality and ensure adequate cleansing before making determinations,” Sullivan said in an interview.

“At the unit level, this metric can identify whether there are opportunities for quality improvement, such as by implementing evidence-based initiatives (provided in the guidance) to enhance outpatient preparation processes,” Sullivan noted.

The task force emphasized that the majority of consensus recommendations focus on individuals at average risk for inadequate bowel prep. Patients at high risk for inadequate bowel prep (eg, diabetes, constipation, opioid use) should receive tailored instructions, including a more extended dietary prep and high-volume purgatives.

 

‘Timely and Important’ Updates

Sullivan said the updated consensus recommendations on optimizing bowel preparation quality for colonoscopy are both “timely and important.” 

“Clear guidance facilitates dissemination and adoption, promoting flexible yet evidence-based approaches that enhance patient and provider satisfaction while potentially improving CRC prevention outcomes. For instance, surveys reveal that some practices still do not utilize split-dose bowel preparation, which is proven to improve preparation quality, particularly for the right-side of the colon. This gap underscores the need for standardized guidance to ensure high-quality colonoscopy and effective CRC screening,” Sullivan said.

He also noted that the inclusion of lower-volume bowel prep regimens and less intensive dietary modifications for selected patients is a “welcome update.”

“These options can improve patient adherence and satisfaction, which are critical not only for the quality of the index exam but also for ensuring patients return for future screenings, thereby supporting long-term CRC prevention efforts,” Sullivan said.

The task force includes representatives from the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy.

The consensus document was published online in the three societies’ respective scientific journals — Gastroenterology, the American Journal of Gastroenterology, and Gastrointestinal Endsocopy.

This research had no financial support. Jacobson is a consultant for Curis and Guardant Health. Sullivan had no disclosures. Johnson is an adviser to ISOThrive and a past president of the American College of Gastroenterology.

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