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Obesity Linked with Malignant Progression of Barrett’s Esophagus
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
New Model Estimates Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Lipophilic Statins May Protect Against HCC In Select Liver Disease Patients
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
Hepatocellular carcinoma (HCC) incidence continues to increase in the United States. Because of its poor prognosis and limited treatment options, prevention strategies are critically needed, yet there are no Food and Drug Administration–approved treatments for HCC prevention. In the United States, metabolic syndrome has a high prevalence and is a significant contributor to HCC burden. Many individuals with metabolic syndrome are eligible for statin therapy, which has been associated with HCC chemoprevention. Evidence suggests that lipophilic statins may be more effective chemopreventive agents than hydrophilic statins. However, previous studies have largely focused on populations with hepatitis C virus, making it unclear whether these findings are generalizable to individuals with other liver disease etiologies.
Our findings support the chemopreventive potential of lipophilic statins in patients with hepatic fibrosis and cirrhosis, regardless of the underlying cause. If lipophilic statins are confirmed as effective chemopreventive agents, HCC prevention could begin in the primary care setting. For example, primary care providers treating patients with metabolic syndrome and an indication for statin therapy could select treatment with lipophilic statins over hydrophilic statins. This approach would be cost-effective, relatively simple to implement, and benefit many patients, including those from lower socioeconomic backgrounds who are at higher risk.
Large-scale clinical trials and basic science studies are necessary to confirm the role of lipophilic statins in HCC prevention. Supporting precision medicine initiatives like the All of Us Research Program could help identify individuals most likely to benefit and address gaps in current HCC prevention strategies.
Erik Almazan, MD, is a resident physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. Raymond T. Chung, MD, is director of the Hepatology and Liver Center at Massachusetts General Hospital and Harvard Medical School, Boston. They have no conflicts to disclose.
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
according to investigators.
These findings also pave the way for new research into targeted therapies, personalized prevention strategies, and broader applications in high-risk populations, Erik Almazan, MD, and Raymond T. Chung, MD, of Harvard Medical School, Boston, Massachusetts, reported.
“Statins, metformin, and aspirin are low-cost medications often prescribed for the management of diseases associated with metabolic syndrome that have been associated with reduced HCC risk, the investigators wrote in Gastro Hep Advances. “Despite these findings, few studies have focused on populations in the US or without hepatitis B virus (HBV) or hepatitis C virus (HCV).”
To address this knowledge gap, Almazan and Chung retrospectively analyzed data from 3,677 patients with hepatic fibrosis and cirrhosis, drawn from the All of Us Controlled Tier Dataset v7, which spans May 2018 to July 2022.
Within this population, 94 patients had HCC, while 3,583 served as controls. Lipophilic statin use was compared with hydrophilic statins, metformin, and aspirin. Multivariable logistic regression controlled for confounders including age, sex, race, and the presence of HBV or HCV.
Participants in the HCC cohort were older (mean age, 64 vs 58 years), more likely to be male (64.1% vs 50.0%), and had higher rates of chronic HBV (9.6% vs 2.5%) and chronic HCV (36.2% vs. 20.5%) compared to controls (P ≤ .01).
As a class, lipophilic statins were associated with a 36% reduced risk of HCC (odds ratio [OR], 0.64; 95% CI, 0.41-1.00; P < .05). Specifically, atorvastatin was associated with a 41% reduced risk (OR, 0.59; 95% CI, 0.37-0.93; P = .02), while simvastatin was associated with a 54% reduced risk (OR, 0.46; 95% CI, 0.22-0.97; P = .04).
In contrast, hydrophilic statins, such as pravastatin and rosuvastatin, showed no significant association with HCC risk. Similarly, no protective association was observed for metformin or aspirin.
These findings suggest that lipophilic statins could provide a practical and cost-effective strategy for HCC prevention, particularly in patients with metabolic syndrome or alcohol-related liver disease, according to Almazan and Chung. These high-risk groups often lack accessible and noninvasive prevention options, further highlighting the clinical relevance of these results.
The investigators proposed that the chemopreventive effects of lipophilic statins may be linked to their ability to passively diffuse into cells and modulate pathways involved in cancer development, such as the mevalonate pathway. These potential mechanisms remain poorly understood.
Almazan and Chung also pointed out several study limitations, including lack of granular data on statin doses and treatment duration, absence of serologic and imaging confirmation of hepatic fibrosis and cirrhosis, and a study cohort drawn from populations historically underrepresented in medical research, potentially limiting generalizability to the broader US population.
“Nevertheless, we believe that our study adds valuable information to the literature on statin use and its association with HCC with data from a US-based sample inclusive of individuals with risk factors other than HBV and HCV,” the investigators wrote. “These results provide further support for trials (such as NCT05028829) evaluating the utility of lipophilic statins for chemoprevention in HCC for persons at risk.”This study was supported by various National Institutes of Health grants. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
AI-Aided Colonoscopy’s ‘Intelligent’ Module Ups Polyp Detection
Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.
They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.
“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.
“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”
Study Details
The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.
Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.
CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.
The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).
From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.
Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).
Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).
As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.
Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.
He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.
The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.
“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”
This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.
A version of this article appeared on Medscape.com.
Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.
They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.
“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.
“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”
Study Details
The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.
Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.
CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.
The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).
From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.
Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).
Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).
As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.
Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.
He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.
The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.
“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”
This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.
A version of this article appeared on Medscape.com.
Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.
They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.
“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.
“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”
Study Details
The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.
Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.
CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.
The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).
From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.
Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).
Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).
As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.
Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.
He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.
The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.
“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”
This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.
A version of this article appeared on Medscape.com.
FROM THE LANCET GASTROENTEROLOGY & HEPATOLOGY
Journal Highlights: Sept.-Oct. 2024
Upper GI
Levinthal DJ et al. AGA Clinical Practice Update on Diagnosis and Management of Cyclic Vomiting Syndrome: Commentary. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.05.031.
Geeratragool T et al. Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.03.036.
Goodoory VC et al. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis. Gastroenterology. 2024 Oct. doi: 10.1053/j.gastro.2024.05.010.
Kurlander JE et al; Gastrointestinal Bleeding Working Group. Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.01.047.
Oliva S et al. Crafting a Therapeutic Pyramid for Eosinophilic Esophagitis in the Age of Biologics. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.020.
Lower GI
Redd WD et al. Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.03.036.
Peyrin-Biroulet L et al. Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn’s Disease Regardless of Prior Biologic Exposure. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.02.026.
Chang PW et al. ChatGPT4 Outperforms Endoscopists for Determination of Postcolonoscopy Rescreening and Surveillance Recommendations. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.022.
Liver
Wang L et al. Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.04.029.
Bajaj JS et al. Serum Ammonia Levels Do Not Correlate With Overt Hepatic Encephalopathy Severity in Hospitalized Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.02.015.
Endoscopy
Steinbrück I, et al. Cold Versus Hot Snare Endoscopic Resection of Large Nonpedunculated Colorectal Polyps: Randomized Controlled German CHRONICLE Trial. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.05.013.
Misc.
Kothari S et al. AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review. Gastroenterology. 2024 Oct. doi: 10.1053/j.gastro.2024.06.014.
Chavannes M et al. AGA Clinical Practice Update on the Role of Intestinal Ultrasound in Inflammatory Bowel Disease: Commentary. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.039.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Upper GI
Levinthal DJ et al. AGA Clinical Practice Update on Diagnosis and Management of Cyclic Vomiting Syndrome: Commentary. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.05.031.
Geeratragool T et al. Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.03.036.
Goodoory VC et al. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis. Gastroenterology. 2024 Oct. doi: 10.1053/j.gastro.2024.05.010.
Kurlander JE et al; Gastrointestinal Bleeding Working Group. Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.01.047.
Oliva S et al. Crafting a Therapeutic Pyramid for Eosinophilic Esophagitis in the Age of Biologics. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.020.
Lower GI
Redd WD et al. Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.03.036.
Peyrin-Biroulet L et al. Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn’s Disease Regardless of Prior Biologic Exposure. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.02.026.
Chang PW et al. ChatGPT4 Outperforms Endoscopists for Determination of Postcolonoscopy Rescreening and Surveillance Recommendations. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.022.
Liver
Wang L et al. Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.04.029.
Bajaj JS et al. Serum Ammonia Levels Do Not Correlate With Overt Hepatic Encephalopathy Severity in Hospitalized Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.02.015.
Endoscopy
Steinbrück I, et al. Cold Versus Hot Snare Endoscopic Resection of Large Nonpedunculated Colorectal Polyps: Randomized Controlled German CHRONICLE Trial. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.05.013.
Misc.
Kothari S et al. AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review. Gastroenterology. 2024 Oct. doi: 10.1053/j.gastro.2024.06.014.
Chavannes M et al. AGA Clinical Practice Update on the Role of Intestinal Ultrasound in Inflammatory Bowel Disease: Commentary. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.039.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Upper GI
Levinthal DJ et al. AGA Clinical Practice Update on Diagnosis and Management of Cyclic Vomiting Syndrome: Commentary. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.05.031.
Geeratragool T et al. Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.03.036.
Goodoory VC et al. Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis. Gastroenterology. 2024 Oct. doi: 10.1053/j.gastro.2024.05.010.
Kurlander JE et al; Gastrointestinal Bleeding Working Group. Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.01.047.
Oliva S et al. Crafting a Therapeutic Pyramid for Eosinophilic Esophagitis in the Age of Biologics. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.020.
Lower GI
Redd WD et al. Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.03.036.
Peyrin-Biroulet L et al. Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn’s Disease Regardless of Prior Biologic Exposure. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.02.026.
Chang PW et al. ChatGPT4 Outperforms Endoscopists for Determination of Postcolonoscopy Rescreening and Surveillance Recommendations. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.022.
Liver
Wang L et al. Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.04.029.
Bajaj JS et al. Serum Ammonia Levels Do Not Correlate With Overt Hepatic Encephalopathy Severity in Hospitalized Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.02.015.
Endoscopy
Steinbrück I, et al. Cold Versus Hot Snare Endoscopic Resection of Large Nonpedunculated Colorectal Polyps: Randomized Controlled German CHRONICLE Trial. Gastroenterology. 2024 Sep. doi: 10.1053/j.gastro.2024.05.013.
Misc.
Kothari S et al. AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review. Gastroenterology. 2024 Oct. doi: 10.1053/j.gastro.2024.06.014.
Chavannes M et al. AGA Clinical Practice Update on the Role of Intestinal Ultrasound in Inflammatory Bowel Disease: Commentary. Clin Gastroenterol Hepatol. 2024 Sep. doi: 10.1016/j.cgh.2024.04.039.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Reassuring Data on GLP-1 RAs and Pancreatic Cancer Risk
PHILADELPHIA —
Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications.
“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin.
He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Important Topic
Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.
Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer.
A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones.
Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis.
The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.
The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).
Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.
The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.
Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.
The study had no specific funding. Alchirazi had no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications.
“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin.
He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Important Topic
Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.
Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer.
A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones.
Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis.
The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.
The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).
Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.
The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.
Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.
The study had no specific funding. Alchirazi had no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications.
“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin.
He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Important Topic
Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.
Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer.
A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones.
Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis.
The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.
The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).
Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.
The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.
Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.
The study had no specific funding. Alchirazi had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ACG 2024
AI-Assisted Colonoscopy Linked to Higher Rate of Benign Lesion Removal
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.
“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.
In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.
In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.
Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.
In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.
Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.
More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”
“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.
Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.
Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey.
“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”
The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.
“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.
In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.
In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.
Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.
In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.
Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.
More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”
“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.
Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.
Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey.
“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”
The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.
“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.
In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.
In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.
Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.
In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.
Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.
More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”
“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.
Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.
Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey.
“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”
The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Screening Options for Rare Malignancies
Dear colleagues,
As gastroenterologists and endoscopists, we spend significant time preventing and diagnosing GI malignancies.
For instance, is it worthwhile screening for pancreatic cancer, and, if so, how should this be done? Likewise, diagnosing cholangiocarcinoma is challenging; how best should one evaluate for this in higher risk populations, such as primary sclerosing cholangitis? And what about the costs, financial and otherwise, associated with screening?
In this issue of Perspectives, Dr. Darshan Kothari and Dr. Daniel Bernstein discuss their approach to pancreatic cancer screening, including who is eligible, the preferred screening modalities, and the barriers to screening. In the accompanying perspective, Dr. Aparna Goel and Dr. Judah Kupferman focus on cholangiocarcinoma screening, identifying high-risk populations and discussing some of the concerns with screening, necessitating shared decision-making.
We welcome your thoughts on this issue. Share with us on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
An Approach to Pancreatic Cancer Screening
BY DANIEL A. BERNSTEIN, MD, AND DARSHAN KOTHARI, MD
Pancreatic cancer carries a dismal prognosis, now accounting for the third-most cancer-related mortality in the United States. A small proportion of patients are diagnosed at a local stage of disease, with over half found to have metastatic disease at presentation. Given the low overall incidence and lifetime risk in the general population, population-based screening is not justified.
About 10% of cases of pancreas cancer are associated with germ-line mutations and/or with a strong family history of pancreatic cancer. Several academic societies and expert committees now recommend regular screening for pancreatic cancer in patients who are considered high-risk individuals, as they carry a fivefold relative risk for pancreatic cancer. Moreover, studies suggest that screening has the potential to identify early-stage resectable disease and decrease mortality in this patient population.
Patients who benefit from pancreatic cancer screening are those who carry an increased lifetime risk (in excess of 5%) of pancreatic cancer. High-risk individuals include those with germ-line mutations and/or those with a family history of pancreatic cancer in first-degree relatives. Consensus guidelines by the International Cancer of the Pancreas Screening Consortium and the American Society for Gastrointestinal Endoscopy provide medical centers with detailed recommendations on who and when to start screening.
High-risk individuals fall into three categories:
- Patients with high-risk germline mutations including: familial atypical multiple mole melanoma syndrome (CDKN2A), hereditary breast and ovarian cancer syndromes (BRCA1, BRCA2, and PALB2), Peutz-Jeghers syndrome (STK11), and hereditary pancreatitis (PRSS1 and SPINK1)
- Patients with low- to moderate-risk germ-line mutations with at least one first-degree relative with pancreatic cancer: Lynch Syndrome (particularly MLH1 mutation), ataxia-telangiectasia (ATM), or Li-Fraumeni syndrome (p53)
- Patients with one first-degree relative with pancreatic cancer who in turn has one first-degree relative with pancreatic cancer (eg, a patient’s mother and maternal aunt or a patient’s father and patient’s sister)
Consistent with established guidelines, we recommend screening for high-risk patients beginning at age 50, or 10 years before the youngest age at which pancreas cancer was diagnosed in an affected relative. Screening is recommended earlier in patients with particularly high risk: at age 40 for patients with CDKN2A and STKI11 mutations and age 40 for patients with PRSS1 mutation or 20 years after the first attack of acute pancreatitis. For patients with a strong family history of pancreas cancer, we recommend comprehensive evaluation by a certified genetic counselor at a high-volume cancer center.
In practice, patients at our institution who are identified as high risk based on the above criteria are referred for an initial consultation at our pancreas center. In most cases, this should occur no sooner than 5 years prior to the recommended starting age for screening. All patients who are identified as high risk should be screened annually for diabetes given the growing evidence base supporting an association between new-onset diabetes and pancreatic cancer.
After an initial visit and discussion of the risks and benefits of screening, most screening protocols start with a baseline endoscopic ultrasound (EUS) and contrast-enhanced magnetic resonance abdomen with magnetic resonance cholangiopancreatography (MRI/MRCP), which will be repeated annually or sooner as the clinical condition warrants. A sooner-interval EUS should be considered for patients already undergoing screening who are newly found to have diabetes.
At our institution, we start with an in-person clinic evaluation followed by EUS. Thereafter, patients undergo MRI/MRCP (synchronized with a same-day clinic visit) alternating with EUS every 6 months to ensure patients are seen twice a year, though there is no specific data to support this approach. Non-diabetics also undergo yearly diabetes screening which will trigger an EUS if patients become diabetic.
We engage in shared decision-making with our high-risk individuals undergoing pancreatic cancer screening and at each visit we review their concurrent medical conditions and suitability to continue screening. We consider discontinuing screening after age 75, at the onset of any life-limiting illness, or after a discussion of risks and benefits if comorbidities lead to a substantial deterioration in a patient’s overall health status.
While a growing body of evidence exists to support the application of pancreatic cancer screening in high-risk individuals, this preventive service remains underutilized. Recent analysis of the screening cohort at our institution showed a demographically homogeneous group of mostly highly educated, high-income White females. These findings are consistent with the patient cohorts described in other pancreatic cancer screening programs and represent only a fraction of people who would qualify for pancreatic cancer screening.
A survey of patients undergoing screening at our institution identified cost, travel, and time associated with pancreatic cancer screening to be frequent challenges to participation. Further studies are needed to fully explore the barriers and psychological burden of pancreas cancer screening in high-risk individuals, and to identify ways to enrich the cohort of patients undergoing screening. This may involve novel methods to identify family members of patients with a new diagnosis of pancreas cancer and increasing health literacy around pancreatic cancer screening among patients and providers.
Pancreatic cancer screening has the potential to identify early-stage disease in patients who are at high risk because of germ-line mutations and/or family history. We recommend that patients engage in pancreatic cancer screening at high-volume centers with well-supported oncology, genetics, and research infrastructure.
Dr. Bernstein is a gastroenterology fellow at Duke University School of Medicine, Durham, North Carolina. Dr. Kothari is an associate professor of medicine in gastroenterology and hepatology at Duke University School of Medicine.
Screening for Cholangiocarcinoma
BY JUDAH KUPFERMAN, MD, AND APARNA GOEL, MD
Cholangiocarcinoma is a rare but aggressive cancer of the bile ducts that poses many diagnostic challenges. Approximately 3% of gastrointestinal cancers are attributed to cholangiocarcinoma, and while the annual incidence of disease in the United States is about 1.26 per 100,000 people, the incidence of intrahepatic disease has been rising considerably.1,2 Screening for cholangiocarcinoma is reserved for high-risk individuals — such as those with primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and biliary tract disorders such as choledochal cysts or Caroli’s disease. The goal is to balance the benefits of early diagnosis with the costs and risks associated with screening, particularly given the limitations of available tools like MRI with cholangiopancreatography (MRCP), which has a sensitivity of 70%-85%. In general, we recommend annual cholangiocarcinoma screening for high-risk individuals with MRI and MRCP as well as with cancer antigen (CA) 19-9. .
Screening in Patients with Primary Sclerosing Cholangitis
The lifetime risk of cholangiocarcinoma in patients with PSC is 10%-15% with an annual risk of 0.5%-1.5%. In our experience, this is often the most feared complication for PSC patients, even more so than the risk of liver transplantation. We recommend annual MRI with MRCP in addition to CA 19-9 for patients with PSC in the first decade of their diagnosis, as most cancers are diagnosed during this period. If a patient’s imaging has remained stable for over a decade and there is minimal hepatic fibrosis, we discuss the option of reducing screening frequency to every 2 years to minimize costs and exposure to MRI contrast risks.
If MRI reveals a concerning new large duct stricture, we will evaluate this with an endoscopic retrograde cholangiopancreatography (ERCP), as differentiating benign and malignant strictures is quite challenging with MRI. We generally recommend ERCP with brush cytology and fluorescence in situ hybridization to improve diagnostic yield. Depending on imaging findings and location of the new large duct stricture, we may consider cholangioscopy during ERCP for direct visualization of the bile duct and directed tissue biopsies. Unfortunately, even in young, asymptomatic patients who undergo regular screening, cholangiocarcinoma is frequently diagnosed at an advanced stage.
Screening in Patients with Secondary Sclerosing Cholangitis
Patients with SSC may develop cholangiocarcinoma because of chronic inflammatory and fibrotic processes, such as IgG4-associated cholangiopathy, sarcoidosis, ischemic cholangiopathy, cystic fibrosis, recurrent pyogenic cholangitis, severe sepsis (as recently seen from SARS-CoV-2), surgical complications, or other etiologies. When the condition is reversible, such as with IgG4-associated cholangiopathy, cancer screening may not be necessary. However, when irreversible damage occurs, the cancer risk increases, though it varies by disease type and severity. In most cases, we recommend routine screening for cholangiocarcinoma with MRI and CA 19-9 in this population.
Screening in Patients with Biliary Tract Disorders
Biliary tract disorders such as choledochal cysts and Caroli’s disease also harbor an increased risk of cholangiocarcinoma. Choledochal cysts are congenital cystic dilations of the bile duct that have a 10%-30% lifetime risk of malignant transformation to cholangiocarcinoma. Surgical intervention to remove the cyst is often recommended because of this high risk. However, some patients may be unable or unwilling to undergo this surgery or they may have residual cysts. We recommend ongoing screening with MRI and CA 19-9 for these patients. Similarly, Caroli’s disease is a congenital disease associated with intrahepatic and extrahepatic bile duct cysts and associated with a 5%-15% lifetime risk of cholangiocarcinoma. MRI with MRCP and CA 19-9 should be performed routinely for patients with Caroli’s disease and syndrome.
Risks and Challenges in Cholangiocarcinoma Screening
While MRI with MRCP is the gold standard for cholangiocarcinoma screening, its limitations must be carefully considered. One growing concern is the potential for gadolinium retention in the brain, bones, or skin following repeated MRI scans. Though the long-term effects of gadolinium retention are not fully understood, we factor this into screening decisions, particularly for younger patients who may undergo decades of regular imaging.
MRI is not always feasible for certain patients, including those with metal implants, on hemodialysis, or with severe allergic reactions. In such cases, CT or ultrasound may serve as alternatives, though with lower sensitivity for detecting cholangiocarcinoma. Additionally, claustrophobia during MRI can be addressed with sedation, but this underscores the importance of shared decision-making.
From our perspective, cholangiocarcinoma screening in high-risk patients is crucial but not without challenges. Our current screening methods, while essential, are far from perfect, often missing early cancers or leading to unnecessary interventions. Because of these limitations, the window for treatment of localized disease can easily be missed. In our practice, we tailor screening strategies to each patient’s specific needs, weighing the potential benefits against the risks, costs, and the inherent uncertainty of early detection tools. We believe it is essential to involve patients in this decision-making process to provide a balanced, individualized approach that considers both clinical evidence and the personal preferences of each person.
Dr. Kupferman is a gastroenterology fellow at Stanford University School of Medicine in California. Dr. Goel is a transplant hepatologist and a clinical associate professor in gastroenterology & hepatology at Stanford.
References
1. Vithayathil M and Khan SA. J Hepatol. 2022 Dec. doi: 10.1016/j.jhep.2022.07.022.
2. Patel N and Benipal B. Cureus. 2019 Jan. doi: 10.7759/cureus.3962.
Dear colleagues,
As gastroenterologists and endoscopists, we spend significant time preventing and diagnosing GI malignancies.
For instance, is it worthwhile screening for pancreatic cancer, and, if so, how should this be done? Likewise, diagnosing cholangiocarcinoma is challenging; how best should one evaluate for this in higher risk populations, such as primary sclerosing cholangitis? And what about the costs, financial and otherwise, associated with screening?
In this issue of Perspectives, Dr. Darshan Kothari and Dr. Daniel Bernstein discuss their approach to pancreatic cancer screening, including who is eligible, the preferred screening modalities, and the barriers to screening. In the accompanying perspective, Dr. Aparna Goel and Dr. Judah Kupferman focus on cholangiocarcinoma screening, identifying high-risk populations and discussing some of the concerns with screening, necessitating shared decision-making.
We welcome your thoughts on this issue. Share with us on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
An Approach to Pancreatic Cancer Screening
BY DANIEL A. BERNSTEIN, MD, AND DARSHAN KOTHARI, MD
Pancreatic cancer carries a dismal prognosis, now accounting for the third-most cancer-related mortality in the United States. A small proportion of patients are diagnosed at a local stage of disease, with over half found to have metastatic disease at presentation. Given the low overall incidence and lifetime risk in the general population, population-based screening is not justified.
About 10% of cases of pancreas cancer are associated with germ-line mutations and/or with a strong family history of pancreatic cancer. Several academic societies and expert committees now recommend regular screening for pancreatic cancer in patients who are considered high-risk individuals, as they carry a fivefold relative risk for pancreatic cancer. Moreover, studies suggest that screening has the potential to identify early-stage resectable disease and decrease mortality in this patient population.
Patients who benefit from pancreatic cancer screening are those who carry an increased lifetime risk (in excess of 5%) of pancreatic cancer. High-risk individuals include those with germ-line mutations and/or those with a family history of pancreatic cancer in first-degree relatives. Consensus guidelines by the International Cancer of the Pancreas Screening Consortium and the American Society for Gastrointestinal Endoscopy provide medical centers with detailed recommendations on who and when to start screening.
High-risk individuals fall into three categories:
- Patients with high-risk germline mutations including: familial atypical multiple mole melanoma syndrome (CDKN2A), hereditary breast and ovarian cancer syndromes (BRCA1, BRCA2, and PALB2), Peutz-Jeghers syndrome (STK11), and hereditary pancreatitis (PRSS1 and SPINK1)
- Patients with low- to moderate-risk germ-line mutations with at least one first-degree relative with pancreatic cancer: Lynch Syndrome (particularly MLH1 mutation), ataxia-telangiectasia (ATM), or Li-Fraumeni syndrome (p53)
- Patients with one first-degree relative with pancreatic cancer who in turn has one first-degree relative with pancreatic cancer (eg, a patient’s mother and maternal aunt or a patient’s father and patient’s sister)
Consistent with established guidelines, we recommend screening for high-risk patients beginning at age 50, or 10 years before the youngest age at which pancreas cancer was diagnosed in an affected relative. Screening is recommended earlier in patients with particularly high risk: at age 40 for patients with CDKN2A and STKI11 mutations and age 40 for patients with PRSS1 mutation or 20 years after the first attack of acute pancreatitis. For patients with a strong family history of pancreas cancer, we recommend comprehensive evaluation by a certified genetic counselor at a high-volume cancer center.
In practice, patients at our institution who are identified as high risk based on the above criteria are referred for an initial consultation at our pancreas center. In most cases, this should occur no sooner than 5 years prior to the recommended starting age for screening. All patients who are identified as high risk should be screened annually for diabetes given the growing evidence base supporting an association between new-onset diabetes and pancreatic cancer.
After an initial visit and discussion of the risks and benefits of screening, most screening protocols start with a baseline endoscopic ultrasound (EUS) and contrast-enhanced magnetic resonance abdomen with magnetic resonance cholangiopancreatography (MRI/MRCP), which will be repeated annually or sooner as the clinical condition warrants. A sooner-interval EUS should be considered for patients already undergoing screening who are newly found to have diabetes.
At our institution, we start with an in-person clinic evaluation followed by EUS. Thereafter, patients undergo MRI/MRCP (synchronized with a same-day clinic visit) alternating with EUS every 6 months to ensure patients are seen twice a year, though there is no specific data to support this approach. Non-diabetics also undergo yearly diabetes screening which will trigger an EUS if patients become diabetic.
We engage in shared decision-making with our high-risk individuals undergoing pancreatic cancer screening and at each visit we review their concurrent medical conditions and suitability to continue screening. We consider discontinuing screening after age 75, at the onset of any life-limiting illness, or after a discussion of risks and benefits if comorbidities lead to a substantial deterioration in a patient’s overall health status.
While a growing body of evidence exists to support the application of pancreatic cancer screening in high-risk individuals, this preventive service remains underutilized. Recent analysis of the screening cohort at our institution showed a demographically homogeneous group of mostly highly educated, high-income White females. These findings are consistent with the patient cohorts described in other pancreatic cancer screening programs and represent only a fraction of people who would qualify for pancreatic cancer screening.
A survey of patients undergoing screening at our institution identified cost, travel, and time associated with pancreatic cancer screening to be frequent challenges to participation. Further studies are needed to fully explore the barriers and psychological burden of pancreas cancer screening in high-risk individuals, and to identify ways to enrich the cohort of patients undergoing screening. This may involve novel methods to identify family members of patients with a new diagnosis of pancreas cancer and increasing health literacy around pancreatic cancer screening among patients and providers.
Pancreatic cancer screening has the potential to identify early-stage disease in patients who are at high risk because of germ-line mutations and/or family history. We recommend that patients engage in pancreatic cancer screening at high-volume centers with well-supported oncology, genetics, and research infrastructure.
Dr. Bernstein is a gastroenterology fellow at Duke University School of Medicine, Durham, North Carolina. Dr. Kothari is an associate professor of medicine in gastroenterology and hepatology at Duke University School of Medicine.
Screening for Cholangiocarcinoma
BY JUDAH KUPFERMAN, MD, AND APARNA GOEL, MD
Cholangiocarcinoma is a rare but aggressive cancer of the bile ducts that poses many diagnostic challenges. Approximately 3% of gastrointestinal cancers are attributed to cholangiocarcinoma, and while the annual incidence of disease in the United States is about 1.26 per 100,000 people, the incidence of intrahepatic disease has been rising considerably.1,2 Screening for cholangiocarcinoma is reserved for high-risk individuals — such as those with primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and biliary tract disorders such as choledochal cysts or Caroli’s disease. The goal is to balance the benefits of early diagnosis with the costs and risks associated with screening, particularly given the limitations of available tools like MRI with cholangiopancreatography (MRCP), which has a sensitivity of 70%-85%. In general, we recommend annual cholangiocarcinoma screening for high-risk individuals with MRI and MRCP as well as with cancer antigen (CA) 19-9. .
Screening in Patients with Primary Sclerosing Cholangitis
The lifetime risk of cholangiocarcinoma in patients with PSC is 10%-15% with an annual risk of 0.5%-1.5%. In our experience, this is often the most feared complication for PSC patients, even more so than the risk of liver transplantation. We recommend annual MRI with MRCP in addition to CA 19-9 for patients with PSC in the first decade of their diagnosis, as most cancers are diagnosed during this period. If a patient’s imaging has remained stable for over a decade and there is minimal hepatic fibrosis, we discuss the option of reducing screening frequency to every 2 years to minimize costs and exposure to MRI contrast risks.
If MRI reveals a concerning new large duct stricture, we will evaluate this with an endoscopic retrograde cholangiopancreatography (ERCP), as differentiating benign and malignant strictures is quite challenging with MRI. We generally recommend ERCP with brush cytology and fluorescence in situ hybridization to improve diagnostic yield. Depending on imaging findings and location of the new large duct stricture, we may consider cholangioscopy during ERCP for direct visualization of the bile duct and directed tissue biopsies. Unfortunately, even in young, asymptomatic patients who undergo regular screening, cholangiocarcinoma is frequently diagnosed at an advanced stage.
Screening in Patients with Secondary Sclerosing Cholangitis
Patients with SSC may develop cholangiocarcinoma because of chronic inflammatory and fibrotic processes, such as IgG4-associated cholangiopathy, sarcoidosis, ischemic cholangiopathy, cystic fibrosis, recurrent pyogenic cholangitis, severe sepsis (as recently seen from SARS-CoV-2), surgical complications, or other etiologies. When the condition is reversible, such as with IgG4-associated cholangiopathy, cancer screening may not be necessary. However, when irreversible damage occurs, the cancer risk increases, though it varies by disease type and severity. In most cases, we recommend routine screening for cholangiocarcinoma with MRI and CA 19-9 in this population.
Screening in Patients with Biliary Tract Disorders
Biliary tract disorders such as choledochal cysts and Caroli’s disease also harbor an increased risk of cholangiocarcinoma. Choledochal cysts are congenital cystic dilations of the bile duct that have a 10%-30% lifetime risk of malignant transformation to cholangiocarcinoma. Surgical intervention to remove the cyst is often recommended because of this high risk. However, some patients may be unable or unwilling to undergo this surgery or they may have residual cysts. We recommend ongoing screening with MRI and CA 19-9 for these patients. Similarly, Caroli’s disease is a congenital disease associated with intrahepatic and extrahepatic bile duct cysts and associated with a 5%-15% lifetime risk of cholangiocarcinoma. MRI with MRCP and CA 19-9 should be performed routinely for patients with Caroli’s disease and syndrome.
Risks and Challenges in Cholangiocarcinoma Screening
While MRI with MRCP is the gold standard for cholangiocarcinoma screening, its limitations must be carefully considered. One growing concern is the potential for gadolinium retention in the brain, bones, or skin following repeated MRI scans. Though the long-term effects of gadolinium retention are not fully understood, we factor this into screening decisions, particularly for younger patients who may undergo decades of regular imaging.
MRI is not always feasible for certain patients, including those with metal implants, on hemodialysis, or with severe allergic reactions. In such cases, CT or ultrasound may serve as alternatives, though with lower sensitivity for detecting cholangiocarcinoma. Additionally, claustrophobia during MRI can be addressed with sedation, but this underscores the importance of shared decision-making.
From our perspective, cholangiocarcinoma screening in high-risk patients is crucial but not without challenges. Our current screening methods, while essential, are far from perfect, often missing early cancers or leading to unnecessary interventions. Because of these limitations, the window for treatment of localized disease can easily be missed. In our practice, we tailor screening strategies to each patient’s specific needs, weighing the potential benefits against the risks, costs, and the inherent uncertainty of early detection tools. We believe it is essential to involve patients in this decision-making process to provide a balanced, individualized approach that considers both clinical evidence and the personal preferences of each person.
Dr. Kupferman is a gastroenterology fellow at Stanford University School of Medicine in California. Dr. Goel is a transplant hepatologist and a clinical associate professor in gastroenterology & hepatology at Stanford.
References
1. Vithayathil M and Khan SA. J Hepatol. 2022 Dec. doi: 10.1016/j.jhep.2022.07.022.
2. Patel N and Benipal B. Cureus. 2019 Jan. doi: 10.7759/cureus.3962.
Dear colleagues,
As gastroenterologists and endoscopists, we spend significant time preventing and diagnosing GI malignancies.
For instance, is it worthwhile screening for pancreatic cancer, and, if so, how should this be done? Likewise, diagnosing cholangiocarcinoma is challenging; how best should one evaluate for this in higher risk populations, such as primary sclerosing cholangitis? And what about the costs, financial and otherwise, associated with screening?
In this issue of Perspectives, Dr. Darshan Kothari and Dr. Daniel Bernstein discuss their approach to pancreatic cancer screening, including who is eligible, the preferred screening modalities, and the barriers to screening. In the accompanying perspective, Dr. Aparna Goel and Dr. Judah Kupferman focus on cholangiocarcinoma screening, identifying high-risk populations and discussing some of the concerns with screening, necessitating shared decision-making.
We welcome your thoughts on this issue. Share with us on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
An Approach to Pancreatic Cancer Screening
BY DANIEL A. BERNSTEIN, MD, AND DARSHAN KOTHARI, MD
Pancreatic cancer carries a dismal prognosis, now accounting for the third-most cancer-related mortality in the United States. A small proportion of patients are diagnosed at a local stage of disease, with over half found to have metastatic disease at presentation. Given the low overall incidence and lifetime risk in the general population, population-based screening is not justified.
About 10% of cases of pancreas cancer are associated with germ-line mutations and/or with a strong family history of pancreatic cancer. Several academic societies and expert committees now recommend regular screening for pancreatic cancer in patients who are considered high-risk individuals, as they carry a fivefold relative risk for pancreatic cancer. Moreover, studies suggest that screening has the potential to identify early-stage resectable disease and decrease mortality in this patient population.
Patients who benefit from pancreatic cancer screening are those who carry an increased lifetime risk (in excess of 5%) of pancreatic cancer. High-risk individuals include those with germ-line mutations and/or those with a family history of pancreatic cancer in first-degree relatives. Consensus guidelines by the International Cancer of the Pancreas Screening Consortium and the American Society for Gastrointestinal Endoscopy provide medical centers with detailed recommendations on who and when to start screening.
High-risk individuals fall into three categories:
- Patients with high-risk germline mutations including: familial atypical multiple mole melanoma syndrome (CDKN2A), hereditary breast and ovarian cancer syndromes (BRCA1, BRCA2, and PALB2), Peutz-Jeghers syndrome (STK11), and hereditary pancreatitis (PRSS1 and SPINK1)
- Patients with low- to moderate-risk germ-line mutations with at least one first-degree relative with pancreatic cancer: Lynch Syndrome (particularly MLH1 mutation), ataxia-telangiectasia (ATM), or Li-Fraumeni syndrome (p53)
- Patients with one first-degree relative with pancreatic cancer who in turn has one first-degree relative with pancreatic cancer (eg, a patient’s mother and maternal aunt or a patient’s father and patient’s sister)
Consistent with established guidelines, we recommend screening for high-risk patients beginning at age 50, or 10 years before the youngest age at which pancreas cancer was diagnosed in an affected relative. Screening is recommended earlier in patients with particularly high risk: at age 40 for patients with CDKN2A and STKI11 mutations and age 40 for patients with PRSS1 mutation or 20 years after the first attack of acute pancreatitis. For patients with a strong family history of pancreas cancer, we recommend comprehensive evaluation by a certified genetic counselor at a high-volume cancer center.
In practice, patients at our institution who are identified as high risk based on the above criteria are referred for an initial consultation at our pancreas center. In most cases, this should occur no sooner than 5 years prior to the recommended starting age for screening. All patients who are identified as high risk should be screened annually for diabetes given the growing evidence base supporting an association between new-onset diabetes and pancreatic cancer.
After an initial visit and discussion of the risks and benefits of screening, most screening protocols start with a baseline endoscopic ultrasound (EUS) and contrast-enhanced magnetic resonance abdomen with magnetic resonance cholangiopancreatography (MRI/MRCP), which will be repeated annually or sooner as the clinical condition warrants. A sooner-interval EUS should be considered for patients already undergoing screening who are newly found to have diabetes.
At our institution, we start with an in-person clinic evaluation followed by EUS. Thereafter, patients undergo MRI/MRCP (synchronized with a same-day clinic visit) alternating with EUS every 6 months to ensure patients are seen twice a year, though there is no specific data to support this approach. Non-diabetics also undergo yearly diabetes screening which will trigger an EUS if patients become diabetic.
We engage in shared decision-making with our high-risk individuals undergoing pancreatic cancer screening and at each visit we review their concurrent medical conditions and suitability to continue screening. We consider discontinuing screening after age 75, at the onset of any life-limiting illness, or after a discussion of risks and benefits if comorbidities lead to a substantial deterioration in a patient’s overall health status.
While a growing body of evidence exists to support the application of pancreatic cancer screening in high-risk individuals, this preventive service remains underutilized. Recent analysis of the screening cohort at our institution showed a demographically homogeneous group of mostly highly educated, high-income White females. These findings are consistent with the patient cohorts described in other pancreatic cancer screening programs and represent only a fraction of people who would qualify for pancreatic cancer screening.
A survey of patients undergoing screening at our institution identified cost, travel, and time associated with pancreatic cancer screening to be frequent challenges to participation. Further studies are needed to fully explore the barriers and psychological burden of pancreas cancer screening in high-risk individuals, and to identify ways to enrich the cohort of patients undergoing screening. This may involve novel methods to identify family members of patients with a new diagnosis of pancreas cancer and increasing health literacy around pancreatic cancer screening among patients and providers.
Pancreatic cancer screening has the potential to identify early-stage disease in patients who are at high risk because of germ-line mutations and/or family history. We recommend that patients engage in pancreatic cancer screening at high-volume centers with well-supported oncology, genetics, and research infrastructure.
Dr. Bernstein is a gastroenterology fellow at Duke University School of Medicine, Durham, North Carolina. Dr. Kothari is an associate professor of medicine in gastroenterology and hepatology at Duke University School of Medicine.
Screening for Cholangiocarcinoma
BY JUDAH KUPFERMAN, MD, AND APARNA GOEL, MD
Cholangiocarcinoma is a rare but aggressive cancer of the bile ducts that poses many diagnostic challenges. Approximately 3% of gastrointestinal cancers are attributed to cholangiocarcinoma, and while the annual incidence of disease in the United States is about 1.26 per 100,000 people, the incidence of intrahepatic disease has been rising considerably.1,2 Screening for cholangiocarcinoma is reserved for high-risk individuals — such as those with primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and biliary tract disorders such as choledochal cysts or Caroli’s disease. The goal is to balance the benefits of early diagnosis with the costs and risks associated with screening, particularly given the limitations of available tools like MRI with cholangiopancreatography (MRCP), which has a sensitivity of 70%-85%. In general, we recommend annual cholangiocarcinoma screening for high-risk individuals with MRI and MRCP as well as with cancer antigen (CA) 19-9. .
Screening in Patients with Primary Sclerosing Cholangitis
The lifetime risk of cholangiocarcinoma in patients with PSC is 10%-15% with an annual risk of 0.5%-1.5%. In our experience, this is often the most feared complication for PSC patients, even more so than the risk of liver transplantation. We recommend annual MRI with MRCP in addition to CA 19-9 for patients with PSC in the first decade of their diagnosis, as most cancers are diagnosed during this period. If a patient’s imaging has remained stable for over a decade and there is minimal hepatic fibrosis, we discuss the option of reducing screening frequency to every 2 years to minimize costs and exposure to MRI contrast risks.
If MRI reveals a concerning new large duct stricture, we will evaluate this with an endoscopic retrograde cholangiopancreatography (ERCP), as differentiating benign and malignant strictures is quite challenging with MRI. We generally recommend ERCP with brush cytology and fluorescence in situ hybridization to improve diagnostic yield. Depending on imaging findings and location of the new large duct stricture, we may consider cholangioscopy during ERCP for direct visualization of the bile duct and directed tissue biopsies. Unfortunately, even in young, asymptomatic patients who undergo regular screening, cholangiocarcinoma is frequently diagnosed at an advanced stage.
Screening in Patients with Secondary Sclerosing Cholangitis
Patients with SSC may develop cholangiocarcinoma because of chronic inflammatory and fibrotic processes, such as IgG4-associated cholangiopathy, sarcoidosis, ischemic cholangiopathy, cystic fibrosis, recurrent pyogenic cholangitis, severe sepsis (as recently seen from SARS-CoV-2), surgical complications, or other etiologies. When the condition is reversible, such as with IgG4-associated cholangiopathy, cancer screening may not be necessary. However, when irreversible damage occurs, the cancer risk increases, though it varies by disease type and severity. In most cases, we recommend routine screening for cholangiocarcinoma with MRI and CA 19-9 in this population.
Screening in Patients with Biliary Tract Disorders
Biliary tract disorders such as choledochal cysts and Caroli’s disease also harbor an increased risk of cholangiocarcinoma. Choledochal cysts are congenital cystic dilations of the bile duct that have a 10%-30% lifetime risk of malignant transformation to cholangiocarcinoma. Surgical intervention to remove the cyst is often recommended because of this high risk. However, some patients may be unable or unwilling to undergo this surgery or they may have residual cysts. We recommend ongoing screening with MRI and CA 19-9 for these patients. Similarly, Caroli’s disease is a congenital disease associated with intrahepatic and extrahepatic bile duct cysts and associated with a 5%-15% lifetime risk of cholangiocarcinoma. MRI with MRCP and CA 19-9 should be performed routinely for patients with Caroli’s disease and syndrome.
Risks and Challenges in Cholangiocarcinoma Screening
While MRI with MRCP is the gold standard for cholangiocarcinoma screening, its limitations must be carefully considered. One growing concern is the potential for gadolinium retention in the brain, bones, or skin following repeated MRI scans. Though the long-term effects of gadolinium retention are not fully understood, we factor this into screening decisions, particularly for younger patients who may undergo decades of regular imaging.
MRI is not always feasible for certain patients, including those with metal implants, on hemodialysis, or with severe allergic reactions. In such cases, CT or ultrasound may serve as alternatives, though with lower sensitivity for detecting cholangiocarcinoma. Additionally, claustrophobia during MRI can be addressed with sedation, but this underscores the importance of shared decision-making.
From our perspective, cholangiocarcinoma screening in high-risk patients is crucial but not without challenges. Our current screening methods, while essential, are far from perfect, often missing early cancers or leading to unnecessary interventions. Because of these limitations, the window for treatment of localized disease can easily be missed. In our practice, we tailor screening strategies to each patient’s specific needs, weighing the potential benefits against the risks, costs, and the inherent uncertainty of early detection tools. We believe it is essential to involve patients in this decision-making process to provide a balanced, individualized approach that considers both clinical evidence and the personal preferences of each person.
Dr. Kupferman is a gastroenterology fellow at Stanford University School of Medicine in California. Dr. Goel is a transplant hepatologist and a clinical associate professor in gastroenterology & hepatology at Stanford.
References
1. Vithayathil M and Khan SA. J Hepatol. 2022 Dec. doi: 10.1016/j.jhep.2022.07.022.
2. Patel N and Benipal B. Cureus. 2019 Jan. doi: 10.7759/cureus.3962.
Low-Volume Bowel Prep Easier, as Effective as Standard Prep in Hospitalized Patients
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.
“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.
Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.
“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.
In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.
After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.
In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.
Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.
Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.
In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
Ease of Use Is a Plus
On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”
In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).
“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.
“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”
Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.
“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”
The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.
“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.
Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.
“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.
In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.
After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.
In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.
Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.
Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.
In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
Ease of Use Is a Plus
On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”
In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).
“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.
“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”
Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.
“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”
The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.
“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.
Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.
“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.
In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.
After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.
In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.
Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.
Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.
In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
Ease of Use Is a Plus
On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”
In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).
“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.
“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”
Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.
“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”
The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ACG 2024
GLP-1 RAs Reduce Early-Onset CRC Risk in Patients With Type 2 Diabetes
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
FROM ACG 2024