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Environment More Than Genes Impacts Age at Inflammatory Bowel Disease Diagnosis
a large study of IBD patients reported.
Published in Clinical Gastroenterology and Hepatology , the study found that environment influences the onset of both ulcerative colitis (UC) and Crohn’s disease (CD), and exposures typical in Western society lower the age of diagnosis. These factors include birth in a developed nation, delivery by C-section, and more bathrooms in the home, according to Oriana M. Damas, MD, MSCTI, an associate professor of clinical medicine at the University of Miami Miller School of Medicine in Florida and colleagues.
Environmental factors explained 21% of the variance in age of CD diagnosis and 39% of the variance in age of UC diagnosis. In models incorporating both genetic and environmental risk scores, the environment was the only significant factor associated with younger age of IBD diagnosis in all groups.
Several epidemiologic studies have examined environmental culprits in IBD, and others have examined genetic risk factors, Dr. Damas said in an interview. “But we had not seen any studies that examined the influence of both [of] these on age of IBD development.” Her group’s working hypothesis that environment would have a greater effect than genetics was borne out.
“Additionally, very few studies have examined the contribution of genetics or environmental factors in Hispanic individuals, and our study examined the contribution of these factors in this understudied population,” she added.
According to Dr. Damas, the findings’ most immediate clinical relevance is for counseling people with a family history of IBD. “I think it’s important for concerned patients to know that IBD is not solely genetic and that several environmental factors can shape disease risk to a greater extent than genetic predisposition,” she said
Westernization is increasingly considered a contributor to the global increase in IBD, which has been diagnosed in an estimated 2.39 million Americans . In genetically predisposed individuals, environmental culprits in developed countries are thought to negatively shape the intestinal microbiome’s composition into a less tolerant and more proinflammatory state, the authors noted.
According to the “hygiene hypothesis,” the oversanitization of life in the developed world is partly to blame. “A cleaner environment at home, part of the hygiene hypothesis, has been postulated as a theory to help explain the rise of autoimmune diseases in the 21st century and may play an important part in explaining our study findings,” the authors wrote.
Population-based studies have also pointed to antibiotics, nonsteroidal anti-inflammatory drugs, smoking, cesarean delivery, lack of breastfeeding, and nonexposure to farm animals as other risk factors for IBD.
Study Details
To compare the effect of environmental vs genetic risk factors, the questionnaire-based study surveyed 2952 IBD patients from a tertiary care referral center — 58.9% with CD, 45.83% of Hispanic background, and 53.18% of non-Hispanic White (NHW) ethnicity. There were too few available Black and Asian patients to be included in the cohort. Data were collected from 2017 to 2022.
The mean age of patients was 39.71 years, and 34.14% were defined as born outside of the US mainland. Foreign-born patients were further characterized as from developed nations vs developing nations; 81.3% in this subgroup came from the latter. A detailed questionnaire probed 13 potential environmental factors from type of birth to domestic living conditions, medications, and smoking across several different age groups. Blood was drawn to genotype participants and to create a genetic risk score.
Early plastic water bottle use — which has been linked to inflammatory microplastics in the intestines — and residing in homes with more than one bathroom (and presumably less exposure to infections) were also associated with younger age at diagnosis. Susceptibility to environmental exposures was similar in Hispanic and NHW patients.
“It was interesting to find an association between reported plastic water bottle use and younger age of IBD diagnosis,” said Dr. Damas. “Because this is a self-reported intake, we need more studies to confirm this. However, this finding falls in line with other recent studies showing a potential association between microplastics and disease states, including IBD. The next step is to measure for traces of environmental contaminants in human samples of patients with IBD.”
Unlike previous studies, this analysis did not find parasitic infections, pets, and antibiotics to be associated with age of IBD diagnosis.
“This is an interesting and important study,” commented Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, who was not involved in the study. “There are few environmental risk factor studies looking at non-White populations and to that end, this is a very large and well-done analysis looking at environmental factors among Hispanic patients with IBD.”
He added that, while most studies have just compared factors between cases and controls, “this is an interesting examination of the impact of such factors on age of onset.”
Dr. Ananthakrishnan stressed, however, that further work is needed to expand on these findings.” The addition of a control group would help determine how these factors actually modify disease risk. It is also intriguing that environmental factors more strongly predict age of onset than genetic risk. That only highlights the fact that IBD is in large part an environmentally influenced disease, suggesting there is exciting opportunity for environmental modification to address disease onset.”
Offering another outsider’s perspective, Manasi Agrawal, MD, MS, an assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York City and not a participant in the study, agreed that the findings highlight the contribution of early life and childhood environmental factors to IBD risk relative to genetic variants. “The relative importance of the environment compared to genetic risk toward IBD, timing of exposure, and impact on age at IBD diagnosis is a novel and important finding. These data will help contextualize how we communicate disease risk and potential prevention approaches.”
She added that future research should measure various exposures, such as pollutants in preclinical biological samples. “Mechanistic data on their downstream effects are needed to understand IBD pathogenesis and develop prevention efforts.”
According to the authors, theirs is the first study of its kind to examine the contribution of cumulative environmental factors, age-dependent exposures, and genetic predisposition to age of IBD diagnosis in a diverse IBD cohort.
The authors listed no specific funding for this study and had no conflicts of interest to declare. Dr. Ananthakrishnan and Dr. Agrawal had no relevant competing interests.
A version of this article appeared on Medscape.com.
a large study of IBD patients reported.
Published in Clinical Gastroenterology and Hepatology , the study found that environment influences the onset of both ulcerative colitis (UC) and Crohn’s disease (CD), and exposures typical in Western society lower the age of diagnosis. These factors include birth in a developed nation, delivery by C-section, and more bathrooms in the home, according to Oriana M. Damas, MD, MSCTI, an associate professor of clinical medicine at the University of Miami Miller School of Medicine in Florida and colleagues.
Environmental factors explained 21% of the variance in age of CD diagnosis and 39% of the variance in age of UC diagnosis. In models incorporating both genetic and environmental risk scores, the environment was the only significant factor associated with younger age of IBD diagnosis in all groups.
Several epidemiologic studies have examined environmental culprits in IBD, and others have examined genetic risk factors, Dr. Damas said in an interview. “But we had not seen any studies that examined the influence of both [of] these on age of IBD development.” Her group’s working hypothesis that environment would have a greater effect than genetics was borne out.
“Additionally, very few studies have examined the contribution of genetics or environmental factors in Hispanic individuals, and our study examined the contribution of these factors in this understudied population,” she added.
According to Dr. Damas, the findings’ most immediate clinical relevance is for counseling people with a family history of IBD. “I think it’s important for concerned patients to know that IBD is not solely genetic and that several environmental factors can shape disease risk to a greater extent than genetic predisposition,” she said
Westernization is increasingly considered a contributor to the global increase in IBD, which has been diagnosed in an estimated 2.39 million Americans . In genetically predisposed individuals, environmental culprits in developed countries are thought to negatively shape the intestinal microbiome’s composition into a less tolerant and more proinflammatory state, the authors noted.
According to the “hygiene hypothesis,” the oversanitization of life in the developed world is partly to blame. “A cleaner environment at home, part of the hygiene hypothesis, has been postulated as a theory to help explain the rise of autoimmune diseases in the 21st century and may play an important part in explaining our study findings,” the authors wrote.
Population-based studies have also pointed to antibiotics, nonsteroidal anti-inflammatory drugs, smoking, cesarean delivery, lack of breastfeeding, and nonexposure to farm animals as other risk factors for IBD.
Study Details
To compare the effect of environmental vs genetic risk factors, the questionnaire-based study surveyed 2952 IBD patients from a tertiary care referral center — 58.9% with CD, 45.83% of Hispanic background, and 53.18% of non-Hispanic White (NHW) ethnicity. There were too few available Black and Asian patients to be included in the cohort. Data were collected from 2017 to 2022.
The mean age of patients was 39.71 years, and 34.14% were defined as born outside of the US mainland. Foreign-born patients were further characterized as from developed nations vs developing nations; 81.3% in this subgroup came from the latter. A detailed questionnaire probed 13 potential environmental factors from type of birth to domestic living conditions, medications, and smoking across several different age groups. Blood was drawn to genotype participants and to create a genetic risk score.
Early plastic water bottle use — which has been linked to inflammatory microplastics in the intestines — and residing in homes with more than one bathroom (and presumably less exposure to infections) were also associated with younger age at diagnosis. Susceptibility to environmental exposures was similar in Hispanic and NHW patients.
“It was interesting to find an association between reported plastic water bottle use and younger age of IBD diagnosis,” said Dr. Damas. “Because this is a self-reported intake, we need more studies to confirm this. However, this finding falls in line with other recent studies showing a potential association between microplastics and disease states, including IBD. The next step is to measure for traces of environmental contaminants in human samples of patients with IBD.”
Unlike previous studies, this analysis did not find parasitic infections, pets, and antibiotics to be associated with age of IBD diagnosis.
“This is an interesting and important study,” commented Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, who was not involved in the study. “There are few environmental risk factor studies looking at non-White populations and to that end, this is a very large and well-done analysis looking at environmental factors among Hispanic patients with IBD.”
He added that, while most studies have just compared factors between cases and controls, “this is an interesting examination of the impact of such factors on age of onset.”
Dr. Ananthakrishnan stressed, however, that further work is needed to expand on these findings.” The addition of a control group would help determine how these factors actually modify disease risk. It is also intriguing that environmental factors more strongly predict age of onset than genetic risk. That only highlights the fact that IBD is in large part an environmentally influenced disease, suggesting there is exciting opportunity for environmental modification to address disease onset.”
Offering another outsider’s perspective, Manasi Agrawal, MD, MS, an assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York City and not a participant in the study, agreed that the findings highlight the contribution of early life and childhood environmental factors to IBD risk relative to genetic variants. “The relative importance of the environment compared to genetic risk toward IBD, timing of exposure, and impact on age at IBD diagnosis is a novel and important finding. These data will help contextualize how we communicate disease risk and potential prevention approaches.”
She added that future research should measure various exposures, such as pollutants in preclinical biological samples. “Mechanistic data on their downstream effects are needed to understand IBD pathogenesis and develop prevention efforts.”
According to the authors, theirs is the first study of its kind to examine the contribution of cumulative environmental factors, age-dependent exposures, and genetic predisposition to age of IBD diagnosis in a diverse IBD cohort.
The authors listed no specific funding for this study and had no conflicts of interest to declare. Dr. Ananthakrishnan and Dr. Agrawal had no relevant competing interests.
A version of this article appeared on Medscape.com.
a large study of IBD patients reported.
Published in Clinical Gastroenterology and Hepatology , the study found that environment influences the onset of both ulcerative colitis (UC) and Crohn’s disease (CD), and exposures typical in Western society lower the age of diagnosis. These factors include birth in a developed nation, delivery by C-section, and more bathrooms in the home, according to Oriana M. Damas, MD, MSCTI, an associate professor of clinical medicine at the University of Miami Miller School of Medicine in Florida and colleagues.
Environmental factors explained 21% of the variance in age of CD diagnosis and 39% of the variance in age of UC diagnosis. In models incorporating both genetic and environmental risk scores, the environment was the only significant factor associated with younger age of IBD diagnosis in all groups.
Several epidemiologic studies have examined environmental culprits in IBD, and others have examined genetic risk factors, Dr. Damas said in an interview. “But we had not seen any studies that examined the influence of both [of] these on age of IBD development.” Her group’s working hypothesis that environment would have a greater effect than genetics was borne out.
“Additionally, very few studies have examined the contribution of genetics or environmental factors in Hispanic individuals, and our study examined the contribution of these factors in this understudied population,” she added.
According to Dr. Damas, the findings’ most immediate clinical relevance is for counseling people with a family history of IBD. “I think it’s important for concerned patients to know that IBD is not solely genetic and that several environmental factors can shape disease risk to a greater extent than genetic predisposition,” she said
Westernization is increasingly considered a contributor to the global increase in IBD, which has been diagnosed in an estimated 2.39 million Americans . In genetically predisposed individuals, environmental culprits in developed countries are thought to negatively shape the intestinal microbiome’s composition into a less tolerant and more proinflammatory state, the authors noted.
According to the “hygiene hypothesis,” the oversanitization of life in the developed world is partly to blame. “A cleaner environment at home, part of the hygiene hypothesis, has been postulated as a theory to help explain the rise of autoimmune diseases in the 21st century and may play an important part in explaining our study findings,” the authors wrote.
Population-based studies have also pointed to antibiotics, nonsteroidal anti-inflammatory drugs, smoking, cesarean delivery, lack of breastfeeding, and nonexposure to farm animals as other risk factors for IBD.
Study Details
To compare the effect of environmental vs genetic risk factors, the questionnaire-based study surveyed 2952 IBD patients from a tertiary care referral center — 58.9% with CD, 45.83% of Hispanic background, and 53.18% of non-Hispanic White (NHW) ethnicity. There were too few available Black and Asian patients to be included in the cohort. Data were collected from 2017 to 2022.
The mean age of patients was 39.71 years, and 34.14% were defined as born outside of the US mainland. Foreign-born patients were further characterized as from developed nations vs developing nations; 81.3% in this subgroup came from the latter. A detailed questionnaire probed 13 potential environmental factors from type of birth to domestic living conditions, medications, and smoking across several different age groups. Blood was drawn to genotype participants and to create a genetic risk score.
Early plastic water bottle use — which has been linked to inflammatory microplastics in the intestines — and residing in homes with more than one bathroom (and presumably less exposure to infections) were also associated with younger age at diagnosis. Susceptibility to environmental exposures was similar in Hispanic and NHW patients.
“It was interesting to find an association between reported plastic water bottle use and younger age of IBD diagnosis,” said Dr. Damas. “Because this is a self-reported intake, we need more studies to confirm this. However, this finding falls in line with other recent studies showing a potential association between microplastics and disease states, including IBD. The next step is to measure for traces of environmental contaminants in human samples of patients with IBD.”
Unlike previous studies, this analysis did not find parasitic infections, pets, and antibiotics to be associated with age of IBD diagnosis.
“This is an interesting and important study,” commented Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, who was not involved in the study. “There are few environmental risk factor studies looking at non-White populations and to that end, this is a very large and well-done analysis looking at environmental factors among Hispanic patients with IBD.”
He added that, while most studies have just compared factors between cases and controls, “this is an interesting examination of the impact of such factors on age of onset.”
Dr. Ananthakrishnan stressed, however, that further work is needed to expand on these findings.” The addition of a control group would help determine how these factors actually modify disease risk. It is also intriguing that environmental factors more strongly predict age of onset than genetic risk. That only highlights the fact that IBD is in large part an environmentally influenced disease, suggesting there is exciting opportunity for environmental modification to address disease onset.”
Offering another outsider’s perspective, Manasi Agrawal, MD, MS, an assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York City and not a participant in the study, agreed that the findings highlight the contribution of early life and childhood environmental factors to IBD risk relative to genetic variants. “The relative importance of the environment compared to genetic risk toward IBD, timing of exposure, and impact on age at IBD diagnosis is a novel and important finding. These data will help contextualize how we communicate disease risk and potential prevention approaches.”
She added that future research should measure various exposures, such as pollutants in preclinical biological samples. “Mechanistic data on their downstream effects are needed to understand IBD pathogenesis and develop prevention efforts.”
According to the authors, theirs is the first study of its kind to examine the contribution of cumulative environmental factors, age-dependent exposures, and genetic predisposition to age of IBD diagnosis in a diverse IBD cohort.
The authors listed no specific funding for this study and had no conflicts of interest to declare. Dr. Ananthakrishnan and Dr. Agrawal had no relevant competing interests.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Family Size, Dog Ownership Linked With Reduced Risk of Crohn’s
, according to investigators.
Those who live with a pet bird may be more likely to develop CD, although few participants in the study lived with birds, requiring a cautious interpretation of this latter finding, lead author Mingyue Xue, PhD, of Mount Sinai Hospital, Toronto, Ontario, Canada, and colleagues reported.
“Environmental factors, such as smoking, large families, urban environments, and exposure to pets, have been shown to be associated with the risk of CD development,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, most of these studies were based on a retrospective study design, which makes it challenging to understand when and how environmental factors trigger the biological changes that lead to disease.”
The present study prospectively followed 4289 asymptomatic first-degree relatives (FDRs) of patients with CD. Environmental factors were identified via regression models that also considered biological factors, including gut inflammation via fecal calprotectin (FCP) levels, altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), and fecal microbiome composition through 16S rRNA sequencing.
After a median follow-up period of 5.62 years, 86 FDRs (1.9%) developed CD.
Living in a household of at least three people in the first year of life was associated with a 57% reduced risk of CD development (hazard ratio [HR], 0.43; P = .019). Similarly, living with a pet dog between the ages of 5 and 15 also demonstrated a protective effect, dropping risk of CD by 39% (HR, 0.61; P = .025).
“Our analysis revealed a protective trend of living with dogs that transcends the age of exposure, suggesting that dog ownership could confer health benefits in reducing the risk of CD,” the investigators wrote. “Our study also found that living in a large family during the first year of life is significantly associated with the future onset of CD, aligning with prior research that indicates that a larger family size in the first year of life can reduce the risk of developing IBD.”
In contrast, the study identified bird ownership at time of recruitment as a risk factor for CD, increasing risk almost three-fold (HR, 2.84; P = .005). The investigators urged a careful interpretation of this latter finding, however, as relatively few FDRs lived with birds.
“[A]lthough our sample size can be considered large, some environmental variables were uncommon, such as the participants having birds as pets, and would greatly benefit from replication of our findings in other cohorts,” Dr. Xue and colleagues noted.
They suggested several possible ways in which the above environmental factors may impact CD risk, including effects on subclinical inflammation, microbiome composition, and gut permeability.
“Understanding the relationship between CD-related environmental factors and these predisease biomarkers may shed light on the underlying mechanisms by which environmental factors impact host health and ultimately lead to CD onset,” the investigators concluded.
The study was supported by Crohn’s and Colitis Canada, Canadian Institutes of Health Research, the Helmsley Charitable Trust, and others. The investigators disclosed no conflicts of interest.
, according to investigators.
Those who live with a pet bird may be more likely to develop CD, although few participants in the study lived with birds, requiring a cautious interpretation of this latter finding, lead author Mingyue Xue, PhD, of Mount Sinai Hospital, Toronto, Ontario, Canada, and colleagues reported.
“Environmental factors, such as smoking, large families, urban environments, and exposure to pets, have been shown to be associated with the risk of CD development,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, most of these studies were based on a retrospective study design, which makes it challenging to understand when and how environmental factors trigger the biological changes that lead to disease.”
The present study prospectively followed 4289 asymptomatic first-degree relatives (FDRs) of patients with CD. Environmental factors were identified via regression models that also considered biological factors, including gut inflammation via fecal calprotectin (FCP) levels, altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), and fecal microbiome composition through 16S rRNA sequencing.
After a median follow-up period of 5.62 years, 86 FDRs (1.9%) developed CD.
Living in a household of at least three people in the first year of life was associated with a 57% reduced risk of CD development (hazard ratio [HR], 0.43; P = .019). Similarly, living with a pet dog between the ages of 5 and 15 also demonstrated a protective effect, dropping risk of CD by 39% (HR, 0.61; P = .025).
“Our analysis revealed a protective trend of living with dogs that transcends the age of exposure, suggesting that dog ownership could confer health benefits in reducing the risk of CD,” the investigators wrote. “Our study also found that living in a large family during the first year of life is significantly associated with the future onset of CD, aligning with prior research that indicates that a larger family size in the first year of life can reduce the risk of developing IBD.”
In contrast, the study identified bird ownership at time of recruitment as a risk factor for CD, increasing risk almost three-fold (HR, 2.84; P = .005). The investigators urged a careful interpretation of this latter finding, however, as relatively few FDRs lived with birds.
“[A]lthough our sample size can be considered large, some environmental variables were uncommon, such as the participants having birds as pets, and would greatly benefit from replication of our findings in other cohorts,” Dr. Xue and colleagues noted.
They suggested several possible ways in which the above environmental factors may impact CD risk, including effects on subclinical inflammation, microbiome composition, and gut permeability.
“Understanding the relationship between CD-related environmental factors and these predisease biomarkers may shed light on the underlying mechanisms by which environmental factors impact host health and ultimately lead to CD onset,” the investigators concluded.
The study was supported by Crohn’s and Colitis Canada, Canadian Institutes of Health Research, the Helmsley Charitable Trust, and others. The investigators disclosed no conflicts of interest.
, according to investigators.
Those who live with a pet bird may be more likely to develop CD, although few participants in the study lived with birds, requiring a cautious interpretation of this latter finding, lead author Mingyue Xue, PhD, of Mount Sinai Hospital, Toronto, Ontario, Canada, and colleagues reported.
“Environmental factors, such as smoking, large families, urban environments, and exposure to pets, have been shown to be associated with the risk of CD development,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, most of these studies were based on a retrospective study design, which makes it challenging to understand when and how environmental factors trigger the biological changes that lead to disease.”
The present study prospectively followed 4289 asymptomatic first-degree relatives (FDRs) of patients with CD. Environmental factors were identified via regression models that also considered biological factors, including gut inflammation via fecal calprotectin (FCP) levels, altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), and fecal microbiome composition through 16S rRNA sequencing.
After a median follow-up period of 5.62 years, 86 FDRs (1.9%) developed CD.
Living in a household of at least three people in the first year of life was associated with a 57% reduced risk of CD development (hazard ratio [HR], 0.43; P = .019). Similarly, living with a pet dog between the ages of 5 and 15 also demonstrated a protective effect, dropping risk of CD by 39% (HR, 0.61; P = .025).
“Our analysis revealed a protective trend of living with dogs that transcends the age of exposure, suggesting that dog ownership could confer health benefits in reducing the risk of CD,” the investigators wrote. “Our study also found that living in a large family during the first year of life is significantly associated with the future onset of CD, aligning with prior research that indicates that a larger family size in the first year of life can reduce the risk of developing IBD.”
In contrast, the study identified bird ownership at time of recruitment as a risk factor for CD, increasing risk almost three-fold (HR, 2.84; P = .005). The investigators urged a careful interpretation of this latter finding, however, as relatively few FDRs lived with birds.
“[A]lthough our sample size can be considered large, some environmental variables were uncommon, such as the participants having birds as pets, and would greatly benefit from replication of our findings in other cohorts,” Dr. Xue and colleagues noted.
They suggested several possible ways in which the above environmental factors may impact CD risk, including effects on subclinical inflammation, microbiome composition, and gut permeability.
“Understanding the relationship between CD-related environmental factors and these predisease biomarkers may shed light on the underlying mechanisms by which environmental factors impact host health and ultimately lead to CD onset,” the investigators concluded.
The study was supported by Crohn’s and Colitis Canada, Canadian Institutes of Health Research, the Helmsley Charitable Trust, and others. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Stool-Based Methylation Test May Improve CRC Screening
based on a prospective, real-world study.
These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.
“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.
The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.
After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.
“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.
based on a prospective, real-world study.
These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.
“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.
The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.
After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.
“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.
based on a prospective, real-world study.
These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.
“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.
The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.
After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.
“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.
FROM GASTROENTEROLOGY
Snare Tip Soft Coagulation Leaves Clean Margins After Resection
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
according to a recent study.
Since STSC was faster to apply than APC and results in lower cost and plastic waste (because of APC requiring an additional catheter), STSC was the preferred option.
“The reduction in recurrence rate with thermal margin treatment is arguably the most important development in endoscopic mucosal resection in the past 2 decades,” said lead author Douglas Rex, MD, AGAF, a distinguished professor emeritus at the Indiana University School of Medicine and director of endoscopy at Indiana University Hospitals, both in Indianapolis.
“Margin thermal therapy with STSC should now be standard treatment after piecemeal EMR in the colorectum,” he said. “Before applying STSC, the endoscopist must ensure that the entire lesion is resected down to the submucosa. Then STSC should be aggressively applied to 100% of the margin.”
The study was published in Clinical Gastroenterology and Hepatology .
Comparing Treatments
Dr. Rex and colleagues performed a randomized three-arm trial in nine U.S. centers, comparing STSC with APC and no margin treatment in patients undergoing colorectal EMR of nonpedunculated lesions of 15 mm or greater.
All lesions underwent conventional injection and snare resection EMR using electrocautery, but the endoscopist chose the injection fluid and snare type and size. Areas with residual polyp that weren’t removable by snare resection because of flat shape or fibrosis were removed by hot or cold avulsion. After that, patients were randomized to one of the three arms.
Patients were scheduled for a follow-up appointment six months after the initial EMR. Any visible recurrence was resected using methods at the discretion of the endoscopist, and if no visible recurrence was present, EMR site biopsies were recommended.
Among 384 patients with 414 lesions, 308 patients with 328 lesions completed at least one follow-up appointment. The median interval to the first follow-up was 6.4 months, ranging from 2 to 37 months. The primary endpoint was the presence of recurrent or residual polyp at first follow-up.
The median polyp size was 25 mm, and 65 of the 414 polyps (15.7%) were 15-19 mm in size. Overall, 14.8% of lesions were resected en bloc, with no difference between the study arms.
The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% among control subjects with no margin treatment.
The odds of having a residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (odds ratio [OR] of 0.182 and 0.341, or P = .001 and P = .01, respectively). There wasn’t a significant difference in the odds of recurrence between STSC and APC (OR, 1.874).
In 259 lesions in 248 patients that were 20 mm or greater, the recurrence rates at first follow-up were 5.9% for STSC, 10.1% for APC, and 25.9% for the control group. In these lesions, STSC and APC remained associated with a lower risk of recurrence versus the control (OR, 0.18 and 0.323, respectively). The difference in recurrence rates between STSC and APC wasn’t significant.
Even still, STSC took less time to apply than APC, with a median time of 3.35 minutes vs 4.08 minutes.
The rates of adverse events were low, with no difference between the three arms. There were no immediate or delayed perforations in any arm, and the overall occurrence of delayed bleeding was low at 3.6%.
“I think STSC won the trial because it was numerically (though not statistically) superior to APC, was faster to apply, and using STSC results in lower cost and less plastic compared to APC,” Dr. Rex said.
Additional Considerations
Based on charges at the nine U.S. centers and a survey of two manufacturers, APC catheters typically cost $175-$275 each, the study authors wrote, noting that APC results in increased cost, plastic waste because of the catheter, and carbon emissions associated with its manufacture.
“What we’re seeing — now over several trials — is STSC appears to be the most effective method of treating the edges, and it’s inexpensive because it uses the same device used for snare resection, so there’s no incremental cost for the device,” said Michael Wallace, MD, professor of medicine and director of the digestive diseases research program at Mayo Clinic, Jacksonville, Florida.
Dr. Wallace, who wasn’t involved with this study, has researched thermal ablation after EMR, including both the margins and the base.
“The single most important message now is that patients shouldn’t be getting surgical resections for endoscopically treatable polyps,” he said. “We see many patients who are told they need to get surgery, but overwhelmingly, the data shows we can remove polyps without surgery.”
Dr. Rex and several authors declared fees and grants from numerous companies outside of this study. Dr. Wallace reported no relevant disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Late ERCP After Cholecystectomy Linked with Worse Outcomes
, according to investigators.
These findings suggest a need for more careful patient selection with ERCP, and greater reliance upon noninvasive imaging prior to considering the procedure, reported lead author Nikhil R. Thiruvengadam, MD, of Loma Linda University Health, Loma Linda, California, and colleagues.
“It is assumed that cholecystectomy is a definitive procedure for symptomatic gallstone disease in patients without concomitant choledocholithiasis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is because the development of primary choledocholithiasis is rare. Despite this, many patients have persistent or new gastrointestinal symptoms post cholecystectomy.”
Symptoms such as a dilated bile duct or abnormal liver function tests may suggest choledocholithiasis or sphincter of Oddi disorders (SOD), they noted, but recent data supporting ERCP for SOD show no significant benefit for patients with normal-sized ducts.
“Guidelines advocate for confirming the presence of choledocholithiasis using magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) given the substantial risks associated with ERCP,” Dr. Thiruvengadam and colleagues wrote.
Real-world implementation of this and associated strategies, however, remain unclear, prompting the present study.
The dataset, drawn from the Optum Clinformatics Data Mart, included 583,712 adults who had undergone cholecystectomy from 2004 to 2019, focusing on 4274 individuals who had their first ERCP more than one year post surgery. The investigators assessed the incidence, characteristics, and outcomes of these late ERCP procedures, exploring their association with patient comorbidities and the use of biliary imaging techniques such as MRCP and EUS.
From 2004 to 2021, use of noninvasive biliary imaging approximately doubled from 35.9% to 65.5% (P < .001). Yet incidence of first-time ERCP more than 1 year after cholecystectomy increased much more — by eightfold — from 0.5 to 4.2 per 1000 person-years (P < .001). Less than half (44%) of these late ERCP procedures involved gallstone removal.
Patients undergoing late ERCP were more likely to have higher baseline comorbidities, including disorders of gut-brain interaction (DGBI) and metabolic dysfunction-associated steatotic liver disease. They were also more likely to be taking an antispasmodic, anxiolytic, or chronic opioid medication.
“Late ERCP is more common and associated with worse outcomes, presumably because of higher baseline comorbidities that overlap with DGBI and mimickers of choledocholithiasis,” the investigators noted. “These highly symptomatic individuals are more likely to undergo noninvasive biliary imaging, which seems to be prompting more late ERCP.”
In turn, late ERCP is incurring more adverse events, including post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%).
“Given the known risks of ERCP, especially in this context, there remains a need to be more restrictive with offering ERCP in this setting,” Dr. Thiruvengadam and colleagues concluded. “ERCP should be used sparingly for patients who do not have confirmed choledocholithiasis until future studies ... can define which patients with a remote history of cholecystectomy respond to ERCP interventions.”
The investigators disclosed relationships with Olympus, Medtronic, ACI, and others.
, according to investigators.
These findings suggest a need for more careful patient selection with ERCP, and greater reliance upon noninvasive imaging prior to considering the procedure, reported lead author Nikhil R. Thiruvengadam, MD, of Loma Linda University Health, Loma Linda, California, and colleagues.
“It is assumed that cholecystectomy is a definitive procedure for symptomatic gallstone disease in patients without concomitant choledocholithiasis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is because the development of primary choledocholithiasis is rare. Despite this, many patients have persistent or new gastrointestinal symptoms post cholecystectomy.”
Symptoms such as a dilated bile duct or abnormal liver function tests may suggest choledocholithiasis or sphincter of Oddi disorders (SOD), they noted, but recent data supporting ERCP for SOD show no significant benefit for patients with normal-sized ducts.
“Guidelines advocate for confirming the presence of choledocholithiasis using magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) given the substantial risks associated with ERCP,” Dr. Thiruvengadam and colleagues wrote.
Real-world implementation of this and associated strategies, however, remain unclear, prompting the present study.
The dataset, drawn from the Optum Clinformatics Data Mart, included 583,712 adults who had undergone cholecystectomy from 2004 to 2019, focusing on 4274 individuals who had their first ERCP more than one year post surgery. The investigators assessed the incidence, characteristics, and outcomes of these late ERCP procedures, exploring their association with patient comorbidities and the use of biliary imaging techniques such as MRCP and EUS.
From 2004 to 2021, use of noninvasive biliary imaging approximately doubled from 35.9% to 65.5% (P < .001). Yet incidence of first-time ERCP more than 1 year after cholecystectomy increased much more — by eightfold — from 0.5 to 4.2 per 1000 person-years (P < .001). Less than half (44%) of these late ERCP procedures involved gallstone removal.
Patients undergoing late ERCP were more likely to have higher baseline comorbidities, including disorders of gut-brain interaction (DGBI) and metabolic dysfunction-associated steatotic liver disease. They were also more likely to be taking an antispasmodic, anxiolytic, or chronic opioid medication.
“Late ERCP is more common and associated with worse outcomes, presumably because of higher baseline comorbidities that overlap with DGBI and mimickers of choledocholithiasis,” the investigators noted. “These highly symptomatic individuals are more likely to undergo noninvasive biliary imaging, which seems to be prompting more late ERCP.”
In turn, late ERCP is incurring more adverse events, including post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%).
“Given the known risks of ERCP, especially in this context, there remains a need to be more restrictive with offering ERCP in this setting,” Dr. Thiruvengadam and colleagues concluded. “ERCP should be used sparingly for patients who do not have confirmed choledocholithiasis until future studies ... can define which patients with a remote history of cholecystectomy respond to ERCP interventions.”
The investigators disclosed relationships with Olympus, Medtronic, ACI, and others.
, according to investigators.
These findings suggest a need for more careful patient selection with ERCP, and greater reliance upon noninvasive imaging prior to considering the procedure, reported lead author Nikhil R. Thiruvengadam, MD, of Loma Linda University Health, Loma Linda, California, and colleagues.
“It is assumed that cholecystectomy is a definitive procedure for symptomatic gallstone disease in patients without concomitant choledocholithiasis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is because the development of primary choledocholithiasis is rare. Despite this, many patients have persistent or new gastrointestinal symptoms post cholecystectomy.”
Symptoms such as a dilated bile duct or abnormal liver function tests may suggest choledocholithiasis or sphincter of Oddi disorders (SOD), they noted, but recent data supporting ERCP for SOD show no significant benefit for patients with normal-sized ducts.
“Guidelines advocate for confirming the presence of choledocholithiasis using magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) given the substantial risks associated with ERCP,” Dr. Thiruvengadam and colleagues wrote.
Real-world implementation of this and associated strategies, however, remain unclear, prompting the present study.
The dataset, drawn from the Optum Clinformatics Data Mart, included 583,712 adults who had undergone cholecystectomy from 2004 to 2019, focusing on 4274 individuals who had their first ERCP more than one year post surgery. The investigators assessed the incidence, characteristics, and outcomes of these late ERCP procedures, exploring their association with patient comorbidities and the use of biliary imaging techniques such as MRCP and EUS.
From 2004 to 2021, use of noninvasive biliary imaging approximately doubled from 35.9% to 65.5% (P < .001). Yet incidence of first-time ERCP more than 1 year after cholecystectomy increased much more — by eightfold — from 0.5 to 4.2 per 1000 person-years (P < .001). Less than half (44%) of these late ERCP procedures involved gallstone removal.
Patients undergoing late ERCP were more likely to have higher baseline comorbidities, including disorders of gut-brain interaction (DGBI) and metabolic dysfunction-associated steatotic liver disease. They were also more likely to be taking an antispasmodic, anxiolytic, or chronic opioid medication.
“Late ERCP is more common and associated with worse outcomes, presumably because of higher baseline comorbidities that overlap with DGBI and mimickers of choledocholithiasis,” the investigators noted. “These highly symptomatic individuals are more likely to undergo noninvasive biliary imaging, which seems to be prompting more late ERCP.”
In turn, late ERCP is incurring more adverse events, including post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%).
“Given the known risks of ERCP, especially in this context, there remains a need to be more restrictive with offering ERCP in this setting,” Dr. Thiruvengadam and colleagues concluded. “ERCP should be used sparingly for patients who do not have confirmed choledocholithiasis until future studies ... can define which patients with a remote history of cholecystectomy respond to ERCP interventions.”
The investigators disclosed relationships with Olympus, Medtronic, ACI, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Issues Guidance on Identifying, Treating Cyclic Vomiting Syndrome
, according to a new clinical practice update from the American Gastroenterological Association.
CVS affects up to 2% of U.S. adults and is more common in women, young adults, and those with a personal or family history of migraine headaches. However, most patients don’t receive a diagnosis or often experience years of delay in receiving effective treatment.
“A diagnosis is a powerful tool. Not only does it help patients make sense of debilitating symptoms, but it allows healthcare providers to create an effective treatment plan,” said author David J. Levinthal, MD, AGAF, director of the Neurogastroenterology and Motility Center at the University of Pittsburgh Medical Center.
“Our goal with this clinical practice update is to increase awareness of cyclic vomiting syndrome to reduce the diagnostic delay and increase patients’ access to treatment,” he said. “We hope to reach primary care, ER, and urgent care providers who are on the frontlines interacting with CVS patients seeking care, especially during an attack.”
The update was published online in Gastroenterology.
Understanding Cyclic Vomiting Syndrome
CVS is a chronic disorder of gut-brain interaction (DGBI), which is characterized by acute episodes of nausea and vomiting, separated by time without symptoms. Patients can usually identify a pattern of symptoms that show up during and between episodes.
CVS can vary, ranging from mild — with less than four episodes per year and lasting less than 2 days — to moderate-severe — with more than four episodes per year, lasting more than 2 days, and requiring at least one emergency department visit or hospitalization.
The disorder has four distinct phases — inter-episodic, prodromal, emetic, and recovery — that align with distinct treatment and management strategies. Between episodes, patients typically don’t experience repetitive vomiting but may experience symptoms such as mild nausea, indigestion, and occasional vomiting. Although CVS episodes can happen at any time, most tend to occur in the early morning.
For diagnosis, clinicians should consider CVS in adults presenting with episodic bouts of repetitive vomiting, following criteria established by the Rome Foundation. Rome IV criteria include acute-onset vomiting lasting less than 7 days, at least three discrete episodes in a year with two in the previous 6 months, and an absence of vomiting between episodes separated by at least 1 week of baseline health.
About 65% of patients with CVS experience prodromal symptoms, which last for about an hour before the onset of vomiting and may include panic, a sense of doom, and an inability to communicate effectively. During prodromal or emetic phases, patients have also reported fatigue, brain fog, restlessness, anxiety, headache, bowel urgency, abdominal pain, flushing, or shakiness.
As with migraines, CVS episodes may often be triggered by psychological and physiological factors, particularly stress. Episodes can stem from both negative stress, such as a death or relationship conflicts, as well as positive stress, such as birthdays and vacations. Other triggers include sleep deprivation, hormonal fluctuations linked to the menstrual cycle, travel, motion sickness, or acute infections.
Adult CVS is associated with several conditions, particularly mood disorders, including anxiety, depression, and panic disorder. Patients may also experience migraines, seizure disorders, or autonomic imbalances, such as postural orthostatic tachycardia syndrome, which may indicate pathophysiological mechanisms and routes for management.
The American Neurogastroenterology and Motility Society recommends testing to rule out similar or overlapping conditions, such as Addison’s disease, hypothyroidism, and hepatic porphyria. Diagnostic workup should include blood work, urinalysis, and one-time esophagogastroduodenoscopy or upper gastrointestinal imaging. Repeated imaging and gastric emptying scans should be avoided.
Providing Treatment and Prevention
For treatment, knowing the CVS phase is “essential,” the authors wrote. For instance, during the prodromal phase, abortive therapies can halt the transition to the emetic phase, and earlier intervention is associated with a higher probability of stopping an episode. The authors recommend intranasal sumatriptan, ondansetron, antihistamines, and sedatives.
During the emetic phase, supportive therapy can help terminate the episode. This may include continuing the abortive regimen and going to the emergency department for hydration and antiemetic medications. Patients may also find relief in a quiet, darker room in the emergency department, along with IV benzodiazepines, with the goal of inducing sedation.
During the recovery phase, patients should rest and focus on rehydration and nutrition to return to the well phase.
During the well or inter-episodic phase, patients can follow lifestyle measures to identify and avoid triggers, such as taking prophylactic medication (tricyclic antidepressants, anticonvulsants, and neurokinin-1 receptor antagonists such as aprepitant), reducing stress, and implementing a good sleep routine.
As part of patient education, clinicians can discuss the four phases and rehearse the actions to take to prevent or stop an episode.
“CVS has a significant impact on patients, families, and the healthcare system. The unpredictable and disruptive nature of episodes can result in reduced health-related quality of life, job loss precipitated by work absenteeism, and even divorce,” said Rosita Frazier, MD, a gastroenterologist at Mayo Clinic Arizona in Scottsdale who specializes in DGBI and CVS. Dr. Frazier, who wasn’t involved with the clinical practice update, has previously written about CVS diagnosis and management.
Patients with CVS often report negative interactions with physicians, particularly in the emergency department, where they may request specific treatments based on past experiences but are labeled as “drug seeking” and denied standard medical treatment, she said.
“Providing an individualized care plan for all patients could potentially address this problem and improve the physician-patient interaction,” she said. “Educational efforts to raise awareness among the medical community and increase both patient and provider engagement can optimize outcomes and are needed to address this critical problem.”
The authors received no specific funding for this update. Dr. Levinthal is a consultant for Takeda Pharmaceuticals and Mahana. Dr. Frazier reported no relevant financial disclosures.
, according to a new clinical practice update from the American Gastroenterological Association.
CVS affects up to 2% of U.S. adults and is more common in women, young adults, and those with a personal or family history of migraine headaches. However, most patients don’t receive a diagnosis or often experience years of delay in receiving effective treatment.
“A diagnosis is a powerful tool. Not only does it help patients make sense of debilitating symptoms, but it allows healthcare providers to create an effective treatment plan,” said author David J. Levinthal, MD, AGAF, director of the Neurogastroenterology and Motility Center at the University of Pittsburgh Medical Center.
“Our goal with this clinical practice update is to increase awareness of cyclic vomiting syndrome to reduce the diagnostic delay and increase patients’ access to treatment,” he said. “We hope to reach primary care, ER, and urgent care providers who are on the frontlines interacting with CVS patients seeking care, especially during an attack.”
The update was published online in Gastroenterology.
Understanding Cyclic Vomiting Syndrome
CVS is a chronic disorder of gut-brain interaction (DGBI), which is characterized by acute episodes of nausea and vomiting, separated by time without symptoms. Patients can usually identify a pattern of symptoms that show up during and between episodes.
CVS can vary, ranging from mild — with less than four episodes per year and lasting less than 2 days — to moderate-severe — with more than four episodes per year, lasting more than 2 days, and requiring at least one emergency department visit or hospitalization.
The disorder has four distinct phases — inter-episodic, prodromal, emetic, and recovery — that align with distinct treatment and management strategies. Between episodes, patients typically don’t experience repetitive vomiting but may experience symptoms such as mild nausea, indigestion, and occasional vomiting. Although CVS episodes can happen at any time, most tend to occur in the early morning.
For diagnosis, clinicians should consider CVS in adults presenting with episodic bouts of repetitive vomiting, following criteria established by the Rome Foundation. Rome IV criteria include acute-onset vomiting lasting less than 7 days, at least three discrete episodes in a year with two in the previous 6 months, and an absence of vomiting between episodes separated by at least 1 week of baseline health.
About 65% of patients with CVS experience prodromal symptoms, which last for about an hour before the onset of vomiting and may include panic, a sense of doom, and an inability to communicate effectively. During prodromal or emetic phases, patients have also reported fatigue, brain fog, restlessness, anxiety, headache, bowel urgency, abdominal pain, flushing, or shakiness.
As with migraines, CVS episodes may often be triggered by psychological and physiological factors, particularly stress. Episodes can stem from both negative stress, such as a death or relationship conflicts, as well as positive stress, such as birthdays and vacations. Other triggers include sleep deprivation, hormonal fluctuations linked to the menstrual cycle, travel, motion sickness, or acute infections.
Adult CVS is associated with several conditions, particularly mood disorders, including anxiety, depression, and panic disorder. Patients may also experience migraines, seizure disorders, or autonomic imbalances, such as postural orthostatic tachycardia syndrome, which may indicate pathophysiological mechanisms and routes for management.
The American Neurogastroenterology and Motility Society recommends testing to rule out similar or overlapping conditions, such as Addison’s disease, hypothyroidism, and hepatic porphyria. Diagnostic workup should include blood work, urinalysis, and one-time esophagogastroduodenoscopy or upper gastrointestinal imaging. Repeated imaging and gastric emptying scans should be avoided.
Providing Treatment and Prevention
For treatment, knowing the CVS phase is “essential,” the authors wrote. For instance, during the prodromal phase, abortive therapies can halt the transition to the emetic phase, and earlier intervention is associated with a higher probability of stopping an episode. The authors recommend intranasal sumatriptan, ondansetron, antihistamines, and sedatives.
During the emetic phase, supportive therapy can help terminate the episode. This may include continuing the abortive regimen and going to the emergency department for hydration and antiemetic medications. Patients may also find relief in a quiet, darker room in the emergency department, along with IV benzodiazepines, with the goal of inducing sedation.
During the recovery phase, patients should rest and focus on rehydration and nutrition to return to the well phase.
During the well or inter-episodic phase, patients can follow lifestyle measures to identify and avoid triggers, such as taking prophylactic medication (tricyclic antidepressants, anticonvulsants, and neurokinin-1 receptor antagonists such as aprepitant), reducing stress, and implementing a good sleep routine.
As part of patient education, clinicians can discuss the four phases and rehearse the actions to take to prevent or stop an episode.
“CVS has a significant impact on patients, families, and the healthcare system. The unpredictable and disruptive nature of episodes can result in reduced health-related quality of life, job loss precipitated by work absenteeism, and even divorce,” said Rosita Frazier, MD, a gastroenterologist at Mayo Clinic Arizona in Scottsdale who specializes in DGBI and CVS. Dr. Frazier, who wasn’t involved with the clinical practice update, has previously written about CVS diagnosis and management.
Patients with CVS often report negative interactions with physicians, particularly in the emergency department, where they may request specific treatments based on past experiences but are labeled as “drug seeking” and denied standard medical treatment, she said.
“Providing an individualized care plan for all patients could potentially address this problem and improve the physician-patient interaction,” she said. “Educational efforts to raise awareness among the medical community and increase both patient and provider engagement can optimize outcomes and are needed to address this critical problem.”
The authors received no specific funding for this update. Dr. Levinthal is a consultant for Takeda Pharmaceuticals and Mahana. Dr. Frazier reported no relevant financial disclosures.
, according to a new clinical practice update from the American Gastroenterological Association.
CVS affects up to 2% of U.S. adults and is more common in women, young adults, and those with a personal or family history of migraine headaches. However, most patients don’t receive a diagnosis or often experience years of delay in receiving effective treatment.
“A diagnosis is a powerful tool. Not only does it help patients make sense of debilitating symptoms, but it allows healthcare providers to create an effective treatment plan,” said author David J. Levinthal, MD, AGAF, director of the Neurogastroenterology and Motility Center at the University of Pittsburgh Medical Center.
“Our goal with this clinical practice update is to increase awareness of cyclic vomiting syndrome to reduce the diagnostic delay and increase patients’ access to treatment,” he said. “We hope to reach primary care, ER, and urgent care providers who are on the frontlines interacting with CVS patients seeking care, especially during an attack.”
The update was published online in Gastroenterology.
Understanding Cyclic Vomiting Syndrome
CVS is a chronic disorder of gut-brain interaction (DGBI), which is characterized by acute episodes of nausea and vomiting, separated by time without symptoms. Patients can usually identify a pattern of symptoms that show up during and between episodes.
CVS can vary, ranging from mild — with less than four episodes per year and lasting less than 2 days — to moderate-severe — with more than four episodes per year, lasting more than 2 days, and requiring at least one emergency department visit or hospitalization.
The disorder has four distinct phases — inter-episodic, prodromal, emetic, and recovery — that align with distinct treatment and management strategies. Between episodes, patients typically don’t experience repetitive vomiting but may experience symptoms such as mild nausea, indigestion, and occasional vomiting. Although CVS episodes can happen at any time, most tend to occur in the early morning.
For diagnosis, clinicians should consider CVS in adults presenting with episodic bouts of repetitive vomiting, following criteria established by the Rome Foundation. Rome IV criteria include acute-onset vomiting lasting less than 7 days, at least three discrete episodes in a year with two in the previous 6 months, and an absence of vomiting between episodes separated by at least 1 week of baseline health.
About 65% of patients with CVS experience prodromal symptoms, which last for about an hour before the onset of vomiting and may include panic, a sense of doom, and an inability to communicate effectively. During prodromal or emetic phases, patients have also reported fatigue, brain fog, restlessness, anxiety, headache, bowel urgency, abdominal pain, flushing, or shakiness.
As with migraines, CVS episodes may often be triggered by psychological and physiological factors, particularly stress. Episodes can stem from both negative stress, such as a death or relationship conflicts, as well as positive stress, such as birthdays and vacations. Other triggers include sleep deprivation, hormonal fluctuations linked to the menstrual cycle, travel, motion sickness, or acute infections.
Adult CVS is associated with several conditions, particularly mood disorders, including anxiety, depression, and panic disorder. Patients may also experience migraines, seizure disorders, or autonomic imbalances, such as postural orthostatic tachycardia syndrome, which may indicate pathophysiological mechanisms and routes for management.
The American Neurogastroenterology and Motility Society recommends testing to rule out similar or overlapping conditions, such as Addison’s disease, hypothyroidism, and hepatic porphyria. Diagnostic workup should include blood work, urinalysis, and one-time esophagogastroduodenoscopy or upper gastrointestinal imaging. Repeated imaging and gastric emptying scans should be avoided.
Providing Treatment and Prevention
For treatment, knowing the CVS phase is “essential,” the authors wrote. For instance, during the prodromal phase, abortive therapies can halt the transition to the emetic phase, and earlier intervention is associated with a higher probability of stopping an episode. The authors recommend intranasal sumatriptan, ondansetron, antihistamines, and sedatives.
During the emetic phase, supportive therapy can help terminate the episode. This may include continuing the abortive regimen and going to the emergency department for hydration and antiemetic medications. Patients may also find relief in a quiet, darker room in the emergency department, along with IV benzodiazepines, with the goal of inducing sedation.
During the recovery phase, patients should rest and focus on rehydration and nutrition to return to the well phase.
During the well or inter-episodic phase, patients can follow lifestyle measures to identify and avoid triggers, such as taking prophylactic medication (tricyclic antidepressants, anticonvulsants, and neurokinin-1 receptor antagonists such as aprepitant), reducing stress, and implementing a good sleep routine.
As part of patient education, clinicians can discuss the four phases and rehearse the actions to take to prevent or stop an episode.
“CVS has a significant impact on patients, families, and the healthcare system. The unpredictable and disruptive nature of episodes can result in reduced health-related quality of life, job loss precipitated by work absenteeism, and even divorce,” said Rosita Frazier, MD, a gastroenterologist at Mayo Clinic Arizona in Scottsdale who specializes in DGBI and CVS. Dr. Frazier, who wasn’t involved with the clinical practice update, has previously written about CVS diagnosis and management.
Patients with CVS often report negative interactions with physicians, particularly in the emergency department, where they may request specific treatments based on past experiences but are labeled as “drug seeking” and denied standard medical treatment, she said.
“Providing an individualized care plan for all patients could potentially address this problem and improve the physician-patient interaction,” she said. “Educational efforts to raise awareness among the medical community and increase both patient and provider engagement can optimize outcomes and are needed to address this critical problem.”
The authors received no specific funding for this update. Dr. Levinthal is a consultant for Takeda Pharmaceuticals and Mahana. Dr. Frazier reported no relevant financial disclosures.
FROM GASTROENTEROLOGY
Esophageal Cancer Risk Unchanged After Helicobacter Eradication
This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”
That study involved only 11 cases of EAC.
For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.
Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.
SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).
“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.
Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”
Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.
“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”
They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.
Understanding the demographic and biomarker risk predictors of esophageal cancer continues to be a research priority. Many esophageal cancer patients fall outside of current screening guidelines. Updated recommendations have suggested including high risk-women, driven by higher quality datasets, emerging biomarkers, and cost effective non-endoscopic screening devices.
In this article, Wiklund et al. challenge another dogma that Helicobacter pylori infection offers protection against esophageal cancer. More specifically that overtreatment of H pylori is associated with increased incidence of esophageal adenocarcinoma. Their Nordic data set identified 550 cases of esophageal cancer in the 661,987 patients treated for H pylori from 1995–2018 who were followed >5 million person-years. Interestingly, standardized incidence ratio of esophageal adenocarcinoma decreased over time.
This large dataset continues to encourage us to treat H pylori in patients at risk of progressing to gastric cancer. This parallels a growing fund of literature encouraging us to move away from the linear pathophysiologic logic that eliminating H pylori-induced gastric atrophy provokes gastroesophageal reflux disease and esophageal cancer. Instead we should factor in other parameters, including the complex interaction between the esophageal microbiome and gastric H pylori. Some postulated mechanisms include an extension of the gastric inflammatory milieu into the esophagus, and potential crosstalk with the esophageal microbiome.
Such studies underscore the need to personalize both foregut cancer screening criteria and treatment of inflammatory conditions at a patient and population level, so that we can make meaningful impacts in disease prevalence and cancer survival.
Fouad Otaki, MD, is associate professor in the Division of Gastroenterology & Hepatology at Oregon Health & Science University, Portland.
Understanding the demographic and biomarker risk predictors of esophageal cancer continues to be a research priority. Many esophageal cancer patients fall outside of current screening guidelines. Updated recommendations have suggested including high risk-women, driven by higher quality datasets, emerging biomarkers, and cost effective non-endoscopic screening devices.
In this article, Wiklund et al. challenge another dogma that Helicobacter pylori infection offers protection against esophageal cancer. More specifically that overtreatment of H pylori is associated with increased incidence of esophageal adenocarcinoma. Their Nordic data set identified 550 cases of esophageal cancer in the 661,987 patients treated for H pylori from 1995–2018 who were followed >5 million person-years. Interestingly, standardized incidence ratio of esophageal adenocarcinoma decreased over time.
This large dataset continues to encourage us to treat H pylori in patients at risk of progressing to gastric cancer. This parallels a growing fund of literature encouraging us to move away from the linear pathophysiologic logic that eliminating H pylori-induced gastric atrophy provokes gastroesophageal reflux disease and esophageal cancer. Instead we should factor in other parameters, including the complex interaction between the esophageal microbiome and gastric H pylori. Some postulated mechanisms include an extension of the gastric inflammatory milieu into the esophagus, and potential crosstalk with the esophageal microbiome.
Such studies underscore the need to personalize both foregut cancer screening criteria and treatment of inflammatory conditions at a patient and population level, so that we can make meaningful impacts in disease prevalence and cancer survival.
Fouad Otaki, MD, is associate professor in the Division of Gastroenterology & Hepatology at Oregon Health & Science University, Portland.
Understanding the demographic and biomarker risk predictors of esophageal cancer continues to be a research priority. Many esophageal cancer patients fall outside of current screening guidelines. Updated recommendations have suggested including high risk-women, driven by higher quality datasets, emerging biomarkers, and cost effective non-endoscopic screening devices.
In this article, Wiklund et al. challenge another dogma that Helicobacter pylori infection offers protection against esophageal cancer. More specifically that overtreatment of H pylori is associated with increased incidence of esophageal adenocarcinoma. Their Nordic data set identified 550 cases of esophageal cancer in the 661,987 patients treated for H pylori from 1995–2018 who were followed >5 million person-years. Interestingly, standardized incidence ratio of esophageal adenocarcinoma decreased over time.
This large dataset continues to encourage us to treat H pylori in patients at risk of progressing to gastric cancer. This parallels a growing fund of literature encouraging us to move away from the linear pathophysiologic logic that eliminating H pylori-induced gastric atrophy provokes gastroesophageal reflux disease and esophageal cancer. Instead we should factor in other parameters, including the complex interaction between the esophageal microbiome and gastric H pylori. Some postulated mechanisms include an extension of the gastric inflammatory milieu into the esophagus, and potential crosstalk with the esophageal microbiome.
Such studies underscore the need to personalize both foregut cancer screening criteria and treatment of inflammatory conditions at a patient and population level, so that we can make meaningful impacts in disease prevalence and cancer survival.
Fouad Otaki, MD, is associate professor in the Division of Gastroenterology & Hepatology at Oregon Health & Science University, Portland.
This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”
That study involved only 11 cases of EAC.
For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.
Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.
SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).
“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.
Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”
Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.
“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”
They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.
This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”
That study involved only 11 cases of EAC.
For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.
Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.
SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).
“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.
Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”
Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.
“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”
They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Eosinophilic Esophagitis Often Persists Despite Treatment
based on a recent retrospective study.
Challenging patient journeys were common across age groups, with a range of ongoing symptoms and histological abnormalities supporting high unmet need among patients with EoE, lead author Olulade Ayodele, MBBS, MPH, of Takeda Development Center Americas and colleagues reported.
“Recent studies have found that patients with EoE experience a complicated journey to diagnosis and a substantial disease burden, which requires significant healthcare resource utilization,” the investigators wrote in Gastro Hep Advances . “Reasons for this may include delays in diagnosis owing to nonspecific symptoms, adaptive behaviors, progression of silent disease, lack of adequate follow-up or referral, or suboptimal treatment after diagnosis.”Two medications are currently Food and Drug administration approved for EoE: dupilumab, a biologic for patients aged 1 year and older, and budesonide oral suspension, a topical corticosteroid for patients aged 11 years and older.
The investigators noted that “biologic therapies may not always be selected as first-line treatment, and are often associated with high costs”; however, the effects of real-world treatment decisions like these are poorly documented, prompting the present study.
The final dataset comprised 613 patients with newly diagnosed EoE treated in a rural integrated healthcare system, all of whom had at least 12 months of data before and after a predetermined index date. Individuals were stratified by age, including 182 children, 146 adolescents, 244 adults, and 41 older adults.
Signs and symptoms of EoE frequently worsened after the index date, including dysphagia (34.6% before, 49.9% after), abdominal pain (33.0% before, 48.1% after), and nausea/vomiting (20.1% before, 31.5% after).
At baseline, 80.5% of endoscopies were abnormal and 87.9% of patients had more than 15 eosinophils/high-power field. These parameters improved post index; however, 3 years later, 62.3% of patients still had abnormal endoscopic appearance and 51.2% had abnormal histologic activity.
Before and after index, the most prescribed treatments were corticosteroids (47.3% before, 87.9% after) and proton pump inhibitors (51.1% before, 96.1% after).
After index, 44.0% of patients discontinued their first-line treatment, and 13.9% experienced disease progression.
“We found that a substantial portion of patients with EoE received variable medical treatments, and did not report undergoing follow-up care, consulting with specialists, or routinely undergoing endoscopy with biopsy after diagnosis; the reasons for this are unknown, but experiences do not appear to be consistent with current guideline recommendations,” Dr. Ayodele and colleagues wrote.
They also noted substantial healthcare resource utilization; more than half of the patients visited emergency departments, and nearly one in five were admitted as inpatients.
“Our findings outline the persistent disease activity and difficult therapeutic journeys faced by patients with EoE irrespective of their age, as well as the substantial disease burden,” the investigators concluded. “These data highlight the potential unmet medical need of patients with EoE in the United States.”The study was funded by Shire Human Genetic Therapies, a member of the Takeda group of companies. The investigators disclosed additional relationships with RTI Health Solutions and Receptos/Celgene.
In a large, retrospective, real-world cohort study, investigators examined the patient journey in 613 child, adolescent, and adult patients with eosinophilic esophagitis (EoE) via healthcare claims database and electronic medical record data. As we enter into an exciting era in novel biologic therapies in EoE, the article provides comprehensive and reliable information in several critical and actionable areas with respect to EoE diagnosis and management.
The study highlights the heterogeneity of the patient experience in EoE and suggests that improvements in the reliability and precision of EoE care models will impact healthcare utilization. In particular, the findings support the need for structured and systematic mechanisms for appropriate follow-up after the index diagnosis and increased use and continued development of novel therapies.
Anand Jain, MD, is assistant professor in the Division of Digestive Diseases at Emory University School of Medicine, Atlanta, Georgia. Ravinder Mittal, MD, AGAF, is professor in the Division of Gastroenterology at the University of California, San Diego, and staff physician at the San Diego VA Hospital. They report no conflicts of interest.
In a large, retrospective, real-world cohort study, investigators examined the patient journey in 613 child, adolescent, and adult patients with eosinophilic esophagitis (EoE) via healthcare claims database and electronic medical record data. As we enter into an exciting era in novel biologic therapies in EoE, the article provides comprehensive and reliable information in several critical and actionable areas with respect to EoE diagnosis and management.
The study highlights the heterogeneity of the patient experience in EoE and suggests that improvements in the reliability and precision of EoE care models will impact healthcare utilization. In particular, the findings support the need for structured and systematic mechanisms for appropriate follow-up after the index diagnosis and increased use and continued development of novel therapies.
Anand Jain, MD, is assistant professor in the Division of Digestive Diseases at Emory University School of Medicine, Atlanta, Georgia. Ravinder Mittal, MD, AGAF, is professor in the Division of Gastroenterology at the University of California, San Diego, and staff physician at the San Diego VA Hospital. They report no conflicts of interest.
In a large, retrospective, real-world cohort study, investigators examined the patient journey in 613 child, adolescent, and adult patients with eosinophilic esophagitis (EoE) via healthcare claims database and electronic medical record data. As we enter into an exciting era in novel biologic therapies in EoE, the article provides comprehensive and reliable information in several critical and actionable areas with respect to EoE diagnosis and management.
The study highlights the heterogeneity of the patient experience in EoE and suggests that improvements in the reliability and precision of EoE care models will impact healthcare utilization. In particular, the findings support the need for structured and systematic mechanisms for appropriate follow-up after the index diagnosis and increased use and continued development of novel therapies.
Anand Jain, MD, is assistant professor in the Division of Digestive Diseases at Emory University School of Medicine, Atlanta, Georgia. Ravinder Mittal, MD, AGAF, is professor in the Division of Gastroenterology at the University of California, San Diego, and staff physician at the San Diego VA Hospital. They report no conflicts of interest.
based on a recent retrospective study.
Challenging patient journeys were common across age groups, with a range of ongoing symptoms and histological abnormalities supporting high unmet need among patients with EoE, lead author Olulade Ayodele, MBBS, MPH, of Takeda Development Center Americas and colleagues reported.
“Recent studies have found that patients with EoE experience a complicated journey to diagnosis and a substantial disease burden, which requires significant healthcare resource utilization,” the investigators wrote in Gastro Hep Advances . “Reasons for this may include delays in diagnosis owing to nonspecific symptoms, adaptive behaviors, progression of silent disease, lack of adequate follow-up or referral, or suboptimal treatment after diagnosis.”Two medications are currently Food and Drug administration approved for EoE: dupilumab, a biologic for patients aged 1 year and older, and budesonide oral suspension, a topical corticosteroid for patients aged 11 years and older.
The investigators noted that “biologic therapies may not always be selected as first-line treatment, and are often associated with high costs”; however, the effects of real-world treatment decisions like these are poorly documented, prompting the present study.
The final dataset comprised 613 patients with newly diagnosed EoE treated in a rural integrated healthcare system, all of whom had at least 12 months of data before and after a predetermined index date. Individuals were stratified by age, including 182 children, 146 adolescents, 244 adults, and 41 older adults.
Signs and symptoms of EoE frequently worsened after the index date, including dysphagia (34.6% before, 49.9% after), abdominal pain (33.0% before, 48.1% after), and nausea/vomiting (20.1% before, 31.5% after).
At baseline, 80.5% of endoscopies were abnormal and 87.9% of patients had more than 15 eosinophils/high-power field. These parameters improved post index; however, 3 years later, 62.3% of patients still had abnormal endoscopic appearance and 51.2% had abnormal histologic activity.
Before and after index, the most prescribed treatments were corticosteroids (47.3% before, 87.9% after) and proton pump inhibitors (51.1% before, 96.1% after).
After index, 44.0% of patients discontinued their first-line treatment, and 13.9% experienced disease progression.
“We found that a substantial portion of patients with EoE received variable medical treatments, and did not report undergoing follow-up care, consulting with specialists, or routinely undergoing endoscopy with biopsy after diagnosis; the reasons for this are unknown, but experiences do not appear to be consistent with current guideline recommendations,” Dr. Ayodele and colleagues wrote.
They also noted substantial healthcare resource utilization; more than half of the patients visited emergency departments, and nearly one in five were admitted as inpatients.
“Our findings outline the persistent disease activity and difficult therapeutic journeys faced by patients with EoE irrespective of their age, as well as the substantial disease burden,” the investigators concluded. “These data highlight the potential unmet medical need of patients with EoE in the United States.”The study was funded by Shire Human Genetic Therapies, a member of the Takeda group of companies. The investigators disclosed additional relationships with RTI Health Solutions and Receptos/Celgene.
based on a recent retrospective study.
Challenging patient journeys were common across age groups, with a range of ongoing symptoms and histological abnormalities supporting high unmet need among patients with EoE, lead author Olulade Ayodele, MBBS, MPH, of Takeda Development Center Americas and colleagues reported.
“Recent studies have found that patients with EoE experience a complicated journey to diagnosis and a substantial disease burden, which requires significant healthcare resource utilization,” the investigators wrote in Gastro Hep Advances . “Reasons for this may include delays in diagnosis owing to nonspecific symptoms, adaptive behaviors, progression of silent disease, lack of adequate follow-up or referral, or suboptimal treatment after diagnosis.”Two medications are currently Food and Drug administration approved for EoE: dupilumab, a biologic for patients aged 1 year and older, and budesonide oral suspension, a topical corticosteroid for patients aged 11 years and older.
The investigators noted that “biologic therapies may not always be selected as first-line treatment, and are often associated with high costs”; however, the effects of real-world treatment decisions like these are poorly documented, prompting the present study.
The final dataset comprised 613 patients with newly diagnosed EoE treated in a rural integrated healthcare system, all of whom had at least 12 months of data before and after a predetermined index date. Individuals were stratified by age, including 182 children, 146 adolescents, 244 adults, and 41 older adults.
Signs and symptoms of EoE frequently worsened after the index date, including dysphagia (34.6% before, 49.9% after), abdominal pain (33.0% before, 48.1% after), and nausea/vomiting (20.1% before, 31.5% after).
At baseline, 80.5% of endoscopies were abnormal and 87.9% of patients had more than 15 eosinophils/high-power field. These parameters improved post index; however, 3 years later, 62.3% of patients still had abnormal endoscopic appearance and 51.2% had abnormal histologic activity.
Before and after index, the most prescribed treatments were corticosteroids (47.3% before, 87.9% after) and proton pump inhibitors (51.1% before, 96.1% after).
After index, 44.0% of patients discontinued their first-line treatment, and 13.9% experienced disease progression.
“We found that a substantial portion of patients with EoE received variable medical treatments, and did not report undergoing follow-up care, consulting with specialists, or routinely undergoing endoscopy with biopsy after diagnosis; the reasons for this are unknown, but experiences do not appear to be consistent with current guideline recommendations,” Dr. Ayodele and colleagues wrote.
They also noted substantial healthcare resource utilization; more than half of the patients visited emergency departments, and nearly one in five were admitted as inpatients.
“Our findings outline the persistent disease activity and difficult therapeutic journeys faced by patients with EoE irrespective of their age, as well as the substantial disease burden,” the investigators concluded. “These data highlight the potential unmet medical need of patients with EoE in the United States.”The study was funded by Shire Human Genetic Therapies, a member of the Takeda group of companies. The investigators disclosed additional relationships with RTI Health Solutions and Receptos/Celgene.
FROM GASTRO HEP ADVANCES
FIB-4 Index Misclassifies Many Patients
, potentially impacting clinical decisions, according to investigators.
These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.
“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.
Yet the performance of the FIB-4 index in this context remains unclear.
“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”
To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.
All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).
Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.
Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.
“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”
They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.
“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”
The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.
, potentially impacting clinical decisions, according to investigators.
These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.
“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.
Yet the performance of the FIB-4 index in this context remains unclear.
“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”
To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.
All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).
Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.
Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.
“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”
They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.
“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”
The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.
, potentially impacting clinical decisions, according to investigators.
These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.
“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.
Yet the performance of the FIB-4 index in this context remains unclear.
“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”
To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.
All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).
Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.
Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.
“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”
They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.
“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”
The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Autonomous AI Outperforms Humans in Optical Diagnosis of Colorectal Polyps
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
FROM GASTROENTEROLOGY