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Mucosal exposure device boosts AI-assisted detection of adenomas

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Mon, 10/02/2023 - 10:29

Performing colonoscopy with a mucosal exposure device and artificial intelligence (AI) software increases detection of adenomas over AI-assisted colonoscopy alone, based on results of a randomized trial.

Using the mucosal exposure device increased adenoma detection rate by 12% without impacting safety or withdrawal time, suggesting that the two approaches have a synergistic effect, reported lead author Marco Spadaccini, MD, of Humanitas University, Pieve Emanuele, Italy, and colleagues.

“Recent advances in AI, deep learning, and computer vision led to implementation of computer-aided detection [CADe] of colorectal polyps,” the investigators wrote in Gastroenterology. “CADe-assisted colonoscopy already proved its efficacy by increasing adenoma detection in randomized parallel and crossover trials. However, such benefit is mostly related to the higher accuracy in spotting lesions already within the visual field, not affecting the amount of mucosa exposed by the endoscopist during the scope withdrawal. Increasing the mucosa exposure represents a complementary strategy to CADe in order to further improve detection of colorectal neoplasia.”

To test their hypothesis, the investigators conducted a randomized trial involving 1,316 subjects undergoing routine colonoscopy at six centers in Italy and Switzerland. Participants were randomized in a 1:1 ratio to undergo colonoscopy with CADe (GI Genius, Medtronic) or CADe plus a mucosal exposure device (Endocuff Vision, Olympus).

The combination approach yielded a 49.6% adenoma detection rate, compared with a 44.0% detection rate for CADe alone (relative risk, 1.12; 95% confidence interval, 1.00-1.26; P = .04). Adding the mucosal exposure device was also associated with a higher number of adenomas detected per colonoscopy. Withdrawal time and rate of unnecessary polypectomies did not differ between groups.

“The benefit of adding [the mucosal exposure device] to AI was expected due to the complementary nature of the interventions,” Dr. Spadaccini and colleagues wrote. “The benefit of [the mucosal exposure device] is limited to increase the quantity of mucosa exposed to the lens by flatting the folds and strengthening the angulations, and the benefit of AI is only in spotting a lesion that is already displayed within the field of view. Thus, we may speculate that the additional mucosal exposure was synergistic to the AI-assisted polyp recognition by AI.”

The benefits of a combination approach were not universal, however, as the mucosal exposure device did not improve detection of either serrated lesions or advanced adenomas. This result was anticipated, the investigators noted, since the miss rate for diminutive or proximal adenomas is higher than it is for larger or distal lesions, and previous research has suggested that AI-assisted and mucosal exposure techniques, when used alone, are most effective for detecting smaller, proximal lesions.

The study was funded by a European Society of Gastrointestinal Endoscopy Artificial Intelligence Award. The investigators disclosed additional relationships with Fujifilm, Medtronic, Olympus, and others.

Body

The paradigm of adenoma detection is rapidly shifting within the context of screening-related colonoscopy. If one considers the various interventions available to improve one’s adenoma detection rate (ADR), the landscape is vastly different than it was 5-10 years ago. Two established interventions with robust supporting data from randomized controlled trials (RCTs) are computer-aided detection (CADe) platforms such as GI Genius (Medtronic) and distal attachment devices such as Endocuff Vision (Olympus). This RCT by Spadaccini and colleagues tested the intuitive hypothesis that these interventions applied together boost ADR, compared with CADe alone.

University of Calgary
Dr. Nauzer Forbes
In a patient cohort that was balanced across major colonoscopy indications of primary screening, positive fecal immunochemical testing, surveillance, and diagnosis, ADR was 12% higher in patients receiving colonoscopy with Endocuff Vision and CADe, compared with CADe alone, with a corresponding significant increase in the adenoma per colonoscopy rate of 26%. Detection of advanced adenomas was not significantly different between groups. Detection of serrated lesions was also similar.

Real-world studies of CADe’s effectiveness on ADR are less impressive than efficacy data from trials. Whereas CADe platforms require a significant one-time investment, distal attachment devices represent a small fraction of single procedural costs which then incrementally add up when used over large volumes. More head-to-head studies, cost-effectiveness analyses, and real-world studies are needed to elucidate the best single and/or combination strategies for optimizing ADR. In the meantime, endoscopists should be aware of all evidence-based techniques for ADR improvement, including those that can be incorporated at little to no cost.

Nauzer Forbes, MD, MSc, FASGE, is an associate professor at the University of Calgary (Alta.), where he is the training program director for advanced/therapeutic endoscopy. He is a consultant for and has received speaker’s fees from Pentax Medical and Boston Scientific, is a consultant for AstraZeneca, and has received research funding from Pentax Medical.

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The paradigm of adenoma detection is rapidly shifting within the context of screening-related colonoscopy. If one considers the various interventions available to improve one’s adenoma detection rate (ADR), the landscape is vastly different than it was 5-10 years ago. Two established interventions with robust supporting data from randomized controlled trials (RCTs) are computer-aided detection (CADe) platforms such as GI Genius (Medtronic) and distal attachment devices such as Endocuff Vision (Olympus). This RCT by Spadaccini and colleagues tested the intuitive hypothesis that these interventions applied together boost ADR, compared with CADe alone.

University of Calgary
Dr. Nauzer Forbes
In a patient cohort that was balanced across major colonoscopy indications of primary screening, positive fecal immunochemical testing, surveillance, and diagnosis, ADR was 12% higher in patients receiving colonoscopy with Endocuff Vision and CADe, compared with CADe alone, with a corresponding significant increase in the adenoma per colonoscopy rate of 26%. Detection of advanced adenomas was not significantly different between groups. Detection of serrated lesions was also similar.

Real-world studies of CADe’s effectiveness on ADR are less impressive than efficacy data from trials. Whereas CADe platforms require a significant one-time investment, distal attachment devices represent a small fraction of single procedural costs which then incrementally add up when used over large volumes. More head-to-head studies, cost-effectiveness analyses, and real-world studies are needed to elucidate the best single and/or combination strategies for optimizing ADR. In the meantime, endoscopists should be aware of all evidence-based techniques for ADR improvement, including those that can be incorporated at little to no cost.

Nauzer Forbes, MD, MSc, FASGE, is an associate professor at the University of Calgary (Alta.), where he is the training program director for advanced/therapeutic endoscopy. He is a consultant for and has received speaker’s fees from Pentax Medical and Boston Scientific, is a consultant for AstraZeneca, and has received research funding from Pentax Medical.

Body

The paradigm of adenoma detection is rapidly shifting within the context of screening-related colonoscopy. If one considers the various interventions available to improve one’s adenoma detection rate (ADR), the landscape is vastly different than it was 5-10 years ago. Two established interventions with robust supporting data from randomized controlled trials (RCTs) are computer-aided detection (CADe) platforms such as GI Genius (Medtronic) and distal attachment devices such as Endocuff Vision (Olympus). This RCT by Spadaccini and colleagues tested the intuitive hypothesis that these interventions applied together boost ADR, compared with CADe alone.

University of Calgary
Dr. Nauzer Forbes
In a patient cohort that was balanced across major colonoscopy indications of primary screening, positive fecal immunochemical testing, surveillance, and diagnosis, ADR was 12% higher in patients receiving colonoscopy with Endocuff Vision and CADe, compared with CADe alone, with a corresponding significant increase in the adenoma per colonoscopy rate of 26%. Detection of advanced adenomas was not significantly different between groups. Detection of serrated lesions was also similar.

Real-world studies of CADe’s effectiveness on ADR are less impressive than efficacy data from trials. Whereas CADe platforms require a significant one-time investment, distal attachment devices represent a small fraction of single procedural costs which then incrementally add up when used over large volumes. More head-to-head studies, cost-effectiveness analyses, and real-world studies are needed to elucidate the best single and/or combination strategies for optimizing ADR. In the meantime, endoscopists should be aware of all evidence-based techniques for ADR improvement, including those that can be incorporated at little to no cost.

Nauzer Forbes, MD, MSc, FASGE, is an associate professor at the University of Calgary (Alta.), where he is the training program director for advanced/therapeutic endoscopy. He is a consultant for and has received speaker’s fees from Pentax Medical and Boston Scientific, is a consultant for AstraZeneca, and has received research funding from Pentax Medical.

Performing colonoscopy with a mucosal exposure device and artificial intelligence (AI) software increases detection of adenomas over AI-assisted colonoscopy alone, based on results of a randomized trial.

Using the mucosal exposure device increased adenoma detection rate by 12% without impacting safety or withdrawal time, suggesting that the two approaches have a synergistic effect, reported lead author Marco Spadaccini, MD, of Humanitas University, Pieve Emanuele, Italy, and colleagues.

“Recent advances in AI, deep learning, and computer vision led to implementation of computer-aided detection [CADe] of colorectal polyps,” the investigators wrote in Gastroenterology. “CADe-assisted colonoscopy already proved its efficacy by increasing adenoma detection in randomized parallel and crossover trials. However, such benefit is mostly related to the higher accuracy in spotting lesions already within the visual field, not affecting the amount of mucosa exposed by the endoscopist during the scope withdrawal. Increasing the mucosa exposure represents a complementary strategy to CADe in order to further improve detection of colorectal neoplasia.”

To test their hypothesis, the investigators conducted a randomized trial involving 1,316 subjects undergoing routine colonoscopy at six centers in Italy and Switzerland. Participants were randomized in a 1:1 ratio to undergo colonoscopy with CADe (GI Genius, Medtronic) or CADe plus a mucosal exposure device (Endocuff Vision, Olympus).

The combination approach yielded a 49.6% adenoma detection rate, compared with a 44.0% detection rate for CADe alone (relative risk, 1.12; 95% confidence interval, 1.00-1.26; P = .04). Adding the mucosal exposure device was also associated with a higher number of adenomas detected per colonoscopy. Withdrawal time and rate of unnecessary polypectomies did not differ between groups.

“The benefit of adding [the mucosal exposure device] to AI was expected due to the complementary nature of the interventions,” Dr. Spadaccini and colleagues wrote. “The benefit of [the mucosal exposure device] is limited to increase the quantity of mucosa exposed to the lens by flatting the folds and strengthening the angulations, and the benefit of AI is only in spotting a lesion that is already displayed within the field of view. Thus, we may speculate that the additional mucosal exposure was synergistic to the AI-assisted polyp recognition by AI.”

The benefits of a combination approach were not universal, however, as the mucosal exposure device did not improve detection of either serrated lesions or advanced adenomas. This result was anticipated, the investigators noted, since the miss rate for diminutive or proximal adenomas is higher than it is for larger or distal lesions, and previous research has suggested that AI-assisted and mucosal exposure techniques, when used alone, are most effective for detecting smaller, proximal lesions.

The study was funded by a European Society of Gastrointestinal Endoscopy Artificial Intelligence Award. The investigators disclosed additional relationships with Fujifilm, Medtronic, Olympus, and others.

Performing colonoscopy with a mucosal exposure device and artificial intelligence (AI) software increases detection of adenomas over AI-assisted colonoscopy alone, based on results of a randomized trial.

Using the mucosal exposure device increased adenoma detection rate by 12% without impacting safety or withdrawal time, suggesting that the two approaches have a synergistic effect, reported lead author Marco Spadaccini, MD, of Humanitas University, Pieve Emanuele, Italy, and colleagues.

“Recent advances in AI, deep learning, and computer vision led to implementation of computer-aided detection [CADe] of colorectal polyps,” the investigators wrote in Gastroenterology. “CADe-assisted colonoscopy already proved its efficacy by increasing adenoma detection in randomized parallel and crossover trials. However, such benefit is mostly related to the higher accuracy in spotting lesions already within the visual field, not affecting the amount of mucosa exposed by the endoscopist during the scope withdrawal. Increasing the mucosa exposure represents a complementary strategy to CADe in order to further improve detection of colorectal neoplasia.”

To test their hypothesis, the investigators conducted a randomized trial involving 1,316 subjects undergoing routine colonoscopy at six centers in Italy and Switzerland. Participants were randomized in a 1:1 ratio to undergo colonoscopy with CADe (GI Genius, Medtronic) or CADe plus a mucosal exposure device (Endocuff Vision, Olympus).

The combination approach yielded a 49.6% adenoma detection rate, compared with a 44.0% detection rate for CADe alone (relative risk, 1.12; 95% confidence interval, 1.00-1.26; P = .04). Adding the mucosal exposure device was also associated with a higher number of adenomas detected per colonoscopy. Withdrawal time and rate of unnecessary polypectomies did not differ between groups.

“The benefit of adding [the mucosal exposure device] to AI was expected due to the complementary nature of the interventions,” Dr. Spadaccini and colleagues wrote. “The benefit of [the mucosal exposure device] is limited to increase the quantity of mucosa exposed to the lens by flatting the folds and strengthening the angulations, and the benefit of AI is only in spotting a lesion that is already displayed within the field of view. Thus, we may speculate that the additional mucosal exposure was synergistic to the AI-assisted polyp recognition by AI.”

The benefits of a combination approach were not universal, however, as the mucosal exposure device did not improve detection of either serrated lesions or advanced adenomas. This result was anticipated, the investigators noted, since the miss rate for diminutive or proximal adenomas is higher than it is for larger or distal lesions, and previous research has suggested that AI-assisted and mucosal exposure techniques, when used alone, are most effective for detecting smaller, proximal lesions.

The study was funded by a European Society of Gastrointestinal Endoscopy Artificial Intelligence Award. The investigators disclosed additional relationships with Fujifilm, Medtronic, Olympus, and others.

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Race and ethnicity loom large in CRC screening

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Mon, 06/26/2023 - 08:06

While increases in colorectal cancer screening have been linked to drops in disease incidence, marginalized racial and ethnic populations in the United States continue to see lower screening rates along with higher disease incidence and mortality. Disparities in colorectal screening represent a serious public health challenge, say the authors of a new literature review that describes specific areas of concern and recommendations for improvement.

For their research, published in Techniques and Innovations in Gastrointestinal Endoscopy, gastroenterologists Abraham Segura, MD, and Shazia Mehmood Siddique, MD, of the University of Pennsylvania, Philadelphia, sought to identify studies that shed light on ethnicity or race-based differences in screening uptake, as well as known barriers and facilitators to screening.

Significant racial and ethnic disparities can be seen in rates of colonoscopy selection as a screening method, and of screening completion, Dr. Segura and Dr. Siddique noted, with White individuals who chose the method three times more likely to complete screening as Asian, Hispanic, or Black individuals. Disparities were also seen reflected in people’s choice of screening method, with non–English-speaking Hispanic individuals less likely to choose colonoscopy compared with other groups.

Use of stool-based screening methods, such as the fecal occult blood test (FOBT) and fecal immunochemical test (FIT), has risen over time across ethnic and racial groups. However, Hispanic and Asian individuals were more likely to complete and adhere to the FOBT, compared with non-Hispanic White individuals. Follow-up colonoscopy rates after FOBT or FIT also differ along ethnic and racial lines, Dr. Segura and Dr. Siddique noted, with Asian and American Indian groups less likely to complete follow-up after an abnormal result.

The study authors pointed to structural racism at the root of some observed disparities, citing barriers to healthcare access and quality that include higher rates of noninsurance among Black and Hispanic populations and a lower likelihood of the same populations to receive physician counseling regarding screening.

Barriers to economic stability, including living in impoverished neighborhoods, were also cited as contributors to lower colorectal screening. Patients covered by Medicaid were more than twice as likely as non-Medicaid patients to have suboptimal bowel preparation at screening, the authors noted. Access to transportation remained another frequently observed barrier to completing recommended testing and follow-up.

Mistrust of doctors has been linked to lower screening uptake among Black men. “Longstanding conscious and implicit racism, differences in communication, and socioeconomic context ... engender medical mistrust among racial and ethnic groups,” the authors wrote. Reversing it “ultimately requires vast societal change, and we as physicians can facilitate this by encouraging patient-centered discussions that humanize and empower traditionally marginalized populations.”

Dr. Segura and Dr. Siddique described strategies that have been shown to result in better uptake in specific populations, including removing out-of-pocket costs for screening and follow-up, and designing faith-based or culturally specific outreach delivered through churches and local businesses.

They recommended that researchers change how they study the disparities that bear on colorectal screening and outcomes. “Collection and use of data on race and ethnicity must be optimized and standardized to ensure that all groups are adequately captured,” they wrote. Standardizing self-reporting of race and ethnicity would help address issues of misclassification.

The authors also advised designing studies with longer follow-up, noting that “we must better understand the mechanisms of long-term adherence.” Additional research is needed, they said, to evaluate the efficacy of older outreach strategies after societal changes resulting from the COVID-19 pandemic. Efforts to increase the number of Black, Hispanic, Asian, and Alaskan Native/American Indian groups in CRC screening interventions and studies “must be prioritized.”

Dr. Segura’s and Dr. Siddique’s study was funded with grants from the National Institutes of Health. They disclosed no conflicts of interest.
 

Body

 

Understanding disparities in medicine is the requisite first step toward achieving health equity. The review by Segura and Siddique highlight reasons for health disparities in colorectal cancer (CRC) screening, and propose some solutions.

Issues such as structural racism, socioeconomic status and lack of health insurance need to be addressed at the societal level. Recent elimination of cost-sharing for colonoscopy after a positive noninvasive screening test, and elimination of cost-sharing for screening exams with polypectomy, reduce financial barriers for those patients who have health care insurance and Medicare.

Dr. David Lieberman
In addition to the issues raised in this review, other factors could contribute to disparities. CRC screening in rural settings can be challenging because of limited access and transportation issues. In all settings, transportation, time away from work or childcare/adult care responsibilities may be obstacles for individuals with limited resources. Redlining defined where people could live, and reflects structural racism. These housing restrictions may have resulted environmental exposures (air, water) that could contribute to CRC disparities.

How can practitioners apply this information? Recognition of implicit bias among health care workers is an essential first step toward achieving equity. Providing equitable access to CRC screening works. In a study from Kaiser Permanente, disparities in CRC outcomes between non-Hispanic White versus Black patients, were eliminated within 10 years after implementing an annual mailed fecal immunochemical test kit. This is an exciting proof of principle – physicians and health care organizations can reduce health disparities.

David Lieberman, MD, professor of medicine and formerly chief of the division of gastroenterology and hepatology (1997-2021), Oregon Health and Science University, Portland. Dr. Lieberman does not have any relevant disclosures.

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Understanding disparities in medicine is the requisite first step toward achieving health equity. The review by Segura and Siddique highlight reasons for health disparities in colorectal cancer (CRC) screening, and propose some solutions.

Issues such as structural racism, socioeconomic status and lack of health insurance need to be addressed at the societal level. Recent elimination of cost-sharing for colonoscopy after a positive noninvasive screening test, and elimination of cost-sharing for screening exams with polypectomy, reduce financial barriers for those patients who have health care insurance and Medicare.

Dr. David Lieberman
In addition to the issues raised in this review, other factors could contribute to disparities. CRC screening in rural settings can be challenging because of limited access and transportation issues. In all settings, transportation, time away from work or childcare/adult care responsibilities may be obstacles for individuals with limited resources. Redlining defined where people could live, and reflects structural racism. These housing restrictions may have resulted environmental exposures (air, water) that could contribute to CRC disparities.

How can practitioners apply this information? Recognition of implicit bias among health care workers is an essential first step toward achieving equity. Providing equitable access to CRC screening works. In a study from Kaiser Permanente, disparities in CRC outcomes between non-Hispanic White versus Black patients, were eliminated within 10 years after implementing an annual mailed fecal immunochemical test kit. This is an exciting proof of principle – physicians and health care organizations can reduce health disparities.

David Lieberman, MD, professor of medicine and formerly chief of the division of gastroenterology and hepatology (1997-2021), Oregon Health and Science University, Portland. Dr. Lieberman does not have any relevant disclosures.

Body

 

Understanding disparities in medicine is the requisite first step toward achieving health equity. The review by Segura and Siddique highlight reasons for health disparities in colorectal cancer (CRC) screening, and propose some solutions.

Issues such as structural racism, socioeconomic status and lack of health insurance need to be addressed at the societal level. Recent elimination of cost-sharing for colonoscopy after a positive noninvasive screening test, and elimination of cost-sharing for screening exams with polypectomy, reduce financial barriers for those patients who have health care insurance and Medicare.

Dr. David Lieberman
In addition to the issues raised in this review, other factors could contribute to disparities. CRC screening in rural settings can be challenging because of limited access and transportation issues. In all settings, transportation, time away from work or childcare/adult care responsibilities may be obstacles for individuals with limited resources. Redlining defined where people could live, and reflects structural racism. These housing restrictions may have resulted environmental exposures (air, water) that could contribute to CRC disparities.

How can practitioners apply this information? Recognition of implicit bias among health care workers is an essential first step toward achieving equity. Providing equitable access to CRC screening works. In a study from Kaiser Permanente, disparities in CRC outcomes between non-Hispanic White versus Black patients, were eliminated within 10 years after implementing an annual mailed fecal immunochemical test kit. This is an exciting proof of principle – physicians and health care organizations can reduce health disparities.

David Lieberman, MD, professor of medicine and formerly chief of the division of gastroenterology and hepatology (1997-2021), Oregon Health and Science University, Portland. Dr. Lieberman does not have any relevant disclosures.

While increases in colorectal cancer screening have been linked to drops in disease incidence, marginalized racial and ethnic populations in the United States continue to see lower screening rates along with higher disease incidence and mortality. Disparities in colorectal screening represent a serious public health challenge, say the authors of a new literature review that describes specific areas of concern and recommendations for improvement.

For their research, published in Techniques and Innovations in Gastrointestinal Endoscopy, gastroenterologists Abraham Segura, MD, and Shazia Mehmood Siddique, MD, of the University of Pennsylvania, Philadelphia, sought to identify studies that shed light on ethnicity or race-based differences in screening uptake, as well as known barriers and facilitators to screening.

Significant racial and ethnic disparities can be seen in rates of colonoscopy selection as a screening method, and of screening completion, Dr. Segura and Dr. Siddique noted, with White individuals who chose the method three times more likely to complete screening as Asian, Hispanic, or Black individuals. Disparities were also seen reflected in people’s choice of screening method, with non–English-speaking Hispanic individuals less likely to choose colonoscopy compared with other groups.

Use of stool-based screening methods, such as the fecal occult blood test (FOBT) and fecal immunochemical test (FIT), has risen over time across ethnic and racial groups. However, Hispanic and Asian individuals were more likely to complete and adhere to the FOBT, compared with non-Hispanic White individuals. Follow-up colonoscopy rates after FOBT or FIT also differ along ethnic and racial lines, Dr. Segura and Dr. Siddique noted, with Asian and American Indian groups less likely to complete follow-up after an abnormal result.

The study authors pointed to structural racism at the root of some observed disparities, citing barriers to healthcare access and quality that include higher rates of noninsurance among Black and Hispanic populations and a lower likelihood of the same populations to receive physician counseling regarding screening.

Barriers to economic stability, including living in impoverished neighborhoods, were also cited as contributors to lower colorectal screening. Patients covered by Medicaid were more than twice as likely as non-Medicaid patients to have suboptimal bowel preparation at screening, the authors noted. Access to transportation remained another frequently observed barrier to completing recommended testing and follow-up.

Mistrust of doctors has been linked to lower screening uptake among Black men. “Longstanding conscious and implicit racism, differences in communication, and socioeconomic context ... engender medical mistrust among racial and ethnic groups,” the authors wrote. Reversing it “ultimately requires vast societal change, and we as physicians can facilitate this by encouraging patient-centered discussions that humanize and empower traditionally marginalized populations.”

Dr. Segura and Dr. Siddique described strategies that have been shown to result in better uptake in specific populations, including removing out-of-pocket costs for screening and follow-up, and designing faith-based or culturally specific outreach delivered through churches and local businesses.

They recommended that researchers change how they study the disparities that bear on colorectal screening and outcomes. “Collection and use of data on race and ethnicity must be optimized and standardized to ensure that all groups are adequately captured,” they wrote. Standardizing self-reporting of race and ethnicity would help address issues of misclassification.

The authors also advised designing studies with longer follow-up, noting that “we must better understand the mechanisms of long-term adherence.” Additional research is needed, they said, to evaluate the efficacy of older outreach strategies after societal changes resulting from the COVID-19 pandemic. Efforts to increase the number of Black, Hispanic, Asian, and Alaskan Native/American Indian groups in CRC screening interventions and studies “must be prioritized.”

Dr. Segura’s and Dr. Siddique’s study was funded with grants from the National Institutes of Health. They disclosed no conflicts of interest.
 

While increases in colorectal cancer screening have been linked to drops in disease incidence, marginalized racial and ethnic populations in the United States continue to see lower screening rates along with higher disease incidence and mortality. Disparities in colorectal screening represent a serious public health challenge, say the authors of a new literature review that describes specific areas of concern and recommendations for improvement.

For their research, published in Techniques and Innovations in Gastrointestinal Endoscopy, gastroenterologists Abraham Segura, MD, and Shazia Mehmood Siddique, MD, of the University of Pennsylvania, Philadelphia, sought to identify studies that shed light on ethnicity or race-based differences in screening uptake, as well as known barriers and facilitators to screening.

Significant racial and ethnic disparities can be seen in rates of colonoscopy selection as a screening method, and of screening completion, Dr. Segura and Dr. Siddique noted, with White individuals who chose the method three times more likely to complete screening as Asian, Hispanic, or Black individuals. Disparities were also seen reflected in people’s choice of screening method, with non–English-speaking Hispanic individuals less likely to choose colonoscopy compared with other groups.

Use of stool-based screening methods, such as the fecal occult blood test (FOBT) and fecal immunochemical test (FIT), has risen over time across ethnic and racial groups. However, Hispanic and Asian individuals were more likely to complete and adhere to the FOBT, compared with non-Hispanic White individuals. Follow-up colonoscopy rates after FOBT or FIT also differ along ethnic and racial lines, Dr. Segura and Dr. Siddique noted, with Asian and American Indian groups less likely to complete follow-up after an abnormal result.

The study authors pointed to structural racism at the root of some observed disparities, citing barriers to healthcare access and quality that include higher rates of noninsurance among Black and Hispanic populations and a lower likelihood of the same populations to receive physician counseling regarding screening.

Barriers to economic stability, including living in impoverished neighborhoods, were also cited as contributors to lower colorectal screening. Patients covered by Medicaid were more than twice as likely as non-Medicaid patients to have suboptimal bowel preparation at screening, the authors noted. Access to transportation remained another frequently observed barrier to completing recommended testing and follow-up.

Mistrust of doctors has been linked to lower screening uptake among Black men. “Longstanding conscious and implicit racism, differences in communication, and socioeconomic context ... engender medical mistrust among racial and ethnic groups,” the authors wrote. Reversing it “ultimately requires vast societal change, and we as physicians can facilitate this by encouraging patient-centered discussions that humanize and empower traditionally marginalized populations.”

Dr. Segura and Dr. Siddique described strategies that have been shown to result in better uptake in specific populations, including removing out-of-pocket costs for screening and follow-up, and designing faith-based or culturally specific outreach delivered through churches and local businesses.

They recommended that researchers change how they study the disparities that bear on colorectal screening and outcomes. “Collection and use of data on race and ethnicity must be optimized and standardized to ensure that all groups are adequately captured,” they wrote. Standardizing self-reporting of race and ethnicity would help address issues of misclassification.

The authors also advised designing studies with longer follow-up, noting that “we must better understand the mechanisms of long-term adherence.” Additional research is needed, they said, to evaluate the efficacy of older outreach strategies after societal changes resulting from the COVID-19 pandemic. Efforts to increase the number of Black, Hispanic, Asian, and Alaskan Native/American Indian groups in CRC screening interventions and studies “must be prioritized.”

Dr. Segura’s and Dr. Siddique’s study was funded with grants from the National Institutes of Health. They disclosed no conflicts of interest.
 

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Upadacitinib shows promise in treatment-resistant UC and Crohn’s

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Mon, 06/26/2023 - 16:49

Treatment-resistant patients with active ulcerative colitis and Crohn’s disease saw high remission rates and fast response after being switched to upadacitinib, according to results from a real-world study at a Chicago treatment center.

The results suggest that upadacitinib may be an appropriate salvage treatment for patients who have failed other advanced therapies, including tofacitinib.

Dr. Scott Friedberg


For their research, published in Clinical Gastroenterology and Hepatology, Scott Friedberg, MD, and colleagues at the University of Chicago’s Inflammatory Bowel Disease Center, looked at results from 44 patients diagnosed with ulcerative colitis and 40 with Crohn’s disease, all with active luminal or perianal disease. All patients in the study had previous exposure to tumor necrosis factor inhibitors, and nearly 90% had exposure to two or more advanced therapies, including tofacitinib (n = 17), before being switched to upadacitinib.

Upadacitinib (Rinvoq, AbbVie) is the second small-molecule Janus kinase (JAK) inhibitor approved for ulcerative colitis by the Food and Drug Administration in March 2022 after tofacitinib (Xeljanz, Pfizer) in 2018. Upadacitinib received an additional indication in May 2023 as a treatment for Crohn’s disease. It selectively inhibits JAK1, while tofacitinib inhibits JAK1 and JAK3.

Among the ulcerative colitis patients in Dr. Friedberg and colleagues’ study (mean age, 39 years; 48% female), 85% had a clinical response and 82% achieved clinical remission by week 8. Of nine patients previously treated with tofacitinib, seven (78%) achieved remission at 8 weeks.

Some 76% of the Crohn’s disease patients in the study (mean age, 37 years; 53% female) saw clinical response by 8 weeks, and 71% achieved remission by that time. More than 60% of all participants who had increased fecal calprotectin and C-reactive protein levels at baseline saw normalization of these biomarkers by week 8.

Some patients saw an especially fast response, with 36% of the ulcerative colitis patients and 56% of the Crohn’s patients experiencing clinical remission by week 2.

Acne was the most common reported adverse event, occurring in 23% of patients. Only one serious adverse event, an anemia requiring hospitalization, occurred during the study.

No wash-out period occurred before starting patients on upadacitinib. There were no adverse events seen associated with this strategy, Dr. Friedberg and colleagues noted, a finding with important implications for real-world practice.

“When patients with active IBD are sick, starting a new therapy as soon as it is available is not only reasonable, it is required,” the investigators wrote. Additionally, the findings support the use of upadacitinib in ulcerative colitis patients with previous exposure to tofacitinib, as “selectivity of JAK targets may have different effectiveness profiles.”

Upadacitinib’s rapid onset “has multiple advantages,” the investigators wrote, “not only by being an option for severely active disease but also by allowing for a rapid taper or complete avoidance of corticosteroids.”

The authors noted their study’s small sample size as a key limitation. Several of Dr. Friedberg’s coauthors disclosed financial relationships with drug manufacturers, including AbbVie.

Body

Understanding the efficacy, onset of action and safety of newly approved inflammatory bowel disease (IBD) therapies is difficult in the absence of real-world data as clinical trial populations are much more restrictive and typically do not reflect the patient populations seen in most IBD clinics. This single-center study by Friedberg and colleagues reports on their experience with upadacitinib use in patients with ulcerative colitis (UC) and Crohn’s disease (CD). One key finding of this study is the rapid onset of action with high rates of clinical response and remission within 2 weeks of initiation (60% and 36%) for UC and (50% and 56%) for CD. Further, these high rates of clinical response and remission were noted despite exposure to multiple prior therapies (including prior tofacitinib use), which has been a limitation with other IBD therapies.

Dr. Jill K.J. Gaidos

With the concerns for safety of tofacitinib use, another Janus kinase inhibitor, raised by the ORAL surveillance study, many patients and practitioners are concerned about the safety of upadacitinib use. This study highlighted the low rate of adverse events including no incidences of herpes zoster infection, venous thromboembolism or major adverse cardiovascular events. Acne was noted to be the most common adverse event, occurring in 22% of the study population.

Further research is needed to assess the long term clinical and endoscopic response rates as well as long-term safety assessments, however these results will facilitate conversations with patients who could potentially benefit from treatment with this new therapy.

Jill K. J. Gaidos, MD, FACG, AGAF, is associate professor of medicine, vice chief of clinical research, section of digestive diseases, Yale University, and director of clinical research, Yale Inflammatory Bowel Disease Program, New Haven, Conn.

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Understanding the efficacy, onset of action and safety of newly approved inflammatory bowel disease (IBD) therapies is difficult in the absence of real-world data as clinical trial populations are much more restrictive and typically do not reflect the patient populations seen in most IBD clinics. This single-center study by Friedberg and colleagues reports on their experience with upadacitinib use in patients with ulcerative colitis (UC) and Crohn’s disease (CD). One key finding of this study is the rapid onset of action with high rates of clinical response and remission within 2 weeks of initiation (60% and 36%) for UC and (50% and 56%) for CD. Further, these high rates of clinical response and remission were noted despite exposure to multiple prior therapies (including prior tofacitinib use), which has been a limitation with other IBD therapies.

Dr. Jill K.J. Gaidos

With the concerns for safety of tofacitinib use, another Janus kinase inhibitor, raised by the ORAL surveillance study, many patients and practitioners are concerned about the safety of upadacitinib use. This study highlighted the low rate of adverse events including no incidences of herpes zoster infection, venous thromboembolism or major adverse cardiovascular events. Acne was noted to be the most common adverse event, occurring in 22% of the study population.

Further research is needed to assess the long term clinical and endoscopic response rates as well as long-term safety assessments, however these results will facilitate conversations with patients who could potentially benefit from treatment with this new therapy.

Jill K. J. Gaidos, MD, FACG, AGAF, is associate professor of medicine, vice chief of clinical research, section of digestive diseases, Yale University, and director of clinical research, Yale Inflammatory Bowel Disease Program, New Haven, Conn.

Body

Understanding the efficacy, onset of action and safety of newly approved inflammatory bowel disease (IBD) therapies is difficult in the absence of real-world data as clinical trial populations are much more restrictive and typically do not reflect the patient populations seen in most IBD clinics. This single-center study by Friedberg and colleagues reports on their experience with upadacitinib use in patients with ulcerative colitis (UC) and Crohn’s disease (CD). One key finding of this study is the rapid onset of action with high rates of clinical response and remission within 2 weeks of initiation (60% and 36%) for UC and (50% and 56%) for CD. Further, these high rates of clinical response and remission were noted despite exposure to multiple prior therapies (including prior tofacitinib use), which has been a limitation with other IBD therapies.

Dr. Jill K.J. Gaidos

With the concerns for safety of tofacitinib use, another Janus kinase inhibitor, raised by the ORAL surveillance study, many patients and practitioners are concerned about the safety of upadacitinib use. This study highlighted the low rate of adverse events including no incidences of herpes zoster infection, venous thromboembolism or major adverse cardiovascular events. Acne was noted to be the most common adverse event, occurring in 22% of the study population.

Further research is needed to assess the long term clinical and endoscopic response rates as well as long-term safety assessments, however these results will facilitate conversations with patients who could potentially benefit from treatment with this new therapy.

Jill K. J. Gaidos, MD, FACG, AGAF, is associate professor of medicine, vice chief of clinical research, section of digestive diseases, Yale University, and director of clinical research, Yale Inflammatory Bowel Disease Program, New Haven, Conn.

Treatment-resistant patients with active ulcerative colitis and Crohn’s disease saw high remission rates and fast response after being switched to upadacitinib, according to results from a real-world study at a Chicago treatment center.

The results suggest that upadacitinib may be an appropriate salvage treatment for patients who have failed other advanced therapies, including tofacitinib.

Dr. Scott Friedberg


For their research, published in Clinical Gastroenterology and Hepatology, Scott Friedberg, MD, and colleagues at the University of Chicago’s Inflammatory Bowel Disease Center, looked at results from 44 patients diagnosed with ulcerative colitis and 40 with Crohn’s disease, all with active luminal or perianal disease. All patients in the study had previous exposure to tumor necrosis factor inhibitors, and nearly 90% had exposure to two or more advanced therapies, including tofacitinib (n = 17), before being switched to upadacitinib.

Upadacitinib (Rinvoq, AbbVie) is the second small-molecule Janus kinase (JAK) inhibitor approved for ulcerative colitis by the Food and Drug Administration in March 2022 after tofacitinib (Xeljanz, Pfizer) in 2018. Upadacitinib received an additional indication in May 2023 as a treatment for Crohn’s disease. It selectively inhibits JAK1, while tofacitinib inhibits JAK1 and JAK3.

Among the ulcerative colitis patients in Dr. Friedberg and colleagues’ study (mean age, 39 years; 48% female), 85% had a clinical response and 82% achieved clinical remission by week 8. Of nine patients previously treated with tofacitinib, seven (78%) achieved remission at 8 weeks.

Some 76% of the Crohn’s disease patients in the study (mean age, 37 years; 53% female) saw clinical response by 8 weeks, and 71% achieved remission by that time. More than 60% of all participants who had increased fecal calprotectin and C-reactive protein levels at baseline saw normalization of these biomarkers by week 8.

Some patients saw an especially fast response, with 36% of the ulcerative colitis patients and 56% of the Crohn’s patients experiencing clinical remission by week 2.

Acne was the most common reported adverse event, occurring in 23% of patients. Only one serious adverse event, an anemia requiring hospitalization, occurred during the study.

No wash-out period occurred before starting patients on upadacitinib. There were no adverse events seen associated with this strategy, Dr. Friedberg and colleagues noted, a finding with important implications for real-world practice.

“When patients with active IBD are sick, starting a new therapy as soon as it is available is not only reasonable, it is required,” the investigators wrote. Additionally, the findings support the use of upadacitinib in ulcerative colitis patients with previous exposure to tofacitinib, as “selectivity of JAK targets may have different effectiveness profiles.”

Upadacitinib’s rapid onset “has multiple advantages,” the investigators wrote, “not only by being an option for severely active disease but also by allowing for a rapid taper or complete avoidance of corticosteroids.”

The authors noted their study’s small sample size as a key limitation. Several of Dr. Friedberg’s coauthors disclosed financial relationships with drug manufacturers, including AbbVie.

Treatment-resistant patients with active ulcerative colitis and Crohn’s disease saw high remission rates and fast response after being switched to upadacitinib, according to results from a real-world study at a Chicago treatment center.

The results suggest that upadacitinib may be an appropriate salvage treatment for patients who have failed other advanced therapies, including tofacitinib.

Dr. Scott Friedberg


For their research, published in Clinical Gastroenterology and Hepatology, Scott Friedberg, MD, and colleagues at the University of Chicago’s Inflammatory Bowel Disease Center, looked at results from 44 patients diagnosed with ulcerative colitis and 40 with Crohn’s disease, all with active luminal or perianal disease. All patients in the study had previous exposure to tumor necrosis factor inhibitors, and nearly 90% had exposure to two or more advanced therapies, including tofacitinib (n = 17), before being switched to upadacitinib.

Upadacitinib (Rinvoq, AbbVie) is the second small-molecule Janus kinase (JAK) inhibitor approved for ulcerative colitis by the Food and Drug Administration in March 2022 after tofacitinib (Xeljanz, Pfizer) in 2018. Upadacitinib received an additional indication in May 2023 as a treatment for Crohn’s disease. It selectively inhibits JAK1, while tofacitinib inhibits JAK1 and JAK3.

Among the ulcerative colitis patients in Dr. Friedberg and colleagues’ study (mean age, 39 years; 48% female), 85% had a clinical response and 82% achieved clinical remission by week 8. Of nine patients previously treated with tofacitinib, seven (78%) achieved remission at 8 weeks.

Some 76% of the Crohn’s disease patients in the study (mean age, 37 years; 53% female) saw clinical response by 8 weeks, and 71% achieved remission by that time. More than 60% of all participants who had increased fecal calprotectin and C-reactive protein levels at baseline saw normalization of these biomarkers by week 8.

Some patients saw an especially fast response, with 36% of the ulcerative colitis patients and 56% of the Crohn’s patients experiencing clinical remission by week 2.

Acne was the most common reported adverse event, occurring in 23% of patients. Only one serious adverse event, an anemia requiring hospitalization, occurred during the study.

No wash-out period occurred before starting patients on upadacitinib. There were no adverse events seen associated with this strategy, Dr. Friedberg and colleagues noted, a finding with important implications for real-world practice.

“When patients with active IBD are sick, starting a new therapy as soon as it is available is not only reasonable, it is required,” the investigators wrote. Additionally, the findings support the use of upadacitinib in ulcerative colitis patients with previous exposure to tofacitinib, as “selectivity of JAK targets may have different effectiveness profiles.”

Upadacitinib’s rapid onset “has multiple advantages,” the investigators wrote, “not only by being an option for severely active disease but also by allowing for a rapid taper or complete avoidance of corticosteroids.”

The authors noted their study’s small sample size as a key limitation. Several of Dr. Friedberg’s coauthors disclosed financial relationships with drug manufacturers, including AbbVie.

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AGA update outlines best scenarios for EUS vascular interventions

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Tue, 07/25/2023 - 14:59

Expert treatment centers should consider performing certain endoscopic ultrasound (EUS)-guided vascular interventions with current levels of supporting evidence, according to a practice update from the American Gastroenterological Association.

The AGA Institute’s Clinical Practice Update on interventional EUS, published in Clinical Gastroenterology and Hepatology , makes the case for broader adoption of two clinically available interventions – EUS-guided coil injection therapy of gastric varices and EUS-guided portosystemic pressure gradient measurement – while listing key research questions that remain to be answered. The update also describes current evidence for several emerging EUS interventions.

Brigham and Women's Hospital
Dr. Marvin Ryou

The update’s authors, led by Marvin Ryou, MD, of Brigham and Women’s Hospital, Boston, advised, when available, EUS-guided coil injection therapy of gastric varices over conventional direct endoscopic injection with cyanoacrylate glue, noting that EUS guidance “enhances the precision of injection,” expands treatment options to include placement of hemostatic coils, and uses Doppler to provide real-time feedback on hemostasis.

Available evidence suggests that EUS-guided gastric variceal therapy is “safe, with excellent acute hemostasis and low re-bleeding rates, and likely superiority over traditional direct endoscopic glue injection,” Dr. Ryou and colleagues wrote in their update.

Nonetheless, they cautioned, “the development of a consensus technique would be helpful,” better training of technicians is needed, and large, multicenter studies comparing EUS with standard interventional radiology approaches are still needed.

EUS-guided direct measurement of the portosystemic pressure gradient (PPG) may offer improved clinical efficiency over a percutaneous endovascular approach, Dr. Ryou and colleagues determined, notably when there is concern for a pre-sinusoidal cause of portal hypertension. The EUS intervention allows for the “concurrent ability to perform esophagogastroduodenoscopy and EUS as a one-stop shop during which PPG, liver biopsy, and endoscopic features of portal hypertension … can all be evaluated, obtained, and potentially treated during a single procedure.” The authors updated guidance on four emerging interventions for which evidence remains limited: EUS-guided injection therapy of rectal varices, EUS-guided splenic artery embolization, EUS-guided injection therapy in patients with splenic artery pseudoaneurysms, and EUS-guided portal vein sampling.

While the last of these interventions appears safe, the authors cautioned, it should be performed only as part of a research protocol. The authors described an experimental intervention tested in animal models using a EUS-guided intrahepatic portosystemic shunt in which a self-expanding metal stent was deployed via EUS to bridge the hepatic and portal vein and decompress a hypertensive portal system.

The authors cautioned that the guidance was not the product of a formal systematic review, but represented a summary of practical advice gleaned from a literature review to provide practical advice. As a general rule, they said, EUS-guided vascular interventions should be considered when the vascular target occurs in or near the gastrointestinal wall, “which may confer an advantage to an endoscopic rather than percutaneous access,” and when the intervention has “a clinical efficacy and safety profile comparable, if not superior, to current alternatives.” All the interventions described in the clinical practice update satisfy the first condition, but not the second.

Dr. Ryou and two of his three coauthors disclosed financial relationships, including consulting fees and research support, from device manufacturers.

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Expert treatment centers should consider performing certain endoscopic ultrasound (EUS)-guided vascular interventions with current levels of supporting evidence, according to a practice update from the American Gastroenterological Association.

The AGA Institute’s Clinical Practice Update on interventional EUS, published in Clinical Gastroenterology and Hepatology , makes the case for broader adoption of two clinically available interventions – EUS-guided coil injection therapy of gastric varices and EUS-guided portosystemic pressure gradient measurement – while listing key research questions that remain to be answered. The update also describes current evidence for several emerging EUS interventions.

Brigham and Women's Hospital
Dr. Marvin Ryou

The update’s authors, led by Marvin Ryou, MD, of Brigham and Women’s Hospital, Boston, advised, when available, EUS-guided coil injection therapy of gastric varices over conventional direct endoscopic injection with cyanoacrylate glue, noting that EUS guidance “enhances the precision of injection,” expands treatment options to include placement of hemostatic coils, and uses Doppler to provide real-time feedback on hemostasis.

Available evidence suggests that EUS-guided gastric variceal therapy is “safe, with excellent acute hemostasis and low re-bleeding rates, and likely superiority over traditional direct endoscopic glue injection,” Dr. Ryou and colleagues wrote in their update.

Nonetheless, they cautioned, “the development of a consensus technique would be helpful,” better training of technicians is needed, and large, multicenter studies comparing EUS with standard interventional radiology approaches are still needed.

EUS-guided direct measurement of the portosystemic pressure gradient (PPG) may offer improved clinical efficiency over a percutaneous endovascular approach, Dr. Ryou and colleagues determined, notably when there is concern for a pre-sinusoidal cause of portal hypertension. The EUS intervention allows for the “concurrent ability to perform esophagogastroduodenoscopy and EUS as a one-stop shop during which PPG, liver biopsy, and endoscopic features of portal hypertension … can all be evaluated, obtained, and potentially treated during a single procedure.” The authors updated guidance on four emerging interventions for which evidence remains limited: EUS-guided injection therapy of rectal varices, EUS-guided splenic artery embolization, EUS-guided injection therapy in patients with splenic artery pseudoaneurysms, and EUS-guided portal vein sampling.

While the last of these interventions appears safe, the authors cautioned, it should be performed only as part of a research protocol. The authors described an experimental intervention tested in animal models using a EUS-guided intrahepatic portosystemic shunt in which a self-expanding metal stent was deployed via EUS to bridge the hepatic and portal vein and decompress a hypertensive portal system.

The authors cautioned that the guidance was not the product of a formal systematic review, but represented a summary of practical advice gleaned from a literature review to provide practical advice. As a general rule, they said, EUS-guided vascular interventions should be considered when the vascular target occurs in or near the gastrointestinal wall, “which may confer an advantage to an endoscopic rather than percutaneous access,” and when the intervention has “a clinical efficacy and safety profile comparable, if not superior, to current alternatives.” All the interventions described in the clinical practice update satisfy the first condition, but not the second.

Dr. Ryou and two of his three coauthors disclosed financial relationships, including consulting fees and research support, from device manufacturers.

Expert treatment centers should consider performing certain endoscopic ultrasound (EUS)-guided vascular interventions with current levels of supporting evidence, according to a practice update from the American Gastroenterological Association.

The AGA Institute’s Clinical Practice Update on interventional EUS, published in Clinical Gastroenterology and Hepatology , makes the case for broader adoption of two clinically available interventions – EUS-guided coil injection therapy of gastric varices and EUS-guided portosystemic pressure gradient measurement – while listing key research questions that remain to be answered. The update also describes current evidence for several emerging EUS interventions.

Brigham and Women's Hospital
Dr. Marvin Ryou

The update’s authors, led by Marvin Ryou, MD, of Brigham and Women’s Hospital, Boston, advised, when available, EUS-guided coil injection therapy of gastric varices over conventional direct endoscopic injection with cyanoacrylate glue, noting that EUS guidance “enhances the precision of injection,” expands treatment options to include placement of hemostatic coils, and uses Doppler to provide real-time feedback on hemostasis.

Available evidence suggests that EUS-guided gastric variceal therapy is “safe, with excellent acute hemostasis and low re-bleeding rates, and likely superiority over traditional direct endoscopic glue injection,” Dr. Ryou and colleagues wrote in their update.

Nonetheless, they cautioned, “the development of a consensus technique would be helpful,” better training of technicians is needed, and large, multicenter studies comparing EUS with standard interventional radiology approaches are still needed.

EUS-guided direct measurement of the portosystemic pressure gradient (PPG) may offer improved clinical efficiency over a percutaneous endovascular approach, Dr. Ryou and colleagues determined, notably when there is concern for a pre-sinusoidal cause of portal hypertension. The EUS intervention allows for the “concurrent ability to perform esophagogastroduodenoscopy and EUS as a one-stop shop during which PPG, liver biopsy, and endoscopic features of portal hypertension … can all be evaluated, obtained, and potentially treated during a single procedure.” The authors updated guidance on four emerging interventions for which evidence remains limited: EUS-guided injection therapy of rectal varices, EUS-guided splenic artery embolization, EUS-guided injection therapy in patients with splenic artery pseudoaneurysms, and EUS-guided portal vein sampling.

While the last of these interventions appears safe, the authors cautioned, it should be performed only as part of a research protocol. The authors described an experimental intervention tested in animal models using a EUS-guided intrahepatic portosystemic shunt in which a self-expanding metal stent was deployed via EUS to bridge the hepatic and portal vein and decompress a hypertensive portal system.

The authors cautioned that the guidance was not the product of a formal systematic review, but represented a summary of practical advice gleaned from a literature review to provide practical advice. As a general rule, they said, EUS-guided vascular interventions should be considered when the vascular target occurs in or near the gastrointestinal wall, “which may confer an advantage to an endoscopic rather than percutaneous access,” and when the intervention has “a clinical efficacy and safety profile comparable, if not superior, to current alternatives.” All the interventions described in the clinical practice update satisfy the first condition, but not the second.

Dr. Ryou and two of his three coauthors disclosed financial relationships, including consulting fees and research support, from device manufacturers.

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Distal fecal washes reveal inflammation across ileac-colonic axis

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Changed
Wed, 06/07/2023 - 09:05

 

Fecal washes of the distal colon combined with single-cell RNA sequencing can provide extensive, accurate information about the severity and location of inflammation, not only in the distal colon itself, but the proximal colon and terminal ileum.

The noninvasive distal washes also reveal information on gene expression that can predict response to therapies in inflammatory bowel disease.

The findings, from the research group of Shalev Itzkovitz, MD, at the Weizmann Institute of Science in Rehovot, Israel, were published online in the journal Cellular and Molecular Gastroenterology and Hepatology.

Dr. Itzkovitz and his colleagues performed colonoscopies on 29 patients with ulcerative colitis (UC) and 30 with Crohn’s disease (CD) recruited from a single center, as well as 50 healthy controls. The researchers took biopsies and obtained fecal washes at different locations on the ileal-colonic axis. Results were analyzed using host transcriptomics, a method to determine which genes are being expressed in tissue samples.

While previous studies established the value of distal fecal washes in disease affecting the distal colon, Dr. Itzkovitz and colleagues found that the washes obtained from the distal colon contained accurate information “not only of distal colonic inflammation in UC patients, but also of CD inflammation, including when the inflammatory segments are ileal and no colonic involvement is observed.”

They also found that the distal fecal washes, including from CD patients with no distal involvement, showed gene expression of immune, stromal, and epithelial origin correlating with disease severity. The sequencing revealed “a strong transcriptomic signature of gene modules” seen in previous studies to be associated with response to biological therapies, the study authors wrote,

Remarkably, the transcriptomics from fecal washes were more sensitive and specific in revealing inflammation, compared with transcriptomics conducted on the tissue biopsies. “This higher statistical power may be a result of the fact that fecal washes capture cells that are shed throughout the gastrointestinal tract and therefore are not sensitive to the precise location from which a biopsy specimen is obtained,” the authors surmised.

Fecal wash host transcriptomics offer a noninvasive option, without the risks associated with colonoscopy, for selecting therapies in inflammatory bowel disease, the researchers wrote. “This is critical, given that current clinical remission rates with different biological agents are only approximately 30%-60%.”

Dr. Itzkovitz and colleagues’ study was supported by outside entities including the Wolfson Family Charitable Trust, the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Dr. Beth Rom-Rymer Stem Cell Research Fund, the Minerva Stiftung grant, the Weizmann-Sheba joint research program, the Israel Science Foundation, and the European Research Council, among others. Three coauthors disclosed financial relationships with drug manufacturers.

Body

 

Distal fecal wash host transcriptomics identifies inflammation throughout the colon and terminal ileum. For assessing disease severity in inflammatory bowel disease, distribution and phenotype, endoscopy has been the standard. In line, calprotectin as fecal inflammation marker has been serving as a monitoring tool. But considering recent suggestions of molecular phenotypes, these diagnostic measures may need to advance in clinical practice.

Dr. Britta Siegmund
In the work by Dan et al., local fecal washes as well as biopsy transcriptomics from the ileum and proximal and distal colon could be associated with clinical, endoscopic, and histologic inflammation, and of notice, fecal wash transcriptomics revealed a superior correlation to local histology in comparison to biopsy transcriptomics. However, the most intriguing finding of the presented study is that distal fecal wash transcriptomics could not only reflect local inflammation, but equally provided information on identifying inflammation in the ileum as well as proximal colon even in the absence of distal inflammation. This can possibly be explained by luminally shed immune cells at the site of inflammation that as a consequence also explains that the transcriptomic pattern of the fecal washes allowed for clustering in the suggested modules of the Powrie group.

Thus, this strategy of distal fecal wash transcriptomics requires prospective validation in larger cohorts, but clearly underlines the potential of a strong diagnostic tool combining the luminal nature of inflammatory bowel disease and modern molecular techniques.

Britta Siegmund, MD, is the medical director for the division of gastroenterology, infectiology and rheumatology at Charité Universitätsmedizin Berlin. She has served as a consultant for Abbvie, Arena, BMS, Boehringer, Celgene, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Lilly, Pfizer, PredictImmune, Prometheus, and Takeda, and received speaker’s fees from Abbvie, CED Service GmbH, Falk, Ferring, Galapagos, Janssen, Lilly, Novartis, Pfizer, and Takeda.

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Body

 

Distal fecal wash host transcriptomics identifies inflammation throughout the colon and terminal ileum. For assessing disease severity in inflammatory bowel disease, distribution and phenotype, endoscopy has been the standard. In line, calprotectin as fecal inflammation marker has been serving as a monitoring tool. But considering recent suggestions of molecular phenotypes, these diagnostic measures may need to advance in clinical practice.

Dr. Britta Siegmund
In the work by Dan et al., local fecal washes as well as biopsy transcriptomics from the ileum and proximal and distal colon could be associated with clinical, endoscopic, and histologic inflammation, and of notice, fecal wash transcriptomics revealed a superior correlation to local histology in comparison to biopsy transcriptomics. However, the most intriguing finding of the presented study is that distal fecal wash transcriptomics could not only reflect local inflammation, but equally provided information on identifying inflammation in the ileum as well as proximal colon even in the absence of distal inflammation. This can possibly be explained by luminally shed immune cells at the site of inflammation that as a consequence also explains that the transcriptomic pattern of the fecal washes allowed for clustering in the suggested modules of the Powrie group.

Thus, this strategy of distal fecal wash transcriptomics requires prospective validation in larger cohorts, but clearly underlines the potential of a strong diagnostic tool combining the luminal nature of inflammatory bowel disease and modern molecular techniques.

Britta Siegmund, MD, is the medical director for the division of gastroenterology, infectiology and rheumatology at Charité Universitätsmedizin Berlin. She has served as a consultant for Abbvie, Arena, BMS, Boehringer, Celgene, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Lilly, Pfizer, PredictImmune, Prometheus, and Takeda, and received speaker’s fees from Abbvie, CED Service GmbH, Falk, Ferring, Galapagos, Janssen, Lilly, Novartis, Pfizer, and Takeda.

Body

 

Distal fecal wash host transcriptomics identifies inflammation throughout the colon and terminal ileum. For assessing disease severity in inflammatory bowel disease, distribution and phenotype, endoscopy has been the standard. In line, calprotectin as fecal inflammation marker has been serving as a monitoring tool. But considering recent suggestions of molecular phenotypes, these diagnostic measures may need to advance in clinical practice.

Dr. Britta Siegmund
In the work by Dan et al., local fecal washes as well as biopsy transcriptomics from the ileum and proximal and distal colon could be associated with clinical, endoscopic, and histologic inflammation, and of notice, fecal wash transcriptomics revealed a superior correlation to local histology in comparison to biopsy transcriptomics. However, the most intriguing finding of the presented study is that distal fecal wash transcriptomics could not only reflect local inflammation, but equally provided information on identifying inflammation in the ileum as well as proximal colon even in the absence of distal inflammation. This can possibly be explained by luminally shed immune cells at the site of inflammation that as a consequence also explains that the transcriptomic pattern of the fecal washes allowed for clustering in the suggested modules of the Powrie group.

Thus, this strategy of distal fecal wash transcriptomics requires prospective validation in larger cohorts, but clearly underlines the potential of a strong diagnostic tool combining the luminal nature of inflammatory bowel disease and modern molecular techniques.

Britta Siegmund, MD, is the medical director for the division of gastroenterology, infectiology and rheumatology at Charité Universitätsmedizin Berlin. She has served as a consultant for Abbvie, Arena, BMS, Boehringer, Celgene, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Lilly, Pfizer, PredictImmune, Prometheus, and Takeda, and received speaker’s fees from Abbvie, CED Service GmbH, Falk, Ferring, Galapagos, Janssen, Lilly, Novartis, Pfizer, and Takeda.

 

Fecal washes of the distal colon combined with single-cell RNA sequencing can provide extensive, accurate information about the severity and location of inflammation, not only in the distal colon itself, but the proximal colon and terminal ileum.

The noninvasive distal washes also reveal information on gene expression that can predict response to therapies in inflammatory bowel disease.

The findings, from the research group of Shalev Itzkovitz, MD, at the Weizmann Institute of Science in Rehovot, Israel, were published online in the journal Cellular and Molecular Gastroenterology and Hepatology.

Dr. Itzkovitz and his colleagues performed colonoscopies on 29 patients with ulcerative colitis (UC) and 30 with Crohn’s disease (CD) recruited from a single center, as well as 50 healthy controls. The researchers took biopsies and obtained fecal washes at different locations on the ileal-colonic axis. Results were analyzed using host transcriptomics, a method to determine which genes are being expressed in tissue samples.

While previous studies established the value of distal fecal washes in disease affecting the distal colon, Dr. Itzkovitz and colleagues found that the washes obtained from the distal colon contained accurate information “not only of distal colonic inflammation in UC patients, but also of CD inflammation, including when the inflammatory segments are ileal and no colonic involvement is observed.”

They also found that the distal fecal washes, including from CD patients with no distal involvement, showed gene expression of immune, stromal, and epithelial origin correlating with disease severity. The sequencing revealed “a strong transcriptomic signature of gene modules” seen in previous studies to be associated with response to biological therapies, the study authors wrote,

Remarkably, the transcriptomics from fecal washes were more sensitive and specific in revealing inflammation, compared with transcriptomics conducted on the tissue biopsies. “This higher statistical power may be a result of the fact that fecal washes capture cells that are shed throughout the gastrointestinal tract and therefore are not sensitive to the precise location from which a biopsy specimen is obtained,” the authors surmised.

Fecal wash host transcriptomics offer a noninvasive option, without the risks associated with colonoscopy, for selecting therapies in inflammatory bowel disease, the researchers wrote. “This is critical, given that current clinical remission rates with different biological agents are only approximately 30%-60%.”

Dr. Itzkovitz and colleagues’ study was supported by outside entities including the Wolfson Family Charitable Trust, the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Dr. Beth Rom-Rymer Stem Cell Research Fund, the Minerva Stiftung grant, the Weizmann-Sheba joint research program, the Israel Science Foundation, and the European Research Council, among others. Three coauthors disclosed financial relationships with drug manufacturers.

 

Fecal washes of the distal colon combined with single-cell RNA sequencing can provide extensive, accurate information about the severity and location of inflammation, not only in the distal colon itself, but the proximal colon and terminal ileum.

The noninvasive distal washes also reveal information on gene expression that can predict response to therapies in inflammatory bowel disease.

The findings, from the research group of Shalev Itzkovitz, MD, at the Weizmann Institute of Science in Rehovot, Israel, were published online in the journal Cellular and Molecular Gastroenterology and Hepatology.

Dr. Itzkovitz and his colleagues performed colonoscopies on 29 patients with ulcerative colitis (UC) and 30 with Crohn’s disease (CD) recruited from a single center, as well as 50 healthy controls. The researchers took biopsies and obtained fecal washes at different locations on the ileal-colonic axis. Results were analyzed using host transcriptomics, a method to determine which genes are being expressed in tissue samples.

While previous studies established the value of distal fecal washes in disease affecting the distal colon, Dr. Itzkovitz and colleagues found that the washes obtained from the distal colon contained accurate information “not only of distal colonic inflammation in UC patients, but also of CD inflammation, including when the inflammatory segments are ileal and no colonic involvement is observed.”

They also found that the distal fecal washes, including from CD patients with no distal involvement, showed gene expression of immune, stromal, and epithelial origin correlating with disease severity. The sequencing revealed “a strong transcriptomic signature of gene modules” seen in previous studies to be associated with response to biological therapies, the study authors wrote,

Remarkably, the transcriptomics from fecal washes were more sensitive and specific in revealing inflammation, compared with transcriptomics conducted on the tissue biopsies. “This higher statistical power may be a result of the fact that fecal washes capture cells that are shed throughout the gastrointestinal tract and therefore are not sensitive to the precise location from which a biopsy specimen is obtained,” the authors surmised.

Fecal wash host transcriptomics offer a noninvasive option, without the risks associated with colonoscopy, for selecting therapies in inflammatory bowel disease, the researchers wrote. “This is critical, given that current clinical remission rates with different biological agents are only approximately 30%-60%.”

Dr. Itzkovitz and colleagues’ study was supported by outside entities including the Wolfson Family Charitable Trust, the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Dr. Beth Rom-Rymer Stem Cell Research Fund, the Minerva Stiftung grant, the Weizmann-Sheba joint research program, the Israel Science Foundation, and the European Research Council, among others. Three coauthors disclosed financial relationships with drug manufacturers.

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New guideline weighs medication options for chronic constipation

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Mon, 06/19/2023 - 15:10

 

A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter and prescription treatment options for chronic idiopathic constipation in otherwise-healthy people.

The guideline, published simultaneously in the American Journal of Gastroenterology and in Gastroenterology, was developed jointly by the American Gastroenterological Association and the American College of Gastroenterology. It marks the AGA’s first update on chronic idiopathic constipation (CIC), also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, of the University of California, Los Angeles, noted that CIC – defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication side effect, or inflammatory bowel disease – is common, affecting between 8% and 12% of all U.S. adults. Most will be treated by primary care physicians, not specialists, Dr. Chang said. And most will see their physicians having already tried different over-the-counter treatments.

“The criteria for CIC or functional constipation hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr. Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide, and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, plecanatide, and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there was too little data available on it to make an assessment, Dr. Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.

As costs of the recommended therapies vary from less than $10 a month to over $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr. Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr. Chang commented. “If that doesn’t work, try over-the-counter remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr. Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr. Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr. Chang said that, while the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr. Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr. Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

For more information, see the related clinical decision support tool in Gastroenterology.

The guideline’s development was funded by the AGA and ACG, without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

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A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter and prescription treatment options for chronic idiopathic constipation in otherwise-healthy people.

The guideline, published simultaneously in the American Journal of Gastroenterology and in Gastroenterology, was developed jointly by the American Gastroenterological Association and the American College of Gastroenterology. It marks the AGA’s first update on chronic idiopathic constipation (CIC), also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, of the University of California, Los Angeles, noted that CIC – defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication side effect, or inflammatory bowel disease – is common, affecting between 8% and 12% of all U.S. adults. Most will be treated by primary care physicians, not specialists, Dr. Chang said. And most will see their physicians having already tried different over-the-counter treatments.

“The criteria for CIC or functional constipation hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr. Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide, and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, plecanatide, and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there was too little data available on it to make an assessment, Dr. Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.

As costs of the recommended therapies vary from less than $10 a month to over $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr. Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr. Chang commented. “If that doesn’t work, try over-the-counter remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr. Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr. Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr. Chang said that, while the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr. Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr. Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

For more information, see the related clinical decision support tool in Gastroenterology.

The guideline’s development was funded by the AGA and ACG, without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

 

A new practice guideline aims to help clinicians navigate an increasingly crowded field of over-the-counter and prescription treatment options for chronic idiopathic constipation in otherwise-healthy people.

The guideline, published simultaneously in the American Journal of Gastroenterology and in Gastroenterology, was developed jointly by the American Gastroenterological Association and the American College of Gastroenterology. It marks the AGA’s first update on chronic idiopathic constipation (CIC), also called functional constipation, in a decade.

In an interview, guideline lead author Lin Chang, MD, of the University of California, Los Angeles, noted that CIC – defined as constipation lasting at least 3 months in the absence of malignancy or obstruction, a medication side effect, or inflammatory bowel disease – is common, affecting between 8% and 12% of all U.S. adults. Most will be treated by primary care physicians, not specialists, Dr. Chang said. And most will see their physicians having already tried different over-the-counter treatments.

“The criteria for CIC or functional constipation hasn’t really changed” since the last AGA guideline on it was published in 2013, Dr. Chang said, adding that the diagnostic standard currently used is the Rome IV criteria for functional constipation. “There are just more medications right now than there were 10 years ago.”

The new guideline, into which evidence from 28 studies was integrated, offers recommendations regarding different types of fiber; the osmotic laxatives polyethylene glycol, magnesium oxide, and lactulose; and the stimulant laxatives bisacodyl, sodium picosulfate, and senna. It also assesses the secretagogues lubiprostone, linaclotide, plecanatide, and the serotonin type 4 agonist prucalopride.

One commonly used agent in clinical practice, the stool softener docusate sodium, does not appear in the guideline, as there was too little data available on it to make an assessment, Dr. Chang said. Fruit-based laxatives were excluded because they were the subject of a recent evidence review. Lifestyle modifications such as exercise, surgical interventions, and probiotics were not assessed.

The guideline’s strongest recommendations are for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride, with conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.

As costs of the recommended therapies vary from less than $10 a month to over $500, the authors also included price information, noting that “patient values, costs, and health equity considerations” must be factored into treatment choices. “For polyethylene glycol there’s a strong recommendation, although the certainty of evidence was moderate,” Dr. Chang said. “And with fiber, even though we made only a conditional recommendation based on the evidence, our remarks and our algorithm make clear that it should be considered as a first-line treatment.”

In general, “if someone has more mild symptoms, you should try fiber or increase their fiber intake in their diet,” Dr. Chang commented. “If that doesn’t work, try over-the-counter remedies like polyethylene glycol. Then if symptoms are more severe, or if they fail the first-line treatments, then you go to prescription agents.”

In clinical practice, “there always considerations besides scientific evidence of safety and efficacy,” Dr. Chang stressed. “You have to personalize treatment for the patient.” A patient may present having already failed with fiber, or who does not want to use magnesium or can’t afford a costlier agent.

The guidelines contain implementation advice that might guide choice of therapy or dosing. With the prescription osmotic laxative lactulose, for example, “you may not wish to use it as a first-line treatment because bloating and flatulence are very common,” Dr. Chang said. “Our implementation advice makes that clear.” For senna, a stimulant laxative derived from the leaves of the senna plant and for which quality evidence is limited, the guideline authors stressed that patients should be started on low doses to avoid cramping.

Dr. Chang said that, while the new guideline covers medication options for otherwise-healthy adults, clinicians should be mindful that patients presenting with CIC might still have a defecatory disorder. “A person could also have pelvic floor dysfunction as a primary cause or contributing factor. If someone fails fiber or polyethylene glycol, consider a digital rectal examination as part of the physical exam. If this is abnormal, consider referring them for anorectal manometry.”

Untreated constipation carries risks, Dr. Chang noted, but “sometimes people with bothersome symptoms don’t treat them because they’re worried they’ll become dependent on treatment. It’s a dependency in the sense that you have to treat any chronic condition, such as high blood pressure or diabetes, but the treatments aren’t addictive, except for some stimulant laxatives to which people can develop tolerance.”

Hemorrhoids and defecatory disorders can occur over time because of straining, Dr. Chang said. “The pelvic wall can also get very lax, and that is hard to fix. Or, one can develop a rectal prolapse. Another thing that happens when people have longstanding constipation for many years is they start losing the urge to have a bowel movement.”

For more information, see the related clinical decision support tool in Gastroenterology.

The guideline’s development was funded by the AGA and ACG, without industry support. Authors with conflicts of interest regarding a specific intervention or drug were not allowed to weigh in on those interventions.

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ChatGPT delivers credible answers to colonoscopy queries

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Tue, 05/16/2023 - 00:00

ChatGPT, an artificial intelligence chatbot, can provide easily understandable, scientifically adequate, and generally satisfactory answers to common patient questions about colonoscopy, new research suggests.

“This study shows that a conversational AI program can generate credible medical information in response to common patient questions,” say the investigators, led by Tsung-Chun Lee, MD, division of gastroenterology and hepatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.

“With dedicated domain training, there is meaningful potential to optimize clinical communication to patients undergoing colonoscopy,” they add.

The study was published online in Gastroenterology.

ChatGPT, developed by OpenAI, is a natural language processing tool that allows users to have personalized conversations with an artificial intelligence (AI) bot capable of providing a detailed response to any question posed.

For their first-of-its-kind study, Dr. Lee and colleagues assessed the quality of ChatGPT-generated answers to eight common patient questions about colonoscopy, including what a colonoscopy entails, why it’s performed, how to prepare for it, potential complications, what to expect after the procedure, and what happens with a positive/negative result.

They retrieved the questions from the websites of three randomly selected top hospitals for gastroenterology and gastrointestinal surgery and had ChatGPT (Jan. 30, 2023, version) answer the questions twice.

Using plagiarism detection software, they found that text similarity was extremely low between ChatGPT answers and those on hospital websites (0%-16%). Text similarity ranged from 28% to 77% between the two ChatGPT answers for the same question, except on the question of what to do after a positive colonoscopy result, which had 0% text similarity.

To objectively gauge the quality of the ChatGPT answers, four gastroenterologists (two senior gastroenterologists and two fellows) rated 36 pairs of common questions and answers on a seven-point Likert scale according to ease of understanding, scientific adequacy, and satisfaction with the answer.

The gastroenterologists rated the ChatGPT answers highly and similarly to non-AI answers for all three quality indicators, with some AI scores even higher than non-AI scores.

Interestingly, they could correctly identify AI-generated answers only 48% of the time. Three raters had an accuracy of less than 50%, whereas one (a fellow) was 81% accurate.

The researchers note that publications about ChatGPT in PubMed grew 10-fold from Feb. 3 to April 14, 2023, with topics such as board examinations authorship, editorial policies, medical education, and clinical decision support.

Although in their early days, ChatGPT and other AI bots may represent a “transformative innovation” in how medical information is created by physicians and consumed by patients, they say.

It could also be a time-saver for health care professionals.

“AI-generated medical information, with appropriate provider oversight, accreditation, and periodic surveillance, could improve efficiency of care and free providers for more cognitively intensive patient communications,” they add.

However, several challenges remain, such as the lack of clinical evidence in constructing AI-generated answers.

In addition, AI-generated answers were written at significantly higher reading levels than were answers on hospital websites, which could be a barrier for some patients.

The study received no specific funding. The authors have declared no relevant conflicts of interest.
 

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

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ChatGPT, an artificial intelligence chatbot, can provide easily understandable, scientifically adequate, and generally satisfactory answers to common patient questions about colonoscopy, new research suggests.

“This study shows that a conversational AI program can generate credible medical information in response to common patient questions,” say the investigators, led by Tsung-Chun Lee, MD, division of gastroenterology and hepatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.

“With dedicated domain training, there is meaningful potential to optimize clinical communication to patients undergoing colonoscopy,” they add.

The study was published online in Gastroenterology.

ChatGPT, developed by OpenAI, is a natural language processing tool that allows users to have personalized conversations with an artificial intelligence (AI) bot capable of providing a detailed response to any question posed.

For their first-of-its-kind study, Dr. Lee and colleagues assessed the quality of ChatGPT-generated answers to eight common patient questions about colonoscopy, including what a colonoscopy entails, why it’s performed, how to prepare for it, potential complications, what to expect after the procedure, and what happens with a positive/negative result.

They retrieved the questions from the websites of three randomly selected top hospitals for gastroenterology and gastrointestinal surgery and had ChatGPT (Jan. 30, 2023, version) answer the questions twice.

Using plagiarism detection software, they found that text similarity was extremely low between ChatGPT answers and those on hospital websites (0%-16%). Text similarity ranged from 28% to 77% between the two ChatGPT answers for the same question, except on the question of what to do after a positive colonoscopy result, which had 0% text similarity.

To objectively gauge the quality of the ChatGPT answers, four gastroenterologists (two senior gastroenterologists and two fellows) rated 36 pairs of common questions and answers on a seven-point Likert scale according to ease of understanding, scientific adequacy, and satisfaction with the answer.

The gastroenterologists rated the ChatGPT answers highly and similarly to non-AI answers for all three quality indicators, with some AI scores even higher than non-AI scores.

Interestingly, they could correctly identify AI-generated answers only 48% of the time. Three raters had an accuracy of less than 50%, whereas one (a fellow) was 81% accurate.

The researchers note that publications about ChatGPT in PubMed grew 10-fold from Feb. 3 to April 14, 2023, with topics such as board examinations authorship, editorial policies, medical education, and clinical decision support.

Although in their early days, ChatGPT and other AI bots may represent a “transformative innovation” in how medical information is created by physicians and consumed by patients, they say.

It could also be a time-saver for health care professionals.

“AI-generated medical information, with appropriate provider oversight, accreditation, and periodic surveillance, could improve efficiency of care and free providers for more cognitively intensive patient communications,” they add.

However, several challenges remain, such as the lack of clinical evidence in constructing AI-generated answers.

In addition, AI-generated answers were written at significantly higher reading levels than were answers on hospital websites, which could be a barrier for some patients.

The study received no specific funding. The authors have declared no relevant conflicts of interest.
 

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

ChatGPT, an artificial intelligence chatbot, can provide easily understandable, scientifically adequate, and generally satisfactory answers to common patient questions about colonoscopy, new research suggests.

“This study shows that a conversational AI program can generate credible medical information in response to common patient questions,” say the investigators, led by Tsung-Chun Lee, MD, division of gastroenterology and hepatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.

“With dedicated domain training, there is meaningful potential to optimize clinical communication to patients undergoing colonoscopy,” they add.

The study was published online in Gastroenterology.

ChatGPT, developed by OpenAI, is a natural language processing tool that allows users to have personalized conversations with an artificial intelligence (AI) bot capable of providing a detailed response to any question posed.

For their first-of-its-kind study, Dr. Lee and colleagues assessed the quality of ChatGPT-generated answers to eight common patient questions about colonoscopy, including what a colonoscopy entails, why it’s performed, how to prepare for it, potential complications, what to expect after the procedure, and what happens with a positive/negative result.

They retrieved the questions from the websites of three randomly selected top hospitals for gastroenterology and gastrointestinal surgery and had ChatGPT (Jan. 30, 2023, version) answer the questions twice.

Using plagiarism detection software, they found that text similarity was extremely low between ChatGPT answers and those on hospital websites (0%-16%). Text similarity ranged from 28% to 77% between the two ChatGPT answers for the same question, except on the question of what to do after a positive colonoscopy result, which had 0% text similarity.

To objectively gauge the quality of the ChatGPT answers, four gastroenterologists (two senior gastroenterologists and two fellows) rated 36 pairs of common questions and answers on a seven-point Likert scale according to ease of understanding, scientific adequacy, and satisfaction with the answer.

The gastroenterologists rated the ChatGPT answers highly and similarly to non-AI answers for all three quality indicators, with some AI scores even higher than non-AI scores.

Interestingly, they could correctly identify AI-generated answers only 48% of the time. Three raters had an accuracy of less than 50%, whereas one (a fellow) was 81% accurate.

The researchers note that publications about ChatGPT in PubMed grew 10-fold from Feb. 3 to April 14, 2023, with topics such as board examinations authorship, editorial policies, medical education, and clinical decision support.

Although in their early days, ChatGPT and other AI bots may represent a “transformative innovation” in how medical information is created by physicians and consumed by patients, they say.

It could also be a time-saver for health care professionals.

“AI-generated medical information, with appropriate provider oversight, accreditation, and periodic surveillance, could improve efficiency of care and free providers for more cognitively intensive patient communications,” they add.

However, several challenges remain, such as the lack of clinical evidence in constructing AI-generated answers.

In addition, AI-generated answers were written at significantly higher reading levels than were answers on hospital websites, which could be a barrier for some patients.

The study received no specific funding. The authors have declared no relevant conflicts of interest.
 

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

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Psyllium may shield against colitis

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Mon, 05/15/2023 - 17:26

Psyllium fiber offered protection against colitis in mice models through its effect on bile acid metabolism, which in turn reduces proinflammatory signaling through activation of the farnesoid X receptor (FXR), shows a study recently published in Cellular and Molecular Gastroenterology and Hepatology

“Our results support the notion that pharmacologic FXR activation might be useful in managing IBD [inflammatory bowel disease], and thus, further investigation of its mechanisms of action are warranted,” wrote the authors, led by Andrew Gewirtz, of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Andrew Gewirtz
Dr. Andrew Gewirtz

Dietary fiber has long been understood to be a key component to a healthy diet by promoting intestinal and metabolic health, but it is unclear whether dietary fiber benefits IBD, specifically Crohn’s disease and ulcerative colitis, and if so, what fiber types are best for these conditions. Some studies have suggested an association between fiber-rich diets and reduced incidence of IBD, but some IBD patients experience intolerance to fiber-rich foods and associated fiber-rich foods with disease flares. In mouse models with colitis, semi-purified fibers have been associated with both the easing and exacerbation of IBD symptoms, with soluble/fermentable fibers like inulin and pectin generally worsening colitis.

The study had two goals: Identify specific fibers that might ameliorate two models of experimental colitis in mice models and to better understand the mechanism by which fiber(s) might suppress inflammation.

Mice were fed high-fiber grain-based chow or diets enriched with semi-purified fibers that included inulin, cellulose, pectin, glucomannan, and psyllium, but only psyllium, a semi-soluble derived from Plantago seeds, improved colitis, and metabolic syndrome. The other fibers often protected against obesity but worsened colitis.

Consuming diets enriched with psyllium were found to “markedly” protected against both dextran sulfate sodium– and T-cell transfer–induced colitis. The protection was independent of fermentation and occurred in animals with minimal microbiota. The animals had increased expression of genes that influence bile acid secretion, and the researchers noted increased levels of both fecal and serum BA.

The increased serum levels prompted the researchers to investigate psyllium’s role in signaling activation through BA receptors, especially FXR. An FXR agonist also reduced colitis severity, while an FXR antagonist worsened it. FXR-deficient mice gained little benefit from psyllium supplementation, further suggesting that FXR mediates psyllium’s effect.

All soluble fibers impacted gut microbiota composition, but none more than psyllium which protected mice from developing dextran sulfate sodium colitis. While other soluble fibers increased in the abundance of bacteria (that is, fecal/luminal bacterial density), psyllium decreased in this area, which may explain why some fermentable fibers, including inulin, exacerbate colitis.

“These results indicate that psyllium’s protection against colitis involves its ability to increase circulating bile acid levels, thus activating FXR signaling,” the authors wrote.

Researchers found some evidence that prolonged psyllium supplementation could lead to mild elevations in AST and ALT, suggesting that the ability of psyllium to chelate BA could lead to lipid deficiency, especially in the presence of a low-fat diet.

“We suggest that future studies of psyllium in humans measure serum BA and consider roles for FXR activation in mediating impacts of this fiber,” the authors wrote.

The study was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation. The authors disclosed no conflicts.

Body

Consumption of dietary fibers can promote general health in most people, but is reported to be difficult to tolerate, and even deleterious, in patients suffering from inflammatory bowel disease. Given the broad structural and biochemical diversity of fibers, their mechanisms of action remain to be fully explored.

In a recent study published in Cellular and Molecular Gastroenterology and Hepatology, Bretin et al. highlight how psyllium, a semi-soluble fiber derived from Plantago seeds, can protect mice against both obesity and colitis — a unique feature when compared to other common fibers, such as pectin and inulin, which can also prevent obesity but, in contrast, exacerbate colon inflammation.

Interestingly, although psyllium intake affected the composition of the gut microbiota, its beneficial effects seemed to be partially microbiota independent. In fact, psyllium contributed to colitis protection by inducing an increase in the luminal concentration of bile acids which, in turn, activated the bile acid sensor FXR, thereby suppressing inflammation. Nonetheless, how psyllium elevates bile acids, which FXR-expressing cell types are involved, and why other fibers can also alter bile acids levels without achieving the same effects remain outstanding questions.

This study illustrates the need to assess individually the role of different fibers to provide practitioners with the rationale for optimizing diet in IBD and possible personalized access to fiber health benefits.

Renan Oliveira Corrêa, PhD, is a postdoctoral researcher and Nadine Cerf-Bensussan, MD, PhD, is Inserm Research Director and head of the laboratory of intestinal immunity at the IMAGINE Institute and Université Paris Cité. They have no conflicts of interest.

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Body

Consumption of dietary fibers can promote general health in most people, but is reported to be difficult to tolerate, and even deleterious, in patients suffering from inflammatory bowel disease. Given the broad structural and biochemical diversity of fibers, their mechanisms of action remain to be fully explored.

In a recent study published in Cellular and Molecular Gastroenterology and Hepatology, Bretin et al. highlight how psyllium, a semi-soluble fiber derived from Plantago seeds, can protect mice against both obesity and colitis — a unique feature when compared to other common fibers, such as pectin and inulin, which can also prevent obesity but, in contrast, exacerbate colon inflammation.

Interestingly, although psyllium intake affected the composition of the gut microbiota, its beneficial effects seemed to be partially microbiota independent. In fact, psyllium contributed to colitis protection by inducing an increase in the luminal concentration of bile acids which, in turn, activated the bile acid sensor FXR, thereby suppressing inflammation. Nonetheless, how psyllium elevates bile acids, which FXR-expressing cell types are involved, and why other fibers can also alter bile acids levels without achieving the same effects remain outstanding questions.

This study illustrates the need to assess individually the role of different fibers to provide practitioners with the rationale for optimizing diet in IBD and possible personalized access to fiber health benefits.

Renan Oliveira Corrêa, PhD, is a postdoctoral researcher and Nadine Cerf-Bensussan, MD, PhD, is Inserm Research Director and head of the laboratory of intestinal immunity at the IMAGINE Institute and Université Paris Cité. They have no conflicts of interest.

Body

Consumption of dietary fibers can promote general health in most people, but is reported to be difficult to tolerate, and even deleterious, in patients suffering from inflammatory bowel disease. Given the broad structural and biochemical diversity of fibers, their mechanisms of action remain to be fully explored.

In a recent study published in Cellular and Molecular Gastroenterology and Hepatology, Bretin et al. highlight how psyllium, a semi-soluble fiber derived from Plantago seeds, can protect mice against both obesity and colitis — a unique feature when compared to other common fibers, such as pectin and inulin, which can also prevent obesity but, in contrast, exacerbate colon inflammation.

Interestingly, although psyllium intake affected the composition of the gut microbiota, its beneficial effects seemed to be partially microbiota independent. In fact, psyllium contributed to colitis protection by inducing an increase in the luminal concentration of bile acids which, in turn, activated the bile acid sensor FXR, thereby suppressing inflammation. Nonetheless, how psyllium elevates bile acids, which FXR-expressing cell types are involved, and why other fibers can also alter bile acids levels without achieving the same effects remain outstanding questions.

This study illustrates the need to assess individually the role of different fibers to provide practitioners with the rationale for optimizing diet in IBD and possible personalized access to fiber health benefits.

Renan Oliveira Corrêa, PhD, is a postdoctoral researcher and Nadine Cerf-Bensussan, MD, PhD, is Inserm Research Director and head of the laboratory of intestinal immunity at the IMAGINE Institute and Université Paris Cité. They have no conflicts of interest.

Psyllium fiber offered protection against colitis in mice models through its effect on bile acid metabolism, which in turn reduces proinflammatory signaling through activation of the farnesoid X receptor (FXR), shows a study recently published in Cellular and Molecular Gastroenterology and Hepatology

“Our results support the notion that pharmacologic FXR activation might be useful in managing IBD [inflammatory bowel disease], and thus, further investigation of its mechanisms of action are warranted,” wrote the authors, led by Andrew Gewirtz, of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Andrew Gewirtz
Dr. Andrew Gewirtz

Dietary fiber has long been understood to be a key component to a healthy diet by promoting intestinal and metabolic health, but it is unclear whether dietary fiber benefits IBD, specifically Crohn’s disease and ulcerative colitis, and if so, what fiber types are best for these conditions. Some studies have suggested an association between fiber-rich diets and reduced incidence of IBD, but some IBD patients experience intolerance to fiber-rich foods and associated fiber-rich foods with disease flares. In mouse models with colitis, semi-purified fibers have been associated with both the easing and exacerbation of IBD symptoms, with soluble/fermentable fibers like inulin and pectin generally worsening colitis.

The study had two goals: Identify specific fibers that might ameliorate two models of experimental colitis in mice models and to better understand the mechanism by which fiber(s) might suppress inflammation.

Mice were fed high-fiber grain-based chow or diets enriched with semi-purified fibers that included inulin, cellulose, pectin, glucomannan, and psyllium, but only psyllium, a semi-soluble derived from Plantago seeds, improved colitis, and metabolic syndrome. The other fibers often protected against obesity but worsened colitis.

Consuming diets enriched with psyllium were found to “markedly” protected against both dextran sulfate sodium– and T-cell transfer–induced colitis. The protection was independent of fermentation and occurred in animals with minimal microbiota. The animals had increased expression of genes that influence bile acid secretion, and the researchers noted increased levels of both fecal and serum BA.

The increased serum levels prompted the researchers to investigate psyllium’s role in signaling activation through BA receptors, especially FXR. An FXR agonist also reduced colitis severity, while an FXR antagonist worsened it. FXR-deficient mice gained little benefit from psyllium supplementation, further suggesting that FXR mediates psyllium’s effect.

All soluble fibers impacted gut microbiota composition, but none more than psyllium which protected mice from developing dextran sulfate sodium colitis. While other soluble fibers increased in the abundance of bacteria (that is, fecal/luminal bacterial density), psyllium decreased in this area, which may explain why some fermentable fibers, including inulin, exacerbate colitis.

“These results indicate that psyllium’s protection against colitis involves its ability to increase circulating bile acid levels, thus activating FXR signaling,” the authors wrote.

Researchers found some evidence that prolonged psyllium supplementation could lead to mild elevations in AST and ALT, suggesting that the ability of psyllium to chelate BA could lead to lipid deficiency, especially in the presence of a low-fat diet.

“We suggest that future studies of psyllium in humans measure serum BA and consider roles for FXR activation in mediating impacts of this fiber,” the authors wrote.

The study was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation. The authors disclosed no conflicts.

Psyllium fiber offered protection against colitis in mice models through its effect on bile acid metabolism, which in turn reduces proinflammatory signaling through activation of the farnesoid X receptor (FXR), shows a study recently published in Cellular and Molecular Gastroenterology and Hepatology

“Our results support the notion that pharmacologic FXR activation might be useful in managing IBD [inflammatory bowel disease], and thus, further investigation of its mechanisms of action are warranted,” wrote the authors, led by Andrew Gewirtz, of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Andrew Gewirtz
Dr. Andrew Gewirtz

Dietary fiber has long been understood to be a key component to a healthy diet by promoting intestinal and metabolic health, but it is unclear whether dietary fiber benefits IBD, specifically Crohn’s disease and ulcerative colitis, and if so, what fiber types are best for these conditions. Some studies have suggested an association between fiber-rich diets and reduced incidence of IBD, but some IBD patients experience intolerance to fiber-rich foods and associated fiber-rich foods with disease flares. In mouse models with colitis, semi-purified fibers have been associated with both the easing and exacerbation of IBD symptoms, with soluble/fermentable fibers like inulin and pectin generally worsening colitis.

The study had two goals: Identify specific fibers that might ameliorate two models of experimental colitis in mice models and to better understand the mechanism by which fiber(s) might suppress inflammation.

Mice were fed high-fiber grain-based chow or diets enriched with semi-purified fibers that included inulin, cellulose, pectin, glucomannan, and psyllium, but only psyllium, a semi-soluble derived from Plantago seeds, improved colitis, and metabolic syndrome. The other fibers often protected against obesity but worsened colitis.

Consuming diets enriched with psyllium were found to “markedly” protected against both dextran sulfate sodium– and T-cell transfer–induced colitis. The protection was independent of fermentation and occurred in animals with minimal microbiota. The animals had increased expression of genes that influence bile acid secretion, and the researchers noted increased levels of both fecal and serum BA.

The increased serum levels prompted the researchers to investigate psyllium’s role in signaling activation through BA receptors, especially FXR. An FXR agonist also reduced colitis severity, while an FXR antagonist worsened it. FXR-deficient mice gained little benefit from psyllium supplementation, further suggesting that FXR mediates psyllium’s effect.

All soluble fibers impacted gut microbiota composition, but none more than psyllium which protected mice from developing dextran sulfate sodium colitis. While other soluble fibers increased in the abundance of bacteria (that is, fecal/luminal bacterial density), psyllium decreased in this area, which may explain why some fermentable fibers, including inulin, exacerbate colitis.

“These results indicate that psyllium’s protection against colitis involves its ability to increase circulating bile acid levels, thus activating FXR signaling,” the authors wrote.

Researchers found some evidence that prolonged psyllium supplementation could lead to mild elevations in AST and ALT, suggesting that the ability of psyllium to chelate BA could lead to lipid deficiency, especially in the presence of a low-fat diet.

“We suggest that future studies of psyllium in humans measure serum BA and consider roles for FXR activation in mediating impacts of this fiber,” the authors wrote.

The study was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation. The authors disclosed no conflicts.

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PDAC surveillance in high-risk cases improves outcomes

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Individuals who are carriers of germline pathogenic variants in susceptibility genes for pancreatic ductal adenocarcinoma (PDAC), or have a strong family history of PDAC, benefit from having annual MRIs, shows a new study published in Gastroenterology.

While other studies have shown potential benefit in screening high-risk individuals, “a concern is that in absence of sufficiently large control groups with unscreened controls,” the outcomes may be influenced by lead-time bias. The current study is the first to address that important limitation.

The study, which was led by Derk C.F. Klatte, MD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands, included 43,762 patients from the Netherlands Cancer Registry who were diagnosed with PDAC between January 2000 and December 2020. Using a 1:5 ratio, researchers matched 31 patients who were diagnosed in the pancreatic cancer surveillance cohort against 155 patients in the non-surveillance group.

Leiden University Medical Center
Dr. Derk C.F. Klatte

“We show that surveillance for PDAC in high-risk individuals results in significant earlier detection, increased resectability, and improved survival as compared with average-risk individuals diagnosed with PDAC not under surveillance. This reaffirms that pancreatic surveillance for certain in high-risk individuals is beneficial and could have a meaningful impact on disease course,” the authors wrote.

PDAC has the worst outcomes all cancers and is on pace to become the second-leading cause of cancer-related mortality. By the time a tumor is detected, it is usually unresectable or has developed distant metastases. In principle, early detection could improve outcomes, but there is no test that is adequate for population-wide screening. Surveillance must therefore concentrate on individuals deemed to be at heightened risk. Prospective studies have shown a benefit of pancreatic cancer screening in patients who are at high-risk. Such studies may be misleading, however, due to the potential for lead-time bias. This can occur when a condition is detected at an earlier time than it would have been identified based on clinical signs, as usually occurs in nonscreened populations, and this asymptomatic lag time between diagnosis and initial symptoms does not get incorporated into a survival analysis. The result can be an artificially longer survival time following diagnosis in the screened population.

Guidelines from the International Cancer of the Pancreas Screening (CAPS) consortium, the American Society for Gastrointestinal Endoscopy, and American Society of Clinical Oncology recommend surveillance in high-risk cases.

In this study, researchers conducted a propensity score matched cohort analysis of patients from the general population with primary PDAC who were diagnosed outside of a screening program, with carriers of a germline CDKN2A/p16 mutation who were diagnosed after surveillance.

The surveillance group received a stage 1 diagnosis in 38.7% of cases, versus 5.8% of those outside of surveillance (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). Surgical resection occurred in 71.0% of surveillance patients, versus 18.7% of non-surveillance patients (OR, 10.62; 95% CI, 4.56-26.63), and stage 4 diagnoses were much more common in the nonsurveillance population (61.3% versus 9.7%). Among the patients who did not undergo surveillance, 61.3% were diagnosed with stage 4 disease compared with 9.7% of those in the surveillance group.

The 5-year survival rate (unadjusted for lead-time) in the surveillance group was 32.4% and 4.3% in the nonsurveillance group. The median overall survival was 26.8 months in the surveillance group compared with 5.2 months in the nonsurveillance group, (hazard ratio, 0.22; 95% CI, 0.14-0.36). The mortality rate per 100 person-years was 114.5 (95% CI, 96.2–135.3) in nonsurveillance patients and 21.9 (95% CI, 13.4–33.8) in surveillance patients.

Despite the apparent benefit of screening, there is room for improvement. “Although the outcomes presented here are encouraging and endorse our earlier findings, a significant proportion of surveillance patients (61%) still had poor outcomes because of diagnosis in a late stage (T2–4N0M0 and nodal or distant metastatic PDAC), with a 5-year survival of 16%,” the authors wrote.

The study received no funding and the authors declared no conflicts.

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Individuals who are carriers of germline pathogenic variants in susceptibility genes for pancreatic ductal adenocarcinoma (PDAC), or have a strong family history of PDAC, benefit from having annual MRIs, shows a new study published in Gastroenterology.

While other studies have shown potential benefit in screening high-risk individuals, “a concern is that in absence of sufficiently large control groups with unscreened controls,” the outcomes may be influenced by lead-time bias. The current study is the first to address that important limitation.

The study, which was led by Derk C.F. Klatte, MD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands, included 43,762 patients from the Netherlands Cancer Registry who were diagnosed with PDAC between January 2000 and December 2020. Using a 1:5 ratio, researchers matched 31 patients who were diagnosed in the pancreatic cancer surveillance cohort against 155 patients in the non-surveillance group.

Leiden University Medical Center
Dr. Derk C.F. Klatte

“We show that surveillance for PDAC in high-risk individuals results in significant earlier detection, increased resectability, and improved survival as compared with average-risk individuals diagnosed with PDAC not under surveillance. This reaffirms that pancreatic surveillance for certain in high-risk individuals is beneficial and could have a meaningful impact on disease course,” the authors wrote.

PDAC has the worst outcomes all cancers and is on pace to become the second-leading cause of cancer-related mortality. By the time a tumor is detected, it is usually unresectable or has developed distant metastases. In principle, early detection could improve outcomes, but there is no test that is adequate for population-wide screening. Surveillance must therefore concentrate on individuals deemed to be at heightened risk. Prospective studies have shown a benefit of pancreatic cancer screening in patients who are at high-risk. Such studies may be misleading, however, due to the potential for lead-time bias. This can occur when a condition is detected at an earlier time than it would have been identified based on clinical signs, as usually occurs in nonscreened populations, and this asymptomatic lag time between diagnosis and initial symptoms does not get incorporated into a survival analysis. The result can be an artificially longer survival time following diagnosis in the screened population.

Guidelines from the International Cancer of the Pancreas Screening (CAPS) consortium, the American Society for Gastrointestinal Endoscopy, and American Society of Clinical Oncology recommend surveillance in high-risk cases.

In this study, researchers conducted a propensity score matched cohort analysis of patients from the general population with primary PDAC who were diagnosed outside of a screening program, with carriers of a germline CDKN2A/p16 mutation who were diagnosed after surveillance.

The surveillance group received a stage 1 diagnosis in 38.7% of cases, versus 5.8% of those outside of surveillance (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). Surgical resection occurred in 71.0% of surveillance patients, versus 18.7% of non-surveillance patients (OR, 10.62; 95% CI, 4.56-26.63), and stage 4 diagnoses were much more common in the nonsurveillance population (61.3% versus 9.7%). Among the patients who did not undergo surveillance, 61.3% were diagnosed with stage 4 disease compared with 9.7% of those in the surveillance group.

The 5-year survival rate (unadjusted for lead-time) in the surveillance group was 32.4% and 4.3% in the nonsurveillance group. The median overall survival was 26.8 months in the surveillance group compared with 5.2 months in the nonsurveillance group, (hazard ratio, 0.22; 95% CI, 0.14-0.36). The mortality rate per 100 person-years was 114.5 (95% CI, 96.2–135.3) in nonsurveillance patients and 21.9 (95% CI, 13.4–33.8) in surveillance patients.

Despite the apparent benefit of screening, there is room for improvement. “Although the outcomes presented here are encouraging and endorse our earlier findings, a significant proportion of surveillance patients (61%) still had poor outcomes because of diagnosis in a late stage (T2–4N0M0 and nodal or distant metastatic PDAC), with a 5-year survival of 16%,” the authors wrote.

The study received no funding and the authors declared no conflicts.

Individuals who are carriers of germline pathogenic variants in susceptibility genes for pancreatic ductal adenocarcinoma (PDAC), or have a strong family history of PDAC, benefit from having annual MRIs, shows a new study published in Gastroenterology.

While other studies have shown potential benefit in screening high-risk individuals, “a concern is that in absence of sufficiently large control groups with unscreened controls,” the outcomes may be influenced by lead-time bias. The current study is the first to address that important limitation.

The study, which was led by Derk C.F. Klatte, MD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands, included 43,762 patients from the Netherlands Cancer Registry who were diagnosed with PDAC between January 2000 and December 2020. Using a 1:5 ratio, researchers matched 31 patients who were diagnosed in the pancreatic cancer surveillance cohort against 155 patients in the non-surveillance group.

Leiden University Medical Center
Dr. Derk C.F. Klatte

“We show that surveillance for PDAC in high-risk individuals results in significant earlier detection, increased resectability, and improved survival as compared with average-risk individuals diagnosed with PDAC not under surveillance. This reaffirms that pancreatic surveillance for certain in high-risk individuals is beneficial and could have a meaningful impact on disease course,” the authors wrote.

PDAC has the worst outcomes all cancers and is on pace to become the second-leading cause of cancer-related mortality. By the time a tumor is detected, it is usually unresectable or has developed distant metastases. In principle, early detection could improve outcomes, but there is no test that is adequate for population-wide screening. Surveillance must therefore concentrate on individuals deemed to be at heightened risk. Prospective studies have shown a benefit of pancreatic cancer screening in patients who are at high-risk. Such studies may be misleading, however, due to the potential for lead-time bias. This can occur when a condition is detected at an earlier time than it would have been identified based on clinical signs, as usually occurs in nonscreened populations, and this asymptomatic lag time between diagnosis and initial symptoms does not get incorporated into a survival analysis. The result can be an artificially longer survival time following diagnosis in the screened population.

Guidelines from the International Cancer of the Pancreas Screening (CAPS) consortium, the American Society for Gastrointestinal Endoscopy, and American Society of Clinical Oncology recommend surveillance in high-risk cases.

In this study, researchers conducted a propensity score matched cohort analysis of patients from the general population with primary PDAC who were diagnosed outside of a screening program, with carriers of a germline CDKN2A/p16 mutation who were diagnosed after surveillance.

The surveillance group received a stage 1 diagnosis in 38.7% of cases, versus 5.8% of those outside of surveillance (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). Surgical resection occurred in 71.0% of surveillance patients, versus 18.7% of non-surveillance patients (OR, 10.62; 95% CI, 4.56-26.63), and stage 4 diagnoses were much more common in the nonsurveillance population (61.3% versus 9.7%). Among the patients who did not undergo surveillance, 61.3% were diagnosed with stage 4 disease compared with 9.7% of those in the surveillance group.

The 5-year survival rate (unadjusted for lead-time) in the surveillance group was 32.4% and 4.3% in the nonsurveillance group. The median overall survival was 26.8 months in the surveillance group compared with 5.2 months in the nonsurveillance group, (hazard ratio, 0.22; 95% CI, 0.14-0.36). The mortality rate per 100 person-years was 114.5 (95% CI, 96.2–135.3) in nonsurveillance patients and 21.9 (95% CI, 13.4–33.8) in surveillance patients.

Despite the apparent benefit of screening, there is room for improvement. “Although the outcomes presented here are encouraging and endorse our earlier findings, a significant proportion of surveillance patients (61%) still had poor outcomes because of diagnosis in a late stage (T2–4N0M0 and nodal or distant metastatic PDAC), with a 5-year survival of 16%,” the authors wrote.

The study received no funding and the authors declared no conflicts.

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AGA clinical practice update: Extraesophageal gastroesophageal reflux disease

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Changed
Fri, 05/12/2023 - 01:16

Extraesophageal reflux (EER) symptoms are a subset of gastroesophageal reflux disease (GERD) that can be difficult to diagnose because of its heterogeneous nature and symptoms that overlap with other conditions.

That puts the onus on physicians to take all symptoms into account and work across disciplines to diagnose, manage, and treat the condition, according to a new clinical practice update from the American Gastroenterological Association, which was published in Clinical Gastroenterology and Hepatology.

University of Michigan Health
Dr. Joan W. Chen

GERD is becoming increasingly common, which in turn has led to greater awareness and consideration of EER symptoms. EER symptoms can present a challenge because they may vary considerably and are not unique to GERD. The symptoms often do not respond well to proton pump inhibitor (PPI) therapy.

EER symptoms can include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, postnasal drip, and throat clearing. Some patients with EER symptoms do not report heartburn or regurgitation, which leaves it up to the physician to determine if acid reflux is present and contributing to symptoms.

“The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies,” wrote the authors, who were led by Joan W. Chen, MD, MS, a gastroenterologist with the University of Michigan, Ann Arbor.

There is also debate over whether fluid refluxate is the source of damage that causes EER symptoms, and if so, whether it is sufficient that the fluid be acidic or that pepsin be present, or if the cause is related to neurogenic signaling and resulting inflammation. Because of these questions, a PPI trial will not necessarily provide insight into the role of acid reflux in EER symptoms.

American Gastroenterological Association
Extraesophageal gastroesophageal reflux treatment guidance.

To guide physicians in diagnosing and managing EER symptoms, the authors created 10 advice statements based on a review of the published literature and expert opinion.

Best practice advice 1: The authors emphasized that gastroenterologists need to be aware of the potential extraesophageal symptoms of GERD. They should inquire with GERD patients to determine if laryngitis, chronic cough, asthma, and dental erosions are present.

Best practice advice 2: Consider a multidisciplinary approach to EER manifestations. Cases may require input from non-GI specialties. Tests performed by other specialists, such as bronchoscopy, thoracic imaging, or laryngoscopy, should be taken into account, since patients will also seek out multiple specialists to address their symptoms.

Best practice advice 3: There is no specific diagnostic test available to determine if GER is the cause of EER symptoms. Instead, physicians should interpret patient symptoms, response to GER therapy, and input from endoscopy and reflux tests.

Best practice advice 4: Rather than subject the patient to the cost and potential for even rare adverse events of a PPI trial, physicians should first consider conducting reflux testing. A PPI trial has clinical value but is insufficient on its own to help diagnose or manage EER. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.

Best practice advice 5: The inconsistent therapeutic response to PPI therapy means that positive effects of PPI therapy on EER symptoms can’t confirm a GERD diagnosis because a placebo effect may be involved, and because symptom improvement can occur through mechanisms other than acid suppression. A meta-analysis found that a PPI trial has a sensitivity of 71%-78% and a specificity of 41%-54% with typical symptoms of heartburn and regurgitation. “Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower,” the authors wrote.

Best practice advice 6: When EER symptoms related to GERD are suspected and a PPI trial of up to 12 weeks does not lead to adequate improvement, the physician should consider testing for pathologic GER. Additional trials employing other PPIs are unlikely to succeed.

Best practice advice 7: Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation. Potential methods to evaluate reflux include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy, which can assist with a GERD diagnosis, particularly when nonerosive reflux is present.

Best practice advice 8: About 50%-60% of patients with EER symptoms will not have GERD. Testing can be considered for those with an established objective diagnosis of GERD who do not respond well to high doses of acid suppression. Cost-effectiveness studies have confirmed the value of starting with ambulatory reflux monitoring, which can include a catheter-based pH sensor, pH impedance, or wireless pH capsule.

Ambulatory esophageal pH monitoring can also assist in making a GERD diagnosis, but it does not indicate whether GERD may be contributing to EER symptoms.

“Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms,” the authors wrote. They also pointed out that ambulatory reflux monitoring in EER patients should be done in the absence of acid suppression unless there is already objective evidence for the presence of GERD.

Best practice advice 9: Aside from acid suppression, EER symptoms can also be managed through other means, including lifestyle modifications, such as eating avoidance prior to lying down, elevation of the head of the bed, sleeping on the left side, and weight loss. Or, alginate containing antacids, external upper esophageal sphincter compression device, cognitive behavioral therapy, and neuromodulators.

Best practice advice 10: In cases where the EER patient has objectively defined evidence of GERD, physicians should employ shared decision-making before considering anti-reflux surgery. If the patient did not respond to PPI therapy, this predicts a lack of response to antireflux surgery.

All four authors reported financial ties to multiple pharmaceutical companies.

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Extraesophageal reflux (EER) symptoms are a subset of gastroesophageal reflux disease (GERD) that can be difficult to diagnose because of its heterogeneous nature and symptoms that overlap with other conditions.

That puts the onus on physicians to take all symptoms into account and work across disciplines to diagnose, manage, and treat the condition, according to a new clinical practice update from the American Gastroenterological Association, which was published in Clinical Gastroenterology and Hepatology.

University of Michigan Health
Dr. Joan W. Chen

GERD is becoming increasingly common, which in turn has led to greater awareness and consideration of EER symptoms. EER symptoms can present a challenge because they may vary considerably and are not unique to GERD. The symptoms often do not respond well to proton pump inhibitor (PPI) therapy.

EER symptoms can include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, postnasal drip, and throat clearing. Some patients with EER symptoms do not report heartburn or regurgitation, which leaves it up to the physician to determine if acid reflux is present and contributing to symptoms.

“The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies,” wrote the authors, who were led by Joan W. Chen, MD, MS, a gastroenterologist with the University of Michigan, Ann Arbor.

There is also debate over whether fluid refluxate is the source of damage that causes EER symptoms, and if so, whether it is sufficient that the fluid be acidic or that pepsin be present, or if the cause is related to neurogenic signaling and resulting inflammation. Because of these questions, a PPI trial will not necessarily provide insight into the role of acid reflux in EER symptoms.

American Gastroenterological Association
Extraesophageal gastroesophageal reflux treatment guidance.

To guide physicians in diagnosing and managing EER symptoms, the authors created 10 advice statements based on a review of the published literature and expert opinion.

Best practice advice 1: The authors emphasized that gastroenterologists need to be aware of the potential extraesophageal symptoms of GERD. They should inquire with GERD patients to determine if laryngitis, chronic cough, asthma, and dental erosions are present.

Best practice advice 2: Consider a multidisciplinary approach to EER manifestations. Cases may require input from non-GI specialties. Tests performed by other specialists, such as bronchoscopy, thoracic imaging, or laryngoscopy, should be taken into account, since patients will also seek out multiple specialists to address their symptoms.

Best practice advice 3: There is no specific diagnostic test available to determine if GER is the cause of EER symptoms. Instead, physicians should interpret patient symptoms, response to GER therapy, and input from endoscopy and reflux tests.

Best practice advice 4: Rather than subject the patient to the cost and potential for even rare adverse events of a PPI trial, physicians should first consider conducting reflux testing. A PPI trial has clinical value but is insufficient on its own to help diagnose or manage EER. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.

Best practice advice 5: The inconsistent therapeutic response to PPI therapy means that positive effects of PPI therapy on EER symptoms can’t confirm a GERD diagnosis because a placebo effect may be involved, and because symptom improvement can occur through mechanisms other than acid suppression. A meta-analysis found that a PPI trial has a sensitivity of 71%-78% and a specificity of 41%-54% with typical symptoms of heartburn and regurgitation. “Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower,” the authors wrote.

Best practice advice 6: When EER symptoms related to GERD are suspected and a PPI trial of up to 12 weeks does not lead to adequate improvement, the physician should consider testing for pathologic GER. Additional trials employing other PPIs are unlikely to succeed.

Best practice advice 7: Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation. Potential methods to evaluate reflux include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy, which can assist with a GERD diagnosis, particularly when nonerosive reflux is present.

Best practice advice 8: About 50%-60% of patients with EER symptoms will not have GERD. Testing can be considered for those with an established objective diagnosis of GERD who do not respond well to high doses of acid suppression. Cost-effectiveness studies have confirmed the value of starting with ambulatory reflux monitoring, which can include a catheter-based pH sensor, pH impedance, or wireless pH capsule.

Ambulatory esophageal pH monitoring can also assist in making a GERD diagnosis, but it does not indicate whether GERD may be contributing to EER symptoms.

“Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms,” the authors wrote. They also pointed out that ambulatory reflux monitoring in EER patients should be done in the absence of acid suppression unless there is already objective evidence for the presence of GERD.

Best practice advice 9: Aside from acid suppression, EER symptoms can also be managed through other means, including lifestyle modifications, such as eating avoidance prior to lying down, elevation of the head of the bed, sleeping on the left side, and weight loss. Or, alginate containing antacids, external upper esophageal sphincter compression device, cognitive behavioral therapy, and neuromodulators.

Best practice advice 10: In cases where the EER patient has objectively defined evidence of GERD, physicians should employ shared decision-making before considering anti-reflux surgery. If the patient did not respond to PPI therapy, this predicts a lack of response to antireflux surgery.

All four authors reported financial ties to multiple pharmaceutical companies.

Extraesophageal reflux (EER) symptoms are a subset of gastroesophageal reflux disease (GERD) that can be difficult to diagnose because of its heterogeneous nature and symptoms that overlap with other conditions.

That puts the onus on physicians to take all symptoms into account and work across disciplines to diagnose, manage, and treat the condition, according to a new clinical practice update from the American Gastroenterological Association, which was published in Clinical Gastroenterology and Hepatology.

University of Michigan Health
Dr. Joan W. Chen

GERD is becoming increasingly common, which in turn has led to greater awareness and consideration of EER symptoms. EER symptoms can present a challenge because they may vary considerably and are not unique to GERD. The symptoms often do not respond well to proton pump inhibitor (PPI) therapy.

EER symptoms can include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, postnasal drip, and throat clearing. Some patients with EER symptoms do not report heartburn or regurgitation, which leaves it up to the physician to determine if acid reflux is present and contributing to symptoms.

“The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies,” wrote the authors, who were led by Joan W. Chen, MD, MS, a gastroenterologist with the University of Michigan, Ann Arbor.

There is also debate over whether fluid refluxate is the source of damage that causes EER symptoms, and if so, whether it is sufficient that the fluid be acidic or that pepsin be present, or if the cause is related to neurogenic signaling and resulting inflammation. Because of these questions, a PPI trial will not necessarily provide insight into the role of acid reflux in EER symptoms.

American Gastroenterological Association
Extraesophageal gastroesophageal reflux treatment guidance.

To guide physicians in diagnosing and managing EER symptoms, the authors created 10 advice statements based on a review of the published literature and expert opinion.

Best practice advice 1: The authors emphasized that gastroenterologists need to be aware of the potential extraesophageal symptoms of GERD. They should inquire with GERD patients to determine if laryngitis, chronic cough, asthma, and dental erosions are present.

Best practice advice 2: Consider a multidisciplinary approach to EER manifestations. Cases may require input from non-GI specialties. Tests performed by other specialists, such as bronchoscopy, thoracic imaging, or laryngoscopy, should be taken into account, since patients will also seek out multiple specialists to address their symptoms.

Best practice advice 3: There is no specific diagnostic test available to determine if GER is the cause of EER symptoms. Instead, physicians should interpret patient symptoms, response to GER therapy, and input from endoscopy and reflux tests.

Best practice advice 4: Rather than subject the patient to the cost and potential for even rare adverse events of a PPI trial, physicians should first consider conducting reflux testing. A PPI trial has clinical value but is insufficient on its own to help diagnose or manage EER. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.

Best practice advice 5: The inconsistent therapeutic response to PPI therapy means that positive effects of PPI therapy on EER symptoms can’t confirm a GERD diagnosis because a placebo effect may be involved, and because symptom improvement can occur through mechanisms other than acid suppression. A meta-analysis found that a PPI trial has a sensitivity of 71%-78% and a specificity of 41%-54% with typical symptoms of heartburn and regurgitation. “Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower,” the authors wrote.

Best practice advice 6: When EER symptoms related to GERD are suspected and a PPI trial of up to 12 weeks does not lead to adequate improvement, the physician should consider testing for pathologic GER. Additional trials employing other PPIs are unlikely to succeed.

Best practice advice 7: Initial testing to evaluate for reflux should be tailored to patients’ clinical presentation. Potential methods to evaluate reflux include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy, which can assist with a GERD diagnosis, particularly when nonerosive reflux is present.

Best practice advice 8: About 50%-60% of patients with EER symptoms will not have GERD. Testing can be considered for those with an established objective diagnosis of GERD who do not respond well to high doses of acid suppression. Cost-effectiveness studies have confirmed the value of starting with ambulatory reflux monitoring, which can include a catheter-based pH sensor, pH impedance, or wireless pH capsule.

Ambulatory esophageal pH monitoring can also assist in making a GERD diagnosis, but it does not indicate whether GERD may be contributing to EER symptoms.

“Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms,” the authors wrote. They also pointed out that ambulatory reflux monitoring in EER patients should be done in the absence of acid suppression unless there is already objective evidence for the presence of GERD.

Best practice advice 9: Aside from acid suppression, EER symptoms can also be managed through other means, including lifestyle modifications, such as eating avoidance prior to lying down, elevation of the head of the bed, sleeping on the left side, and weight loss. Or, alginate containing antacids, external upper esophageal sphincter compression device, cognitive behavioral therapy, and neuromodulators.

Best practice advice 10: In cases where the EER patient has objectively defined evidence of GERD, physicians should employ shared decision-making before considering anti-reflux surgery. If the patient did not respond to PPI therapy, this predicts a lack of response to antireflux surgery.

All four authors reported financial ties to multiple pharmaceutical companies.

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