Will Pass

Employing a targeted nano drug delivery system for patients with hepatocellular carcinoma (HCC) could overcome issues with liver toxicity, leading to safer treatment and better outcomes, according to a recent review.

Nanomedicines homing in on the Wnt/beta-catenin signaling pathway could be particularly impactful, Mamatha Bhat, MD, PhD, a hepatologist and clinician-scientist at Toronto General Hospital Research Institute, and colleagues reported, as this is one of the most up-regulated pathways in HCC.

To date, however, agents addressing this pathway have been hindered by off-target toxicity, suggesting that more work is needed to develop the right payload for nanoparticle delivery, the investigators wrote in Gastro Hep Advances.

“Although nanotherapeutics offers an unmatched improvement in drug delivery, due to the limited impact and treatment-resistance demonstrated by the current systemic therapies, there is currently no approved nanomedicine for the treatment of HCC,” the investigators wrote. “Therefore, it is of utmost importance to dig deeper into understanding the signaling pathways that govern hepatocarcinogenesis and identify novel targets that can be used to develop more specific and targeted nanotherapies.”

Their review focused on the Wnt/beta-catenin signaling pathway, but first, Dr. Bhat and colleagues discussed the characteristics of inorganic versus lipid nanoparticles, as these differences can determine liver uptake.

Inorganic nanoparticles have a high surface-to-volume ratio, leading to increased surface charges that enhance cellular uptake. However, they are prone to oxidation, requiring surface modifications or short circulation times to prevent degradation. These nanoparticles are limited in delivering chemotherapeutic drugs and peptides, and are not suitable for encapsulating nucleic acids.

In contrast, lipid nanoparticles are preferred for targeted delivery in HCC, according to the investigators. They have a natural affinity for apolipoprotein E (apo E), resembling lipoproteins, which aids in specific liver cell targeting. When lipid nanoparticles enter the bloodstream, they interact with apo E–rich lipoproteins like HDL cholesterol and LDL cholesterol, leading to formation of complexes recognized by LDL cholesterol receptors on liver cells. This triggers receptor-mediated endocytosis, internalizing apo E–lipid nanoparticle complexes into HCC cells.

The other major variable is the selected treatment target. Dr. Bhat and colleagues made the case for the Wnt/beta-catenin signaling pathway based on alterations found in approximately two-thirds of patients with HCC.

“Aberrant activation of this pathway and mutations in genes encoding key components are characteristic to hepatocarcinogenesis and promote tumor growth and dedifferentiation,” they wrote.

Although beta-catenin itself makes for an obvious molecular target, especially considering known associations with drug resistance, its flat structure lacks deep binding pockets that would be suitable for small-molecule inhibitors, and any available pockets may be altered by numerous posttranscriptional modifications. Instead, beta-catenin could be indirectly modulated by nanoparticle-mediated siRNA therapy, as this would allow for precise delivery of siRNA to cancer cells, minimizing off-target toxicity.

Alternative approaches could involve targeting proteasomal degradation of beta-catenin, transcriptional coactivators of beta-catenin, or different oncogenes in HCC, all of which are described in further detail in the review, along with promising preclinical findings.

“With ongoing advancements in nanotechnology, there is optimism that it will continue to play a vital role in overcoming the challenges associated with HCC management and contribute to further advancements in therapeutic outcomes for patients,” the authors concluded.

One coauthor disclosed external funding by a Mitacs Elevate postdoctoral fellowship in collaboration with Highland Therapeutics. The remaining authors disclosed no conflicts of interest.

Employing a targeted nano drug delivery system for patients with hepatocellular carcinoma (HCC) could overcome issues with liver toxicity, leading to safer treatment and better outcomes, according to a recent review.

Nanomedicines homing in on the Wnt/beta-catenin signaling pathway could be particularly impactful, Mamatha Bhat, MD, PhD, a hepatologist and clinician-scientist at Toronto General Hospital Research Institute, and colleagues reported, as this is one of the most up-regulated pathways in HCC.

To date, however, agents addressing this pathway have been hindered by off-target toxicity, suggesting that more work is needed to develop the right payload for nanoparticle delivery, the investigators wrote in Gastro Hep Advances.

“Although nanotherapeutics offers an unmatched improvement in drug delivery, due to the limited impact and treatment-resistance demonstrated by the current systemic therapies, there is currently no approved nanomedicine for the treatment of HCC,” the investigators wrote. “Therefore, it is of utmost importance to dig deeper into understanding the signaling pathways that govern hepatocarcinogenesis and identify novel targets that can be used to develop more specific and targeted nanotherapies.”

Their review focused on the Wnt/beta-catenin signaling pathway, but first, Dr. Bhat and colleagues discussed the characteristics of inorganic versus lipid nanoparticles, as these differences can determine liver uptake.

Inorganic nanoparticles have a high surface-to-volume ratio, leading to increased surface charges that enhance cellular uptake. However, they are prone to oxidation, requiring surface modifications or short circulation times to prevent degradation. These nanoparticles are limited in delivering chemotherapeutic drugs and peptides, and are not suitable for encapsulating nucleic acids.

In contrast, lipid nanoparticles are preferred for targeted delivery in HCC, according to the investigators. They have a natural affinity for apolipoprotein E (apo E), resembling lipoproteins, which aids in specific liver cell targeting. When lipid nanoparticles enter the bloodstream, they interact with apo E–rich lipoproteins like HDL cholesterol and LDL cholesterol, leading to formation of complexes recognized by LDL cholesterol receptors on liver cells. This triggers receptor-mediated endocytosis, internalizing apo E–lipid nanoparticle complexes into HCC cells.

The other major variable is the selected treatment target. Dr. Bhat and colleagues made the case for the Wnt/beta-catenin signaling pathway based on alterations found in approximately two-thirds of patients with HCC.

“Aberrant activation of this pathway and mutations in genes encoding key components are characteristic to hepatocarcinogenesis and promote tumor growth and dedifferentiation,” they wrote.

Although beta-catenin itself makes for an obvious molecular target, especially considering known associations with drug resistance, its flat structure lacks deep binding pockets that would be suitable for small-molecule inhibitors, and any available pockets may be altered by numerous posttranscriptional modifications. Instead, beta-catenin could be indirectly modulated by nanoparticle-mediated siRNA therapy, as this would allow for precise delivery of siRNA to cancer cells, minimizing off-target toxicity.

Alternative approaches could involve targeting proteasomal degradation of beta-catenin, transcriptional coactivators of beta-catenin, or different oncogenes in HCC, all of which are described in further detail in the review, along with promising preclinical findings.

“With ongoing advancements in nanotechnology, there is optimism that it will continue to play a vital role in overcoming the challenges associated with HCC management and contribute to further advancements in therapeutic outcomes for patients,” the authors concluded.

One coauthor disclosed external funding by a Mitacs Elevate postdoctoral fellowship in collaboration with Highland Therapeutics. The remaining authors disclosed no conflicts of interest.

Employing a targeted nano drug delivery system for patients with hepatocellular carcinoma (HCC) could overcome issues with liver toxicity, leading to safer treatment and better outcomes, according to a recent review.

Nanomedicines homing in on the Wnt/beta-catenin signaling pathway could be particularly impactful, Mamatha Bhat, MD, PhD, a hepatologist and clinician-scientist at Toronto General Hospital Research Institute, and colleagues reported, as this is one of the most up-regulated pathways in HCC.

To date, however, agents addressing this pathway have been hindered by off-target toxicity, suggesting that more work is needed to develop the right payload for nanoparticle delivery, the investigators wrote in Gastro Hep Advances.

“Although nanotherapeutics offers an unmatched improvement in drug delivery, due to the limited impact and treatment-resistance demonstrated by the current systemic therapies, there is currently no approved nanomedicine for the treatment of HCC,” the investigators wrote. “Therefore, it is of utmost importance to dig deeper into understanding the signaling pathways that govern hepatocarcinogenesis and identify novel targets that can be used to develop more specific and targeted nanotherapies.”

Their review focused on the Wnt/beta-catenin signaling pathway, but first, Dr. Bhat and colleagues discussed the characteristics of inorganic versus lipid nanoparticles, as these differences can determine liver uptake.

Inorganic nanoparticles have a high surface-to-volume ratio, leading to increased surface charges that enhance cellular uptake. However, they are prone to oxidation, requiring surface modifications or short circulation times to prevent degradation. These nanoparticles are limited in delivering chemotherapeutic drugs and peptides, and are not suitable for encapsulating nucleic acids.

In contrast, lipid nanoparticles are preferred for targeted delivery in HCC, according to the investigators. They have a natural affinity for apolipoprotein E (apo E), resembling lipoproteins, which aids in specific liver cell targeting. When lipid nanoparticles enter the bloodstream, they interact with apo E–rich lipoproteins like HDL cholesterol and LDL cholesterol, leading to formation of complexes recognized by LDL cholesterol receptors on liver cells. This triggers receptor-mediated endocytosis, internalizing apo E–lipid nanoparticle complexes into HCC cells.

The other major variable is the selected treatment target. Dr. Bhat and colleagues made the case for the Wnt/beta-catenin signaling pathway based on alterations found in approximately two-thirds of patients with HCC.

“Aberrant activation of this pathway and mutations in genes encoding key components are characteristic to hepatocarcinogenesis and promote tumor growth and dedifferentiation,” they wrote.

Although beta-catenin itself makes for an obvious molecular target, especially considering known associations with drug resistance, its flat structure lacks deep binding pockets that would be suitable for small-molecule inhibitors, and any available pockets may be altered by numerous posttranscriptional modifications. Instead, beta-catenin could be indirectly modulated by nanoparticle-mediated siRNA therapy, as this would allow for precise delivery of siRNA to cancer cells, minimizing off-target toxicity.

Alternative approaches could involve targeting proteasomal degradation of beta-catenin, transcriptional coactivators of beta-catenin, or different oncogenes in HCC, all of which are described in further detail in the review, along with promising preclinical findings.

“With ongoing advancements in nanotechnology, there is optimism that it will continue to play a vital role in overcoming the challenges associated with HCC management and contribute to further advancements in therapeutic outcomes for patients,” the authors concluded.

One coauthor disclosed external funding by a Mitacs Elevate postdoctoral fellowship in collaboration with Highland Therapeutics. The remaining authors disclosed no conflicts of interest.

Modulating N2-neutrophil activity could offer a new therapeutic approach to Wilson’s disease, according to a preclinical study.

Inhibiting neutrophil function via transforming growth factor (TGF-beta 1) inhibition or methylation inhibition reduced parenchymal liver fibrosis and injury while improving liver function in a mouse model of Wilson’s disease, shows new research published in Cellular and Molecular Gastroenterology and Hepatology.

Also called progressive hepatolenticular degeneration, Wilson’s disease is an inherited nervous system disorder that can occur as a result of severe liver disease. It is caused by variants in the ATP7B gene which can lead to abnormalities in copper metabolism that lead to accumulation of the heavy metal in the liver and brain, resulting in damage to both organs. Approximately 60% of patients with Wilson’s disease present with hepatic syndromes, and of those 50%-60% go on to develop liver cirrhosis.

Current treatments aim to address metal deposition, but this approach is poorly tolerated by many patients, wrote investigators who were led by Junping Shi, MD, PhD, of the Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, China.

“Drug interventions (such as copper chelators and zinc salts) reduce pathologic copper deposition, but side effects can be observed in up to 40% of patients during treatment and even after years of treatment, particularly nephropathy, autoimmune conditions, and skin changes,” the investigators wrote. “Liver transplantation is an effective treatment for Wilson’s disease, particularly for patients with end-stage liver disease, but donor shortages and lifelong immunosuppression limit its use. Therefore, alternative treatments with higher specificity in Wilson’s disease patients are urgently needed.”

The present study explored the underlying metabolic abnormalities in Wilson’s disease that result in liver injury and fibrosis, and related therapeutic approaches. Based on previous studies that have shown a relationship between persistent neutrophil infiltration and chronic tissue inflammation and damage, the investigators sought to explore the role of neutrophils in Wilson’s disease, with a focus on the N2 subtype.

First, they analyzed neutrophil populations in the livers of Atp7b–/– mice and atp7b–/– zebrafish, both of which are established animal models of Wilson’s disease. Compared with the wild-type comparison animals, the livers of disease model animals showed increased neutrophil infiltration, in terms of both count and density.

In one of several related experiments, administering a neutrophil agonist in the presence of copper led to significantly greater neutrophil infiltration in mutant versus wild-type fish, as well as greater increases in lipid droplets and disorganized tissue structure, which serve as markers of disease activity.

“Collectively, these data suggested that neutrophils infiltrated the liver and accelerated liver defects in Wilson’s disease,” the investigators wrote.

Additional experiments with the mouse model showed that pharmacologic ablation of N2 neutrophils via two approaches led to reduced liver fibrosis, offering a glimpse at therapeutic potential.

These findings were further supported by experiments involving a cellular model of Wilson’s disease with isolated bone marrow neutrophils. These analyses revealed the role of the TGF1–DNMT3A/STAT3 signaling axis in neutrophil polarization, and resultant liver disease progression, in Wilson’s disease.

“Neutrophil heterogeneity shows therapeutic potential, and pharmacologic modulation of N2-neutrophil activity should be explored as an alternative therapeutic to improve liver function in Wilson’s disease,” the investigators concluded, noting that TGF-beta 1, DNMT3A, or STAT3 could all serve as rational therapeutic targets.

Beyond Wilson’s disease, the findings may offer broader value for understanding the mechanisms driving other neutrophil-related diseases, as well as possible therapeutic approaches for those conditions, the authors added.

The authors disclosed no conflicts of interest.

Modulating N2-neutrophil activity could offer a new therapeutic approach to Wilson’s disease, according to a preclinical study.

Inhibiting neutrophil function via transforming growth factor (TGF-beta 1) inhibition or methylation inhibition reduced parenchymal liver fibrosis and injury while improving liver function in a mouse model of Wilson’s disease, shows new research published in Cellular and Molecular Gastroenterology and Hepatology.

Also called progressive hepatolenticular degeneration, Wilson’s disease is an inherited nervous system disorder that can occur as a result of severe liver disease. It is caused by variants in the ATP7B gene which can lead to abnormalities in copper metabolism that lead to accumulation of the heavy metal in the liver and brain, resulting in damage to both organs. Approximately 60% of patients with Wilson’s disease present with hepatic syndromes, and of those 50%-60% go on to develop liver cirrhosis.

Current treatments aim to address metal deposition, but this approach is poorly tolerated by many patients, wrote investigators who were led by Junping Shi, MD, PhD, of the Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, China.

“Drug interventions (such as copper chelators and zinc salts) reduce pathologic copper deposition, but side effects can be observed in up to 40% of patients during treatment and even after years of treatment, particularly nephropathy, autoimmune conditions, and skin changes,” the investigators wrote. “Liver transplantation is an effective treatment for Wilson’s disease, particularly for patients with end-stage liver disease, but donor shortages and lifelong immunosuppression limit its use. Therefore, alternative treatments with higher specificity in Wilson’s disease patients are urgently needed.”

The present study explored the underlying metabolic abnormalities in Wilson’s disease that result in liver injury and fibrosis, and related therapeutic approaches. Based on previous studies that have shown a relationship between persistent neutrophil infiltration and chronic tissue inflammation and damage, the investigators sought to explore the role of neutrophils in Wilson’s disease, with a focus on the N2 subtype.

First, they analyzed neutrophil populations in the livers of Atp7b–/– mice and atp7b–/– zebrafish, both of which are established animal models of Wilson’s disease. Compared with the wild-type comparison animals, the livers of disease model animals showed increased neutrophil infiltration, in terms of both count and density.

In one of several related experiments, administering a neutrophil agonist in the presence of copper led to significantly greater neutrophil infiltration in mutant versus wild-type fish, as well as greater increases in lipid droplets and disorganized tissue structure, which serve as markers of disease activity.

“Collectively, these data suggested that neutrophils infiltrated the liver and accelerated liver defects in Wilson’s disease,” the investigators wrote.

Additional experiments with the mouse model showed that pharmacologic ablation of N2 neutrophils via two approaches led to reduced liver fibrosis, offering a glimpse at therapeutic potential.

These findings were further supported by experiments involving a cellular model of Wilson’s disease with isolated bone marrow neutrophils. These analyses revealed the role of the TGF1–DNMT3A/STAT3 signaling axis in neutrophil polarization, and resultant liver disease progression, in Wilson’s disease.

“Neutrophil heterogeneity shows therapeutic potential, and pharmacologic modulation of N2-neutrophil activity should be explored as an alternative therapeutic to improve liver function in Wilson’s disease,” the investigators concluded, noting that TGF-beta 1, DNMT3A, or STAT3 could all serve as rational therapeutic targets.

Beyond Wilson’s disease, the findings may offer broader value for understanding the mechanisms driving other neutrophil-related diseases, as well as possible therapeutic approaches for those conditions, the authors added.

The authors disclosed no conflicts of interest.

Modulating N2-neutrophil activity could offer a new therapeutic approach to Wilson’s disease, according to a preclinical study.

Inhibiting neutrophil function via transforming growth factor (TGF-beta 1) inhibition or methylation inhibition reduced parenchymal liver fibrosis and injury while improving liver function in a mouse model of Wilson’s disease, shows new research published in Cellular and Molecular Gastroenterology and Hepatology.

Also called progressive hepatolenticular degeneration, Wilson’s disease is an inherited nervous system disorder that can occur as a result of severe liver disease. It is caused by variants in the ATP7B gene which can lead to abnormalities in copper metabolism that lead to accumulation of the heavy metal in the liver and brain, resulting in damage to both organs. Approximately 60% of patients with Wilson’s disease present with hepatic syndromes, and of those 50%-60% go on to develop liver cirrhosis.

Current treatments aim to address metal deposition, but this approach is poorly tolerated by many patients, wrote investigators who were led by Junping Shi, MD, PhD, of the Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, China.

“Drug interventions (such as copper chelators and zinc salts) reduce pathologic copper deposition, but side effects can be observed in up to 40% of patients during treatment and even after years of treatment, particularly nephropathy, autoimmune conditions, and skin changes,” the investigators wrote. “Liver transplantation is an effective treatment for Wilson’s disease, particularly for patients with end-stage liver disease, but donor shortages and lifelong immunosuppression limit its use. Therefore, alternative treatments with higher specificity in Wilson’s disease patients are urgently needed.”

The present study explored the underlying metabolic abnormalities in Wilson’s disease that result in liver injury and fibrosis, and related therapeutic approaches. Based on previous studies that have shown a relationship between persistent neutrophil infiltration and chronic tissue inflammation and damage, the investigators sought to explore the role of neutrophils in Wilson’s disease, with a focus on the N2 subtype.

First, they analyzed neutrophil populations in the livers of Atp7b–/– mice and atp7b–/– zebrafish, both of which are established animal models of Wilson’s disease. Compared with the wild-type comparison animals, the livers of disease model animals showed increased neutrophil infiltration, in terms of both count and density.

In one of several related experiments, administering a neutrophil agonist in the presence of copper led to significantly greater neutrophil infiltration in mutant versus wild-type fish, as well as greater increases in lipid droplets and disorganized tissue structure, which serve as markers of disease activity.

“Collectively, these data suggested that neutrophils infiltrated the liver and accelerated liver defects in Wilson’s disease,” the investigators wrote.

Additional experiments with the mouse model showed that pharmacologic ablation of N2 neutrophils via two approaches led to reduced liver fibrosis, offering a glimpse at therapeutic potential.

These findings were further supported by experiments involving a cellular model of Wilson’s disease with isolated bone marrow neutrophils. These analyses revealed the role of the TGF1–DNMT3A/STAT3 signaling axis in neutrophil polarization, and resultant liver disease progression, in Wilson’s disease.

“Neutrophil heterogeneity shows therapeutic potential, and pharmacologic modulation of N2-neutrophil activity should be explored as an alternative therapeutic to improve liver function in Wilson’s disease,” the investigators concluded, noting that TGF-beta 1, DNMT3A, or STAT3 could all serve as rational therapeutic targets.

Beyond Wilson’s disease, the findings may offer broader value for understanding the mechanisms driving other neutrophil-related diseases, as well as possible therapeutic approaches for those conditions, the authors added.

The authors disclosed no conflicts of interest.

Approximately two out of three patients with microscopic colitis respond to bile acid sequestrants (BAS), and therapy is generally well tolerated, based on a recent retrospective study from the Mayo Clinic.

The findings support use of BAS in patients with microscopic colitis who fail first-line therapy, or have intolerance to those agents, wrote researchers who were led by Darrell S. Pardi, MD, AGAF, a gastroenterologist with Mayo Clinic, Rochester, Minn. To date, the American Gastroenterological Association (AGA) has refrained from issuing any recommendations for BAS monotherapy in microscopic colitis (MC), the study authors wrote, citing a lack of relevant data.

The AGA recommends budesonide as first-line therapy for patients with moderate to severe symptoms of microscopic colitis. However, the treatment is associated with a high rate of relapse (40%-81%) once the patient stops taking the drug. Its long-term use is associated with a risk of side effects.

“At present, there are no randomized controlled trials that have evaluated the efficacy of BAS monotherapy for MC,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Studies investigating the role of BAM [bile acid malabsorption] in MC are comprised of small cohorts and have shown inconsistent results. Patients without BAM may also respond to BAS therapy. Therefore, the role of BAM and treatment with BAS in MC merits further investigation.”

The study analyzed data from 282 patients (88.3% women) with microscopic colitis treated between 2010 to 2020. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing. After a median follow-up of 4.5 years, cholestyramine was the most prescribed BAS (64.9%), followed by colesevelam (21.6%) and colestipol (13.5%). Approximately half of the patients achieved a complete response (49.3%), while 16.3% had a partial response. Nonresponders accounted for 24.8% of the population, and 9.6% of patients did not tolerate BAS therapy. These outcomes were not significantly impacted by BAS dose or combination with other agents. Additional logistic regression analysis revealed no predictors of response.

After discontinuing BAS, 41.6% of patients had recurrence in a median of 21 weeks, ranging from 1 to 172 weeks.

“Consistent with prior studies evaluating the clinical course of MC and similar to the high rate of recurrence after discontinuation of budesonide, relapse was common after cessation of BAS therapy,” the investigators noted.

Still, the findings suggest that BAS is a valid second-line option with a favorable risk-benefit profile, and an elevated dose appears unnecessary to achieve clinical response.

“These results suggest that BAS may be considered as a treatment option in those that do not respond to first-line options or have intolerance to these agents,” the researchers wrote.

They suggested that BAS may be particularly useful as long-term maintenance therapy for patients wishing to avoid prolonged corticosteroid exposure.

“However, BAS have the potential to interfere with the administration and absorption of other medications, particularly in older populations with polypharmacy,” the researchers wrote. “Patients should thus be closely monitored for drug interactions, especially those taking concurrent medications. BAS should be administered separately from other medications to avoid the potential for drug interactions.”

Ideally, prospective studies will be conducted to confirm these findings, and to identify the subset of patients who are most likely to respond to BAS, the investigators concluded.

Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda; and has consulted for Vedanta, Seres, Phantom Pharmaceuticals, Abbvie, Immunic, and Otsuka.

Approximately two out of three patients with microscopic colitis respond to bile acid sequestrants (BAS), and therapy is generally well tolerated, based on a recent retrospective study from the Mayo Clinic.

The findings support use of BAS in patients with microscopic colitis who fail first-line therapy, or have intolerance to those agents, wrote researchers who were led by Darrell S. Pardi, MD, AGAF, a gastroenterologist with Mayo Clinic, Rochester, Minn. To date, the American Gastroenterological Association (AGA) has refrained from issuing any recommendations for BAS monotherapy in microscopic colitis (MC), the study authors wrote, citing a lack of relevant data.

The AGA recommends budesonide as first-line therapy for patients with moderate to severe symptoms of microscopic colitis. However, the treatment is associated with a high rate of relapse (40%-81%) once the patient stops taking the drug. Its long-term use is associated with a risk of side effects.

“At present, there are no randomized controlled trials that have evaluated the efficacy of BAS monotherapy for MC,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Studies investigating the role of BAM [bile acid malabsorption] in MC are comprised of small cohorts and have shown inconsistent results. Patients without BAM may also respond to BAS therapy. Therefore, the role of BAM and treatment with BAS in MC merits further investigation.”

The study analyzed data from 282 patients (88.3% women) with microscopic colitis treated between 2010 to 2020. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing. After a median follow-up of 4.5 years, cholestyramine was the most prescribed BAS (64.9%), followed by colesevelam (21.6%) and colestipol (13.5%). Approximately half of the patients achieved a complete response (49.3%), while 16.3% had a partial response. Nonresponders accounted for 24.8% of the population, and 9.6% of patients did not tolerate BAS therapy. These outcomes were not significantly impacted by BAS dose or combination with other agents. Additional logistic regression analysis revealed no predictors of response.

After discontinuing BAS, 41.6% of patients had recurrence in a median of 21 weeks, ranging from 1 to 172 weeks.

“Consistent with prior studies evaluating the clinical course of MC and similar to the high rate of recurrence after discontinuation of budesonide, relapse was common after cessation of BAS therapy,” the investigators noted.

Still, the findings suggest that BAS is a valid second-line option with a favorable risk-benefit profile, and an elevated dose appears unnecessary to achieve clinical response.

“These results suggest that BAS may be considered as a treatment option in those that do not respond to first-line options or have intolerance to these agents,” the researchers wrote.

They suggested that BAS may be particularly useful as long-term maintenance therapy for patients wishing to avoid prolonged corticosteroid exposure.

“However, BAS have the potential to interfere with the administration and absorption of other medications, particularly in older populations with polypharmacy,” the researchers wrote. “Patients should thus be closely monitored for drug interactions, especially those taking concurrent medications. BAS should be administered separately from other medications to avoid the potential for drug interactions.”

Ideally, prospective studies will be conducted to confirm these findings, and to identify the subset of patients who are most likely to respond to BAS, the investigators concluded.

Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda; and has consulted for Vedanta, Seres, Phantom Pharmaceuticals, Abbvie, Immunic, and Otsuka.

Approximately two out of three patients with microscopic colitis respond to bile acid sequestrants (BAS), and therapy is generally well tolerated, based on a recent retrospective study from the Mayo Clinic.

The findings support use of BAS in patients with microscopic colitis who fail first-line therapy, or have intolerance to those agents, wrote researchers who were led by Darrell S. Pardi, MD, AGAF, a gastroenterologist with Mayo Clinic, Rochester, Minn. To date, the American Gastroenterological Association (AGA) has refrained from issuing any recommendations for BAS monotherapy in microscopic colitis (MC), the study authors wrote, citing a lack of relevant data.

The AGA recommends budesonide as first-line therapy for patients with moderate to severe symptoms of microscopic colitis. However, the treatment is associated with a high rate of relapse (40%-81%) once the patient stops taking the drug. Its long-term use is associated with a risk of side effects.

“At present, there are no randomized controlled trials that have evaluated the efficacy of BAS monotherapy for MC,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Studies investigating the role of BAM [bile acid malabsorption] in MC are comprised of small cohorts and have shown inconsistent results. Patients without BAM may also respond to BAS therapy. Therefore, the role of BAM and treatment with BAS in MC merits further investigation.”

The study analyzed data from 282 patients (88.3% women) with microscopic colitis treated between 2010 to 2020. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing. After a median follow-up of 4.5 years, cholestyramine was the most prescribed BAS (64.9%), followed by colesevelam (21.6%) and colestipol (13.5%). Approximately half of the patients achieved a complete response (49.3%), while 16.3% had a partial response. Nonresponders accounted for 24.8% of the population, and 9.6% of patients did not tolerate BAS therapy. These outcomes were not significantly impacted by BAS dose or combination with other agents. Additional logistic regression analysis revealed no predictors of response.

After discontinuing BAS, 41.6% of patients had recurrence in a median of 21 weeks, ranging from 1 to 172 weeks.

“Consistent with prior studies evaluating the clinical course of MC and similar to the high rate of recurrence after discontinuation of budesonide, relapse was common after cessation of BAS therapy,” the investigators noted.

Still, the findings suggest that BAS is a valid second-line option with a favorable risk-benefit profile, and an elevated dose appears unnecessary to achieve clinical response.

“These results suggest that BAS may be considered as a treatment option in those that do not respond to first-line options or have intolerance to these agents,” the researchers wrote.

They suggested that BAS may be particularly useful as long-term maintenance therapy for patients wishing to avoid prolonged corticosteroid exposure.

“However, BAS have the potential to interfere with the administration and absorption of other medications, particularly in older populations with polypharmacy,” the researchers wrote. “Patients should thus be closely monitored for drug interactions, especially those taking concurrent medications. BAS should be administered separately from other medications to avoid the potential for drug interactions.”

Ideally, prospective studies will be conducted to confirm these findings, and to identify the subset of patients who are most likely to respond to BAS, the investigators concluded.

Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda; and has consulted for Vedanta, Seres, Phantom Pharmaceuticals, Abbvie, Immunic, and Otsuka.

A variety of probiotics may relieve symptoms in patients with irritable bowel syndrome (IBS), but most evidence from randomized controlled trials remains low certainty or very low certainty, with many studies suffering from bias, according to a recent review and meta-analysis.

These shortcomings in the probiotic research landscape should be kept in mind when making treatment recommendations, reported researchers who were led by Alexander C. Ford, MBChB, of the Leeds Gastroenterology Institute, University of Leeds (England). They suggested these issues need to be addressed in the methodology of future clinical trials.

“Although multiple probiotics have been tested in IBS in randomized clinical trials, understanding of which probiotics may be beneficial is limited,” the investigators wrote in Gastroenterology.

They noted that previous efforts – including their own – to meta-analyze these findings have been hindered by a scarcity of trial data coupled with heterogeneity across probiotic strains, combinations, and doses, resulting in clinical uncertainty.

“Making recommendations concerning which probiotics, or combinations of probiotics, are beneficial according to IBS subtype or individual symptom has been difficult to date,” they wrote.

To narrow this knowledge gap, the researchers conducted an updated systematic review and meta-analysis with newly identified trials.

“There is continued interest in the role of probiotics in the management of IBS, as evidenced by the publication of more than 20 new randomized clinical trials since the prior version of this meta-analysis in 2018,” they wrote.

The new dataset included 82 RCTs comprising 10,332 patients with IBS. Along with safety, three separate efficacy endpoints were evaluated: global symptoms, abdominal pain, and abdominal bloating or distension.

For global symptoms, moderate-certainty evidence supported the efficacy of Escherichia coli strains; low-certainty data supported Lactobacillus plantarum 299V and other Lactobacillus strains; and very-low-certainty evidence supported Bacillus, LacClean Gold S, and Duolac 7s strains, and combination probiotics.

For abdominal pain, low-certainty evidence supported Bifidobacterium strains and Saccharomyces cerevisiae I-3856. Very-low-certainty data supported Lactobacillus, Saccharomyces, and Bacillus strains, and combination probiotics.

Very-low-certainty evidence supported the benefits of Bacillus strains and combination probiotics for alleviating abdominal bloating or distension.

In a safety analysis of 55 trials involving more than 7,000 patients, risk of adverse events was no higher for probiotics than placebo.

“Our analyses provide some support for the use of certain probiotics in IBS, and also for particular strains for specific symptoms,” the investigators wrote. “However, there is a paucity of data for their use in patients with IBS-C [IBS with constipation], with only seven RCTs reporting efficacy in this subtype, and no evidence of efficacy in any of these analyses. Their use in patients with IBS-C is, therefore, not supported by current evidence.”

A broader discussion in the publication called out the general lack of high certainty evidence in this area of clinical research.

“Only 24 of 82 eligible RCTs were low risk of bias across all domains, and there was significant heterogeneity between trials in many of our analyses, as well as evidence of publication bias, or other small study effects, in some of our analyses,” the researchers wrote. “The fact that few of the included studies were low risk of bias across all domains should be borne in mind when making treatment recommendations.”

The investigators disclosed relationships with Salix, Biocodex, 4D Pharma, and others.

A variety of probiotics may relieve symptoms in patients with irritable bowel syndrome (IBS), but most evidence from randomized controlled trials remains low certainty or very low certainty, with many studies suffering from bias, according to a recent review and meta-analysis.

These shortcomings in the probiotic research landscape should be kept in mind when making treatment recommendations, reported researchers who were led by Alexander C. Ford, MBChB, of the Leeds Gastroenterology Institute, University of Leeds (England). They suggested these issues need to be addressed in the methodology of future clinical trials.

“Although multiple probiotics have been tested in IBS in randomized clinical trials, understanding of which probiotics may be beneficial is limited,” the investigators wrote in Gastroenterology.

They noted that previous efforts – including their own – to meta-analyze these findings have been hindered by a scarcity of trial data coupled with heterogeneity across probiotic strains, combinations, and doses, resulting in clinical uncertainty.

“Making recommendations concerning which probiotics, or combinations of probiotics, are beneficial according to IBS subtype or individual symptom has been difficult to date,” they wrote.

To narrow this knowledge gap, the researchers conducted an updated systematic review and meta-analysis with newly identified trials.

“There is continued interest in the role of probiotics in the management of IBS, as evidenced by the publication of more than 20 new randomized clinical trials since the prior version of this meta-analysis in 2018,” they wrote.

The new dataset included 82 RCTs comprising 10,332 patients with IBS. Along with safety, three separate efficacy endpoints were evaluated: global symptoms, abdominal pain, and abdominal bloating or distension.

For global symptoms, moderate-certainty evidence supported the efficacy of Escherichia coli strains; low-certainty data supported Lactobacillus plantarum 299V and other Lactobacillus strains; and very-low-certainty evidence supported Bacillus, LacClean Gold S, and Duolac 7s strains, and combination probiotics.

For abdominal pain, low-certainty evidence supported Bifidobacterium strains and Saccharomyces cerevisiae I-3856. Very-low-certainty data supported Lactobacillus, Saccharomyces, and Bacillus strains, and combination probiotics.

Very-low-certainty evidence supported the benefits of Bacillus strains and combination probiotics for alleviating abdominal bloating or distension.

In a safety analysis of 55 trials involving more than 7,000 patients, risk of adverse events was no higher for probiotics than placebo.

“Our analyses provide some support for the use of certain probiotics in IBS, and also for particular strains for specific symptoms,” the investigators wrote. “However, there is a paucity of data for their use in patients with IBS-C [IBS with constipation], with only seven RCTs reporting efficacy in this subtype, and no evidence of efficacy in any of these analyses. Their use in patients with IBS-C is, therefore, not supported by current evidence.”

A broader discussion in the publication called out the general lack of high certainty evidence in this area of clinical research.

“Only 24 of 82 eligible RCTs were low risk of bias across all domains, and there was significant heterogeneity between trials in many of our analyses, as well as evidence of publication bias, or other small study effects, in some of our analyses,” the researchers wrote. “The fact that few of the included studies were low risk of bias across all domains should be borne in mind when making treatment recommendations.”

The investigators disclosed relationships with Salix, Biocodex, 4D Pharma, and others.

A variety of probiotics may relieve symptoms in patients with irritable bowel syndrome (IBS), but most evidence from randomized controlled trials remains low certainty or very low certainty, with many studies suffering from bias, according to a recent review and meta-analysis.

These shortcomings in the probiotic research landscape should be kept in mind when making treatment recommendations, reported researchers who were led by Alexander C. Ford, MBChB, of the Leeds Gastroenterology Institute, University of Leeds (England). They suggested these issues need to be addressed in the methodology of future clinical trials.

“Although multiple probiotics have been tested in IBS in randomized clinical trials, understanding of which probiotics may be beneficial is limited,” the investigators wrote in Gastroenterology.

They noted that previous efforts – including their own – to meta-analyze these findings have been hindered by a scarcity of trial data coupled with heterogeneity across probiotic strains, combinations, and doses, resulting in clinical uncertainty.

“Making recommendations concerning which probiotics, or combinations of probiotics, are beneficial according to IBS subtype or individual symptom has been difficult to date,” they wrote.

To narrow this knowledge gap, the researchers conducted an updated systematic review and meta-analysis with newly identified trials.

“There is continued interest in the role of probiotics in the management of IBS, as evidenced by the publication of more than 20 new randomized clinical trials since the prior version of this meta-analysis in 2018,” they wrote.

The new dataset included 82 RCTs comprising 10,332 patients with IBS. Along with safety, three separate efficacy endpoints were evaluated: global symptoms, abdominal pain, and abdominal bloating or distension.

For global symptoms, moderate-certainty evidence supported the efficacy of Escherichia coli strains; low-certainty data supported Lactobacillus plantarum 299V and other Lactobacillus strains; and very-low-certainty evidence supported Bacillus, LacClean Gold S, and Duolac 7s strains, and combination probiotics.

For abdominal pain, low-certainty evidence supported Bifidobacterium strains and Saccharomyces cerevisiae I-3856. Very-low-certainty data supported Lactobacillus, Saccharomyces, and Bacillus strains, and combination probiotics.

Very-low-certainty evidence supported the benefits of Bacillus strains and combination probiotics for alleviating abdominal bloating or distension.

In a safety analysis of 55 trials involving more than 7,000 patients, risk of adverse events was no higher for probiotics than placebo.

“Our analyses provide some support for the use of certain probiotics in IBS, and also for particular strains for specific symptoms,” the investigators wrote. “However, there is a paucity of data for their use in patients with IBS-C [IBS with constipation], with only seven RCTs reporting efficacy in this subtype, and no evidence of efficacy in any of these analyses. Their use in patients with IBS-C is, therefore, not supported by current evidence.”

A broader discussion in the publication called out the general lack of high certainty evidence in this area of clinical research.

“Only 24 of 82 eligible RCTs were low risk of bias across all domains, and there was significant heterogeneity between trials in many of our analyses, as well as evidence of publication bias, or other small study effects, in some of our analyses,” the researchers wrote. “The fact that few of the included studies were low risk of bias across all domains should be borne in mind when making treatment recommendations.”

The investigators disclosed relationships with Salix, Biocodex, 4D Pharma, and others.

The American Gastroenterological Association (AGA) has published a Clinical Practice Update for managing exocrine pancreatic insufficiency (EPI). The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.

“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”

To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
 

Clinical features and risk factors

The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.

The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.

Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
 

Diagnostic strategies

The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).

Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.

The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.

“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.

While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
 

Treatment strategies

Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.

PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.

Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
 

Surveillance

EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.

The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.

The American Gastroenterological Association (AGA) has published a Clinical Practice Update for managing exocrine pancreatic insufficiency (EPI). The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.

“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”

To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
 

Clinical features and risk factors

The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.

The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.

Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
 

Diagnostic strategies

The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).

Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.

The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.

“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.

While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
 

Treatment strategies

Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.

PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.

Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
 

Surveillance

EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.

The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.

The American Gastroenterological Association (AGA) has published a Clinical Practice Update for managing exocrine pancreatic insufficiency (EPI). The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.

“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”

To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
 

Clinical features and risk factors

The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.

The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.

Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
 

Diagnostic strategies

The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).

Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.

The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.

“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.

While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
 

Treatment strategies

Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.

PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.

Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
 

Surveillance

EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.

The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.

The American Gastroenterological Association has published a Clinical Practice Update with new best practice advice for colorectal cancer screening (CRC) and postpolypectomy surveillance.

Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.

“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.

With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.

To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.

Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.

“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”

The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.

According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.

The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.

“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”

The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.

The American Gastroenterological Association has published a Clinical Practice Update with new best practice advice for colorectal cancer screening (CRC) and postpolypectomy surveillance.

Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.

“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.

With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.

To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.

Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.

“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”

The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.

According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.

The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.

“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”

The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.

The American Gastroenterological Association has published a Clinical Practice Update with new best practice advice for colorectal cancer screening (CRC) and postpolypectomy surveillance.

Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.

“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.

With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.

To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.

Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.

“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”

The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.

According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.

The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.

“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”

The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.

Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Michigan Medicine

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.
 

Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Michigan Medicine

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.
 

Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Michigan Medicine

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.
 

Patients with inflammatory bowel disease (IBD) who undergo subtotal colectomy and diverted rectum may face a ”markedly increased” risk of rectal cancer in the diverted rectum at 10 years post colectomy, shows a Danish population-based cohort study.

These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.

“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.

Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.

The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.

The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.

This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.

Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).

A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).

Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.

The findings should inform surveillance guidelines, they wrote.

“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.

The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
 

Patients with inflammatory bowel disease (IBD) who undergo subtotal colectomy and diverted rectum may face a ”markedly increased” risk of rectal cancer in the diverted rectum at 10 years post colectomy, shows a Danish population-based cohort study.

These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.

“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.

Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.

The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.

The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.

This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.

Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).

A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).

Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.

The findings should inform surveillance guidelines, they wrote.

“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.

The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
 

Patients with inflammatory bowel disease (IBD) who undergo subtotal colectomy and diverted rectum may face a ”markedly increased” risk of rectal cancer in the diverted rectum at 10 years post colectomy, shows a Danish population-based cohort study.

These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.

“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.

Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.

The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.

The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.

This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.

Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).

A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).

Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.

The findings should inform surveillance guidelines, they wrote.

“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.

The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
 

The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.

Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.

The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.

Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.

Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.

Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.

Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.

Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.

Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.

“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.

This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.

The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.

Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.

The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.

Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.

Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.

Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.

Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.

Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.

Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.

“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.

This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.

The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.

Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.

The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.

Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.

Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.

Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.

Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.

Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.

Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.

“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.

This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.

Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.

The update, published online in Gastroenterology, includes eight best practice advice statements.

“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.

“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.

Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.

The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave

elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.

“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.

Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).

Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.

The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”

Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.

Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.

The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.

“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.

Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).

This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
 

Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.

The update, published online in Gastroenterology, includes eight best practice advice statements.

“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.

“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.

Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.

The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave

elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.

“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.

Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).

Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.

The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”

Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.

Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.

The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.

“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.

Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).

This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
 

Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.

The update, published online in Gastroenterology, includes eight best practice advice statements.

“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.

“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.

Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.

The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave

elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.

“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.

Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).

Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.

The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”

Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.

Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.

The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.

“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.

Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).

This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.