From the AGA Journals

Early ileocecal resection is associated with better long-term outcomes compared with anti–tumor necrosis factor (TNF) therapy for patients with Crohn’s disease (CD), based on new real-world evidence.

These findings add weight to previously reported data from the LIR!C trial, suggesting that ileocecal resection should be considered a first-line treatment option for CD, reported principal investigator Kristine H. Allin, MD, PhD, of Aalborg University, Copenhagen.

“The LIR!C randomized clinical trial has demonstrated comparable quality of life with ileocecal resection and infliximab as a first-line treatment for limited, nonstricturing ileocecal CD at 1 year of follow-up, and improved outcomes with ileocecal resection on retrospective analysis of long-term follow-up data,” the investigators wrote in Gastroenterology. “However, in the real world, the long-term impact of early ileocecal resection for CD, compared with medical therapy, remains largely unexplored.”

To gather these real-world data, the investigators turned to the Danish National Patient Registry and the Danish National Prescription Registry, which included 1,279 individuals diagnosed with CD between 2003 and 2018 who received anti-TNF therapy or underwent ileocecal resection within 1 year of diagnosis. Within this group, slightly less than half underwent ileocecal resection (45.4%) while the remainder (54.6%) received anti-TNF therapy.

The primary outcome was a composite of one or more events: perianal CD, CD-related surgery, systemic corticosteroid exposure, and CD-related hospitalization. Secondary analyses evaluated the relative risks of these same four events as independent entities.

Multifactor-adjusted Cox proportional hazards regression analysis revealed that patients who underwent ileocecal resection had a 33% lower risk of the composite outcome compared with those who received anti-TNF therapy (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.54-0.83).

In the secondary analyses, which examined risks for each component of the composite outcome, the surgery group had a significantly lower risk of CD-related surgery (aHR, 0.56; 95% CI, 0.39-0.80) and corticosteroid exposure (aHR, 0.71; 95% CI, 0.54-0.92), but not perianal CD or CD-related hospitalization.

After 5 years, half of the patients (49.7%) who underwent ileocecal resection were not receiving any treatment for CD. At the same timepoint, a slightly lower percentage of this group (46.3%) had started immunomodulator therapy, while 16.8% started anti-TNF therapy. Just 1.8% of these patients required a second intestinal resection.

Icahn School of Medicine at Mount Sinai

“To our knowledge, these are the first real-world data in a population-based cohort with long-term follow-up of early ileocecal resection compared with anti-TNF therapy for newly diagnosed ileal and ileocecal CD,” the investigators wrote. “These data suggest that ileocecal resection may have a role as first-line therapy in Crohn’s disease management and challenge the current paradigm of reserving surgery for complicated Crohn’s disease refractory or intolerant to medications.”

Corresponding author Manasi Agrawal, MD, of Icahn School of Medicine at Mount Sinai, New York, suggested that “validation of our findings in external cohorts [is needed], and understanding of factors associated with improved outcomes following ileocecal resection.”

For clinicians and patients choosing between first-line anti-TNF therapy versus ileocecal resection using currently available evidence, Dr. Agrawal suggested that a variety of factors need to be considered, including disease location, extent of terminal ileum involved, presence of complications such as stricture, fistula, comorbid conditions, access to biologics, financial considerations, and patient preferences.

Cleveland Clinic

Benjamin Cohen, MD, staff physician and co-section head and clinical director for inflammatory bowel diseases in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic, called this “an important study” because it offers the first real-world evidence to support the findings from the LIR!C trial.

Dr. Cohen agreed with Dr. Agrawal that more work is needed to determine which patients benefit most from early ileocecal resection, although he suggested that known risk factors for worse outcomes — such as early age at diagnosis, penetrating features of disease, or perianal disease — may increase strength of surgical candidacy.

Still, based on the “fairly strong” body of data now available, he suggested that all patients should be educated about first-line ileocecal resection, as it is “reasonable” approach.

“It’s always important to present surgery as a treatment option,” Dr. Cohen said in an interview. “We don’t want to think of surgery as a last resort, or a failure, because that really colors it in a negative light, and then that ultimately impacts patients’ quality of life, and their perception of outcomes.”

The study was supported by the Danish National Research Foundation. The investigators disclosed no conflicts of interest. Dr. Cohen disclosed consulting and speaking honoraria from AbbVie.

Early ileocecal resection is associated with better long-term outcomes compared with anti–tumor necrosis factor (TNF) therapy for patients with Crohn’s disease (CD), based on new real-world evidence.

These findings add weight to previously reported data from the LIR!C trial, suggesting that ileocecal resection should be considered a first-line treatment option for CD, reported principal investigator Kristine H. Allin, MD, PhD, of Aalborg University, Copenhagen.

“The LIR!C randomized clinical trial has demonstrated comparable quality of life with ileocecal resection and infliximab as a first-line treatment for limited, nonstricturing ileocecal CD at 1 year of follow-up, and improved outcomes with ileocecal resection on retrospective analysis of long-term follow-up data,” the investigators wrote in Gastroenterology. “However, in the real world, the long-term impact of early ileocecal resection for CD, compared with medical therapy, remains largely unexplored.”

To gather these real-world data, the investigators turned to the Danish National Patient Registry and the Danish National Prescription Registry, which included 1,279 individuals diagnosed with CD between 2003 and 2018 who received anti-TNF therapy or underwent ileocecal resection within 1 year of diagnosis. Within this group, slightly less than half underwent ileocecal resection (45.4%) while the remainder (54.6%) received anti-TNF therapy.

The primary outcome was a composite of one or more events: perianal CD, CD-related surgery, systemic corticosteroid exposure, and CD-related hospitalization. Secondary analyses evaluated the relative risks of these same four events as independent entities.

Multifactor-adjusted Cox proportional hazards regression analysis revealed that patients who underwent ileocecal resection had a 33% lower risk of the composite outcome compared with those who received anti-TNF therapy (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.54-0.83).

In the secondary analyses, which examined risks for each component of the composite outcome, the surgery group had a significantly lower risk of CD-related surgery (aHR, 0.56; 95% CI, 0.39-0.80) and corticosteroid exposure (aHR, 0.71; 95% CI, 0.54-0.92), but not perianal CD or CD-related hospitalization.

After 5 years, half of the patients (49.7%) who underwent ileocecal resection were not receiving any treatment for CD. At the same timepoint, a slightly lower percentage of this group (46.3%) had started immunomodulator therapy, while 16.8% started anti-TNF therapy. Just 1.8% of these patients required a second intestinal resection.

Icahn School of Medicine at Mount Sinai

“To our knowledge, these are the first real-world data in a population-based cohort with long-term follow-up of early ileocecal resection compared with anti-TNF therapy for newly diagnosed ileal and ileocecal CD,” the investigators wrote. “These data suggest that ileocecal resection may have a role as first-line therapy in Crohn’s disease management and challenge the current paradigm of reserving surgery for complicated Crohn’s disease refractory or intolerant to medications.”

Corresponding author Manasi Agrawal, MD, of Icahn School of Medicine at Mount Sinai, New York, suggested that “validation of our findings in external cohorts [is needed], and understanding of factors associated with improved outcomes following ileocecal resection.”

For clinicians and patients choosing between first-line anti-TNF therapy versus ileocecal resection using currently available evidence, Dr. Agrawal suggested that a variety of factors need to be considered, including disease location, extent of terminal ileum involved, presence of complications such as stricture, fistula, comorbid conditions, access to biologics, financial considerations, and patient preferences.

Cleveland Clinic

Benjamin Cohen, MD, staff physician and co-section head and clinical director for inflammatory bowel diseases in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic, called this “an important study” because it offers the first real-world evidence to support the findings from the LIR!C trial.

Dr. Cohen agreed with Dr. Agrawal that more work is needed to determine which patients benefit most from early ileocecal resection, although he suggested that known risk factors for worse outcomes — such as early age at diagnosis, penetrating features of disease, or perianal disease — may increase strength of surgical candidacy.

Still, based on the “fairly strong” body of data now available, he suggested that all patients should be educated about first-line ileocecal resection, as it is “reasonable” approach.

“It’s always important to present surgery as a treatment option,” Dr. Cohen said in an interview. “We don’t want to think of surgery as a last resort, or a failure, because that really colors it in a negative light, and then that ultimately impacts patients’ quality of life, and their perception of outcomes.”

The study was supported by the Danish National Research Foundation. The investigators disclosed no conflicts of interest. Dr. Cohen disclosed consulting and speaking honoraria from AbbVie.

Early ileocecal resection is associated with better long-term outcomes compared with anti–tumor necrosis factor (TNF) therapy for patients with Crohn’s disease (CD), based on new real-world evidence.

These findings add weight to previously reported data from the LIR!C trial, suggesting that ileocecal resection should be considered a first-line treatment option for CD, reported principal investigator Kristine H. Allin, MD, PhD, of Aalborg University, Copenhagen.

“The LIR!C randomized clinical trial has demonstrated comparable quality of life with ileocecal resection and infliximab as a first-line treatment for limited, nonstricturing ileocecal CD at 1 year of follow-up, and improved outcomes with ileocecal resection on retrospective analysis of long-term follow-up data,” the investigators wrote in Gastroenterology. “However, in the real world, the long-term impact of early ileocecal resection for CD, compared with medical therapy, remains largely unexplored.”

To gather these real-world data, the investigators turned to the Danish National Patient Registry and the Danish National Prescription Registry, which included 1,279 individuals diagnosed with CD between 2003 and 2018 who received anti-TNF therapy or underwent ileocecal resection within 1 year of diagnosis. Within this group, slightly less than half underwent ileocecal resection (45.4%) while the remainder (54.6%) received anti-TNF therapy.

The primary outcome was a composite of one or more events: perianal CD, CD-related surgery, systemic corticosteroid exposure, and CD-related hospitalization. Secondary analyses evaluated the relative risks of these same four events as independent entities.

Multifactor-adjusted Cox proportional hazards regression analysis revealed that patients who underwent ileocecal resection had a 33% lower risk of the composite outcome compared with those who received anti-TNF therapy (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.54-0.83).

In the secondary analyses, which examined risks for each component of the composite outcome, the surgery group had a significantly lower risk of CD-related surgery (aHR, 0.56; 95% CI, 0.39-0.80) and corticosteroid exposure (aHR, 0.71; 95% CI, 0.54-0.92), but not perianal CD or CD-related hospitalization.

After 5 years, half of the patients (49.7%) who underwent ileocecal resection were not receiving any treatment for CD. At the same timepoint, a slightly lower percentage of this group (46.3%) had started immunomodulator therapy, while 16.8% started anti-TNF therapy. Just 1.8% of these patients required a second intestinal resection.

Icahn School of Medicine at Mount Sinai

“To our knowledge, these are the first real-world data in a population-based cohort with long-term follow-up of early ileocecal resection compared with anti-TNF therapy for newly diagnosed ileal and ileocecal CD,” the investigators wrote. “These data suggest that ileocecal resection may have a role as first-line therapy in Crohn’s disease management and challenge the current paradigm of reserving surgery for complicated Crohn’s disease refractory or intolerant to medications.”

Corresponding author Manasi Agrawal, MD, of Icahn School of Medicine at Mount Sinai, New York, suggested that “validation of our findings in external cohorts [is needed], and understanding of factors associated with improved outcomes following ileocecal resection.”

For clinicians and patients choosing between first-line anti-TNF therapy versus ileocecal resection using currently available evidence, Dr. Agrawal suggested that a variety of factors need to be considered, including disease location, extent of terminal ileum involved, presence of complications such as stricture, fistula, comorbid conditions, access to biologics, financial considerations, and patient preferences.

Cleveland Clinic

Benjamin Cohen, MD, staff physician and co-section head and clinical director for inflammatory bowel diseases in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic, called this “an important study” because it offers the first real-world evidence to support the findings from the LIR!C trial.

Dr. Cohen agreed with Dr. Agrawal that more work is needed to determine which patients benefit most from early ileocecal resection, although he suggested that known risk factors for worse outcomes — such as early age at diagnosis, penetrating features of disease, or perianal disease — may increase strength of surgical candidacy.

Still, based on the “fairly strong” body of data now available, he suggested that all patients should be educated about first-line ileocecal resection, as it is “reasonable” approach.

“It’s always important to present surgery as a treatment option,” Dr. Cohen said in an interview. “We don’t want to think of surgery as a last resort, or a failure, because that really colors it in a negative light, and then that ultimately impacts patients’ quality of life, and their perception of outcomes.”

The study was supported by the Danish National Research Foundation. The investigators disclosed no conflicts of interest. Dr. Cohen disclosed consulting and speaking honoraria from AbbVie.

A new risk model for nonalcoholic fatty liver disease (NAFLD) could offer a simpler and more accurate way of predicting advanced fibrosis in first-degree relatives, according to investigators.

By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.

“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”

To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.

Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.

Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.

Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.

When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).

“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”

Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.

“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”

The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.

A new risk model for nonalcoholic fatty liver disease (NAFLD) could offer a simpler and more accurate way of predicting advanced fibrosis in first-degree relatives, according to investigators.

By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.

“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”

To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.

Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.

Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.

Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.

When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).

“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”

Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.

“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”

The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.

A new risk model for nonalcoholic fatty liver disease (NAFLD) could offer a simpler and more accurate way of predicting advanced fibrosis in first-degree relatives, according to investigators.

By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.

“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”

To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.

Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.

Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.

Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.

When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).

“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”

Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.

“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”

The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.

A new Clinical Practice Guideline from American Gastroenterological Association points to a stronger and better defined role for fecal and blood biomarkers in the management of Crohn’s disease, offering the most specific evidence-based recommendations yet for the use of fecal calprotectin (FCP) and serum C-reactive protein (CRP) in assessing disease activity.

Repeated monitoring with endoscopy allows for an objective assessment of inflammation and mucosal healing compared with symptoms alone. However, relying solely on endoscopy to guide management is an approach “limited by cost and resource utilization, invasiveness, and reduced patient acceptability,” wrote guideline authors on behalf of the AGA Clinical Guidelines Committee. The guideline was published online Nov. 17 in Gastroenterology.

“Use of biomarkers is no longer considered experimental and should be an integral part of IBD care and monitoring,” said Ashwin Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston and first author of the guideline. “We need further studies to define their optimal longitudinal use, but at a given time point, there is now abundant evidence that biomarkers provide significant incremental benefit over symptoms alone in assessing a patient’s status.”

Using evidence from randomized controlled trials and observational studies, and applying it to common clinical scenarios, there are conditional recommendations on the use of biomarkers in patients with established, diagnosed disease who were asymptomatic, symptomatic, or in surgically induced remission. Those recommendations, laid out in a detailed Clinical Decision Support Tool, include the following:

For asymptomatic patients: Check CRP and FCP every 6-12 months. Patients with normal levels, and who have endoscopically confirmed remission within the last 3 years without any subsequent change in symptoms or treatment, need not undergo endoscopy and can be followed with biomarker and clinical checks alone. If CRP or FCP are elevated (defined as CRP ≥ 5 mg/L, FCP ≥ 150 mcg/g), consider repeating biomarkers and/or performing endoscopic assessment of disease activity before adjusting treatment.

For mildly symptomatic patients: Role of biomarker testing may be limited and endoscopic or radiologic assessment may be required to assess active inflammation given the higher rate of false positive and false negative results with biomarkers in this population.

For patients with more severe symptoms: Elevated CRP or FCP can be used to guide treatment adjustment without endoscopic confirmation in certain situations. Normal levels may be false negative and should be confirmed by endoscopic assessment of disease activity.

For patients in surgically induced remission with a low likelihood of recurrence: FCP levels below 50 mcg/g can be used in lieu of routine endoscopic assessment within the first year after surgery. Higher FCP levels should prompt endoscopic assessment.

For patients in surgically induced remission with a high risk of recurrence: Do not rely on biomarkers. Perform endoscopic assessment.

All recommendations were deemed of low to moderate certainty based on results from randomized clinical trials and observational studies that utilized these biomarkers in patients with Crohn’s disease. Citing a dearth of quality evidence, the guideline authors determined they could not make recommendations on the use of a third proprietary biomarker — the endoscopic healing index (EHI).

Recent AGA Clinical Practice Guidelines on the role of biomarkers in ulcerative colitis, published in March, also support a strong role for fecal and blood biomarkers, determining when these can be used to avoid unneeded endoscopic assessments. However, in patients with Crohn’s disease, symptoms correlate less well with endoscopic activity.

As a result, “biomarker performance was acceptable only in asymptomatic individuals who had recently confirmed endoscopic remission; in those without recent endoscopic assessment, test performance was suboptimal.” In addition, the weaker correlation between symptoms and endoscopic activity in Crohn’s “reduced the utility of biomarker measurement to infer disease activity in those with mild symptoms.”

The guidelines were fully funded by the AGA Institute. The authors disclosed a number of potential conflicts of interest, including receiving research grants, as well as consulting and speaking fees, from pharmaceutical companies.

A new Clinical Practice Guideline from American Gastroenterological Association points to a stronger and better defined role for fecal and blood biomarkers in the management of Crohn’s disease, offering the most specific evidence-based recommendations yet for the use of fecal calprotectin (FCP) and serum C-reactive protein (CRP) in assessing disease activity.

Repeated monitoring with endoscopy allows for an objective assessment of inflammation and mucosal healing compared with symptoms alone. However, relying solely on endoscopy to guide management is an approach “limited by cost and resource utilization, invasiveness, and reduced patient acceptability,” wrote guideline authors on behalf of the AGA Clinical Guidelines Committee. The guideline was published online Nov. 17 in Gastroenterology.

“Use of biomarkers is no longer considered experimental and should be an integral part of IBD care and monitoring,” said Ashwin Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston and first author of the guideline. “We need further studies to define their optimal longitudinal use, but at a given time point, there is now abundant evidence that biomarkers provide significant incremental benefit over symptoms alone in assessing a patient’s status.”

Using evidence from randomized controlled trials and observational studies, and applying it to common clinical scenarios, there are conditional recommendations on the use of biomarkers in patients with established, diagnosed disease who were asymptomatic, symptomatic, or in surgically induced remission. Those recommendations, laid out in a detailed Clinical Decision Support Tool, include the following:

For asymptomatic patients: Check CRP and FCP every 6-12 months. Patients with normal levels, and who have endoscopically confirmed remission within the last 3 years without any subsequent change in symptoms or treatment, need not undergo endoscopy and can be followed with biomarker and clinical checks alone. If CRP or FCP are elevated (defined as CRP ≥ 5 mg/L, FCP ≥ 150 mcg/g), consider repeating biomarkers and/or performing endoscopic assessment of disease activity before adjusting treatment.

For mildly symptomatic patients: Role of biomarker testing may be limited and endoscopic or radiologic assessment may be required to assess active inflammation given the higher rate of false positive and false negative results with biomarkers in this population.

For patients with more severe symptoms: Elevated CRP or FCP can be used to guide treatment adjustment without endoscopic confirmation in certain situations. Normal levels may be false negative and should be confirmed by endoscopic assessment of disease activity.

For patients in surgically induced remission with a low likelihood of recurrence: FCP levels below 50 mcg/g can be used in lieu of routine endoscopic assessment within the first year after surgery. Higher FCP levels should prompt endoscopic assessment.

For patients in surgically induced remission with a high risk of recurrence: Do not rely on biomarkers. Perform endoscopic assessment.

All recommendations were deemed of low to moderate certainty based on results from randomized clinical trials and observational studies that utilized these biomarkers in patients with Crohn’s disease. Citing a dearth of quality evidence, the guideline authors determined they could not make recommendations on the use of a third proprietary biomarker — the endoscopic healing index (EHI).

Recent AGA Clinical Practice Guidelines on the role of biomarkers in ulcerative colitis, published in March, also support a strong role for fecal and blood biomarkers, determining when these can be used to avoid unneeded endoscopic assessments. However, in patients with Crohn’s disease, symptoms correlate less well with endoscopic activity.

As a result, “biomarker performance was acceptable only in asymptomatic individuals who had recently confirmed endoscopic remission; in those without recent endoscopic assessment, test performance was suboptimal.” In addition, the weaker correlation between symptoms and endoscopic activity in Crohn’s “reduced the utility of biomarker measurement to infer disease activity in those with mild symptoms.”

The guidelines were fully funded by the AGA Institute. The authors disclosed a number of potential conflicts of interest, including receiving research grants, as well as consulting and speaking fees, from pharmaceutical companies.

A new Clinical Practice Guideline from American Gastroenterological Association points to a stronger and better defined role for fecal and blood biomarkers in the management of Crohn’s disease, offering the most specific evidence-based recommendations yet for the use of fecal calprotectin (FCP) and serum C-reactive protein (CRP) in assessing disease activity.

Repeated monitoring with endoscopy allows for an objective assessment of inflammation and mucosal healing compared with symptoms alone. However, relying solely on endoscopy to guide management is an approach “limited by cost and resource utilization, invasiveness, and reduced patient acceptability,” wrote guideline authors on behalf of the AGA Clinical Guidelines Committee. The guideline was published online Nov. 17 in Gastroenterology.

“Use of biomarkers is no longer considered experimental and should be an integral part of IBD care and monitoring,” said Ashwin Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston and first author of the guideline. “We need further studies to define their optimal longitudinal use, but at a given time point, there is now abundant evidence that biomarkers provide significant incremental benefit over symptoms alone in assessing a patient’s status.”

Using evidence from randomized controlled trials and observational studies, and applying it to common clinical scenarios, there are conditional recommendations on the use of biomarkers in patients with established, diagnosed disease who were asymptomatic, symptomatic, or in surgically induced remission. Those recommendations, laid out in a detailed Clinical Decision Support Tool, include the following:

For asymptomatic patients: Check CRP and FCP every 6-12 months. Patients with normal levels, and who have endoscopically confirmed remission within the last 3 years without any subsequent change in symptoms or treatment, need not undergo endoscopy and can be followed with biomarker and clinical checks alone. If CRP or FCP are elevated (defined as CRP ≥ 5 mg/L, FCP ≥ 150 mcg/g), consider repeating biomarkers and/or performing endoscopic assessment of disease activity before adjusting treatment.

For mildly symptomatic patients: Role of biomarker testing may be limited and endoscopic or radiologic assessment may be required to assess active inflammation given the higher rate of false positive and false negative results with biomarkers in this population.

For patients with more severe symptoms: Elevated CRP or FCP can be used to guide treatment adjustment without endoscopic confirmation in certain situations. Normal levels may be false negative and should be confirmed by endoscopic assessment of disease activity.

For patients in surgically induced remission with a low likelihood of recurrence: FCP levels below 50 mcg/g can be used in lieu of routine endoscopic assessment within the first year after surgery. Higher FCP levels should prompt endoscopic assessment.

For patients in surgically induced remission with a high risk of recurrence: Do not rely on biomarkers. Perform endoscopic assessment.

All recommendations were deemed of low to moderate certainty based on results from randomized clinical trials and observational studies that utilized these biomarkers in patients with Crohn’s disease. Citing a dearth of quality evidence, the guideline authors determined they could not make recommendations on the use of a third proprietary biomarker — the endoscopic healing index (EHI).

Recent AGA Clinical Practice Guidelines on the role of biomarkers in ulcerative colitis, published in March, also support a strong role for fecal and blood biomarkers, determining when these can be used to avoid unneeded endoscopic assessments. However, in patients with Crohn’s disease, symptoms correlate less well with endoscopic activity.

As a result, “biomarker performance was acceptable only in asymptomatic individuals who had recently confirmed endoscopic remission; in those without recent endoscopic assessment, test performance was suboptimal.” In addition, the weaker correlation between symptoms and endoscopic activity in Crohn’s “reduced the utility of biomarker measurement to infer disease activity in those with mild symptoms.”

The guidelines were fully funded by the AGA Institute. The authors disclosed a number of potential conflicts of interest, including receiving research grants, as well as consulting and speaking fees, from pharmaceutical companies.

Increased levels of carnitine and acylcarnitines are associated with increased dysbiosis and disease activity in pediatric inflammatory bowel disease (IBD), according to investigators.

These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.

“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”

The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.

First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.

Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.

To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.

“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.

Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.

“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”

The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.

Increased levels of carnitine and acylcarnitines are associated with increased dysbiosis and disease activity in pediatric inflammatory bowel disease (IBD), according to investigators.

These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.

“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”

The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.

First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.

Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.

To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.

“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.

Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.

“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”

The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.

Increased levels of carnitine and acylcarnitines are associated with increased dysbiosis and disease activity in pediatric inflammatory bowel disease (IBD), according to investigators.

These findings improve our understanding of IBD pathogenesis and disease course, and could prove valuable in biomarker research, reported lead author Gary D. Wu, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

In health, carnitine and acylcarnitines aid in fatty acid transport, the investigators wrote in September in Cellular and Molecular Gastroenterology and Hepatology. Acylcarnitines are also involved in metabolic signaling, and in the absence of sufficient short-chain fatty acids may serve as an alternative energy source for the intestinal epithelium.

“Recently, we and others have shown that fecal acylcarnitines are increased in patients with IBD, especially during dysbiosis,” they noted. “However, the mechanism(s) responsible for the increase of fecal acylcarnitines in IBD and their biological function have not been elucidated.”

The present study aimed to address this knowledge gap by characterizing both carnitine and acylcarnitines in pediatric IBD.

First, the investigators confirmed that both carnitine and acylcarnitines were elevated in fecal samples from pediatric patients with IBD.

Next, they analyzed fecal samples from subjects in the Food and Resulting Microbiota and Metabolome (FARMM) study, which compared microbiota recovery after gut purge and antibiotics among participants eating an omnivorous diet, a vegan diet, or an exclusive enteral nutrition (EEN) diet lacking in fiber. After the antibiotics, levels of fecal carnitine and acylcarnitines increased significantly in all groups, suggesting that microbiota were consuming these molecules.

To clarify the relationship between inflammation and levels of carnitine and acylcarnitines in the absence of microbiota, Dr. Wu and colleagues employed a germ-free mouse model with dextran sodium sulfate (DSS)–induced colitis. Levels of both molecule types were significantly increased in bile and plasma of mice with colitis versus those that were not exposed to DSS.

“Because the gut microbiota consumes both carnitine and acylcarnitines, these results are consistent with the notion that the increase of these metabolites in the feces of patients with IBD is driven by increased biliary delivery of acylcarnitines to the lumen combined with the reduced number and function of mitochondria in the colonic epithelium as previously reported,” the investigators wrote.

Further experiments with plated cultures and mice revealed that various bacterial species consumed carnitine and acylcarnitines in distinct patterns. Enterobacteriaceae demonstrated a notable proclivity for consumption in vitro and within the murine gut.

“As a high-dimensional analytic feature, the pattern of fecal acylcarnitines, perhaps together with bacterial taxonomy, may have utility as a biomarker for the presence or prognosis of IBD,” Dr. Wu and colleagues concluded. “In addition, based on currently available information about the impact of carnitine on the biology of Enterobacteriaceae, acylcarnitines also may have an important functional effect on the biology of the gut microbiota that is relevant to the pathogenesis or course of disease in patients with IBD.”

The study was supported by the Crohn’s and Colitis Foundation, the PennCHOP Microbiome Program, the Penn Center for Nutritional Science and Medicine, and others. The investigators disclosed no conflicts of interest.

American Gastroenterological Association (AGA) has released a new Clinical Practice Update (CPU) guiding the use of vasoactive drugs and intravenous albumin in patients with cirrhosis.

The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.

These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
 

Variceal Hemorrhage

Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.

“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.

In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.

The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.

“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
 

Ascites and Spontaneous Bacterial Peritonitis

In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.

Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.

Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.

The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
 

Acute Kidney Injury and Hepatorenal Syndrome

In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”

The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.

Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.

The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.

American Gastroenterological Association (AGA) has released a new Clinical Practice Update (CPU) guiding the use of vasoactive drugs and intravenous albumin in patients with cirrhosis.

The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.

These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
 

Variceal Hemorrhage

Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.

“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.

In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.

The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.

“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
 

Ascites and Spontaneous Bacterial Peritonitis

In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.

Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.

Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.

The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
 

Acute Kidney Injury and Hepatorenal Syndrome

In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”

The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.

Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.

The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.

American Gastroenterological Association (AGA) has released a new Clinical Practice Update (CPU) guiding the use of vasoactive drugs and intravenous albumin in patients with cirrhosis.

The publication, authored by Vincent Wai-Sun Wong, MBChB, MD, and colleagues, includes 12 best-practice-advice statements concerning 3 common clinical scenarios: variceal hemorrhage, ascites and spontaneous bacterial peritonitis, and acute kidney injury and hepatorenal syndrome.

These complications of liver decompensation “are manifestations of portal hypertension with a [consequent] vasodilatory–hyperdynamic circulatory state, resulting in progressive decreases in effective arterial blood volume and renal perfusion,” the update authors wrote in November in Gastroenterology. “Because a potent vasoconstrictor, terlipressin, was recently approved by the United States Food and Drug Administration and because recent trials have explored use of intravenous albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and intravenous albumin in these 3 specific scenarios.”
 

Variceal Hemorrhage

Comprising 70% of all upper GI hemorrhage in patients with cirrhosis, and carrying a 6-week mortality rate as high as 43%, Dr. Wong and colleagues advise immediate initiation of vasoactive drugs upon suspision of variceal hemorrhage, ideally before therapeutic and/or diagnostic endoscopy.

“The goals of management of acute variceal hemorrhage include initial hemostasis, preventing early rebleeding, and reducing in-hospital and 6-week mortality,” they wrote, noting that vasoactive drugs are effective at stopping bleeding in up to 8 out of 10 cases.

In patients with acute variceal hemorrhage undergoing endoscopic hemostasis, vasoactive agents should be continued for 2-5 days to prevent early rebleeding, according to the second best-practice-advice statement.

The third statement suggests octreotide as the drug of choice for variceal hemorrhage due to its favorable safety profile.

“Nowadays, vasopressin is no longer advised in patients with acute variceal hemorrhage because of a high risk of cardiovascular adverse events,” the update authors noted.
 

Ascites and Spontaneous Bacterial Peritonitis

In cases requiring large-volume (greater than 5 L) paracentesis, intravenous albumin should be administered at time of fluid removal, according to the update. In these patients, albumin reduces the risk of post-paracentesis circulatory dysfunction (defined as an increase in plasma renin activity), thereby reducing the risk of acute kidney injury.

Intravenous albumin should also be considered in patients with spontaneous bacterial peritonitis as this can overcome associated vasodilatation and decreased effective arterial blood volume, which may lead to acute kidney injury if untreated. In contrast, because of a demonstrated lack of efficacy, albumin is not advised in infections other than spontaneous bacterial peritonitis, unless associated with acute kidney injury.

Long-term albumin administration should be avoided in patients with cirrhosis and uncomplicated ascites, whether they are hospitalized or not, as evidence is lacking to support a consistent beneficial effect.

The update also advises against vasoconstrictors in patients with uncomplicated ascites, bacterial peritonitis, and after large-volume paracentesis, again due to a lack of supporting evidence.
 

Acute Kidney Injury and Hepatorenal Syndrome

In hospitalized patients with cirrhosis and ascites presenting with acute kidney injury, Dr. Wong and colleagues called albumin “the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with acute kidney injury,” however, the authors caution the dose of albumin “should be tailored to the volume status of the patient.”

The update authors suggested that terlipressin and norepinephrine are suitable options for patients with cirrhosis and the hepatorenal syndrome; however, they suggest terlipressin above the others based on available evidence and suggested concomitant albumin administration as it may further improve renal blood flow by filling the central circulation.

Terlipressin also has the advantage (over norepinephrine) of being administrable via a peripheral line without the need for intensive care unit monitoring, the update authors wrote. The agent is contraindicated in patients with hypoxia or with coronary, peripheral, or mesenteric ischemia, and it should be used with caution in patients with ACLF grade 3, according to the publication. Risks of terlipressin may also outweigh benefits in patients with a serum creatine greater than 5 mg/dL and those listed for transplant with a MELD score of 35 or higher.

The Clinical Practice Update was commissioned and supported by AGA. The authors disclosed relationships with Advanz, Boehringer Ingelheim, 89bio, and others.

Antireflux surgery may be no more effective than antireflux medication for reducing risk of esophageal adenocarcinoma (EAC) among patients with Barrett’s esophagus, according to a Nordic retrospective study.

Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.

Karolinska Institutet

“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”

Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.

“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.

For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.

In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.

After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.

The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).

“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”

Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.

“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.

“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.

The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.

Antireflux surgery may be no more effective than antireflux medication for reducing risk of esophageal adenocarcinoma (EAC) among patients with Barrett’s esophagus, according to a Nordic retrospective study.

Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.

Karolinska Institutet

“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”

Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.

“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.

For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.

In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.

After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.

The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).

“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”

Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.

“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.

“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.

The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.

Antireflux surgery may be no more effective than antireflux medication for reducing risk of esophageal adenocarcinoma (EAC) among patients with Barrett’s esophagus, according to a Nordic retrospective study.

Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.

Karolinska Institutet

“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”

Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.

“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.

For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.

In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.

After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.

The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).

“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”

Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.

“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.

“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.

The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.

Individuals with intraductal papillary mucinous neoplasms (IPMNs) that lack “worrisome or high-risk features” have no greater risk of pancreatic cancer than individuals without IPMNs, based on a retrospective cohort study from Mayo Clinic.

These findings, if validated in a larger population, could challenge current surveillance practices for IPMNs, reported researchers who were led by Shounak Majumder, MD, a gastroenterologist in the pancreas clinic at Mayo Clinic, Rochester, Minn. The study was published in JAMA Network Open.

“Among intraductal papillary mucinous neoplasms (IPMNs) that were Fukuoka negative at baseline, fewer than 10% developed worrisome or high-risk features on follow-up. Pancreatic cancer development in IPMN was a rare event overall,” the authors wrote.

“Current international consensus guidelines for the management of IPMNs recommend image-based surveillance with the aim to detect clinical and imaging features of advanced neoplasia,” the authors wrote. Yet “there are no population-based estimates of the burden of pancreatic cancer in individuals with IPMNs or the proportion of pancreatic cancers that develop from or adjacent to an IPMN.”

Researchers aimed to address this knowledge gap with a population-based cohort study. Drawing data from the Rochester Epidemiology Project, which includes longitudinal medical records from residents of Olmsted County, Minn., investigators identified two cohorts. The first group comprised 2,114 patients 50 years old or older who had undergone abdominal CT scans between 2000 and 2015, among whom 231 (10.9%) had IPMNs. The second cohort included 320 patients diagnosed with pancreatic cancer between 2000 and 2019, among whom 31 (9.8%) had IPMNs.

Further analysis showed that 81% of the patients with IPMNs in the first cohort lacked Fukuoka high-risk or worrisome features. Within this subgroup, the incidence rate of pancreatic cancer per 100 years was not significantly different than among individuals without IPMNs.

“Although the risk of IPMN-PC is has been extensively described, our population-based study further demonstrates that most IPMNs did not progress in Fukuoka stage and did not transform into pancreatic cancer, a similar message was expressed by the current American Gastroenterological Association pancreatic cyst guidelines, published in 2015, and studies published in 2022 and 2016,” the investigators wrote.

Analyzing the cohort of 320 patients with pancreatic cancer showed those with IPMNs had significantly better outcomes than those without IPMNs, including longer survival and lower rate of metastatic disease upon diagnosis. These findings align with previous research, the investigators wrote.

In an accompanying editorial, Stefano Crippa, MD, PhD, of Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, and colleagues offered their perspective on the findings.

“Although results of this study should be validated in larger cohorts, they represent useful clinical data from an unselected population-based cohort that helps challenge current IPMN surveillance policies that recommend lifetime active surveillance for all fit individuals,” they wrote. “Currently, we can use follow-up data from studies like this one to identify patients with IPMNs who are not at risk of progression based on clinical-radiological parameters. We can furthermore start selecting subgroups of patients with limited life expectancy due to age or comorbidities to be considered for surveillance discontinuation.”

Timothy Louis Frankel, MD, a gastrointestinal surgeon at the University of Michigan, Ann Arbor, specializing in malignancies, said the findings are most useful for reassuring patients who have been diagnosed with an IPMN.

“The real take-home message is that in the absence of worrisome features people [with an IPMN] should feel comfortable that their risk is no higher than the general population for developing pancreatic cancer,” Dr. Frankel said in an interview.

Before any changes to surveillance can be considered, however, Dr. Frankel echoed the investigators’ call for a larger study, noting the relatively small population, most of whom (92%) were White.

“We do know that pancreas cancer and pancreas diseases vary significantly by race,” Dr. Frankel said. “So we do need to be a little bit cautious about changing the way that we manage patients based on a fairly homogeneous subset.”

He also pointed out that two patients had IPMNs that developed increased risk over time.

“They actually went from no risk features to having features that put them at risk,” Dr. Frankel said. “Those are patients who were saved by surveillance. So I’m not sure that this study was necessarily designed to let us know if and when we can stop following these lesions.”

Study authors had no relevant disclosures. The editorial writers reported no conflicts of interest.

Individuals with intraductal papillary mucinous neoplasms (IPMNs) that lack “worrisome or high-risk features” have no greater risk of pancreatic cancer than individuals without IPMNs, based on a retrospective cohort study from Mayo Clinic.

These findings, if validated in a larger population, could challenge current surveillance practices for IPMNs, reported researchers who were led by Shounak Majumder, MD, a gastroenterologist in the pancreas clinic at Mayo Clinic, Rochester, Minn. The study was published in JAMA Network Open.

“Among intraductal papillary mucinous neoplasms (IPMNs) that were Fukuoka negative at baseline, fewer than 10% developed worrisome or high-risk features on follow-up. Pancreatic cancer development in IPMN was a rare event overall,” the authors wrote.

“Current international consensus guidelines for the management of IPMNs recommend image-based surveillance with the aim to detect clinical and imaging features of advanced neoplasia,” the authors wrote. Yet “there are no population-based estimates of the burden of pancreatic cancer in individuals with IPMNs or the proportion of pancreatic cancers that develop from or adjacent to an IPMN.”

Researchers aimed to address this knowledge gap with a population-based cohort study. Drawing data from the Rochester Epidemiology Project, which includes longitudinal medical records from residents of Olmsted County, Minn., investigators identified two cohorts. The first group comprised 2,114 patients 50 years old or older who had undergone abdominal CT scans between 2000 and 2015, among whom 231 (10.9%) had IPMNs. The second cohort included 320 patients diagnosed with pancreatic cancer between 2000 and 2019, among whom 31 (9.8%) had IPMNs.

Further analysis showed that 81% of the patients with IPMNs in the first cohort lacked Fukuoka high-risk or worrisome features. Within this subgroup, the incidence rate of pancreatic cancer per 100 years was not significantly different than among individuals without IPMNs.

“Although the risk of IPMN-PC is has been extensively described, our population-based study further demonstrates that most IPMNs did not progress in Fukuoka stage and did not transform into pancreatic cancer, a similar message was expressed by the current American Gastroenterological Association pancreatic cyst guidelines, published in 2015, and studies published in 2022 and 2016,” the investigators wrote.

Analyzing the cohort of 320 patients with pancreatic cancer showed those with IPMNs had significantly better outcomes than those without IPMNs, including longer survival and lower rate of metastatic disease upon diagnosis. These findings align with previous research, the investigators wrote.

In an accompanying editorial, Stefano Crippa, MD, PhD, of Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, and colleagues offered their perspective on the findings.

“Although results of this study should be validated in larger cohorts, they represent useful clinical data from an unselected population-based cohort that helps challenge current IPMN surveillance policies that recommend lifetime active surveillance for all fit individuals,” they wrote. “Currently, we can use follow-up data from studies like this one to identify patients with IPMNs who are not at risk of progression based on clinical-radiological parameters. We can furthermore start selecting subgroups of patients with limited life expectancy due to age or comorbidities to be considered for surveillance discontinuation.”

Timothy Louis Frankel, MD, a gastrointestinal surgeon at the University of Michigan, Ann Arbor, specializing in malignancies, said the findings are most useful for reassuring patients who have been diagnosed with an IPMN.

“The real take-home message is that in the absence of worrisome features people [with an IPMN] should feel comfortable that their risk is no higher than the general population for developing pancreatic cancer,” Dr. Frankel said in an interview.

Before any changes to surveillance can be considered, however, Dr. Frankel echoed the investigators’ call for a larger study, noting the relatively small population, most of whom (92%) were White.

“We do know that pancreas cancer and pancreas diseases vary significantly by race,” Dr. Frankel said. “So we do need to be a little bit cautious about changing the way that we manage patients based on a fairly homogeneous subset.”

He also pointed out that two patients had IPMNs that developed increased risk over time.

“They actually went from no risk features to having features that put them at risk,” Dr. Frankel said. “Those are patients who were saved by surveillance. So I’m not sure that this study was necessarily designed to let us know if and when we can stop following these lesions.”

Study authors had no relevant disclosures. The editorial writers reported no conflicts of interest.

Individuals with intraductal papillary mucinous neoplasms (IPMNs) that lack “worrisome or high-risk features” have no greater risk of pancreatic cancer than individuals without IPMNs, based on a retrospective cohort study from Mayo Clinic.

These findings, if validated in a larger population, could challenge current surveillance practices for IPMNs, reported researchers who were led by Shounak Majumder, MD, a gastroenterologist in the pancreas clinic at Mayo Clinic, Rochester, Minn. The study was published in JAMA Network Open.

“Among intraductal papillary mucinous neoplasms (IPMNs) that were Fukuoka negative at baseline, fewer than 10% developed worrisome or high-risk features on follow-up. Pancreatic cancer development in IPMN was a rare event overall,” the authors wrote.

“Current international consensus guidelines for the management of IPMNs recommend image-based surveillance with the aim to detect clinical and imaging features of advanced neoplasia,” the authors wrote. Yet “there are no population-based estimates of the burden of pancreatic cancer in individuals with IPMNs or the proportion of pancreatic cancers that develop from or adjacent to an IPMN.”

Researchers aimed to address this knowledge gap with a population-based cohort study. Drawing data from the Rochester Epidemiology Project, which includes longitudinal medical records from residents of Olmsted County, Minn., investigators identified two cohorts. The first group comprised 2,114 patients 50 years old or older who had undergone abdominal CT scans between 2000 and 2015, among whom 231 (10.9%) had IPMNs. The second cohort included 320 patients diagnosed with pancreatic cancer between 2000 and 2019, among whom 31 (9.8%) had IPMNs.

Further analysis showed that 81% of the patients with IPMNs in the first cohort lacked Fukuoka high-risk or worrisome features. Within this subgroup, the incidence rate of pancreatic cancer per 100 years was not significantly different than among individuals without IPMNs.

“Although the risk of IPMN-PC is has been extensively described, our population-based study further demonstrates that most IPMNs did not progress in Fukuoka stage and did not transform into pancreatic cancer, a similar message was expressed by the current American Gastroenterological Association pancreatic cyst guidelines, published in 2015, and studies published in 2022 and 2016,” the investigators wrote.

Analyzing the cohort of 320 patients with pancreatic cancer showed those with IPMNs had significantly better outcomes than those without IPMNs, including longer survival and lower rate of metastatic disease upon diagnosis. These findings align with previous research, the investigators wrote.

In an accompanying editorial, Stefano Crippa, MD, PhD, of Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, and colleagues offered their perspective on the findings.

“Although results of this study should be validated in larger cohorts, they represent useful clinical data from an unselected population-based cohort that helps challenge current IPMN surveillance policies that recommend lifetime active surveillance for all fit individuals,” they wrote. “Currently, we can use follow-up data from studies like this one to identify patients with IPMNs who are not at risk of progression based on clinical-radiological parameters. We can furthermore start selecting subgroups of patients with limited life expectancy due to age or comorbidities to be considered for surveillance discontinuation.”

Timothy Louis Frankel, MD, a gastrointestinal surgeon at the University of Michigan, Ann Arbor, specializing in malignancies, said the findings are most useful for reassuring patients who have been diagnosed with an IPMN.

“The real take-home message is that in the absence of worrisome features people [with an IPMN] should feel comfortable that their risk is no higher than the general population for developing pancreatic cancer,” Dr. Frankel said in an interview.

Before any changes to surveillance can be considered, however, Dr. Frankel echoed the investigators’ call for a larger study, noting the relatively small population, most of whom (92%) were White.

“We do know that pancreas cancer and pancreas diseases vary significantly by race,” Dr. Frankel said. “So we do need to be a little bit cautious about changing the way that we manage patients based on a fairly homogeneous subset.”

He also pointed out that two patients had IPMNs that developed increased risk over time.

“They actually went from no risk features to having features that put them at risk,” Dr. Frankel said. “Those are patients who were saved by surveillance. So I’m not sure that this study was necessarily designed to let us know if and when we can stop following these lesions.”

Study authors had no relevant disclosures. The editorial writers reported no conflicts of interest.

Liver-resident gamma delta T cells that produce interleukin(IL)-17 coordinate with hepatic macrophages to offer early protection against Listeria monocytogenes infection, according to investigators.

These finding suggest that gamma delta T17 cells could be a target for novel cell-based therapies against liver diseases, reported lead author Yanan Wang, PhD, of Shandong University, Jinan, China, and colleagues.

“Gamma delta T cells are located in mucosal tissues and other peripheral lymphoid tissues and are considered to act as the first line of defense within the immune system,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Several studies have reported that IL-17A produced by gamma delta T cells plays a critical role in host defense after Listeria monocytogenes [infection] in the liver. However, in those studies, the details of the phenotypes, dynamic changes, proliferation activity, and cytokine production of the responding gamma delta T cell populations in the overall process of hepatic infection are unclear, and how they accumulated into the infection sites has not been elucidated.”

To address this knowledge gap, Dr. Wang and colleagues conducted a series of experiments involving gamma delta T cells from murine liver samples.

First, using single-cell RNA-sequencing (scRNA-seq), the investigators identified six clusters of hepatic gamma delta T cells.

“[This first step] revealed the unique gene expression characteristics and indicated the possible important roles in immune responses of hepatic gamma delta T17 cells,” they noted.

Next, the investigators measured expression of CD44 and CD27 in liver gamma delta cells.

“Expression of CD44 and CD27 has been used to distinguish IL-17A–, interferon gamma–producing, and other subsets of gamma delta T cells in the thymus, lymph nodes, lungs, and other peripheral lymphoid tissues,” they wrote.

These efforts revealed three subsets of hepatic gamma delta T cells, of which CD44hiCD27– gamma delta T cells were most abundant. Further analysis revealed expression profiles consistent with liver residency.

The next phases of the study characterized the immune roles of hepatic gamma delta T cells.

A comparison of Listeria monocytogenes infection in wild-type versus T-cell antigen receptor knockout mice, for example, showed that knockout mice had significantly more weight loss than did wild-type mice, greater bacterial load in the liver, and shorter survival times.

“As expected, the proportion and absolute numbers of gamma delta T cells in the liver of wild-type mice increased at day 3 and reached a peak at day 7 after infection,” the investigators wrote. “These data suggested that hepatic gamma delta T cells proliferated after infection and contributed to Lm clearance.”

Parabiosis experiments showed that the increased number of CD44hiCD27– gamma delta T cells in the livers of Listeria monocytogenes-infected mice were due to migration and proliferation of liver-resident gamma delta T cells instead of circulating gamma delta T cells. A transwell assay revealed that Kupffer cells and monocyte-derived macrophages promoted migration of CD44hiCD27– gamma delta T cells upon infection.

“Our study provides additional insight into liver-resident lymphocytes and will aid in targeting such tissue-resident lymphocyte populations to promote local immune surveillance,” the investigators concluded.

The study was supported by grants from the National Natural Science Foundation of China and the Shandong Provincial Natural Science Foundation. The investigators disclosed no conflicts of interest.

Liver-resident gamma delta T cells that produce interleukin(IL)-17 coordinate with hepatic macrophages to offer early protection against Listeria monocytogenes infection, according to investigators.

These finding suggest that gamma delta T17 cells could be a target for novel cell-based therapies against liver diseases, reported lead author Yanan Wang, PhD, of Shandong University, Jinan, China, and colleagues.

“Gamma delta T cells are located in mucosal tissues and other peripheral lymphoid tissues and are considered to act as the first line of defense within the immune system,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Several studies have reported that IL-17A produced by gamma delta T cells plays a critical role in host defense after Listeria monocytogenes [infection] in the liver. However, in those studies, the details of the phenotypes, dynamic changes, proliferation activity, and cytokine production of the responding gamma delta T cell populations in the overall process of hepatic infection are unclear, and how they accumulated into the infection sites has not been elucidated.”

To address this knowledge gap, Dr. Wang and colleagues conducted a series of experiments involving gamma delta T cells from murine liver samples.

First, using single-cell RNA-sequencing (scRNA-seq), the investigators identified six clusters of hepatic gamma delta T cells.

“[This first step] revealed the unique gene expression characteristics and indicated the possible important roles in immune responses of hepatic gamma delta T17 cells,” they noted.

Next, the investigators measured expression of CD44 and CD27 in liver gamma delta cells.

“Expression of CD44 and CD27 has been used to distinguish IL-17A–, interferon gamma–producing, and other subsets of gamma delta T cells in the thymus, lymph nodes, lungs, and other peripheral lymphoid tissues,” they wrote.

These efforts revealed three subsets of hepatic gamma delta T cells, of which CD44hiCD27– gamma delta T cells were most abundant. Further analysis revealed expression profiles consistent with liver residency.

The next phases of the study characterized the immune roles of hepatic gamma delta T cells.

A comparison of Listeria monocytogenes infection in wild-type versus T-cell antigen receptor knockout mice, for example, showed that knockout mice had significantly more weight loss than did wild-type mice, greater bacterial load in the liver, and shorter survival times.

“As expected, the proportion and absolute numbers of gamma delta T cells in the liver of wild-type mice increased at day 3 and reached a peak at day 7 after infection,” the investigators wrote. “These data suggested that hepatic gamma delta T cells proliferated after infection and contributed to Lm clearance.”

Parabiosis experiments showed that the increased number of CD44hiCD27– gamma delta T cells in the livers of Listeria monocytogenes-infected mice were due to migration and proliferation of liver-resident gamma delta T cells instead of circulating gamma delta T cells. A transwell assay revealed that Kupffer cells and monocyte-derived macrophages promoted migration of CD44hiCD27– gamma delta T cells upon infection.

“Our study provides additional insight into liver-resident lymphocytes and will aid in targeting such tissue-resident lymphocyte populations to promote local immune surveillance,” the investigators concluded.

The study was supported by grants from the National Natural Science Foundation of China and the Shandong Provincial Natural Science Foundation. The investigators disclosed no conflicts of interest.

Liver-resident gamma delta T cells that produce interleukin(IL)-17 coordinate with hepatic macrophages to offer early protection against Listeria monocytogenes infection, according to investigators.

These finding suggest that gamma delta T17 cells could be a target for novel cell-based therapies against liver diseases, reported lead author Yanan Wang, PhD, of Shandong University, Jinan, China, and colleagues.

“Gamma delta T cells are located in mucosal tissues and other peripheral lymphoid tissues and are considered to act as the first line of defense within the immune system,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Several studies have reported that IL-17A produced by gamma delta T cells plays a critical role in host defense after Listeria monocytogenes [infection] in the liver. However, in those studies, the details of the phenotypes, dynamic changes, proliferation activity, and cytokine production of the responding gamma delta T cell populations in the overall process of hepatic infection are unclear, and how they accumulated into the infection sites has not been elucidated.”

To address this knowledge gap, Dr. Wang and colleagues conducted a series of experiments involving gamma delta T cells from murine liver samples.

First, using single-cell RNA-sequencing (scRNA-seq), the investigators identified six clusters of hepatic gamma delta T cells.

“[This first step] revealed the unique gene expression characteristics and indicated the possible important roles in immune responses of hepatic gamma delta T17 cells,” they noted.

Next, the investigators measured expression of CD44 and CD27 in liver gamma delta cells.

“Expression of CD44 and CD27 has been used to distinguish IL-17A–, interferon gamma–producing, and other subsets of gamma delta T cells in the thymus, lymph nodes, lungs, and other peripheral lymphoid tissues,” they wrote.

These efforts revealed three subsets of hepatic gamma delta T cells, of which CD44hiCD27– gamma delta T cells were most abundant. Further analysis revealed expression profiles consistent with liver residency.

The next phases of the study characterized the immune roles of hepatic gamma delta T cells.

A comparison of Listeria monocytogenes infection in wild-type versus T-cell antigen receptor knockout mice, for example, showed that knockout mice had significantly more weight loss than did wild-type mice, greater bacterial load in the liver, and shorter survival times.

“As expected, the proportion and absolute numbers of gamma delta T cells in the liver of wild-type mice increased at day 3 and reached a peak at day 7 after infection,” the investigators wrote. “These data suggested that hepatic gamma delta T cells proliferated after infection and contributed to Lm clearance.”

Parabiosis experiments showed that the increased number of CD44hiCD27– gamma delta T cells in the livers of Listeria monocytogenes-infected mice were due to migration and proliferation of liver-resident gamma delta T cells instead of circulating gamma delta T cells. A transwell assay revealed that Kupffer cells and monocyte-derived macrophages promoted migration of CD44hiCD27– gamma delta T cells upon infection.

“Our study provides additional insight into liver-resident lymphocytes and will aid in targeting such tissue-resident lymphocyte populations to promote local immune surveillance,” the investigators concluded.

The study was supported by grants from the National Natural Science Foundation of China and the Shandong Provincial Natural Science Foundation. The investigators disclosed no conflicts of interest.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Pharmaceutical-grade cannabidiol (CBD) relieved symptoms in patients with idiopathic and diabetic gastroparesis and increased tolerance of liquid nutrient intake after 4 weeks of treatment in a phase 2 randomized double-blinded, placebo-controlled study recently published in Clinical Gastroenterology and Hepatology.

There is “significant unmet medical need in gastroparesis,” and compared with cannabis, which has been used to relieve nausea and pain in patients with the condition, CBD has limited psychic effects with the added potential to reduce gut sensation and inflammation, wrote Ting Zheng, MD, and colleagues at Mayo Clinic in Rochester, Minn.

The researchers assessed the symptoms of 44 patients (21 randomized to receive CBD and 23 to receive placebo) – each of whom had nonsurgical gastroparesis with documented delayed gastric emptying of solids (GES) by scintigraphy for at least 3 months – with the American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom Index (GCSI) Daily Diary.

They measured GES at baseline, and at 4 weeks, they measured GES again as well as fasting and postprandial gastric volumes and satiation using a validated Ensure drink test. (Patients ingested Ensure [Abbott Laboratories] at a rate of 30 mL/min and recorded their sensations every 5 minutes.) The two treatment arms were compared via 2-way analysis of covariance that included body mass index and, when applicable, baseline measurements.

Patients in the CBD group received twice-daily oral Epidiolex (Jazz Pharmaceuticals, Dublin), which is Food and Drug Administration–approved for the treatment of seizures associated with two rare forms of epilepsy and with another rare genetic disease in patients 1 year of age and older.

The researchers documented significant improvements in the CBD group in total GCSI score (P = .0008) and in scores measuring the inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall perceived severity of symptoms (P = .034).

CBD treatment was also associated with greater tolerated volume of Ensure – “without increases in scores for nausea, fullness, bloating, and pain” – and, in another component of the GCSI, there was “a borderline reduction in upper abdominal pain,” Dr. Zheng and coauthors wrote.

There was a significant slowing of GES in the CBD group, however, and no significant differences were seen at 4 weeks in the fasting or accommodation gastric volumes between the two treatment groups. That beneficial effects of CBD were seen despite slowing of GES “raises the question of the contribution of the delayed GE of solids to development of symptoms in patients with gastroparesis, which is supported by some but not all meta-analyses on this topic,” they noted.

Patients had a mean age of 44 and most were female. Of the 44 patients, 32 had idiopathic gastroparesis, 6 had type 1 diabetes, and 6 had type 2 diabetes. Four patients in the study did not tolerate the FDA-recommended full-dose escalation of CBD to 20 mg/kg per day, but completed the study on the highest tolerated dose.

Adverse effects (fatigue, headache, nausea) were distributed equally between the two groups, but diarrhea was more common in the CBD group. Diarrhea was the most common adverse event in a recently published analysis of 892 pediatric patients receiving Epidiolex over an estimated 1,755.7 patient-years of CBD exposure, the researchers noted.

CBD is a cannabinoid receptor 2 inverse agonist with central nervous system effects, but it also affects visceral or somatic sensation peripherally, the authors noted. The beneficial effects of CBD in gastroparesis are “presumed to reflect effects on sensory mechanisms or anti-inflammatory effects mediated via CBR2 (cannabinoid receptor type 2) reversing the hypersensitivity and intrinsic inflammatory pathogenesis recorded in idiopathic and diabetic gastroparesis,” Dr. Zheng and colleagues wrote. CBD may also, in a mechanism unrelated to CB receptors, inhibit smooth muscle contractile activity, they said.

Larger randomized controlled trials of longer-term administration of CBD in both idiopathic and diabetic gastroparesis are warranted, the investigators said.

The researchers disclosed no conflicts. The study was supported by a grant from the National Institutes of Health.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.