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AGA aims to increase awareness of exocrine pancreatic insufficiency
The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.
“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”
To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
Clinical features and risk factors
The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.
The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.
Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
Diagnostic strategies
The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).
Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.
The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.
“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.
While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
Treatment strategies
Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.
PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.
Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
Surveillance
EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.
The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.
The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.
“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”
To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
Clinical features and risk factors
The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.
The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.
Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
Diagnostic strategies
The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).
Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.
The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.
“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.
While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
Treatment strategies
Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.
PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.
Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
Surveillance
EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.
The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.
The update, which was led by Anna M. Buchner, MD, PhD, University of Pennsylvania, Philadelphia, includes 15 best practice advice statements based on available literature and expert opinion.
“EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately,” the authors wrote in Gastroenterology. “There is an urgent need to increase awareness of and treatment for this condition.”
To this end, the authors offered guidance spanning the patient journey, with recommendations broadly grouped into four categories: clinical features and risk factors, diagnostic strategies, treatment approaches, and disease monitoring.
Clinical features and risk factors
The CPU begins by listing the key clinical features of EPI, including bloating, excessive flatulence, fat-soluble vitamin deficiencies, protein-calorie malnutrition, steatorrhea with or without diarrhea, and weight loss.
The authors went on to suggest that EPI should also be considered in patients with high-risk clinical conditions, including previous pancreatic surgery, chronic pancreatitis, cystic fibrosis, pancreatic ductal adenocarcinoma, and relapsing acute pancreatitis.
Similarly, suspicion should be increased for individuals with moderate-risk clinical conditions, such as prior intestinal surgery, Zollinger-Ellison syndrome, longstanding diabetes mellitus, and duodenal diseases such as celiac and Crohn’s disease.
Diagnostic strategies
The primary diagnostic tool for EPI is the fecal elastase test, according to the update. Levels below 100 mcg/g indicate EPI, whereas levels between 100-200 mcg/g are considered indeterminate. The investigators noted that this test can be conducted even during pancreatic enzyme replacement therapy (PERT).
Other tests for EPI are rarely used, such as fecal fat testing, which must be performed on a high-fat diet, and quantitative testing, which is generally impractical for routine clinical use.
The authors also noted that a therapeutic trial of PERT is an unreliable method for diagnosing EPI.
“Patients with nonspecific symptoms, such as bloating, excess gas, and foul-smelling or floating stools may note some improvement in these symptoms while taking PERT, but these symptoms are nonspecific and symptomatic changes may be a placebo effect or masking other disorders, such as celiac disease, causing delays in a correct diagnosis,” they wrote.
While cross-sectional imaging methods such as CT scans, MRI, and endoscopic ultrasound play a significant role in detecting other pancreatic diseases, they cannot identify EPI. Breath tests and direct pancreatic function tests do hold promise, but they are not widely available in the United States.
Treatment strategies
Once EPI is diagnosed, treatment with PERT is indicated to prevent complications related to fat malabsorption and malnutrition.
PERT formulations are all equally effective at equivalent doses, according to the update, but non–enteric-coated preparations require concurrent H2 or proton pump inhibitor therapy. PERT should be taken during meals, with an initial adult dose of at least 40,000 USP units of lipase during each meal. Half that dose may be considered for snacks, with further dosage refinements based on meal size and fat content.
Dietary modifications may include supplementation with fat-soluble vitamins alongside smaller, more frequent, low- to moderate-fat meals. Very-low-fat diets should be avoided, the authors cautioned.
Surveillance
EPI treatment success can be identified by reduction in steatorrhea and associated gastrointestinal symptoms, as well as weight gain, improved muscle mass and function, and enhanced fat-soluble vitamin levels, Dr. Whitcomb and colleagues wrote, noting that a dual-energy x-ray absorptiometry scan also should be performed at baseline, then repeated every 1-2 years.
The update was commissioned and approved by the AGA. The investigators disclosed relationships with AbbVie, Nestlé, Regeneron, and others.
FROM GASTROENTEROLOGY
AGA issues CPU for CRC screening, postpolypectomy surveillance
Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.
“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.
With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.
To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.
Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.
“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”
The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.
According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.
The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.
“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”
The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.
Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.
“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.
With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.
To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.
Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.
“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”
The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.
According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.
The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.
“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”
The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.
Led by Rachel B. Issaka, MD, of Fred Hutchinson Cancer Center, Seattle, the Clinical Practice Update focuses primarily on time frames for surveillance based on known risk factors, plus a caution against widespread use of emerging risk-stratification tools that need more real-world evidence among diverse populations.
“Based on current evidence, risk stratification for initiating CRC screening or surveillance should be based on age, family history, predisposing hereditary CRC syndromes, prior screening, or other CRC predisposing conditions,” the authors wrote in Gastroenterology.
With these parameters in mind, Dr. Issaka and colleagues issued nine best practice advice statements, noting that systematic reviews were not conducted, so statements are not rated based on quality of evidence or strength of presented considerations.
To begin, the investigators characterized two risk strata for CRC. Individuals with a first-degree relative who was diagnosed with CRC have an increased risk of CRC, particularly if that relative was diagnosed before age 50. In contrast, people with no such family history, or a personal history of CRC, hereditary CRC syndromes, inflammatory bowel disease, or other predisposing conditions, have average risk for CRC.
Those with average risk should start CRC screening at age 45, while those with high risk should start screening at age 40, or 10 years before the age of diagnosis of their youngest affected relative, whichever is sooner.
“The age to initiate screening according to family history of CRC could be optimized based on the number of affected family members, age at diagnosis of the affected relatives, as well as the 10-year cumulative incidence of CRC according to age within a specific source population (e.g., country),” the investigators wrote. “However, in the absence of widely available risk calculators developed for such risk-adapted screenings, a simplified approach to consider is initiating screening approximately 10 years before the age of diagnosis of the youngest affected relative or at age 40 years.”
The decision to screen and conduct postpolypectomy surveillance beyond age 75 should factor in risks, benefits, screening history, and comorbidities.
According to Dr. Issaka and colleagues, individuals with average risk can choose between several options for screening based on preference and availability, including fecal immunochemical test, colonoscopy, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography. Those with high risk, however, should undergo colonoscopy.
The final best practice advice statement offers a word of caution against widespread use of new risk-stratification tools for CRC and postpolypectomy surveillance that have yet to demonstrate real-world effectiveness and cost-effectiveness in diverse populations.
“Validation within diverse racial and ethnic populations is critical for models that include genetic factors, because genetic discovery studies have focused largely on individuals with European ancestry, and because risk-relevant genetic factors may vary according to individual’s origin of genetic ancestry,” the investigators wrote. “Although many studies differentiate individuals by race and ethnicity, which may capture some information about the likely presence of certain genetic variants, ancestry is a better predictor and should be captured in validation studies.”
The update was commissioned and approved by the AGA, and supported by the National Cancer Institute of the National Institutes of Health. The investigators disclosed relationships with Geneoscopy, CellMax Life, Universal Diagnostics, and others.
FROM GASTROENTEROLOGY
Real-world data confirm efficacy of dupilumab in severe EoE
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dupilumab provides histologic, endoscopic, and symptomatic improvement in patients with severe, treatment-refractory, fibrostenotic eosinophilic esophagitis (EoE), new research shows.
METHODOLOGY:
- The researchers conducted a retrospective cohort study of 46 patients with severe, treatment-refractory fibrostenotic EoE who were prescribed dupilumab 300 mg subcutaneously every other week or weekly.
- Histologic response, endoscopic severity, and symptom improvement were assessed using the results of esophagogastroduodenoscopy (EGD) conducted before and after dupilumab therapy.
TAKEAWAY:
- Most patients demonstrated endoscopic, histologic, and symptomatic improvement on dupilumab, compared with predupilumab EGD results.
- The average peak eosinophil count improved from 70 eosinophils/high-power field to 9 eosinophils/HPF while on dupilumab, and 80% of patients achieved histologic remission (< 15 eosinophils/HPF), compared with 11% before dupilumab.
- Endoscopic features also improved on dupilumab, with a significant reduction in exudates, rings, edema, and furrows. The total EoE Endoscopic Reference Score decreased from 4.62 to 1.89 (P < .001).
- With dupilumab, a significant increase in predilation esophageal diameter (from 13.9 to 16 mm; P < .001) was observed, with no change in the proportion of strictures.
- Global symptom improvement was reported in 91% of patients while on dupilumab versus 2% before dupilumab.
IN PRACTICE:
“These results echo the results from the prior phase 3 study, but in a population where most subjects would likely have been excluded due to stricture severity and need for dilation,” the authors wrote. “ Further studies are needed to determine not only long-term efficacy of dupilumab for this group of EoE patients, but whether dupilumab could be moved earlier in the treatment algorithm for this severe subgroup.”
SOURCE:
The study, by Christopher Lee, MD, and Evan Dellon, MD, MPH, with the Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, was published online in Clinical Gastroenterology and Hepatology.
LIMITATIONS:
The study involved a single tertiary care center, which could limit the generalizability of the findings. The patients were primarily adults, so the results may not be able to be extended to younger children.
DISCLOSURES:
The study had no specific funding. Dr. Dellon has received research funding and consulting fees from multiple pharmaceutical companies. Dr. Lee has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA CPU stresses brain-gut aspects of bloating, distention and belching
A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.
The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.
Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”
The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.
For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.
Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.
Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.
When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.
Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.
“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.
For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.
Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.
Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.
A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.
The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.
Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”
The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.
For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.
Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.
Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.
When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.
Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.
“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.
For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.
Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.
Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.
A new Clinical Practice Update from the AGA on belching, abdominal bloating, and distention offers practical management strategies for a class of disorders that, while highly prevalent, can be confusing to clinicians because of their nonspecific and overlapping symptomatology and wide range of possible causes.
The expert review, published online in Gastroenterology, is dedicated to these specific disorders, which, when not caused by bacteria, food intolerance, or autoimmune disease, are increasingly viewed as stemming from dysregulation of the brain-gut axis, and therefore responsive to interventions such as biofeedback therapy and central nervous system modulators, including antidepressants referred to as neuromodulators due to their pain modulating effects in the gut.
Baharak Moshiree, MD, of Atrium Health, Wake Forest Medical University, Charlotte, N.C., the lead author, said the guidance is aimed at GI specialists as much as primary care physicians and other providers who treat patients with these disorders.
Clinicians may not always know which diagnostic studies to order for a patient with bloating, distention, or belching, Dr. Moshiree said, and since large randomized controlled trials in these patient groups are not available, making evidence-based treatment recommendations is challenging. Because the disorders are ubiquitous, “there’s a lot of social media attention around them, and these include fad diets and drugs labeled as medical foods, like probiotics, that patients will often try.”
The guidance includes 15 best practice advice statements along with two diagnostic and treatment algorithms, one for belching and the other for bloating and distention.
For belching, the authors stress discerning between gastric and supragastric belching using clinical history and examination, and if needed, impedance Ph monitoring. For supragastric belching, or esophageal belching, treatment considerations may include cognitive behavioral therapy, biofeedback training, and neuromodulator (antidepressant) drugs either alone or combined with psychological therapies.
Abdominal bloating and distention should be diagnosed using the Rome IV criteria, and in patients with suspected carbohydrate enzyme deficiencies, dietary restriction of potentially problematic carbohydrates or breath testing may be used to rule out intolerance. In a subset of at-risk patients, “small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth,” the guidance says. Blood testing may be used to rule out celiac disease, and, if positive, a definitive diagnosis should be confirmed with small bowel tissue biopsy obtained during an upper endoscopy, Dr. Moshiree and her colleagues wrote.
Endoscopy and imaging should be restricted to patients with alarm features such as vomiting or weight loss, rapid worsening of symptoms, or an abnormal physical exam. Tests such as gastric emptying transit studies should not be routinely ordered unless nausea and vomiting are present. Similarly, whole-gut motility studies should be ordered only if there are symptoms suggestive of motility disorders, with testing carried out at specialized centers.
When constipation occurs with bloating, clinicians should use anorectal physiology testing to rule out a pelvic-floor disorder, which, if present, can be treated with pelvic floor biofeedback training. Constipation in the context of bloating may also be treated with laxatives. Probiotics are not advised as treatment for bloating and distention in this guidance, given a lack of robust studies. However, neuromodulators may help reduce visceral or gut hypersensitivity and improve psychological comorbidities if these are present, the authors wrote.
Conditions treated with dietary modifications should be overseen by dietitians, and diaphragmatic breathing and neuromodulators can be used to treat a condition called abdominophrenic dyssynergia, the guidance says.
“We tried to make it clinically useful,” Dr. Moshiree said of the practice update, which was not the result of systematic reviews or meta-analyses of multicenter randomized controlled trials. The update contains no ratings on its recommendations and does not grade the evidence used. Rather, the three coauthors looked to results from published randomized trials and observational studies, along with their own expert opinion.
For example, the guidance’s best practice advice on abdominophrenic dyssynergia came from single center studies in Italy where bloating improved with use of biofeedback therapy for this condition. Although this was a single center study, experts have found that biofeedback therapy is helpful for relaxing the pelvic floor muscles which can help bloating and distension symptoms.
Dr. Moshiree also pointed to a 2021 narrative review by Brian E. Lacy, MD. and David Cangemi, MD, of the Mayo Clinic in Jacksonville, Fla., that helped inform the framework for this clinical practice update.
Dr. Moshiree disclosed financial relationships with several pharmaceutical companies including Salix, AbbVie, Medtronic, and Takeda. Her two coauthors, Douglas Drossman, MD, of the Rome Foundation and the University of North Carolina, Chapel Hill, and Aasma Shaukat, MD, of New York University, also disclosed industry support.
FROM GASTROENTEROLOGY
Rectal cancer risk is markedly higher at 10 years post colectomy
, shows a Danish population-based cohort study.
These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.
“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.
Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.
The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.
The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.
This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.
Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).
A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).
Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.
The findings should inform surveillance guidelines, they wrote.
“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.
The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
Rectal cancer risk in colectomized IBD patients is poorly understood, and most guidelines do not specify unique surveillance protocols for this subset of patients. As such, gastroenterologists are often left using their best judgement to decide surveillance intervals in this group.
In a Danish population-based cohort study, Akimenko and colleagues identify a markedly increased risk of rectal cancer 10 years after colectomy in patients with a diverted rectum. This risk is 8-fold compared to a matched IBD cohort without colectomy, 10-fold compared to the background population, and is slightly higher in ulcerative colitis than Crohn’s disease. The relative risk is similar to that identified in a Swedish nationwide study.
The study benefits from a large, unselected cohort and its use of a matched IBD population without colectomy. However, it is not sufficiently powered to assess cancer risk in patients with IRA or IPAA, thus limiting its generalizability. The lengthy 40-year inclusion period, while providing strength in numbers, may also impact the study findings, as significant changes have occurred in IBD management during this timeframe.
The authors herald an important reminder that post-colectomy IBD patients are not ‘out of the woods’ with regards to rectal cancer risk. Inconsistency exists amongst providers when it comes to surveillance intervals in these patients.
The study highlights the need for specific surveillance guidelines for this group, particularly in patients with a diverted rectum. Additional studies are needed to assess risk in patients with IRA or IPAA.
Dr. Maté Gergely is an assistant professor of medicine within the division of gastroenterology at Washington University School of Medicine, St. Louis. He has no relevant disclosures.
Rectal cancer risk in colectomized IBD patients is poorly understood, and most guidelines do not specify unique surveillance protocols for this subset of patients. As such, gastroenterologists are often left using their best judgement to decide surveillance intervals in this group.
In a Danish population-based cohort study, Akimenko and colleagues identify a markedly increased risk of rectal cancer 10 years after colectomy in patients with a diverted rectum. This risk is 8-fold compared to a matched IBD cohort without colectomy, 10-fold compared to the background population, and is slightly higher in ulcerative colitis than Crohn’s disease. The relative risk is similar to that identified in a Swedish nationwide study.
The study benefits from a large, unselected cohort and its use of a matched IBD population without colectomy. However, it is not sufficiently powered to assess cancer risk in patients with IRA or IPAA, thus limiting its generalizability. The lengthy 40-year inclusion period, while providing strength in numbers, may also impact the study findings, as significant changes have occurred in IBD management during this timeframe.
The authors herald an important reminder that post-colectomy IBD patients are not ‘out of the woods’ with regards to rectal cancer risk. Inconsistency exists amongst providers when it comes to surveillance intervals in these patients.
The study highlights the need for specific surveillance guidelines for this group, particularly in patients with a diverted rectum. Additional studies are needed to assess risk in patients with IRA or IPAA.
Dr. Maté Gergely is an assistant professor of medicine within the division of gastroenterology at Washington University School of Medicine, St. Louis. He has no relevant disclosures.
Rectal cancer risk in colectomized IBD patients is poorly understood, and most guidelines do not specify unique surveillance protocols for this subset of patients. As such, gastroenterologists are often left using their best judgement to decide surveillance intervals in this group.
In a Danish population-based cohort study, Akimenko and colleagues identify a markedly increased risk of rectal cancer 10 years after colectomy in patients with a diverted rectum. This risk is 8-fold compared to a matched IBD cohort without colectomy, 10-fold compared to the background population, and is slightly higher in ulcerative colitis than Crohn’s disease. The relative risk is similar to that identified in a Swedish nationwide study.
The study benefits from a large, unselected cohort and its use of a matched IBD population without colectomy. However, it is not sufficiently powered to assess cancer risk in patients with IRA or IPAA, thus limiting its generalizability. The lengthy 40-year inclusion period, while providing strength in numbers, may also impact the study findings, as significant changes have occurred in IBD management during this timeframe.
The authors herald an important reminder that post-colectomy IBD patients are not ‘out of the woods’ with regards to rectal cancer risk. Inconsistency exists amongst providers when it comes to surveillance intervals in these patients.
The study highlights the need for specific surveillance guidelines for this group, particularly in patients with a diverted rectum. Additional studies are needed to assess risk in patients with IRA or IPAA.
Dr. Maté Gergely is an assistant professor of medicine within the division of gastroenterology at Washington University School of Medicine, St. Louis. He has no relevant disclosures.
, shows a Danish population-based cohort study.
These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.
“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.
Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.
The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.
The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.
This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.
Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).
A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).
Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.
The findings should inform surveillance guidelines, they wrote.
“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.
The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
, shows a Danish population-based cohort study.
These findings suggest that more intensive long-term surveillance is needed for colectomized patients with IBD, wrote researchers who were led by Tine Jess, MD, DMSc, of the Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen.
“Our nationwide population-based cohort study covering 4 decades shows that despite a relatively low absolute number of RC cases following colectomy for IBD, the risk of RC is markedly increased 10 years after the surgery. This calls for better long-term surveillance of colectomized IBD patients,” the authors wrote in Gastro Hep Advances.
Previous studies have suggested that patients with IBD have an increased risk of rectal cancer after colectomy, but these data “cannot stand alone,” and “need to be confirmed in other unselected patient cohorts,” investigators wrote.
The new study was based on an analysis of data from more than 9 million individuals in the Danish Civil Registration System between 1978 and 2018. The analyses were restricted to risk of rectal cancer in the population with diverted rectum.
The final dataset included 4,931 patients with IBD who had subtotal colectomy and diverted rectum, 49,251 matched patients with IBD who did not undergo colectomy, and 246,550 matched individuals without IBD to serve as a background population. Within these groups, rectal cancer occurred at a rate of 0.9%, 0.4%, and 0.4%, respectively, hinting at an increased risk of rectal cancer after colectomy among patients with IBD.
This signal was clarified by comparing rates of rectal cancer 10 years before and after colectomy. Rates 10 years before colectomy were not significantly different between groups.
Comparing colectomized IBD patients with the noncolectomized IBD patients at the 10-year postcolectomy mark revealed an eightfold increased risk of rectal cancer (hazard ratio, 7.56; 95% confidence interval, 5.21-10.86). Risk was slightly lower for patients with Crohn’s disease (HR, 5.10; 95% CI, 2.41-10.81) than for those with ulcerative colitis (HR, 9.42; 95% CI, 6.18-14.36).
A comparison at the same time point for colectomized IBD patients versus the background population showed an even higher relative risk for rectal cancer, up 10-fold (HR, 10.01; 95% CI, 7.20-13.94).
Despite variations in surgical methods, researchers concluded that the long-term risk of rectal cancer post colectomy increased among patients with IBD.
The findings should inform surveillance guidelines, they wrote.
“To reduce the risk of CRC in IBD, endoscopic surveillance guidelines have been developed both nationally and internationally. However, guidelines do not include clear recommendations for patients with a residual rectum, ileo-rectal anastomosis, or ileal pouch-anal anastomosis. The Danish guidelines, the Danish Society of Gastroenterology and Hepatology, mention a potential increased risk of rectal cancer post colectomy ... The European Crohn’s and Colitis Organization guideline consensus paper ‘European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies’ mentions that ‘the risk of rectal cancer is relatively high in IBD patients after subtotal colectomy’ [but] without further recommendation,” study authors wrote.
The study was supported by Laege Carl Emil Friis, Hustru Olga Doris Friis, and the Danish National Research Foundation. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
AGA CPU: Essentials to prevent complications with ostomies
The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.
Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.
The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.
Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.
Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.
Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.
Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.
Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.
Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.
“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.
This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.
The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.
Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.
The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.
Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.
Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.
Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.
Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.
Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.
Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.
“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.
This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.
The American Gastroenterological Association has published a new Clinical Practice Update for the management of enteral ostomies, which are common in the management of patients with colorectal cancer, inflammatory bowel disease, diverticular disease, intestinal trauma, and intestinal perforation.
Approximately 750,000 people in the United States live with an ostomy, including colostomy, ileostomy, and continent ileostomy. Complications and challenges with self-care are common among patients with an enteral stoma, but most available guidance documents fail to offer management principles beyond the immediate perioperative period, wrote authors of the guidance which was led by Traci Hedrick, MD, of the University of Virginia Health, Charlottesville.
The update was published online in Clinical Gastroenterology and Hepatology. It includes best practice updates for managing short- and long-term complications, and perioperative considerations.
Early high ostomy output, defined by ostomy output greater than fluid intake that occurs within 3 weeks of stoma formation, causing dehydration, is a short-term complication associated with ostomies. It is more common among patients with an ileostomy than a colostomy, and requires rapid evaluation for infection and other associated complications. The cornerstone of treatment is rehydration, usually intravenously during hospital stay. Additional treatments may include bulking agents, antimotility agents, antisecretory agents, anti-inflammatory agents, adaptation-promoting agents, and surgery to reverse the ostomy.
Other short-term complications include ostomy leakage, stomal retraction, and mucocutaneous separation.
Dermatological problems are the most common of long-term complications. These typically involve skin irritation due to leakage. Other dermatological complaints include folliculitis, fungal rash, and allergic reaction to the appliance. Each of these must be addressed based on the nature and underlying cause of the complication.
Other long-term complications include chronic high ostomy output, parastomal hernia, and stomal prolapse.
Clinicians should also be aware of the psychological impact on patients. They may fear having a leakage or emitting an odor. They may also have anxiety in disclosing having an ostomy to partners and fear travel. “Difficulty with self-care should be addressed through preoperative and postoperative education. Preoperative education and stoma site marking has been shown to improve quality of life and decrease peristomal skin and pouching complications,” the authors wrote.
Health care providers should discuss and manage expectations for life with an ostomy, including managing ostomy output, maintaining pouching appliances, and the regular passage of mucus from the native rectum.
“High-quality ostomy care begins at the preoperative visit with wound ostomy and continence consultation. Stoma education and counseling are essential to prevent complications and manage patient expectations for living with a stoma. The early diagnosis and management of both early and late ostomy complications require ongoing communication between patients and care teams. Multidisciplinary coordination is imperative to prevent hospital readmissions and to improve the quality of life for our patients living with ostomies,” the authors wrote.
This Clinical Practice Update was commissioned by the AGA Institute. The investigators disclosed relationships with Johnson & Johnson, AbbVie, BMS, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA CPU focuses on noninvasive tests in patients with NAFLD
Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.
The update, published online in Gastroenterology, includes eight best practice advice statements.
“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.
“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.
Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.
The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave
elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.
“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.
Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).
Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.
The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”
Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.
Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.
The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.
“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.
Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).
This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.
The update, published online in Gastroenterology, includes eight best practice advice statements.
“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.
“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.
Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.
The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave
elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.
“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.
Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).
Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.
The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”
Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.
Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.
The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.
“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.
Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).
This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
Noninvasive testing allows for routine risk stratification and long-term monitoring of patients with nonalcoholic fatty liver disease (NAFLD), offering a safer, more practical approach than biopsy, according to a recent Clinical Practice Update Expert Review by the American Gastroenterological Association.
The update, published online in Gastroenterology, includes eight best practice advice statements.
“The health care burden of longitudinal management of patients with NAFLD is significant. The emergence and utilization of noninvasive testing (NIT) in gastroenterology practices has the potential to significantly enhance the care of patients with NAFLD by improving detection of patients with advanced fibrosis who are at increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), thereby facilitating timely clinical management,” wrote authors who were led by Julia J. Wattacheril, MD, MPH, of the Columbia University–New York Presbyterian Hospital nonalcoholic fatty liver disease program and center for liver disease and transplantation.
“In this Expert Review, we have provided clinicians with best practice advice for optimal utilization of NITs in patients with NAFLD,” the authors wrote.
Consensus best practice for implementing NITs in practice are scarce, giving rise to the present clinical practice update. The expert panel reviewed available evidence for these tests during longitudinal care of patients with advanced fibrosis as a means of predicting liver-related outcomes and informing treatment decisions.
The first statement encourages use of NITs for risk stratification during the diagnosis of NAFLD, typically in the form of clinical calculators like fibrosis 4 index (FIB-4), vibration controlled transient elastography (VCTE), shear wave
elastography (SWE), or magnetic resonance elastography (MRE), all of which have been validated in NAFLD.
“Ultrasound-based 3-dimensional elastography (Velacur) and iron-corrected T1 magnetic resonance imaging, although used less frequently, are emerging technologies,” the panelists noted.
Second, the update suggests that patients with a FIB-4 less than 1.3 are unlikely to have advanced hepatic fibrosis, based on this threshold’s strong negative predictive value (NPV).
Still, clinicians should remember that this FIB-4 threshold may be less reliable among patients younger than 35 years or older than 65 years, making it necessary to also consider other clinical measurements, according to the update. The third best practice advice encourages use of two or more NITs among patients with a FIB-4 score greater than 1.3.
The fourth piece of best practice advice suggests that clinicians follow manufacturer’s specifications when implementing NITs, as misuse may lead to “discordant results and adverse events.”
Fifth, to increase the positive predictive value (PPV) for detecting advanced fibrosis, NITs are best interpreted in the context of relevant clinical data, such as physical exam and endoscopy findings.
Next, the document encourages use of liver biopsy when NIT findings are discordant or indeterminate, conflict with findings from other test modalities, or if alternative, non–NAFLD etiologies are suspected.
The penultimate best practice advice suggests use of NITs for serial longitudinal disease monitoring, with signs of progression or regression used to guide clinical decisions.
“Additional evidence for longitudinal prediction of fibrosis regression and progression and response to intervention (lifestyle and pharmacologic) is needed in trials and real-world clinical practice,” Dr. Wattacheril and colleagues noted.
Finally, the clinical practice update advises surveillance of liver complications, such as hepatocellular carcinoma, among patients with NIT results that suggest advanced fibrosis (F3) or cirrhosis (F4).
This clinical practice update was commissioned by the AGA Institute. The investigators disclosed relationships with AstraZeneca, BMS, Novo Nordisk, and others.
FROM GASTROENTEROLOGY
Crohn’s disease indicators manifest years before diagnosis
Changes in proteins and antibodies suggesting immune dysregulation may be detectable in serum years before clinical manifestation of complicated Crohn’s disease, shows a study recently published in Clinical Gastroenterology and Hepatology.
These preclinical signatures could one day play a role in screening for complicated Crohn’s disease (CD) and in mapping underlying disease pathways, potentially opening doors to new preventive approaches, wrote study authors who were led by Joseph A. Murray, MD, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“Mounting evidence suggests that the diagnosis of CD is preceded by a lengthy asymptomatic preclinical period,” investigators wrote. “Gaining insight into this phase may allow a better understanding of the primary events that lead to its development and offer potential strategies to predict and prevent the disease including its complications.”
The study, which was a nested case-control study based on the PREDICTS study, included 201 patients with CD who had serum samples archived 2, 4, and 6 years prior to diagnosis, as well as 201 healthy controls who provided serum samples for comparison. Serum samples were analyzed with a comprehensive panel of 1,129 proteomic markers and antimicrobial antibodies.
At time of diagnosis, 47 of the patients with CD (24%) had a complicated phenotype, including stricturing behavior, penetrating behavior, or need for early surgery.
“The unique availability of preclinical samples collected at multiple time points allowed us to examine the sequence of immunological changes and protein biomarkers that occurred before diagnosis,” the investigators wrote. “We also evaluated a wide array of protein biomarkers, utilizing a novel proteomic platform, and applied novel rigorous statistical approaches, which allowed us to discover the potential biomarkers and biologic pathways for the complicated phenotypes even before diagnosis.”
As early as 6 years before diagnosis, patients with complicated CD had significantly higher levels of antimicrobial antibodies than patients with noncomplicated CD, as well as elevations in 22 protein biomarkers indicating immune dysregulation.
Specifically, complicated CD was preceded by elevated anti–Saccharomyces cerevisiae antibodies (ASCA) IgA/IgG, anti-Flagellin antibodies, and other proteins linked with fibrosis, adaptive immunity, and innate immunity. Simultaneously, the same patients had reduced levels of protein biomarkers linked with protection against fibrosis and tissue damage. Network analysis added weight to these findings by demonstrating a significant correlation between ASCA IgA/IgG and protein biomarkers tied to innate immunity and lack of factors for tissue protection.
“Altogether, the hypothesis can be proposed that the combination of increasing levels of inflammatory cytokines, loss of anti-inflammatory proteins, and production of antimicrobial antibodies could accelerate and magnify tissue destruction and fibrosis driving complications at diagnosis in CD,” the investigators wrote. “These data support the concept that complicated CD may not always be the result of the progression of an uncontrolled inflammatory disease but may also be the consequence of a unique pathophysiological process.”
The findings deserve further investigation as they could lead to new clinical tools for screening and intervention. “The serological signature that we identified could help to further select subjects at risk of developing complicated CD who could be preferential candidates for preventative strategies,” investigators wrote.
The investigators disclosed relationships with Janssen, AbbVie, Galapagos, and others.
Certainly, insights into the preclinical phase of a disease state such as IBD may allow for potential preventive interventions and possible avoidance of disease-related complications. In this important study by Choung and colleagues, pre-diagnosis serum analyses of protein biomarkers and antimicrobial antibodies revealed that certain signatures are associated with a complicated phenotype of Crohn’s disease at time of diagnosis compared to patients with uncomplicated Crohn’s disease. Specifically, patients with complicated Crohn’s disease at diagnosis had higher levels of anti-microbial antibodies and altered protein biomarkers with overproduction of inflammatory proteins 6 years before their date of diagnosis, likely reflecting a dysregulated innate immune system, excessive adaptive response to microbial antigens, and fibrosis.
Although the results of this study are very exciting and may help support further research to risk stratify and possibly prevent progression of Crohn’s disease in the pre-clinical stage, additional confirmatory studies are needed before these observations are ready for real world application.
Jana G. Al Hashash, MD, MSc, associate professor of medicine, Mayo Clinic, Florida. She has no conflicts.
Certainly, insights into the preclinical phase of a disease state such as IBD may allow for potential preventive interventions and possible avoidance of disease-related complications. In this important study by Choung and colleagues, pre-diagnosis serum analyses of protein biomarkers and antimicrobial antibodies revealed that certain signatures are associated with a complicated phenotype of Crohn’s disease at time of diagnosis compared to patients with uncomplicated Crohn’s disease. Specifically, patients with complicated Crohn’s disease at diagnosis had higher levels of anti-microbial antibodies and altered protein biomarkers with overproduction of inflammatory proteins 6 years before their date of diagnosis, likely reflecting a dysregulated innate immune system, excessive adaptive response to microbial antigens, and fibrosis.
Although the results of this study are very exciting and may help support further research to risk stratify and possibly prevent progression of Crohn’s disease in the pre-clinical stage, additional confirmatory studies are needed before these observations are ready for real world application.
Jana G. Al Hashash, MD, MSc, associate professor of medicine, Mayo Clinic, Florida. She has no conflicts.
Certainly, insights into the preclinical phase of a disease state such as IBD may allow for potential preventive interventions and possible avoidance of disease-related complications. In this important study by Choung and colleagues, pre-diagnosis serum analyses of protein biomarkers and antimicrobial antibodies revealed that certain signatures are associated with a complicated phenotype of Crohn’s disease at time of diagnosis compared to patients with uncomplicated Crohn’s disease. Specifically, patients with complicated Crohn’s disease at diagnosis had higher levels of anti-microbial antibodies and altered protein biomarkers with overproduction of inflammatory proteins 6 years before their date of diagnosis, likely reflecting a dysregulated innate immune system, excessive adaptive response to microbial antigens, and fibrosis.
Although the results of this study are very exciting and may help support further research to risk stratify and possibly prevent progression of Crohn’s disease in the pre-clinical stage, additional confirmatory studies are needed before these observations are ready for real world application.
Jana G. Al Hashash, MD, MSc, associate professor of medicine, Mayo Clinic, Florida. She has no conflicts.
Changes in proteins and antibodies suggesting immune dysregulation may be detectable in serum years before clinical manifestation of complicated Crohn’s disease, shows a study recently published in Clinical Gastroenterology and Hepatology.
These preclinical signatures could one day play a role in screening for complicated Crohn’s disease (CD) and in mapping underlying disease pathways, potentially opening doors to new preventive approaches, wrote study authors who were led by Joseph A. Murray, MD, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“Mounting evidence suggests that the diagnosis of CD is preceded by a lengthy asymptomatic preclinical period,” investigators wrote. “Gaining insight into this phase may allow a better understanding of the primary events that lead to its development and offer potential strategies to predict and prevent the disease including its complications.”
The study, which was a nested case-control study based on the PREDICTS study, included 201 patients with CD who had serum samples archived 2, 4, and 6 years prior to diagnosis, as well as 201 healthy controls who provided serum samples for comparison. Serum samples were analyzed with a comprehensive panel of 1,129 proteomic markers and antimicrobial antibodies.
At time of diagnosis, 47 of the patients with CD (24%) had a complicated phenotype, including stricturing behavior, penetrating behavior, or need for early surgery.
“The unique availability of preclinical samples collected at multiple time points allowed us to examine the sequence of immunological changes and protein biomarkers that occurred before diagnosis,” the investigators wrote. “We also evaluated a wide array of protein biomarkers, utilizing a novel proteomic platform, and applied novel rigorous statistical approaches, which allowed us to discover the potential biomarkers and biologic pathways for the complicated phenotypes even before diagnosis.”
As early as 6 years before diagnosis, patients with complicated CD had significantly higher levels of antimicrobial antibodies than patients with noncomplicated CD, as well as elevations in 22 protein biomarkers indicating immune dysregulation.
Specifically, complicated CD was preceded by elevated anti–Saccharomyces cerevisiae antibodies (ASCA) IgA/IgG, anti-Flagellin antibodies, and other proteins linked with fibrosis, adaptive immunity, and innate immunity. Simultaneously, the same patients had reduced levels of protein biomarkers linked with protection against fibrosis and tissue damage. Network analysis added weight to these findings by demonstrating a significant correlation between ASCA IgA/IgG and protein biomarkers tied to innate immunity and lack of factors for tissue protection.
“Altogether, the hypothesis can be proposed that the combination of increasing levels of inflammatory cytokines, loss of anti-inflammatory proteins, and production of antimicrobial antibodies could accelerate and magnify tissue destruction and fibrosis driving complications at diagnosis in CD,” the investigators wrote. “These data support the concept that complicated CD may not always be the result of the progression of an uncontrolled inflammatory disease but may also be the consequence of a unique pathophysiological process.”
The findings deserve further investigation as they could lead to new clinical tools for screening and intervention. “The serological signature that we identified could help to further select subjects at risk of developing complicated CD who could be preferential candidates for preventative strategies,” investigators wrote.
The investigators disclosed relationships with Janssen, AbbVie, Galapagos, and others.
Changes in proteins and antibodies suggesting immune dysregulation may be detectable in serum years before clinical manifestation of complicated Crohn’s disease, shows a study recently published in Clinical Gastroenterology and Hepatology.
These preclinical signatures could one day play a role in screening for complicated Crohn’s disease (CD) and in mapping underlying disease pathways, potentially opening doors to new preventive approaches, wrote study authors who were led by Joseph A. Murray, MD, of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.
“Mounting evidence suggests that the diagnosis of CD is preceded by a lengthy asymptomatic preclinical period,” investigators wrote. “Gaining insight into this phase may allow a better understanding of the primary events that lead to its development and offer potential strategies to predict and prevent the disease including its complications.”
The study, which was a nested case-control study based on the PREDICTS study, included 201 patients with CD who had serum samples archived 2, 4, and 6 years prior to diagnosis, as well as 201 healthy controls who provided serum samples for comparison. Serum samples were analyzed with a comprehensive panel of 1,129 proteomic markers and antimicrobial antibodies.
At time of diagnosis, 47 of the patients with CD (24%) had a complicated phenotype, including stricturing behavior, penetrating behavior, or need for early surgery.
“The unique availability of preclinical samples collected at multiple time points allowed us to examine the sequence of immunological changes and protein biomarkers that occurred before diagnosis,” the investigators wrote. “We also evaluated a wide array of protein biomarkers, utilizing a novel proteomic platform, and applied novel rigorous statistical approaches, which allowed us to discover the potential biomarkers and biologic pathways for the complicated phenotypes even before diagnosis.”
As early as 6 years before diagnosis, patients with complicated CD had significantly higher levels of antimicrobial antibodies than patients with noncomplicated CD, as well as elevations in 22 protein biomarkers indicating immune dysregulation.
Specifically, complicated CD was preceded by elevated anti–Saccharomyces cerevisiae antibodies (ASCA) IgA/IgG, anti-Flagellin antibodies, and other proteins linked with fibrosis, adaptive immunity, and innate immunity. Simultaneously, the same patients had reduced levels of protein biomarkers linked with protection against fibrosis and tissue damage. Network analysis added weight to these findings by demonstrating a significant correlation between ASCA IgA/IgG and protein biomarkers tied to innate immunity and lack of factors for tissue protection.
“Altogether, the hypothesis can be proposed that the combination of increasing levels of inflammatory cytokines, loss of anti-inflammatory proteins, and production of antimicrobial antibodies could accelerate and magnify tissue destruction and fibrosis driving complications at diagnosis in CD,” the investigators wrote. “These data support the concept that complicated CD may not always be the result of the progression of an uncontrolled inflammatory disease but may also be the consequence of a unique pathophysiological process.”
The findings deserve further investigation as they could lead to new clinical tools for screening and intervention. “The serological signature that we identified could help to further select subjects at risk of developing complicated CD who could be preferential candidates for preventative strategies,” investigators wrote.
The investigators disclosed relationships with Janssen, AbbVie, Galapagos, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Hemostatic powder superior in controlling tumor bleeding
The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.
For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.
The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.
Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).
None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.
The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.
“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.
“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”
Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”
Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.
The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.
One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.
Gastrointestinal tumor bleeding is a challenging problem that can lead to prolonged hospitalization and interruption of curative or palliative oncologic interventions. Standard endoscopic hemostasis interventions, such as subepithelial epinephrine injection and mechanical and thermal treatments, can be limited because of the underlying tumor biology that alters angiogenesis, distorts the surrounding mucosa, and undermines the normal coagulation process. This randomized trial by Pittayanon et al. demonstrated that the hemostatic powder TC-325 (Hemospray, Cook Medical) was superior to standard endoscopic intervention in achieving immediate hemostasis (100% vs. 69%) and reducing 30-day rebleeding rate (2% vs. 21%).
As clinicians and endoscopists, our ultimate goals in treating GI tumor bleeding are to provide safe and efficient hemostasis, to decrease hospital stay and to minimize delay and interruption of oncologic or palliative treatments. This study advocates that TC-325 may be a better primary option than standard endoscopic treatments for GI tumor bleeding in the appropriate setting. Safety, efficacy, and feasibility studies comparing TC-325 to the other hemostatic powder products are needed.
Malorie K. Simons, MD, is an interventional endoscopist with Fox Chase Cancer Center, Temple University Health System, Philadelphia. She specializes in colorectal cancer, esophageal cancer, and gastric cancer. She has no conflicts of interest.
Gastrointestinal tumor bleeding is a challenging problem that can lead to prolonged hospitalization and interruption of curative or palliative oncologic interventions. Standard endoscopic hemostasis interventions, such as subepithelial epinephrine injection and mechanical and thermal treatments, can be limited because of the underlying tumor biology that alters angiogenesis, distorts the surrounding mucosa, and undermines the normal coagulation process. This randomized trial by Pittayanon et al. demonstrated that the hemostatic powder TC-325 (Hemospray, Cook Medical) was superior to standard endoscopic intervention in achieving immediate hemostasis (100% vs. 69%) and reducing 30-day rebleeding rate (2% vs. 21%).
As clinicians and endoscopists, our ultimate goals in treating GI tumor bleeding are to provide safe and efficient hemostasis, to decrease hospital stay and to minimize delay and interruption of oncologic or palliative treatments. This study advocates that TC-325 may be a better primary option than standard endoscopic treatments for GI tumor bleeding in the appropriate setting. Safety, efficacy, and feasibility studies comparing TC-325 to the other hemostatic powder products are needed.
Malorie K. Simons, MD, is an interventional endoscopist with Fox Chase Cancer Center, Temple University Health System, Philadelphia. She specializes in colorectal cancer, esophageal cancer, and gastric cancer. She has no conflicts of interest.
Gastrointestinal tumor bleeding is a challenging problem that can lead to prolonged hospitalization and interruption of curative or palliative oncologic interventions. Standard endoscopic hemostasis interventions, such as subepithelial epinephrine injection and mechanical and thermal treatments, can be limited because of the underlying tumor biology that alters angiogenesis, distorts the surrounding mucosa, and undermines the normal coagulation process. This randomized trial by Pittayanon et al. demonstrated that the hemostatic powder TC-325 (Hemospray, Cook Medical) was superior to standard endoscopic intervention in achieving immediate hemostasis (100% vs. 69%) and reducing 30-day rebleeding rate (2% vs. 21%).
As clinicians and endoscopists, our ultimate goals in treating GI tumor bleeding are to provide safe and efficient hemostasis, to decrease hospital stay and to minimize delay and interruption of oncologic or palliative treatments. This study advocates that TC-325 may be a better primary option than standard endoscopic treatments for GI tumor bleeding in the appropriate setting. Safety, efficacy, and feasibility studies comparing TC-325 to the other hemostatic powder products are needed.
Malorie K. Simons, MD, is an interventional endoscopist with Fox Chase Cancer Center, Temple University Health System, Philadelphia. She specializes in colorectal cancer, esophageal cancer, and gastric cancer. She has no conflicts of interest.
The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.
For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.
The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.
Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).
None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.
The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.
“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.
“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”
Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”
Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.
The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.
One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.
The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.
For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.
The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.
Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).
None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.
The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.
“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.
“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”
Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”
Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.
The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.
One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Crohn’s link seen for ultraprocessed foods
Ultraprocessed foods contain large amounts of artificial flavors, stabilizers, emulsifiers, sweeteners, or preservatives. Studies have linked higher consumption of them to cardiovascular disease, diabetes, obesity, and cancers.
For their research, published in Clinical Gastroenterology and Hepatology, Neeraj Nerula, MD of McMaster University, Hamilton, Ont., and colleagues pooled data from five recent cohort studies to assess whether their consumption was also linked to inflammatory bowel disease.
The included cohort studies together enrolled more than 1 million participants (mean age, 43-56; 55%-85% female). Of these, 916 developed Crohn’s disease, and 1,934 developed ulcerative colitis, during follow-up. None of the participants had IBD at baseline, and all were followed up at least 1 year. All the studies used the same food classification system, called NOVA, to assess foods eaten, and all were conducted between 2020 and 2022.
People who consumed more ultraprocessed foods saw higher Crohn’s risk, compared with those classed as consuming lower amounts of these foods (hazard ratio, 1.71; 95% confidence interval, 1.37-2.14). Also, lower risk of Crohn’s was observed among participants who consumed more unprocessed or minimally processed foods, such as vegetables, chicken, milk, and eggs (HR, 0.71; 95% CI, 0.53-0.94). The same associations were not seen for ulcerative colitis.
“Our findings support the hypothesis that consumption of [ultraprocessed foods] and low consumption of unprocessed/minimally processed foods may increase the risk for CD,” Dr. Nerula and colleagues wrote. The lack of association seen with ulcerative colitis might be explained by differences in the pathogenesis of each disease.
Ultraprocessed foods might contribute to Crohn’s by disrupting gut microbiota, the authors wrote. “For instance, emulsifiers have been shown to increase epithelial permeability, disruption of the intestinal barrier, and gut dysbiosis in mice. Carboxymethyl cellulose has been shown to facilitate bacterial adherence to gut epithelium, possibly leading to bacterial overgrowth and invasion of bacteria in between the intestinal villi. Furthermore, additives such as carrageenan, titanium dioxide, and maltodextrin have been shown to promote intestinal inflammation.”
Dr. Nerula and colleagues described as strengths of their study its large size, the low heterogenicity of the included studies, and the use of validated, standardized questionnaires to measure dietary intake in each study. Nonetheless, they cautioned, the results might not apply to younger age groups, and the majority of participants were White North Americans and Europeans, making it difficult to generalize results.
“Advancements in food processing and associated changes in dietary patterns could explain the rise of IBD incidence during the 20th and 21st centuries,” Dr. Narula and colleagues concluded. “Further investigations are needed to identify the specific potential culprits among processed foods that could account for the increased risk of CD observed.”
The study authors did not report outside funding. Dr. Narula disclosed receiving fees from pharmaceutical manufacturers including Janssen, AbbVie, Takeda, Pfizer, Merck, and others. Two of coauthors also disclosed receiving funds from industry, and five additional coauthors had no conflicts.
The causes of inflammatory bowel disease (IBD) are thought to be multifactorial and include genetic predisposition, dysregulated immune responses, imbalances in the intestinal microbiota, and environmental exposures.
Incidence and prevalence of IBD has increased over time, including in developing countries, and appear to parallel industrialization and “Westernization” of societies. One of the potential contributors to IBD risk is diet. Dietary changes associated with more modern or “Westernized” diets, including increases in processed foods, are some of the factors hypothesized to contribute to rising rates of IBD.
In the meta-analysis by Narula and colleagues, the authors observed a significant increase in the risk of CD, but not UC, in individuals who consumed significantly higher amounts of ultraprocessed foods (that is, frozen or long-shelf-life foods, products with thickeners/emulsifiers, etc.). Although there are limitations to the studies included in the meta-analysis, the association is intriguing and could point to potential lifestyle modifications that could form the basis of preventative interventions for individuals at higher risk for IBD, such as first-degree relatives.
More immediately, prospective research is needed to understand if restricting ultraprocessed foods (or increasing less-processed foods) can decrease disease activity or prevent flares in patients with IBD.
Understanding factors that predispose to or trigger IBD, such as specific dietary components, will lead to improved management strategies and ultimately preventative interventions.
Ryan Ungaro, MD, MS, is an associate professor of medicine in the division of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. He is director of the Comprehensive Care for the Recently Diagnosed IBD Patient (COMPASS-IBD). He has served as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Celltrion, Lilly, Janssen, Pfizer, Roivant, and Takeda, and has received research support from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Lily, and Pfizer.
The causes of inflammatory bowel disease (IBD) are thought to be multifactorial and include genetic predisposition, dysregulated immune responses, imbalances in the intestinal microbiota, and environmental exposures.
Incidence and prevalence of IBD has increased over time, including in developing countries, and appear to parallel industrialization and “Westernization” of societies. One of the potential contributors to IBD risk is diet. Dietary changes associated with more modern or “Westernized” diets, including increases in processed foods, are some of the factors hypothesized to contribute to rising rates of IBD.
In the meta-analysis by Narula and colleagues, the authors observed a significant increase in the risk of CD, but not UC, in individuals who consumed significantly higher amounts of ultraprocessed foods (that is, frozen or long-shelf-life foods, products with thickeners/emulsifiers, etc.). Although there are limitations to the studies included in the meta-analysis, the association is intriguing and could point to potential lifestyle modifications that could form the basis of preventative interventions for individuals at higher risk for IBD, such as first-degree relatives.
More immediately, prospective research is needed to understand if restricting ultraprocessed foods (or increasing less-processed foods) can decrease disease activity or prevent flares in patients with IBD.
Understanding factors that predispose to or trigger IBD, such as specific dietary components, will lead to improved management strategies and ultimately preventative interventions.
Ryan Ungaro, MD, MS, is an associate professor of medicine in the division of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. He is director of the Comprehensive Care for the Recently Diagnosed IBD Patient (COMPASS-IBD). He has served as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Celltrion, Lilly, Janssen, Pfizer, Roivant, and Takeda, and has received research support from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Lily, and Pfizer.
The causes of inflammatory bowel disease (IBD) are thought to be multifactorial and include genetic predisposition, dysregulated immune responses, imbalances in the intestinal microbiota, and environmental exposures.
Incidence and prevalence of IBD has increased over time, including in developing countries, and appear to parallel industrialization and “Westernization” of societies. One of the potential contributors to IBD risk is diet. Dietary changes associated with more modern or “Westernized” diets, including increases in processed foods, are some of the factors hypothesized to contribute to rising rates of IBD.
In the meta-analysis by Narula and colleagues, the authors observed a significant increase in the risk of CD, but not UC, in individuals who consumed significantly higher amounts of ultraprocessed foods (that is, frozen or long-shelf-life foods, products with thickeners/emulsifiers, etc.). Although there are limitations to the studies included in the meta-analysis, the association is intriguing and could point to potential lifestyle modifications that could form the basis of preventative interventions for individuals at higher risk for IBD, such as first-degree relatives.
More immediately, prospective research is needed to understand if restricting ultraprocessed foods (or increasing less-processed foods) can decrease disease activity or prevent flares in patients with IBD.
Understanding factors that predispose to or trigger IBD, such as specific dietary components, will lead to improved management strategies and ultimately preventative interventions.
Ryan Ungaro, MD, MS, is an associate professor of medicine in the division of gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. He is director of the Comprehensive Care for the Recently Diagnosed IBD Patient (COMPASS-IBD). He has served as an advisory board member or consultant for AbbVie, Bristol-Myers Squibb, Celltrion, Lilly, Janssen, Pfizer, Roivant, and Takeda, and has received research support from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Lily, and Pfizer.
Ultraprocessed foods contain large amounts of artificial flavors, stabilizers, emulsifiers, sweeteners, or preservatives. Studies have linked higher consumption of them to cardiovascular disease, diabetes, obesity, and cancers.
For their research, published in Clinical Gastroenterology and Hepatology, Neeraj Nerula, MD of McMaster University, Hamilton, Ont., and colleagues pooled data from five recent cohort studies to assess whether their consumption was also linked to inflammatory bowel disease.
The included cohort studies together enrolled more than 1 million participants (mean age, 43-56; 55%-85% female). Of these, 916 developed Crohn’s disease, and 1,934 developed ulcerative colitis, during follow-up. None of the participants had IBD at baseline, and all were followed up at least 1 year. All the studies used the same food classification system, called NOVA, to assess foods eaten, and all were conducted between 2020 and 2022.
People who consumed more ultraprocessed foods saw higher Crohn’s risk, compared with those classed as consuming lower amounts of these foods (hazard ratio, 1.71; 95% confidence interval, 1.37-2.14). Also, lower risk of Crohn’s was observed among participants who consumed more unprocessed or minimally processed foods, such as vegetables, chicken, milk, and eggs (HR, 0.71; 95% CI, 0.53-0.94). The same associations were not seen for ulcerative colitis.
“Our findings support the hypothesis that consumption of [ultraprocessed foods] and low consumption of unprocessed/minimally processed foods may increase the risk for CD,” Dr. Nerula and colleagues wrote. The lack of association seen with ulcerative colitis might be explained by differences in the pathogenesis of each disease.
Ultraprocessed foods might contribute to Crohn’s by disrupting gut microbiota, the authors wrote. “For instance, emulsifiers have been shown to increase epithelial permeability, disruption of the intestinal barrier, and gut dysbiosis in mice. Carboxymethyl cellulose has been shown to facilitate bacterial adherence to gut epithelium, possibly leading to bacterial overgrowth and invasion of bacteria in between the intestinal villi. Furthermore, additives such as carrageenan, titanium dioxide, and maltodextrin have been shown to promote intestinal inflammation.”
Dr. Nerula and colleagues described as strengths of their study its large size, the low heterogenicity of the included studies, and the use of validated, standardized questionnaires to measure dietary intake in each study. Nonetheless, they cautioned, the results might not apply to younger age groups, and the majority of participants were White North Americans and Europeans, making it difficult to generalize results.
“Advancements in food processing and associated changes in dietary patterns could explain the rise of IBD incidence during the 20th and 21st centuries,” Dr. Narula and colleagues concluded. “Further investigations are needed to identify the specific potential culprits among processed foods that could account for the increased risk of CD observed.”
The study authors did not report outside funding. Dr. Narula disclosed receiving fees from pharmaceutical manufacturers including Janssen, AbbVie, Takeda, Pfizer, Merck, and others. Two of coauthors also disclosed receiving funds from industry, and five additional coauthors had no conflicts.
Ultraprocessed foods contain large amounts of artificial flavors, stabilizers, emulsifiers, sweeteners, or preservatives. Studies have linked higher consumption of them to cardiovascular disease, diabetes, obesity, and cancers.
For their research, published in Clinical Gastroenterology and Hepatology, Neeraj Nerula, MD of McMaster University, Hamilton, Ont., and colleagues pooled data from five recent cohort studies to assess whether their consumption was also linked to inflammatory bowel disease.
The included cohort studies together enrolled more than 1 million participants (mean age, 43-56; 55%-85% female). Of these, 916 developed Crohn’s disease, and 1,934 developed ulcerative colitis, during follow-up. None of the participants had IBD at baseline, and all were followed up at least 1 year. All the studies used the same food classification system, called NOVA, to assess foods eaten, and all were conducted between 2020 and 2022.
People who consumed more ultraprocessed foods saw higher Crohn’s risk, compared with those classed as consuming lower amounts of these foods (hazard ratio, 1.71; 95% confidence interval, 1.37-2.14). Also, lower risk of Crohn’s was observed among participants who consumed more unprocessed or minimally processed foods, such as vegetables, chicken, milk, and eggs (HR, 0.71; 95% CI, 0.53-0.94). The same associations were not seen for ulcerative colitis.
“Our findings support the hypothesis that consumption of [ultraprocessed foods] and low consumption of unprocessed/minimally processed foods may increase the risk for CD,” Dr. Nerula and colleagues wrote. The lack of association seen with ulcerative colitis might be explained by differences in the pathogenesis of each disease.
Ultraprocessed foods might contribute to Crohn’s by disrupting gut microbiota, the authors wrote. “For instance, emulsifiers have been shown to increase epithelial permeability, disruption of the intestinal barrier, and gut dysbiosis in mice. Carboxymethyl cellulose has been shown to facilitate bacterial adherence to gut epithelium, possibly leading to bacterial overgrowth and invasion of bacteria in between the intestinal villi. Furthermore, additives such as carrageenan, titanium dioxide, and maltodextrin have been shown to promote intestinal inflammation.”
Dr. Nerula and colleagues described as strengths of their study its large size, the low heterogenicity of the included studies, and the use of validated, standardized questionnaires to measure dietary intake in each study. Nonetheless, they cautioned, the results might not apply to younger age groups, and the majority of participants were White North Americans and Europeans, making it difficult to generalize results.
“Advancements in food processing and associated changes in dietary patterns could explain the rise of IBD incidence during the 20th and 21st centuries,” Dr. Narula and colleagues concluded. “Further investigations are needed to identify the specific potential culprits among processed foods that could account for the increased risk of CD observed.”
The study authors did not report outside funding. Dr. Narula disclosed receiving fees from pharmaceutical manufacturers including Janssen, AbbVie, Takeda, Pfizer, Merck, and others. Two of coauthors also disclosed receiving funds from industry, and five additional coauthors had no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY