David A. Johnson, MD

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 

Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 

This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
 

Who Should Be Tested and Treated? 

The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 

Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 

New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 

The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.

The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
 

Caveats to Treatment 

Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.

In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 

Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.

Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 

Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
 

Treatment-Naive Patients

In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 

Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.

The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.

Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.

Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
 

Treatment-Experienced Patients

Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 

The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 

In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 

Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
 

A New Standard 

The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 

We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 

Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.

Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 

Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 

This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
 

Who Should Be Tested and Treated? 

The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 

Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 

New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 

The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.

The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
 

Caveats to Treatment 

Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.

In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 

Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.

Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 

Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
 

Treatment-Naive Patients

In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 

Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.

The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.

Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.

Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
 

Treatment-Experienced Patients

Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 

The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 

In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 

Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
 

A New Standard 

The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 

We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 

Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.

Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

Helicobacter pylori is one of the most common human bacterial chronic infections globally. Its prevalence has actually decreased in North America in recent years, although its current range of approximately 30%-40% remains substantial given the potential clinical implications of infection. 

Standards have changed considerably regarding the testing, treatment, and follow-up of H pylori. This is made clear by the just-published clinical practice guideline from the American College of Gastroenterology (ACG), which provides several new recommendations based on recent scientific evidence that should change your clinical approach to managing this common infection. 

This discussion aims to synthesize and highlight key concepts from the ACG’s comprehensive publication. 
 

Who Should Be Tested and Treated? 

The cardinal diseases caused by H pylori have traditionally included peptic ulcer disease, marginal zone B-cell lymphoma, gastric adenocarcinoma, and dyspepsia. 

Additional associations have been made with idiopathic thrombocytopenic purpura and otherwise unexplained iron deficiency. 

New evidence suggests that patients taking long-term nonsteroidal anti-inflammatory drugs, including low-dose aspirin, are relatively more susceptible to infection. 

The ACG’s guideline also recommends testing persons at an increased risk for gastric adenocarcinoma (eg, those with autoimmune gastritis, current or history of premalignant conditions, or first-degree relative with gastric cancer), as well as household members of patients with a positive nonserologic test for H pylori.

The authors note that those with an indication for testing should be offered treatment if determined to have an infection. These patients should also undergo a posttreatment test-of-cure, which should occur at least 4 weeks afterwards using a urea breath test, fecal antigen test, or gastric biopsy. 
 

Caveats to Treatment 

Patients with H pylori infections are advised to undergo treatment for a duration of 14 days. Some of the commercial prepackaged H pylori treatment options (eg, Pylera, which contains bismuth subcitrate/metronidazole/tetracycline) are dispensed in regimens lasting only 10 days and currently are viewed as inadequate.

In the United States, the patterns of antibiotic resistance for the previously used standard drugs in the treatment of H pylori have increased considerably. They range from 32% for clarithromycin, 38% for levofloxacin, and 42% for metronidazole, in contrast to 3% for amoxicillin, 1% for tetracycline, and 0% for rifabutin. 

Clarithromycin- and levofloxacin-containing treatments should be avoided in treatment-naive patients unless specifically directed following the results of susceptibility tests with either a phenotypic method (culture-based) or a molecular method (polymerase chain reaction or next-generation sequencing). Notably, the mutations responsible for both clarithromycin and levofloxacin resistance may be detectable by stool-based testing.

Maintenance of intragastric acid suppression is key to H pylori eradication, as elevated intragastric pH promotes active replication of H pylori and makes it more susceptible to bactericidal antibiotics. 

Therefore, the use of histamine-2 receptors is not recommended, as they are inadequate for achieving acid suppression. Instead, a dual-based therapy of either the potassium-competitive acid blocker (PCAB) vonoprazan (20 mg) or a high-dose proton pump inhibitor (PPI) and amoxicillin, administered twice daily, is effective, although this finding is based on limited evidence. 
 

Treatment-Naive Patients

In treatment-naive patients without penicillin allergy and for whom antibiotic susceptibility testing has not been obtained, the guideline offers its strongest recommendation for bismuth quadruple therapy. This therapy typically consists of a PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. 

Among those with a penicillin allergy, bismuth quadruple therapy is also the primary treatment choice. The authors suggest that patients with a suspected allergy are referred to an allergist for possible penicillin desensitization, given that less than 1% of the population is thought to present with a “true” allergy.

The guideline also presented conditional recommendations, based on low- to moderate-quality evidence, for using a rifabutin-based triple regimen of omeprazole, amoxicillin, and rifabutin (Talicia); a PCAB-based dual regimen of vonoprazan and amoxicillin (Voquezna Dual Pak); and a PCAB-based triple regimen of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak). In patients with unknown clarithromycin susceptibility, the PCAB-based triple therapy is preferred over PPI-clarithromycin triple therapy.

Although probiotics have been suggested to possibly lead to increased effectiveness or tolerability for H pylori eradication, this was based on studies with significant heterogeneity in their designs. At present, no high-quality data support probiotic therapy.

Clinicians may substitute doxycycline for tetracycline due to availability or cost, and also may prescribe metronidazole at a lower dose than recommended (1.5-2 g/d) to limit side effects. Both modifications have been associated with lower rates of H pylori eradication and are not recommended.
 

Treatment-Experienced Patients

Quadruple bismuth therapy is the optimal approach among treatment-experienced patients with persistent H pylori infection who have not previously received this therapy. However, this recommendation was rated as conditional, given that it was based on a low quality of evidence. 

The guideline offered other recommendations for treatment-experienced patients with persistent infection who had received bismuth quadruple therapy — also conditionally based on a low quality of evidence. 

In such patients, it is recommended to consider the use of a rifabutin-based triple therapy (ie, a PPI standard to double dose, amoxicillin, and rifabutin) and a levofloxacin-based triple therapy (ie, a PPI standard dose, levofloxacin, and amoxicillin or metronidazole). 

Although significant evidence gaps prevented the authors from providing formal recommendations, they included a PCAB-based triple therapy of vonoprazan, clarithromycin, and amoxicillin (Voquezna Triple Pak) and a high-dose dual therapy of either vonoprazan (20 mg) or PPI (double dose) and amoxicillin among their suggested salvage regimens for these patients.
 

A New Standard 

The ACG’s excellent clinical guideline offers new standards for clinicians involved in the diagnosis and treatment of H pylori. 

We must recognize, however, that there are still substantial evidence gaps, particularly around the use of a PCAB-based regimen and its relative advantages over a standard or high-dose PPI-based regimen. This may be of particular importance based on the variable prevalence of cytochrome P450 2C19 (CYP2C19) polymorphisms in the specific patient populations, as PCABs are not metabolized by CYP2C19. 

Reviewing the entirety of the ACG’s clinical guideline is encouraged for additional details about the management of H pylori beyond what is highlighted herein.

Dr. Johnson, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

The rapid adoption of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for the treatment of diabetes and weight loss has led to a corresponding interest in their potential side effects. Several recent studies have sought to expound upon what role, if any, GLP-1 RAs may have in increasing the risk for specific gastrointestinal (GI) adverse events. 

Herein is a summary of the most current information on this topic, as well as my best guidance for clinicians on integrating it into the clinical care of their patients. 
 

Aspiration Risks

Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide are among the class of medications known as GLP-1 RAs. These medications all work by mimicking the action of hormonal incretins, which are released postprandially. Incretins affect the pancreatic glucose-dependent release of insulin, inhibit release of glucagon, stimulate satiety, and reduce gastric emptying. This last effect has raised concerns that patients taking GLP-1 RAs might be at an elevated risk for endoscopy-related aspiration. 

In June 2023, the American Society of Anesthesiologists released recommendations asking providers to consider holding back GLP-1 RAs in patients with scheduled elective procedures. 

In August 2023, five national GI societies — the American Gastroenterological Association, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition — issued their own joint statement on the issue. 

In the absence of sufficient evidence, these groups suggested that healthcare providers “exercise best practices when performing endoscopy on these patients on GLP-1 [RAs].” They called for more data and encouraged key stakeholders to work together to develop the necessary evidence to provide guidance for these patients prior to elective endoscopy. A rapid clinical update issued by the American Gastroenterological Association in 2024 was consistent with these earlier multisociety recommendations. 

Two studies presented at 2024’s Digestive Disease Week provided additional reassurance that concerns about aspiration with these medications were perhaps unwarranted. 

The first (since published in The American Journal of Gastroenterology ) was a case-control study of 16,295 patients undergoing upper endoscopy, among whom 306 were taking GLP-1 RAs. It showed a higher rate of solid gastric residue among those taking GLP-1 RAs compared with controls (14% vs 4%, respectively). Patients who had prolonged fasting and clear liquids for concurrent colonoscopy had lower residue rates (2% vs 11%, respectively). However, there were no recorded incidents of procedural complications or aspiration. 

The second was a retrospective cohort study using TriNetX, a federated cloud-based network pulling millions of data points from multiple US healthcare organizations. It found that the incidence of aspiration pneumonitis and emergent intubation during or immediately after esophagogastroduodenoscopy and colonoscopy among those taking GLP-1 RAs was not increased compared with those not taking these medications. 

These were followed in June 2024 by a systematic review and meta-analysis published by Hiramoto and colleagues, which included 15 studies. The researchers showed a 36-minute prolongation for solid-food emptying and no delay in liquid emptying for patients taking GLP-1 RAs vs controls. The authors concluded that the minimal delay in solid-food emptying would be offset by standard preprocedural fasting periods. 

There is concern that patients with complicated type 2 diabetes may have a bit more of a risk for aspiration. However, this was not supported by an analysis from Barlowe and colleagues, who used a national claims database to identify 15,119 patients with type 2 diabetes on GLP-1 RAs. They found no increased events of pulmonary complications (ie, aspiration, pneumonia, respiratory failure) within 14 days following esophagogastroduodenoscopy. Additional evidence suggests that the risk for aspiration in these patients seems to be offset by prolonged fasting and intake of clear liquids. 

Although physicians clearly need to use clinical judgment when performing endoscopic procedures on these patients, the emerging evidence on safety has been encouraging. 
 

Association With GI Adverse Events

A recent retrospective analysis of real-world data from 10,328 new users of GLP-1 RAs with diabetes/obesity reported that the most common GI adverse events in this cohort were abdominal pain (57.6%), constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%). 

Notably, dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than did semaglutide and exenatide. Compared with semaglutide, dulaglutide and liraglutide had slightly higher odds of abdominal pain, gastroparesis, and nausea and vomiting. There were no significant differences between the GLP-1 RAs in the risk for GI bleeding or pancreatitis. 

A 2023 report in JAMA observed that the risk for bowel obstruction is also elevated among patients using these agents for weight loss. Possible reasons for this are currently unknown. 

Studies are needed to analyze possible variations in safety profiles between GLP-1 RAs to better guide selection of these drugs, particularly in patients with GI risk factors. Furthermore, the causal relationship between GLP-1 RAs with other concomitant medications requires further investigation. 

Although relatively infrequent, the risk for GI adverse events should be given special consideration by providers when prescribing them for weight loss, because the risk/benefit ratios may be different from those in patients with diabetes. 
 

A Lack of Hepatic Concerns

GLP-1 RAs have demonstrated a significant impact on body weight and glycemic control, as well as beneficial effects on clinical, biochemical, and histologic markers in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). These favorable changes are evident by reductions in the hepatic cytolysis markers (ie, aspartate aminotransferase and alanine aminotransferase). 

GLP-1 RAs may provide a protective function by reducing the accumulation of hepatic triglycerides and expression of several collagen genes. Some preclinical data suggest a risk reduction for progression to hepatocellular carcinoma, and animal studies indicate that complete suppression of hepatic carcinogenesis is achieved with liraglutide.

The most recent assessment of risk reduction for MASLD progression comes from a Scandinavian cohort analysis of national registries. In looking at 91,479 patients using GLP-1 RAs, investigators demonstrated this treatment was associated with a significant reduction in the composite primary endpoint of hepatocellular carcinoma, as well as both compensated and decompensated cirrhosis. 

Given the various favorable hepatic effects of GLP-1 RAs, it is likely that the composite benefit on MASLD is multifactorial. The current literature is clear that it is safe to use these agents across the spectrum of MASLD with or without fibrosis, although it must be noted that GLP-1 RAs are not approved by the Food and Drug Administration for this indication. 
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

The rapid adoption of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for the treatment of diabetes and weight loss has led to a corresponding interest in their potential side effects. Several recent studies have sought to expound upon what role, if any, GLP-1 RAs may have in increasing the risk for specific gastrointestinal (GI) adverse events. 

Herein is a summary of the most current information on this topic, as well as my best guidance for clinicians on integrating it into the clinical care of their patients. 
 

Aspiration Risks

Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide are among the class of medications known as GLP-1 RAs. These medications all work by mimicking the action of hormonal incretins, which are released postprandially. Incretins affect the pancreatic glucose-dependent release of insulin, inhibit release of glucagon, stimulate satiety, and reduce gastric emptying. This last effect has raised concerns that patients taking GLP-1 RAs might be at an elevated risk for endoscopy-related aspiration. 

In June 2023, the American Society of Anesthesiologists released recommendations asking providers to consider holding back GLP-1 RAs in patients with scheduled elective procedures. 

In August 2023, five national GI societies — the American Gastroenterological Association, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition — issued their own joint statement on the issue. 

In the absence of sufficient evidence, these groups suggested that healthcare providers “exercise best practices when performing endoscopy on these patients on GLP-1 [RAs].” They called for more data and encouraged key stakeholders to work together to develop the necessary evidence to provide guidance for these patients prior to elective endoscopy. A rapid clinical update issued by the American Gastroenterological Association in 2024 was consistent with these earlier multisociety recommendations. 

Two studies presented at 2024’s Digestive Disease Week provided additional reassurance that concerns about aspiration with these medications were perhaps unwarranted. 

The first (since published in The American Journal of Gastroenterology ) was a case-control study of 16,295 patients undergoing upper endoscopy, among whom 306 were taking GLP-1 RAs. It showed a higher rate of solid gastric residue among those taking GLP-1 RAs compared with controls (14% vs 4%, respectively). Patients who had prolonged fasting and clear liquids for concurrent colonoscopy had lower residue rates (2% vs 11%, respectively). However, there were no recorded incidents of procedural complications or aspiration. 

The second was a retrospective cohort study using TriNetX, a federated cloud-based network pulling millions of data points from multiple US healthcare organizations. It found that the incidence of aspiration pneumonitis and emergent intubation during or immediately after esophagogastroduodenoscopy and colonoscopy among those taking GLP-1 RAs was not increased compared with those not taking these medications. 

These were followed in June 2024 by a systematic review and meta-analysis published by Hiramoto and colleagues, which included 15 studies. The researchers showed a 36-minute prolongation for solid-food emptying and no delay in liquid emptying for patients taking GLP-1 RAs vs controls. The authors concluded that the minimal delay in solid-food emptying would be offset by standard preprocedural fasting periods. 

There is concern that patients with complicated type 2 diabetes may have a bit more of a risk for aspiration. However, this was not supported by an analysis from Barlowe and colleagues, who used a national claims database to identify 15,119 patients with type 2 diabetes on GLP-1 RAs. They found no increased events of pulmonary complications (ie, aspiration, pneumonia, respiratory failure) within 14 days following esophagogastroduodenoscopy. Additional evidence suggests that the risk for aspiration in these patients seems to be offset by prolonged fasting and intake of clear liquids. 

Although physicians clearly need to use clinical judgment when performing endoscopic procedures on these patients, the emerging evidence on safety has been encouraging. 
 

Association With GI Adverse Events

A recent retrospective analysis of real-world data from 10,328 new users of GLP-1 RAs with diabetes/obesity reported that the most common GI adverse events in this cohort were abdominal pain (57.6%), constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%). 

Notably, dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than did semaglutide and exenatide. Compared with semaglutide, dulaglutide and liraglutide had slightly higher odds of abdominal pain, gastroparesis, and nausea and vomiting. There were no significant differences between the GLP-1 RAs in the risk for GI bleeding or pancreatitis. 

A 2023 report in JAMA observed that the risk for bowel obstruction is also elevated among patients using these agents for weight loss. Possible reasons for this are currently unknown. 

Studies are needed to analyze possible variations in safety profiles between GLP-1 RAs to better guide selection of these drugs, particularly in patients with GI risk factors. Furthermore, the causal relationship between GLP-1 RAs with other concomitant medications requires further investigation. 

Although relatively infrequent, the risk for GI adverse events should be given special consideration by providers when prescribing them for weight loss, because the risk/benefit ratios may be different from those in patients with diabetes. 
 

A Lack of Hepatic Concerns

GLP-1 RAs have demonstrated a significant impact on body weight and glycemic control, as well as beneficial effects on clinical, biochemical, and histologic markers in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). These favorable changes are evident by reductions in the hepatic cytolysis markers (ie, aspartate aminotransferase and alanine aminotransferase). 

GLP-1 RAs may provide a protective function by reducing the accumulation of hepatic triglycerides and expression of several collagen genes. Some preclinical data suggest a risk reduction for progression to hepatocellular carcinoma, and animal studies indicate that complete suppression of hepatic carcinogenesis is achieved with liraglutide.

The most recent assessment of risk reduction for MASLD progression comes from a Scandinavian cohort analysis of national registries. In looking at 91,479 patients using GLP-1 RAs, investigators demonstrated this treatment was associated with a significant reduction in the composite primary endpoint of hepatocellular carcinoma, as well as both compensated and decompensated cirrhosis. 

Given the various favorable hepatic effects of GLP-1 RAs, it is likely that the composite benefit on MASLD is multifactorial. The current literature is clear that it is safe to use these agents across the spectrum of MASLD with or without fibrosis, although it must be noted that GLP-1 RAs are not approved by the Food and Drug Administration for this indication. 
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

The rapid adoption of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for the treatment of diabetes and weight loss has led to a corresponding interest in their potential side effects. Several recent studies have sought to expound upon what role, if any, GLP-1 RAs may have in increasing the risk for specific gastrointestinal (GI) adverse events. 

Herein is a summary of the most current information on this topic, as well as my best guidance for clinicians on integrating it into the clinical care of their patients. 
 

Aspiration Risks

Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide are among the class of medications known as GLP-1 RAs. These medications all work by mimicking the action of hormonal incretins, which are released postprandially. Incretins affect the pancreatic glucose-dependent release of insulin, inhibit release of glucagon, stimulate satiety, and reduce gastric emptying. This last effect has raised concerns that patients taking GLP-1 RAs might be at an elevated risk for endoscopy-related aspiration. 

In June 2023, the American Society of Anesthesiologists released recommendations asking providers to consider holding back GLP-1 RAs in patients with scheduled elective procedures. 

In August 2023, five national GI societies — the American Gastroenterological Association, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition — issued their own joint statement on the issue. 

In the absence of sufficient evidence, these groups suggested that healthcare providers “exercise best practices when performing endoscopy on these patients on GLP-1 [RAs].” They called for more data and encouraged key stakeholders to work together to develop the necessary evidence to provide guidance for these patients prior to elective endoscopy. A rapid clinical update issued by the American Gastroenterological Association in 2024 was consistent with these earlier multisociety recommendations. 

Two studies presented at 2024’s Digestive Disease Week provided additional reassurance that concerns about aspiration with these medications were perhaps unwarranted. 

The first (since published in The American Journal of Gastroenterology ) was a case-control study of 16,295 patients undergoing upper endoscopy, among whom 306 were taking GLP-1 RAs. It showed a higher rate of solid gastric residue among those taking GLP-1 RAs compared with controls (14% vs 4%, respectively). Patients who had prolonged fasting and clear liquids for concurrent colonoscopy had lower residue rates (2% vs 11%, respectively). However, there were no recorded incidents of procedural complications or aspiration. 

The second was a retrospective cohort study using TriNetX, a federated cloud-based network pulling millions of data points from multiple US healthcare organizations. It found that the incidence of aspiration pneumonitis and emergent intubation during or immediately after esophagogastroduodenoscopy and colonoscopy among those taking GLP-1 RAs was not increased compared with those not taking these medications. 

These were followed in June 2024 by a systematic review and meta-analysis published by Hiramoto and colleagues, which included 15 studies. The researchers showed a 36-minute prolongation for solid-food emptying and no delay in liquid emptying for patients taking GLP-1 RAs vs controls. The authors concluded that the minimal delay in solid-food emptying would be offset by standard preprocedural fasting periods. 

There is concern that patients with complicated type 2 diabetes may have a bit more of a risk for aspiration. However, this was not supported by an analysis from Barlowe and colleagues, who used a national claims database to identify 15,119 patients with type 2 diabetes on GLP-1 RAs. They found no increased events of pulmonary complications (ie, aspiration, pneumonia, respiratory failure) within 14 days following esophagogastroduodenoscopy. Additional evidence suggests that the risk for aspiration in these patients seems to be offset by prolonged fasting and intake of clear liquids. 

Although physicians clearly need to use clinical judgment when performing endoscopic procedures on these patients, the emerging evidence on safety has been encouraging. 
 

Association With GI Adverse Events

A recent retrospective analysis of real-world data from 10,328 new users of GLP-1 RAs with diabetes/obesity reported that the most common GI adverse events in this cohort were abdominal pain (57.6%), constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%). 

Notably, dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than did semaglutide and exenatide. Compared with semaglutide, dulaglutide and liraglutide had slightly higher odds of abdominal pain, gastroparesis, and nausea and vomiting. There were no significant differences between the GLP-1 RAs in the risk for GI bleeding or pancreatitis. 

A 2023 report in JAMA observed that the risk for bowel obstruction is also elevated among patients using these agents for weight loss. Possible reasons for this are currently unknown. 

Studies are needed to analyze possible variations in safety profiles between GLP-1 RAs to better guide selection of these drugs, particularly in patients with GI risk factors. Furthermore, the causal relationship between GLP-1 RAs with other concomitant medications requires further investigation. 

Although relatively infrequent, the risk for GI adverse events should be given special consideration by providers when prescribing them for weight loss, because the risk/benefit ratios may be different from those in patients with diabetes. 
 

A Lack of Hepatic Concerns

GLP-1 RAs have demonstrated a significant impact on body weight and glycemic control, as well as beneficial effects on clinical, biochemical, and histologic markers in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). These favorable changes are evident by reductions in the hepatic cytolysis markers (ie, aspartate aminotransferase and alanine aminotransferase). 

GLP-1 RAs may provide a protective function by reducing the accumulation of hepatic triglycerides and expression of several collagen genes. Some preclinical data suggest a risk reduction for progression to hepatocellular carcinoma, and animal studies indicate that complete suppression of hepatic carcinogenesis is achieved with liraglutide.

The most recent assessment of risk reduction for MASLD progression comes from a Scandinavian cohort analysis of national registries. In looking at 91,479 patients using GLP-1 RAs, investigators demonstrated this treatment was associated with a significant reduction in the composite primary endpoint of hepatocellular carcinoma, as well as both compensated and decompensated cirrhosis. 

Given the various favorable hepatic effects of GLP-1 RAs, it is likely that the composite benefit on MASLD is multifactorial. The current literature is clear that it is safe to use these agents across the spectrum of MASLD with or without fibrosis, although it must be noted that GLP-1 RAs are not approved by the Food and Drug Administration for this indication. 
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

Rumination syndrome is a well-recognized functional disorder characterized by the regurgitation of food or liquid in the absence of retching or nausea.

Evidence suggests that the prevalence of rumination syndrome is increasing. In a 2022 health survey study conducted across 26 countries — the largest epidemiologic study to date on rumination syndrome — investigators reported that it had a global prevalence of 3.1% in adults. This was higher than reported in most prior country-specific studies. More recently, a systematic review and meta-analysis from 2024 reported the pooled prevalence of rumination syndrome as 3.7% in adults and 0.4% in children. Both reports noted that female gender, anxiety, and depression were independent risk factors associated with rumination syndrome.

Recognition of this disorder is crucial in order for clinicians to better diagnose and manage it in their patients.
 

Making the Diagnosis

The diagnosis of rumination syndrome is currently based on the Rome IV consensus criteria, which were last updated in 2016. These include three diagnostic criteria essential to remember as discriminant for rumination syndrome:

• Regurgitation is the effortless return of gastric contents (recognizable food) retrograde back into the esophagus and/or mouth.
• This is not preceded by retching and not associated with nausea.
• These symptoms must have started at least 6 months before evaluation, been evident over the past 3 months, and occurred at least two to three times per month.

Although this diagnosis will be highly suspected after taking an astute clinical history, you will still need to rule out the presence of underlying organic disease.

Nearly one quarter of patients with eating disorders — which commonly accompany gastrointestinal disorders — will not have been diagnosed by the time they visit with a gastroenterologist. Therefore, gastroenterologists should be vigilant in screening for eating disorders. Notably, severe weight loss, malnutrition, electrolyte abnormalities, and dental erosions (due to acid etching) are uncommon in rumination syndrome. If such symptoms are present, it increases the possibility of an underlying eating disorder rather than primary regurgitation.

Previously, there were no published, validated questionnaires to assess the diagnosis or symptomatic response to therapies for rumination syndrome. This has recently changed with the development of a novel eight-point questionnaire that assesses frequency, severity, type of regurgitant, timing of regurgitation in relation to the meal, weight loss, and use of and response to proton pump inhibitors.

This questionnaire was recently implemented in five patients diagnosed with rumination syndrome. Albeit an extremely small trial, it nonetheless showed clinical improvement in scores associated with therapeutic intervention. Further evaluation of this tool is needed.

The diagnosis of rumination syndrome can be confirmed using impedance manometry in persons with evidence of reflux extending to the proximal esophagus, which is associated with an intragastric pressure > 30 mmHg in adults or > 25 mmHg in children. 

Gastric emptying studies are typically not required to make a diagnosis unless the clinical symptoms are atypical and an alternative motility disorder is suspected. Endoscopy is performed to rule out a mechanical disorder.
 

Histopathologic Evidence

New data indicate that there may be specific histologic changes associated with rumination syndrome. A 2023 meta-analysis reported that patients with rumination syndrome had duodenal histologic evidence of increased lymphocytes and eosinophils, which have been associated with epithelial barrier dysfunction, microbial changes, and systemic immune activation in eosinophilic duodenitis.

If these histologic changes are validated, they may suggest future novel diagnostic and treatment approaches, at least for a subset of people with rumination syndrome.
 

Best Available Treatments

The first-line therapeutic treatment for rumination syndrome is diaphragmatic breathing.

I recommended using diaphragmatic breathing for this indication in a previous commentary, in which I noted that it can essentially serve as yoga for the diaphragm and abdominal muscles and advised patients to focus on breathing “through” their belly button.

Patients are instructed to breath in through their nose for 4-6 seconds, hold their breath for 2-3 seconds, and then breath out slowly against pursed lips. They can be supine or upright but should sense their abdominal muscles expand with inhaling, not move their chest wall, and completely relax their abdominal muscles upon exhaling.

Although there is no standard frequency or duration for diaphragmatic breathing, I routinely recommend patients try it after each meal for 10-15 minutes and, if possible, more during the day and in times of stress or anxiety.

Cognitive-behavioral therapies have been shown to be effective alternatives to diaphragmatic breathing.

There is some evidence that hypnosis and biofeedback-guided control of abdominothoracic muscle activity can also be effective options in treating rumination syndrome.

Robust data on pharmacologic treatments for rumination syndrome are lacking, with the exception of a randomized crossover study of baclofen. In this study, baclofen (10 mg three times daily) was significantly more effective than placebo (P = .04) in reducing regurgitation events. Investigators theorized that baclofen counteracts transient lower esophageal sphincter (LES) relaxations by increasing basal LES pressure, thereby potentially reducing regurgitation episodes. The most notable treatment side effects were somnolence, confusion, and dizziness, which may limit its extended use.
 

A Potentially Reversible Habit

Rumination syndrome is considered an acquired habit and, therefore, should be reversible.

Although there is no recent evidence in the literature that rumination syndrome contributes to a reduced survival rate, older data suggested adult mortality rates of 12%-20% (mostly in patients who were institutionalized). Additionally, rumination syndrome has been shown to diminish quality of life.

The best approach to improving the clinical outcomes of patients with rumination syndrome is to enlist a collaborative interprofessional team that includes physicians, behavioral therapists, and nurses to coordinate and optimize existing treatment strategies.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed the following relevant financial relationships: advisor to ISOTHRIVE and Johnson & Johnson.

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

Rumination syndrome is a well-recognized functional disorder characterized by the regurgitation of food or liquid in the absence of retching or nausea.

Evidence suggests that the prevalence of rumination syndrome is increasing. In a 2022 health survey study conducted across 26 countries — the largest epidemiologic study to date on rumination syndrome — investigators reported that it had a global prevalence of 3.1% in adults. This was higher than reported in most prior country-specific studies. More recently, a systematic review and meta-analysis from 2024 reported the pooled prevalence of rumination syndrome as 3.7% in adults and 0.4% in children. Both reports noted that female gender, anxiety, and depression were independent risk factors associated with rumination syndrome.

Recognition of this disorder is crucial in order for clinicians to better diagnose and manage it in their patients.
 

Making the Diagnosis

The diagnosis of rumination syndrome is currently based on the Rome IV consensus criteria, which were last updated in 2016. These include three diagnostic criteria essential to remember as discriminant for rumination syndrome:

• Regurgitation is the effortless return of gastric contents (recognizable food) retrograde back into the esophagus and/or mouth.
• This is not preceded by retching and not associated with nausea.
• These symptoms must have started at least 6 months before evaluation, been evident over the past 3 months, and occurred at least two to three times per month.

Although this diagnosis will be highly suspected after taking an astute clinical history, you will still need to rule out the presence of underlying organic disease.

Nearly one quarter of patients with eating disorders — which commonly accompany gastrointestinal disorders — will not have been diagnosed by the time they visit with a gastroenterologist. Therefore, gastroenterologists should be vigilant in screening for eating disorders. Notably, severe weight loss, malnutrition, electrolyte abnormalities, and dental erosions (due to acid etching) are uncommon in rumination syndrome. If such symptoms are present, it increases the possibility of an underlying eating disorder rather than primary regurgitation.

Previously, there were no published, validated questionnaires to assess the diagnosis or symptomatic response to therapies for rumination syndrome. This has recently changed with the development of a novel eight-point questionnaire that assesses frequency, severity, type of regurgitant, timing of regurgitation in relation to the meal, weight loss, and use of and response to proton pump inhibitors.

This questionnaire was recently implemented in five patients diagnosed with rumination syndrome. Albeit an extremely small trial, it nonetheless showed clinical improvement in scores associated with therapeutic intervention. Further evaluation of this tool is needed.

The diagnosis of rumination syndrome can be confirmed using impedance manometry in persons with evidence of reflux extending to the proximal esophagus, which is associated with an intragastric pressure > 30 mmHg in adults or > 25 mmHg in children. 

Gastric emptying studies are typically not required to make a diagnosis unless the clinical symptoms are atypical and an alternative motility disorder is suspected. Endoscopy is performed to rule out a mechanical disorder.
 

Histopathologic Evidence

New data indicate that there may be specific histologic changes associated with rumination syndrome. A 2023 meta-analysis reported that patients with rumination syndrome had duodenal histologic evidence of increased lymphocytes and eosinophils, which have been associated with epithelial barrier dysfunction, microbial changes, and systemic immune activation in eosinophilic duodenitis.

If these histologic changes are validated, they may suggest future novel diagnostic and treatment approaches, at least for a subset of people with rumination syndrome.
 

Best Available Treatments

The first-line therapeutic treatment for rumination syndrome is diaphragmatic breathing.

I recommended using diaphragmatic breathing for this indication in a previous commentary, in which I noted that it can essentially serve as yoga for the diaphragm and abdominal muscles and advised patients to focus on breathing “through” their belly button.

Patients are instructed to breath in through their nose for 4-6 seconds, hold their breath for 2-3 seconds, and then breath out slowly against pursed lips. They can be supine or upright but should sense their abdominal muscles expand with inhaling, not move their chest wall, and completely relax their abdominal muscles upon exhaling.

Although there is no standard frequency or duration for diaphragmatic breathing, I routinely recommend patients try it after each meal for 10-15 minutes and, if possible, more during the day and in times of stress or anxiety.

Cognitive-behavioral therapies have been shown to be effective alternatives to diaphragmatic breathing.

There is some evidence that hypnosis and biofeedback-guided control of abdominothoracic muscle activity can also be effective options in treating rumination syndrome.

Robust data on pharmacologic treatments for rumination syndrome are lacking, with the exception of a randomized crossover study of baclofen. In this study, baclofen (10 mg three times daily) was significantly more effective than placebo (P = .04) in reducing regurgitation events. Investigators theorized that baclofen counteracts transient lower esophageal sphincter (LES) relaxations by increasing basal LES pressure, thereby potentially reducing regurgitation episodes. The most notable treatment side effects were somnolence, confusion, and dizziness, which may limit its extended use.
 

A Potentially Reversible Habit

Rumination syndrome is considered an acquired habit and, therefore, should be reversible.

Although there is no recent evidence in the literature that rumination syndrome contributes to a reduced survival rate, older data suggested adult mortality rates of 12%-20% (mostly in patients who were institutionalized). Additionally, rumination syndrome has been shown to diminish quality of life.

The best approach to improving the clinical outcomes of patients with rumination syndrome is to enlist a collaborative interprofessional team that includes physicians, behavioral therapists, and nurses to coordinate and optimize existing treatment strategies.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed the following relevant financial relationships: advisor to ISOTHRIVE and Johnson & Johnson.

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

Rumination syndrome is a well-recognized functional disorder characterized by the regurgitation of food or liquid in the absence of retching or nausea.

Evidence suggests that the prevalence of rumination syndrome is increasing. In a 2022 health survey study conducted across 26 countries — the largest epidemiologic study to date on rumination syndrome — investigators reported that it had a global prevalence of 3.1% in adults. This was higher than reported in most prior country-specific studies. More recently, a systematic review and meta-analysis from 2024 reported the pooled prevalence of rumination syndrome as 3.7% in adults and 0.4% in children. Both reports noted that female gender, anxiety, and depression were independent risk factors associated with rumination syndrome.

Recognition of this disorder is crucial in order for clinicians to better diagnose and manage it in their patients.
 

Making the Diagnosis

The diagnosis of rumination syndrome is currently based on the Rome IV consensus criteria, which were last updated in 2016. These include three diagnostic criteria essential to remember as discriminant for rumination syndrome:

• Regurgitation is the effortless return of gastric contents (recognizable food) retrograde back into the esophagus and/or mouth.
• This is not preceded by retching and not associated with nausea.
• These symptoms must have started at least 6 months before evaluation, been evident over the past 3 months, and occurred at least two to three times per month.

Although this diagnosis will be highly suspected after taking an astute clinical history, you will still need to rule out the presence of underlying organic disease.

Nearly one quarter of patients with eating disorders — which commonly accompany gastrointestinal disorders — will not have been diagnosed by the time they visit with a gastroenterologist. Therefore, gastroenterologists should be vigilant in screening for eating disorders. Notably, severe weight loss, malnutrition, electrolyte abnormalities, and dental erosions (due to acid etching) are uncommon in rumination syndrome. If such symptoms are present, it increases the possibility of an underlying eating disorder rather than primary regurgitation.

Previously, there were no published, validated questionnaires to assess the diagnosis or symptomatic response to therapies for rumination syndrome. This has recently changed with the development of a novel eight-point questionnaire that assesses frequency, severity, type of regurgitant, timing of regurgitation in relation to the meal, weight loss, and use of and response to proton pump inhibitors.

This questionnaire was recently implemented in five patients diagnosed with rumination syndrome. Albeit an extremely small trial, it nonetheless showed clinical improvement in scores associated with therapeutic intervention. Further evaluation of this tool is needed.

The diagnosis of rumination syndrome can be confirmed using impedance manometry in persons with evidence of reflux extending to the proximal esophagus, which is associated with an intragastric pressure > 30 mmHg in adults or > 25 mmHg in children. 

Gastric emptying studies are typically not required to make a diagnosis unless the clinical symptoms are atypical and an alternative motility disorder is suspected. Endoscopy is performed to rule out a mechanical disorder.
 

Histopathologic Evidence

New data indicate that there may be specific histologic changes associated with rumination syndrome. A 2023 meta-analysis reported that patients with rumination syndrome had duodenal histologic evidence of increased lymphocytes and eosinophils, which have been associated with epithelial barrier dysfunction, microbial changes, and systemic immune activation in eosinophilic duodenitis.

If these histologic changes are validated, they may suggest future novel diagnostic and treatment approaches, at least for a subset of people with rumination syndrome.
 

Best Available Treatments

The first-line therapeutic treatment for rumination syndrome is diaphragmatic breathing.

I recommended using diaphragmatic breathing for this indication in a previous commentary, in which I noted that it can essentially serve as yoga for the diaphragm and abdominal muscles and advised patients to focus on breathing “through” their belly button.

Patients are instructed to breath in through their nose for 4-6 seconds, hold their breath for 2-3 seconds, and then breath out slowly against pursed lips. They can be supine or upright but should sense their abdominal muscles expand with inhaling, not move their chest wall, and completely relax their abdominal muscles upon exhaling.

Although there is no standard frequency or duration for diaphragmatic breathing, I routinely recommend patients try it after each meal for 10-15 minutes and, if possible, more during the day and in times of stress or anxiety.

Cognitive-behavioral therapies have been shown to be effective alternatives to diaphragmatic breathing.

There is some evidence that hypnosis and biofeedback-guided control of abdominothoracic muscle activity can also be effective options in treating rumination syndrome.

Robust data on pharmacologic treatments for rumination syndrome are lacking, with the exception of a randomized crossover study of baclofen. In this study, baclofen (10 mg three times daily) was significantly more effective than placebo (P = .04) in reducing regurgitation events. Investigators theorized that baclofen counteracts transient lower esophageal sphincter (LES) relaxations by increasing basal LES pressure, thereby potentially reducing regurgitation episodes. The most notable treatment side effects were somnolence, confusion, and dizziness, which may limit its extended use.
 

A Potentially Reversible Habit

Rumination syndrome is considered an acquired habit and, therefore, should be reversible.

Although there is no recent evidence in the literature that rumination syndrome contributes to a reduced survival rate, older data suggested adult mortality rates of 12%-20% (mostly in patients who were institutionalized). Additionally, rumination syndrome has been shown to diminish quality of life.

The best approach to improving the clinical outcomes of patients with rumination syndrome is to enlist a collaborative interprofessional team that includes physicians, behavioral therapists, and nurses to coordinate and optimize existing treatment strategies.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed the following relevant financial relationships: advisor to ISOTHRIVE and Johnson & Johnson.

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

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The American Cancer Society has just published its cancer statistics for 2024. This is an annual report, the latest version of which has some alarming news for gastroenterologists. Usually, we think of being “number one” as a positive thing, but that’s not the case this year when it comes to the projections for colorectal cancer.

But first, let’s discuss the report’s overall findings. Broadly speaking, the news is quite good in that there’s been an aversion of over 4 million deaths since 1991. That decline over the past four decades is due to reductions in smoking, earlier detection, and improved screening and treatments for localized or metastatic disease. But these gains are now threatened by some offsets that we’re seeing, with increasing rates of six of the top 10 cancers in the past several years.
 

Increasing Rates of Gastrointestinal Cancers

The incidence rate of pancreas cancer has increased from 0.6% to 1% annually.

Pancreas cancer has a 5-year relative survival rate of 13%, which ranks as one of the three worst rates for cancers. This cancer represents a real screening challenge for us, as it typically presents asymptomatically.

Women have experienced a 2%-3% annual increase in incidence rates for liver cancer.

I suspect that this is due to cases of fibrotic liver disease resulting from viral hepatitis and metabolic liver diseases with nonalcoholic fatty liver and advanced fibrosis (F3 and F4). These cases may be carried over from before, thereby contributing to the increasing incremental cancer risk.

We can’t overlook the need for risk reduction here and should focus on applying regular screening efforts in our female patients. However, it’s also true that we require better liver cancer screening tests to accomplish that goal.
 

In Those Under 50, CRC the Leading Cause of Cancer Death in Men, Second in Women

I really want to focus on the news around colorectal cancer.

To put this in perspective, in the late 1990s, colorectal cancer was the fourth leading cause of death in men and women. The current report extrapolated 2024 projections using the Surveillance, Epidemiology, and End Results (SEER) database ending in 2020, which was necessary given the incremental time it takes to develop cancers. The SEER database suggests that in 2024, colorectal cancer in those younger than 50 years of age will become the number-one leading cause of cancer death in men and number-two in women. The increasing incidence of colorectal cancer in younger people is probably the result of a number of epidemiologic and other reasons.

The current report offers evidence of racial disparities in cancer mortality rates in general, which are twofold higher in Black people compared with White people, particularly for gastric cancer. There is also an evident disparity in Native Americans, who have higher rates of gastric and liver cancer. This is a reminder of the increasing need for equity to address racial disparities across these populations.

But returning to colon cancer, it’s a marked change to go from being the fourth-leading cause of cancer death in those younger than 50 years of age to being number one for men and number two for women.

Being “number one” is supposed to make you famous. This “number one,” however, should in fact be infamous. It’s a travesty, because colorectal cancer is a potentially preventable disease.

As we move into March, which happens to be Colorectal Cancer Awareness Month, hopefully this fires up some of the conversations you have with your younger at-risk population, who may be reticent or resistant to colorectal cancer screening.

We have to do better at getting this message out to that population at large. “Number one” is not where we want to be for this potentially preventable problem.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When it comes to the use of colonoscopy to reduce the risk for cancer, quality is key.

There are a number of performance improvements we can make in our practices so that we can do better. This is evident in several recently published studies and a recent review article on the topic, which I’d like to profile for you; many of these key quality indicators you can implement now.

Even though it may take more time before they’re supported in the guidelines, you’ll see that the evidence behind these is extraordinarily strong.
 

Increasing the Adenoma Detection Rate

Certainly, we all do what we can to increase the adenoma detection rate (ADR).

However, at the moment, the nationally recommended benchmark is to achieve an ADR of 25%, which is inordinately low. The ADR rate reported in the GIQuIC registry data is closer to 39%, and in high-level detectors, it’s actually in the greater-than-50% range.

There’s no question that we can do more, and there are a number of ways to do that.

First, we can consider using mucosal exposure techniques in our colonoscopies. These techniques incorporate the use of a hood, cap, or device that faces the mucosal folds on withdrawal from the cecum. This may actually decrease your withdrawal time because you don’t spend so much time trying to face these folds.

In considering tools to aid ADR, don’t forget electronic chromoendoscopy (eg, narrow-band imaging).

There are a number of new artificial intelligence options out there as well, which have been reported to increase the ADR by approximately 10%. Of importance, this improvement even occurs among expert endoscopists.

There’s also important emerging data about ADR in fecal immunochemical test (FIT)–positive patients. FIT-positive status increases the ADR threshold by 15%-20%. This places you in an ADR range of approximately 50%, which is really the norm when screening patients that present for colonoscopy because of FIT positivity.
 

Adenoma Per Colonoscopy: A Possible ADR Substitute

Growing evidence supports the use of adenoma per colonoscopy (APC) as a substitute to ADR. This would allow you to record every adenoma and attribute it to that index colonoscopy.

A high-quality paper showed that the APC value should be around 0.6 to achieve the current ADR minimum threshold of 25%. Having the APC < 0.6 seems to be associated with an increased risk for residual polyp. Sessile serrated lesions also increased the hazard ratio for interval colorectal cancer. This was evaluated recently with data from the New Hampshire Colonoscopy Registry, which Dr Joseph Anderson has led for so long. They showed that 21% of endoscopists had an ADR of 25% or greater but still had APCs < 0.6.

Therefore, when it comes to remedial corrective work, doctors need to be reevaluated, retrained, and educated in the ways that they can incorporate this. The APC in high-level detectors is > 1.0.

APC may be something you want to consider using internally. It does require that you place each polyp into an individual jar, which can increase incremental cost. Nonetheless, there is clear evidence that APC positively changes outcomes.
 

Including Sessile Serrated Lesions in ADR Detectors

Unfortunately, some of the high-level ADR detectors aren’t so “high level” when it comes to detecting sessile serrated lesions. It’s not quite as concordant as we had previously thought.

Nonetheless, there are many adjunctive things you can do with sessile serrated lesions, including narrow-band imaging and chromoendoscopy.

When it comes to establishing a discriminant, the numbers should be 5%-6% if we’re going to set a quality ratio and an index. However, this is somewhat dependent on your pathologist because they have to read these correctly. Lesions that are ≥ 6 mm above the sigmoid colon and anything in the right colon should be evaluated really closely as a sessile serrated lesion.

I’ve had indications where the pathologist says the lesion is hyperplastic, to which I say, “I’m going to follow as a sessile serrated lesion.” This is because it’s apparent to me in the endoscopic appearance and the narrow-band imaging appearance that it was characteristic of sessile serrated lesions.
 

Best Practices in Bowel Preparations

The US Multi-Society Task Force recommends that adequate bowel preparation should occur in 85% or more of outpatients, and for the European Society for Gastrointestinal Endoscopy, it’s 90% or more.

I’ll pass along a tip I use in my patients undergoing bowel preparation: I make them aware that during this process, they want to see a clear, yellow, urine-like color to their stool. Otherwise, many patients will think if they’ve had some diarrhea, they don’t need to finish prep. Setting that expectation for them upfront is really important.

The nurses also should be aware of this because if there’s a murky brown effluent upon presentation for the colonoscopy, there’s a greater than 50% chance that they’re going to have had an inadequate preparation. In such cases, you would want to preempt the colonoscopy and perhaps send them out for a re-prep that day or bring them back for a rescheduled appointment.
 

Resection Considerations

There is substantial variation when it comes to lesion resection, which makes it an important quality indicator on which to focus: High-level detectors aren’t always high-level resectors.

There are two validated instruments that you can use to gauge the adequacy of resection. Those aren’t really ready for prime time in every practice, though they may be seen in fellowship programs.

The idea here is that you want to get a ≥ 2 mm margin for cold snare polypectomy in lesions 1-10 mm in size. This has been a challenge, as findings indicate we don’t do this that well.

Joseph Anderson and colleagues recently published a study using a 2-mm resection margin. They reported that this was only possible in approximately 28% of polyps. For a 1-mm margin, the rate was 84%.

We simply need to set clearer margins when setting our snare. Make sure you’re close enough to the polyp, push down on the snare, and get a good margin of tissue.

When the sample contracts are placed into the formalin, it’s not quite so simple to define the margin at the time of the surgical resection. This often requires an audit evaluation by the pathologist.

There are two other considerations regarding resection.

The first is about the referral for surgery. Referral should not occur for any benign lesions ascribed by your endoscopic advanced imaging techniques and classifications that are not thought to have intramucosal carcinoma. These should be referred to an expert endoscopic evaluation. If you can’t do it, then somebody else should. And you shouldn’t attempt it unless you can get it totally because resection of partially resected lesions is much more complicated. The European Society of Gastrointestinal Endoscopy says this applies to any benign lesion of any size, which I think really is the emerging standard of care. You should consider and offer that to the patient. It may require a referral for outside of your institution.

The second additional consideration is around the minimization of cold forceps for removal of polyps. The US Multi-Society Task Force says cold forceps shouldn’t be used for any lesions > 2 mm, whereas for the European Society of Gastrointestinal Endoscopy, it is > 3 mm. However, it’s still done very commonly in clinical practice. Nibbling the polyp is not an option. Cold snare is actually quicker, more effective, has better outcomes, and is something that you can bill for when you look at the coding.

In summary, there are a lot of things that we can do now to improve colonoscopy. Quality indicators continue to emerge with a compelling, excellent evidence base that strongly supports their use. Given that, I think most of these are actionable now, and it’s not necessary to wait for the guidelines to begin using them. I’d therefore challenge all of us to incorporate them in our continual efforts to do better.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When it comes to the use of colonoscopy to reduce the risk for cancer, quality is key.

There are a number of performance improvements we can make in our practices so that we can do better. This is evident in several recently published studies and a recent review article on the topic, which I’d like to profile for you; many of these key quality indicators you can implement now.

Even though it may take more time before they’re supported in the guidelines, you’ll see that the evidence behind these is extraordinarily strong.
 

Increasing the Adenoma Detection Rate

Certainly, we all do what we can to increase the adenoma detection rate (ADR).

However, at the moment, the nationally recommended benchmark is to achieve an ADR of 25%, which is inordinately low. The ADR rate reported in the GIQuIC registry data is closer to 39%, and in high-level detectors, it’s actually in the greater-than-50% range.

There’s no question that we can do more, and there are a number of ways to do that.

First, we can consider using mucosal exposure techniques in our colonoscopies. These techniques incorporate the use of a hood, cap, or device that faces the mucosal folds on withdrawal from the cecum. This may actually decrease your withdrawal time because you don’t spend so much time trying to face these folds.

In considering tools to aid ADR, don’t forget electronic chromoendoscopy (eg, narrow-band imaging).

There are a number of new artificial intelligence options out there as well, which have been reported to increase the ADR by approximately 10%. Of importance, this improvement even occurs among expert endoscopists.

There’s also important emerging data about ADR in fecal immunochemical test (FIT)–positive patients. FIT-positive status increases the ADR threshold by 15%-20%. This places you in an ADR range of approximately 50%, which is really the norm when screening patients that present for colonoscopy because of FIT positivity.
 

Adenoma Per Colonoscopy: A Possible ADR Substitute

Growing evidence supports the use of adenoma per colonoscopy (APC) as a substitute to ADR. This would allow you to record every adenoma and attribute it to that index colonoscopy.

A high-quality paper showed that the APC value should be around 0.6 to achieve the current ADR minimum threshold of 25%. Having the APC < 0.6 seems to be associated with an increased risk for residual polyp. Sessile serrated lesions also increased the hazard ratio for interval colorectal cancer. This was evaluated recently with data from the New Hampshire Colonoscopy Registry, which Dr Joseph Anderson has led for so long. They showed that 21% of endoscopists had an ADR of 25% or greater but still had APCs < 0.6.

Therefore, when it comes to remedial corrective work, doctors need to be reevaluated, retrained, and educated in the ways that they can incorporate this. The APC in high-level detectors is > 1.0.

APC may be something you want to consider using internally. It does require that you place each polyp into an individual jar, which can increase incremental cost. Nonetheless, there is clear evidence that APC positively changes outcomes.
 

Including Sessile Serrated Lesions in ADR Detectors

Unfortunately, some of the high-level ADR detectors aren’t so “high level” when it comes to detecting sessile serrated lesions. It’s not quite as concordant as we had previously thought.

Nonetheless, there are many adjunctive things you can do with sessile serrated lesions, including narrow-band imaging and chromoendoscopy.

When it comes to establishing a discriminant, the numbers should be 5%-6% if we’re going to set a quality ratio and an index. However, this is somewhat dependent on your pathologist because they have to read these correctly. Lesions that are ≥ 6 mm above the sigmoid colon and anything in the right colon should be evaluated really closely as a sessile serrated lesion.

I’ve had indications where the pathologist says the lesion is hyperplastic, to which I say, “I’m going to follow as a sessile serrated lesion.” This is because it’s apparent to me in the endoscopic appearance and the narrow-band imaging appearance that it was characteristic of sessile serrated lesions.
 

Best Practices in Bowel Preparations

The US Multi-Society Task Force recommends that adequate bowel preparation should occur in 85% or more of outpatients, and for the European Society for Gastrointestinal Endoscopy, it’s 90% or more.

I’ll pass along a tip I use in my patients undergoing bowel preparation: I make them aware that during this process, they want to see a clear, yellow, urine-like color to their stool. Otherwise, many patients will think if they’ve had some diarrhea, they don’t need to finish prep. Setting that expectation for them upfront is really important.

The nurses also should be aware of this because if there’s a murky brown effluent upon presentation for the colonoscopy, there’s a greater than 50% chance that they’re going to have had an inadequate preparation. In such cases, you would want to preempt the colonoscopy and perhaps send them out for a re-prep that day or bring them back for a rescheduled appointment.
 

Resection Considerations

There is substantial variation when it comes to lesion resection, which makes it an important quality indicator on which to focus: High-level detectors aren’t always high-level resectors.

There are two validated instruments that you can use to gauge the adequacy of resection. Those aren’t really ready for prime time in every practice, though they may be seen in fellowship programs.

The idea here is that you want to get a ≥ 2 mm margin for cold snare polypectomy in lesions 1-10 mm in size. This has been a challenge, as findings indicate we don’t do this that well.

Joseph Anderson and colleagues recently published a study using a 2-mm resection margin. They reported that this was only possible in approximately 28% of polyps. For a 1-mm margin, the rate was 84%.

We simply need to set clearer margins when setting our snare. Make sure you’re close enough to the polyp, push down on the snare, and get a good margin of tissue.

When the sample contracts are placed into the formalin, it’s not quite so simple to define the margin at the time of the surgical resection. This often requires an audit evaluation by the pathologist.

There are two other considerations regarding resection.

The first is about the referral for surgery. Referral should not occur for any benign lesions ascribed by your endoscopic advanced imaging techniques and classifications that are not thought to have intramucosal carcinoma. These should be referred to an expert endoscopic evaluation. If you can’t do it, then somebody else should. And you shouldn’t attempt it unless you can get it totally because resection of partially resected lesions is much more complicated. The European Society of Gastrointestinal Endoscopy says this applies to any benign lesion of any size, which I think really is the emerging standard of care. You should consider and offer that to the patient. It may require a referral for outside of your institution.

The second additional consideration is around the minimization of cold forceps for removal of polyps. The US Multi-Society Task Force says cold forceps shouldn’t be used for any lesions > 2 mm, whereas for the European Society of Gastrointestinal Endoscopy, it is > 3 mm. However, it’s still done very commonly in clinical practice. Nibbling the polyp is not an option. Cold snare is actually quicker, more effective, has better outcomes, and is something that you can bill for when you look at the coding.

In summary, there are a lot of things that we can do now to improve colonoscopy. Quality indicators continue to emerge with a compelling, excellent evidence base that strongly supports their use. Given that, I think most of these are actionable now, and it’s not necessary to wait for the guidelines to begin using them. I’d therefore challenge all of us to incorporate them in our continual efforts to do better.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When it comes to the use of colonoscopy to reduce the risk for cancer, quality is key.

There are a number of performance improvements we can make in our practices so that we can do better. This is evident in several recently published studies and a recent review article on the topic, which I’d like to profile for you; many of these key quality indicators you can implement now.

Even though it may take more time before they’re supported in the guidelines, you’ll see that the evidence behind these is extraordinarily strong.
 

Increasing the Adenoma Detection Rate

Certainly, we all do what we can to increase the adenoma detection rate (ADR).

However, at the moment, the nationally recommended benchmark is to achieve an ADR of 25%, which is inordinately low. The ADR rate reported in the GIQuIC registry data is closer to 39%, and in high-level detectors, it’s actually in the greater-than-50% range.

There’s no question that we can do more, and there are a number of ways to do that.

First, we can consider using mucosal exposure techniques in our colonoscopies. These techniques incorporate the use of a hood, cap, or device that faces the mucosal folds on withdrawal from the cecum. This may actually decrease your withdrawal time because you don’t spend so much time trying to face these folds.

In considering tools to aid ADR, don’t forget electronic chromoendoscopy (eg, narrow-band imaging).

There are a number of new artificial intelligence options out there as well, which have been reported to increase the ADR by approximately 10%. Of importance, this improvement even occurs among expert endoscopists.

There’s also important emerging data about ADR in fecal immunochemical test (FIT)–positive patients. FIT-positive status increases the ADR threshold by 15%-20%. This places you in an ADR range of approximately 50%, which is really the norm when screening patients that present for colonoscopy because of FIT positivity.
 

Adenoma Per Colonoscopy: A Possible ADR Substitute

Growing evidence supports the use of adenoma per colonoscopy (APC) as a substitute to ADR. This would allow you to record every adenoma and attribute it to that index colonoscopy.

A high-quality paper showed that the APC value should be around 0.6 to achieve the current ADR minimum threshold of 25%. Having the APC < 0.6 seems to be associated with an increased risk for residual polyp. Sessile serrated lesions also increased the hazard ratio for interval colorectal cancer. This was evaluated recently with data from the New Hampshire Colonoscopy Registry, which Dr Joseph Anderson has led for so long. They showed that 21% of endoscopists had an ADR of 25% or greater but still had APCs < 0.6.

Therefore, when it comes to remedial corrective work, doctors need to be reevaluated, retrained, and educated in the ways that they can incorporate this. The APC in high-level detectors is > 1.0.

APC may be something you want to consider using internally. It does require that you place each polyp into an individual jar, which can increase incremental cost. Nonetheless, there is clear evidence that APC positively changes outcomes.
 

Including Sessile Serrated Lesions in ADR Detectors

Unfortunately, some of the high-level ADR detectors aren’t so “high level” when it comes to detecting sessile serrated lesions. It’s not quite as concordant as we had previously thought.

Nonetheless, there are many adjunctive things you can do with sessile serrated lesions, including narrow-band imaging and chromoendoscopy.

When it comes to establishing a discriminant, the numbers should be 5%-6% if we’re going to set a quality ratio and an index. However, this is somewhat dependent on your pathologist because they have to read these correctly. Lesions that are ≥ 6 mm above the sigmoid colon and anything in the right colon should be evaluated really closely as a sessile serrated lesion.

I’ve had indications where the pathologist says the lesion is hyperplastic, to which I say, “I’m going to follow as a sessile serrated lesion.” This is because it’s apparent to me in the endoscopic appearance and the narrow-band imaging appearance that it was characteristic of sessile serrated lesions.
 

Best Practices in Bowel Preparations

The US Multi-Society Task Force recommends that adequate bowel preparation should occur in 85% or more of outpatients, and for the European Society for Gastrointestinal Endoscopy, it’s 90% or more.

I’ll pass along a tip I use in my patients undergoing bowel preparation: I make them aware that during this process, they want to see a clear, yellow, urine-like color to their stool. Otherwise, many patients will think if they’ve had some diarrhea, they don’t need to finish prep. Setting that expectation for them upfront is really important.

The nurses also should be aware of this because if there’s a murky brown effluent upon presentation for the colonoscopy, there’s a greater than 50% chance that they’re going to have had an inadequate preparation. In such cases, you would want to preempt the colonoscopy and perhaps send them out for a re-prep that day or bring them back for a rescheduled appointment.
 

Resection Considerations

There is substantial variation when it comes to lesion resection, which makes it an important quality indicator on which to focus: High-level detectors aren’t always high-level resectors.

There are two validated instruments that you can use to gauge the adequacy of resection. Those aren’t really ready for prime time in every practice, though they may be seen in fellowship programs.

The idea here is that you want to get a ≥ 2 mm margin for cold snare polypectomy in lesions 1-10 mm in size. This has been a challenge, as findings indicate we don’t do this that well.

Joseph Anderson and colleagues recently published a study using a 2-mm resection margin. They reported that this was only possible in approximately 28% of polyps. For a 1-mm margin, the rate was 84%.

We simply need to set clearer margins when setting our snare. Make sure you’re close enough to the polyp, push down on the snare, and get a good margin of tissue.

When the sample contracts are placed into the formalin, it’s not quite so simple to define the margin at the time of the surgical resection. This often requires an audit evaluation by the pathologist.

There are two other considerations regarding resection.

The first is about the referral for surgery. Referral should not occur for any benign lesions ascribed by your endoscopic advanced imaging techniques and classifications that are not thought to have intramucosal carcinoma. These should be referred to an expert endoscopic evaluation. If you can’t do it, then somebody else should. And you shouldn’t attempt it unless you can get it totally because resection of partially resected lesions is much more complicated. The European Society of Gastrointestinal Endoscopy says this applies to any benign lesion of any size, which I think really is the emerging standard of care. You should consider and offer that to the patient. It may require a referral for outside of your institution.

The second additional consideration is around the minimization of cold forceps for removal of polyps. The US Multi-Society Task Force says cold forceps shouldn’t be used for any lesions > 2 mm, whereas for the European Society of Gastrointestinal Endoscopy, it is > 3 mm. However, it’s still done very commonly in clinical practice. Nibbling the polyp is not an option. Cold snare is actually quicker, more effective, has better outcomes, and is something that you can bill for when you look at the coding.

In summary, there are a lot of things that we can do now to improve colonoscopy. Quality indicators continue to emerge with a compelling, excellent evidence base that strongly supports their use. Given that, I think most of these are actionable now, and it’s not necessary to wait for the guidelines to begin using them. I’d therefore challenge all of us to incorporate them in our continual efforts to do better.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome back to another GI Common Concerns.

Today, I want to highlight some information about menopause.

Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.

Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
 

Impact on GI motility

One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.

One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.

When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.

Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.

When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.

This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.

Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.

Choosing such a multidisciplinary approach can be quite helpful.
 

The metabolic consequences of altering hormonal balance

Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.

Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.

This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.

Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.

Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.

Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
 

Sleep disturbances: fragmentation, duration, and quality

Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.

Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.

Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.

In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.

As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”

These questions can provide good insights into the sleep efficiency of the previous night.
 

The effect of the microbiome on osteoporosis

One final topic I found very interesting pertains to the effects of menopause on osteoporosis.

We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.

However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.

This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.

Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.

Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.

Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?

We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.

I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.

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

This transcript has been edited for clarity.

Welcome back to another GI Common Concerns.

Today, I want to highlight some information about menopause.

Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.

Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
 

Impact on GI motility

One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.

One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.

When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.

Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.

When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.

This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.

Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.

Choosing such a multidisciplinary approach can be quite helpful.
 

The metabolic consequences of altering hormonal balance

Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.

Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.

This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.

Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.

Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.

Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
 

Sleep disturbances: fragmentation, duration, and quality

Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.

Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.

Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.

In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.

As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”

These questions can provide good insights into the sleep efficiency of the previous night.
 

The effect of the microbiome on osteoporosis

One final topic I found very interesting pertains to the effects of menopause on osteoporosis.

We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.

However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.

This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.

Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.

Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.

Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?

We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.

I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.

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

This transcript has been edited for clarity.

Welcome back to another GI Common Concerns.

Today, I want to highlight some information about menopause.

Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.

Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
 

Impact on GI motility

One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.

One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.

When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.

Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.

When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.

This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.

Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.

Choosing such a multidisciplinary approach can be quite helpful.
 

The metabolic consequences of altering hormonal balance

Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.

Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.

This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.

Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.

Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.

Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
 

Sleep disturbances: fragmentation, duration, and quality

Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.

Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.

Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.

In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.

As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”

These questions can provide good insights into the sleep efficiency of the previous night.
 

The effect of the microbiome on osteoporosis

One final topic I found very interesting pertains to the effects of menopause on osteoporosis.

We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.

However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.

This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.

Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.

Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.

Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?

We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.

I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
 

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.

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

This transcript has been edited for clarity.

The ongoing longitudinal Nurses’ Health Study has served as an incredible database for evaluating disease states prospectively over decades, thanks to the robust input of its participants. Most recently, this allowed for an important analysis of the association between gastroesophageal reflux (GER) symptoms and sleep quality, the results of which were published in JAMA Network Open.

Approximately 49,000 women with a median age of 59 years (range, 48-69 years) provided data for this analysis. Starting in 2005, they were asked about their experience of GER symptoms. In 2017, they were also asked to respond to a questionnaire, a modified Pittsburgh Sleep Quality Index (PSQI). This is a tool we’ve used a lot in prospective studies looking at gastrointestinal diseases and sleep-related abnormalities. It’s unique in that it looks not only at sleep but also at next-day function and daytime sleepiness, which is important here for its implications related to reflux disease and sleep fragmentation.

In assessing these outcomes, the investigators found that the relative risk for association with sleep fragmentation was approximately 15% greater in those with GER symptoms occurring one to three times a month. For those with GER symptoms occurring once a week and more than once a week, the approximate relative risk increased by 30% and 53%, respectively. Clearly, the association of GER symptoms and relative sleep quality was really important.

It should be noted that the PSQI is a disease-independent, validated instrument. It’s not specific to GER disease or any diseases. It’s cross validated across 17 different languages. I think what’s most important about its use in the assessment here is the incorporation of next-day function and asking participants about daytime sleepiness, which we’ll discuss in more detail shortly.
 

The many causes of interrupted sleep

We’ve all experienced sleep fragmentation, whether in the form of having been on call during our medical training or common experiences like hearing a child cry in the night, a noisy truck pass by, or a dog barking. You may or may not remember that these happened the next day, but they’ve nonetheless interrupted your sleep efficiency.

When you transition laterally across the stages of sleep, that’s what establishes the circadian rhythm and ensures sleep hygiene. Typically, we require approximately 7 hours of restful sleep to do that. But if you fragment or interrupt this process, you more or less move your way erratically through the night, disrupting sleep hygiene and efficiency.

If you have a cognitive awakening during those disruptions, you may recall those events the next day. Or, you may not remember it at all, and such amnestic events are normal for some people with sleep disruptions.

You may also have a sensory arousal, whether it’s due to GER symptoms, auditory stimuli, bumping your toe, or whatever disruptive event. Any of these can cause you to lose that laterality of smooth transition through sleep.

Approximately 20% of the U.S. population have reported GER symptoms at least once a week. Incident data indicate that number may be increasing by as much as 5% a year. Much of that increase is tied to obesity. But nonetheless, it’s a problem on the rise.

It’s important to know this as we start to look at sleep. If GER is acting as a trigger to sleep disruption, you need to ask your patients with this condition about next-day function.

In particular, the next-day function questions to ask are, “How do you feel when you get up? Are you awake and refreshed? Do you have early fatigue? Do you drag yourself out of bed, have daytime somnolence, loss of concentration, or irritability?”

Those are key parameters we can use for looking back to the night before and gauging sleep efficiency. If you’re not asking those questions, you may miss out on identifying a patient having sleep fragmentation.
 

Sleep’s role in inflammatory disease processes

I now perform an interval assessment of this type not just in my patients with GER disease but across all my patients. I do so because sleep is physiologically important in so many ways.

In patients who have nonalcoholic fatty liver disease and a variety of other liver diseases, we’re finding an increased association with sleep fragmentation outside of sleep apnea.

The same is true with irritable bowel and other functional diseases.

When you have sleep fragmentation in inflammatory bowel disease, you turn on a variety of inflammatory proteins (e.g., C-reactive protein) and cytokines, such as interleukins and tumor necrosis factor alpha. These processes may actually tip somebody over to a pro-inflammatory state.

When it comes to what might be considered a relatively simpler condition like GER disease, Ronnie Fass and colleagues showed a number of years ago via Bernstein testing performed in patients with both fragmented and normal sleep that the sensory thresholds all get lowered in the former group. This is irrespective of whether you have a functional symptom or you’re awakened by bumping your toe, a headache, or having heartburn; your sensory thresholds are lower. As a result, the same stimulus provides a higher sense of awareness. By ramping up that awareness, you increase the interference with the next-day function.

We’ve shown that sleep fragmentation affects a variety of things, including immune function. This may be why many people get sick when they travel in between time zones.

There are also implications relating to things like obesity. When you have sleep dysfunction, you have effects on leptin and ghrelin, contrary to what you would normally want to have. This, in turn, causes adverse effects on stimulation or suppression of satiety or appetite. These are things that I counsel my patients about when I talk about reflux as well as those trying to lose weight.

Sleep disruption affects cortisol stimulation and has a significant correlation with type 2 diabetes, cardiovascular diseases, and even mortality statistics. 
 

Advice for counseling patients

This latest analysis from the Nurses’ Health Study reminds us that a lot of people have reflux and a lot of people have sleep fragmentation. We need to do better in asking our patients if they have symptoms specific not only to reflux but also to potentially sleep-related complications.

The more we do that, the more we individualize patient treatment rather than treating them as a disease state. This, in turn, will allow us to practice personalized medicine. The more we can engage our patients with reflux disease by asking the right questions about next-day function, the better we can do in improving their outcomes.

It’s time for us all to open our eyes to the value of closing them. Let’s talk to our patients with reflux disease in a little bit of a different light, providing a new perspective on strategies we can use to mitigate and deal with those symptoms, thereby preventing the consequences of sleep fragmentation.

Hopefully, this overview gives you some guidance the next time you have a conversation with your patients. It will apply across many, many disease states, and in almost everything we do in gastroenterology.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, Va., and a past president of the American College of Gastroenterology. He reported advising with ISOTHRIVE and Johnson & Johnson.

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

This transcript has been edited for clarity.

The ongoing longitudinal Nurses’ Health Study has served as an incredible database for evaluating disease states prospectively over decades, thanks to the robust input of its participants. Most recently, this allowed for an important analysis of the association between gastroesophageal reflux (GER) symptoms and sleep quality, the results of which were published in JAMA Network Open.

Approximately 49,000 women with a median age of 59 years (range, 48-69 years) provided data for this analysis. Starting in 2005, they were asked about their experience of GER symptoms. In 2017, they were also asked to respond to a questionnaire, a modified Pittsburgh Sleep Quality Index (PSQI). This is a tool we’ve used a lot in prospective studies looking at gastrointestinal diseases and sleep-related abnormalities. It’s unique in that it looks not only at sleep but also at next-day function and daytime sleepiness, which is important here for its implications related to reflux disease and sleep fragmentation.

In assessing these outcomes, the investigators found that the relative risk for association with sleep fragmentation was approximately 15% greater in those with GER symptoms occurring one to three times a month. For those with GER symptoms occurring once a week and more than once a week, the approximate relative risk increased by 30% and 53%, respectively. Clearly, the association of GER symptoms and relative sleep quality was really important.

It should be noted that the PSQI is a disease-independent, validated instrument. It’s not specific to GER disease or any diseases. It’s cross validated across 17 different languages. I think what’s most important about its use in the assessment here is the incorporation of next-day function and asking participants about daytime sleepiness, which we’ll discuss in more detail shortly.
 

The many causes of interrupted sleep

We’ve all experienced sleep fragmentation, whether in the form of having been on call during our medical training or common experiences like hearing a child cry in the night, a noisy truck pass by, or a dog barking. You may or may not remember that these happened the next day, but they’ve nonetheless interrupted your sleep efficiency.

When you transition laterally across the stages of sleep, that’s what establishes the circadian rhythm and ensures sleep hygiene. Typically, we require approximately 7 hours of restful sleep to do that. But if you fragment or interrupt this process, you more or less move your way erratically through the night, disrupting sleep hygiene and efficiency.

If you have a cognitive awakening during those disruptions, you may recall those events the next day. Or, you may not remember it at all, and such amnestic events are normal for some people with sleep disruptions.

You may also have a sensory arousal, whether it’s due to GER symptoms, auditory stimuli, bumping your toe, or whatever disruptive event. Any of these can cause you to lose that laterality of smooth transition through sleep.

Approximately 20% of the U.S. population have reported GER symptoms at least once a week. Incident data indicate that number may be increasing by as much as 5% a year. Much of that increase is tied to obesity. But nonetheless, it’s a problem on the rise.

It’s important to know this as we start to look at sleep. If GER is acting as a trigger to sleep disruption, you need to ask your patients with this condition about next-day function.

In particular, the next-day function questions to ask are, “How do you feel when you get up? Are you awake and refreshed? Do you have early fatigue? Do you drag yourself out of bed, have daytime somnolence, loss of concentration, or irritability?”

Those are key parameters we can use for looking back to the night before and gauging sleep efficiency. If you’re not asking those questions, you may miss out on identifying a patient having sleep fragmentation.
 

Sleep’s role in inflammatory disease processes

I now perform an interval assessment of this type not just in my patients with GER disease but across all my patients. I do so because sleep is physiologically important in so many ways.

In patients who have nonalcoholic fatty liver disease and a variety of other liver diseases, we’re finding an increased association with sleep fragmentation outside of sleep apnea.

The same is true with irritable bowel and other functional diseases.

When you have sleep fragmentation in inflammatory bowel disease, you turn on a variety of inflammatory proteins (e.g., C-reactive protein) and cytokines, such as interleukins and tumor necrosis factor alpha. These processes may actually tip somebody over to a pro-inflammatory state.

When it comes to what might be considered a relatively simpler condition like GER disease, Ronnie Fass and colleagues showed a number of years ago via Bernstein testing performed in patients with both fragmented and normal sleep that the sensory thresholds all get lowered in the former group. This is irrespective of whether you have a functional symptom or you’re awakened by bumping your toe, a headache, or having heartburn; your sensory thresholds are lower. As a result, the same stimulus provides a higher sense of awareness. By ramping up that awareness, you increase the interference with the next-day function.

We’ve shown that sleep fragmentation affects a variety of things, including immune function. This may be why many people get sick when they travel in between time zones.

There are also implications relating to things like obesity. When you have sleep dysfunction, you have effects on leptin and ghrelin, contrary to what you would normally want to have. This, in turn, causes adverse effects on stimulation or suppression of satiety or appetite. These are things that I counsel my patients about when I talk about reflux as well as those trying to lose weight.

Sleep disruption affects cortisol stimulation and has a significant correlation with type 2 diabetes, cardiovascular diseases, and even mortality statistics. 
 

Advice for counseling patients

This latest analysis from the Nurses’ Health Study reminds us that a lot of people have reflux and a lot of people have sleep fragmentation. We need to do better in asking our patients if they have symptoms specific not only to reflux but also to potentially sleep-related complications.

The more we do that, the more we individualize patient treatment rather than treating them as a disease state. This, in turn, will allow us to practice personalized medicine. The more we can engage our patients with reflux disease by asking the right questions about next-day function, the better we can do in improving their outcomes.

It’s time for us all to open our eyes to the value of closing them. Let’s talk to our patients with reflux disease in a little bit of a different light, providing a new perspective on strategies we can use to mitigate and deal with those symptoms, thereby preventing the consequences of sleep fragmentation.

Hopefully, this overview gives you some guidance the next time you have a conversation with your patients. It will apply across many, many disease states, and in almost everything we do in gastroenterology.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, Va., and a past president of the American College of Gastroenterology. He reported advising with ISOTHRIVE and Johnson & Johnson.

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

This transcript has been edited for clarity.

The ongoing longitudinal Nurses’ Health Study has served as an incredible database for evaluating disease states prospectively over decades, thanks to the robust input of its participants. Most recently, this allowed for an important analysis of the association between gastroesophageal reflux (GER) symptoms and sleep quality, the results of which were published in JAMA Network Open.

Approximately 49,000 women with a median age of 59 years (range, 48-69 years) provided data for this analysis. Starting in 2005, they were asked about their experience of GER symptoms. In 2017, they were also asked to respond to a questionnaire, a modified Pittsburgh Sleep Quality Index (PSQI). This is a tool we’ve used a lot in prospective studies looking at gastrointestinal diseases and sleep-related abnormalities. It’s unique in that it looks not only at sleep but also at next-day function and daytime sleepiness, which is important here for its implications related to reflux disease and sleep fragmentation.

In assessing these outcomes, the investigators found that the relative risk for association with sleep fragmentation was approximately 15% greater in those with GER symptoms occurring one to three times a month. For those with GER symptoms occurring once a week and more than once a week, the approximate relative risk increased by 30% and 53%, respectively. Clearly, the association of GER symptoms and relative sleep quality was really important.

It should be noted that the PSQI is a disease-independent, validated instrument. It’s not specific to GER disease or any diseases. It’s cross validated across 17 different languages. I think what’s most important about its use in the assessment here is the incorporation of next-day function and asking participants about daytime sleepiness, which we’ll discuss in more detail shortly.
 

The many causes of interrupted sleep

We’ve all experienced sleep fragmentation, whether in the form of having been on call during our medical training or common experiences like hearing a child cry in the night, a noisy truck pass by, or a dog barking. You may or may not remember that these happened the next day, but they’ve nonetheless interrupted your sleep efficiency.

When you transition laterally across the stages of sleep, that’s what establishes the circadian rhythm and ensures sleep hygiene. Typically, we require approximately 7 hours of restful sleep to do that. But if you fragment or interrupt this process, you more or less move your way erratically through the night, disrupting sleep hygiene and efficiency.

If you have a cognitive awakening during those disruptions, you may recall those events the next day. Or, you may not remember it at all, and such amnestic events are normal for some people with sleep disruptions.

You may also have a sensory arousal, whether it’s due to GER symptoms, auditory stimuli, bumping your toe, or whatever disruptive event. Any of these can cause you to lose that laterality of smooth transition through sleep.

Approximately 20% of the U.S. population have reported GER symptoms at least once a week. Incident data indicate that number may be increasing by as much as 5% a year. Much of that increase is tied to obesity. But nonetheless, it’s a problem on the rise.

It’s important to know this as we start to look at sleep. If GER is acting as a trigger to sleep disruption, you need to ask your patients with this condition about next-day function.

In particular, the next-day function questions to ask are, “How do you feel when you get up? Are you awake and refreshed? Do you have early fatigue? Do you drag yourself out of bed, have daytime somnolence, loss of concentration, or irritability?”

Those are key parameters we can use for looking back to the night before and gauging sleep efficiency. If you’re not asking those questions, you may miss out on identifying a patient having sleep fragmentation.
 

Sleep’s role in inflammatory disease processes

I now perform an interval assessment of this type not just in my patients with GER disease but across all my patients. I do so because sleep is physiologically important in so many ways.

In patients who have nonalcoholic fatty liver disease and a variety of other liver diseases, we’re finding an increased association with sleep fragmentation outside of sleep apnea.

The same is true with irritable bowel and other functional diseases.

When you have sleep fragmentation in inflammatory bowel disease, you turn on a variety of inflammatory proteins (e.g., C-reactive protein) and cytokines, such as interleukins and tumor necrosis factor alpha. These processes may actually tip somebody over to a pro-inflammatory state.

When it comes to what might be considered a relatively simpler condition like GER disease, Ronnie Fass and colleagues showed a number of years ago via Bernstein testing performed in patients with both fragmented and normal sleep that the sensory thresholds all get lowered in the former group. This is irrespective of whether you have a functional symptom or you’re awakened by bumping your toe, a headache, or having heartburn; your sensory thresholds are lower. As a result, the same stimulus provides a higher sense of awareness. By ramping up that awareness, you increase the interference with the next-day function.

We’ve shown that sleep fragmentation affects a variety of things, including immune function. This may be why many people get sick when they travel in between time zones.

There are also implications relating to things like obesity. When you have sleep dysfunction, you have effects on leptin and ghrelin, contrary to what you would normally want to have. This, in turn, causes adverse effects on stimulation or suppression of satiety or appetite. These are things that I counsel my patients about when I talk about reflux as well as those trying to lose weight.

Sleep disruption affects cortisol stimulation and has a significant correlation with type 2 diabetes, cardiovascular diseases, and even mortality statistics. 
 

Advice for counseling patients

This latest analysis from the Nurses’ Health Study reminds us that a lot of people have reflux and a lot of people have sleep fragmentation. We need to do better in asking our patients if they have symptoms specific not only to reflux but also to potentially sleep-related complications.

The more we do that, the more we individualize patient treatment rather than treating them as a disease state. This, in turn, will allow us to practice personalized medicine. The more we can engage our patients with reflux disease by asking the right questions about next-day function, the better we can do in improving their outcomes.

It’s time for us all to open our eyes to the value of closing them. Let’s talk to our patients with reflux disease in a little bit of a different light, providing a new perspective on strategies we can use to mitigate and deal with those symptoms, thereby preventing the consequences of sleep fragmentation.

Hopefully, this overview gives you some guidance the next time you have a conversation with your patients. It will apply across many, many disease states, and in almost everything we do in gastroenterology.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, Va., and a past president of the American College of Gastroenterology. He reported advising with ISOTHRIVE and Johnson & Johnson.

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

Incidence of C difficile infection has been increasing over the past two decades, accounting for nearly 460,000 cases of illness and 20,000 deaths annually in the United States.  

Antibiotic treatment is the standard of care for C difficile infection, but the treatment can disrupt a patient's gastrointestinal microbiome, thereby contributing to the risk for disease recurrence.  

Recurrence rates are proven to increase with each episode of C difficile, making prevention essential.  

In this ReCAP, Dr David Johnson, of Eastern Virginia Medical School, discusses treatment options to avoid recurrence. He considers multiple means of prevention, including disinfection, infusions of monoclonal antibodies, and the latest advances in fecal microbiota-based biotherapies. Dr Johnson provides data regarding the success rates of pharmaceutical-grade options for prevention of relapse of C difficile. 

--

David A. Johnson, MD, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School; Chief of Gastroenterology, Digestive and Liver Disease Specialists, Division of Capital Digestive Care, Norfolk, Virginia 

David A. Johnson, MD, has disclosed the following relevant financial relationships: 

 
Serve(d) on a board for: ACG Institute for Clinical Research and Education; Adjudication Board Parexel 
Serve(d) as a consultant for: Johnson & Johnson; Isothrive 
Received research grant from: ISOThrive 
Have a 5% or greater equity interest in: American College of Gastroenterology 
Received income in an amount equal to or greater than $250 from: Parexel; Johnson & Johnson 

Incidence of C difficile infection has been increasing over the past two decades, accounting for nearly 460,000 cases of illness and 20,000 deaths annually in the United States.  

Antibiotic treatment is the standard of care for C difficile infection, but the treatment can disrupt a patient's gastrointestinal microbiome, thereby contributing to the risk for disease recurrence.  

Recurrence rates are proven to increase with each episode of C difficile, making prevention essential.  

In this ReCAP, Dr David Johnson, of Eastern Virginia Medical School, discusses treatment options to avoid recurrence. He considers multiple means of prevention, including disinfection, infusions of monoclonal antibodies, and the latest advances in fecal microbiota-based biotherapies. Dr Johnson provides data regarding the success rates of pharmaceutical-grade options for prevention of relapse of C difficile. 

--

David A. Johnson, MD, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School; Chief of Gastroenterology, Digestive and Liver Disease Specialists, Division of Capital Digestive Care, Norfolk, Virginia 

David A. Johnson, MD, has disclosed the following relevant financial relationships: 

 
Serve(d) on a board for: ACG Institute for Clinical Research and Education; Adjudication Board Parexel 
Serve(d) as a consultant for: Johnson & Johnson; Isothrive 
Received research grant from: ISOThrive 
Have a 5% or greater equity interest in: American College of Gastroenterology 
Received income in an amount equal to or greater than $250 from: Parexel; Johnson & Johnson 

Incidence of C difficile infection has been increasing over the past two decades, accounting for nearly 460,000 cases of illness and 20,000 deaths annually in the United States.  

Antibiotic treatment is the standard of care for C difficile infection, but the treatment can disrupt a patient's gastrointestinal microbiome, thereby contributing to the risk for disease recurrence.  

Recurrence rates are proven to increase with each episode of C difficile, making prevention essential.  

In this ReCAP, Dr David Johnson, of Eastern Virginia Medical School, discusses treatment options to avoid recurrence. He considers multiple means of prevention, including disinfection, infusions of monoclonal antibodies, and the latest advances in fecal microbiota-based biotherapies. Dr Johnson provides data regarding the success rates of pharmaceutical-grade options for prevention of relapse of C difficile. 

--

David A. Johnson, MD, Professor of Medicine, Chief of Gastroenterology, Eastern Virginia Medical School; Chief of Gastroenterology, Digestive and Liver Disease Specialists, Division of Capital Digestive Care, Norfolk, Virginia 

David A. Johnson, MD, has disclosed the following relevant financial relationships: 

 
Serve(d) on a board for: ACG Institute for Clinical Research and Education; Adjudication Board Parexel 
Serve(d) as a consultant for: Johnson & Johnson; Isothrive 
Received research grant from: ISOThrive 
Have a 5% or greater equity interest in: American College of Gastroenterology 
Received income in an amount equal to or greater than $250 from: Parexel; Johnson & Johnson 

Colorectal cancer (CRC) remains the second most common cause of cancer-related death in the United States. Although the past several decades have seen significantly greater emphasis on screening and disease prevention for CRC, it has also become increasingly apparent that the age profile and associated risks for this cancer are rapidly changing.

Evidence of this can be found in recently released CRC statistics from the American Cancer Society, which are updated every 3 years using population-based cancer registries.

The incidence in CRC has shown a progressive decline over the past 4 decades. However, whereas in the 2000s there was an average decline of approximately 3%-4% annually, it slowed to 1% per year between 2011 and 2019. This effect is in part because of the trends among younger individuals (< 55 years), in whom the incidence of CRC has increased by 9% over the past 25 years.

The incidence of regional-stage disease also increased by 2%-3% per year for those younger than 65 years, with an additional increase in the incidence of more advanced/distant disease by 0.5%-3% per year. The latter finding represents a reversal of earlier trends observed for staged disease in the decade from 1995 to 2005.

These recent statistics reveal other notable changes that occurred in parallel with the increased incidence of younger-onset CRC. There was a significant shift to left-sided tumors, with a 4% increase in rectal cancers in the decades spanning 1995–2019.

Although the overall mortality declined 2% from 2011 to 2020, the reverse was seen in patients younger than 50 years, in whom there was an increase by 0.5%-3% annually.

Available incidence and mortality data for the current year are understandably lacking, as there is a 2- to 4-year lag for data collection and assimilation, and there have also been methodological changes for tracking and projections. Nonetheless, 2023 projections estimate that there will be 153,020 new cases in the United States, with 19,550 (13%) to occur in those younger than 50 years and 33% in those aged 50-64 years. Overall, 43% of cases are projected to occur in those aged 45-49 years, which is noteworthy given that these ages are now included in the most current CRC screening recommendations.

Further underscoring the risks posed by earlier-onset trends is the projection of 52,550 CRC-related deaths in 2023, with 7% estimated to occur in those younger than 50 years.
 

What’s behind the trend toward younger onset?

The specific factors contributing to increasing rates of CRC in younger individuals are not well known, but there are several plausible explanations. Notable possible contributing factors reported in the literature include obesity, smoking, alcohol, diet, and microbial changes, among other demographic variables. Exposure to high-fructose corn syrup, sugar-sweetened beverages, and processed meats has also recently received attention as contributing dietary risk factors.

The shifting trends toward the onset of CRC among younger patients are now clearly established, with approximately 20% of new cases occurring in those in their early 50s or younger and a higher rate of left-sided tumor development. Unfortunately, these shifts are also associated with a more advanced stage of disease.

There are unique clinical challenges when it comes to identifying younger-onset CRC. A low level of suspicion among primary care providers that their younger patients may have CRC can result in delays in their receiving clinically appropriate diagnostic testing (particularly for overt or occult bleeding/iron deficiency). Younger patients may also be less likely to know about or adhere to new recommendations that they undergo screening.

The landscape for age-related CRC is changing. Although there are many obstacles for implementing new practices, these recent findings from the ACS also highlight a clear path for improvement.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, and a past president of the American College of Gastroenterology.

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

Colorectal cancer (CRC) remains the second most common cause of cancer-related death in the United States. Although the past several decades have seen significantly greater emphasis on screening and disease prevention for CRC, it has also become increasingly apparent that the age profile and associated risks for this cancer are rapidly changing.

Evidence of this can be found in recently released CRC statistics from the American Cancer Society, which are updated every 3 years using population-based cancer registries.

The incidence in CRC has shown a progressive decline over the past 4 decades. However, whereas in the 2000s there was an average decline of approximately 3%-4% annually, it slowed to 1% per year between 2011 and 2019. This effect is in part because of the trends among younger individuals (< 55 years), in whom the incidence of CRC has increased by 9% over the past 25 years.

The incidence of regional-stage disease also increased by 2%-3% per year for those younger than 65 years, with an additional increase in the incidence of more advanced/distant disease by 0.5%-3% per year. The latter finding represents a reversal of earlier trends observed for staged disease in the decade from 1995 to 2005.

These recent statistics reveal other notable changes that occurred in parallel with the increased incidence of younger-onset CRC. There was a significant shift to left-sided tumors, with a 4% increase in rectal cancers in the decades spanning 1995–2019.

Although the overall mortality declined 2% from 2011 to 2020, the reverse was seen in patients younger than 50 years, in whom there was an increase by 0.5%-3% annually.

Available incidence and mortality data for the current year are understandably lacking, as there is a 2- to 4-year lag for data collection and assimilation, and there have also been methodological changes for tracking and projections. Nonetheless, 2023 projections estimate that there will be 153,020 new cases in the United States, with 19,550 (13%) to occur in those younger than 50 years and 33% in those aged 50-64 years. Overall, 43% of cases are projected to occur in those aged 45-49 years, which is noteworthy given that these ages are now included in the most current CRC screening recommendations.

Further underscoring the risks posed by earlier-onset trends is the projection of 52,550 CRC-related deaths in 2023, with 7% estimated to occur in those younger than 50 years.
 

What’s behind the trend toward younger onset?

The specific factors contributing to increasing rates of CRC in younger individuals are not well known, but there are several plausible explanations. Notable possible contributing factors reported in the literature include obesity, smoking, alcohol, diet, and microbial changes, among other demographic variables. Exposure to high-fructose corn syrup, sugar-sweetened beverages, and processed meats has also recently received attention as contributing dietary risk factors.

The shifting trends toward the onset of CRC among younger patients are now clearly established, with approximately 20% of new cases occurring in those in their early 50s or younger and a higher rate of left-sided tumor development. Unfortunately, these shifts are also associated with a more advanced stage of disease.

There are unique clinical challenges when it comes to identifying younger-onset CRC. A low level of suspicion among primary care providers that their younger patients may have CRC can result in delays in their receiving clinically appropriate diagnostic testing (particularly for overt or occult bleeding/iron deficiency). Younger patients may also be less likely to know about or adhere to new recommendations that they undergo screening.

The landscape for age-related CRC is changing. Although there are many obstacles for implementing new practices, these recent findings from the ACS also highlight a clear path for improvement.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, and a past president of the American College of Gastroenterology.

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

Colorectal cancer (CRC) remains the second most common cause of cancer-related death in the United States. Although the past several decades have seen significantly greater emphasis on screening and disease prevention for CRC, it has also become increasingly apparent that the age profile and associated risks for this cancer are rapidly changing.

Evidence of this can be found in recently released CRC statistics from the American Cancer Society, which are updated every 3 years using population-based cancer registries.

The incidence in CRC has shown a progressive decline over the past 4 decades. However, whereas in the 2000s there was an average decline of approximately 3%-4% annually, it slowed to 1% per year between 2011 and 2019. This effect is in part because of the trends among younger individuals (< 55 years), in whom the incidence of CRC has increased by 9% over the past 25 years.

The incidence of regional-stage disease also increased by 2%-3% per year for those younger than 65 years, with an additional increase in the incidence of more advanced/distant disease by 0.5%-3% per year. The latter finding represents a reversal of earlier trends observed for staged disease in the decade from 1995 to 2005.

These recent statistics reveal other notable changes that occurred in parallel with the increased incidence of younger-onset CRC. There was a significant shift to left-sided tumors, with a 4% increase in rectal cancers in the decades spanning 1995–2019.

Although the overall mortality declined 2% from 2011 to 2020, the reverse was seen in patients younger than 50 years, in whom there was an increase by 0.5%-3% annually.

Available incidence and mortality data for the current year are understandably lacking, as there is a 2- to 4-year lag for data collection and assimilation, and there have also been methodological changes for tracking and projections. Nonetheless, 2023 projections estimate that there will be 153,020 new cases in the United States, with 19,550 (13%) to occur in those younger than 50 years and 33% in those aged 50-64 years. Overall, 43% of cases are projected to occur in those aged 45-49 years, which is noteworthy given that these ages are now included in the most current CRC screening recommendations.

Further underscoring the risks posed by earlier-onset trends is the projection of 52,550 CRC-related deaths in 2023, with 7% estimated to occur in those younger than 50 years.
 

What’s behind the trend toward younger onset?

The specific factors contributing to increasing rates of CRC in younger individuals are not well known, but there are several plausible explanations. Notable possible contributing factors reported in the literature include obesity, smoking, alcohol, diet, and microbial changes, among other demographic variables. Exposure to high-fructose corn syrup, sugar-sweetened beverages, and processed meats has also recently received attention as contributing dietary risk factors.

The shifting trends toward the onset of CRC among younger patients are now clearly established, with approximately 20% of new cases occurring in those in their early 50s or younger and a higher rate of left-sided tumor development. Unfortunately, these shifts are also associated with a more advanced stage of disease.

There are unique clinical challenges when it comes to identifying younger-onset CRC. A low level of suspicion among primary care providers that their younger patients may have CRC can result in delays in their receiving clinically appropriate diagnostic testing (particularly for overt or occult bleeding/iron deficiency). Younger patients may also be less likely to know about or adhere to new recommendations that they undergo screening.

The landscape for age-related CRC is changing. Although there are many obstacles for implementing new practices, these recent findings from the ACS also highlight a clear path for improvement.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, and a past president of the American College of Gastroenterology.

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

This transcript has been edited for clarity.

F. Perry Wilson, MD, MSCE: Hello, and thank you for joining us today for what promises to be a lively discussion about screening for colon cancer.

My name is Perry Wilson. I’m an associate professor of medicine and director of the Clinical and Translational Research Accelerator at the Yale School of Medicine. My new book, “How Medicine Works and When It Doesn’t: Learning Who to Trust to Get and Stay Healthy,” is available for pre-order now anywhere that books are sold.

I’m joined by two wonderful experts. Dr. David Johnson is a professor of medicine and the chief of gastroenterology at the Eastern Virginia School of Medicine. He is the past president of the American College of Gastroenterology. And I’m very encouraged to see that he’s won a Distinguished Educator Award for his efforts in gastroenterology.

I’m also joined by Dr Kenny Lin. He’s a frequent contributor to Medscape and WebMD. He’s a family physician and public health consultant from Lancaster, Pa., and deputy editor of the American Family Physician journal. He’s also a teacher of residents and students at Lancaster General Health and the Penn Medicine Family Medicine Residency program.

So, we have two great educators with us today to hopefully help teach us something about colon cancer and colon cancer screening. Thank you for joining me today.

David A. Johnson, MD: Thanks for having us.

Kenneth W. Lin, MD, MPH: Good to be here.

Dr. Wilson: Colon cancer is the second leading cause of cancer mortality in the United States. A little over 50,000 people die every year in the United States due to colon cancer.

A month ago, I would have said that there was a pretty broad consensus, at least from my perspective, that people should be getting colonoscopies. That’s certainly what we tell our patients.

Then a paper came out in the New England Journal of Medicine, a very prestigious journal, that has caused a lot of consternation online and led to my receiving a lot questions from patients and their family members. Today, I’d like to talk about this randomized trial of screening colonoscopy for colon cancer, and why it has caused so much – perhaps – confusion, calls for change, and concern out there.

Dr Johnson, can you give us a brief overview of what this trial was about?

Dr. Johnson: This was a randomized trial looking at screening colonoscopy versus no screening test whatsoever. They looked at the outcomes of prevention of cancer and the prevention of colon cancer–related death.

The short answer was that it was disappointing as it relates to colonoscopy. The study looked at patients from four European countries, with data from three of them (Norway, Poland, and Sweden) ultimately analyzed in this report in NEJM. It got a lot of attention because it surprised a lot of people by saying maybe colonoscopy wasn’t quite as good as we thought it was.

They tried to correct that by only looking at the numbers of patients who got their colonoscopy screening, which still showed value, but it was less than that we’ve seen before. There’s lots of reasons for that, which we’ll discuss shortly.
 

An invitation to a screening

Dr. Wilson: This was a bit of an interesting trial design. I think I’m correct, Dr Lin, that this was the first randomized trial of screening colonoscopy. But they didn’t really randomize people to get a colonoscopy versus not get a colonoscopy. Can you tell us why this differed from that study design, which I’d have thought would be simpler way of assessing this?

Dr. Lin: It’s definitely an important point to highlight about the study. What investigators did was randomize patients to receive an invitation to get a screening colonoscopy. When the trial was set up, they randomized people before they were asked whether they wanted to participate in the study. If you did it the other way around, by first asking them whether they wanted to be in the study and then randomizing them, you would have been assured that more of them probably would have gotten the colonoscopy.

But in this case, they were more interested in figuring out the real-life results of having a national program that invited patients to receive screening colonoscopy. Because we know that everyone that you recommend to get a colonoscopy doesn’t necessarily want to do that, forgets to do it, or something happens that prevents their actually getting it.

When it comes to measuring the effectiveness of the colonoscopy, it perhaps wasn’t the greatest type of study to do that. But I think it did provide some information about what would happen if you invited people to get colonoscopy, in terms of how many would do it and the results overall for that population.
 

Lower participation numbers than expected

Dr. Wilson: Dr. Johnson, the data show that 42% of people who were in that invitation arm followed through and got their colonoscopy. You’re a gastroenterologist. Does that seem low or about right? Do about half of people who should get a colonoscopy end up getting one?

Dr. Johnson: No, it’s low. In the United States, those numbers are probably in the 70% range. Certainly, the test doesn’t work for people who don’t get the test performed. So, if 42% of those randomized to receive an invitation to get the colonoscopy got one, that really means the majority of patients never got the test.

Dr. Wilson: Certainly, we wouldn’t expect impressive results if they don’t get the test. But on the other hand, I imagine that people who choose to get the test when they’re invited are sort of a different breed. Perhaps they’re more health conscious or living in other healthy ways. Is that something we should worry about when we look at these results?

Dr. Johnson: I don’t think you can stratify based on this study. Factors like ethnicities and diet weren’t really explained. The key element that will hopefully have the major take-home impact is quality. It’s not just the test. It’s how the test is done.

The key results

Dr. Wilson: Let’s start with the big picture. This was a study looking at everyone invited; not the subgroup of people who got the colonoscopy, but the real randomized study population.

Dr. Lin, the study did show that the invited group had a lower risk of colon cancer over the next 10 years. That’s a good thing, I imagine.

Dr. Lin: I think that’s a significant benefit. Initially in the first few years, they had more colon cancers diagnosed. But that’s probably because those were cancers that were already existing and couldn’t be prevented by the test.

But then over the years the curves crossed, and by the end of the average follow-up of 10 years, there was a significantly lower rate of colon cancers being detected. That’s as you would expect, because you’re finding polyps and removing them before they became colon cancer.

Dr. Wilson: Dr. Johnson, is that the natural history of colon cancer? It starts out as a polyp that maybe can be easily removed and doesn’t require more therapy. Is that why screening colonoscopy is helpful?

Dr. Johnson: The ultimate goal of screening is prevention of cancer, rather than detection of cancer. That occurs by identification and complete removal of the polyps that we find that are precancerous. The key is, first, detection, and second, resection. Adequate resection comes down to some very significant issues of quality, which are questions that I’d raised about this study, and we can talk about momentarily.

Dr. Wilson: Absolutely. Let me first go through the two other big findings in this study.

The fact that there were fewer cases of colon cancer over 10 years seems good. But colon cancer mortality was not significantly different in the two groups. Now, of course, we know that not everyone got a colonoscopy. I would have expected though, if you had less colon cancer, you’d have less death from colon cancer.

Dr. Lin, what might explain this disconnect?

Dr. Lin: I think there are a couple of possible explanations.

One explanation is that they just didn’t follow the people long enough. Colon cancer takes a long time to go from an adenoma to cancer, and from cancer to something that would cause the patient’s death. You may need to follow them for longer than the 10 years that most of these patients were followed to see that benefit. I think there probably will be benefit after a while, because if you are removing colon cancers that otherwise would have progressed and metastasized, you often see a benefit.

We also have to consider the other possibility that not all the polyps removed necessarily were going to progress to advanced cancer. Therefore, you weren’t seeing the death benefit because not every polyp that was removed was necessarily going to cause health consequences.

In colonoscopy, quality is key to success

Dr. Wilson: You’re removing things and have no way of knowing in advance which are the bad ones and which aren’t.

Dr. Johnson, you’ve mentioned several times now that the quality of colonoscopy matters here. So, I’m intuiting that it’s not one-size-fits-all, that it’s not all the same. What do you mean by quality of colonoscopy, and what was it in the NEJM study?

Dr. Johnson: Quality colonoscopy is the quality of the whole process. It starts with the warm-up, if you will, and the clean out for the procedure. That allows the colonoscopist to be able to identify precancerous polyps, which we call adenomas (there are other precancerous polyps called sessile serrated lesions).

The identification of adenomas is extremely important. Even a small increase in the detection of those precancerous polyps has benefits. Well-performed studies looking at large databases show that a small, 1% increase in the adenoma detection leads to a 3% decrease in colon cancer and a 5% decrease in colon cancer–related death. There’s a huge array of effect when we talk about small increases in the adenoma detection rate.

Now, let’s go back to this study in NEJM.

If we base quality on the physician performing the colonoscopy, and say that the colonoscopy is achieving the act of getting all the way around the colon, but not all physicians in the study were able to do that, it starts to raise the question about quality, because adenoma detection is so important. Earlier reports from this group [Nordic-European Initiative on Colorectal Cancer Study Group] have shown that the adenoma detection rates have been way below the national thresholds. So, this raises the question of whether they found the polyp, and then whether they resected the polyp. They also don’t tell us where these cancers were. It is about the colonoscopy quality. It’s not the instrument. It’s the process.
 

An overview of other screening tools

Dr. Wilson: Dr. Lin, colonoscopy, which requires prep and anesthesia, is not the only colon cancer screening method we have. In fact, there are a bunch. I think we’re on board saying it’s probably better to detect colon cancer early than not detect it. But what are our other options aside from colonoscopy that can allow for early detection of colon cancer?

Dr. Lin: For most of my career, there were three options that I presented patients with. The first was the fecal test, which used to be in the form of initial hemoccult tests. These have been mostly replaced by fecal immunochemical testing. But they’re both just basically looking for the presence of blood in the stool. Anyone who has a positive test would be referred for a diagnostic colonoscopy.

The other test besides colonoscopy, which has been largely phased out in the United States, although it is still very much used in Canada and much of Europe, is flexible sigmoidoscopy. Until this study, the tests supported by randomized controlled trials were the fecal tests and flexible sigmoidoscopy.

Interestingly, there was a recent systematic review of flexible sigmoidoscopy looking at four trials and their effects over 15 years. They showed not only a reduction in colon cancer, but also a reduction in colon cancer mortality, and even a small reduction in all-cause mortality.

I believe three out of the four trials were done where the patients were consented and then randomized, so they had a higher uptake of the procedure.

But when you compare this with the colonoscopy trial, it really isn’t that impressive. You would expect a much larger benefit, because obviously you’re looking at the entire colon. But you really didn’t see that. It was, at best, maybe equivalent to sigmoidoscopy, but not a whole lot better.

Dr. Johnson: Perry, you mentioned sedation. It’s important to understand that this particular cohort of patients are from Norway, Sweden, and Poland, where it’s very much the norm to not get sedation for your colonoscopy. Any of the [audience] who have had colonoscopy will tell you that they are not ones to say, “Don’t give me sedation.” The rate of sedation is around 11% in Norway, maybe 23% in Sweden, and around 45% in Poland. So, the examiner and the patient were never really super comfortable.

I’ve done 50,000 colonoscopies in my career, and many nonsedated. We know that taking time increases the finding of polyps and the adequate identification and resection. So, that ability to perform at a high quality is very much impacted when the patients aren’t comfortable.

Dr. Wilson: Dr. Johnson, we brought up flexible sigmoidoscopy. For the patients watching whose doctors are talking to them about screening colonoscopy, what’s the difference?

Dr. Johnson: Flexible sigmoidoscopy is just a short scope examination, in which you see about one-third of the colon. I’ve been in the field for 45 years, and during that time we’ve seen that there’s a progressive increase in the development of cancers above that bottom third of the colon to the higher end, the two-thirds of the colon that you would miss without doing a full colonoscopy. Also, flexible sigmoidoscopy typically does not get covered for sedation.

Again, if you do the exam and find something, then you’re going to have to come back and do an adequate resection with a colonoscopy. So, one-stop-shopping colon cancer screening is not about detection of cancer, it’s about prevention of cancer, and that’s what colonoscopy does.

Patients want convenience, but at what cost?

Dr. Wilson: Dr. Lin, how are your patients in your family practice handling this study? Have conversations changed around colon cancer screening? What are people asking about these days?

Dr. Lin: I don’t think the conversations have changed in my practice that much. When patients ask about this study, we do discuss the limitations, that it wasn’t designed to assess the maximum benefit of getting a colonoscopy because the majority of people assigned to that group didn’t get colonoscopy.

But I think it is an opportunity in primary care to consider the way we present the options to patients. Because I would guess that a majority of primary care physicians, when they present the options, would say colonoscopy is the gold standard and recommend their patients get it. And they only offer fecal testing to patients who don’t want the colonoscopy or really refuse.

That hasn’t been my practice. I’m usually more agnostic, because there are both harms and benefits. If you get a fecal test, the chance of you having a complication from colonoscopy is automatically lower because most of those people will not get colonoscopy. Now obviously, the complications with colonoscopy are pretty rare and usually self-limited, but they do exist. If you’re doing lots and lots of these, eventually you’ll see them. Probably all primary care physicians have patients who’ve had a complication from colonoscopy and may or may not have regretted it depending on how information was presented.

But I feel like this study reinforces my feeling that we ought to be presenting these, and not saying one is superior or inferior to the other. Instead, I’d base it on what the patient’s priorities are. But I feel like this study reinforces my feeling that we ought to be presenting these, and not saying one is superior or inferior to the other. Instead, I’d base it on what the patient’s priorities are. Is your priority finding every single cancer? Do you want to know exactly what the benefit is? I think with colonoscopy, we’re still trying to figure out exactly what the benefit is. Whereas we can say it pretty confidently for fecal tests because we have those randomized trials.

Dr. Wilson: Dr. Johnson, I think patients who are watching need to know, first of all, that if they do the fecal test route, a positive fecal test does lead to colonoscopy. In some sense, all roads lead to colonoscopy once you have a positive screening test. So, I can certainly see the value of just sort of skipping to that point. But what about this risk-versus-benefit relationship? Colonoscopy, albeit a relatively safe procedure, is still a procedure. There is some risk associated with it. If we can get the same benefit from yearly fecal immunochemical testing, is that a better choice potentially, at least for patients at average risk?

Dr. Johnson: The stool-based testing is really more effective for detection of cancer. That’s not screening, where the entire goal is the prevention of cancer. The fecal-based testing, including the stool-based DNA testing, misses the majority of precancerous polyps. And the fecal immunochemical tests, which Dr. Lin just mentioned, misses virtually all of them. We really want to get to the prevention of cancer, meaning identification and removal of polyps, not just screening for cancer.

Dr. Wilson: Do you see anything on the horizon that could unseat colonoscopy as, to quote Dr. Lin, the potential gold standard for screening for colon cancer?

Dr. Johnson: I think not on the horizon for identification and removal of polyps. That’s really the gold standard. Technology continues to advance. We’ll see what happens. But on the short and intermediate horizon, colonoscopy is going to be needed.

We are finding that some patients are starting to acquiesce to stool-based testing because they can do it at home. Maybe they don’t have to do a prep. We’re talking about screening only here, not about the follow-up of patients who have a family history, patients who have colitis, patients who have had colon polyps, or other reasons. Stool-based testing is not an option for the follow-up of those patients.

Convenience testing, in the face of COVID, also has thrown a wrench into things. Patients may have wanted to stay home and do these tests. Again, we need to be proactive, not reactive. We want to prevent cancer, not detect it.
 

Changing advice in the face of younger screening thresholds

Dr. Wilson: Dr. Lin, I’m 42 years old. I don’t believe I’m at any increased risk of colon cancer based on my family history or other risk factors. I’m 3 years away from when the U.S. Preventive Services Task Force tells me I should potentially consider starting to screen for colon cancer. That recommendation has recently been moved down from 50 years old to 45 years old. So, it’s on my mind as I approach that age. What do you advise younger patients approaching 45 right now in terms of screening for colon cancer?

Dr. Lin: For patients with the risk factors that Dr. Johnson mentioned, I would recommend screening colonoscopy as the initial test.

Assuming you don’t have those risk factors, I present it as we have a couple of different fecal tests. There’s the traditional one that just looks for blood. Then there’s the newer one that also adds DNA, which is more sensitive for colorectal cancer, but a little less specific, which is a problem just because there are more false positives.

But you need to compare that with colonoscopy, which you only need to get done ideally every 10 years if there are no findings. That is more complete. And theoretically, as we’ve been talking about, it would also prevent as well as detect early cancers.

So, I think it’s really down to your preference in terms of how the various factors that come into play, such as convenience of the test and your level of concern about cancer. I do tell patients that family history of cancer is not terribly predictive of whether you get it or not. A lot of people unfortunately who develop colorectal cancer have no previous family history. Diet will come into play to some extent. There are some things that point to increased risk for colorectal cancer if you have a diet high in red meat and things like that. But ultimately, it really is up to the patient. I lay out the options, and whatever they choose, I’m happy to pursue.

But the most important thing is that they do some test, because doing no test is not going to help anyone. I do agree with the notion that the best test is the test that gets done.

Dr. Wilson: Absolutely. I think the NEJM study supports that, even when we’re talking about colonoscopy.

Dr. Johnson, you’ve had some criticisms about the NEJM study, and I think they make sense. At the same time, as this is the first randomized trial of colonoscopy, it’s kind of the only data we have. Are we going to get better data? Are there other studies going on out there that might help shed some light on what’s turning out to be a complicated issue?

Dr. Johnson: Yes, there are ongoing studies. They’re not taking place within the United States, because you couldn’t get through a no-screening option trial. There are comparative studies that are probably still 5 years away looking at stool-based testing.

But again, we have to recognize that if you do these alternative tests that were eloquently discussed by Dr. Lin, and not the colonoscopy, which would be every 10 years with high-quality performance, that you have to annualize or do them in sequence. It’s important that you follow up on those with regularity. It’s not just a one-time test every 10 years for these individual tests.

And any of the time that those tests are ordered, the patient should be instructed that if it’s positive you need a colonoscopy. We’re seeing a lot of slippage on that front for the stool-based testing. Convenience is not the answer. It’s getting the job done.

Dr. Wilson: Would you agree, Dr. Johnson, that for patients that really don’t want to do the colonoscopy for one reason or another, and you’ve done your best in explaining what you think the risks and benefits are, that you’d rather have them get something than nothing?

Dr. Johnson: Absolutely. It comes down to what I recommend and then what you decide. But I still make the point explicit: If we’ve gone through those checkpoints and it’s positive, we agree that you understand that colonoscopy is the next step.

Final take-home messages

Dr. Wilson: Dr. Lin, I’ll turn the last word over to you, as the person who is probably discussing the choice of screening modalities more than any of us, before someone would get referred to someone like Dr. Johnson. What’s your final take-home message about the NEJM study and the state of colon cancer screening in the United States?

Dr. Lin: My take-home points about the study are that there were some limitations, but it is good to finally have a randomized trial of colonoscopy screening 2 decades after we really started doing that in the United States. It won’t immediately change – nor do I think it should – the way we practice and discuss different options. I think that some of Dr. Johnson’s points about making sure that whoever’s doing the colonoscopies for your practices is doing it in a high-quality way are really important. Just as it’s important, if you’re doing the fecal tests, to make sure that all patients who have positives get expeditiously referred for colonoscopy.

Dr. Johnson: Perry, I’d like to make one concluding comment as the gastroenterology expert in this discussion. I’ve had countless questions about this study from my patients and my peers. I tell them the following: Don’t let the headlines mislead you.

When you look at this study, the instrument is not so much the question. We know that getting the test is the first step in colon cancer screening. But we also know that getting the test done, with the highest-quality providers and the best-quality performance, is really the key to optimizing the true value of colonoscopy for colon cancer prevention.

So please don’t lose sight of this when reading the headlines in the media around this study. We really need to analyze the true characteristics of what we call a quality performance, because that’s what drives success and that’s what prevents colon cancer.

Dr. Wilson: Dr. Johnson and Dr. Lin, thank you very much. I appreciate you spending time with me here today and wish you all the best.

I guess I’ll sum up by saying that if you’re getting a colonoscopy, make sure it’s a good one. But do get screened.

This video originally appeared on WebMD. A transcript appeared on Medscape.com.

This transcript has been edited for clarity.

F. Perry Wilson, MD, MSCE: Hello, and thank you for joining us today for what promises to be a lively discussion about screening for colon cancer.

My name is Perry Wilson. I’m an associate professor of medicine and director of the Clinical and Translational Research Accelerator at the Yale School of Medicine. My new book, “How Medicine Works and When It Doesn’t: Learning Who to Trust to Get and Stay Healthy,” is available for pre-order now anywhere that books are sold.

I’m joined by two wonderful experts. Dr. David Johnson is a professor of medicine and the chief of gastroenterology at the Eastern Virginia School of Medicine. He is the past president of the American College of Gastroenterology. And I’m very encouraged to see that he’s won a Distinguished Educator Award for his efforts in gastroenterology.

I’m also joined by Dr Kenny Lin. He’s a frequent contributor to Medscape and WebMD. He’s a family physician and public health consultant from Lancaster, Pa., and deputy editor of the American Family Physician journal. He’s also a teacher of residents and students at Lancaster General Health and the Penn Medicine Family Medicine Residency program.

So, we have two great educators with us today to hopefully help teach us something about colon cancer and colon cancer screening. Thank you for joining me today.

David A. Johnson, MD: Thanks for having us.

Kenneth W. Lin, MD, MPH: Good to be here.

Dr. Wilson: Colon cancer is the second leading cause of cancer mortality in the United States. A little over 50,000 people die every year in the United States due to colon cancer.

A month ago, I would have said that there was a pretty broad consensus, at least from my perspective, that people should be getting colonoscopies. That’s certainly what we tell our patients.

Then a paper came out in the New England Journal of Medicine, a very prestigious journal, that has caused a lot of consternation online and led to my receiving a lot questions from patients and their family members. Today, I’d like to talk about this randomized trial of screening colonoscopy for colon cancer, and why it has caused so much – perhaps – confusion, calls for change, and concern out there.

Dr Johnson, can you give us a brief overview of what this trial was about?

Dr. Johnson: This was a randomized trial looking at screening colonoscopy versus no screening test whatsoever. They looked at the outcomes of prevention of cancer and the prevention of colon cancer–related death.

The short answer was that it was disappointing as it relates to colonoscopy. The study looked at patients from four European countries, with data from three of them (Norway, Poland, and Sweden) ultimately analyzed in this report in NEJM. It got a lot of attention because it surprised a lot of people by saying maybe colonoscopy wasn’t quite as good as we thought it was.

They tried to correct that by only looking at the numbers of patients who got their colonoscopy screening, which still showed value, but it was less than that we’ve seen before. There’s lots of reasons for that, which we’ll discuss shortly.
 

An invitation to a screening

Dr. Wilson: This was a bit of an interesting trial design. I think I’m correct, Dr Lin, that this was the first randomized trial of screening colonoscopy. But they didn’t really randomize people to get a colonoscopy versus not get a colonoscopy. Can you tell us why this differed from that study design, which I’d have thought would be simpler way of assessing this?

Dr. Lin: It’s definitely an important point to highlight about the study. What investigators did was randomize patients to receive an invitation to get a screening colonoscopy. When the trial was set up, they randomized people before they were asked whether they wanted to participate in the study. If you did it the other way around, by first asking them whether they wanted to be in the study and then randomizing them, you would have been assured that more of them probably would have gotten the colonoscopy.

But in this case, they were more interested in figuring out the real-life results of having a national program that invited patients to receive screening colonoscopy. Because we know that everyone that you recommend to get a colonoscopy doesn’t necessarily want to do that, forgets to do it, or something happens that prevents their actually getting it.

When it comes to measuring the effectiveness of the colonoscopy, it perhaps wasn’t the greatest type of study to do that. But I think it did provide some information about what would happen if you invited people to get colonoscopy, in terms of how many would do it and the results overall for that population.
 

Lower participation numbers than expected

Dr. Wilson: Dr. Johnson, the data show that 42% of people who were in that invitation arm followed through and got their colonoscopy. You’re a gastroenterologist. Does that seem low or about right? Do about half of people who should get a colonoscopy end up getting one?

Dr. Johnson: No, it’s low. In the United States, those numbers are probably in the 70% range. Certainly, the test doesn’t work for people who don’t get the test performed. So, if 42% of those randomized to receive an invitation to get the colonoscopy got one, that really means the majority of patients never got the test.

Dr. Wilson: Certainly, we wouldn’t expect impressive results if they don’t get the test. But on the other hand, I imagine that people who choose to get the test when they’re invited are sort of a different breed. Perhaps they’re more health conscious or living in other healthy ways. Is that something we should worry about when we look at these results?

Dr. Johnson: I don’t think you can stratify based on this study. Factors like ethnicities and diet weren’t really explained. The key element that will hopefully have the major take-home impact is quality. It’s not just the test. It’s how the test is done.

The key results

Dr. Wilson: Let’s start with the big picture. This was a study looking at everyone invited; not the subgroup of people who got the colonoscopy, but the real randomized study population.

Dr. Lin, the study did show that the invited group had a lower risk of colon cancer over the next 10 years. That’s a good thing, I imagine.

Dr. Lin: I think that’s a significant benefit. Initially in the first few years, they had more colon cancers diagnosed. But that’s probably because those were cancers that were already existing and couldn’t be prevented by the test.

But then over the years the curves crossed, and by the end of the average follow-up of 10 years, there was a significantly lower rate of colon cancers being detected. That’s as you would expect, because you’re finding polyps and removing them before they became colon cancer.

Dr. Wilson: Dr. Johnson, is that the natural history of colon cancer? It starts out as a polyp that maybe can be easily removed and doesn’t require more therapy. Is that why screening colonoscopy is helpful?

Dr. Johnson: The ultimate goal of screening is prevention of cancer, rather than detection of cancer. That occurs by identification and complete removal of the polyps that we find that are precancerous. The key is, first, detection, and second, resection. Adequate resection comes down to some very significant issues of quality, which are questions that I’d raised about this study, and we can talk about momentarily.

Dr. Wilson: Absolutely. Let me first go through the two other big findings in this study.

The fact that there were fewer cases of colon cancer over 10 years seems good. But colon cancer mortality was not significantly different in the two groups. Now, of course, we know that not everyone got a colonoscopy. I would have expected though, if you had less colon cancer, you’d have less death from colon cancer.

Dr. Lin, what might explain this disconnect?

Dr. Lin: I think there are a couple of possible explanations.

One explanation is that they just didn’t follow the people long enough. Colon cancer takes a long time to go from an adenoma to cancer, and from cancer to something that would cause the patient’s death. You may need to follow them for longer than the 10 years that most of these patients were followed to see that benefit. I think there probably will be benefit after a while, because if you are removing colon cancers that otherwise would have progressed and metastasized, you often see a benefit.

We also have to consider the other possibility that not all the polyps removed necessarily were going to progress to advanced cancer. Therefore, you weren’t seeing the death benefit because not every polyp that was removed was necessarily going to cause health consequences.

In colonoscopy, quality is key to success

Dr. Wilson: You’re removing things and have no way of knowing in advance which are the bad ones and which aren’t.

Dr. Johnson, you’ve mentioned several times now that the quality of colonoscopy matters here. So, I’m intuiting that it’s not one-size-fits-all, that it’s not all the same. What do you mean by quality of colonoscopy, and what was it in the NEJM study?

Dr. Johnson: Quality colonoscopy is the quality of the whole process. It starts with the warm-up, if you will, and the clean out for the procedure. That allows the colonoscopist to be able to identify precancerous polyps, which we call adenomas (there are other precancerous polyps called sessile serrated lesions).

The identification of adenomas is extremely important. Even a small increase in the detection of those precancerous polyps has benefits. Well-performed studies looking at large databases show that a small, 1% increase in the adenoma detection leads to a 3% decrease in colon cancer and a 5% decrease in colon cancer–related death. There’s a huge array of effect when we talk about small increases in the adenoma detection rate.

Now, let’s go back to this study in NEJM.

If we base quality on the physician performing the colonoscopy, and say that the colonoscopy is achieving the act of getting all the way around the colon, but not all physicians in the study were able to do that, it starts to raise the question about quality, because adenoma detection is so important. Earlier reports from this group [Nordic-European Initiative on Colorectal Cancer Study Group] have shown that the adenoma detection rates have been way below the national thresholds. So, this raises the question of whether they found the polyp, and then whether they resected the polyp. They also don’t tell us where these cancers were. It is about the colonoscopy quality. It’s not the instrument. It’s the process.
 

An overview of other screening tools

Dr. Wilson: Dr. Lin, colonoscopy, which requires prep and anesthesia, is not the only colon cancer screening method we have. In fact, there are a bunch. I think we’re on board saying it’s probably better to detect colon cancer early than not detect it. But what are our other options aside from colonoscopy that can allow for early detection of colon cancer?

Dr. Lin: For most of my career, there were three options that I presented patients with. The first was the fecal test, which used to be in the form of initial hemoccult tests. These have been mostly replaced by fecal immunochemical testing. But they’re both just basically looking for the presence of blood in the stool. Anyone who has a positive test would be referred for a diagnostic colonoscopy.

The other test besides colonoscopy, which has been largely phased out in the United States, although it is still very much used in Canada and much of Europe, is flexible sigmoidoscopy. Until this study, the tests supported by randomized controlled trials were the fecal tests and flexible sigmoidoscopy.

Interestingly, there was a recent systematic review of flexible sigmoidoscopy looking at four trials and their effects over 15 years. They showed not only a reduction in colon cancer, but also a reduction in colon cancer mortality, and even a small reduction in all-cause mortality.

I believe three out of the four trials were done where the patients were consented and then randomized, so they had a higher uptake of the procedure.

But when you compare this with the colonoscopy trial, it really isn’t that impressive. You would expect a much larger benefit, because obviously you’re looking at the entire colon. But you really didn’t see that. It was, at best, maybe equivalent to sigmoidoscopy, but not a whole lot better.

Dr. Johnson: Perry, you mentioned sedation. It’s important to understand that this particular cohort of patients are from Norway, Sweden, and Poland, where it’s very much the norm to not get sedation for your colonoscopy. Any of the [audience] who have had colonoscopy will tell you that they are not ones to say, “Don’t give me sedation.” The rate of sedation is around 11% in Norway, maybe 23% in Sweden, and around 45% in Poland. So, the examiner and the patient were never really super comfortable.

I’ve done 50,000 colonoscopies in my career, and many nonsedated. We know that taking time increases the finding of polyps and the adequate identification and resection. So, that ability to perform at a high quality is very much impacted when the patients aren’t comfortable.

Dr. Wilson: Dr. Johnson, we brought up flexible sigmoidoscopy. For the patients watching whose doctors are talking to them about screening colonoscopy, what’s the difference?

Dr. Johnson: Flexible sigmoidoscopy is just a short scope examination, in which you see about one-third of the colon. I’ve been in the field for 45 years, and during that time we’ve seen that there’s a progressive increase in the development of cancers above that bottom third of the colon to the higher end, the two-thirds of the colon that you would miss without doing a full colonoscopy. Also, flexible sigmoidoscopy typically does not get covered for sedation.

Again, if you do the exam and find something, then you’re going to have to come back and do an adequate resection with a colonoscopy. So, one-stop-shopping colon cancer screening is not about detection of cancer, it’s about prevention of cancer, and that’s what colonoscopy does.

Patients want convenience, but at what cost?

Dr. Wilson: Dr. Lin, how are your patients in your family practice handling this study? Have conversations changed around colon cancer screening? What are people asking about these days?

Dr. Lin: I don’t think the conversations have changed in my practice that much. When patients ask about this study, we do discuss the limitations, that it wasn’t designed to assess the maximum benefit of getting a colonoscopy because the majority of people assigned to that group didn’t get colonoscopy.

But I think it is an opportunity in primary care to consider the way we present the options to patients. Because I would guess that a majority of primary care physicians, when they present the options, would say colonoscopy is the gold standard and recommend their patients get it. And they only offer fecal testing to patients who don’t want the colonoscopy or really refuse.

That hasn’t been my practice. I’m usually more agnostic, because there are both harms and benefits. If you get a fecal test, the chance of you having a complication from colonoscopy is automatically lower because most of those people will not get colonoscopy. Now obviously, the complications with colonoscopy are pretty rare and usually self-limited, but they do exist. If you’re doing lots and lots of these, eventually you’ll see them. Probably all primary care physicians have patients who’ve had a complication from colonoscopy and may or may not have regretted it depending on how information was presented.

But I feel like this study reinforces my feeling that we ought to be presenting these, and not saying one is superior or inferior to the other. Instead, I’d base it on what the patient’s priorities are. But I feel like this study reinforces my feeling that we ought to be presenting these, and not saying one is superior or inferior to the other. Instead, I’d base it on what the patient’s priorities are. Is your priority finding every single cancer? Do you want to know exactly what the benefit is? I think with colonoscopy, we’re still trying to figure out exactly what the benefit is. Whereas we can say it pretty confidently for fecal tests because we have those randomized trials.

Dr. Wilson: Dr. Johnson, I think patients who are watching need to know, first of all, that if they do the fecal test route, a positive fecal test does lead to colonoscopy. In some sense, all roads lead to colonoscopy once you have a positive screening test. So, I can certainly see the value of just sort of skipping to that point. But what about this risk-versus-benefit relationship? Colonoscopy, albeit a relatively safe procedure, is still a procedure. There is some risk associated with it. If we can get the same benefit from yearly fecal immunochemical testing, is that a better choice potentially, at least for patients at average risk?

Dr. Johnson: The stool-based testing is really more effective for detection of cancer. That’s not screening, where the entire goal is the prevention of cancer. The fecal-based testing, including the stool-based DNA testing, misses the majority of precancerous polyps. And the fecal immunochemical tests, which Dr. Lin just mentioned, misses virtually all of them. We really want to get to the prevention of cancer, meaning identification and removal of polyps, not just screening for cancer.

Dr. Wilson: Do you see anything on the horizon that could unseat colonoscopy as, to quote Dr. Lin, the potential gold standard for screening for colon cancer?

Dr. Johnson: I think not on the horizon for identification and removal of polyps. That’s really the gold standard. Technology continues to advance. We’ll see what happens. But on the short and intermediate horizon, colonoscopy is going to be needed.

We are finding that some patients are starting to acquiesce to stool-based testing because they can do it at home. Maybe they don’t have to do a prep. We’re talking about screening only here, not about the follow-up of patients who have a family history, patients who have colitis, patients who have had colon polyps, or other reasons. Stool-based testing is not an option for the follow-up of those patients.

Convenience testing, in the face of COVID, also has thrown a wrench into things. Patients may have wanted to stay home and do these tests. Again, we need to be proactive, not reactive. We want to prevent cancer, not detect it.
 

Changing advice in the face of younger screening thresholds

Dr. Wilson: Dr. Lin, I’m 42 years old. I don’t believe I’m at any increased risk of colon cancer based on my family history or other risk factors. I’m 3 years away from when the U.S. Preventive Services Task Force tells me I should potentially consider starting to screen for colon cancer. That recommendation has recently been moved down from 50 years old to 45 years old. So, it’s on my mind as I approach that age. What do you advise younger patients approaching 45 right now in terms of screening for colon cancer?

Dr. Lin: For patients with the risk factors that Dr. Johnson mentioned, I would recommend screening colonoscopy as the initial test.

Assuming you don’t have those risk factors, I present it as we have a couple of different fecal tests. There’s the traditional one that just looks for blood. Then there’s the newer one that also adds DNA, which is more sensitive for colorectal cancer, but a little less specific, which is a problem just because there are more false positives.

But you need to compare that with colonoscopy, which you only need to get done ideally every 10 years if there are no findings. That is more complete. And theoretically, as we’ve been talking about, it would also prevent as well as detect early cancers.

So, I think it’s really down to your preference in terms of how the various factors that come into play, such as convenience of the test and your level of concern about cancer. I do tell patients that family history of cancer is not terribly predictive of whether you get it or not. A lot of people unfortunately who develop colorectal cancer have no previous family history. Diet will come into play to some extent. There are some things that point to increased risk for colorectal cancer if you have a diet high in red meat and things like that. But ultimately, it really is up to the patient. I lay out the options, and whatever they choose, I’m happy to pursue.

But the most important thing is that they do some test, because doing no test is not going to help anyone. I do agree with the notion that the best test is the test that gets done.

Dr. Wilson: Absolutely. I think the NEJM study supports that, even when we’re talking about colonoscopy.

Dr. Johnson, you’ve had some criticisms about the NEJM study, and I think they make sense. At the same time, as this is the first randomized trial of colonoscopy, it’s kind of the only data we have. Are we going to get better data? Are there other studies going on out there that might help shed some light on what’s turning out to be a complicated issue?

Dr. Johnson: Yes, there are ongoing studies. They’re not taking place within the United States, because you couldn’t get through a no-screening option trial. There are comparative studies that are probably still 5 years away looking at stool-based testing.

But again, we have to recognize that if you do these alternative tests that were eloquently discussed by Dr. Lin, and not the colonoscopy, which would be every 10 years with high-quality performance, that you have to annualize or do them in sequence. It’s important that you follow up on those with regularity. It’s not just a one-time test every 10 years for these individual tests.

And any of the time that those tests are ordered, the patient should be instructed that if it’s positive you need a colonoscopy. We’re seeing a lot of slippage on that front for the stool-based testing. Convenience is not the answer. It’s getting the job done.

Dr. Wilson: Would you agree, Dr. Johnson, that for patients that really don’t want to do the colonoscopy for one reason or another, and you’ve done your best in explaining what you think the risks and benefits are, that you’d rather have them get something than nothing?

Dr. Johnson: Absolutely. It comes down to what I recommend and then what you decide. But I still make the point explicit: If we’ve gone through those checkpoints and it’s positive, we agree that you understand that colonoscopy is the next step.

Final take-home messages

Dr. Wilson: Dr. Lin, I’ll turn the last word over to you, as the person who is probably discussing the choice of screening modalities more than any of us, before someone would get referred to someone like Dr. Johnson. What’s your final take-home message about the NEJM study and the state of colon cancer screening in the United States?

Dr. Lin: My take-home points about the study are that there were some limitations, but it is good to finally have a randomized trial of colonoscopy screening 2 decades after we really started doing that in the United States. It won’t immediately change – nor do I think it should – the way we practice and discuss different options. I think that some of Dr. Johnson’s points about making sure that whoever’s doing the colonoscopies for your practices is doing it in a high-quality way are really important. Just as it’s important, if you’re doing the fecal tests, to make sure that all patients who have positives get expeditiously referred for colonoscopy.

Dr. Johnson: Perry, I’d like to make one concluding comment as the gastroenterology expert in this discussion. I’ve had countless questions about this study from my patients and my peers. I tell them the following: Don’t let the headlines mislead you.

When you look at this study, the instrument is not so much the question. We know that getting the test is the first step in colon cancer screening. But we also know that getting the test done, with the highest-quality providers and the best-quality performance, is really the key to optimizing the true value of colonoscopy for colon cancer prevention.

So please don’t lose sight of this when reading the headlines in the media around this study. We really need to analyze the true characteristics of what we call a quality performance, because that’s what drives success and that’s what prevents colon cancer.

Dr. Wilson: Dr. Johnson and Dr. Lin, thank you very much. I appreciate you spending time with me here today and wish you all the best.

I guess I’ll sum up by saying that if you’re getting a colonoscopy, make sure it’s a good one. But do get screened.

This video originally appeared on WebMD. A transcript appeared on Medscape.com.

This transcript has been edited for clarity.

F. Perry Wilson, MD, MSCE: Hello, and thank you for joining us today for what promises to be a lively discussion about screening for colon cancer.

My name is Perry Wilson. I’m an associate professor of medicine and director of the Clinical and Translational Research Accelerator at the Yale School of Medicine. My new book, “How Medicine Works and When It Doesn’t: Learning Who to Trust to Get and Stay Healthy,” is available for pre-order now anywhere that books are sold.

I’m joined by two wonderful experts. Dr. David Johnson is a professor of medicine and the chief of gastroenterology at the Eastern Virginia School of Medicine. He is the past president of the American College of Gastroenterology. And I’m very encouraged to see that he’s won a Distinguished Educator Award for his efforts in gastroenterology.

I’m also joined by Dr Kenny Lin. He’s a frequent contributor to Medscape and WebMD. He’s a family physician and public health consultant from Lancaster, Pa., and deputy editor of the American Family Physician journal. He’s also a teacher of residents and students at Lancaster General Health and the Penn Medicine Family Medicine Residency program.

So, we have two great educators with us today to hopefully help teach us something about colon cancer and colon cancer screening. Thank you for joining me today.

David A. Johnson, MD: Thanks for having us.

Kenneth W. Lin, MD, MPH: Good to be here.

Dr. Wilson: Colon cancer is the second leading cause of cancer mortality in the United States. A little over 50,000 people die every year in the United States due to colon cancer.

A month ago, I would have said that there was a pretty broad consensus, at least from my perspective, that people should be getting colonoscopies. That’s certainly what we tell our patients.

Then a paper came out in the New England Journal of Medicine, a very prestigious journal, that has caused a lot of consternation online and led to my receiving a lot questions from patients and their family members. Today, I’d like to talk about this randomized trial of screening colonoscopy for colon cancer, and why it has caused so much – perhaps – confusion, calls for change, and concern out there.

Dr Johnson, can you give us a brief overview of what this trial was about?

Dr. Johnson: This was a randomized trial looking at screening colonoscopy versus no screening test whatsoever. They looked at the outcomes of prevention of cancer and the prevention of colon cancer–related death.

The short answer was that it was disappointing as it relates to colonoscopy. The study looked at patients from four European countries, with data from three of them (Norway, Poland, and Sweden) ultimately analyzed in this report in NEJM. It got a lot of attention because it surprised a lot of people by saying maybe colonoscopy wasn’t quite as good as we thought it was.

They tried to correct that by only looking at the numbers of patients who got their colonoscopy screening, which still showed value, but it was less than that we’ve seen before. There’s lots of reasons for that, which we’ll discuss shortly.
 

An invitation to a screening

Dr. Wilson: This was a bit of an interesting trial design. I think I’m correct, Dr Lin, that this was the first randomized trial of screening colonoscopy. But they didn’t really randomize people to get a colonoscopy versus not get a colonoscopy. Can you tell us why this differed from that study design, which I’d have thought would be simpler way of assessing this?

Dr. Lin: It’s definitely an important point to highlight about the study. What investigators did was randomize patients to receive an invitation to get a screening colonoscopy. When the trial was set up, they randomized people before they were asked whether they wanted to participate in the study. If you did it the other way around, by first asking them whether they wanted to be in the study and then randomizing them, you would have been assured that more of them probably would have gotten the colonoscopy.

But in this case, they were more interested in figuring out the real-life results of having a national program that invited patients to receive screening colonoscopy. Because we know that everyone that you recommend to get a colonoscopy doesn’t necessarily want to do that, forgets to do it, or something happens that prevents their actually getting it.

When it comes to measuring the effectiveness of the colonoscopy, it perhaps wasn’t the greatest type of study to do that. But I think it did provide some information about what would happen if you invited people to get colonoscopy, in terms of how many would do it and the results overall for that population.
 

Lower participation numbers than expected

Dr. Wilson: Dr. Johnson, the data show that 42% of people who were in that invitation arm followed through and got their colonoscopy. You’re a gastroenterologist. Does that seem low or about right? Do about half of people who should get a colonoscopy end up getting one?

Dr. Johnson: No, it’s low. In the United States, those numbers are probably in the 70% range. Certainly, the test doesn’t work for people who don’t get the test performed. So, if 42% of those randomized to receive an invitation to get the colonoscopy got one, that really means the majority of patients never got the test.

Dr. Wilson: Certainly, we wouldn’t expect impressive results if they don’t get the test. But on the other hand, I imagine that people who choose to get the test when they’re invited are sort of a different breed. Perhaps they’re more health conscious or living in other healthy ways. Is that something we should worry about when we look at these results?

Dr. Johnson: I don’t think you can stratify based on this study. Factors like ethnicities and diet weren’t really explained. The key element that will hopefully have the major take-home impact is quality. It’s not just the test. It’s how the test is done.

The key results

Dr. Wilson: Let’s start with the big picture. This was a study looking at everyone invited; not the subgroup of people who got the colonoscopy, but the real randomized study population.

Dr. Lin, the study did show that the invited group had a lower risk of colon cancer over the next 10 years. That’s a good thing, I imagine.

Dr. Lin: I think that’s a significant benefit. Initially in the first few years, they had more colon cancers diagnosed. But that’s probably because those were cancers that were already existing and couldn’t be prevented by the test.

But then over the years the curves crossed, and by the end of the average follow-up of 10 years, there was a significantly lower rate of colon cancers being detected. That’s as you would expect, because you’re finding polyps and removing them before they became colon cancer.

Dr. Wilson: Dr. Johnson, is that the natural history of colon cancer? It starts out as a polyp that maybe can be easily removed and doesn’t require more therapy. Is that why screening colonoscopy is helpful?

Dr. Johnson: The ultimate goal of screening is prevention of cancer, rather than detection of cancer. That occurs by identification and complete removal of the polyps that we find that are precancerous. The key is, first, detection, and second, resection. Adequate resection comes down to some very significant issues of quality, which are questions that I’d raised about this study, and we can talk about momentarily.

Dr. Wilson: Absolutely. Let me first go through the two other big findings in this study.

The fact that there were fewer cases of colon cancer over 10 years seems good. But colon cancer mortality was not significantly different in the two groups. Now, of course, we know that not everyone got a colonoscopy. I would have expected though, if you had less colon cancer, you’d have less death from colon cancer.

Dr. Lin, what might explain this disconnect?

Dr. Lin: I think there are a couple of possible explanations.

One explanation is that they just didn’t follow the people long enough. Colon cancer takes a long time to go from an adenoma to cancer, and from cancer to something that would cause the patient’s death. You may need to follow them for longer than the 10 years that most of these patients were followed to see that benefit. I think there probably will be benefit after a while, because if you are removing colon cancers that otherwise would have progressed and metastasized, you often see a benefit.

We also have to consider the other possibility that not all the polyps removed necessarily were going to progress to advanced cancer. Therefore, you weren’t seeing the death benefit because not every polyp that was removed was necessarily going to cause health consequences.

In colonoscopy, quality is key to success

Dr. Wilson: You’re removing things and have no way of knowing in advance which are the bad ones and which aren’t.

Dr. Johnson, you’ve mentioned several times now that the quality of colonoscopy matters here. So, I’m intuiting that it’s not one-size-fits-all, that it’s not all the same. What do you mean by quality of colonoscopy, and what was it in the NEJM study?

Dr. Johnson: Quality colonoscopy is the quality of the whole process. It starts with the warm-up, if you will, and the clean out for the procedure. That allows the colonoscopist to be able to identify precancerous polyps, which we call adenomas (there are other precancerous polyps called sessile serrated lesions).

The identification of adenomas is extremely important. Even a small increase in the detection of those precancerous polyps has benefits. Well-performed studies looking at large databases show that a small, 1% increase in the adenoma detection leads to a 3% decrease in colon cancer and a 5% decrease in colon cancer–related death. There’s a huge array of effect when we talk about small increases in the adenoma detection rate.

Now, let’s go back to this study in NEJM.

If we base quality on the physician performing the colonoscopy, and say that the colonoscopy is achieving the act of getting all the way around the colon, but not all physicians in the study were able to do that, it starts to raise the question about quality, because adenoma detection is so important. Earlier reports from this group [Nordic-European Initiative on Colorectal Cancer Study Group] have shown that the adenoma detection rates have been way below the national thresholds. So, this raises the question of whether they found the polyp, and then whether they resected the polyp. They also don’t tell us where these cancers were. It is about the colonoscopy quality. It’s not the instrument. It’s the process.
 

An overview of other screening tools

Dr. Wilson: Dr. Lin, colonoscopy, which requires prep and anesthesia, is not the only colon cancer screening method we have. In fact, there are a bunch. I think we’re on board saying it’s probably better to detect colon cancer early than not detect it. But what are our other options aside from colonoscopy that can allow for early detection of colon cancer?

Dr. Lin: For most of my career, there were three options that I presented patients with. The first was the fecal test, which used to be in the form of initial hemoccult tests. These have been mostly replaced by fecal immunochemical testing. But they’re both just basically looking for the presence of blood in the stool. Anyone who has a positive test would be referred for a diagnostic colonoscopy.

The other test besides colonoscopy, which has been largely phased out in the United States, although it is still very much used in Canada and much of Europe, is flexible sigmoidoscopy. Until this study, the tests supported by randomized controlled trials were the fecal tests and flexible sigmoidoscopy.

Interestingly, there was a recent systematic review of flexible sigmoidoscopy looking at four trials and their effects over 15 years. They showed not only a reduction in colon cancer, but also a reduction in colon cancer mortality, and even a small reduction in all-cause mortality.

I believe three out of the four trials were done where the patients were consented and then randomized, so they had a higher uptake of the procedure.

But when you compare this with the colonoscopy trial, it really isn’t that impressive. You would expect a much larger benefit, because obviously you’re looking at the entire colon. But you really didn’t see that. It was, at best, maybe equivalent to sigmoidoscopy, but not a whole lot better.

Dr. Johnson: Perry, you mentioned sedation. It’s important to understand that this particular cohort of patients are from Norway, Sweden, and Poland, where it’s very much the norm to not get sedation for your colonoscopy. Any of the [audience] who have had colonoscopy will tell you that they are not ones to say, “Don’t give me sedation.” The rate of sedation is around 11% in Norway, maybe 23% in Sweden, and around 45% in Poland. So, the examiner and the patient were never really super comfortable.

I’ve done 50,000 colonoscopies in my career, and many nonsedated. We know that taking time increases the finding of polyps and the adequate identification and resection. So, that ability to perform at a high quality is very much impacted when the patients aren’t comfortable.

Dr. Wilson: Dr. Johnson, we brought up flexible sigmoidoscopy. For the patients watching whose doctors are talking to them about screening colonoscopy, what’s the difference?

Dr. Johnson: Flexible sigmoidoscopy is just a short scope examination, in which you see about one-third of the colon. I’ve been in the field for 45 years, and during that time we’ve seen that there’s a progressive increase in the development of cancers above that bottom third of the colon to the higher end, the two-thirds of the colon that you would miss without doing a full colonoscopy. Also, flexible sigmoidoscopy typically does not get covered for sedation.

Again, if you do the exam and find something, then you’re going to have to come back and do an adequate resection with a colonoscopy. So, one-stop-shopping colon cancer screening is not about detection of cancer, it’s about prevention of cancer, and that’s what colonoscopy does.

Patients want convenience, but at what cost?

Dr. Wilson: Dr. Lin, how are your patients in your family practice handling this study? Have conversations changed around colon cancer screening? What are people asking about these days?

Dr. Lin: I don’t think the conversations have changed in my practice that much. When patients ask about this study, we do discuss the limitations, that it wasn’t designed to assess the maximum benefit of getting a colonoscopy because the majority of people assigned to that group didn’t get colonoscopy.

But I think it is an opportunity in primary care to consider the way we present the options to patients. Because I would guess that a majority of primary care physicians, when they present the options, would say colonoscopy is the gold standard and recommend their patients get it. And they only offer fecal testing to patients who don’t want the colonoscopy or really refuse.

That hasn’t been my practice. I’m usually more agnostic, because there are both harms and benefits. If you get a fecal test, the chance of you having a complication from colonoscopy is automatically lower because most of those people will not get colonoscopy. Now obviously, the complications with colonoscopy are pretty rare and usually self-limited, but they do exist. If you’re doing lots and lots of these, eventually you’ll see them. Probably all primary care physicians have patients who’ve had a complication from colonoscopy and may or may not have regretted it depending on how information was presented.

But I feel like this study reinforces my feeling that we ought to be presenting these, and not saying one is superior or inferior to the other. Instead, I’d base it on what the patient’s priorities are. But I feel like this study reinforces my feeling that we ought to be presenting these, and not saying one is superior or inferior to the other. Instead, I’d base it on what the patient’s priorities are. Is your priority finding every single cancer? Do you want to know exactly what the benefit is? I think with colonoscopy, we’re still trying to figure out exactly what the benefit is. Whereas we can say it pretty confidently for fecal tests because we have those randomized trials.

Dr. Wilson: Dr. Johnson, I think patients who are watching need to know, first of all, that if they do the fecal test route, a positive fecal test does lead to colonoscopy. In some sense, all roads lead to colonoscopy once you have a positive screening test. So, I can certainly see the value of just sort of skipping to that point. But what about this risk-versus-benefit relationship? Colonoscopy, albeit a relatively safe procedure, is still a procedure. There is some risk associated with it. If we can get the same benefit from yearly fecal immunochemical testing, is that a better choice potentially, at least for patients at average risk?

Dr. Johnson: The stool-based testing is really more effective for detection of cancer. That’s not screening, where the entire goal is the prevention of cancer. The fecal-based testing, including the stool-based DNA testing, misses the majority of precancerous polyps. And the fecal immunochemical tests, which Dr. Lin just mentioned, misses virtually all of them. We really want to get to the prevention of cancer, meaning identification and removal of polyps, not just screening for cancer.

Dr. Wilson: Do you see anything on the horizon that could unseat colonoscopy as, to quote Dr. Lin, the potential gold standard for screening for colon cancer?

Dr. Johnson: I think not on the horizon for identification and removal of polyps. That’s really the gold standard. Technology continues to advance. We’ll see what happens. But on the short and intermediate horizon, colonoscopy is going to be needed.

We are finding that some patients are starting to acquiesce to stool-based testing because they can do it at home. Maybe they don’t have to do a prep. We’re talking about screening only here, not about the follow-up of patients who have a family history, patients who have colitis, patients who have had colon polyps, or other reasons. Stool-based testing is not an option for the follow-up of those patients.

Convenience testing, in the face of COVID, also has thrown a wrench into things. Patients may have wanted to stay home and do these tests. Again, we need to be proactive, not reactive. We want to prevent cancer, not detect it.
 

Changing advice in the face of younger screening thresholds

Dr. Wilson: Dr. Lin, I’m 42 years old. I don’t believe I’m at any increased risk of colon cancer based on my family history or other risk factors. I’m 3 years away from when the U.S. Preventive Services Task Force tells me I should potentially consider starting to screen for colon cancer. That recommendation has recently been moved down from 50 years old to 45 years old. So, it’s on my mind as I approach that age. What do you advise younger patients approaching 45 right now in terms of screening for colon cancer?

Dr. Lin: For patients with the risk factors that Dr. Johnson mentioned, I would recommend screening colonoscopy as the initial test.

Assuming you don’t have those risk factors, I present it as we have a couple of different fecal tests. There’s the traditional one that just looks for blood. Then there’s the newer one that also adds DNA, which is more sensitive for colorectal cancer, but a little less specific, which is a problem just because there are more false positives.

But you need to compare that with colonoscopy, which you only need to get done ideally every 10 years if there are no findings. That is more complete. And theoretically, as we’ve been talking about, it would also prevent as well as detect early cancers.

So, I think it’s really down to your preference in terms of how the various factors that come into play, such as convenience of the test and your level of concern about cancer. I do tell patients that family history of cancer is not terribly predictive of whether you get it or not. A lot of people unfortunately who develop colorectal cancer have no previous family history. Diet will come into play to some extent. There are some things that point to increased risk for colorectal cancer if you have a diet high in red meat and things like that. But ultimately, it really is up to the patient. I lay out the options, and whatever they choose, I’m happy to pursue.

But the most important thing is that they do some test, because doing no test is not going to help anyone. I do agree with the notion that the best test is the test that gets done.

Dr. Wilson: Absolutely. I think the NEJM study supports that, even when we’re talking about colonoscopy.

Dr. Johnson, you’ve had some criticisms about the NEJM study, and I think they make sense. At the same time, as this is the first randomized trial of colonoscopy, it’s kind of the only data we have. Are we going to get better data? Are there other studies going on out there that might help shed some light on what’s turning out to be a complicated issue?

Dr. Johnson: Yes, there are ongoing studies. They’re not taking place within the United States, because you couldn’t get through a no-screening option trial. There are comparative studies that are probably still 5 years away looking at stool-based testing.

But again, we have to recognize that if you do these alternative tests that were eloquently discussed by Dr. Lin, and not the colonoscopy, which would be every 10 years with high-quality performance, that you have to annualize or do them in sequence. It’s important that you follow up on those with regularity. It’s not just a one-time test every 10 years for these individual tests.

And any of the time that those tests are ordered, the patient should be instructed that if it’s positive you need a colonoscopy. We’re seeing a lot of slippage on that front for the stool-based testing. Convenience is not the answer. It’s getting the job done.

Dr. Wilson: Would you agree, Dr. Johnson, that for patients that really don’t want to do the colonoscopy for one reason or another, and you’ve done your best in explaining what you think the risks and benefits are, that you’d rather have them get something than nothing?

Dr. Johnson: Absolutely. It comes down to what I recommend and then what you decide. But I still make the point explicit: If we’ve gone through those checkpoints and it’s positive, we agree that you understand that colonoscopy is the next step.

Final take-home messages

Dr. Wilson: Dr. Lin, I’ll turn the last word over to you, as the person who is probably discussing the choice of screening modalities more than any of us, before someone would get referred to someone like Dr. Johnson. What’s your final take-home message about the NEJM study and the state of colon cancer screening in the United States?

Dr. Lin: My take-home points about the study are that there were some limitations, but it is good to finally have a randomized trial of colonoscopy screening 2 decades after we really started doing that in the United States. It won’t immediately change – nor do I think it should – the way we practice and discuss different options. I think that some of Dr. Johnson’s points about making sure that whoever’s doing the colonoscopies for your practices is doing it in a high-quality way are really important. Just as it’s important, if you’re doing the fecal tests, to make sure that all patients who have positives get expeditiously referred for colonoscopy.

Dr. Johnson: Perry, I’d like to make one concluding comment as the gastroenterology expert in this discussion. I’ve had countless questions about this study from my patients and my peers. I tell them the following: Don’t let the headlines mislead you.

When you look at this study, the instrument is not so much the question. We know that getting the test is the first step in colon cancer screening. But we also know that getting the test done, with the highest-quality providers and the best-quality performance, is really the key to optimizing the true value of colonoscopy for colon cancer prevention.

So please don’t lose sight of this when reading the headlines in the media around this study. We really need to analyze the true characteristics of what we call a quality performance, because that’s what drives success and that’s what prevents colon cancer.

Dr. Wilson: Dr. Johnson and Dr. Lin, thank you very much. I appreciate you spending time with me here today and wish you all the best.

I guess I’ll sum up by saying that if you’re getting a colonoscopy, make sure it’s a good one. But do get screened.

This video originally appeared on WebMD. A transcript appeared on Medscape.com.