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Increased stroke risk linked with excess sitting in those under 60
While the risk of stroke increased more than fourfold among sedentary people under the age of 60, no significant increase in risk was observed among older individuals, according to the study based on self-reported data from more than 140,000 people. This highlights the need for relevant public health messaging directed at younger people, reported lead author, Raed A. Joundi, MD, DPhil, a stroke fellow at the University of Calgary (Alta.), and colleagues, in the paper published in Stroke.
“Sedentary time has increased over the past 2 decades in the United States and Canada, particularly in the young, raising the importance of characterizing its effect on long-term health , ” the investigators wrote. “A better understanding of the risk of sedentary time specific to stroke may be important for public health campaigns to reduce sedentary behavior.” Dr. Joundi and colleagues reviewed data from the Canadian Community Health Survey, including 143,180 healthy individuals without baseline history of cancer, heart disease, or stroke. Those under the age of 40 years were also excluded from the analysis.
Excess sedentary leisure time was defined as 8 or more hours of sedentary leisure time per day, whereas low physical activity was defined as less than 3.5 metabolic equivalent hours per week. The analysis also included a range of demographic and medical covariates, such as age, sex, marital status, smoking status, presence of hypertension, and others.
After a median follow-up of 9.4 years, 2,965 stroke events occurred, with a median time from survey response of 5.6 years. Risk of stroke among individuals aged younger than 60 years who engaged in low physical activity and excess sedentary leisure time was increased 4.5-fold, compared with individuals with low physical activity who were sedentary less than 4 hours per day (fully adjusted hazard ratio, 4.50; 95% confidence interval, 1.64-12.3).
Findings highlight benefits of physical activity
Similar risk elevations were not observed among individuals aged 60-79 years, or those older than 80. And among people younger than 60, high physical activity appeared to eliminate the additional risk imposed by excess sedentary leisure time.
“Sedentary time is associated with higher risk of stroke in inactive individuals, but not an active individual, ” Dr. Joundi said in an interview. “So it suggests that there’s two ways to lower risk: One would be to lower your sedentary time, and the other would be to engage in physical activity.”
These interpretations are speculative, Dr. Joundi cautioned, as the study was not interventional. Even so, he said that the findings “bring the spotlight back on physical activity,” thereby aligning with previous research.
“The more you exercise, the more that relationship between sedentary time and poor health outcomes is blunted, and in fact, can be completely negated with enough physical activity,” he said.
How exactly physical activity offers such protection remains unclear, Dr. Joundi added. He speculated that regularity of exercise may be key, with each session counteracting the adverse effects of prolonged sedentary time, which may include reduced blood flow, increased insulin resistance, and inflammatory changes that can affect blood vessels.
“This study is particularly a message for younger individuals,” Dr. Joundi said, suggesting that the findings may alter behavior, as many people have witnessed, or are aware of, the long-term impacts of stroke.
“There’s a sort of social or cognitive aversion to stroke, I think, in the general population, because of how disabling it can be, and how it can lower your quality of life,” he said.
Subtle lifestyle changes may be enough.
For those aiming to lower their risk of stroke, Dr. Joundi suggested that subtle lifestyle changes may be enough.
“Ultimately, what we saw is that even minimal amounts of physical activity – walking 3 hours a week, for example – could blunt the impact of sedentary time,” he said. “Doing what you can, even if it’s a small amount, tends to be quite meaningful over a long period of time.”
Daniel T. Lackland, DrPH, professor of epidemiology in the department of neurology at the Medical University of South Carolina, Charleston, offered a similar takeaway, noting that small efforts can lead to great benefits.
“Less intense activity is still better than being sedentary,” he said in an interview. “For many people, if you do get up and you just walk around, move your arms around – do any kind of movement – that’s better than being sedentary.”
Dr. Lackland applauded the practicality of studying sedentary leisure time, versus overall leisure time, as many people can’t control their work environment.
“You can’t do very much about how you work your job,” Dr. Lackland said. “Sometimes we have to sit, and I guess there are things you can do – you can put a treadmill instead of a chair and that kind of thing – but more often than not, you don’t really have that choice to do something. With leisure time, though, you’re in full control. And so what do you do with your leisure time? Do you sit and watch TV, or do you engage in some type of activity? Not necessarily aerobic activity, but some type of activity that would not let you be sedentary. You want to be active as much as you possibly can.”
Dr. Joundi disclosed grant support from the Canadian Institutes of Health Research. The other investigators and Dr. Lackland reported no relevant disclosures.
While the risk of stroke increased more than fourfold among sedentary people under the age of 60, no significant increase in risk was observed among older individuals, according to the study based on self-reported data from more than 140,000 people. This highlights the need for relevant public health messaging directed at younger people, reported lead author, Raed A. Joundi, MD, DPhil, a stroke fellow at the University of Calgary (Alta.), and colleagues, in the paper published in Stroke.
“Sedentary time has increased over the past 2 decades in the United States and Canada, particularly in the young, raising the importance of characterizing its effect on long-term health , ” the investigators wrote. “A better understanding of the risk of sedentary time specific to stroke may be important for public health campaigns to reduce sedentary behavior.” Dr. Joundi and colleagues reviewed data from the Canadian Community Health Survey, including 143,180 healthy individuals without baseline history of cancer, heart disease, or stroke. Those under the age of 40 years were also excluded from the analysis.
Excess sedentary leisure time was defined as 8 or more hours of sedentary leisure time per day, whereas low physical activity was defined as less than 3.5 metabolic equivalent hours per week. The analysis also included a range of demographic and medical covariates, such as age, sex, marital status, smoking status, presence of hypertension, and others.
After a median follow-up of 9.4 years, 2,965 stroke events occurred, with a median time from survey response of 5.6 years. Risk of stroke among individuals aged younger than 60 years who engaged in low physical activity and excess sedentary leisure time was increased 4.5-fold, compared with individuals with low physical activity who were sedentary less than 4 hours per day (fully adjusted hazard ratio, 4.50; 95% confidence interval, 1.64-12.3).
Findings highlight benefits of physical activity
Similar risk elevations were not observed among individuals aged 60-79 years, or those older than 80. And among people younger than 60, high physical activity appeared to eliminate the additional risk imposed by excess sedentary leisure time.
“Sedentary time is associated with higher risk of stroke in inactive individuals, but not an active individual, ” Dr. Joundi said in an interview. “So it suggests that there’s two ways to lower risk: One would be to lower your sedentary time, and the other would be to engage in physical activity.”
These interpretations are speculative, Dr. Joundi cautioned, as the study was not interventional. Even so, he said that the findings “bring the spotlight back on physical activity,” thereby aligning with previous research.
“The more you exercise, the more that relationship between sedentary time and poor health outcomes is blunted, and in fact, can be completely negated with enough physical activity,” he said.
How exactly physical activity offers such protection remains unclear, Dr. Joundi added. He speculated that regularity of exercise may be key, with each session counteracting the adverse effects of prolonged sedentary time, which may include reduced blood flow, increased insulin resistance, and inflammatory changes that can affect blood vessels.
“This study is particularly a message for younger individuals,” Dr. Joundi said, suggesting that the findings may alter behavior, as many people have witnessed, or are aware of, the long-term impacts of stroke.
“There’s a sort of social or cognitive aversion to stroke, I think, in the general population, because of how disabling it can be, and how it can lower your quality of life,” he said.
Subtle lifestyle changes may be enough.
For those aiming to lower their risk of stroke, Dr. Joundi suggested that subtle lifestyle changes may be enough.
“Ultimately, what we saw is that even minimal amounts of physical activity – walking 3 hours a week, for example – could blunt the impact of sedentary time,” he said. “Doing what you can, even if it’s a small amount, tends to be quite meaningful over a long period of time.”
Daniel T. Lackland, DrPH, professor of epidemiology in the department of neurology at the Medical University of South Carolina, Charleston, offered a similar takeaway, noting that small efforts can lead to great benefits.
“Less intense activity is still better than being sedentary,” he said in an interview. “For many people, if you do get up and you just walk around, move your arms around – do any kind of movement – that’s better than being sedentary.”
Dr. Lackland applauded the practicality of studying sedentary leisure time, versus overall leisure time, as many people can’t control their work environment.
“You can’t do very much about how you work your job,” Dr. Lackland said. “Sometimes we have to sit, and I guess there are things you can do – you can put a treadmill instead of a chair and that kind of thing – but more often than not, you don’t really have that choice to do something. With leisure time, though, you’re in full control. And so what do you do with your leisure time? Do you sit and watch TV, or do you engage in some type of activity? Not necessarily aerobic activity, but some type of activity that would not let you be sedentary. You want to be active as much as you possibly can.”
Dr. Joundi disclosed grant support from the Canadian Institutes of Health Research. The other investigators and Dr. Lackland reported no relevant disclosures.
While the risk of stroke increased more than fourfold among sedentary people under the age of 60, no significant increase in risk was observed among older individuals, according to the study based on self-reported data from more than 140,000 people. This highlights the need for relevant public health messaging directed at younger people, reported lead author, Raed A. Joundi, MD, DPhil, a stroke fellow at the University of Calgary (Alta.), and colleagues, in the paper published in Stroke.
“Sedentary time has increased over the past 2 decades in the United States and Canada, particularly in the young, raising the importance of characterizing its effect on long-term health , ” the investigators wrote. “A better understanding of the risk of sedentary time specific to stroke may be important for public health campaigns to reduce sedentary behavior.” Dr. Joundi and colleagues reviewed data from the Canadian Community Health Survey, including 143,180 healthy individuals without baseline history of cancer, heart disease, or stroke. Those under the age of 40 years were also excluded from the analysis.
Excess sedentary leisure time was defined as 8 or more hours of sedentary leisure time per day, whereas low physical activity was defined as less than 3.5 metabolic equivalent hours per week. The analysis also included a range of demographic and medical covariates, such as age, sex, marital status, smoking status, presence of hypertension, and others.
After a median follow-up of 9.4 years, 2,965 stroke events occurred, with a median time from survey response of 5.6 years. Risk of stroke among individuals aged younger than 60 years who engaged in low physical activity and excess sedentary leisure time was increased 4.5-fold, compared with individuals with low physical activity who were sedentary less than 4 hours per day (fully adjusted hazard ratio, 4.50; 95% confidence interval, 1.64-12.3).
Findings highlight benefits of physical activity
Similar risk elevations were not observed among individuals aged 60-79 years, or those older than 80. And among people younger than 60, high physical activity appeared to eliminate the additional risk imposed by excess sedentary leisure time.
“Sedentary time is associated with higher risk of stroke in inactive individuals, but not an active individual, ” Dr. Joundi said in an interview. “So it suggests that there’s two ways to lower risk: One would be to lower your sedentary time, and the other would be to engage in physical activity.”
These interpretations are speculative, Dr. Joundi cautioned, as the study was not interventional. Even so, he said that the findings “bring the spotlight back on physical activity,” thereby aligning with previous research.
“The more you exercise, the more that relationship between sedentary time and poor health outcomes is blunted, and in fact, can be completely negated with enough physical activity,” he said.
How exactly physical activity offers such protection remains unclear, Dr. Joundi added. He speculated that regularity of exercise may be key, with each session counteracting the adverse effects of prolonged sedentary time, which may include reduced blood flow, increased insulin resistance, and inflammatory changes that can affect blood vessels.
“This study is particularly a message for younger individuals,” Dr. Joundi said, suggesting that the findings may alter behavior, as many people have witnessed, or are aware of, the long-term impacts of stroke.
“There’s a sort of social or cognitive aversion to stroke, I think, in the general population, because of how disabling it can be, and how it can lower your quality of life,” he said.
Subtle lifestyle changes may be enough.
For those aiming to lower their risk of stroke, Dr. Joundi suggested that subtle lifestyle changes may be enough.
“Ultimately, what we saw is that even minimal amounts of physical activity – walking 3 hours a week, for example – could blunt the impact of sedentary time,” he said. “Doing what you can, even if it’s a small amount, tends to be quite meaningful over a long period of time.”
Daniel T. Lackland, DrPH, professor of epidemiology in the department of neurology at the Medical University of South Carolina, Charleston, offered a similar takeaway, noting that small efforts can lead to great benefits.
“Less intense activity is still better than being sedentary,” he said in an interview. “For many people, if you do get up and you just walk around, move your arms around – do any kind of movement – that’s better than being sedentary.”
Dr. Lackland applauded the practicality of studying sedentary leisure time, versus overall leisure time, as many people can’t control their work environment.
“You can’t do very much about how you work your job,” Dr. Lackland said. “Sometimes we have to sit, and I guess there are things you can do – you can put a treadmill instead of a chair and that kind of thing – but more often than not, you don’t really have that choice to do something. With leisure time, though, you’re in full control. And so what do you do with your leisure time? Do you sit and watch TV, or do you engage in some type of activity? Not necessarily aerobic activity, but some type of activity that would not let you be sedentary. You want to be active as much as you possibly can.”
Dr. Joundi disclosed grant support from the Canadian Institutes of Health Research. The other investigators and Dr. Lackland reported no relevant disclosures.
FROM STROKE
AGA Clinical Practice Update: Expert Review on colonoscopy quality improvement
The American Gastroenterological Association recently issued a clinical practice update expert review outlining tenets of high-quality colonoscopy screening and surveillance.
The update includes 15 best practice advice statements aimed at the endoscopist and/or endoscopy unit, reported lead author Rajesh N. Keswani, MD, of Northwestern University, Chicago, and colleagues.
“The efficacy of colonoscopy varies widely among endoscopists, and lower-quality colonoscopies are associated with higher interval CRC [colorectal cancer] incidence and mortality,” the investigators wrote in Gastroenterology.
According to Dr. Keswani and colleagues, quality of colonoscopy screening and surveillance is shaped by three parameters: safety, effectiveness, and value. Some metrics may be best measured at a unit level, they noted, while others are more clinician specific.
“For uncommon outcomes (e.g., adverse events) or metrics that reflect system-based practice (e.g., bowel preparation quality), measurement of aggregate unit-level performance is best,” the investigators wrote. “In contrast, for metrics that primarily reflect colonoscopist skill (e.g., adenoma detection rate), endoscopist-level measurement is preferred to enable individual feedback.”
Endoscopy unit best practice advice
According to the update, endoscopy units should prepare patients for, and monitor, adverse events. Prior to the procedure, patients should be informed about possible adverse events and warning symptoms, and emergency contact information should be recorded. Following the procedure, systematic monitoring of delayed adverse events may be considered, including “postprocedure bleeding, perforation, hospital readmission, 30-day mortality, and/or interval colorectal cancer cases,” with rates reported at the unit level.
Ensuring high-quality bowel preparation is also the responsibility of the endoscopy unit, according to Dr. Keswani and colleagues, and should be measured at least annually. Units should aim for a Boston Bowel Preparation Scale score of at least 6, with each segment scoring at least 2, in at least 90% of colonoscopies. The update provides best practice advice on split-dose bowel prep, with patient instructions written at a sixth-grade level in their native language. If routine quality measurement reveals suboptimal bowel prep quality, instruction revision may be needed, as well as further patient education and support.
During the actual procedure, a high-definition colonoscope should be used, the expert panel wrote. They called for measurement of endoscopist performance via four parameters: cecal intubation rate, which should be at least 90%; mean withdrawal time, which should be at least 6 minutes (aspirational, ≥9 minutes); adenoma detection rate, measured annually or when a given endoscopist has accrued 250 screening colonoscopies; and serrated lesion detection rate.
Endoscopist best practice advice
Both adenoma detection rate and serrated lesion detection rate should also be measured at an endoscopist level, with rates of at least 30% for adenomas and at least 7% for serrated lesions (aspirational, ≥35% and ≥10%, respectively).
“If rates are low, improvement efforts should be oriented toward both colonoscopists and pathologists,” the investigators noted.
A variety of strategies are advised to improve outcomes at the endoscopist level, including a second look at the right colon to detect polyps, either in forward or retroflexed view; use of cold-snare polypectomy for nonpedunculated polyps 3-9 mm in size and avoidance of forceps in polyps greater than 2 mm in size; evaluation by an expert in polypectomy with attempted resection for patients with complex polyps lacking “overt malignant endoscopic features or pathology consistent with invasive adenocarcinoma”; and thorough documentation of all findings.
More broadly, the update advises endoscopists to follow guideline-recommended intervals for screening and surveillance, including repeat colonoscopy in 3 years for all patients with advanced adenomas versus a 10-year interval for patients with normal risk or “only distal hyperplastic polyps.”
Resource-limited institutions and a look ahead
Dr. Keswani and colleagues concluded the clinical practice update with a nod to the challenges of real-world practice, noting that some institutions may not have the resources to comply with all the best practice advice statements.
“If limited resources are available, measurement of cecal intubation rates, bowel preparation quality, and adenoma detection rate should be prioritized,” they wrote.
They also offered a succinct summary of outstanding research needs, saying “we anticipate future work to clarify optimal polyp resection techniques, refine surveillance intervals based on provider skill and patient risk, and highlight the benefits of artificial intelligence in improving colonoscopy quality.”
This clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Keswani consults for Boston Scientific. The other authors had no disclosures.
This article was updated Aug. 20, 2021.
The American Gastroenterological Association recently issued a clinical practice update expert review outlining tenets of high-quality colonoscopy screening and surveillance.
The update includes 15 best practice advice statements aimed at the endoscopist and/or endoscopy unit, reported lead author Rajesh N. Keswani, MD, of Northwestern University, Chicago, and colleagues.
“The efficacy of colonoscopy varies widely among endoscopists, and lower-quality colonoscopies are associated with higher interval CRC [colorectal cancer] incidence and mortality,” the investigators wrote in Gastroenterology.
According to Dr. Keswani and colleagues, quality of colonoscopy screening and surveillance is shaped by three parameters: safety, effectiveness, and value. Some metrics may be best measured at a unit level, they noted, while others are more clinician specific.
“For uncommon outcomes (e.g., adverse events) or metrics that reflect system-based practice (e.g., bowel preparation quality), measurement of aggregate unit-level performance is best,” the investigators wrote. “In contrast, for metrics that primarily reflect colonoscopist skill (e.g., adenoma detection rate), endoscopist-level measurement is preferred to enable individual feedback.”
Endoscopy unit best practice advice
According to the update, endoscopy units should prepare patients for, and monitor, adverse events. Prior to the procedure, patients should be informed about possible adverse events and warning symptoms, and emergency contact information should be recorded. Following the procedure, systematic monitoring of delayed adverse events may be considered, including “postprocedure bleeding, perforation, hospital readmission, 30-day mortality, and/or interval colorectal cancer cases,” with rates reported at the unit level.
Ensuring high-quality bowel preparation is also the responsibility of the endoscopy unit, according to Dr. Keswani and colleagues, and should be measured at least annually. Units should aim for a Boston Bowel Preparation Scale score of at least 6, with each segment scoring at least 2, in at least 90% of colonoscopies. The update provides best practice advice on split-dose bowel prep, with patient instructions written at a sixth-grade level in their native language. If routine quality measurement reveals suboptimal bowel prep quality, instruction revision may be needed, as well as further patient education and support.
During the actual procedure, a high-definition colonoscope should be used, the expert panel wrote. They called for measurement of endoscopist performance via four parameters: cecal intubation rate, which should be at least 90%; mean withdrawal time, which should be at least 6 minutes (aspirational, ≥9 minutes); adenoma detection rate, measured annually or when a given endoscopist has accrued 250 screening colonoscopies; and serrated lesion detection rate.
Endoscopist best practice advice
Both adenoma detection rate and serrated lesion detection rate should also be measured at an endoscopist level, with rates of at least 30% for adenomas and at least 7% for serrated lesions (aspirational, ≥35% and ≥10%, respectively).
“If rates are low, improvement efforts should be oriented toward both colonoscopists and pathologists,” the investigators noted.
A variety of strategies are advised to improve outcomes at the endoscopist level, including a second look at the right colon to detect polyps, either in forward or retroflexed view; use of cold-snare polypectomy for nonpedunculated polyps 3-9 mm in size and avoidance of forceps in polyps greater than 2 mm in size; evaluation by an expert in polypectomy with attempted resection for patients with complex polyps lacking “overt malignant endoscopic features or pathology consistent with invasive adenocarcinoma”; and thorough documentation of all findings.
More broadly, the update advises endoscopists to follow guideline-recommended intervals for screening and surveillance, including repeat colonoscopy in 3 years for all patients with advanced adenomas versus a 10-year interval for patients with normal risk or “only distal hyperplastic polyps.”
Resource-limited institutions and a look ahead
Dr. Keswani and colleagues concluded the clinical practice update with a nod to the challenges of real-world practice, noting that some institutions may not have the resources to comply with all the best practice advice statements.
“If limited resources are available, measurement of cecal intubation rates, bowel preparation quality, and adenoma detection rate should be prioritized,” they wrote.
They also offered a succinct summary of outstanding research needs, saying “we anticipate future work to clarify optimal polyp resection techniques, refine surveillance intervals based on provider skill and patient risk, and highlight the benefits of artificial intelligence in improving colonoscopy quality.”
This clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Keswani consults for Boston Scientific. The other authors had no disclosures.
This article was updated Aug. 20, 2021.
The American Gastroenterological Association recently issued a clinical practice update expert review outlining tenets of high-quality colonoscopy screening and surveillance.
The update includes 15 best practice advice statements aimed at the endoscopist and/or endoscopy unit, reported lead author Rajesh N. Keswani, MD, of Northwestern University, Chicago, and colleagues.
“The efficacy of colonoscopy varies widely among endoscopists, and lower-quality colonoscopies are associated with higher interval CRC [colorectal cancer] incidence and mortality,” the investigators wrote in Gastroenterology.
According to Dr. Keswani and colleagues, quality of colonoscopy screening and surveillance is shaped by three parameters: safety, effectiveness, and value. Some metrics may be best measured at a unit level, they noted, while others are more clinician specific.
“For uncommon outcomes (e.g., adverse events) or metrics that reflect system-based practice (e.g., bowel preparation quality), measurement of aggregate unit-level performance is best,” the investigators wrote. “In contrast, for metrics that primarily reflect colonoscopist skill (e.g., adenoma detection rate), endoscopist-level measurement is preferred to enable individual feedback.”
Endoscopy unit best practice advice
According to the update, endoscopy units should prepare patients for, and monitor, adverse events. Prior to the procedure, patients should be informed about possible adverse events and warning symptoms, and emergency contact information should be recorded. Following the procedure, systematic monitoring of delayed adverse events may be considered, including “postprocedure bleeding, perforation, hospital readmission, 30-day mortality, and/or interval colorectal cancer cases,” with rates reported at the unit level.
Ensuring high-quality bowel preparation is also the responsibility of the endoscopy unit, according to Dr. Keswani and colleagues, and should be measured at least annually. Units should aim for a Boston Bowel Preparation Scale score of at least 6, with each segment scoring at least 2, in at least 90% of colonoscopies. The update provides best practice advice on split-dose bowel prep, with patient instructions written at a sixth-grade level in their native language. If routine quality measurement reveals suboptimal bowel prep quality, instruction revision may be needed, as well as further patient education and support.
During the actual procedure, a high-definition colonoscope should be used, the expert panel wrote. They called for measurement of endoscopist performance via four parameters: cecal intubation rate, which should be at least 90%; mean withdrawal time, which should be at least 6 minutes (aspirational, ≥9 minutes); adenoma detection rate, measured annually or when a given endoscopist has accrued 250 screening colonoscopies; and serrated lesion detection rate.
Endoscopist best practice advice
Both adenoma detection rate and serrated lesion detection rate should also be measured at an endoscopist level, with rates of at least 30% for adenomas and at least 7% for serrated lesions (aspirational, ≥35% and ≥10%, respectively).
“If rates are low, improvement efforts should be oriented toward both colonoscopists and pathologists,” the investigators noted.
A variety of strategies are advised to improve outcomes at the endoscopist level, including a second look at the right colon to detect polyps, either in forward or retroflexed view; use of cold-snare polypectomy for nonpedunculated polyps 3-9 mm in size and avoidance of forceps in polyps greater than 2 mm in size; evaluation by an expert in polypectomy with attempted resection for patients with complex polyps lacking “overt malignant endoscopic features or pathology consistent with invasive adenocarcinoma”; and thorough documentation of all findings.
More broadly, the update advises endoscopists to follow guideline-recommended intervals for screening and surveillance, including repeat colonoscopy in 3 years for all patients with advanced adenomas versus a 10-year interval for patients with normal risk or “only distal hyperplastic polyps.”
Resource-limited institutions and a look ahead
Dr. Keswani and colleagues concluded the clinical practice update with a nod to the challenges of real-world practice, noting that some institutions may not have the resources to comply with all the best practice advice statements.
“If limited resources are available, measurement of cecal intubation rates, bowel preparation quality, and adenoma detection rate should be prioritized,” they wrote.
They also offered a succinct summary of outstanding research needs, saying “we anticipate future work to clarify optimal polyp resection techniques, refine surveillance intervals based on provider skill and patient risk, and highlight the benefits of artificial intelligence in improving colonoscopy quality.”
This clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Keswani consults for Boston Scientific. The other authors had no disclosures.
This article was updated Aug. 20, 2021.
FROM GASTROENTEROLOGY
CAG Clinical Practice Guideline: Vaccination in patients with IBD
The Canadian Association of Gastroenterology (CAG) has published a two-part clinical practice guideline for immunizing patients with inflammatory bowel disease (IBD) that covers both live and inactivated vaccines across pediatric and adult patients.
The guideline, which has been endorsed by the American Gastroenterological Association, is composed of recommendations drawn from a broader body of data than prior publications on the same topic, according to Eric I. Benchimol, MD, PhD, of the University of Ottawa and the University of Toronto, and colleagues.
“Previous guidelines on immunizations of patients with IBD considered only the limited available evidence of vaccine safety and effectiveness in IBD populations, and failed to consider the ample evidence available in the general population or in other immune-mediated inflammatory diseases when assessing the certainty of evidence or developing their recommendations,” they wrote in Gastroenterology.
Part 1: Live vaccine recommendations
The first part of the guideline includes seven recommendations for use of live vaccines in patients with IBD.
In this area, decision-making is largely dependent upon use of immunosuppressive therapy, which the investigators defined as “corticosteroids, thiopurines, biologics, small molecules such as JAK [Janus kinase] inhibitors, and combinations thereof,” with the caveat that “there is no standard definition of immunosuppression,” and “the degree to which immunosuppressive therapy causes clinically significant immunosuppression generally is dose related and varies by drug.”
Before offering specific recommendations, Dr. Benchimol and colleagues provided three general principles to abide by: 1. Clinicians should review each patient’s history of immunization and vaccine-preventable diseases at diagnosis and on a routine basis; 2. Appropriate vaccinations should ideally be given prior to starting immunosuppressive therapy; and 3. Immunosuppressive therapy (when urgently needed) should not be delayed so that immunizations can be given in advance.
“[Delaying therapy] could lead to more anticipated harms than benefits, due to the risk of progression of the inflammatory activity and resulting complications,” the investigators wrote.
Specific recommendations in the guideline address measles, mumps, and rubella (MMR); and varicella. Both vaccines are recommended for susceptible pediatric and adult patients not taking immunosuppressive therapy. In contrast, neither vaccine is recommended for immunosuppressed patients of any age. Certainty of evidence ranged from very low to moderate.
Concerning vaccination within the first 6 months of life for infants born of mothers taking biologics, the expert panel did not reach a consensus.
“[T]he group was unable to recommend for or against their routine use because the desirable and undesirable effects were closely balanced and the evidence on safety outcomes was insufficient to justify a recommendation,” wrote Dr. Benchimol and colleagues. “Health care providers should be cautious with the administration of live vaccines in the first year of life in the infants of mothers using biologics. These infants should be evaluated by clinicians with expertise in the impact of exposure to monoclonal antibody biologics in utero.”
Part 2: Inactivated vaccine recommendations
The second part of the guideline, by lead author Jennifer L. Jones, MD, of Dalhousie University, Queen Elizabeth II Health Sciences Center, Halifax, N.S., and colleagues, provides 15 recommendations for giving inactivated vaccines to patients with IBD.
The panel considered eight vaccines: Haemophilus influenzae type B (Hib); herpes zoster (HZ); hepatitis B; influenza; Streptococcus pneumoniae (pneumococcal vaccine); Neisseria meningitidis (meningococcal vaccine); human papillomavirus (HPV); and diphtheria, tetanus, and pertussis.
Generally, the above vaccines are recommended on an age-appropriate basis, regardless of immunosuppression status, albeit with varying levels of confidence. For example, the Hib vaccine is strongly recommended for pediatric patients 5 years and younger, whereas the same recommendation for older children and adults is conditional.
For several patient populations and vaccines, the guideline panel did not reach a consensus, including use of double-dose hepatitis B vaccine for immunosuppressed adults, timing seasonal flu shots with dosing of biologics, use of pneumococcal vaccines in nonimmunosuppressed patents without a risk factor for pneumococcal disease, use of meningococcal vaccines in adults not at risk for invasive meningococcal disease, and use of HPV vaccine in patients aged 27-45 years.
While immunosuppressive therapy is not a contraindication for giving inactivated vaccines, Dr. Jones and colleagues noted that immunosuppression may hinder vaccine responses.
“Given that patients with IBD on immunosuppressive therapy may have lower immune response to vaccine, further research will be needed to assess the safety and effectiveness of high-dose vs. standard-dose vaccination strategy,” they wrote, also noting that more work is needed to determine if accelerated vaccinations strategies may be feasible prior to initiation of immunosuppressive therapy.
Because of a lack of evidence, the guideline panel did not issue IBD-specific recommendations for vaccines against SARS-CoV-2; however, Dr. Jones and colleagues suggested that clinicians reference a CAG publication on the subject published earlier this year.
The guideline was supported by grants to the Canadian Association of Gastroenterology from the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes; and CANImmunize. Dr. Benchimol disclosed additional relationships with the Canadian Institutes of Health Research, Crohn’s and Colitis Canada; and the Canadian Child Health Clinician Scientist Program.
The Canadian Association of Gastroenterology (CAG) has published a two-part clinical practice guideline for immunizing patients with inflammatory bowel disease (IBD) that covers both live and inactivated vaccines across pediatric and adult patients.
The guideline, which has been endorsed by the American Gastroenterological Association, is composed of recommendations drawn from a broader body of data than prior publications on the same topic, according to Eric I. Benchimol, MD, PhD, of the University of Ottawa and the University of Toronto, and colleagues.
“Previous guidelines on immunizations of patients with IBD considered only the limited available evidence of vaccine safety and effectiveness in IBD populations, and failed to consider the ample evidence available in the general population or in other immune-mediated inflammatory diseases when assessing the certainty of evidence or developing their recommendations,” they wrote in Gastroenterology.
Part 1: Live vaccine recommendations
The first part of the guideline includes seven recommendations for use of live vaccines in patients with IBD.
In this area, decision-making is largely dependent upon use of immunosuppressive therapy, which the investigators defined as “corticosteroids, thiopurines, biologics, small molecules such as JAK [Janus kinase] inhibitors, and combinations thereof,” with the caveat that “there is no standard definition of immunosuppression,” and “the degree to which immunosuppressive therapy causes clinically significant immunosuppression generally is dose related and varies by drug.”
Before offering specific recommendations, Dr. Benchimol and colleagues provided three general principles to abide by: 1. Clinicians should review each patient’s history of immunization and vaccine-preventable diseases at diagnosis and on a routine basis; 2. Appropriate vaccinations should ideally be given prior to starting immunosuppressive therapy; and 3. Immunosuppressive therapy (when urgently needed) should not be delayed so that immunizations can be given in advance.
“[Delaying therapy] could lead to more anticipated harms than benefits, due to the risk of progression of the inflammatory activity and resulting complications,” the investigators wrote.
Specific recommendations in the guideline address measles, mumps, and rubella (MMR); and varicella. Both vaccines are recommended for susceptible pediatric and adult patients not taking immunosuppressive therapy. In contrast, neither vaccine is recommended for immunosuppressed patients of any age. Certainty of evidence ranged from very low to moderate.
Concerning vaccination within the first 6 months of life for infants born of mothers taking biologics, the expert panel did not reach a consensus.
“[T]he group was unable to recommend for or against their routine use because the desirable and undesirable effects were closely balanced and the evidence on safety outcomes was insufficient to justify a recommendation,” wrote Dr. Benchimol and colleagues. “Health care providers should be cautious with the administration of live vaccines in the first year of life in the infants of mothers using biologics. These infants should be evaluated by clinicians with expertise in the impact of exposure to monoclonal antibody biologics in utero.”
Part 2: Inactivated vaccine recommendations
The second part of the guideline, by lead author Jennifer L. Jones, MD, of Dalhousie University, Queen Elizabeth II Health Sciences Center, Halifax, N.S., and colleagues, provides 15 recommendations for giving inactivated vaccines to patients with IBD.
The panel considered eight vaccines: Haemophilus influenzae type B (Hib); herpes zoster (HZ); hepatitis B; influenza; Streptococcus pneumoniae (pneumococcal vaccine); Neisseria meningitidis (meningococcal vaccine); human papillomavirus (HPV); and diphtheria, tetanus, and pertussis.
Generally, the above vaccines are recommended on an age-appropriate basis, regardless of immunosuppression status, albeit with varying levels of confidence. For example, the Hib vaccine is strongly recommended for pediatric patients 5 years and younger, whereas the same recommendation for older children and adults is conditional.
For several patient populations and vaccines, the guideline panel did not reach a consensus, including use of double-dose hepatitis B vaccine for immunosuppressed adults, timing seasonal flu shots with dosing of biologics, use of pneumococcal vaccines in nonimmunosuppressed patents without a risk factor for pneumococcal disease, use of meningococcal vaccines in adults not at risk for invasive meningococcal disease, and use of HPV vaccine in patients aged 27-45 years.
While immunosuppressive therapy is not a contraindication for giving inactivated vaccines, Dr. Jones and colleagues noted that immunosuppression may hinder vaccine responses.
“Given that patients with IBD on immunosuppressive therapy may have lower immune response to vaccine, further research will be needed to assess the safety and effectiveness of high-dose vs. standard-dose vaccination strategy,” they wrote, also noting that more work is needed to determine if accelerated vaccinations strategies may be feasible prior to initiation of immunosuppressive therapy.
Because of a lack of evidence, the guideline panel did not issue IBD-specific recommendations for vaccines against SARS-CoV-2; however, Dr. Jones and colleagues suggested that clinicians reference a CAG publication on the subject published earlier this year.
The guideline was supported by grants to the Canadian Association of Gastroenterology from the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes; and CANImmunize. Dr. Benchimol disclosed additional relationships with the Canadian Institutes of Health Research, Crohn’s and Colitis Canada; and the Canadian Child Health Clinician Scientist Program.
The Canadian Association of Gastroenterology (CAG) has published a two-part clinical practice guideline for immunizing patients with inflammatory bowel disease (IBD) that covers both live and inactivated vaccines across pediatric and adult patients.
The guideline, which has been endorsed by the American Gastroenterological Association, is composed of recommendations drawn from a broader body of data than prior publications on the same topic, according to Eric I. Benchimol, MD, PhD, of the University of Ottawa and the University of Toronto, and colleagues.
“Previous guidelines on immunizations of patients with IBD considered only the limited available evidence of vaccine safety and effectiveness in IBD populations, and failed to consider the ample evidence available in the general population or in other immune-mediated inflammatory diseases when assessing the certainty of evidence or developing their recommendations,” they wrote in Gastroenterology.
Part 1: Live vaccine recommendations
The first part of the guideline includes seven recommendations for use of live vaccines in patients with IBD.
In this area, decision-making is largely dependent upon use of immunosuppressive therapy, which the investigators defined as “corticosteroids, thiopurines, biologics, small molecules such as JAK [Janus kinase] inhibitors, and combinations thereof,” with the caveat that “there is no standard definition of immunosuppression,” and “the degree to which immunosuppressive therapy causes clinically significant immunosuppression generally is dose related and varies by drug.”
Before offering specific recommendations, Dr. Benchimol and colleagues provided three general principles to abide by: 1. Clinicians should review each patient’s history of immunization and vaccine-preventable diseases at diagnosis and on a routine basis; 2. Appropriate vaccinations should ideally be given prior to starting immunosuppressive therapy; and 3. Immunosuppressive therapy (when urgently needed) should not be delayed so that immunizations can be given in advance.
“[Delaying therapy] could lead to more anticipated harms than benefits, due to the risk of progression of the inflammatory activity and resulting complications,” the investigators wrote.
Specific recommendations in the guideline address measles, mumps, and rubella (MMR); and varicella. Both vaccines are recommended for susceptible pediatric and adult patients not taking immunosuppressive therapy. In contrast, neither vaccine is recommended for immunosuppressed patients of any age. Certainty of evidence ranged from very low to moderate.
Concerning vaccination within the first 6 months of life for infants born of mothers taking biologics, the expert panel did not reach a consensus.
“[T]he group was unable to recommend for or against their routine use because the desirable and undesirable effects were closely balanced and the evidence on safety outcomes was insufficient to justify a recommendation,” wrote Dr. Benchimol and colleagues. “Health care providers should be cautious with the administration of live vaccines in the first year of life in the infants of mothers using biologics. These infants should be evaluated by clinicians with expertise in the impact of exposure to monoclonal antibody biologics in utero.”
Part 2: Inactivated vaccine recommendations
The second part of the guideline, by lead author Jennifer L. Jones, MD, of Dalhousie University, Queen Elizabeth II Health Sciences Center, Halifax, N.S., and colleagues, provides 15 recommendations for giving inactivated vaccines to patients with IBD.
The panel considered eight vaccines: Haemophilus influenzae type B (Hib); herpes zoster (HZ); hepatitis B; influenza; Streptococcus pneumoniae (pneumococcal vaccine); Neisseria meningitidis (meningococcal vaccine); human papillomavirus (HPV); and diphtheria, tetanus, and pertussis.
Generally, the above vaccines are recommended on an age-appropriate basis, regardless of immunosuppression status, albeit with varying levels of confidence. For example, the Hib vaccine is strongly recommended for pediatric patients 5 years and younger, whereas the same recommendation for older children and adults is conditional.
For several patient populations and vaccines, the guideline panel did not reach a consensus, including use of double-dose hepatitis B vaccine for immunosuppressed adults, timing seasonal flu shots with dosing of biologics, use of pneumococcal vaccines in nonimmunosuppressed patents without a risk factor for pneumococcal disease, use of meningococcal vaccines in adults not at risk for invasive meningococcal disease, and use of HPV vaccine in patients aged 27-45 years.
While immunosuppressive therapy is not a contraindication for giving inactivated vaccines, Dr. Jones and colleagues noted that immunosuppression may hinder vaccine responses.
“Given that patients with IBD on immunosuppressive therapy may have lower immune response to vaccine, further research will be needed to assess the safety and effectiveness of high-dose vs. standard-dose vaccination strategy,” they wrote, also noting that more work is needed to determine if accelerated vaccinations strategies may be feasible prior to initiation of immunosuppressive therapy.
Because of a lack of evidence, the guideline panel did not issue IBD-specific recommendations for vaccines against SARS-CoV-2; however, Dr. Jones and colleagues suggested that clinicians reference a CAG publication on the subject published earlier this year.
The guideline was supported by grants to the Canadian Association of Gastroenterology from the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes; and CANImmunize. Dr. Benchimol disclosed additional relationships with the Canadian Institutes of Health Research, Crohn’s and Colitis Canada; and the Canadian Child Health Clinician Scientist Program.
FROM GASTROENTEROLOGY
AGA Clinical Practice Update Expert Review: Management of malignant alimentary tract obstruction
The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.
“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”
First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”
The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
Esophageal obstruction
For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”
If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.
Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.
“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.
If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
Gastric outlet obstruction
According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.
For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
Colonic obstruction
For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”
Extracolonic obstruction
Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”
The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.
“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.
The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.
The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.
“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”
First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”
The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
Esophageal obstruction
For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”
If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.
Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.
“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.
If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
Gastric outlet obstruction
According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.
For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
Colonic obstruction
For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”
Extracolonic obstruction
Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”
The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.
“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.
The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.
The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.
“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”
First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”
The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
Esophageal obstruction
For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”
If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.
Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.
“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.
If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
Gastric outlet obstruction
According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.
For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
Colonic obstruction
For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”
Extracolonic obstruction
Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”
The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.
“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.
The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Obstetric units place twice as many wrong-patient orders as medical-surgical units
Clinicians in obstetric units place nearly twice as many wrong-patient orders as their medical-surgical counterparts, based on a retrospective look at more than 1.3 million orders.
These findings suggest that obstetric patients are at particular risk for this type of medical error, and that steps are needed to address obstetric clinical culture, work flow, and electronic medical record interfaces, reported lead author Adina R. Kern-Goldberger, MD, of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, and colleagues.
The root of the issue may come from the very nature of obstetrics, and the homogeneity of the patient population, they wrote in Obstetrics & Gynecology.
“Obstetrics is a unique clinical environment because all patients are admitted with a common diagnosis – pregnancy – and have much more overlap in demographic characteristics than a typical inpatient unit given that they are all females of reproductive age,” the investigators wrote. “The labor and delivery environment also is distinct in the hospital given its dynamic tempo and unpredictable work flow. There also is the added risk of neonates typically being registered in the hospital record under the mother’s name after birth. This generates abundant opportunity for errors in order placement, both between obstetric patients and between postpartum patients and their newborns.”
To determine the relative magnitude of this risk, Dr. Kern-Goldberger and colleagues analyzed EMRs from 45,436 obstetric patients and 12,915 medical-surgical patients at “a large, urban, integrated health system in New York City,” including 1,329,463 order sessions placed between 2016 and 2018.
The primary outcome was near-miss wrong-patient orders, which were identified by the Wrong-Patient Retract-and-Reorder measure.
“The measure uses an electronic query to detect retract-and-reorder events, defined as one or more orders placed for patient A, canceled by the same clinician within 10 minutes, and reordered by the same clinician for patient B within the next 10 minutes,” the investigators wrote.In obstetric units, 79.5 wrong-patient orders were placed per 100,000 order sessions, which was 98% higher than the rate of 42.3 wrong-patient orders per 100,000 order sessions in medical-surgical units (odds ratio, 1.98; 95% confidence interval, 1.64-2.39), a disparity that was observed across clinician types and times of day.Advanced practice clinicians in obstetrics placed 47.3 wrong-patient orders per 100,000 order sessions, which was significantly lower than that of their colleagues: attending physicians (127.0 per 100,000) and house staff (119.9 per 100,000).
Wrong-patient orders in obstetrics most often involved medication (73.2 per 100,000), particularly nifedipine, antibiotics, tocolytics, and nonoxytocin uterotonics. The “other” category, including but not limited to lab studies and nursing orders, was associated with 51.0 wrong-patient orders per 100,000 order sessions, while errors in diagnostic imaging orders followed distantly behind, at a rate of 5.7 per 1000,000.
“Although the obstetric clinical environment – particularly labor and delivery – is vibrant and frequently chaotic, it is critical to establish a calm, orderly, and safe culture around order entry,” the investigators wrote. “This, combined with efforts to improve house staff work flow and to optimize EMR interfaces, is likely to help mitigate the threat of wrong order errors to patient care and ultimately improve maternal health and safety.”
According to Catherine D. Cansino, MD, associate clinical professor of obstetrics and gynecology at UC Davis (Calif.) Health, the findings highlight the value of medical informatics while revealing a need to improve EMR interfaces.
“Medical informatics is a growing field and expertise among ob.gyns. is very important,” Dr. Cansino said in an interview. “This study by Kern-Goldberger and colleagues highlights the vulnerability of our EMR systems (and our patients, indirectly) when medical informatics systems are not optimized. The investigators present a study that advocates for greater emphasis on optimizing such systems in obstetrics units, especially in the context of high acuity settings such as obstetrics, compared to medical-surgical units. Appropriately, the study highlights the avoided harm when correcting medical errors for obstetric patients since such errors potentially affect both the delivering patient and the newborn.”
The study was funded by AHRQ. One coauthor disclosed funding from the Icahn School of Medicine at Mount Sinai, Georgetown University, the National Institutes of Health – Office of Scientific Review, and the Social Science Research Council. Another reported funding from Roche.
Clinicians in obstetric units place nearly twice as many wrong-patient orders as their medical-surgical counterparts, based on a retrospective look at more than 1.3 million orders.
These findings suggest that obstetric patients are at particular risk for this type of medical error, and that steps are needed to address obstetric clinical culture, work flow, and electronic medical record interfaces, reported lead author Adina R. Kern-Goldberger, MD, of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, and colleagues.
The root of the issue may come from the very nature of obstetrics, and the homogeneity of the patient population, they wrote in Obstetrics & Gynecology.
“Obstetrics is a unique clinical environment because all patients are admitted with a common diagnosis – pregnancy – and have much more overlap in demographic characteristics than a typical inpatient unit given that they are all females of reproductive age,” the investigators wrote. “The labor and delivery environment also is distinct in the hospital given its dynamic tempo and unpredictable work flow. There also is the added risk of neonates typically being registered in the hospital record under the mother’s name after birth. This generates abundant opportunity for errors in order placement, both between obstetric patients and between postpartum patients and their newborns.”
To determine the relative magnitude of this risk, Dr. Kern-Goldberger and colleagues analyzed EMRs from 45,436 obstetric patients and 12,915 medical-surgical patients at “a large, urban, integrated health system in New York City,” including 1,329,463 order sessions placed between 2016 and 2018.
The primary outcome was near-miss wrong-patient orders, which were identified by the Wrong-Patient Retract-and-Reorder measure.
“The measure uses an electronic query to detect retract-and-reorder events, defined as one or more orders placed for patient A, canceled by the same clinician within 10 minutes, and reordered by the same clinician for patient B within the next 10 minutes,” the investigators wrote.In obstetric units, 79.5 wrong-patient orders were placed per 100,000 order sessions, which was 98% higher than the rate of 42.3 wrong-patient orders per 100,000 order sessions in medical-surgical units (odds ratio, 1.98; 95% confidence interval, 1.64-2.39), a disparity that was observed across clinician types and times of day.Advanced practice clinicians in obstetrics placed 47.3 wrong-patient orders per 100,000 order sessions, which was significantly lower than that of their colleagues: attending physicians (127.0 per 100,000) and house staff (119.9 per 100,000).
Wrong-patient orders in obstetrics most often involved medication (73.2 per 100,000), particularly nifedipine, antibiotics, tocolytics, and nonoxytocin uterotonics. The “other” category, including but not limited to lab studies and nursing orders, was associated with 51.0 wrong-patient orders per 100,000 order sessions, while errors in diagnostic imaging orders followed distantly behind, at a rate of 5.7 per 1000,000.
“Although the obstetric clinical environment – particularly labor and delivery – is vibrant and frequently chaotic, it is critical to establish a calm, orderly, and safe culture around order entry,” the investigators wrote. “This, combined with efforts to improve house staff work flow and to optimize EMR interfaces, is likely to help mitigate the threat of wrong order errors to patient care and ultimately improve maternal health and safety.”
According to Catherine D. Cansino, MD, associate clinical professor of obstetrics and gynecology at UC Davis (Calif.) Health, the findings highlight the value of medical informatics while revealing a need to improve EMR interfaces.
“Medical informatics is a growing field and expertise among ob.gyns. is very important,” Dr. Cansino said in an interview. “This study by Kern-Goldberger and colleagues highlights the vulnerability of our EMR systems (and our patients, indirectly) when medical informatics systems are not optimized. The investigators present a study that advocates for greater emphasis on optimizing such systems in obstetrics units, especially in the context of high acuity settings such as obstetrics, compared to medical-surgical units. Appropriately, the study highlights the avoided harm when correcting medical errors for obstetric patients since such errors potentially affect both the delivering patient and the newborn.”
The study was funded by AHRQ. One coauthor disclosed funding from the Icahn School of Medicine at Mount Sinai, Georgetown University, the National Institutes of Health – Office of Scientific Review, and the Social Science Research Council. Another reported funding from Roche.
Clinicians in obstetric units place nearly twice as many wrong-patient orders as their medical-surgical counterparts, based on a retrospective look at more than 1.3 million orders.
These findings suggest that obstetric patients are at particular risk for this type of medical error, and that steps are needed to address obstetric clinical culture, work flow, and electronic medical record interfaces, reported lead author Adina R. Kern-Goldberger, MD, of the department of obstetrics and gynecology at the University of Pennsylvania, Philadelphia, and colleagues.
The root of the issue may come from the very nature of obstetrics, and the homogeneity of the patient population, they wrote in Obstetrics & Gynecology.
“Obstetrics is a unique clinical environment because all patients are admitted with a common diagnosis – pregnancy – and have much more overlap in demographic characteristics than a typical inpatient unit given that they are all females of reproductive age,” the investigators wrote. “The labor and delivery environment also is distinct in the hospital given its dynamic tempo and unpredictable work flow. There also is the added risk of neonates typically being registered in the hospital record under the mother’s name after birth. This generates abundant opportunity for errors in order placement, both between obstetric patients and between postpartum patients and their newborns.”
To determine the relative magnitude of this risk, Dr. Kern-Goldberger and colleagues analyzed EMRs from 45,436 obstetric patients and 12,915 medical-surgical patients at “a large, urban, integrated health system in New York City,” including 1,329,463 order sessions placed between 2016 and 2018.
The primary outcome was near-miss wrong-patient orders, which were identified by the Wrong-Patient Retract-and-Reorder measure.
“The measure uses an electronic query to detect retract-and-reorder events, defined as one or more orders placed for patient A, canceled by the same clinician within 10 minutes, and reordered by the same clinician for patient B within the next 10 minutes,” the investigators wrote.In obstetric units, 79.5 wrong-patient orders were placed per 100,000 order sessions, which was 98% higher than the rate of 42.3 wrong-patient orders per 100,000 order sessions in medical-surgical units (odds ratio, 1.98; 95% confidence interval, 1.64-2.39), a disparity that was observed across clinician types and times of day.Advanced practice clinicians in obstetrics placed 47.3 wrong-patient orders per 100,000 order sessions, which was significantly lower than that of their colleagues: attending physicians (127.0 per 100,000) and house staff (119.9 per 100,000).
Wrong-patient orders in obstetrics most often involved medication (73.2 per 100,000), particularly nifedipine, antibiotics, tocolytics, and nonoxytocin uterotonics. The “other” category, including but not limited to lab studies and nursing orders, was associated with 51.0 wrong-patient orders per 100,000 order sessions, while errors in diagnostic imaging orders followed distantly behind, at a rate of 5.7 per 1000,000.
“Although the obstetric clinical environment – particularly labor and delivery – is vibrant and frequently chaotic, it is critical to establish a calm, orderly, and safe culture around order entry,” the investigators wrote. “This, combined with efforts to improve house staff work flow and to optimize EMR interfaces, is likely to help mitigate the threat of wrong order errors to patient care and ultimately improve maternal health and safety.”
According to Catherine D. Cansino, MD, associate clinical professor of obstetrics and gynecology at UC Davis (Calif.) Health, the findings highlight the value of medical informatics while revealing a need to improve EMR interfaces.
“Medical informatics is a growing field and expertise among ob.gyns. is very important,” Dr. Cansino said in an interview. “This study by Kern-Goldberger and colleagues highlights the vulnerability of our EMR systems (and our patients, indirectly) when medical informatics systems are not optimized. The investigators present a study that advocates for greater emphasis on optimizing such systems in obstetrics units, especially in the context of high acuity settings such as obstetrics, compared to medical-surgical units. Appropriately, the study highlights the avoided harm when correcting medical errors for obstetric patients since such errors potentially affect both the delivering patient and the newborn.”
The study was funded by AHRQ. One coauthor disclosed funding from the Icahn School of Medicine at Mount Sinai, Georgetown University, the National Institutes of Health – Office of Scientific Review, and the Social Science Research Council. Another reported funding from Roche.
FROM OBSTETRICS & GYNECOLOGY
South Asian ancestry associated with twice the risk of heart disease
according to the results of a new study.
These findings confirm previous reports and practice guidelines that identify South Asian ancestry as a risk enhancer for atherosclerotic cardiovascular disease (ASCVD), suggesting that earlier heart disease screening and prevention is warranted in this patient population, lead author Aniruddh P. Patel, MD, research fellow at the Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues said.
“Previous studies in multiple countries have estimated a 1.7- to 4-fold higher risk of ASCVD among South Asian individuals, compared with other ancestries, but have important potential limitations,” Dr. Patel and colleagues wrote in the paper on their prospective cohort study, published in Circulation.
The INTERHEART case-control study, for example, which assessed risk factors for acute myocardial infarction among more than 15,000 cases from 52 countries, is now 2 decades old, and “may not reflect recent advances in cardiovascular disease prevention,” the investigators wrote.
Most studies in the area have been small and retrospective, they added, and have not adequately assessed emerging risk factors, such as prediabetes, which appear to play a relatively greater role in the development of heart disease among South Asians.
Methods and results
To address this knowledge gap, Dr. Patel and colleagues analyzed data from the UK Biobank prospective cohort study, including 449,349 middle-aged participants of European ancestry and 8,124 similarly aged participants of South Asian descent who did not have heart disease upon enrollment. Respective rates of incident ASCVD (i.e., MI, ischemic stroke, or coronary revascularization) were analyzed in the context of a variety of lifestyle, anthropometric, and clinical factors.
After a median follow-up of 11.1 years, individuals of South Asian descent had an incident ASCVD rate of 6.8%, compared with 4.4% for individuals of European descent, representing twice the relative risk (adjusted hazard ratio, 2.03; 95% CI, 1.86-2.22; P < .001). Even after accounting for all covariates, risk of ASCVD remained 45% higher for South Asian individuals (aHR, 1.45; 95% CI, 1.28-1.65; P < .001). This elevation in risk was not captured by existing risk calculators, including the American College of Cardiology/American Heart Association Pooled Cohort Equations, or the QRISK3 equations.
The findings were “largely consistent across a range of age, sex, and clinical subgroups,” and “confirm and extend previous reports that hypertension, diabetes, and central adiposity are the leading associations in this observed disparity,” the investigators wrote.
Two diabetes subtypes are more prevalent in South Asians
Hypertension, diabetes, and central adiposity do not fully explain South Asians’ higher risk for ASCVD, wrote Namratha R. Kandula, MD, of Northwestern University Medical Center, Chicago, and Alka M. Kanaya, MD, of the University of California, San Francisco, in an accompanying editorial published in Circulation.
Some of the undetected risk may stem from unique diabetes disease factors, Dr. Kandula and Dr. Kanaya added.
“Newer data have demonstrated distinct subtypes of type 2 diabetes, with South Asians having a higher prevalence of both a severe insulin resistant with obesity subtype and a less recognized severe insulin deficient subtype,” they wrote. “Importantly, both of these more prevalent diabetes subtypes in South Asians were associated with a higher incidence of coronary artery calcium, a marker of subclinical atherosclerosis and strong predictor of future ASCVD, compared to other diabetes subtypes.”
Diabetes rate is higher for South Asians in the U.S.
Although the present study was conducted in the United Kingdom, the findings likely apply to individuals of South Asian ancestry living in the United States, according to principal author Amit V. Khera, MD, associate director of the precision medicine unit at the Center for Genomic Medicine, Massachusetts General Hospital.
“There are already more than 5 million individuals of South Asian ancestry in the U.S. and this represents one of the fastest-growing ethnic subgroups,” Dr. Khera said in an interview. “As in our study of individuals in the U.K., South Asians in the U.S. suffer from diabetes at much higher rates – 23% versus 12% – and this often occurs even in the absence of obesity.”
Dr. Khera noted that the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease identify South Asian ancestry as a risk-enhancing factor, calling this a “stopgap measure.” More work is needed, he said, in the research arena and in the clinic.
Zero South Asians included in studies used to develop risk estimator
“I think the first step is to simply acknowledge that the risk estimators we use in clinical practice have important limitations when it comes to diverse patient populations,” Dr. Khera said in an interview. “We saw this in our study, where – despite a more than doubling of risk – the predicted risk based on the equations used in primary care showed no difference. This risk estimator was developed based on legacy cohort studies, in [which] zero South Asians were included. Despite important differences across race/ethnicity, the current state-of-the-art in the U.S. is to use one equation for Black individuals and another for all other ethnicities.”
Experts suggest steps for reducing heart disease risk
While risk modeling remains suboptimal, Dr. Khera suggested that clinicians can take immediate steps to reduce the risk of heart disease among individuals with South Asian ancestry.
“Despite all of the uncertainty – we still don’t have a complete understanding of why the risk is so high – there are still several things primary care doctors can do for their patients,” Dr. Khera said.
Foremost, he recommended lifestyle and dietary counseling.
“Dietary counseling is particularly effective if put in the context of cultural norms,” Dr. Khera said. “Many South Asians consider fruit juices or white rice to be healthy, when they lead to rapid spikes in blood sugar.”
Dr. Khera also advised earlier heart disease screening, such as coronary calcium scanning “sometime between age 40-50 years,” noting that positive test results may motivate patients to start or adhere to medications, such as cholesterol-lowering therapies. If necessary, clinicians can also refer to heart centers for South Asian patients, which are becoming increasingly common.
According to Cheryl A.M. Anderson, PhD, chair of the AHA’s Council on Epidemiology and Prevention, and professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, the current study suggests that heart disease management strategies for South Asian patients may be lacking.
“We have had a tradition of preventing or trying to treat heart disease in a fashion that doesn’t yet account for the increased risk that might be prevalent in those of South Asian ancestry,” Dr. Anderson said in an interview.
She suggested that improving associated risk-analysis tools could be beneficial, although the tools themselves, in the context of race or ethnicity, may present their own risks.
“We want to be mindful of potential adverse implications from having everything linked to one’s ancestry, which I think this tool doesn’t do,” Dr. Anderson said, referring to the AHA/ACC Pooled Cohort Equations. “But in sort of the bigger picture of things, we always want to expand and refine our toolkit.”
According to Rajesh Dash, MD, PhD, associate professor, cardiologist, and director of the South Asian Translational Heart Initiative (SSATHI) Prevention Clinic and CardioClick Telemedicine Clinic at Stanford (Calif.) HealthCare, the science supports more active risk mitigation strategies for South Asian patients, and the AHA and the ACC “are the two entities that need to lead the way.”
“Certainly the American Heart Association and the American College of Cardiology should be taking a more active leadership role in this,” Dr. Dash said in an interview.
In 2018, the AHA issued a scientific statement about the elevated risk of ASCVD among South Asian individuals, “but it did not rise to the level of specific recommendations, and did not necessarily go as far as to incorporate new screening parameters for that population,” Dr. Dash said. He also noted that the most recent AHA/ACC guideline identifies South Asian ancestry as a risk-enhancing feature, a statement similarly lacking in actionable value.
“That does not definitively lead someone like a primary care physician to a decision to start a statin, or to be more aggressive with a diagnostic workup, like a stress test, for instance, for a patient who they otherwise would not have done one in had they not been South Asian,” Dr. Dash said.
The steps taken by the AHA and the ACC are “a healthy step forward,” he noted, “but not nearly the degree of attention or vigilance that is required, as well as the level of action that is required to change the narrative for the population.”
At the SSATHI Prevention Clinic, Dr. Dash and colleagues aren’t waiting for the narrative to change, and are already taking a more aggressive approach.
The clinic has an average patient age of 41 years, “easily 15 years younger than the average age in most cardiology clinics,” Dr. Dash said, based on the fact that approximately two-thirds of heart attacks in South Asian individuals occur under the age of 55. “We have to look earlier.”
The SSATHI Prevention Clinic screens for both traditional and emerging risk factors, and Dr. Dash suggested that primary care doctors should do the same.
“If you have a South Asian patient as a primary care physician, you should be aggressively looking for risk factors, traditional ones to start, like elevated cholesterol, hypertension, diabetes, or – and I would argue strongly – prediabetes or insulin resistance.”
Dr. Dash also recommended looking into family history, and considering screening for inflammatory biomarkers, the latter of which are commonly elevated at an earlier age among South Asian individuals, and may have a relatively greater prognostic impact.
To encourage broader implementation of this kind of approach, Dr. Dash called for more large-scale studies. Ideally, these would be randomized clinical trials, but, realistically, real-world datasets may be the answer.
The study was supported by the National Heart, Lung, and Blood Institute; the Broad Institute at MIT and Harvard; the National Human Genome Research Institute; and others. The investigators disclosed relationships with IBM Research, Sanofi, Amgen, and others. Dr. Dash disclosed relationships with HealthPals and AstraZeneca. Dr. Anderson reported no relevant conflicts of interest.
according to the results of a new study.
These findings confirm previous reports and practice guidelines that identify South Asian ancestry as a risk enhancer for atherosclerotic cardiovascular disease (ASCVD), suggesting that earlier heart disease screening and prevention is warranted in this patient population, lead author Aniruddh P. Patel, MD, research fellow at the Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues said.
“Previous studies in multiple countries have estimated a 1.7- to 4-fold higher risk of ASCVD among South Asian individuals, compared with other ancestries, but have important potential limitations,” Dr. Patel and colleagues wrote in the paper on their prospective cohort study, published in Circulation.
The INTERHEART case-control study, for example, which assessed risk factors for acute myocardial infarction among more than 15,000 cases from 52 countries, is now 2 decades old, and “may not reflect recent advances in cardiovascular disease prevention,” the investigators wrote.
Most studies in the area have been small and retrospective, they added, and have not adequately assessed emerging risk factors, such as prediabetes, which appear to play a relatively greater role in the development of heart disease among South Asians.
Methods and results
To address this knowledge gap, Dr. Patel and colleagues analyzed data from the UK Biobank prospective cohort study, including 449,349 middle-aged participants of European ancestry and 8,124 similarly aged participants of South Asian descent who did not have heart disease upon enrollment. Respective rates of incident ASCVD (i.e., MI, ischemic stroke, or coronary revascularization) were analyzed in the context of a variety of lifestyle, anthropometric, and clinical factors.
After a median follow-up of 11.1 years, individuals of South Asian descent had an incident ASCVD rate of 6.8%, compared with 4.4% for individuals of European descent, representing twice the relative risk (adjusted hazard ratio, 2.03; 95% CI, 1.86-2.22; P < .001). Even after accounting for all covariates, risk of ASCVD remained 45% higher for South Asian individuals (aHR, 1.45; 95% CI, 1.28-1.65; P < .001). This elevation in risk was not captured by existing risk calculators, including the American College of Cardiology/American Heart Association Pooled Cohort Equations, or the QRISK3 equations.
The findings were “largely consistent across a range of age, sex, and clinical subgroups,” and “confirm and extend previous reports that hypertension, diabetes, and central adiposity are the leading associations in this observed disparity,” the investigators wrote.
Two diabetes subtypes are more prevalent in South Asians
Hypertension, diabetes, and central adiposity do not fully explain South Asians’ higher risk for ASCVD, wrote Namratha R. Kandula, MD, of Northwestern University Medical Center, Chicago, and Alka M. Kanaya, MD, of the University of California, San Francisco, in an accompanying editorial published in Circulation.
Some of the undetected risk may stem from unique diabetes disease factors, Dr. Kandula and Dr. Kanaya added.
“Newer data have demonstrated distinct subtypes of type 2 diabetes, with South Asians having a higher prevalence of both a severe insulin resistant with obesity subtype and a less recognized severe insulin deficient subtype,” they wrote. “Importantly, both of these more prevalent diabetes subtypes in South Asians were associated with a higher incidence of coronary artery calcium, a marker of subclinical atherosclerosis and strong predictor of future ASCVD, compared to other diabetes subtypes.”
Diabetes rate is higher for South Asians in the U.S.
Although the present study was conducted in the United Kingdom, the findings likely apply to individuals of South Asian ancestry living in the United States, according to principal author Amit V. Khera, MD, associate director of the precision medicine unit at the Center for Genomic Medicine, Massachusetts General Hospital.
“There are already more than 5 million individuals of South Asian ancestry in the U.S. and this represents one of the fastest-growing ethnic subgroups,” Dr. Khera said in an interview. “As in our study of individuals in the U.K., South Asians in the U.S. suffer from diabetes at much higher rates – 23% versus 12% – and this often occurs even in the absence of obesity.”
Dr. Khera noted that the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease identify South Asian ancestry as a risk-enhancing factor, calling this a “stopgap measure.” More work is needed, he said, in the research arena and in the clinic.
Zero South Asians included in studies used to develop risk estimator
“I think the first step is to simply acknowledge that the risk estimators we use in clinical practice have important limitations when it comes to diverse patient populations,” Dr. Khera said in an interview. “We saw this in our study, where – despite a more than doubling of risk – the predicted risk based on the equations used in primary care showed no difference. This risk estimator was developed based on legacy cohort studies, in [which] zero South Asians were included. Despite important differences across race/ethnicity, the current state-of-the-art in the U.S. is to use one equation for Black individuals and another for all other ethnicities.”
Experts suggest steps for reducing heart disease risk
While risk modeling remains suboptimal, Dr. Khera suggested that clinicians can take immediate steps to reduce the risk of heart disease among individuals with South Asian ancestry.
“Despite all of the uncertainty – we still don’t have a complete understanding of why the risk is so high – there are still several things primary care doctors can do for their patients,” Dr. Khera said.
Foremost, he recommended lifestyle and dietary counseling.
“Dietary counseling is particularly effective if put in the context of cultural norms,” Dr. Khera said. “Many South Asians consider fruit juices or white rice to be healthy, when they lead to rapid spikes in blood sugar.”
Dr. Khera also advised earlier heart disease screening, such as coronary calcium scanning “sometime between age 40-50 years,” noting that positive test results may motivate patients to start or adhere to medications, such as cholesterol-lowering therapies. If necessary, clinicians can also refer to heart centers for South Asian patients, which are becoming increasingly common.
According to Cheryl A.M. Anderson, PhD, chair of the AHA’s Council on Epidemiology and Prevention, and professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, the current study suggests that heart disease management strategies for South Asian patients may be lacking.
“We have had a tradition of preventing or trying to treat heart disease in a fashion that doesn’t yet account for the increased risk that might be prevalent in those of South Asian ancestry,” Dr. Anderson said in an interview.
She suggested that improving associated risk-analysis tools could be beneficial, although the tools themselves, in the context of race or ethnicity, may present their own risks.
“We want to be mindful of potential adverse implications from having everything linked to one’s ancestry, which I think this tool doesn’t do,” Dr. Anderson said, referring to the AHA/ACC Pooled Cohort Equations. “But in sort of the bigger picture of things, we always want to expand and refine our toolkit.”
According to Rajesh Dash, MD, PhD, associate professor, cardiologist, and director of the South Asian Translational Heart Initiative (SSATHI) Prevention Clinic and CardioClick Telemedicine Clinic at Stanford (Calif.) HealthCare, the science supports more active risk mitigation strategies for South Asian patients, and the AHA and the ACC “are the two entities that need to lead the way.”
“Certainly the American Heart Association and the American College of Cardiology should be taking a more active leadership role in this,” Dr. Dash said in an interview.
In 2018, the AHA issued a scientific statement about the elevated risk of ASCVD among South Asian individuals, “but it did not rise to the level of specific recommendations, and did not necessarily go as far as to incorporate new screening parameters for that population,” Dr. Dash said. He also noted that the most recent AHA/ACC guideline identifies South Asian ancestry as a risk-enhancing feature, a statement similarly lacking in actionable value.
“That does not definitively lead someone like a primary care physician to a decision to start a statin, or to be more aggressive with a diagnostic workup, like a stress test, for instance, for a patient who they otherwise would not have done one in had they not been South Asian,” Dr. Dash said.
The steps taken by the AHA and the ACC are “a healthy step forward,” he noted, “but not nearly the degree of attention or vigilance that is required, as well as the level of action that is required to change the narrative for the population.”
At the SSATHI Prevention Clinic, Dr. Dash and colleagues aren’t waiting for the narrative to change, and are already taking a more aggressive approach.
The clinic has an average patient age of 41 years, “easily 15 years younger than the average age in most cardiology clinics,” Dr. Dash said, based on the fact that approximately two-thirds of heart attacks in South Asian individuals occur under the age of 55. “We have to look earlier.”
The SSATHI Prevention Clinic screens for both traditional and emerging risk factors, and Dr. Dash suggested that primary care doctors should do the same.
“If you have a South Asian patient as a primary care physician, you should be aggressively looking for risk factors, traditional ones to start, like elevated cholesterol, hypertension, diabetes, or – and I would argue strongly – prediabetes or insulin resistance.”
Dr. Dash also recommended looking into family history, and considering screening for inflammatory biomarkers, the latter of which are commonly elevated at an earlier age among South Asian individuals, and may have a relatively greater prognostic impact.
To encourage broader implementation of this kind of approach, Dr. Dash called for more large-scale studies. Ideally, these would be randomized clinical trials, but, realistically, real-world datasets may be the answer.
The study was supported by the National Heart, Lung, and Blood Institute; the Broad Institute at MIT and Harvard; the National Human Genome Research Institute; and others. The investigators disclosed relationships with IBM Research, Sanofi, Amgen, and others. Dr. Dash disclosed relationships with HealthPals and AstraZeneca. Dr. Anderson reported no relevant conflicts of interest.
according to the results of a new study.
These findings confirm previous reports and practice guidelines that identify South Asian ancestry as a risk enhancer for atherosclerotic cardiovascular disease (ASCVD), suggesting that earlier heart disease screening and prevention is warranted in this patient population, lead author Aniruddh P. Patel, MD, research fellow at the Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues said.
“Previous studies in multiple countries have estimated a 1.7- to 4-fold higher risk of ASCVD among South Asian individuals, compared with other ancestries, but have important potential limitations,” Dr. Patel and colleagues wrote in the paper on their prospective cohort study, published in Circulation.
The INTERHEART case-control study, for example, which assessed risk factors for acute myocardial infarction among more than 15,000 cases from 52 countries, is now 2 decades old, and “may not reflect recent advances in cardiovascular disease prevention,” the investigators wrote.
Most studies in the area have been small and retrospective, they added, and have not adequately assessed emerging risk factors, such as prediabetes, which appear to play a relatively greater role in the development of heart disease among South Asians.
Methods and results
To address this knowledge gap, Dr. Patel and colleagues analyzed data from the UK Biobank prospective cohort study, including 449,349 middle-aged participants of European ancestry and 8,124 similarly aged participants of South Asian descent who did not have heart disease upon enrollment. Respective rates of incident ASCVD (i.e., MI, ischemic stroke, or coronary revascularization) were analyzed in the context of a variety of lifestyle, anthropometric, and clinical factors.
After a median follow-up of 11.1 years, individuals of South Asian descent had an incident ASCVD rate of 6.8%, compared with 4.4% for individuals of European descent, representing twice the relative risk (adjusted hazard ratio, 2.03; 95% CI, 1.86-2.22; P < .001). Even after accounting for all covariates, risk of ASCVD remained 45% higher for South Asian individuals (aHR, 1.45; 95% CI, 1.28-1.65; P < .001). This elevation in risk was not captured by existing risk calculators, including the American College of Cardiology/American Heart Association Pooled Cohort Equations, or the QRISK3 equations.
The findings were “largely consistent across a range of age, sex, and clinical subgroups,” and “confirm and extend previous reports that hypertension, diabetes, and central adiposity are the leading associations in this observed disparity,” the investigators wrote.
Two diabetes subtypes are more prevalent in South Asians
Hypertension, diabetes, and central adiposity do not fully explain South Asians’ higher risk for ASCVD, wrote Namratha R. Kandula, MD, of Northwestern University Medical Center, Chicago, and Alka M. Kanaya, MD, of the University of California, San Francisco, in an accompanying editorial published in Circulation.
Some of the undetected risk may stem from unique diabetes disease factors, Dr. Kandula and Dr. Kanaya added.
“Newer data have demonstrated distinct subtypes of type 2 diabetes, with South Asians having a higher prevalence of both a severe insulin resistant with obesity subtype and a less recognized severe insulin deficient subtype,” they wrote. “Importantly, both of these more prevalent diabetes subtypes in South Asians were associated with a higher incidence of coronary artery calcium, a marker of subclinical atherosclerosis and strong predictor of future ASCVD, compared to other diabetes subtypes.”
Diabetes rate is higher for South Asians in the U.S.
Although the present study was conducted in the United Kingdom, the findings likely apply to individuals of South Asian ancestry living in the United States, according to principal author Amit V. Khera, MD, associate director of the precision medicine unit at the Center for Genomic Medicine, Massachusetts General Hospital.
“There are already more than 5 million individuals of South Asian ancestry in the U.S. and this represents one of the fastest-growing ethnic subgroups,” Dr. Khera said in an interview. “As in our study of individuals in the U.K., South Asians in the U.S. suffer from diabetes at much higher rates – 23% versus 12% – and this often occurs even in the absence of obesity.”
Dr. Khera noted that the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease identify South Asian ancestry as a risk-enhancing factor, calling this a “stopgap measure.” More work is needed, he said, in the research arena and in the clinic.
Zero South Asians included in studies used to develop risk estimator
“I think the first step is to simply acknowledge that the risk estimators we use in clinical practice have important limitations when it comes to diverse patient populations,” Dr. Khera said in an interview. “We saw this in our study, where – despite a more than doubling of risk – the predicted risk based on the equations used in primary care showed no difference. This risk estimator was developed based on legacy cohort studies, in [which] zero South Asians were included. Despite important differences across race/ethnicity, the current state-of-the-art in the U.S. is to use one equation for Black individuals and another for all other ethnicities.”
Experts suggest steps for reducing heart disease risk
While risk modeling remains suboptimal, Dr. Khera suggested that clinicians can take immediate steps to reduce the risk of heart disease among individuals with South Asian ancestry.
“Despite all of the uncertainty – we still don’t have a complete understanding of why the risk is so high – there are still several things primary care doctors can do for their patients,” Dr. Khera said.
Foremost, he recommended lifestyle and dietary counseling.
“Dietary counseling is particularly effective if put in the context of cultural norms,” Dr. Khera said. “Many South Asians consider fruit juices or white rice to be healthy, when they lead to rapid spikes in blood sugar.”
Dr. Khera also advised earlier heart disease screening, such as coronary calcium scanning “sometime between age 40-50 years,” noting that positive test results may motivate patients to start or adhere to medications, such as cholesterol-lowering therapies. If necessary, clinicians can also refer to heart centers for South Asian patients, which are becoming increasingly common.
According to Cheryl A.M. Anderson, PhD, chair of the AHA’s Council on Epidemiology and Prevention, and professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, the current study suggests that heart disease management strategies for South Asian patients may be lacking.
“We have had a tradition of preventing or trying to treat heart disease in a fashion that doesn’t yet account for the increased risk that might be prevalent in those of South Asian ancestry,” Dr. Anderson said in an interview.
She suggested that improving associated risk-analysis tools could be beneficial, although the tools themselves, in the context of race or ethnicity, may present their own risks.
“We want to be mindful of potential adverse implications from having everything linked to one’s ancestry, which I think this tool doesn’t do,” Dr. Anderson said, referring to the AHA/ACC Pooled Cohort Equations. “But in sort of the bigger picture of things, we always want to expand and refine our toolkit.”
According to Rajesh Dash, MD, PhD, associate professor, cardiologist, and director of the South Asian Translational Heart Initiative (SSATHI) Prevention Clinic and CardioClick Telemedicine Clinic at Stanford (Calif.) HealthCare, the science supports more active risk mitigation strategies for South Asian patients, and the AHA and the ACC “are the two entities that need to lead the way.”
“Certainly the American Heart Association and the American College of Cardiology should be taking a more active leadership role in this,” Dr. Dash said in an interview.
In 2018, the AHA issued a scientific statement about the elevated risk of ASCVD among South Asian individuals, “but it did not rise to the level of specific recommendations, and did not necessarily go as far as to incorporate new screening parameters for that population,” Dr. Dash said. He also noted that the most recent AHA/ACC guideline identifies South Asian ancestry as a risk-enhancing feature, a statement similarly lacking in actionable value.
“That does not definitively lead someone like a primary care physician to a decision to start a statin, or to be more aggressive with a diagnostic workup, like a stress test, for instance, for a patient who they otherwise would not have done one in had they not been South Asian,” Dr. Dash said.
The steps taken by the AHA and the ACC are “a healthy step forward,” he noted, “but not nearly the degree of attention or vigilance that is required, as well as the level of action that is required to change the narrative for the population.”
At the SSATHI Prevention Clinic, Dr. Dash and colleagues aren’t waiting for the narrative to change, and are already taking a more aggressive approach.
The clinic has an average patient age of 41 years, “easily 15 years younger than the average age in most cardiology clinics,” Dr. Dash said, based on the fact that approximately two-thirds of heart attacks in South Asian individuals occur under the age of 55. “We have to look earlier.”
The SSATHI Prevention Clinic screens for both traditional and emerging risk factors, and Dr. Dash suggested that primary care doctors should do the same.
“If you have a South Asian patient as a primary care physician, you should be aggressively looking for risk factors, traditional ones to start, like elevated cholesterol, hypertension, diabetes, or – and I would argue strongly – prediabetes or insulin resistance.”
Dr. Dash also recommended looking into family history, and considering screening for inflammatory biomarkers, the latter of which are commonly elevated at an earlier age among South Asian individuals, and may have a relatively greater prognostic impact.
To encourage broader implementation of this kind of approach, Dr. Dash called for more large-scale studies. Ideally, these would be randomized clinical trials, but, realistically, real-world datasets may be the answer.
The study was supported by the National Heart, Lung, and Blood Institute; the Broad Institute at MIT and Harvard; the National Human Genome Research Institute; and others. The investigators disclosed relationships with IBM Research, Sanofi, Amgen, and others. Dr. Dash disclosed relationships with HealthPals and AstraZeneca. Dr. Anderson reported no relevant conflicts of interest.
FROM CIRCULATION
Mutational signature may reveal underlying link between red meat and CRC
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
FROM CANCER DISCOVERY
AGA Clinical Practice Update: Early complications after bariatric/metabolic surgery
The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.
The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.
According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.
“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”
Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.
“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.
The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.
Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.
“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”
The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.
“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”
Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.
“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”
Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.
“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”
Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”
To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.
Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”
As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.
To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.
For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.
“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.
The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.
The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.
The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.
According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.
“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”
Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.
“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.
The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.
Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.
“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”
The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.
“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”
Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.
“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”
Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.
“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”
Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”
To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.
Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”
As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.
To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.
For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.
“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.
The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.
The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.
The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.
According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.
“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”
Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.
“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.
The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.
Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.
“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”
The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.
“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”
Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.
“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”
Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.
“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”
Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”
To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.
Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”
As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.
To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.
For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.
“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.
The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Mutational signature may reveal underlying link between red meat and CRC
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
FROM CANCER DISCOVERY
Early-onset CRC associated with longer survival
Individuals diagnosed with primary colorectal cancer (CRC) at less than 50 years of age have better survival outcomes than individuals diagnosed at 51-55 years, based on data from more than 750,000 patients.
This finding emphasizes the importance of early CRC detection in younger individuals, reported lead author En Cheng, MD, PhD, of Yale University, New Haven, Conn., and colleagues.
“Early-onset CRC (i.e., CRC diagnosed at age less than 50 years) has been characterized by unique clinical, genetic, and epigenetic characteristics, and thus it may be associated with different survival from CRC diagnosed among individuals older than 50 years,” the investigators wrote in JAMA Network Open. Previous studies comparing survival times across age groups have yielded inconsistent results.
To gain a better understanding, the investigator conducted a retrospective study using data from the National Cancer Database. Excluding patients with primary CRC who had concomitant diagnosis, history of other malignant tumors, noninvasive adenocarcinoma, or missing data, the final dataset included 769,871 patients. Early-onset CRC was defined by age less than 50 years, whereas later-onset CRC was defined by ages 51-55 years.
“Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at age 50 years in our population, given that these individuals disproportionately presented with earlier stages,” the investigators wrote.
Initial comparisons across groups revealed several significant differences. Individuals in the early-onset group were more often women (47.3% vs. 43.8%; P < .001), members of races in the “other” category (6.9% vs. 5.9%; P < .001), and Medicaid patients (12.3% vs. 10.3%; P < .001). They were also more likely to be diagnosed with stage IV cancer (27.8% vs 24.1%; P < .001) and have rectal tumors (29.3% vs. 28.7%; P = .004).
In the unadjusted Kaplan-Meier analysis, patients with early-onset CRC had a lower 10-year survival rate (53.6%; 95% CI, 53.2%-54.0% vs. 54.3%; 95% CI, 53.8%-54.8%; P < .001). The fully adjusted model revealed significantly higher survival for early-onset patients, compared with later-onset patients (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.96; P < .001) . This disparity deepened when adjusting only for stage (HR, 0.89; 95% CI, 0.88-0.90; P < .001).
Survival was longest among patients 35-39 years (aHR, 0.88; 95% CI, 0.84-0.92; P < .001), compared with those aged 51-55, and among early-onset individuals with stage I disease (a HR, 0.87; 95% CI, 0.81-0.93; P < .001) or stage II disease (a HR, 0.86; 95% CI, 0.82-0.90; P < .001), compared with those having the same stages of later-onset CRC. No survival advantage was observed among patients diagnosed at age 25 or younger or those with stage III or IV disease.
“Interestingly, hereditary nonpolyposis colorectal cancer, owing to underlying mismatch repair deficiency, is associated with superior survival and is often diagnosed in individuals from ages 35-45 years,” the investigators noted. “In contrast, adenomatous polyposis coli syndrome is more common in individuals who are diagnosed with CRC at age younger than 20 years (10%), compared with those diagnosed at later ages (0.1%), and adenomatous polyposis coli syndrome is not associated with a survival advantage. These high penetrance syndromes could partly account for the relative heterogeneity in survival across ages among individuals with early-onset CRC.”
Cautious about interpretation
Dr. Cheng and colleagues concluded their publication with a disclaimer: “Our finding of a survival advantage associated with early-onset CRC among younger individuals should be interpreted cautiously, given that the advantage had a small magnitude and was heterogeneous by age and stage,” they wrote. “Further study is needed to understand the underlying heterogeneity of survival by age and stage among individuals with early-onset CRC.”
Kirbi L. Yelorda, MD, of Stanford (Calif.) University, and colleagues, had a similar interpretation.
“These results offer support for effectiveness of treatment in patients diagnosed with CRC at younger ages; however, they must be interpreted within the context of epidemiological and biological factors,” Dr. Yelorda and colleagues wrote in an accompanying editorial.
The findings also suggest that the recent reduction in recommended screening age by the U.S. Preventive Services Task Force – from 50 years to 45 years – is warranted, they added, but screening younger patients remains unnecessary.
“While these results do not suggest that screening should start for patients younger than 45 years, they do support the benefit of early detection in young patients,” Dr. Yelorda and colleagues wrote, noting a “fairly low incidence rate” among individuals younger than 45, which is insufficient to justify the risk-to-benefit ratio and increased costs associated with expanded screening.
Important but not surprising
It’s “not surprising” that early-onset patients typically have better survival than later-onset patients, according to Joseph C. Anderson, MD, associate professor at White River Junction Veterans Affairs Medical Center, Hartford, Vt.; Geisel School of Medicine at Dartmouth, Hanover, N.H.; and the University of Connecticut, Farmington.
“They’re younger, have less comorbidities, and can tolerate chemotherapy,” Dr. Anderson said in an interview. “It’s not surprising that people do poorly with later stages. Younger people are no exception.”
Dr. Anderson, who previously coauthored an editorial weighing the pros and cons of earlier screening, noted that earlier screening is needed because of the rising incidence of late-stage diagnoses among younger patients, which, as the study found, are associated with worse outcomes.
Beyond adherence to screening recommendations, Dr. Anderson urged clinicians to be aggressive when doing a workup of CRC symptoms in younger patients, among whom delayed diagnoses are more common.
“We can’t just say it’s something more benign, like hemorrhoids, like we used to,” Dr. Anderson said. “Somebody who’s 30 years old and having rectal bleeding needs to be evaluated promptly – there can’t be a delay.”
The study was supported by the National Institutes of Health and Stand Up To Cancer (grant administered by the American Association for Cancer Research). The investigators disclosed relationships with Evergrande Group, Janssen, Revolution Medicines, and others. One editorialist reported serving as a member of the USPSTF when the guideline for colorectal cancer was developed, and being a coauthor on the guideline. No other disclosures were reported among editorialists. Dr. Anderson reported no relevant conflicts of interest.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
Individuals diagnosed with primary colorectal cancer (CRC) at less than 50 years of age have better survival outcomes than individuals diagnosed at 51-55 years, based on data from more than 750,000 patients.
This finding emphasizes the importance of early CRC detection in younger individuals, reported lead author En Cheng, MD, PhD, of Yale University, New Haven, Conn., and colleagues.
“Early-onset CRC (i.e., CRC diagnosed at age less than 50 years) has been characterized by unique clinical, genetic, and epigenetic characteristics, and thus it may be associated with different survival from CRC diagnosed among individuals older than 50 years,” the investigators wrote in JAMA Network Open. Previous studies comparing survival times across age groups have yielded inconsistent results.
To gain a better understanding, the investigator conducted a retrospective study using data from the National Cancer Database. Excluding patients with primary CRC who had concomitant diagnosis, history of other malignant tumors, noninvasive adenocarcinoma, or missing data, the final dataset included 769,871 patients. Early-onset CRC was defined by age less than 50 years, whereas later-onset CRC was defined by ages 51-55 years.
“Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at age 50 years in our population, given that these individuals disproportionately presented with earlier stages,” the investigators wrote.
Initial comparisons across groups revealed several significant differences. Individuals in the early-onset group were more often women (47.3% vs. 43.8%; P < .001), members of races in the “other” category (6.9% vs. 5.9%; P < .001), and Medicaid patients (12.3% vs. 10.3%; P < .001). They were also more likely to be diagnosed with stage IV cancer (27.8% vs 24.1%; P < .001) and have rectal tumors (29.3% vs. 28.7%; P = .004).
In the unadjusted Kaplan-Meier analysis, patients with early-onset CRC had a lower 10-year survival rate (53.6%; 95% CI, 53.2%-54.0% vs. 54.3%; 95% CI, 53.8%-54.8%; P < .001). The fully adjusted model revealed significantly higher survival for early-onset patients, compared with later-onset patients (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.96; P < .001) . This disparity deepened when adjusting only for stage (HR, 0.89; 95% CI, 0.88-0.90; P < .001).
Survival was longest among patients 35-39 years (aHR, 0.88; 95% CI, 0.84-0.92; P < .001), compared with those aged 51-55, and among early-onset individuals with stage I disease (a HR, 0.87; 95% CI, 0.81-0.93; P < .001) or stage II disease (a HR, 0.86; 95% CI, 0.82-0.90; P < .001), compared with those having the same stages of later-onset CRC. No survival advantage was observed among patients diagnosed at age 25 or younger or those with stage III or IV disease.
“Interestingly, hereditary nonpolyposis colorectal cancer, owing to underlying mismatch repair deficiency, is associated with superior survival and is often diagnosed in individuals from ages 35-45 years,” the investigators noted. “In contrast, adenomatous polyposis coli syndrome is more common in individuals who are diagnosed with CRC at age younger than 20 years (10%), compared with those diagnosed at later ages (0.1%), and adenomatous polyposis coli syndrome is not associated with a survival advantage. These high penetrance syndromes could partly account for the relative heterogeneity in survival across ages among individuals with early-onset CRC.”
Cautious about interpretation
Dr. Cheng and colleagues concluded their publication with a disclaimer: “Our finding of a survival advantage associated with early-onset CRC among younger individuals should be interpreted cautiously, given that the advantage had a small magnitude and was heterogeneous by age and stage,” they wrote. “Further study is needed to understand the underlying heterogeneity of survival by age and stage among individuals with early-onset CRC.”
Kirbi L. Yelorda, MD, of Stanford (Calif.) University, and colleagues, had a similar interpretation.
“These results offer support for effectiveness of treatment in patients diagnosed with CRC at younger ages; however, they must be interpreted within the context of epidemiological and biological factors,” Dr. Yelorda and colleagues wrote in an accompanying editorial.
The findings also suggest that the recent reduction in recommended screening age by the U.S. Preventive Services Task Force – from 50 years to 45 years – is warranted, they added, but screening younger patients remains unnecessary.
“While these results do not suggest that screening should start for patients younger than 45 years, they do support the benefit of early detection in young patients,” Dr. Yelorda and colleagues wrote, noting a “fairly low incidence rate” among individuals younger than 45, which is insufficient to justify the risk-to-benefit ratio and increased costs associated with expanded screening.
Important but not surprising
It’s “not surprising” that early-onset patients typically have better survival than later-onset patients, according to Joseph C. Anderson, MD, associate professor at White River Junction Veterans Affairs Medical Center, Hartford, Vt.; Geisel School of Medicine at Dartmouth, Hanover, N.H.; and the University of Connecticut, Farmington.
“They’re younger, have less comorbidities, and can tolerate chemotherapy,” Dr. Anderson said in an interview. “It’s not surprising that people do poorly with later stages. Younger people are no exception.”
Dr. Anderson, who previously coauthored an editorial weighing the pros and cons of earlier screening, noted that earlier screening is needed because of the rising incidence of late-stage diagnoses among younger patients, which, as the study found, are associated with worse outcomes.
Beyond adherence to screening recommendations, Dr. Anderson urged clinicians to be aggressive when doing a workup of CRC symptoms in younger patients, among whom delayed diagnoses are more common.
“We can’t just say it’s something more benign, like hemorrhoids, like we used to,” Dr. Anderson said. “Somebody who’s 30 years old and having rectal bleeding needs to be evaluated promptly – there can’t be a delay.”
The study was supported by the National Institutes of Health and Stand Up To Cancer (grant administered by the American Association for Cancer Research). The investigators disclosed relationships with Evergrande Group, Janssen, Revolution Medicines, and others. One editorialist reported serving as a member of the USPSTF when the guideline for colorectal cancer was developed, and being a coauthor on the guideline. No other disclosures were reported among editorialists. Dr. Anderson reported no relevant conflicts of interest.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
Individuals diagnosed with primary colorectal cancer (CRC) at less than 50 years of age have better survival outcomes than individuals diagnosed at 51-55 years, based on data from more than 750,000 patients.
This finding emphasizes the importance of early CRC detection in younger individuals, reported lead author En Cheng, MD, PhD, of Yale University, New Haven, Conn., and colleagues.
“Early-onset CRC (i.e., CRC diagnosed at age less than 50 years) has been characterized by unique clinical, genetic, and epigenetic characteristics, and thus it may be associated with different survival from CRC diagnosed among individuals older than 50 years,” the investigators wrote in JAMA Network Open. Previous studies comparing survival times across age groups have yielded inconsistent results.
To gain a better understanding, the investigator conducted a retrospective study using data from the National Cancer Database. Excluding patients with primary CRC who had concomitant diagnosis, history of other malignant tumors, noninvasive adenocarcinoma, or missing data, the final dataset included 769,871 patients. Early-onset CRC was defined by age less than 50 years, whereas later-onset CRC was defined by ages 51-55 years.
“Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at age 50 years in our population, given that these individuals disproportionately presented with earlier stages,” the investigators wrote.
Initial comparisons across groups revealed several significant differences. Individuals in the early-onset group were more often women (47.3% vs. 43.8%; P < .001), members of races in the “other” category (6.9% vs. 5.9%; P < .001), and Medicaid patients (12.3% vs. 10.3%; P < .001). They were also more likely to be diagnosed with stage IV cancer (27.8% vs 24.1%; P < .001) and have rectal tumors (29.3% vs. 28.7%; P = .004).
In the unadjusted Kaplan-Meier analysis, patients with early-onset CRC had a lower 10-year survival rate (53.6%; 95% CI, 53.2%-54.0% vs. 54.3%; 95% CI, 53.8%-54.8%; P < .001). The fully adjusted model revealed significantly higher survival for early-onset patients, compared with later-onset patients (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.96; P < .001) . This disparity deepened when adjusting only for stage (HR, 0.89; 95% CI, 0.88-0.90; P < .001).
Survival was longest among patients 35-39 years (aHR, 0.88; 95% CI, 0.84-0.92; P < .001), compared with those aged 51-55, and among early-onset individuals with stage I disease (a HR, 0.87; 95% CI, 0.81-0.93; P < .001) or stage II disease (a HR, 0.86; 95% CI, 0.82-0.90; P < .001), compared with those having the same stages of later-onset CRC. No survival advantage was observed among patients diagnosed at age 25 or younger or those with stage III or IV disease.
“Interestingly, hereditary nonpolyposis colorectal cancer, owing to underlying mismatch repair deficiency, is associated with superior survival and is often diagnosed in individuals from ages 35-45 years,” the investigators noted. “In contrast, adenomatous polyposis coli syndrome is more common in individuals who are diagnosed with CRC at age younger than 20 years (10%), compared with those diagnosed at later ages (0.1%), and adenomatous polyposis coli syndrome is not associated with a survival advantage. These high penetrance syndromes could partly account for the relative heterogeneity in survival across ages among individuals with early-onset CRC.”
Cautious about interpretation
Dr. Cheng and colleagues concluded their publication with a disclaimer: “Our finding of a survival advantage associated with early-onset CRC among younger individuals should be interpreted cautiously, given that the advantage had a small magnitude and was heterogeneous by age and stage,” they wrote. “Further study is needed to understand the underlying heterogeneity of survival by age and stage among individuals with early-onset CRC.”
Kirbi L. Yelorda, MD, of Stanford (Calif.) University, and colleagues, had a similar interpretation.
“These results offer support for effectiveness of treatment in patients diagnosed with CRC at younger ages; however, they must be interpreted within the context of epidemiological and biological factors,” Dr. Yelorda and colleagues wrote in an accompanying editorial.
The findings also suggest that the recent reduction in recommended screening age by the U.S. Preventive Services Task Force – from 50 years to 45 years – is warranted, they added, but screening younger patients remains unnecessary.
“While these results do not suggest that screening should start for patients younger than 45 years, they do support the benefit of early detection in young patients,” Dr. Yelorda and colleagues wrote, noting a “fairly low incidence rate” among individuals younger than 45, which is insufficient to justify the risk-to-benefit ratio and increased costs associated with expanded screening.
Important but not surprising
It’s “not surprising” that early-onset patients typically have better survival than later-onset patients, according to Joseph C. Anderson, MD, associate professor at White River Junction Veterans Affairs Medical Center, Hartford, Vt.; Geisel School of Medicine at Dartmouth, Hanover, N.H.; and the University of Connecticut, Farmington.
“They’re younger, have less comorbidities, and can tolerate chemotherapy,” Dr. Anderson said in an interview. “It’s not surprising that people do poorly with later stages. Younger people are no exception.”
Dr. Anderson, who previously coauthored an editorial weighing the pros and cons of earlier screening, noted that earlier screening is needed because of the rising incidence of late-stage diagnoses among younger patients, which, as the study found, are associated with worse outcomes.
Beyond adherence to screening recommendations, Dr. Anderson urged clinicians to be aggressive when doing a workup of CRC symptoms in younger patients, among whom delayed diagnoses are more common.
“We can’t just say it’s something more benign, like hemorrhoids, like we used to,” Dr. Anderson said. “Somebody who’s 30 years old and having rectal bleeding needs to be evaluated promptly – there can’t be a delay.”
The study was supported by the National Institutes of Health and Stand Up To Cancer (grant administered by the American Association for Cancer Research). The investigators disclosed relationships with Evergrande Group, Janssen, Revolution Medicines, and others. One editorialist reported serving as a member of the USPSTF when the guideline for colorectal cancer was developed, and being a coauthor on the guideline. No other disclosures were reported among editorialists. Dr. Anderson reported no relevant conflicts of interest.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
FROM JAMA NETWORK OPEN