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AGA releases POWER – an obesity practice guide for gastroenterologists
The obesity epidemic has reached critical proportions. A new practice guide from the American Gastroenterological Association aims to help gastroenterologists engage in a multidisciplinary effort to tackle the problem.
The guide, entitled “POWER: Practice Guide on Obesity and Weight Management, Education and Resources,” includes a comprehensive clinical process for assessing and safely and effectively managing patients with obesity, as well as a framework focused on helping practitioners navigate the business operational issues related to the management of obesity. Both are in press for the May issue of Clinical Gastroenterology and Hepatology (2016. doi: 10.1016/j.cgh.2016.10.023).
The POWER model recognizes obesity as an epidemic and as an economic and societal burden that should be embraced as a chronic, relapsing disease best managed across a flexible care cycle using a team approach.
“Every single gastroenterologist is at the front line of this obesity epidemic. Before patients develop diabetes or joint problems or cardiovascular disease, they are already in our clinics, they already have [gastroesophageal reflux disease], they have nonalcoholic fatty liver disease, they have colon cancer – and those conditions present even earlier than the other complications of obesity,” said Dr. Acosta of the Mayo Clinic, Rochester, Minn.
The guide is a model for addressing obesity – the root cause of many of these conditions – rather than simply treating its symptoms, he added.
The approach to obesity management promoted by POWER involves four phases along a continuum of care: assessment, intensive weight loss intervention, weight stabilization and reintensification when needed, and prevention of weight regain.
Lifestyle changes are the cornerstones of obesity management and maintenance of weight loss, but the POWER model includes much more, as it incorporates guidance on the use of pharmacotherapy, bariatric endoscopy, and surgery.
“We tried to make it extremely simple, bringing it down to the busy clinician level,” Dr. Acosta said. “We want to be able to embrace and tackle obesity... in a very straightforward manner.”
Gastroenterologists shouldn’t be afraid of taking on obesity, he added.
“We feel comfortable managing extremely complicated medications, so we should be able to handle the obesity medications. We are already endoscopists... so we want all gastroenterologists to say, ‘I can do this, too; I can incorporate this into my practice,’ ” he said.
Further, gastroenterologists already have a relationship with bariatric surgeons, so referring those with obesity for surgery if appropriate is also simple, he added.
When it comes to moving through the four phases of care, each should be addressed separately using the best evidence available. Realistic goals should be set, and only when those goals are met should care move to the next phase, according to the guide. Learn how to implement the AGA Obesity Practice Guide at www.gastro.org/obesity.
The assessment phase should include a medical evaluation to identify underlying etiologies, screen for causes of secondary weight gain, and identify related comorbidities. A nutrition evaluation should focus not only on nutritional status and appetite, but also on the patient’s relationship with food, food allergies and intolerances, and food environment. A physical activity/exercise evaluation should explore the patient’s activity level and preferences, as well as limiting factors such as joint disease.
A psychosocial evaluation is particularly important, as behavioral modification is a critical component of successful obesity management, and some patients – such as those with a low score on the weight Efficacy Lifestyle Questionnaire Short-Form – may benefit from referral to a health care professional experienced in obesity counseling and behavioral therapy.
Gastroenterologists already work with other specialists, including nutritionists, psychiatrists, and psychologists within their institutions and communities, so the POWER model is an extension of that.
“That’s what this proposes – a multidisciplinary team effort,” he said.
The approach to treatment should be based on the findings of these assessments.
“Physicians should discuss all the appropriate options and their expected weight loss, potential side effects, and figure in the patient’s wishes and goals. Furthermore, physicians should recognize special comorbidities that may favor one intervention over another,” the authors wrote.
The intensive weight loss intervention phase should be based on modest initial weight loss goals, which increase the likelihood of success, increase patient confidence, and encourage ongoing efforts to lose weight. Further, modest weight loss vs. larger amounts of weight loss is more easily achieved and maintained. In addition to lifestyle changes, an evaluation of whether other interventions are needed is important, particularly in patients with weight regain or plateaus in weight loss.
The weight stabilization and intensification therapy for relapse phase is essential to prevent weight regain and its associated consequences. This phase introduces patients to the attitudes and behaviors that are likely to lead to long-term maintenance of weight loss, the authors note.
The prevention of weight regain phase – a maintenance phase – is unique among obesity care guidelines, and is a critical component of obesity management, Dr. Acosta said.
“Helping patients lose weight and keep it off requires a comprehensive and sustained effort that involves devising an individualized approach to diet, behavior, and exercise,” he and his colleagues wrote.
In addition to detailed steps and tips for moving through this care cycle, the POWER guide also details the various tools to facilitate adherence to a healthier diet and lifestyle. Various medications, including phentermine, extended-release phentermine/topiramate, lorcaserin, and liraglutide are described, as are various types of bariatric endoscopy and bariatric surgery.
A section on addressing the unique needs of obese children and adolescents is also included in the guide for those gastroenterologists who treat children.
“Obesity really begins in childhood, so it is a pediatric disease in its origin, so it was important to us to incorporate issues unique to children for our pediatric GI colleagues,” Dr. Streett said.
Importantly, the practice guide was developed with input from the Society of American Gastrointestinal and Endoscopic Surgeons, The Obesity Society, the Academy of Nutrition and Dietetics, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. and the program has been endorsed with additional input by the American Society for Gastrointestinal Endoscopy, American Society for Metabolic and Bariatric Surgery, American Association for the Study of Liver Diseases, and the Obesity Medicine Association.
This collaborative approach is also unique among existing guidelines, and is important, given the need for practitioners across the care spectrum to work together to address obesity, she said.
“What we’ve been doing [individually] hasn’t worked successfully, so that is something that people recognize in the field of medicine: Obesity is something that has physiological, nutritional, dietetic, socioeconomic, and behavioral aspects and we need to have a multipronged approach for success. We need patients to be hearing similar messages and having their care integrated,” she said, adding that “as we move toward a value-based schema, this is the perfect disorder to address in that way.”
Dr. Acosta is a stockholder of Gila Therapeutics and serves on the scientific advisory board or board of directors of Gila Therapeutics, Inversago, and General Mills. Dr. Streett reported having no disclosures.
The obesity epidemic has reached critical proportions. A new practice guide from the American Gastroenterological Association aims to help gastroenterologists engage in a multidisciplinary effort to tackle the problem.
The guide, entitled “POWER: Practice Guide on Obesity and Weight Management, Education and Resources,” includes a comprehensive clinical process for assessing and safely and effectively managing patients with obesity, as well as a framework focused on helping practitioners navigate the business operational issues related to the management of obesity. Both are in press for the May issue of Clinical Gastroenterology and Hepatology (2016. doi: 10.1016/j.cgh.2016.10.023).
The POWER model recognizes obesity as an epidemic and as an economic and societal burden that should be embraced as a chronic, relapsing disease best managed across a flexible care cycle using a team approach.
“Every single gastroenterologist is at the front line of this obesity epidemic. Before patients develop diabetes or joint problems or cardiovascular disease, they are already in our clinics, they already have [gastroesophageal reflux disease], they have nonalcoholic fatty liver disease, they have colon cancer – and those conditions present even earlier than the other complications of obesity,” said Dr. Acosta of the Mayo Clinic, Rochester, Minn.
The guide is a model for addressing obesity – the root cause of many of these conditions – rather than simply treating its symptoms, he added.
The approach to obesity management promoted by POWER involves four phases along a continuum of care: assessment, intensive weight loss intervention, weight stabilization and reintensification when needed, and prevention of weight regain.
Lifestyle changes are the cornerstones of obesity management and maintenance of weight loss, but the POWER model includes much more, as it incorporates guidance on the use of pharmacotherapy, bariatric endoscopy, and surgery.
“We tried to make it extremely simple, bringing it down to the busy clinician level,” Dr. Acosta said. “We want to be able to embrace and tackle obesity... in a very straightforward manner.”
Gastroenterologists shouldn’t be afraid of taking on obesity, he added.
“We feel comfortable managing extremely complicated medications, so we should be able to handle the obesity medications. We are already endoscopists... so we want all gastroenterologists to say, ‘I can do this, too; I can incorporate this into my practice,’ ” he said.
Further, gastroenterologists already have a relationship with bariatric surgeons, so referring those with obesity for surgery if appropriate is also simple, he added.
When it comes to moving through the four phases of care, each should be addressed separately using the best evidence available. Realistic goals should be set, and only when those goals are met should care move to the next phase, according to the guide. Learn how to implement the AGA Obesity Practice Guide at www.gastro.org/obesity.
The assessment phase should include a medical evaluation to identify underlying etiologies, screen for causes of secondary weight gain, and identify related comorbidities. A nutrition evaluation should focus not only on nutritional status and appetite, but also on the patient’s relationship with food, food allergies and intolerances, and food environment. A physical activity/exercise evaluation should explore the patient’s activity level and preferences, as well as limiting factors such as joint disease.
A psychosocial evaluation is particularly important, as behavioral modification is a critical component of successful obesity management, and some patients – such as those with a low score on the weight Efficacy Lifestyle Questionnaire Short-Form – may benefit from referral to a health care professional experienced in obesity counseling and behavioral therapy.
Gastroenterologists already work with other specialists, including nutritionists, psychiatrists, and psychologists within their institutions and communities, so the POWER model is an extension of that.
“That’s what this proposes – a multidisciplinary team effort,” he said.
The approach to treatment should be based on the findings of these assessments.
“Physicians should discuss all the appropriate options and their expected weight loss, potential side effects, and figure in the patient’s wishes and goals. Furthermore, physicians should recognize special comorbidities that may favor one intervention over another,” the authors wrote.
The intensive weight loss intervention phase should be based on modest initial weight loss goals, which increase the likelihood of success, increase patient confidence, and encourage ongoing efforts to lose weight. Further, modest weight loss vs. larger amounts of weight loss is more easily achieved and maintained. In addition to lifestyle changes, an evaluation of whether other interventions are needed is important, particularly in patients with weight regain or plateaus in weight loss.
The weight stabilization and intensification therapy for relapse phase is essential to prevent weight regain and its associated consequences. This phase introduces patients to the attitudes and behaviors that are likely to lead to long-term maintenance of weight loss, the authors note.
The prevention of weight regain phase – a maintenance phase – is unique among obesity care guidelines, and is a critical component of obesity management, Dr. Acosta said.
“Helping patients lose weight and keep it off requires a comprehensive and sustained effort that involves devising an individualized approach to diet, behavior, and exercise,” he and his colleagues wrote.
In addition to detailed steps and tips for moving through this care cycle, the POWER guide also details the various tools to facilitate adherence to a healthier diet and lifestyle. Various medications, including phentermine, extended-release phentermine/topiramate, lorcaserin, and liraglutide are described, as are various types of bariatric endoscopy and bariatric surgery.
A section on addressing the unique needs of obese children and adolescents is also included in the guide for those gastroenterologists who treat children.
“Obesity really begins in childhood, so it is a pediatric disease in its origin, so it was important to us to incorporate issues unique to children for our pediatric GI colleagues,” Dr. Streett said.
Importantly, the practice guide was developed with input from the Society of American Gastrointestinal and Endoscopic Surgeons, The Obesity Society, the Academy of Nutrition and Dietetics, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. and the program has been endorsed with additional input by the American Society for Gastrointestinal Endoscopy, American Society for Metabolic and Bariatric Surgery, American Association for the Study of Liver Diseases, and the Obesity Medicine Association.
This collaborative approach is also unique among existing guidelines, and is important, given the need for practitioners across the care spectrum to work together to address obesity, she said.
“What we’ve been doing [individually] hasn’t worked successfully, so that is something that people recognize in the field of medicine: Obesity is something that has physiological, nutritional, dietetic, socioeconomic, and behavioral aspects and we need to have a multipronged approach for success. We need patients to be hearing similar messages and having their care integrated,” she said, adding that “as we move toward a value-based schema, this is the perfect disorder to address in that way.”
Dr. Acosta is a stockholder of Gila Therapeutics and serves on the scientific advisory board or board of directors of Gila Therapeutics, Inversago, and General Mills. Dr. Streett reported having no disclosures.
The obesity epidemic has reached critical proportions. A new practice guide from the American Gastroenterological Association aims to help gastroenterologists engage in a multidisciplinary effort to tackle the problem.
The guide, entitled “POWER: Practice Guide on Obesity and Weight Management, Education and Resources,” includes a comprehensive clinical process for assessing and safely and effectively managing patients with obesity, as well as a framework focused on helping practitioners navigate the business operational issues related to the management of obesity. Both are in press for the May issue of Clinical Gastroenterology and Hepatology (2016. doi: 10.1016/j.cgh.2016.10.023).
The POWER model recognizes obesity as an epidemic and as an economic and societal burden that should be embraced as a chronic, relapsing disease best managed across a flexible care cycle using a team approach.
“Every single gastroenterologist is at the front line of this obesity epidemic. Before patients develop diabetes or joint problems or cardiovascular disease, they are already in our clinics, they already have [gastroesophageal reflux disease], they have nonalcoholic fatty liver disease, they have colon cancer – and those conditions present even earlier than the other complications of obesity,” said Dr. Acosta of the Mayo Clinic, Rochester, Minn.
The guide is a model for addressing obesity – the root cause of many of these conditions – rather than simply treating its symptoms, he added.
The approach to obesity management promoted by POWER involves four phases along a continuum of care: assessment, intensive weight loss intervention, weight stabilization and reintensification when needed, and prevention of weight regain.
Lifestyle changes are the cornerstones of obesity management and maintenance of weight loss, but the POWER model includes much more, as it incorporates guidance on the use of pharmacotherapy, bariatric endoscopy, and surgery.
“We tried to make it extremely simple, bringing it down to the busy clinician level,” Dr. Acosta said. “We want to be able to embrace and tackle obesity... in a very straightforward manner.”
Gastroenterologists shouldn’t be afraid of taking on obesity, he added.
“We feel comfortable managing extremely complicated medications, so we should be able to handle the obesity medications. We are already endoscopists... so we want all gastroenterologists to say, ‘I can do this, too; I can incorporate this into my practice,’ ” he said.
Further, gastroenterologists already have a relationship with bariatric surgeons, so referring those with obesity for surgery if appropriate is also simple, he added.
When it comes to moving through the four phases of care, each should be addressed separately using the best evidence available. Realistic goals should be set, and only when those goals are met should care move to the next phase, according to the guide. Learn how to implement the AGA Obesity Practice Guide at www.gastro.org/obesity.
The assessment phase should include a medical evaluation to identify underlying etiologies, screen for causes of secondary weight gain, and identify related comorbidities. A nutrition evaluation should focus not only on nutritional status and appetite, but also on the patient’s relationship with food, food allergies and intolerances, and food environment. A physical activity/exercise evaluation should explore the patient’s activity level and preferences, as well as limiting factors such as joint disease.
A psychosocial evaluation is particularly important, as behavioral modification is a critical component of successful obesity management, and some patients – such as those with a low score on the weight Efficacy Lifestyle Questionnaire Short-Form – may benefit from referral to a health care professional experienced in obesity counseling and behavioral therapy.
Gastroenterologists already work with other specialists, including nutritionists, psychiatrists, and psychologists within their institutions and communities, so the POWER model is an extension of that.
“That’s what this proposes – a multidisciplinary team effort,” he said.
The approach to treatment should be based on the findings of these assessments.
“Physicians should discuss all the appropriate options and their expected weight loss, potential side effects, and figure in the patient’s wishes and goals. Furthermore, physicians should recognize special comorbidities that may favor one intervention over another,” the authors wrote.
The intensive weight loss intervention phase should be based on modest initial weight loss goals, which increase the likelihood of success, increase patient confidence, and encourage ongoing efforts to lose weight. Further, modest weight loss vs. larger amounts of weight loss is more easily achieved and maintained. In addition to lifestyle changes, an evaluation of whether other interventions are needed is important, particularly in patients with weight regain or plateaus in weight loss.
The weight stabilization and intensification therapy for relapse phase is essential to prevent weight regain and its associated consequences. This phase introduces patients to the attitudes and behaviors that are likely to lead to long-term maintenance of weight loss, the authors note.
The prevention of weight regain phase – a maintenance phase – is unique among obesity care guidelines, and is a critical component of obesity management, Dr. Acosta said.
“Helping patients lose weight and keep it off requires a comprehensive and sustained effort that involves devising an individualized approach to diet, behavior, and exercise,” he and his colleagues wrote.
In addition to detailed steps and tips for moving through this care cycle, the POWER guide also details the various tools to facilitate adherence to a healthier diet and lifestyle. Various medications, including phentermine, extended-release phentermine/topiramate, lorcaserin, and liraglutide are described, as are various types of bariatric endoscopy and bariatric surgery.
A section on addressing the unique needs of obese children and adolescents is also included in the guide for those gastroenterologists who treat children.
“Obesity really begins in childhood, so it is a pediatric disease in its origin, so it was important to us to incorporate issues unique to children for our pediatric GI colleagues,” Dr. Streett said.
Importantly, the practice guide was developed with input from the Society of American Gastrointestinal and Endoscopic Surgeons, The Obesity Society, the Academy of Nutrition and Dietetics, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. and the program has been endorsed with additional input by the American Society for Gastrointestinal Endoscopy, American Society for Metabolic and Bariatric Surgery, American Association for the Study of Liver Diseases, and the Obesity Medicine Association.
This collaborative approach is also unique among existing guidelines, and is important, given the need for practitioners across the care spectrum to work together to address obesity, she said.
“What we’ve been doing [individually] hasn’t worked successfully, so that is something that people recognize in the field of medicine: Obesity is something that has physiological, nutritional, dietetic, socioeconomic, and behavioral aspects and we need to have a multipronged approach for success. We need patients to be hearing similar messages and having their care integrated,” she said, adding that “as we move toward a value-based schema, this is the perfect disorder to address in that way.”
Dr. Acosta is a stockholder of Gila Therapeutics and serves on the scientific advisory board or board of directors of Gila Therapeutics, Inversago, and General Mills. Dr. Streett reported having no disclosures.
South dominates rankings of most obese U.S. cities
Jackson, Miss., is the most obese city in the United States for 2017, according to the personal finance website WalletHub.
The city topped the ranking of the 100 heaviest metro areas in the country with a score of 84.9 out of a possible 100 points based on 17 key metrics in three broad categories: obese and overweight people (50 points), weight-related health problems (30 points), and health environment (20 points), according to WalletHub.
The second-most obese city for 2017 is Memphis, with Little Rock, Ark.; McAllen, Tex.; and Shreveport, La., occupying the rest of the top five. All of the cities in the top 10 – all of the cities in the top 20, actually – are located in the South, with the first non–Southern city (Indianapolis) making its appearance at number 21, the WalletHub analysis shows. At number 100 in the rankings is Seattle/Tacoma.
Data for the analysis came from the Centers for Disease Control and Prevention, County Health Rankings, the Department of Agriculture’s Economic Research Service, the Child and Adolescent Health Measurement Initiative, the Trust for America’s Health, and WalletHub’s own research, including its report Best & Worst Cities for an Active Lifestyle.
Jackson, Miss., is the most obese city in the United States for 2017, according to the personal finance website WalletHub.
The city topped the ranking of the 100 heaviest metro areas in the country with a score of 84.9 out of a possible 100 points based on 17 key metrics in three broad categories: obese and overweight people (50 points), weight-related health problems (30 points), and health environment (20 points), according to WalletHub.
The second-most obese city for 2017 is Memphis, with Little Rock, Ark.; McAllen, Tex.; and Shreveport, La., occupying the rest of the top five. All of the cities in the top 10 – all of the cities in the top 20, actually – are located in the South, with the first non–Southern city (Indianapolis) making its appearance at number 21, the WalletHub analysis shows. At number 100 in the rankings is Seattle/Tacoma.
Data for the analysis came from the Centers for Disease Control and Prevention, County Health Rankings, the Department of Agriculture’s Economic Research Service, the Child and Adolescent Health Measurement Initiative, the Trust for America’s Health, and WalletHub’s own research, including its report Best & Worst Cities for an Active Lifestyle.
Jackson, Miss., is the most obese city in the United States for 2017, according to the personal finance website WalletHub.
The city topped the ranking of the 100 heaviest metro areas in the country with a score of 84.9 out of a possible 100 points based on 17 key metrics in three broad categories: obese and overweight people (50 points), weight-related health problems (30 points), and health environment (20 points), according to WalletHub.
The second-most obese city for 2017 is Memphis, with Little Rock, Ark.; McAllen, Tex.; and Shreveport, La., occupying the rest of the top five. All of the cities in the top 10 – all of the cities in the top 20, actually – are located in the South, with the first non–Southern city (Indianapolis) making its appearance at number 21, the WalletHub analysis shows. At number 100 in the rankings is Seattle/Tacoma.
Data for the analysis came from the Centers for Disease Control and Prevention, County Health Rankings, the Department of Agriculture’s Economic Research Service, the Child and Adolescent Health Measurement Initiative, the Trust for America’s Health, and WalletHub’s own research, including its report Best & Worst Cities for an Active Lifestyle.
Open-capsule PPIs linked to faster ulcer healing after Roux-en-Y
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules. 
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed ulcers at the gastrojejunal anastomosis after Roux-en-Y gastric bypass.
Major finding: The median time to ulcer healing was 91.0 versus 342.0 days for the open- and closed-capsule groups, respectively (P less than .001).
Data source: A single-center retrospective study of 162 patients.
Disclosures: The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
AGA Clinical Practice Update: Best practice advice on EBT use released
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes. 
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
FROM GASTROENTEROLOGY
Low-volume PEG linked to hypokalemia in at-risk patients
FROM GASTROINTESTINAL ENDOSCOPY
Bowel preparation with low-volume polyethylene glycol led to hypokalemia in nearly 25% of high-risk patients who were normokalemic at baseline, according to a first-in-kind large single-center prospective study.
“Hypokalemia is frequently encountered after low-volume PEG bowel cleansing in high-risk patients,” wrote Ankie Reumkens, MD, and her associates at Maastricht University Medical Center, Maastricht, the Netherlands. The report was published online in Gastrointestinal Endoscopy. “Additional large-scale studies are needed on the prevalence of hypokalemia in nonselected populations undergoing bowel cleansing and on the occurrence of potentially very serious side effects in order to decide on screening of high-risk groups in daily clinical practice.”
Good bowel preparation is crucial to colonoscopy. Bowel preparation with both sodium phosphate and high-volume polyethylene glycol (PEG) has caused hypokalemia, but whether this is true of low-volume PEG is unclear, the investigators said. Recently, at their institution, two colonoscopy patients developed severe hypokalemia and died of ventricular arrhythmias after receiving low-volume PEG. These deaths spurred the researchers to prospectively study 1,822 colonoscopy patients who underwent bowel preparation with low-volume PEG in 2014 and who were considered at high risk of hypokalemia by their gastroenterologists or because of hospitalization or diuretic use.
The researchers measured serum potassium levels of all patients before bowel cleansing. After bowel testing, they retested a subgroup of 301 patients who were normokalemic (3.5-5 mmol/L) at baseline (Gastrointest Endosc. 2017 Feb 7. doi: 10.1016/j.gie.2017.01.040).
In all, 77 patients (4%) were hypokalemic before bowel cleansing, the researchers said. Fully one-third were hospitalized, and hospitalization remained a significant risk factor for baseline hypokalemia even after the researchers controlled for diuretic use, age, sex, and reason for colonoscopy (odds ratio, 2.5; 95% confidence interval, 1.5 to 4.2; P less than .001).
Follow-up testing showed that 71 patients (24%) who were normokalemic at baseline became hypokalemic (serum potassium less than 3.5 mmol/L) after bowel preparation with low-volume PEG. Only diuretic use remained significantly associated with this outcome after researchers accounted for age, sex, reason for colonoscopy, and hospitalization status (odds ratio, 2.3; 95% confidence interval, 1.3 to 4.0; P = .004).
This study included preselected groups of diuretic users and hospitalized patients, making it difficult to assess specific and detailed risk factors for hypokalemia, the researchers said. “Despite this limitation, our study clearly shows that hypokalemia may develop in a substantial percentage of patients after the ingestion of low-volume PEG,” they emphasized. But they recommended population-based studies to determine the true prevalence of hypokalemia after colonoscopy, examine risk factors for this outcome, and consider whether it makes sense to screen subgroups at risk.
The protocol at their hospital is to measure serum potassium before bowel cleansing in hospitalized patients and those on diuretics, they noted. Hypokalemic patients then receive oral potassium if their potassium level was 2.5-3.0 mmol/L, and intravenous potassium if their level was below 2.5 mmol/L.
The investigators reported having no funding sources and no competing interests.
FROM GASTROINTESTINAL ENDOSCOPY
Bowel preparation with low-volume polyethylene glycol led to hypokalemia in nearly 25% of high-risk patients who were normokalemic at baseline, according to a first-in-kind large single-center prospective study.
“Hypokalemia is frequently encountered after low-volume PEG bowel cleansing in high-risk patients,” wrote Ankie Reumkens, MD, and her associates at Maastricht University Medical Center, Maastricht, the Netherlands. The report was published online in Gastrointestinal Endoscopy. “Additional large-scale studies are needed on the prevalence of hypokalemia in nonselected populations undergoing bowel cleansing and on the occurrence of potentially very serious side effects in order to decide on screening of high-risk groups in daily clinical practice.”
Good bowel preparation is crucial to colonoscopy. Bowel preparation with both sodium phosphate and high-volume polyethylene glycol (PEG) has caused hypokalemia, but whether this is true of low-volume PEG is unclear, the investigators said. Recently, at their institution, two colonoscopy patients developed severe hypokalemia and died of ventricular arrhythmias after receiving low-volume PEG. These deaths spurred the researchers to prospectively study 1,822 colonoscopy patients who underwent bowel preparation with low-volume PEG in 2014 and who were considered at high risk of hypokalemia by their gastroenterologists or because of hospitalization or diuretic use.
The researchers measured serum potassium levels of all patients before bowel cleansing. After bowel testing, they retested a subgroup of 301 patients who were normokalemic (3.5-5 mmol/L) at baseline (Gastrointest Endosc. 2017 Feb 7. doi: 10.1016/j.gie.2017.01.040).
In all, 77 patients (4%) were hypokalemic before bowel cleansing, the researchers said. Fully one-third were hospitalized, and hospitalization remained a significant risk factor for baseline hypokalemia even after the researchers controlled for diuretic use, age, sex, and reason for colonoscopy (odds ratio, 2.5; 95% confidence interval, 1.5 to 4.2; P less than .001).
Follow-up testing showed that 71 patients (24%) who were normokalemic at baseline became hypokalemic (serum potassium less than 3.5 mmol/L) after bowel preparation with low-volume PEG. Only diuretic use remained significantly associated with this outcome after researchers accounted for age, sex, reason for colonoscopy, and hospitalization status (odds ratio, 2.3; 95% confidence interval, 1.3 to 4.0; P = .004).
This study included preselected groups of diuretic users and hospitalized patients, making it difficult to assess specific and detailed risk factors for hypokalemia, the researchers said. “Despite this limitation, our study clearly shows that hypokalemia may develop in a substantial percentage of patients after the ingestion of low-volume PEG,” they emphasized. But they recommended population-based studies to determine the true prevalence of hypokalemia after colonoscopy, examine risk factors for this outcome, and consider whether it makes sense to screen subgroups at risk.
The protocol at their hospital is to measure serum potassium before bowel cleansing in hospitalized patients and those on diuretics, they noted. Hypokalemic patients then receive oral potassium if their potassium level was 2.5-3.0 mmol/L, and intravenous potassium if their level was below 2.5 mmol/L.
The investigators reported having no funding sources and no competing interests.
FROM GASTROINTESTINAL ENDOSCOPY
Bowel preparation with low-volume polyethylene glycol led to hypokalemia in nearly 25% of high-risk patients who were normokalemic at baseline, according to a first-in-kind large single-center prospective study.
“Hypokalemia is frequently encountered after low-volume PEG bowel cleansing in high-risk patients,” wrote Ankie Reumkens, MD, and her associates at Maastricht University Medical Center, Maastricht, the Netherlands. The report was published online in Gastrointestinal Endoscopy. “Additional large-scale studies are needed on the prevalence of hypokalemia in nonselected populations undergoing bowel cleansing and on the occurrence of potentially very serious side effects in order to decide on screening of high-risk groups in daily clinical practice.”
Good bowel preparation is crucial to colonoscopy. Bowel preparation with both sodium phosphate and high-volume polyethylene glycol (PEG) has caused hypokalemia, but whether this is true of low-volume PEG is unclear, the investigators said. Recently, at their institution, two colonoscopy patients developed severe hypokalemia and died of ventricular arrhythmias after receiving low-volume PEG. These deaths spurred the researchers to prospectively study 1,822 colonoscopy patients who underwent bowel preparation with low-volume PEG in 2014 and who were considered at high risk of hypokalemia by their gastroenterologists or because of hospitalization or diuretic use.
The researchers measured serum potassium levels of all patients before bowel cleansing. After bowel testing, they retested a subgroup of 301 patients who were normokalemic (3.5-5 mmol/L) at baseline (Gastrointest Endosc. 2017 Feb 7. doi: 10.1016/j.gie.2017.01.040).
In all, 77 patients (4%) were hypokalemic before bowel cleansing, the researchers said. Fully one-third were hospitalized, and hospitalization remained a significant risk factor for baseline hypokalemia even after the researchers controlled for diuretic use, age, sex, and reason for colonoscopy (odds ratio, 2.5; 95% confidence interval, 1.5 to 4.2; P less than .001).
Follow-up testing showed that 71 patients (24%) who were normokalemic at baseline became hypokalemic (serum potassium less than 3.5 mmol/L) after bowel preparation with low-volume PEG. Only diuretic use remained significantly associated with this outcome after researchers accounted for age, sex, reason for colonoscopy, and hospitalization status (odds ratio, 2.3; 95% confidence interval, 1.3 to 4.0; P = .004).
This study included preselected groups of diuretic users and hospitalized patients, making it difficult to assess specific and detailed risk factors for hypokalemia, the researchers said. “Despite this limitation, our study clearly shows that hypokalemia may develop in a substantial percentage of patients after the ingestion of low-volume PEG,” they emphasized. But they recommended population-based studies to determine the true prevalence of hypokalemia after colonoscopy, examine risk factors for this outcome, and consider whether it makes sense to screen subgroups at risk.
The protocol at their hospital is to measure serum potassium before bowel cleansing in hospitalized patients and those on diuretics, they noted. Hypokalemic patients then receive oral potassium if their potassium level was 2.5-3.0 mmol/L, and intravenous potassium if their level was below 2.5 mmol/L.
The investigators reported having no funding sources and no competing interests.
Key clinical point. Bowel preparation with low-volume polyethylene glycol (PEG) led to hypokalemia in at-risk patients.
Major finding: In all, 24% of patients who were normokalemic before bowel cleansing developed hypokalemia afterward. Diuretic use was a significant risk factor for hypokalemia (odds ratio, 2.3; P = .004).
Data source: A prospective study of 1,822 colonoscopy patients considered at high risk of hypokalemia.
Disclosures: The investigators reported having no funding sources and no competing interests.
FDA confirms complications from intragastric balloons
Complications from overinflation and acute pancreatitis can create problems for obesity patients treated with intragastric balloons, according to a statement from the Food and Drug Administration. In a letter to health care providers published on February 9, 2017, the FDA warned of the two specific issues that have been the subject of multiple adverse event reports.
“We recommend that you closely monitor patients with these devices for these adverse events, and to submit reports to help us better understand any complications from the use of these obesity treatment devices,” the letter said.
Most of the overinflation reports involved the Orbera Intragastric Balloon System (Apollo Endosurgery) that uses a single balloon, although some reports involved the ReShape Integrated Dual Balloon System (ReShape Medical) that uses two balloons. Neither product mentions overinflation risk in its labeling. “At this moment there is not enough information to determine what is causing the balloon to overinflate,” according to the FDA letter.
A separate set of adverse event reports noted the development of acute pancreatitis caused when the balloons compressed other gastrointestinal structures. Both the Orbera and ReShape products were associated with pancreatitis, although neither lists pancreatitis as a potential complication on their labels. Pancreatitis was reported as early as 3 days after implantation, and symptoms included severe back and abdominal pain.
The FDA letter recommends that health care providers consider overinflation and pancreatitis in their differential diagnoses of obesity patients with intragastric balloons who present with the symptoms described, and to report any type of serious adverse events associated with intragastric balloons to the FDA through the MedWatch program. For more information about reporting adverse events to the FDA, visit the MedWatch site.
Complications from overinflation and acute pancreatitis can create problems for obesity patients treated with intragastric balloons, according to a statement from the Food and Drug Administration. In a letter to health care providers published on February 9, 2017, the FDA warned of the two specific issues that have been the subject of multiple adverse event reports.
“We recommend that you closely monitor patients with these devices for these adverse events, and to submit reports to help us better understand any complications from the use of these obesity treatment devices,” the letter said.
Most of the overinflation reports involved the Orbera Intragastric Balloon System (Apollo Endosurgery) that uses a single balloon, although some reports involved the ReShape Integrated Dual Balloon System (ReShape Medical) that uses two balloons. Neither product mentions overinflation risk in its labeling. “At this moment there is not enough information to determine what is causing the balloon to overinflate,” according to the FDA letter.
A separate set of adverse event reports noted the development of acute pancreatitis caused when the balloons compressed other gastrointestinal structures. Both the Orbera and ReShape products were associated with pancreatitis, although neither lists pancreatitis as a potential complication on their labels. Pancreatitis was reported as early as 3 days after implantation, and symptoms included severe back and abdominal pain.
The FDA letter recommends that health care providers consider overinflation and pancreatitis in their differential diagnoses of obesity patients with intragastric balloons who present with the symptoms described, and to report any type of serious adverse events associated with intragastric balloons to the FDA through the MedWatch program. For more information about reporting adverse events to the FDA, visit the MedWatch site.
Complications from overinflation and acute pancreatitis can create problems for obesity patients treated with intragastric balloons, according to a statement from the Food and Drug Administration. In a letter to health care providers published on February 9, 2017, the FDA warned of the two specific issues that have been the subject of multiple adverse event reports.
“We recommend that you closely monitor patients with these devices for these adverse events, and to submit reports to help us better understand any complications from the use of these obesity treatment devices,” the letter said.
Most of the overinflation reports involved the Orbera Intragastric Balloon System (Apollo Endosurgery) that uses a single balloon, although some reports involved the ReShape Integrated Dual Balloon System (ReShape Medical) that uses two balloons. Neither product mentions overinflation risk in its labeling. “At this moment there is not enough information to determine what is causing the balloon to overinflate,” according to the FDA letter.
A separate set of adverse event reports noted the development of acute pancreatitis caused when the balloons compressed other gastrointestinal structures. Both the Orbera and ReShape products were associated with pancreatitis, although neither lists pancreatitis as a potential complication on their labels. Pancreatitis was reported as early as 3 days after implantation, and symptoms included severe back and abdominal pain.
The FDA letter recommends that health care providers consider overinflation and pancreatitis in their differential diagnoses of obesity patients with intragastric balloons who present with the symptoms described, and to report any type of serious adverse events associated with intragastric balloons to the FDA through the MedWatch program. For more information about reporting adverse events to the FDA, visit the MedWatch site.
IgG4-related disease can strike any organ system
SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.
This new understanding of IgG4-RD, he added, is opening the door to novel treatments.
“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.
IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.
Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.
“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.
Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.
“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.
Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).
Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.
Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.
Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.
But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.
Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.
“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.
He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.
Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.
Treatment with rituxumab
Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.
Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).
“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.
So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.
Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.
Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.
SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.
This new understanding of IgG4-RD, he added, is opening the door to novel treatments.
“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.
IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.
Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.
“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.
Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.
“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.
Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).
Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.
Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.
Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.
But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.
Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.
“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.
He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.
Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.
Treatment with rituxumab
Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.
Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).
“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.
So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.
Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.
Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.
SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.
This new understanding of IgG4-RD, he added, is opening the door to novel treatments.
“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.
IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.
Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.
“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.
Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.
“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.
Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).
Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.
Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.
Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.
But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.
Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.
“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.
He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.
Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.
Treatment with rituxumab
Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.
Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).
“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.
So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).
The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.
Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.
Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM
Urgent colonoscopy for LGIB: Consider case by case
Colonoscopy performed within 24 hours of lower gastrointestinal bleeding appears safe and well tolerated but does not appear to improve a number of important clinical outcomes when compared with elective colonoscopy, according to the findings of a systematic review and meta-analysis.
Such “urgent colonoscopy” may, however, reduce hospital length of stay and cost, Abdul M. Kouanda, MD, of the University of California, San Francisco, and his colleagues reported online in Gastrointestinal Endoscopy.
In a pooled analysis of data from 12 studies with a total of 10,172 patients who underwent urgent colonoscopy, and 14,224 patients who underwent elective colonoscopy, the former was associated with increased use of endoscopic therapeutic interventions, compared with elective colonoscopy (relative risk, 1.70), but not with improved bleeding source localization (RR, 1.08), adverse event rates (RR, 1.05), rebleeding rates (RR, 1.14), transfusion requirements (RR, 1.02), or mortality (RR, 1.17), the investigators found (Gastrointest Endosc. 2017 Feb 4. doi: 10.1016/j.gie.2017.01.035).
The findings are based on nine studies from the United States, two from Japan, and one from Spain. Nine were retrospective cohort studies, two were randomized controlled trials, and one was a prospective cohort study.
With respect to the 70% greater use of therapeutic interventions with urgent colonoscopy, a subanalysis showed that the difference between urgent and elective colonoscopy was evident only in the randomized trials; no difference was seen in the prospective trials. With further stratification of urgent colonoscopy into procedures performed within 12 hours, the observation of increased therapeutic interventions was no longer statistically significant (RR, 3.46), they said.
As for bleeding source localization, the outcomes remained similar when retrospective studies were analyzed separately, and with colonoscopy performed within 12 hours. Blood transfusions decreased with urgent colonoscopy when only retrospective studies were analyzed (RR, 0.84).
The investigators noted that there was a trend toward decreased length of hospital stay among those undergoing urgent colonoscopy (mean of 4.8 days vs. 6.4 days with elective colonoscopy). Only two studies looked at cost: One showed a decrease in hospital costs with urgent vs. elective colonoscopy, while one showed no difference.
“In our pooled analysis, the mean hospital costs in the urgent colonoscopy group were $24,866, compared with $27,691 in the elective group; however, the difference between the two was not statistically significant,” they wrote.
The annual incidence of lower gastrointestinal bleeding (LGIB) in the United States is 20.5-35.7 out of 100,000 patients, and the incidence increases with age; there is a 200-fold increase in incidence from the 3rd to 9th decade of life, the investigators said, adding that the incidence is rising as the population ages.
“Such a trend has important implications for both the quality of care for treating LGIB and the associated costs to the overall U.S. health care system,” they wrote, noting that while colonoscopy is appropriate for evaluating LGIB in most cases, no clear consensus exists with respect to timing of colonoscopy.
Even a recent American Society for Gastrointestinal Endoscopy guideline recommending that initial colonoscopy for severe and hemodynamically stable hematochezia be performed within 8-24 hours of admission is based only on moderate-quality level evidence that is “fraught with a number of limitations,” they wrote.
The current study was designed to “further clarify the utility of urgent versus elective colonoscopy in evaluating patients hospitalized with a lower GI bleed,” they added.
The lack of clinical benefit seen in this study “may be secondary to the benign, often self-resolving natural history in the majority of LGIB cases. However, there may be a subset of patients who could benefit from early intervention (such as severe blood loss, hemodynamically unstable patients), and thus the decision to pursue urgent colonoscopy should be made on a case-by-case basis,” they said.
Further, although several critical patient outcomes did not appear to be impacted by urgent vs. elective colonoscopy in this study, the trends toward a decrease in length of stay suggest that earlier performance of colonoscopy may lead to earlier and better identification of low-risk and high-risk stigmata, allowing those with low-risk lesions to be discharged much earlier.
“Additionally, earlier discharge of patients could also reduce their risk of health care–associated infections and adverse events,” the investigators noted.
The findings with respect to length of stay and cost “align perfectly with the new focus in health care on providing high quality and safe care to patients while at the same time containing medical costs,” they wrote, adding that clinicians should carefully consider all factors when deciding to pursue urgent colonoscopy.”
The study is limited by heterogeneity and publications bias, and by factors inherent in meta-analyses, but it also has several strengths, including a large number of studies and patients. Also, it is the first of its kind to examine “all of the available literature to elucidate the time frame for performing colonoscopy in patients with hematochezia,” the investigators said, concluding that further research is needed to identify subsets of patients who will benefit from early intervention, to evaluate the cost effectiveness of urgent colonoscopy, and to look at – in larger randomized controlled trials – the overall benefit of urgent colonoscopy.
The authors reported having no disclosures.
Colonoscopy performed within 24 hours of lower gastrointestinal bleeding appears safe and well tolerated but does not appear to improve a number of important clinical outcomes when compared with elective colonoscopy, according to the findings of a systematic review and meta-analysis.
Such “urgent colonoscopy” may, however, reduce hospital length of stay and cost, Abdul M. Kouanda, MD, of the University of California, San Francisco, and his colleagues reported online in Gastrointestinal Endoscopy.
In a pooled analysis of data from 12 studies with a total of 10,172 patients who underwent urgent colonoscopy, and 14,224 patients who underwent elective colonoscopy, the former was associated with increased use of endoscopic therapeutic interventions, compared with elective colonoscopy (relative risk, 1.70), but not with improved bleeding source localization (RR, 1.08), adverse event rates (RR, 1.05), rebleeding rates (RR, 1.14), transfusion requirements (RR, 1.02), or mortality (RR, 1.17), the investigators found (Gastrointest Endosc. 2017 Feb 4. doi: 10.1016/j.gie.2017.01.035).
The findings are based on nine studies from the United States, two from Japan, and one from Spain. Nine were retrospective cohort studies, two were randomized controlled trials, and one was a prospective cohort study.
With respect to the 70% greater use of therapeutic interventions with urgent colonoscopy, a subanalysis showed that the difference between urgent and elective colonoscopy was evident only in the randomized trials; no difference was seen in the prospective trials. With further stratification of urgent colonoscopy into procedures performed within 12 hours, the observation of increased therapeutic interventions was no longer statistically significant (RR, 3.46), they said.
As for bleeding source localization, the outcomes remained similar when retrospective studies were analyzed separately, and with colonoscopy performed within 12 hours. Blood transfusions decreased with urgent colonoscopy when only retrospective studies were analyzed (RR, 0.84).
The investigators noted that there was a trend toward decreased length of hospital stay among those undergoing urgent colonoscopy (mean of 4.8 days vs. 6.4 days with elective colonoscopy). Only two studies looked at cost: One showed a decrease in hospital costs with urgent vs. elective colonoscopy, while one showed no difference.
“In our pooled analysis, the mean hospital costs in the urgent colonoscopy group were $24,866, compared with $27,691 in the elective group; however, the difference between the two was not statistically significant,” they wrote.
The annual incidence of lower gastrointestinal bleeding (LGIB) in the United States is 20.5-35.7 out of 100,000 patients, and the incidence increases with age; there is a 200-fold increase in incidence from the 3rd to 9th decade of life, the investigators said, adding that the incidence is rising as the population ages.
“Such a trend has important implications for both the quality of care for treating LGIB and the associated costs to the overall U.S. health care system,” they wrote, noting that while colonoscopy is appropriate for evaluating LGIB in most cases, no clear consensus exists with respect to timing of colonoscopy.
Even a recent American Society for Gastrointestinal Endoscopy guideline recommending that initial colonoscopy for severe and hemodynamically stable hematochezia be performed within 8-24 hours of admission is based only on moderate-quality level evidence that is “fraught with a number of limitations,” they wrote.
The current study was designed to “further clarify the utility of urgent versus elective colonoscopy in evaluating patients hospitalized with a lower GI bleed,” they added.
The lack of clinical benefit seen in this study “may be secondary to the benign, often self-resolving natural history in the majority of LGIB cases. However, there may be a subset of patients who could benefit from early intervention (such as severe blood loss, hemodynamically unstable patients), and thus the decision to pursue urgent colonoscopy should be made on a case-by-case basis,” they said.
Further, although several critical patient outcomes did not appear to be impacted by urgent vs. elective colonoscopy in this study, the trends toward a decrease in length of stay suggest that earlier performance of colonoscopy may lead to earlier and better identification of low-risk and high-risk stigmata, allowing those with low-risk lesions to be discharged much earlier.
“Additionally, earlier discharge of patients could also reduce their risk of health care–associated infections and adverse events,” the investigators noted.
The findings with respect to length of stay and cost “align perfectly with the new focus in health care on providing high quality and safe care to patients while at the same time containing medical costs,” they wrote, adding that clinicians should carefully consider all factors when deciding to pursue urgent colonoscopy.”
The study is limited by heterogeneity and publications bias, and by factors inherent in meta-analyses, but it also has several strengths, including a large number of studies and patients. Also, it is the first of its kind to examine “all of the available literature to elucidate the time frame for performing colonoscopy in patients with hematochezia,” the investigators said, concluding that further research is needed to identify subsets of patients who will benefit from early intervention, to evaluate the cost effectiveness of urgent colonoscopy, and to look at – in larger randomized controlled trials – the overall benefit of urgent colonoscopy.
The authors reported having no disclosures.
Colonoscopy performed within 24 hours of lower gastrointestinal bleeding appears safe and well tolerated but does not appear to improve a number of important clinical outcomes when compared with elective colonoscopy, according to the findings of a systematic review and meta-analysis.
Such “urgent colonoscopy” may, however, reduce hospital length of stay and cost, Abdul M. Kouanda, MD, of the University of California, San Francisco, and his colleagues reported online in Gastrointestinal Endoscopy.
In a pooled analysis of data from 12 studies with a total of 10,172 patients who underwent urgent colonoscopy, and 14,224 patients who underwent elective colonoscopy, the former was associated with increased use of endoscopic therapeutic interventions, compared with elective colonoscopy (relative risk, 1.70), but not with improved bleeding source localization (RR, 1.08), adverse event rates (RR, 1.05), rebleeding rates (RR, 1.14), transfusion requirements (RR, 1.02), or mortality (RR, 1.17), the investigators found (Gastrointest Endosc. 2017 Feb 4. doi: 10.1016/j.gie.2017.01.035).
The findings are based on nine studies from the United States, two from Japan, and one from Spain. Nine were retrospective cohort studies, two were randomized controlled trials, and one was a prospective cohort study.
With respect to the 70% greater use of therapeutic interventions with urgent colonoscopy, a subanalysis showed that the difference between urgent and elective colonoscopy was evident only in the randomized trials; no difference was seen in the prospective trials. With further stratification of urgent colonoscopy into procedures performed within 12 hours, the observation of increased therapeutic interventions was no longer statistically significant (RR, 3.46), they said.
As for bleeding source localization, the outcomes remained similar when retrospective studies were analyzed separately, and with colonoscopy performed within 12 hours. Blood transfusions decreased with urgent colonoscopy when only retrospective studies were analyzed (RR, 0.84).
The investigators noted that there was a trend toward decreased length of hospital stay among those undergoing urgent colonoscopy (mean of 4.8 days vs. 6.4 days with elective colonoscopy). Only two studies looked at cost: One showed a decrease in hospital costs with urgent vs. elective colonoscopy, while one showed no difference.
“In our pooled analysis, the mean hospital costs in the urgent colonoscopy group were $24,866, compared with $27,691 in the elective group; however, the difference between the two was not statistically significant,” they wrote.
The annual incidence of lower gastrointestinal bleeding (LGIB) in the United States is 20.5-35.7 out of 100,000 patients, and the incidence increases with age; there is a 200-fold increase in incidence from the 3rd to 9th decade of life, the investigators said, adding that the incidence is rising as the population ages.
“Such a trend has important implications for both the quality of care for treating LGIB and the associated costs to the overall U.S. health care system,” they wrote, noting that while colonoscopy is appropriate for evaluating LGIB in most cases, no clear consensus exists with respect to timing of colonoscopy.
Even a recent American Society for Gastrointestinal Endoscopy guideline recommending that initial colonoscopy for severe and hemodynamically stable hematochezia be performed within 8-24 hours of admission is based only on moderate-quality level evidence that is “fraught with a number of limitations,” they wrote.
The current study was designed to “further clarify the utility of urgent versus elective colonoscopy in evaluating patients hospitalized with a lower GI bleed,” they added.
The lack of clinical benefit seen in this study “may be secondary to the benign, often self-resolving natural history in the majority of LGIB cases. However, there may be a subset of patients who could benefit from early intervention (such as severe blood loss, hemodynamically unstable patients), and thus the decision to pursue urgent colonoscopy should be made on a case-by-case basis,” they said.
Further, although several critical patient outcomes did not appear to be impacted by urgent vs. elective colonoscopy in this study, the trends toward a decrease in length of stay suggest that earlier performance of colonoscopy may lead to earlier and better identification of low-risk and high-risk stigmata, allowing those with low-risk lesions to be discharged much earlier.
“Additionally, earlier discharge of patients could also reduce their risk of health care–associated infections and adverse events,” the investigators noted.
The findings with respect to length of stay and cost “align perfectly with the new focus in health care on providing high quality and safe care to patients while at the same time containing medical costs,” they wrote, adding that clinicians should carefully consider all factors when deciding to pursue urgent colonoscopy.”
The study is limited by heterogeneity and publications bias, and by factors inherent in meta-analyses, but it also has several strengths, including a large number of studies and patients. Also, it is the first of its kind to examine “all of the available literature to elucidate the time frame for performing colonoscopy in patients with hematochezia,” the investigators said, concluding that further research is needed to identify subsets of patients who will benefit from early intervention, to evaluate the cost effectiveness of urgent colonoscopy, and to look at – in larger randomized controlled trials – the overall benefit of urgent colonoscopy.
The authors reported having no disclosures.
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point:
Major finding: Urgent vs. elective colonoscopy was not associated with improved bleeding source localization (RR, 1.08), adverse event rates (RR, 1.05), rebleeding rates (RR, 1.14), transfusion requirements (RR, 1.02) or mortality (RR, 1.17).
Data source: A systematic review and meta-analysis of 12 studies including more than 24,000 patients.
Disclosures: The authors reported having no disclosures.
Endoscopic resection alone sufficed in many T1 colorectal cancers
Patients with T1 colorectal cancer might not benefit from additional surgery after endoscopic resection unless they have positive or indeterminate resection margins or high-risk histology, according to a retrospective, population-based study of 1,315 patients.
After a median follow-up of 6.6 years, the rates of colorectal cancer (CRC) recurrence were 6.2% in patients who underwent endoscopic resection only and 6.4% in patients who also had additional surgery (P = .9), reported Tim D.G. Belderbos, MD, of University Medical Center Utrecht (the Netherlands). Rates of local recurrence also were similar between these groups (4.1% and 3.7%, P = .3), he and his associates reported in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.08.041).
Among high-risk patients, however, the rates of overall recurrence were 14% with endoscopic resection only and 7% with endoscopic resection plus additional surgery (P = .06), and the rates of local recurrence were 12% and 1%, respectively (P = .004). “Based on our study, we recommend performing additional surgery after initial endoscopic resection in cases of high-risk T1 CRC, determined by high-risk histology and/or positive resection margins,” the researchers concluded. Invasive CRCs confined to the colonic submucosa (T1 CRC) present a treatment dilemma – they are usually cured by complete endoscopic resection, but up to 13% involve lymph node metastases and need additional surgery, the investigators noted. To identify predictors of recurrence and metastasis, they studied all patients diagnosed with T1 CRC in the Southeast Netherlands from 1995 through 2011. A total of 370 patients (28%) underwent endoscopic resection only, 220 (17%) underwent endoscopic resection with additional surgery, and 725 (55%) had an initial surgical resection.
Surgery after endoscopic resection was more likely when patients had positive or doubtful resection margins (P less than .001), and this link remained significant after high-risk histology, tumor location, time period, age, sex, and comorbidities were controlled for. Endoscopic resection plus surgery did not reduce the risk of recurrence, compared with endoscopic resection only (P = .3), after the investigators accounted for age, sex, year of procedure, tumor location, and margin characteristics. Initial surgery was associated with significantly lower rates of overall and local recurrence, compared with endoscopic resection only, but the differences also lost significance in the multivariable analysis (P = .2).
Only the presence of positive resection margins significantly predicted recurrence among patients undergoing endoscopic resection (hazard ratio, 6.9; 95% confidence interval, 2.3-20.9). Positive or doubtful resection margins also predicted recurrence after initial surgery, with hazard ratios of 13.2 and 3.4, respectively. High-risk histology – that is, poor differentiation, deep submucosal invasion, or lymphangioinvasion – was significantly associated with lymph node metastasis (OR, 2.2; 95% CI, 1.3-3.7; P less than .002), but not with recurrence after resection margins were accounted for. This might result from missing histology data or the fact that patients with high-risk histology tended to undergo surgical rather than endoscopic resection, the researchers said.
They noted several other study limitations, including a lack of details about lesions and procedures. Also, endoscopic submucosal resection was not practiced in the Netherlands during the study period, they said.
The investigators did not report funding sources and had no disclosures.
Patients with T1 colorectal cancer might not benefit from additional surgery after endoscopic resection unless they have positive or indeterminate resection margins or high-risk histology, according to a retrospective, population-based study of 1,315 patients.
After a median follow-up of 6.6 years, the rates of colorectal cancer (CRC) recurrence were 6.2% in patients who underwent endoscopic resection only and 6.4% in patients who also had additional surgery (P = .9), reported Tim D.G. Belderbos, MD, of University Medical Center Utrecht (the Netherlands). Rates of local recurrence also were similar between these groups (4.1% and 3.7%, P = .3), he and his associates reported in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.08.041).
Among high-risk patients, however, the rates of overall recurrence were 14% with endoscopic resection only and 7% with endoscopic resection plus additional surgery (P = .06), and the rates of local recurrence were 12% and 1%, respectively (P = .004). “Based on our study, we recommend performing additional surgery after initial endoscopic resection in cases of high-risk T1 CRC, determined by high-risk histology and/or positive resection margins,” the researchers concluded. Invasive CRCs confined to the colonic submucosa (T1 CRC) present a treatment dilemma – they are usually cured by complete endoscopic resection, but up to 13% involve lymph node metastases and need additional surgery, the investigators noted. To identify predictors of recurrence and metastasis, they studied all patients diagnosed with T1 CRC in the Southeast Netherlands from 1995 through 2011. A total of 370 patients (28%) underwent endoscopic resection only, 220 (17%) underwent endoscopic resection with additional surgery, and 725 (55%) had an initial surgical resection.
Surgery after endoscopic resection was more likely when patients had positive or doubtful resection margins (P less than .001), and this link remained significant after high-risk histology, tumor location, time period, age, sex, and comorbidities were controlled for. Endoscopic resection plus surgery did not reduce the risk of recurrence, compared with endoscopic resection only (P = .3), after the investigators accounted for age, sex, year of procedure, tumor location, and margin characteristics. Initial surgery was associated with significantly lower rates of overall and local recurrence, compared with endoscopic resection only, but the differences also lost significance in the multivariable analysis (P = .2).
Only the presence of positive resection margins significantly predicted recurrence among patients undergoing endoscopic resection (hazard ratio, 6.9; 95% confidence interval, 2.3-20.9). Positive or doubtful resection margins also predicted recurrence after initial surgery, with hazard ratios of 13.2 and 3.4, respectively. High-risk histology – that is, poor differentiation, deep submucosal invasion, or lymphangioinvasion – was significantly associated with lymph node metastasis (OR, 2.2; 95% CI, 1.3-3.7; P less than .002), but not with recurrence after resection margins were accounted for. This might result from missing histology data or the fact that patients with high-risk histology tended to undergo surgical rather than endoscopic resection, the researchers said.
They noted several other study limitations, including a lack of details about lesions and procedures. Also, endoscopic submucosal resection was not practiced in the Netherlands during the study period, they said.
The investigators did not report funding sources and had no disclosures.
Patients with T1 colorectal cancer might not benefit from additional surgery after endoscopic resection unless they have positive or indeterminate resection margins or high-risk histology, according to a retrospective, population-based study of 1,315 patients.
After a median follow-up of 6.6 years, the rates of colorectal cancer (CRC) recurrence were 6.2% in patients who underwent endoscopic resection only and 6.4% in patients who also had additional surgery (P = .9), reported Tim D.G. Belderbos, MD, of University Medical Center Utrecht (the Netherlands). Rates of local recurrence also were similar between these groups (4.1% and 3.7%, P = .3), he and his associates reported in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.08.041).
Among high-risk patients, however, the rates of overall recurrence were 14% with endoscopic resection only and 7% with endoscopic resection plus additional surgery (P = .06), and the rates of local recurrence were 12% and 1%, respectively (P = .004). “Based on our study, we recommend performing additional surgery after initial endoscopic resection in cases of high-risk T1 CRC, determined by high-risk histology and/or positive resection margins,” the researchers concluded. Invasive CRCs confined to the colonic submucosa (T1 CRC) present a treatment dilemma – they are usually cured by complete endoscopic resection, but up to 13% involve lymph node metastases and need additional surgery, the investigators noted. To identify predictors of recurrence and metastasis, they studied all patients diagnosed with T1 CRC in the Southeast Netherlands from 1995 through 2011. A total of 370 patients (28%) underwent endoscopic resection only, 220 (17%) underwent endoscopic resection with additional surgery, and 725 (55%) had an initial surgical resection.
Surgery after endoscopic resection was more likely when patients had positive or doubtful resection margins (P less than .001), and this link remained significant after high-risk histology, tumor location, time period, age, sex, and comorbidities were controlled for. Endoscopic resection plus surgery did not reduce the risk of recurrence, compared with endoscopic resection only (P = .3), after the investigators accounted for age, sex, year of procedure, tumor location, and margin characteristics. Initial surgery was associated with significantly lower rates of overall and local recurrence, compared with endoscopic resection only, but the differences also lost significance in the multivariable analysis (P = .2).
Only the presence of positive resection margins significantly predicted recurrence among patients undergoing endoscopic resection (hazard ratio, 6.9; 95% confidence interval, 2.3-20.9). Positive or doubtful resection margins also predicted recurrence after initial surgery, with hazard ratios of 13.2 and 3.4, respectively. High-risk histology – that is, poor differentiation, deep submucosal invasion, or lymphangioinvasion – was significantly associated with lymph node metastasis (OR, 2.2; 95% CI, 1.3-3.7; P less than .002), but not with recurrence after resection margins were accounted for. This might result from missing histology data or the fact that patients with high-risk histology tended to undergo surgical rather than endoscopic resection, the researchers said.
They noted several other study limitations, including a lack of details about lesions and procedures. Also, endoscopic submucosal resection was not practiced in the Netherlands during the study period, they said.
The investigators did not report funding sources and had no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point. Patients with T1 colorectal cancer might not benefit from additional surgery after endoscopic resection unless they have positive or indeterminate resection margins or high-risk histology.
Major finding: After a median follow-up of 6.6 years, rates of CRC recurrence were 6.2% in patients who underwent endoscopic resection only, and 6.4% in patients who also had additional surgery (P = .9). Among high-risk patients, these rates were 14% and 7%, respectively (P = .06).
Data source: A retrospective population-based study of 1,315 patients who underwent endoscopic or surgical resection of T1 colorectal cancer.
Disclosures: The investigators did not report funding sources and had no disclosures.
Flashback to April 2008
The April 2008 issue of GI & Hepatology News (GIHN) featured an article by Roy M. Soetikno, MD, MS, FASGE and his colleagues from the Palo Alto VA Medical Center in California. They drew our attention to nonpolypoid (flat) colonic lesions in an article from JAMA (2008;299:1027-35).
Coincidentally, the week before this article appeared, I was sitting with Roy in Kyoto, Japan, at a conference of international experts focused on flat colonic lesions. The Japanese definitions of flat and depressed lesions were markedly different from those used by Western physicians. We now know that most flat lesions seen by U.S.-based endoscopists are sessile serrated adenomas (SSAs). SSAs at that time also were a new and controversial classification. SSAs were first described by Torlakovic and Snover in 1996 (Gastroenterology 1996;110:748-55).
Dale Snover, MD, was my golfing partner and read pathology slides for our practice in Minneapolis, so we were the first gastroenterologists in the country to grapple with the clinical implications of SSAs. Roy’s article was accompanied by an excellent commentary by Jerome D. Waye, MD, FASGE, who emphasized the importance of a slow withdrawal time and meticulous visual technique during colonoscopy.
Key points in the JAMA article were a) prevalence of flat lesions was about 9% in a screening population, b) small flat polyps can harbor advanced histologic changes including cancers, and c) many physicians who perform colonoscopy missed these lesions putting patients at risk for interval colon cancers. 
The GIHN piece, referencing Soetikno’s article, helped inform us about an important (and confusing) problem in our colon cancer prevention efforts. As numerous authors subsequently highlighted (see Gastroenterology 2016;151:870-8) most cancers, missed at initial colonoscopy, are proximal and frequently develop from SSAs. We continue to work to reduce missed cancers and thanks to this seminal article, we have better insights about how to achieve this goal.
John I. Allen, MD, MBA, AGAF, is professor of medicine in the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor, and the Editor in Chief of GI & Hepatology News.
The April 2008 issue of GI & Hepatology News (GIHN) featured an article by Roy M. Soetikno, MD, MS, FASGE and his colleagues from the Palo Alto VA Medical Center in California. They drew our attention to nonpolypoid (flat) colonic lesions in an article from JAMA (2008;299:1027-35).
Coincidentally, the week before this article appeared, I was sitting with Roy in Kyoto, Japan, at a conference of international experts focused on flat colonic lesions. The Japanese definitions of flat and depressed lesions were markedly different from those used by Western physicians. We now know that most flat lesions seen by U.S.-based endoscopists are sessile serrated adenomas (SSAs). SSAs at that time also were a new and controversial classification. SSAs were first described by Torlakovic and Snover in 1996 (Gastroenterology 1996;110:748-55).
Dale Snover, MD, was my golfing partner and read pathology slides for our practice in Minneapolis, so we were the first gastroenterologists in the country to grapple with the clinical implications of SSAs. Roy’s article was accompanied by an excellent commentary by Jerome D. Waye, MD, FASGE, who emphasized the importance of a slow withdrawal time and meticulous visual technique during colonoscopy.
Key points in the JAMA article were a) prevalence of flat lesions was about 9% in a screening population, b) small flat polyps can harbor advanced histologic changes including cancers, and c) many physicians who perform colonoscopy missed these lesions putting patients at risk for interval colon cancers.
The GIHN piece, referencing Soetikno’s article, helped inform us about an important (and confusing) problem in our colon cancer prevention efforts. As numerous authors subsequently highlighted (see Gastroenterology 2016;151:870-8) most cancers, missed at initial colonoscopy, are proximal and frequently develop from SSAs. We continue to work to reduce missed cancers and thanks to this seminal article, we have better insights about how to achieve this goal.
John I. Allen, MD, MBA, AGAF, is professor of medicine in the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor, and the Editor in Chief of GI & Hepatology News.
The April 2008 issue of GI & Hepatology News (GIHN) featured an article by Roy M. Soetikno, MD, MS, FASGE and his colleagues from the Palo Alto VA Medical Center in California. They drew our attention to nonpolypoid (flat) colonic lesions in an article from JAMA (2008;299:1027-35).
Coincidentally, the week before this article appeared, I was sitting with Roy in Kyoto, Japan, at a conference of international experts focused on flat colonic lesions. The Japanese definitions of flat and depressed lesions were markedly different from those used by Western physicians. We now know that most flat lesions seen by U.S.-based endoscopists are sessile serrated adenomas (SSAs). SSAs at that time also were a new and controversial classification. SSAs were first described by Torlakovic and Snover in 1996 (Gastroenterology 1996;110:748-55).
Dale Snover, MD, was my golfing partner and read pathology slides for our practice in Minneapolis, so we were the first gastroenterologists in the country to grapple with the clinical implications of SSAs. Roy’s article was accompanied by an excellent commentary by Jerome D. Waye, MD, FASGE, who emphasized the importance of a slow withdrawal time and meticulous visual technique during colonoscopy.
Key points in the JAMA article were a) prevalence of flat lesions was about 9% in a screening population, b) small flat polyps can harbor advanced histologic changes including cancers, and c) many physicians who perform colonoscopy missed these lesions putting patients at risk for interval colon cancers.
The GIHN piece, referencing Soetikno’s article, helped inform us about an important (and confusing) problem in our colon cancer prevention efforts. As numerous authors subsequently highlighted (see Gastroenterology 2016;151:870-8) most cancers, missed at initial colonoscopy, are proximal and frequently develop from SSAs. We continue to work to reduce missed cancers and thanks to this seminal article, we have better insights about how to achieve this goal.
John I. Allen, MD, MBA, AGAF, is professor of medicine in the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor, and the Editor in Chief of GI & Hepatology News.
