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GLP-1s May Increase Post-Endoscopy Aspiration Pneumonia Risk
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
AGA Defines Diagnostic, Treatment Approach to Cannabinoid Hyperemesis Syndrome
.
CHS, which is triggered by chronic cannabis usage and manifests with GI and autonomic symptoms, is on the rise in the United States, yet underdiagnosis remains a challenge and clinical data are scarce, reported lead update panelist Alberto Rubio Tapia, MD, of Cleveland Clinic, Cleveland, Ohio, and colleagues.
“Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed CHS, were noted relatively recently,” the panelists wrote in Gastroenterology. “The objective of this article was to help practitioners define the appropriate approach to the diagnosis and management of CHS.”
According to the update, the typical CHS patient is male with a years-long history of daily or near-daily cannabis use. Paradoxically, while cannabis use drives this condition, some patients with CHS report that cannabis use relieves their symptoms.The update describes CHS as a subtype of cyclical vomiting syndrome (CVS), and offers diagnostic criteria for CHS, reproduced below verbatim:
- Clinical features: stereotypical episodic vomiting resembling CVS in terms of onset, with frequency 3 or more times annually;
- Cannabis use patterns: duration of cannabis use more than 1 year before symptom onset; frequency more than 4 times per week, on average;
- Cannabis cessation: resolution of symptoms after a period of abstinence from cannabis use for at least 6 months, or at least equal to the total duration of 3 typical vomiting cycles in that patient.
As CHS is a subtype of CVS, the update also provides an outline and management guide for this broader condition, which is characterized by four phases: inter-episodic, prodromal, emetic, and recovery.
During the inter-episodic phase, patients will have minimal or no symptoms, although almost one third will describe dyspepsia or nausea. Prophylactic medications in this period include tricyclics, mitochondrial supplements like CoQ10 and vitamin B12, NK1 antagonists, and anticonvulsants.
The prodromal phase is characterized by abdominal pain and nausea with a duration of 30-90 minutes. During this time patients may have autonomic symptoms like sweating and feeling hot or cold. Psychological symptoms may include feelings of panic and being “out of control.” Abortive medications are appropriate during this period, according to the update, like triptans and antiemetics.
Next comes the emetic phase, in which patients exhibit “relentless vomiting,” retching, abdominal pain, neurological symptoms and extreme thirst. Because an empty stomach may provide relief, inducing emesis may be considered, along with rest in a quiet dark room and supportive care.
Finally, the vomiting subsides during the recovery phase, when it is possible to restart oral intake and resume normal activities.
While this framework may be useful when managing patients with CHS, intervention should be centered around cannabis cessation, according to the update.
“For long-term management, counseling to achieve marijuana cessation and tricyclic antidepressants, such as amitriptyline, are the mainstay of therapy,” Dr. Rubio Tapia and colleagues wrote.
Advising patients to stop cannabis “cold turkey” is not recommended, they added, as this may bring on withdrawal symptoms, and it tends to be ineffective in this population, which has a high recidivism rate.
“Co-management with a psychologist or psychiatrist may be helpful for patients who have a lack of response to standard therapies or extensive psychiatric comorbidity,” the panelists wrote. “Anxiety and depression are very common associated conditions.”
Dr. Rubio Tapia and colleagues concluded with a call for more research.
“Further understanding of CHS pathophysiology and evidence-based therapies are urgently needed,” they wrote.
This update was commissioned and approved by the AGA. The update panelists disclosed relationships with Evoke Pharma, RedHill Biopharma, Takeda, and others.
.
CHS, which is triggered by chronic cannabis usage and manifests with GI and autonomic symptoms, is on the rise in the United States, yet underdiagnosis remains a challenge and clinical data are scarce, reported lead update panelist Alberto Rubio Tapia, MD, of Cleveland Clinic, Cleveland, Ohio, and colleagues.
“Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed CHS, were noted relatively recently,” the panelists wrote in Gastroenterology. “The objective of this article was to help practitioners define the appropriate approach to the diagnosis and management of CHS.”
According to the update, the typical CHS patient is male with a years-long history of daily or near-daily cannabis use. Paradoxically, while cannabis use drives this condition, some patients with CHS report that cannabis use relieves their symptoms.The update describes CHS as a subtype of cyclical vomiting syndrome (CVS), and offers diagnostic criteria for CHS, reproduced below verbatim:
- Clinical features: stereotypical episodic vomiting resembling CVS in terms of onset, with frequency 3 or more times annually;
- Cannabis use patterns: duration of cannabis use more than 1 year before symptom onset; frequency more than 4 times per week, on average;
- Cannabis cessation: resolution of symptoms after a period of abstinence from cannabis use for at least 6 months, or at least equal to the total duration of 3 typical vomiting cycles in that patient.
As CHS is a subtype of CVS, the update also provides an outline and management guide for this broader condition, which is characterized by four phases: inter-episodic, prodromal, emetic, and recovery.
During the inter-episodic phase, patients will have minimal or no symptoms, although almost one third will describe dyspepsia or nausea. Prophylactic medications in this period include tricyclics, mitochondrial supplements like CoQ10 and vitamin B12, NK1 antagonists, and anticonvulsants.
The prodromal phase is characterized by abdominal pain and nausea with a duration of 30-90 minutes. During this time patients may have autonomic symptoms like sweating and feeling hot or cold. Psychological symptoms may include feelings of panic and being “out of control.” Abortive medications are appropriate during this period, according to the update, like triptans and antiemetics.
Next comes the emetic phase, in which patients exhibit “relentless vomiting,” retching, abdominal pain, neurological symptoms and extreme thirst. Because an empty stomach may provide relief, inducing emesis may be considered, along with rest in a quiet dark room and supportive care.
Finally, the vomiting subsides during the recovery phase, when it is possible to restart oral intake and resume normal activities.
While this framework may be useful when managing patients with CHS, intervention should be centered around cannabis cessation, according to the update.
“For long-term management, counseling to achieve marijuana cessation and tricyclic antidepressants, such as amitriptyline, are the mainstay of therapy,” Dr. Rubio Tapia and colleagues wrote.
Advising patients to stop cannabis “cold turkey” is not recommended, they added, as this may bring on withdrawal symptoms, and it tends to be ineffective in this population, which has a high recidivism rate.
“Co-management with a psychologist or psychiatrist may be helpful for patients who have a lack of response to standard therapies or extensive psychiatric comorbidity,” the panelists wrote. “Anxiety and depression are very common associated conditions.”
Dr. Rubio Tapia and colleagues concluded with a call for more research.
“Further understanding of CHS pathophysiology and evidence-based therapies are urgently needed,” they wrote.
This update was commissioned and approved by the AGA. The update panelists disclosed relationships with Evoke Pharma, RedHill Biopharma, Takeda, and others.
.
CHS, which is triggered by chronic cannabis usage and manifests with GI and autonomic symptoms, is on the rise in the United States, yet underdiagnosis remains a challenge and clinical data are scarce, reported lead update panelist Alberto Rubio Tapia, MD, of Cleveland Clinic, Cleveland, Ohio, and colleagues.
“Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed CHS, were noted relatively recently,” the panelists wrote in Gastroenterology. “The objective of this article was to help practitioners define the appropriate approach to the diagnosis and management of CHS.”
According to the update, the typical CHS patient is male with a years-long history of daily or near-daily cannabis use. Paradoxically, while cannabis use drives this condition, some patients with CHS report that cannabis use relieves their symptoms.The update describes CHS as a subtype of cyclical vomiting syndrome (CVS), and offers diagnostic criteria for CHS, reproduced below verbatim:
- Clinical features: stereotypical episodic vomiting resembling CVS in terms of onset, with frequency 3 or more times annually;
- Cannabis use patterns: duration of cannabis use more than 1 year before symptom onset; frequency more than 4 times per week, on average;
- Cannabis cessation: resolution of symptoms after a period of abstinence from cannabis use for at least 6 months, or at least equal to the total duration of 3 typical vomiting cycles in that patient.
As CHS is a subtype of CVS, the update also provides an outline and management guide for this broader condition, which is characterized by four phases: inter-episodic, prodromal, emetic, and recovery.
During the inter-episodic phase, patients will have minimal or no symptoms, although almost one third will describe dyspepsia or nausea. Prophylactic medications in this period include tricyclics, mitochondrial supplements like CoQ10 and vitamin B12, NK1 antagonists, and anticonvulsants.
The prodromal phase is characterized by abdominal pain and nausea with a duration of 30-90 minutes. During this time patients may have autonomic symptoms like sweating and feeling hot or cold. Psychological symptoms may include feelings of panic and being “out of control.” Abortive medications are appropriate during this period, according to the update, like triptans and antiemetics.
Next comes the emetic phase, in which patients exhibit “relentless vomiting,” retching, abdominal pain, neurological symptoms and extreme thirst. Because an empty stomach may provide relief, inducing emesis may be considered, along with rest in a quiet dark room and supportive care.
Finally, the vomiting subsides during the recovery phase, when it is possible to restart oral intake and resume normal activities.
While this framework may be useful when managing patients with CHS, intervention should be centered around cannabis cessation, according to the update.
“For long-term management, counseling to achieve marijuana cessation and tricyclic antidepressants, such as amitriptyline, are the mainstay of therapy,” Dr. Rubio Tapia and colleagues wrote.
Advising patients to stop cannabis “cold turkey” is not recommended, they added, as this may bring on withdrawal symptoms, and it tends to be ineffective in this population, which has a high recidivism rate.
“Co-management with a psychologist or psychiatrist may be helpful for patients who have a lack of response to standard therapies or extensive psychiatric comorbidity,” the panelists wrote. “Anxiety and depression are very common associated conditions.”
Dr. Rubio Tapia and colleagues concluded with a call for more research.
“Further understanding of CHS pathophysiology and evidence-based therapies are urgently needed,” they wrote.
This update was commissioned and approved by the AGA. The update panelists disclosed relationships with Evoke Pharma, RedHill Biopharma, Takeda, and others.
FROM GASTROENTEROLOGY
TRAIL-targeting Therapies Still Hold Promise in Cholangiocarcinoma
primarily due to the adaptive resistance and unexpected immune modulation, according to investigators.
Those prior studies evaluated a combination of immunotherapy and TRAIL agonism, but selective TRAIL antagonism shows greater potential via dual ligand/receptor (TRAIL/TRAIL-R) targeting to block immunosuppression, reported lead author Emilien J. Loeuillard, PhD, of Mayo Clinic, Rochester, Minnesota, and colleagues.
“The TRAIL/TRAIL-R system has garnered considerable interest in cancer biology, especially as a potential anticancer therapy,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “However, TRAIL-R agonists have had very limited anticancer activity in human beings, challenging this concept of TRAIL as an anticancer agent.”
This may be because they were working in the wrong direction, Dr. Loeuillard and colleagues suggested, citing recent work linking TRAIL with tumor proliferation and invasion, possibly via modification of the tumor immune microenvironment.
Exact mechanisms of modification, however, remain unclear. While TRAIL has been associated with tumor-promoting effects like induction of a promyeloid secretome in adenocarcinoma, it has also been linked with anticancer effects like activation of natural killer cells and cytotoxic T lymphocytes.
“Thus, the potency and hierarchy of TRAIL anticancer vs procancer processes in cancer biology has yet to be defined,” the investigators wrote.
While TRAIL ligation of cognate receptors has been previously investigated and shown to trigger proapoptotic signaling pathways, noncanonical TRAIL-mediated signaling remains largely unexplored, particularly in CCA.
The present study evaluated TRAIL biology in CCA using immunocompetent mouse models.
These experiments showed that noncanonical TRAIL signaling immunosuppresses the tumor microenvironment by increasing quantity and activity of myeloid-derived suppressor cells (MDSCs). Blocking noncanonical TRAIL signaling by selective deletion of TRAIL-R in immune cells had significantly reduced tumor volumes alongside fewer MDSCs, driven by FLICE inhibitory protein (cFLIP)-dependent nuclear factor kappa-B activation (NF-kappa-B) in MDSCs, which has antiapoptotic activity. While MDSCs present one possible target in this chain of immunosuppression, “therapeutic strategies for targeting MDSCs are limited,” the investigators wrote, noting that available myeloid modulators have fallen short in clinical trials.
Instead, cFLIP may be a convincing option, they suggested, as targeting cFLIP can sensitize cancer cells to proapoptotic TRAIL signaling. What’s more, cFLIP appears to protect MDSCs from TRAIL-mediated apoptosis, so taking out this barrier could render MDSCs susceptible to therapy.
“Our studies suggest that switching prosurvival/proliferation TRAIL signaling to canonical proapoptotic TRAIL signaling will promote MDSC apoptosis, which in turn has therapeutic implications for CCA suppression,” the investigators wrote.
Hope therefore remains for targeting TRAIL in patients with CCA, but with selective antagonism instead of agonism, as previously attempted.
“In summary, our findings support the role of selective therapeutic targeting of TRAIL-positive cancer cells in an effort to block TRAIL/TRAIL-R–mediated tumor immunosuppression,” Dr. Loeuillard and colleagues concluded.
This study was funded by the Cholangiocarcinoma Foundation and the Mayo Clinic Eagles 5th District Cancer Telethon Funds for Research Fellowship Program, the CTSA/National Center for Advancing Translational Science, the National Institutes of Health/National Cancer Institute, and others. The investigators disclosed no conflicts of interest.
The dismal response of cholangiocarcinoma to immune checkpoint inhibitors (ICI) is particularly concerning, as it impedes the adoption of combination regimens, now standard in most solid tumors. Strategies modulating selective genes involved in the tumor inflammatory environment and tumor cell viability, including those within the tumor necrosis factor superfamily, parallel the mechanism of action of ICI and present a double-edged sword due to the context-dependent pro- and/or anticancer effects of their canonical and/or phantom roles.
Recent investigations suggest that selectively antagonizing TRAIL via (TRAIL/TRAIL-R) targeting may be more effective than agonism. Dr. Ilyas’ group from Mayo Clinic delved into the potential of TRAIL in cancer biology, particularly in CCA, shedding light on the complexities of TRAIL’s role in cancer, where both procancer and anticancer effects are observed.
Further investigation is warranted to explore how TRAIL/TRAIL-R therapy can be effectively combined with other broad-spectrum and/or targeted therapies to maximize selective toxicity to CCA cells, sparing the nonmalignant tissue, thereby extending the lifespan of CCA patients as well as assessing its preventive potential in predisposed premalignant stages, including cholestasis patients.
Sungjin Ko, DVM, PhD, is assistant professor in the Division of Experimental Pathology at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. He is also a member of the Pittsburgh Liver Research Center. He reported no conflicts of interest.
The dismal response of cholangiocarcinoma to immune checkpoint inhibitors (ICI) is particularly concerning, as it impedes the adoption of combination regimens, now standard in most solid tumors. Strategies modulating selective genes involved in the tumor inflammatory environment and tumor cell viability, including those within the tumor necrosis factor superfamily, parallel the mechanism of action of ICI and present a double-edged sword due to the context-dependent pro- and/or anticancer effects of their canonical and/or phantom roles.
Recent investigations suggest that selectively antagonizing TRAIL via (TRAIL/TRAIL-R) targeting may be more effective than agonism. Dr. Ilyas’ group from Mayo Clinic delved into the potential of TRAIL in cancer biology, particularly in CCA, shedding light on the complexities of TRAIL’s role in cancer, where both procancer and anticancer effects are observed.
Further investigation is warranted to explore how TRAIL/TRAIL-R therapy can be effectively combined with other broad-spectrum and/or targeted therapies to maximize selective toxicity to CCA cells, sparing the nonmalignant tissue, thereby extending the lifespan of CCA patients as well as assessing its preventive potential in predisposed premalignant stages, including cholestasis patients.
Sungjin Ko, DVM, PhD, is assistant professor in the Division of Experimental Pathology at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. He is also a member of the Pittsburgh Liver Research Center. He reported no conflicts of interest.
The dismal response of cholangiocarcinoma to immune checkpoint inhibitors (ICI) is particularly concerning, as it impedes the adoption of combination regimens, now standard in most solid tumors. Strategies modulating selective genes involved in the tumor inflammatory environment and tumor cell viability, including those within the tumor necrosis factor superfamily, parallel the mechanism of action of ICI and present a double-edged sword due to the context-dependent pro- and/or anticancer effects of their canonical and/or phantom roles.
Recent investigations suggest that selectively antagonizing TRAIL via (TRAIL/TRAIL-R) targeting may be more effective than agonism. Dr. Ilyas’ group from Mayo Clinic delved into the potential of TRAIL in cancer biology, particularly in CCA, shedding light on the complexities of TRAIL’s role in cancer, where both procancer and anticancer effects are observed.
Further investigation is warranted to explore how TRAIL/TRAIL-R therapy can be effectively combined with other broad-spectrum and/or targeted therapies to maximize selective toxicity to CCA cells, sparing the nonmalignant tissue, thereby extending the lifespan of CCA patients as well as assessing its preventive potential in predisposed premalignant stages, including cholestasis patients.
Sungjin Ko, DVM, PhD, is assistant professor in the Division of Experimental Pathology at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. He is also a member of the Pittsburgh Liver Research Center. He reported no conflicts of interest.
primarily due to the adaptive resistance and unexpected immune modulation, according to investigators.
Those prior studies evaluated a combination of immunotherapy and TRAIL agonism, but selective TRAIL antagonism shows greater potential via dual ligand/receptor (TRAIL/TRAIL-R) targeting to block immunosuppression, reported lead author Emilien J. Loeuillard, PhD, of Mayo Clinic, Rochester, Minnesota, and colleagues.
“The TRAIL/TRAIL-R system has garnered considerable interest in cancer biology, especially as a potential anticancer therapy,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “However, TRAIL-R agonists have had very limited anticancer activity in human beings, challenging this concept of TRAIL as an anticancer agent.”
This may be because they were working in the wrong direction, Dr. Loeuillard and colleagues suggested, citing recent work linking TRAIL with tumor proliferation and invasion, possibly via modification of the tumor immune microenvironment.
Exact mechanisms of modification, however, remain unclear. While TRAIL has been associated with tumor-promoting effects like induction of a promyeloid secretome in adenocarcinoma, it has also been linked with anticancer effects like activation of natural killer cells and cytotoxic T lymphocytes.
“Thus, the potency and hierarchy of TRAIL anticancer vs procancer processes in cancer biology has yet to be defined,” the investigators wrote.
While TRAIL ligation of cognate receptors has been previously investigated and shown to trigger proapoptotic signaling pathways, noncanonical TRAIL-mediated signaling remains largely unexplored, particularly in CCA.
The present study evaluated TRAIL biology in CCA using immunocompetent mouse models.
These experiments showed that noncanonical TRAIL signaling immunosuppresses the tumor microenvironment by increasing quantity and activity of myeloid-derived suppressor cells (MDSCs). Blocking noncanonical TRAIL signaling by selective deletion of TRAIL-R in immune cells had significantly reduced tumor volumes alongside fewer MDSCs, driven by FLICE inhibitory protein (cFLIP)-dependent nuclear factor kappa-B activation (NF-kappa-B) in MDSCs, which has antiapoptotic activity. While MDSCs present one possible target in this chain of immunosuppression, “therapeutic strategies for targeting MDSCs are limited,” the investigators wrote, noting that available myeloid modulators have fallen short in clinical trials.
Instead, cFLIP may be a convincing option, they suggested, as targeting cFLIP can sensitize cancer cells to proapoptotic TRAIL signaling. What’s more, cFLIP appears to protect MDSCs from TRAIL-mediated apoptosis, so taking out this barrier could render MDSCs susceptible to therapy.
“Our studies suggest that switching prosurvival/proliferation TRAIL signaling to canonical proapoptotic TRAIL signaling will promote MDSC apoptosis, which in turn has therapeutic implications for CCA suppression,” the investigators wrote.
Hope therefore remains for targeting TRAIL in patients with CCA, but with selective antagonism instead of agonism, as previously attempted.
“In summary, our findings support the role of selective therapeutic targeting of TRAIL-positive cancer cells in an effort to block TRAIL/TRAIL-R–mediated tumor immunosuppression,” Dr. Loeuillard and colleagues concluded.
This study was funded by the Cholangiocarcinoma Foundation and the Mayo Clinic Eagles 5th District Cancer Telethon Funds for Research Fellowship Program, the CTSA/National Center for Advancing Translational Science, the National Institutes of Health/National Cancer Institute, and others. The investigators disclosed no conflicts of interest.
primarily due to the adaptive resistance and unexpected immune modulation, according to investigators.
Those prior studies evaluated a combination of immunotherapy and TRAIL agonism, but selective TRAIL antagonism shows greater potential via dual ligand/receptor (TRAIL/TRAIL-R) targeting to block immunosuppression, reported lead author Emilien J. Loeuillard, PhD, of Mayo Clinic, Rochester, Minnesota, and colleagues.
“The TRAIL/TRAIL-R system has garnered considerable interest in cancer biology, especially as a potential anticancer therapy,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “However, TRAIL-R agonists have had very limited anticancer activity in human beings, challenging this concept of TRAIL as an anticancer agent.”
This may be because they were working in the wrong direction, Dr. Loeuillard and colleagues suggested, citing recent work linking TRAIL with tumor proliferation and invasion, possibly via modification of the tumor immune microenvironment.
Exact mechanisms of modification, however, remain unclear. While TRAIL has been associated with tumor-promoting effects like induction of a promyeloid secretome in adenocarcinoma, it has also been linked with anticancer effects like activation of natural killer cells and cytotoxic T lymphocytes.
“Thus, the potency and hierarchy of TRAIL anticancer vs procancer processes in cancer biology has yet to be defined,” the investigators wrote.
While TRAIL ligation of cognate receptors has been previously investigated and shown to trigger proapoptotic signaling pathways, noncanonical TRAIL-mediated signaling remains largely unexplored, particularly in CCA.
The present study evaluated TRAIL biology in CCA using immunocompetent mouse models.
These experiments showed that noncanonical TRAIL signaling immunosuppresses the tumor microenvironment by increasing quantity and activity of myeloid-derived suppressor cells (MDSCs). Blocking noncanonical TRAIL signaling by selective deletion of TRAIL-R in immune cells had significantly reduced tumor volumes alongside fewer MDSCs, driven by FLICE inhibitory protein (cFLIP)-dependent nuclear factor kappa-B activation (NF-kappa-B) in MDSCs, which has antiapoptotic activity. While MDSCs present one possible target in this chain of immunosuppression, “therapeutic strategies for targeting MDSCs are limited,” the investigators wrote, noting that available myeloid modulators have fallen short in clinical trials.
Instead, cFLIP may be a convincing option, they suggested, as targeting cFLIP can sensitize cancer cells to proapoptotic TRAIL signaling. What’s more, cFLIP appears to protect MDSCs from TRAIL-mediated apoptosis, so taking out this barrier could render MDSCs susceptible to therapy.
“Our studies suggest that switching prosurvival/proliferation TRAIL signaling to canonical proapoptotic TRAIL signaling will promote MDSC apoptosis, which in turn has therapeutic implications for CCA suppression,” the investigators wrote.
Hope therefore remains for targeting TRAIL in patients with CCA, but with selective antagonism instead of agonism, as previously attempted.
“In summary, our findings support the role of selective therapeutic targeting of TRAIL-positive cancer cells in an effort to block TRAIL/TRAIL-R–mediated tumor immunosuppression,” Dr. Loeuillard and colleagues concluded.
This study was funded by the Cholangiocarcinoma Foundation and the Mayo Clinic Eagles 5th District Cancer Telethon Funds for Research Fellowship Program, the CTSA/National Center for Advancing Translational Science, the National Institutes of Health/National Cancer Institute, and others. The investigators disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
IBD: Histologic Inflammation Linked With Lower Female Fertility
, according to a Swedish nationwide cohort study.
Reduced fertility was linked with histologic inflammation even in the absence of clinical disease activity, highlighting the importance of achieving deep remission in women planning pregnancy, reported lead author Karl Mårild, MD, PhD, of Sahlgrenska Academy, Gothenburg, Sweden, and colleagues.
“Reduced female fertility (ie, number of live births) is believed to be primarily confined to women with clinically active IBD, especially in Crohn’s disease (CD), where symptoms may inhibit sexual activity, and inflammation may affect the fallopian tubes and ovaries,” the investigators wrote in Gastroenterology. “Despite the increasing appreciation of histologic activity in IBD, its association with female fertility has not been clarified, including whether histologic activity in the absence of clinical disease activity impairs fertility.”
Dr. Mårild and colleagues aimed to address this knowledge gap by analyzing fertility rates and histologic inflammation or IBD activity in two cohorts of women with IBD aged 15-44 years. The first group included approximately 21,000 women with and without histologic inflammation from 1990 to 2016. The second group included approximately 25,000 women with or without IBD clinical activity from 2006 to 2020. In each group, the relationship between fertility and IBD was compared with fertility in matched general population comparator individuals.
This approach showed that clinical IBD activity was associated with an adjusted fertility rate ratio (aFRR) of 0.76 (95% CI, 0.72-0.79), which equates to one fewer child per six women with 10 years of clinical activity. Impacts on fertility were similar for UC (aFRR, 0.75) and CD (aFRR, 0.76).
“Fertility rates were notably reduced during periods of clinical IBD activity and, contrary to a generally accepted belief, equally reduced in clinically active UC and CD,” the investigators wrote. “Besides inflammation, clinically active IBD may reduce fertility through psychological mechanisms (eg, depression), dyspareunia (especially in perianal CD), bowel pain, urgency, and other symptoms that hinder sexual activity.”
Compared with histologic remission, histologic inflammation was also associated with reduced fertility (aFRR, 0.90). This means that in periods of histologic inflammation, 6.35 live births occurred per 100 person-years of follow-up, compared with 7.09 lives births for periods of histologic remission. This amounts to one fewer child per 14 women with 10 years of histologic inflammation.
Finally, the study revealed that, in women with clinically quiescent IBD, those with histologic inflammation had significantly reduced fertility, compared with those in histologic remission (aFRR, 0.85). This association persisted after controlling for contraceptive use.
“Even if histologic inflammation was associated with an overall modest fertility reduction … its impact on the individual might be substantial, with potential ramifications beyond reproductive health, given that reduced female fertility is linked to poor quality of life and mental health,” Dr. Mårild and colleagues wrote. “At a societal level, involuntary childlessness causes high and increasing costs, highlighting the need to focus on preventable causes of reduced fertility.”
The investigators suggested that inflammation may be driving infertility by reducing ovulation and fertilization, or by reducing endometrial receptivity, which increases risk of pregnancy loss.
“This is the first study, to our knowledge, to show reduced fertility during histologic inflammation in IBD compared to histologic remission,” the investigators wrote. “Our findings suggest that achieving histologic remission may improve the fertility of women with IBD, even in the absence of clinically defined disease activity.”
The investigators disclosed relationships with AbbVie, Pfizer, Janssen, and others.
The importance of controlling inflammation to ensure a healthy pregnancy cannot be overstated. With regard to fertility, the literature has emphasized that surgery has been the major risk factor for decreasing fertility in both ulcerative colitis and Crohn’s disease. Disease activity has been more influential on Crohn’s disease versus ulcerative colitis. Other factors such as voluntary childlessness, premature ovarian failure, and malnutrition can also play a role. There have been data to show that anti–tumor necrosis factor use increases the chances of successful implantation for women with sub-fertility who do not have concomitant IBD, perhaps by decreasing inflammation in the pelvis.
Sunanda Kane, MD, MSPH, AGAF, is based in the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. She reports serving as a consultant to Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, Gilead, Janssen, and Takeda. She is also Section Editor for IBD for UptoDate.
The importance of controlling inflammation to ensure a healthy pregnancy cannot be overstated. With regard to fertility, the literature has emphasized that surgery has been the major risk factor for decreasing fertility in both ulcerative colitis and Crohn’s disease. Disease activity has been more influential on Crohn’s disease versus ulcerative colitis. Other factors such as voluntary childlessness, premature ovarian failure, and malnutrition can also play a role. There have been data to show that anti–tumor necrosis factor use increases the chances of successful implantation for women with sub-fertility who do not have concomitant IBD, perhaps by decreasing inflammation in the pelvis.
Sunanda Kane, MD, MSPH, AGAF, is based in the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. She reports serving as a consultant to Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, Gilead, Janssen, and Takeda. She is also Section Editor for IBD for UptoDate.
The importance of controlling inflammation to ensure a healthy pregnancy cannot be overstated. With regard to fertility, the literature has emphasized that surgery has been the major risk factor for decreasing fertility in both ulcerative colitis and Crohn’s disease. Disease activity has been more influential on Crohn’s disease versus ulcerative colitis. Other factors such as voluntary childlessness, premature ovarian failure, and malnutrition can also play a role. There have been data to show that anti–tumor necrosis factor use increases the chances of successful implantation for women with sub-fertility who do not have concomitant IBD, perhaps by decreasing inflammation in the pelvis.
Sunanda Kane, MD, MSPH, AGAF, is based in the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. She reports serving as a consultant to Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, Gilead, Janssen, and Takeda. She is also Section Editor for IBD for UptoDate.
, according to a Swedish nationwide cohort study.
Reduced fertility was linked with histologic inflammation even in the absence of clinical disease activity, highlighting the importance of achieving deep remission in women planning pregnancy, reported lead author Karl Mårild, MD, PhD, of Sahlgrenska Academy, Gothenburg, Sweden, and colleagues.
“Reduced female fertility (ie, number of live births) is believed to be primarily confined to women with clinically active IBD, especially in Crohn’s disease (CD), where symptoms may inhibit sexual activity, and inflammation may affect the fallopian tubes and ovaries,” the investigators wrote in Gastroenterology. “Despite the increasing appreciation of histologic activity in IBD, its association with female fertility has not been clarified, including whether histologic activity in the absence of clinical disease activity impairs fertility.”
Dr. Mårild and colleagues aimed to address this knowledge gap by analyzing fertility rates and histologic inflammation or IBD activity in two cohorts of women with IBD aged 15-44 years. The first group included approximately 21,000 women with and without histologic inflammation from 1990 to 2016. The second group included approximately 25,000 women with or without IBD clinical activity from 2006 to 2020. In each group, the relationship between fertility and IBD was compared with fertility in matched general population comparator individuals.
This approach showed that clinical IBD activity was associated with an adjusted fertility rate ratio (aFRR) of 0.76 (95% CI, 0.72-0.79), which equates to one fewer child per six women with 10 years of clinical activity. Impacts on fertility were similar for UC (aFRR, 0.75) and CD (aFRR, 0.76).
“Fertility rates were notably reduced during periods of clinical IBD activity and, contrary to a generally accepted belief, equally reduced in clinically active UC and CD,” the investigators wrote. “Besides inflammation, clinically active IBD may reduce fertility through psychological mechanisms (eg, depression), dyspareunia (especially in perianal CD), bowel pain, urgency, and other symptoms that hinder sexual activity.”
Compared with histologic remission, histologic inflammation was also associated with reduced fertility (aFRR, 0.90). This means that in periods of histologic inflammation, 6.35 live births occurred per 100 person-years of follow-up, compared with 7.09 lives births for periods of histologic remission. This amounts to one fewer child per 14 women with 10 years of histologic inflammation.
Finally, the study revealed that, in women with clinically quiescent IBD, those with histologic inflammation had significantly reduced fertility, compared with those in histologic remission (aFRR, 0.85). This association persisted after controlling for contraceptive use.
“Even if histologic inflammation was associated with an overall modest fertility reduction … its impact on the individual might be substantial, with potential ramifications beyond reproductive health, given that reduced female fertility is linked to poor quality of life and mental health,” Dr. Mårild and colleagues wrote. “At a societal level, involuntary childlessness causes high and increasing costs, highlighting the need to focus on preventable causes of reduced fertility.”
The investigators suggested that inflammation may be driving infertility by reducing ovulation and fertilization, or by reducing endometrial receptivity, which increases risk of pregnancy loss.
“This is the first study, to our knowledge, to show reduced fertility during histologic inflammation in IBD compared to histologic remission,” the investigators wrote. “Our findings suggest that achieving histologic remission may improve the fertility of women with IBD, even in the absence of clinically defined disease activity.”
The investigators disclosed relationships with AbbVie, Pfizer, Janssen, and others.
, according to a Swedish nationwide cohort study.
Reduced fertility was linked with histologic inflammation even in the absence of clinical disease activity, highlighting the importance of achieving deep remission in women planning pregnancy, reported lead author Karl Mårild, MD, PhD, of Sahlgrenska Academy, Gothenburg, Sweden, and colleagues.
“Reduced female fertility (ie, number of live births) is believed to be primarily confined to women with clinically active IBD, especially in Crohn’s disease (CD), where symptoms may inhibit sexual activity, and inflammation may affect the fallopian tubes and ovaries,” the investigators wrote in Gastroenterology. “Despite the increasing appreciation of histologic activity in IBD, its association with female fertility has not been clarified, including whether histologic activity in the absence of clinical disease activity impairs fertility.”
Dr. Mårild and colleagues aimed to address this knowledge gap by analyzing fertility rates and histologic inflammation or IBD activity in two cohorts of women with IBD aged 15-44 years. The first group included approximately 21,000 women with and without histologic inflammation from 1990 to 2016. The second group included approximately 25,000 women with or without IBD clinical activity from 2006 to 2020. In each group, the relationship between fertility and IBD was compared with fertility in matched general population comparator individuals.
This approach showed that clinical IBD activity was associated with an adjusted fertility rate ratio (aFRR) of 0.76 (95% CI, 0.72-0.79), which equates to one fewer child per six women with 10 years of clinical activity. Impacts on fertility were similar for UC (aFRR, 0.75) and CD (aFRR, 0.76).
“Fertility rates were notably reduced during periods of clinical IBD activity and, contrary to a generally accepted belief, equally reduced in clinically active UC and CD,” the investigators wrote. “Besides inflammation, clinically active IBD may reduce fertility through psychological mechanisms (eg, depression), dyspareunia (especially in perianal CD), bowel pain, urgency, and other symptoms that hinder sexual activity.”
Compared with histologic remission, histologic inflammation was also associated with reduced fertility (aFRR, 0.90). This means that in periods of histologic inflammation, 6.35 live births occurred per 100 person-years of follow-up, compared with 7.09 lives births for periods of histologic remission. This amounts to one fewer child per 14 women with 10 years of histologic inflammation.
Finally, the study revealed that, in women with clinically quiescent IBD, those with histologic inflammation had significantly reduced fertility, compared with those in histologic remission (aFRR, 0.85). This association persisted after controlling for contraceptive use.
“Even if histologic inflammation was associated with an overall modest fertility reduction … its impact on the individual might be substantial, with potential ramifications beyond reproductive health, given that reduced female fertility is linked to poor quality of life and mental health,” Dr. Mårild and colleagues wrote. “At a societal level, involuntary childlessness causes high and increasing costs, highlighting the need to focus on preventable causes of reduced fertility.”
The investigators suggested that inflammation may be driving infertility by reducing ovulation and fertilization, or by reducing endometrial receptivity, which increases risk of pregnancy loss.
“This is the first study, to our knowledge, to show reduced fertility during histologic inflammation in IBD compared to histologic remission,” the investigators wrote. “Our findings suggest that achieving histologic remission may improve the fertility of women with IBD, even in the absence of clinically defined disease activity.”
The investigators disclosed relationships with AbbVie, Pfizer, Janssen, and others.
FROM GASTROENTEROLOGY
AGA Clinical Practice Update Describes High-Quality Upper Endoscopy
The update, authored by Satish Nagula, MD, of Icahn School of Medicine at Mount Sinai, New York, NY, and colleagues, includes nine pieces of best practice advice that address procedure optimization, evaluation of suspected premalignancy, and postprocedure follow-up evaluation.
“Defining what constitutes a high-quality esophagogastroduodenoscopy (EGD) poses somewhat of a challenge because the spectrum of indications and the breadth of benign and (pre)malignant disease pathology in the upper GI tract is very broad,” the update panelists wrote in Clinical Gastroenterology and Hepatology. “Standardizing the measures defining a high-quality upper endoscopic examination is one of the first steps for assessing quality.”
Preprocedure Recommendations
Dr. Nagula and colleagues first emphasized that EGD should be performed for an appropriate indication, citing a recent meta-analysis that found 21.7% of upper endoscopy procedures were performed for an inappropriate indication. Of note, diagnostic yields were 42% higher in procedures performed for an appropriate indication.
After ensuring an appropriate indication, the update also encourages clinicians to inform patients of the various benefits, risks, and alternatives of the procedure prior to providing consent.
Intraprocedure Recommendations
During the procedure, endoscopists should take several steps to ensure optimal visualization of tissues, according to the update.
First, a high-definition (HD) white-light endoscopy system should be employed.
“Although HD imaging is a standard feature of newer-generation endoscopes, legacy standard-definition scopes remain in use,” Dr. Nagula and colleagues noted. “Moreover, to provide true HD image resolution, each component of the system (eg, the endoscope video chip, the processor, the monitor, and transmission cables) must be HD compatible.”
This HD-compatible system should be coupled with image-enhancing technology to further improve lesion detection. In Barrett’s esophagus, the panelists noted, image enhancement can improve lesion detection as much as 20%.
They predicted that AI-assisted software may boost detection rates even higher: “Computer-aided detection and computer-aided diagnosis systems for upper endoscopy are still in the early phases of development but do show similar promise for improving the detection and characterization of upper GI tract neoplasia.”
Beyond selection of best available technologies, the update encourages more fundamental strategies to improve visualization, including mucosal cleansing and insufflation, with sufficient time spent inspecting the foregut mucosa via anterograde and retroflexed views.
Where appropriate, standardized biopsy protocols should be followed to evaluate and manage foregut conditions.
Postprocedure Recommendations
After the procedure, endoscopists should offer patients management recommendations based on the endoscopic findings and, if necessary, notify them that more recommendations may be forthcoming based on histopathology results, according to the update.
Similarly, endoscopists should follow established surveillance intervals for future procedures, with modifications made as needed, based on histopathology findings.
Document, Document, Document
Throughout the update, Dr. Nagula and colleagues repeatedly emphasize the importance of documentation, from preprocedural discussions with patients through planned surveillance schedules.
However, the recommendations are clear about “weighing the practical implications” of “onerous” documentation, particularly photodocumentation requirements. For instance, the authors note that “there are some scenarios in which more rigorous photodocumentation standards during upper endoscopy should be considered, such as patients with risk factors for neoplasia,” but at the very least “photodocumentation of any suspicious abnormalities, ideally with annotations, is strongly advised.”
Moving Toward Quality Standardization for Upper Endoscopy
“These best practice advice statements are intended to improve measurable clinical, patient-reported, and economic healthcare outcomes and are not meant to put an additional burden on endoscopists,” the panelists wrote. “Ideally, future research will set threshold indicators of adherence to these best practices that optimally are associated with these aforementioned objective outcomes.”
This update was commissioned and approved by AGA. The update panelists disclosed relationships with Covidien LP, Fujifilm USA, Mahana Therapeutics, and others.
The update, authored by Satish Nagula, MD, of Icahn School of Medicine at Mount Sinai, New York, NY, and colleagues, includes nine pieces of best practice advice that address procedure optimization, evaluation of suspected premalignancy, and postprocedure follow-up evaluation.
“Defining what constitutes a high-quality esophagogastroduodenoscopy (EGD) poses somewhat of a challenge because the spectrum of indications and the breadth of benign and (pre)malignant disease pathology in the upper GI tract is very broad,” the update panelists wrote in Clinical Gastroenterology and Hepatology. “Standardizing the measures defining a high-quality upper endoscopic examination is one of the first steps for assessing quality.”
Preprocedure Recommendations
Dr. Nagula and colleagues first emphasized that EGD should be performed for an appropriate indication, citing a recent meta-analysis that found 21.7% of upper endoscopy procedures were performed for an inappropriate indication. Of note, diagnostic yields were 42% higher in procedures performed for an appropriate indication.
After ensuring an appropriate indication, the update also encourages clinicians to inform patients of the various benefits, risks, and alternatives of the procedure prior to providing consent.
Intraprocedure Recommendations
During the procedure, endoscopists should take several steps to ensure optimal visualization of tissues, according to the update.
First, a high-definition (HD) white-light endoscopy system should be employed.
“Although HD imaging is a standard feature of newer-generation endoscopes, legacy standard-definition scopes remain in use,” Dr. Nagula and colleagues noted. “Moreover, to provide true HD image resolution, each component of the system (eg, the endoscope video chip, the processor, the monitor, and transmission cables) must be HD compatible.”
This HD-compatible system should be coupled with image-enhancing technology to further improve lesion detection. In Barrett’s esophagus, the panelists noted, image enhancement can improve lesion detection as much as 20%.
They predicted that AI-assisted software may boost detection rates even higher: “Computer-aided detection and computer-aided diagnosis systems for upper endoscopy are still in the early phases of development but do show similar promise for improving the detection and characterization of upper GI tract neoplasia.”
Beyond selection of best available technologies, the update encourages more fundamental strategies to improve visualization, including mucosal cleansing and insufflation, with sufficient time spent inspecting the foregut mucosa via anterograde and retroflexed views.
Where appropriate, standardized biopsy protocols should be followed to evaluate and manage foregut conditions.
Postprocedure Recommendations
After the procedure, endoscopists should offer patients management recommendations based on the endoscopic findings and, if necessary, notify them that more recommendations may be forthcoming based on histopathology results, according to the update.
Similarly, endoscopists should follow established surveillance intervals for future procedures, with modifications made as needed, based on histopathology findings.
Document, Document, Document
Throughout the update, Dr. Nagula and colleagues repeatedly emphasize the importance of documentation, from preprocedural discussions with patients through planned surveillance schedules.
However, the recommendations are clear about “weighing the practical implications” of “onerous” documentation, particularly photodocumentation requirements. For instance, the authors note that “there are some scenarios in which more rigorous photodocumentation standards during upper endoscopy should be considered, such as patients with risk factors for neoplasia,” but at the very least “photodocumentation of any suspicious abnormalities, ideally with annotations, is strongly advised.”
Moving Toward Quality Standardization for Upper Endoscopy
“These best practice advice statements are intended to improve measurable clinical, patient-reported, and economic healthcare outcomes and are not meant to put an additional burden on endoscopists,” the panelists wrote. “Ideally, future research will set threshold indicators of adherence to these best practices that optimally are associated with these aforementioned objective outcomes.”
This update was commissioned and approved by AGA. The update panelists disclosed relationships with Covidien LP, Fujifilm USA, Mahana Therapeutics, and others.
The update, authored by Satish Nagula, MD, of Icahn School of Medicine at Mount Sinai, New York, NY, and colleagues, includes nine pieces of best practice advice that address procedure optimization, evaluation of suspected premalignancy, and postprocedure follow-up evaluation.
“Defining what constitutes a high-quality esophagogastroduodenoscopy (EGD) poses somewhat of a challenge because the spectrum of indications and the breadth of benign and (pre)malignant disease pathology in the upper GI tract is very broad,” the update panelists wrote in Clinical Gastroenterology and Hepatology. “Standardizing the measures defining a high-quality upper endoscopic examination is one of the first steps for assessing quality.”
Preprocedure Recommendations
Dr. Nagula and colleagues first emphasized that EGD should be performed for an appropriate indication, citing a recent meta-analysis that found 21.7% of upper endoscopy procedures were performed for an inappropriate indication. Of note, diagnostic yields were 42% higher in procedures performed for an appropriate indication.
After ensuring an appropriate indication, the update also encourages clinicians to inform patients of the various benefits, risks, and alternatives of the procedure prior to providing consent.
Intraprocedure Recommendations
During the procedure, endoscopists should take several steps to ensure optimal visualization of tissues, according to the update.
First, a high-definition (HD) white-light endoscopy system should be employed.
“Although HD imaging is a standard feature of newer-generation endoscopes, legacy standard-definition scopes remain in use,” Dr. Nagula and colleagues noted. “Moreover, to provide true HD image resolution, each component of the system (eg, the endoscope video chip, the processor, the monitor, and transmission cables) must be HD compatible.”
This HD-compatible system should be coupled with image-enhancing technology to further improve lesion detection. In Barrett’s esophagus, the panelists noted, image enhancement can improve lesion detection as much as 20%.
They predicted that AI-assisted software may boost detection rates even higher: “Computer-aided detection and computer-aided diagnosis systems for upper endoscopy are still in the early phases of development but do show similar promise for improving the detection and characterization of upper GI tract neoplasia.”
Beyond selection of best available technologies, the update encourages more fundamental strategies to improve visualization, including mucosal cleansing and insufflation, with sufficient time spent inspecting the foregut mucosa via anterograde and retroflexed views.
Where appropriate, standardized biopsy protocols should be followed to evaluate and manage foregut conditions.
Postprocedure Recommendations
After the procedure, endoscopists should offer patients management recommendations based on the endoscopic findings and, if necessary, notify them that more recommendations may be forthcoming based on histopathology results, according to the update.
Similarly, endoscopists should follow established surveillance intervals for future procedures, with modifications made as needed, based on histopathology findings.
Document, Document, Document
Throughout the update, Dr. Nagula and colleagues repeatedly emphasize the importance of documentation, from preprocedural discussions with patients through planned surveillance schedules.
However, the recommendations are clear about “weighing the practical implications” of “onerous” documentation, particularly photodocumentation requirements. For instance, the authors note that “there are some scenarios in which more rigorous photodocumentation standards during upper endoscopy should be considered, such as patients with risk factors for neoplasia,” but at the very least “photodocumentation of any suspicious abnormalities, ideally with annotations, is strongly advised.”
Moving Toward Quality Standardization for Upper Endoscopy
“These best practice advice statements are intended to improve measurable clinical, patient-reported, and economic healthcare outcomes and are not meant to put an additional burden on endoscopists,” the panelists wrote. “Ideally, future research will set threshold indicators of adherence to these best practices that optimally are associated with these aforementioned objective outcomes.”
This update was commissioned and approved by AGA. The update panelists disclosed relationships with Covidien LP, Fujifilm USA, Mahana Therapeutics, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Power-Washing Moves Beyond Home Improvement, Into Gastroenterology
Power-washing is no longer just for blasting grimy driveways and stripping flaky paint. It’s good for work inside the gut, too.
In a proof-of-concept study, a “novel systematically directed high-pressure liquid spray,” delivered via the ERBEJET flexible probe, showed promise for collecting cytology specimens from the stomachs of patients undergoing endoscopy for gastric cancer screening or surveillance, reported lead author Charles J. Lightdale, MD, of Columbia University Irving Medical Center, New York City, and colleagues.
“Systematic random biopsies (updated Sydney protocol) have been recommended to increase detection of gastric intestinal metaplasia (GIM) and dysplasia,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “However, random biopsies can be laborious, time consuming, costly, and susceptible to sampling error owing to the large surface area of the stomach.”
Power-washing, in contrast, with the pressure dial turned to 10 bar, involves spraying the gut in a systematic fashion “using sweeping and painting motions” to dislodge cells from the mucosa. These specimens are then suctioned from the resultant pools of liquid, mixed 1:1 with 10% formalin, and shipped to the lab.
Boom! Cytology!
Just to be sure, however, the nine patients involved in the study also underwent standard-of-care biopsy collection from areas of interest, followed by random sampling according to the updated Sydney protocol. Two of the patients were power-washed again 12 months later for endoscopic surveillance.
Power-washing added 7-10 minutes to standard endoscopy time and generated 60-100 mL of liquid for collection. Post suction, a closer look at the gastric mucosa revealed “scattered superficial erosions,” while blood loss was deemed “minimal.” The procedure appeared well tolerated, with no aspiration or esophageal reflux during endoscopy, or adverse events reported by patients after 1 week of follow-up.
Cytopathology samples were deemed satisfactory and yielded “multiple strips and large clusters of cells.” These were sufficient to diagnose GIM in three patients and reactive glandular changes with inflammation in one patient, with findings confirmed on biopsy. In contrast, the power-washed cells from one patient were “highly suspicious” for dysplasia, but biopsies were negative.
Although the study was too small for a reliable comparison with the Sydney protocol, Dr. Lightdale and colleagues concluded that the power-wash approach deserves further investigation.
“ and to reduce morbidity and mortality from gastric cancer,” they wrote.
The investigators predicted that power-washing is likely safe in most patients, although it may be unsuitable for those with noncorrectable coagulopathies or in patients who cannot stop anticoagulants. Postsurgical patients, on the other hand, should tolerate the procedure just fine.
Patients with risk of gastric cancer “might be an important group” for evaluating the power-wash procedure, the investigators wrote, noting that combining the approach with artificial intelligence could one day yield even better results.
In the meantime, Dr. Lightdale and colleagues — like so many weekend warriors wielding a power-washer — are going to see if a different nozzle will take their work to the next level.
“We are actively studying a catheter with a broader stream and the potential to increase efficiency and decrease procedure time,” they wrote. “Another catheter design might allow for simultaneous spray and suction, so that cytology samples from specific regions of the stomach could be separately analyzed.”
This study was funded by Dalio Philanthropies, the Price Family Foundation, and the Frederic and Patricia Salerno Foundation. The investigators disclosed relationships with Boston Scientific, Interscope, Medtronic, and others.
The optimal surveillance endoscopic modality for gastric intestinal metaplasia (GIM) is yet to be determined. Although the updated Sydney System, a comprehensive endoscopic biopsy protocol, has been advocated for GIM mapping, challenges are the heterogeneous distribution of GIM, suboptimal diagnostic accuracy of endoscopy to detect GIM, and the cost burden of multiple biopsies.
This study by Lightdale et al. demonstrated the technical feasibility and safety of obtaining cytology for the detection of gastric intestinal metaplasia by using a systemic endoscopy-guided high-pressure spray “power-wash” method. In this study, all cytophathology samples in nine subjects were deemed satisfactory for evaluation. All three subjects who were cytology positive for GIM on H&E stain and confirmed with positive immunohistochemistry (IHC) showed GIM on biopsy, and one subject had cells highly suspicious for dysplasia on cytology but biopsy was negative. Although all patients showed multiple superficial erosions after power-wash, bleeding was minimal and no adverse events related to power-wash were observed.
Applying cytology for detection of GIM appears promising as the way of collecting samples from the large surface area of the stomach. As clinicians, however, we are still left with some challenges. Even if cells collected are suspicious for dysplasia/neoplasia by this power-wash method, it would not be useful unless we precisely localize the area as we can not provide a focal curative endoscopic treatment. It is critical to increase the yield of localization of cytology sampling. Further research is also needed to standardize the cytopathologic diagnostic criteria of GIM and cost-effectiveness of the cytology-based approach compared to the current gold-standard biopsy protocol for the diagnosis of GIM.
Yutaka Tomizawa, MD, MSc, is a therapeutic endoscopist and clinical associate professor of medicine, Division of Gastroenterology, University of Washington, Seattle. He has no conflicts related to this report.
The optimal surveillance endoscopic modality for gastric intestinal metaplasia (GIM) is yet to be determined. Although the updated Sydney System, a comprehensive endoscopic biopsy protocol, has been advocated for GIM mapping, challenges are the heterogeneous distribution of GIM, suboptimal diagnostic accuracy of endoscopy to detect GIM, and the cost burden of multiple biopsies.
This study by Lightdale et al. demonstrated the technical feasibility and safety of obtaining cytology for the detection of gastric intestinal metaplasia by using a systemic endoscopy-guided high-pressure spray “power-wash” method. In this study, all cytophathology samples in nine subjects were deemed satisfactory for evaluation. All three subjects who were cytology positive for GIM on H&E stain and confirmed with positive immunohistochemistry (IHC) showed GIM on biopsy, and one subject had cells highly suspicious for dysplasia on cytology but biopsy was negative. Although all patients showed multiple superficial erosions after power-wash, bleeding was minimal and no adverse events related to power-wash were observed.
Applying cytology for detection of GIM appears promising as the way of collecting samples from the large surface area of the stomach. As clinicians, however, we are still left with some challenges. Even if cells collected are suspicious for dysplasia/neoplasia by this power-wash method, it would not be useful unless we precisely localize the area as we can not provide a focal curative endoscopic treatment. It is critical to increase the yield of localization of cytology sampling. Further research is also needed to standardize the cytopathologic diagnostic criteria of GIM and cost-effectiveness of the cytology-based approach compared to the current gold-standard biopsy protocol for the diagnosis of GIM.
Yutaka Tomizawa, MD, MSc, is a therapeutic endoscopist and clinical associate professor of medicine, Division of Gastroenterology, University of Washington, Seattle. He has no conflicts related to this report.
The optimal surveillance endoscopic modality for gastric intestinal metaplasia (GIM) is yet to be determined. Although the updated Sydney System, a comprehensive endoscopic biopsy protocol, has been advocated for GIM mapping, challenges are the heterogeneous distribution of GIM, suboptimal diagnostic accuracy of endoscopy to detect GIM, and the cost burden of multiple biopsies.
This study by Lightdale et al. demonstrated the technical feasibility and safety of obtaining cytology for the detection of gastric intestinal metaplasia by using a systemic endoscopy-guided high-pressure spray “power-wash” method. In this study, all cytophathology samples in nine subjects were deemed satisfactory for evaluation. All three subjects who were cytology positive for GIM on H&E stain and confirmed with positive immunohistochemistry (IHC) showed GIM on biopsy, and one subject had cells highly suspicious for dysplasia on cytology but biopsy was negative. Although all patients showed multiple superficial erosions after power-wash, bleeding was minimal and no adverse events related to power-wash were observed.
Applying cytology for detection of GIM appears promising as the way of collecting samples from the large surface area of the stomach. As clinicians, however, we are still left with some challenges. Even if cells collected are suspicious for dysplasia/neoplasia by this power-wash method, it would not be useful unless we precisely localize the area as we can not provide a focal curative endoscopic treatment. It is critical to increase the yield of localization of cytology sampling. Further research is also needed to standardize the cytopathologic diagnostic criteria of GIM and cost-effectiveness of the cytology-based approach compared to the current gold-standard biopsy protocol for the diagnosis of GIM.
Yutaka Tomizawa, MD, MSc, is a therapeutic endoscopist and clinical associate professor of medicine, Division of Gastroenterology, University of Washington, Seattle. He has no conflicts related to this report.
Power-washing is no longer just for blasting grimy driveways and stripping flaky paint. It’s good for work inside the gut, too.
In a proof-of-concept study, a “novel systematically directed high-pressure liquid spray,” delivered via the ERBEJET flexible probe, showed promise for collecting cytology specimens from the stomachs of patients undergoing endoscopy for gastric cancer screening or surveillance, reported lead author Charles J. Lightdale, MD, of Columbia University Irving Medical Center, New York City, and colleagues.
“Systematic random biopsies (updated Sydney protocol) have been recommended to increase detection of gastric intestinal metaplasia (GIM) and dysplasia,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “However, random biopsies can be laborious, time consuming, costly, and susceptible to sampling error owing to the large surface area of the stomach.”
Power-washing, in contrast, with the pressure dial turned to 10 bar, involves spraying the gut in a systematic fashion “using sweeping and painting motions” to dislodge cells from the mucosa. These specimens are then suctioned from the resultant pools of liquid, mixed 1:1 with 10% formalin, and shipped to the lab.
Boom! Cytology!
Just to be sure, however, the nine patients involved in the study also underwent standard-of-care biopsy collection from areas of interest, followed by random sampling according to the updated Sydney protocol. Two of the patients were power-washed again 12 months later for endoscopic surveillance.
Power-washing added 7-10 minutes to standard endoscopy time and generated 60-100 mL of liquid for collection. Post suction, a closer look at the gastric mucosa revealed “scattered superficial erosions,” while blood loss was deemed “minimal.” The procedure appeared well tolerated, with no aspiration or esophageal reflux during endoscopy, or adverse events reported by patients after 1 week of follow-up.
Cytopathology samples were deemed satisfactory and yielded “multiple strips and large clusters of cells.” These were sufficient to diagnose GIM in three patients and reactive glandular changes with inflammation in one patient, with findings confirmed on biopsy. In contrast, the power-washed cells from one patient were “highly suspicious” for dysplasia, but biopsies were negative.
Although the study was too small for a reliable comparison with the Sydney protocol, Dr. Lightdale and colleagues concluded that the power-wash approach deserves further investigation.
“ and to reduce morbidity and mortality from gastric cancer,” they wrote.
The investigators predicted that power-washing is likely safe in most patients, although it may be unsuitable for those with noncorrectable coagulopathies or in patients who cannot stop anticoagulants. Postsurgical patients, on the other hand, should tolerate the procedure just fine.
Patients with risk of gastric cancer “might be an important group” for evaluating the power-wash procedure, the investigators wrote, noting that combining the approach with artificial intelligence could one day yield even better results.
In the meantime, Dr. Lightdale and colleagues — like so many weekend warriors wielding a power-washer — are going to see if a different nozzle will take their work to the next level.
“We are actively studying a catheter with a broader stream and the potential to increase efficiency and decrease procedure time,” they wrote. “Another catheter design might allow for simultaneous spray and suction, so that cytology samples from specific regions of the stomach could be separately analyzed.”
This study was funded by Dalio Philanthropies, the Price Family Foundation, and the Frederic and Patricia Salerno Foundation. The investigators disclosed relationships with Boston Scientific, Interscope, Medtronic, and others.
Power-washing is no longer just for blasting grimy driveways and stripping flaky paint. It’s good for work inside the gut, too.
In a proof-of-concept study, a “novel systematically directed high-pressure liquid spray,” delivered via the ERBEJET flexible probe, showed promise for collecting cytology specimens from the stomachs of patients undergoing endoscopy for gastric cancer screening or surveillance, reported lead author Charles J. Lightdale, MD, of Columbia University Irving Medical Center, New York City, and colleagues.
“Systematic random biopsies (updated Sydney protocol) have been recommended to increase detection of gastric intestinal metaplasia (GIM) and dysplasia,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “However, random biopsies can be laborious, time consuming, costly, and susceptible to sampling error owing to the large surface area of the stomach.”
Power-washing, in contrast, with the pressure dial turned to 10 bar, involves spraying the gut in a systematic fashion “using sweeping and painting motions” to dislodge cells from the mucosa. These specimens are then suctioned from the resultant pools of liquid, mixed 1:1 with 10% formalin, and shipped to the lab.
Boom! Cytology!
Just to be sure, however, the nine patients involved in the study also underwent standard-of-care biopsy collection from areas of interest, followed by random sampling according to the updated Sydney protocol. Two of the patients were power-washed again 12 months later for endoscopic surveillance.
Power-washing added 7-10 minutes to standard endoscopy time and generated 60-100 mL of liquid for collection. Post suction, a closer look at the gastric mucosa revealed “scattered superficial erosions,” while blood loss was deemed “minimal.” The procedure appeared well tolerated, with no aspiration or esophageal reflux during endoscopy, or adverse events reported by patients after 1 week of follow-up.
Cytopathology samples were deemed satisfactory and yielded “multiple strips and large clusters of cells.” These were sufficient to diagnose GIM in three patients and reactive glandular changes with inflammation in one patient, with findings confirmed on biopsy. In contrast, the power-washed cells from one patient were “highly suspicious” for dysplasia, but biopsies were negative.
Although the study was too small for a reliable comparison with the Sydney protocol, Dr. Lightdale and colleagues concluded that the power-wash approach deserves further investigation.
“ and to reduce morbidity and mortality from gastric cancer,” they wrote.
The investigators predicted that power-washing is likely safe in most patients, although it may be unsuitable for those with noncorrectable coagulopathies or in patients who cannot stop anticoagulants. Postsurgical patients, on the other hand, should tolerate the procedure just fine.
Patients with risk of gastric cancer “might be an important group” for evaluating the power-wash procedure, the investigators wrote, noting that combining the approach with artificial intelligence could one day yield even better results.
In the meantime, Dr. Lightdale and colleagues — like so many weekend warriors wielding a power-washer — are going to see if a different nozzle will take their work to the next level.
“We are actively studying a catheter with a broader stream and the potential to increase efficiency and decrease procedure time,” they wrote. “Another catheter design might allow for simultaneous spray and suction, so that cytology samples from specific regions of the stomach could be separately analyzed.”
This study was funded by Dalio Philanthropies, the Price Family Foundation, and the Frederic and Patricia Salerno Foundation. The investigators disclosed relationships with Boston Scientific, Interscope, Medtronic, and others.
FROM TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY
Real-World HDV Study Characterizes Responses to Bulevirtide
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
, based on real-world experience.
These findings suggest that longer follow-up is needed to determine the optimal treatment duration for bulevirtide monotherapy, reported lead author Alexander Killer, MD, of Heinrich Heine University Düsseldorf, Germany, and colleagues.
Bulevirtide was conditionally approved by the European Medicines Agency in 2020 and is on track for full marketing approval in Europe, but it remains unavailable in the United States, where Gilead, the manufacturer, has faced regulatory hurdles.
In the MYR202 and 301 clinical trials, bulevirtide significantly reduced HDV-RNA levels in 54% of patients after 24 weeks, and reduced viremia while normalizing ALT in 48% of patients after 48 weeks.
“Given its standalone status and good treatment tolerance even in patients with compensated cirrhosis, this represents a step change in the treatment of HDV-coinfected individuals,” Dr. Killer and colleagues wrote in Gastro Hep Advances.
Yet dynamics of response and clinical predictors of treatment outcome remain unclear, prompting Dr. Killer and colleagues to conduct the present retrospective study. The dataset included 15 patients who received bulevirtide for at least 1 year at a single center in Germany.
The analysis focused on monthly changes in biochemical and virologic parameters. The investigators also screened for clinical factors that might predict responses to therapy.
Treatment response rate and safety profile aligned with data from clinical trials, suggesting that bulevirtide is safe and effective in a real-world setting.
Patients typically achieved ALT normalization 2-6 months into therapy, followed by virologic response at least 6 months after starting treatment, with one-third of patients requiring at least 1 year to achieve HDV-RNA negativity.
“Of note, normalization of ALT under bulevirtide treatment occurs earlier than the decline of HDV-RNA levels, which contrasts with the response seen to nucleos(t)ide analog treatment in hepatitis B,” the investigators wrote. They suggested that this may be due to bulevirtide’s distinct mechanism of action.
Severe hepatitis was associated with lower response rates in the first year. Possible predictors of delayed response included low body mass index and high alpha-fetoprotein.
Of note, two patients had ALT normalization without virologic response.
“It is unclear whether these patients actually have worse outcomes in terms of overall success than patients with a combined response, especially since these patients experienced a decline of more than 1 log,” Dr. Killer and colleagues wrote, noting that a 1 log reduction is considered an intermediate virologic response, and hepatitis B virus (HBV) studies have shown that severe liver events are prevented by early ALT normalization. “Therefore, it does not seem appropriate to categorize patients with biochemical responses as ‘treatment nonresponders’ [according to FDA criteria].”
The investigators called for longer observational studies to determine the optimal duration of bulevirtide monotherapy.
This study was funded by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Research Foundation. The investigators disclosed relationships with Novartis, GSK, AbbVie, and others.
FROM GASTRO HEP ADVANCES
Computer-Aided Colonoscopy Falls Short in Real-World Practice
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
, according to investigators.
Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.
CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”
RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.
The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.
“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”
This approach revealed less favorable outcomes than those reported by RCTs.
CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).
“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.
While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.
Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).
Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.
“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”
Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.
“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.
This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Liquid Biopsy for Colorectal Cancer Appears Promising But Still Lacks Robust Efficacy
, according to two new modeling studies and an expert consensus commentary.
Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.
“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.
The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.
The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.
Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
Comparing CRC Screening Methods
In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.
Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).
However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.
In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.
Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.
Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.
Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.
“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
Additional Considerations
The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.
However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.
In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.
Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.
“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.
Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.
, according to two new modeling studies and an expert consensus commentary.
Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.
“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.
The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.
The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.
Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
Comparing CRC Screening Methods
In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.
Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).
However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.
In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.
Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.
Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.
Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.
“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
Additional Considerations
The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.
However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.
In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.
Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.
“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.
Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.
, according to two new modeling studies and an expert consensus commentary.
Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.
“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.
The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.
The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.
Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
Comparing CRC Screening Methods
In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.
Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).
However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.
In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.
Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.
Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.
Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.
“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
Additional Considerations
The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.
However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.
In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.
Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.
“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.
Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.
IBS Placebo Responses Predicted By Patient Beliefs, Relationship with Provider
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.
“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”
While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES