Will Pass

First-time endoscopic retrograde cholangiopancreatography (ERCP) is increasingly being performed more than one year after cholecystectomy, leading to a rise in morbidity and adverse outcomes, according to investigators.

These findings suggest a need for more careful patient selection with ERCP, and greater reliance upon noninvasive imaging prior to considering the procedure, reported lead author Nikhil R. Thiruvengadam, MD, of Loma Linda University Health, Loma Linda, California, and colleagues.

“It is assumed that cholecystectomy is a definitive procedure for symptomatic gallstone disease in patients without concomitant choledocholithiasis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is because the development of primary choledocholithiasis is rare. Despite this, many patients have persistent or new gastrointestinal symptoms post cholecystectomy.”

Symptoms such as a dilated bile duct or abnormal liver function tests may suggest choledocholithiasis or sphincter of Oddi disorders (SOD), they noted, but recent data supporting ERCP for SOD show no significant benefit for patients with normal-sized ducts.

“Guidelines advocate for confirming the presence of choledocholithiasis using magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) given the substantial risks associated with ERCP,” Dr. Thiruvengadam and colleagues wrote.

Real-world implementation of this and associated strategies, however, remain unclear, prompting the present study.

The dataset, drawn from the Optum Clinformatics Data Mart, included 583,712 adults who had undergone cholecystectomy from 2004 to 2019, focusing on 4274 individuals who had their first ERCP more than one year post surgery. The investigators assessed the incidence, characteristics, and outcomes of these late ERCP procedures, exploring their association with patient comorbidities and the use of biliary imaging techniques such as MRCP and EUS.

From 2004 to 2021, use of noninvasive biliary imaging approximately doubled from 35.9% to 65.5% (P < .001). Yet incidence of first-time ERCP more than 1 year after cholecystectomy increased much more — by eightfold — from 0.5 to 4.2 per 1000 person-years (P < .001). Less than half (44%) of these late ERCP procedures involved gallstone removal.

Patients undergoing late ERCP were more likely to have higher baseline comorbidities, including disorders of gut-brain interaction (DGBI) and metabolic dysfunction-associated steatotic liver disease. They were also more likely to be taking an antispasmodic, anxiolytic, or chronic opioid medication.

“Late ERCP is more common and associated with worse outcomes, presumably because of higher baseline comorbidities that overlap with DGBI and mimickers of choledocholithiasis,” the investigators noted. “These highly symptomatic individuals are more likely to undergo noninvasive biliary imaging, which seems to be prompting more late ERCP.”

In turn, late ERCP is incurring more adverse events, including post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%).

“Given the known risks of ERCP, especially in this context, there remains a need to be more restrictive with offering ERCP in this setting,” Dr. Thiruvengadam and colleagues concluded. “ERCP should be used sparingly for patients who do not have confirmed choledocholithiasis until future studies ... can define which patients with a remote history of cholecystectomy respond to ERCP interventions.”

The investigators disclosed relationships with Olympus, Medtronic, ACI, and others.

First-time endoscopic retrograde cholangiopancreatography (ERCP) is increasingly being performed more than one year after cholecystectomy, leading to a rise in morbidity and adverse outcomes, according to investigators.

These findings suggest a need for more careful patient selection with ERCP, and greater reliance upon noninvasive imaging prior to considering the procedure, reported lead author Nikhil R. Thiruvengadam, MD, of Loma Linda University Health, Loma Linda, California, and colleagues.

“It is assumed that cholecystectomy is a definitive procedure for symptomatic gallstone disease in patients without concomitant choledocholithiasis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is because the development of primary choledocholithiasis is rare. Despite this, many patients have persistent or new gastrointestinal symptoms post cholecystectomy.”

Symptoms such as a dilated bile duct or abnormal liver function tests may suggest choledocholithiasis or sphincter of Oddi disorders (SOD), they noted, but recent data supporting ERCP for SOD show no significant benefit for patients with normal-sized ducts.

“Guidelines advocate for confirming the presence of choledocholithiasis using magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) given the substantial risks associated with ERCP,” Dr. Thiruvengadam and colleagues wrote.

Real-world implementation of this and associated strategies, however, remain unclear, prompting the present study.

The dataset, drawn from the Optum Clinformatics Data Mart, included 583,712 adults who had undergone cholecystectomy from 2004 to 2019, focusing on 4274 individuals who had their first ERCP more than one year post surgery. The investigators assessed the incidence, characteristics, and outcomes of these late ERCP procedures, exploring their association with patient comorbidities and the use of biliary imaging techniques such as MRCP and EUS.

From 2004 to 2021, use of noninvasive biliary imaging approximately doubled from 35.9% to 65.5% (P < .001). Yet incidence of first-time ERCP more than 1 year after cholecystectomy increased much more — by eightfold — from 0.5 to 4.2 per 1000 person-years (P < .001). Less than half (44%) of these late ERCP procedures involved gallstone removal.

Patients undergoing late ERCP were more likely to have higher baseline comorbidities, including disorders of gut-brain interaction (DGBI) and metabolic dysfunction-associated steatotic liver disease. They were also more likely to be taking an antispasmodic, anxiolytic, or chronic opioid medication.

“Late ERCP is more common and associated with worse outcomes, presumably because of higher baseline comorbidities that overlap with DGBI and mimickers of choledocholithiasis,” the investigators noted. “These highly symptomatic individuals are more likely to undergo noninvasive biliary imaging, which seems to be prompting more late ERCP.”

In turn, late ERCP is incurring more adverse events, including post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%).

“Given the known risks of ERCP, especially in this context, there remains a need to be more restrictive with offering ERCP in this setting,” Dr. Thiruvengadam and colleagues concluded. “ERCP should be used sparingly for patients who do not have confirmed choledocholithiasis until future studies ... can define which patients with a remote history of cholecystectomy respond to ERCP interventions.”

The investigators disclosed relationships with Olympus, Medtronic, ACI, and others.

First-time endoscopic retrograde cholangiopancreatography (ERCP) is increasingly being performed more than one year after cholecystectomy, leading to a rise in morbidity and adverse outcomes, according to investigators.

These findings suggest a need for more careful patient selection with ERCP, and greater reliance upon noninvasive imaging prior to considering the procedure, reported lead author Nikhil R. Thiruvengadam, MD, of Loma Linda University Health, Loma Linda, California, and colleagues.

“It is assumed that cholecystectomy is a definitive procedure for symptomatic gallstone disease in patients without concomitant choledocholithiasis,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is because the development of primary choledocholithiasis is rare. Despite this, many patients have persistent or new gastrointestinal symptoms post cholecystectomy.”

Symptoms such as a dilated bile duct or abnormal liver function tests may suggest choledocholithiasis or sphincter of Oddi disorders (SOD), they noted, but recent data supporting ERCP for SOD show no significant benefit for patients with normal-sized ducts.

“Guidelines advocate for confirming the presence of choledocholithiasis using magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) given the substantial risks associated with ERCP,” Dr. Thiruvengadam and colleagues wrote.

Real-world implementation of this and associated strategies, however, remain unclear, prompting the present study.

The dataset, drawn from the Optum Clinformatics Data Mart, included 583,712 adults who had undergone cholecystectomy from 2004 to 2019, focusing on 4274 individuals who had their first ERCP more than one year post surgery. The investigators assessed the incidence, characteristics, and outcomes of these late ERCP procedures, exploring their association with patient comorbidities and the use of biliary imaging techniques such as MRCP and EUS.

From 2004 to 2021, use of noninvasive biliary imaging approximately doubled from 35.9% to 65.5% (P < .001). Yet incidence of first-time ERCP more than 1 year after cholecystectomy increased much more — by eightfold — from 0.5 to 4.2 per 1000 person-years (P < .001). Less than half (44%) of these late ERCP procedures involved gallstone removal.

Patients undergoing late ERCP were more likely to have higher baseline comorbidities, including disorders of gut-brain interaction (DGBI) and metabolic dysfunction-associated steatotic liver disease. They were also more likely to be taking an antispasmodic, anxiolytic, or chronic opioid medication.

“Late ERCP is more common and associated with worse outcomes, presumably because of higher baseline comorbidities that overlap with DGBI and mimickers of choledocholithiasis,” the investigators noted. “These highly symptomatic individuals are more likely to undergo noninvasive biliary imaging, which seems to be prompting more late ERCP.”

In turn, late ERCP is incurring more adverse events, including post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%).

“Given the known risks of ERCP, especially in this context, there remains a need to be more restrictive with offering ERCP in this setting,” Dr. Thiruvengadam and colleagues concluded. “ERCP should be used sparingly for patients who do not have confirmed choledocholithiasis until future studies ... can define which patients with a remote history of cholecystectomy respond to ERCP interventions.”

The investigators disclosed relationships with Olympus, Medtronic, ACI, and others.

Total mesometrial resection (TMMR) is associated with significantly longer recurrence-free survival (RFS) and overall survival (OS) than standard treatment for patients with early-stage cervical cancer, while outcomes were not different among those with locally advanced disease, according to a new study.

These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
 

What is the rationale behind TMMR?

“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”

This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.

To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
 

What methods were used to compare TMMR with standard treatment?

The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.

Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.

Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
 

How did TMMR compare with standard treatment?

TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.

Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).

Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
 

Are these data strong enough to make TMMR the new standard treatment?

Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”

While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”

How does TMMR fit into the current treatment landscape for cervical cancer?

“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.

She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.

“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”

Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.

“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”

This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.

Total mesometrial resection (TMMR) is associated with significantly longer recurrence-free survival (RFS) and overall survival (OS) than standard treatment for patients with early-stage cervical cancer, while outcomes were not different among those with locally advanced disease, according to a new study.

These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
 

What is the rationale behind TMMR?

“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”

This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.

To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
 

What methods were used to compare TMMR with standard treatment?

The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.

Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.

Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
 

How did TMMR compare with standard treatment?

TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.

Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).

Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
 

Are these data strong enough to make TMMR the new standard treatment?

Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”

While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”

How does TMMR fit into the current treatment landscape for cervical cancer?

“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.

She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.

“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”

Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.

“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”

This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.

Total mesometrial resection (TMMR) is associated with significantly longer recurrence-free survival (RFS) and overall survival (OS) than standard treatment for patients with early-stage cervical cancer, while outcomes were not different among those with locally advanced disease, according to a new study.

These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
 

What is the rationale behind TMMR?

“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”

This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.

To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
 

What methods were used to compare TMMR with standard treatment?

The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.

Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.

Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
 

How did TMMR compare with standard treatment?

TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.

Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).

Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
 

Are these data strong enough to make TMMR the new standard treatment?

Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”

While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”

How does TMMR fit into the current treatment landscape for cervical cancer?

“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.

She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.

“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”

Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.

“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”

This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.

An electronic health record (EHR)–based nudge intervention could reduce potentially unnecessary sentinel lymph node biopsies (SLNB) among older women with early-stage breast cancer, the authors of new research say.

Participating surgeons noted that the reminder system added minimal friction to their workflow, as it did not require additional clicks or actions on the day of the patient visit, reported lead author Neil Carleton, PhD, of UPMC Hillman Cancer Center, Pittsburgh, and colleagues in JAMA Surgery (JAMA Surg. 2024 Jul 17. doi: 10.1001/jamasurg.2024.2407).

This effort to reduce the rate of SLNB stems from the Choosing Wisely campaign, which recommends against axillary staging in women 70 years and older with early-stage, clinically node-negative (cN0), hormone receptor–positive (HR+) breast cancer, the investigators said.

“These recommendations were developed because axillary staging did not impact survival, and rates of SLN positivity were low because of the tumor’s biological phenotype,” they wrote. “Even in older patients with tumors that exhibit concerning clinicopathologic features, limited nodal involvement does not often alter receipt of chemotherapy independently from genomic testing. Despite these recommendations, most women still receive axillary surgery.”
 

How Did the Nudge System Aim to Reduce the Rate of SLNB?

The nudge intervention involved adding a new column to the Epic schedule view, which flagged eligible patients during their first outpatient surgical consultation. The flag appeared as a caution sign or red clipboard icon. When surgeons hovered over the icon, a text box appeared, reminding them to consider omitting SLNB after a detailed review of core biopsy pathology and ultrasonographic imaging.

The intervention was evaluated at eight outpatient clinics within an integrated healthcare system that included seven breast surgical oncologists.

The study began with a 12-month preintervention period to serve as a control, during which time SLNB rate was determined via 194 patients in the target demographic. SLNB rate was again collected during the 12-month intervention period, which involved 193 patients meeting enrollment criteria. Between these periods, the investigators conducted a brief session lasting less than 30 minutes to introduce the surgeons to the rationale and design of the nudge column.
 

How Effective Was the Nudge System?

The intervention reduced the SLNB rate from 46.9% to 23.8%, representing a 49.3% decrease in use of SLNB. Efficacy was further supported by a significant reduction in SLNB according to an interrupted time series model (adjusted odds ratio, 0.26; 95% confidence interval, 0.07 to 0.90; P = .03). Extended follow-up showed that this effect was durable beyond the intervention period, with a 6-month mean reduction in SLNB of 15.6%.

Omission of SLNB led to higher rates of pathological node positivity during the intervention period (15.2% vs 8.8%), with all positive cases staged as pN1. Adjuvant therapy recommendations were similar between groups and driven by genomic testing, not nodal status. The intervention period also saw a decrease in referrals for lymphedema evaluation (3.6% vs. 6.2%).

How Might the Nudge System Be Implemented in Other Practices?

Although the SLNB nudge system was effective in the present study, likelihood of uptake among practices could vary widely, according to Anne M. Wallace, MD, professor of clinical surgery at UC San Diego Health and director of the Moores Comprehensive Breast Health Program.

On a fundamental level, not all centers use Epic software, which could present issues with compatibility, Dr. Wallace said in an interview. More importantly, she added, many institutions already have EHR-based alerts and reminders in place, so it is not always feasible to add a new nudge for every possible clinical scenario.

“Already there are so many little icons that we have to go through now when we close a note,” she said. “That’s why electronic medical records are becoming one of the leading stressors in medicine.”

This presents a more complex challenge, Dr. Wallace said, particularly as potentially practice-changing data are becoming available, and physicians may not have time to learn about them and integrate them into routine practice. She suggested that the present system may be most appropriate for oncologists in solo practice, or in small group practices where it is more challenging to have routine conversations about changing standards of care.

What Are the Risks of Using the Nudge System?

One of those conversations may surround the validity of the recommendation implemented in the present study.

Although the Society of Surgical Oncology recommends against SLNB in the described demographic, other experts, including Dr. Wallace, take a more nuanced view of the decision.

She noted that some patients with a chronological age of 70 may have a lower biological age, casting doubt on the legitimacy of the age threshold, and those near the threshold may wish to make the decision about staging for themselves.

Beyond these concerns, Dr. Wallace described two potential risks involved in forgoing SLNB.

First, there’s the potential for underestimating the tumor’s severity, she said, as this could mean a trip back to the operating room. A tumor initially thought to be low-grade might later be found to be high-grade, necessitating further surgery. Some patients might refuse additional surgery, leaving the more aggressive tumor untreated.

Second, the nudge system could complicate radiation treatment decisions, Dr. Wallace said. Without full nodal status, some radiation oncologists might push for additional radiation therapy, which incurs a greater treatment burden than SNLB.
 

What Are Some Alternatives to the Nudge System?

After discussing the strengths and weaknesses of the present EHR-based nudge system, and others like it, Dr. Wallace returned to the importance of ongoing communication among colleagues managing complex cases.

At UC San Diego Health, where oncologists meet weekly for a 2-hour breast cancer conference, “we nudge each other,” she said.

This study was supported by the Shear Family Foundation, UPMC eRecord Ambulatory Decision Support and Analytics, UPMC Hillman Cancer Center Biostatistics Facility, and National Institutes of Health. The investigators disclosed relationships with Pfizer, Amgen, the Lewin Group, and Milestone Pennsylvania, and others.

An electronic health record (EHR)–based nudge intervention could reduce potentially unnecessary sentinel lymph node biopsies (SLNB) among older women with early-stage breast cancer, the authors of new research say.

Participating surgeons noted that the reminder system added minimal friction to their workflow, as it did not require additional clicks or actions on the day of the patient visit, reported lead author Neil Carleton, PhD, of UPMC Hillman Cancer Center, Pittsburgh, and colleagues in JAMA Surgery (JAMA Surg. 2024 Jul 17. doi: 10.1001/jamasurg.2024.2407).

This effort to reduce the rate of SLNB stems from the Choosing Wisely campaign, which recommends against axillary staging in women 70 years and older with early-stage, clinically node-negative (cN0), hormone receptor–positive (HR+) breast cancer, the investigators said.

“These recommendations were developed because axillary staging did not impact survival, and rates of SLN positivity were low because of the tumor’s biological phenotype,” they wrote. “Even in older patients with tumors that exhibit concerning clinicopathologic features, limited nodal involvement does not often alter receipt of chemotherapy independently from genomic testing. Despite these recommendations, most women still receive axillary surgery.”
 

How Did the Nudge System Aim to Reduce the Rate of SLNB?

The nudge intervention involved adding a new column to the Epic schedule view, which flagged eligible patients during their first outpatient surgical consultation. The flag appeared as a caution sign or red clipboard icon. When surgeons hovered over the icon, a text box appeared, reminding them to consider omitting SLNB after a detailed review of core biopsy pathology and ultrasonographic imaging.

The intervention was evaluated at eight outpatient clinics within an integrated healthcare system that included seven breast surgical oncologists.

The study began with a 12-month preintervention period to serve as a control, during which time SLNB rate was determined via 194 patients in the target demographic. SLNB rate was again collected during the 12-month intervention period, which involved 193 patients meeting enrollment criteria. Between these periods, the investigators conducted a brief session lasting less than 30 minutes to introduce the surgeons to the rationale and design of the nudge column.
 

How Effective Was the Nudge System?

The intervention reduced the SLNB rate from 46.9% to 23.8%, representing a 49.3% decrease in use of SLNB. Efficacy was further supported by a significant reduction in SLNB according to an interrupted time series model (adjusted odds ratio, 0.26; 95% confidence interval, 0.07 to 0.90; P = .03). Extended follow-up showed that this effect was durable beyond the intervention period, with a 6-month mean reduction in SLNB of 15.6%.

Omission of SLNB led to higher rates of pathological node positivity during the intervention period (15.2% vs 8.8%), with all positive cases staged as pN1. Adjuvant therapy recommendations were similar between groups and driven by genomic testing, not nodal status. The intervention period also saw a decrease in referrals for lymphedema evaluation (3.6% vs. 6.2%).

How Might the Nudge System Be Implemented in Other Practices?

Although the SLNB nudge system was effective in the present study, likelihood of uptake among practices could vary widely, according to Anne M. Wallace, MD, professor of clinical surgery at UC San Diego Health and director of the Moores Comprehensive Breast Health Program.

On a fundamental level, not all centers use Epic software, which could present issues with compatibility, Dr. Wallace said in an interview. More importantly, she added, many institutions already have EHR-based alerts and reminders in place, so it is not always feasible to add a new nudge for every possible clinical scenario.

“Already there are so many little icons that we have to go through now when we close a note,” she said. “That’s why electronic medical records are becoming one of the leading stressors in medicine.”

This presents a more complex challenge, Dr. Wallace said, particularly as potentially practice-changing data are becoming available, and physicians may not have time to learn about them and integrate them into routine practice. She suggested that the present system may be most appropriate for oncologists in solo practice, or in small group practices where it is more challenging to have routine conversations about changing standards of care.

What Are the Risks of Using the Nudge System?

One of those conversations may surround the validity of the recommendation implemented in the present study.

Although the Society of Surgical Oncology recommends against SLNB in the described demographic, other experts, including Dr. Wallace, take a more nuanced view of the decision.

She noted that some patients with a chronological age of 70 may have a lower biological age, casting doubt on the legitimacy of the age threshold, and those near the threshold may wish to make the decision about staging for themselves.

Beyond these concerns, Dr. Wallace described two potential risks involved in forgoing SLNB.

First, there’s the potential for underestimating the tumor’s severity, she said, as this could mean a trip back to the operating room. A tumor initially thought to be low-grade might later be found to be high-grade, necessitating further surgery. Some patients might refuse additional surgery, leaving the more aggressive tumor untreated.

Second, the nudge system could complicate radiation treatment decisions, Dr. Wallace said. Without full nodal status, some radiation oncologists might push for additional radiation therapy, which incurs a greater treatment burden than SNLB.
 

What Are Some Alternatives to the Nudge System?

After discussing the strengths and weaknesses of the present EHR-based nudge system, and others like it, Dr. Wallace returned to the importance of ongoing communication among colleagues managing complex cases.

At UC San Diego Health, where oncologists meet weekly for a 2-hour breast cancer conference, “we nudge each other,” she said.

This study was supported by the Shear Family Foundation, UPMC eRecord Ambulatory Decision Support and Analytics, UPMC Hillman Cancer Center Biostatistics Facility, and National Institutes of Health. The investigators disclosed relationships with Pfizer, Amgen, the Lewin Group, and Milestone Pennsylvania, and others.

An electronic health record (EHR)–based nudge intervention could reduce potentially unnecessary sentinel lymph node biopsies (SLNB) among older women with early-stage breast cancer, the authors of new research say.

Participating surgeons noted that the reminder system added minimal friction to their workflow, as it did not require additional clicks or actions on the day of the patient visit, reported lead author Neil Carleton, PhD, of UPMC Hillman Cancer Center, Pittsburgh, and colleagues in JAMA Surgery (JAMA Surg. 2024 Jul 17. doi: 10.1001/jamasurg.2024.2407).

This effort to reduce the rate of SLNB stems from the Choosing Wisely campaign, which recommends against axillary staging in women 70 years and older with early-stage, clinically node-negative (cN0), hormone receptor–positive (HR+) breast cancer, the investigators said.

“These recommendations were developed because axillary staging did not impact survival, and rates of SLN positivity were low because of the tumor’s biological phenotype,” they wrote. “Even in older patients with tumors that exhibit concerning clinicopathologic features, limited nodal involvement does not often alter receipt of chemotherapy independently from genomic testing. Despite these recommendations, most women still receive axillary surgery.”
 

How Did the Nudge System Aim to Reduce the Rate of SLNB?

The nudge intervention involved adding a new column to the Epic schedule view, which flagged eligible patients during their first outpatient surgical consultation. The flag appeared as a caution sign or red clipboard icon. When surgeons hovered over the icon, a text box appeared, reminding them to consider omitting SLNB after a detailed review of core biopsy pathology and ultrasonographic imaging.

The intervention was evaluated at eight outpatient clinics within an integrated healthcare system that included seven breast surgical oncologists.

The study began with a 12-month preintervention period to serve as a control, during which time SLNB rate was determined via 194 patients in the target demographic. SLNB rate was again collected during the 12-month intervention period, which involved 193 patients meeting enrollment criteria. Between these periods, the investigators conducted a brief session lasting less than 30 minutes to introduce the surgeons to the rationale and design of the nudge column.
 

How Effective Was the Nudge System?

The intervention reduced the SLNB rate from 46.9% to 23.8%, representing a 49.3% decrease in use of SLNB. Efficacy was further supported by a significant reduction in SLNB according to an interrupted time series model (adjusted odds ratio, 0.26; 95% confidence interval, 0.07 to 0.90; P = .03). Extended follow-up showed that this effect was durable beyond the intervention period, with a 6-month mean reduction in SLNB of 15.6%.

Omission of SLNB led to higher rates of pathological node positivity during the intervention period (15.2% vs 8.8%), with all positive cases staged as pN1. Adjuvant therapy recommendations were similar between groups and driven by genomic testing, not nodal status. The intervention period also saw a decrease in referrals for lymphedema evaluation (3.6% vs. 6.2%).

How Might the Nudge System Be Implemented in Other Practices?

Although the SLNB nudge system was effective in the present study, likelihood of uptake among practices could vary widely, according to Anne M. Wallace, MD, professor of clinical surgery at UC San Diego Health and director of the Moores Comprehensive Breast Health Program.

On a fundamental level, not all centers use Epic software, which could present issues with compatibility, Dr. Wallace said in an interview. More importantly, she added, many institutions already have EHR-based alerts and reminders in place, so it is not always feasible to add a new nudge for every possible clinical scenario.

“Already there are so many little icons that we have to go through now when we close a note,” she said. “That’s why electronic medical records are becoming one of the leading stressors in medicine.”

This presents a more complex challenge, Dr. Wallace said, particularly as potentially practice-changing data are becoming available, and physicians may not have time to learn about them and integrate them into routine practice. She suggested that the present system may be most appropriate for oncologists in solo practice, or in small group practices where it is more challenging to have routine conversations about changing standards of care.

What Are the Risks of Using the Nudge System?

One of those conversations may surround the validity of the recommendation implemented in the present study.

Although the Society of Surgical Oncology recommends against SLNB in the described demographic, other experts, including Dr. Wallace, take a more nuanced view of the decision.

She noted that some patients with a chronological age of 70 may have a lower biological age, casting doubt on the legitimacy of the age threshold, and those near the threshold may wish to make the decision about staging for themselves.

Beyond these concerns, Dr. Wallace described two potential risks involved in forgoing SLNB.

First, there’s the potential for underestimating the tumor’s severity, she said, as this could mean a trip back to the operating room. A tumor initially thought to be low-grade might later be found to be high-grade, necessitating further surgery. Some patients might refuse additional surgery, leaving the more aggressive tumor untreated.

Second, the nudge system could complicate radiation treatment decisions, Dr. Wallace said. Without full nodal status, some radiation oncologists might push for additional radiation therapy, which incurs a greater treatment burden than SNLB.
 

What Are Some Alternatives to the Nudge System?

After discussing the strengths and weaknesses of the present EHR-based nudge system, and others like it, Dr. Wallace returned to the importance of ongoing communication among colleagues managing complex cases.

At UC San Diego Health, where oncologists meet weekly for a 2-hour breast cancer conference, “we nudge each other,” she said.

This study was supported by the Shear Family Foundation, UPMC eRecord Ambulatory Decision Support and Analytics, UPMC Hillman Cancer Center Biostatistics Facility, and National Institutes of Health. The investigators disclosed relationships with Pfizer, Amgen, the Lewin Group, and Milestone Pennsylvania, and others.

Decreased prevalence of Helicobacter pylori infection is not associated with an increased rate of esophageal cancer, based on a multinational cohort study.

This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”

That study involved only 11 cases of EAC.

For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.

Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.

SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).

“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.

Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”

Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.

“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”

They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.

Decreased prevalence of Helicobacter pylori infection is not associated with an increased rate of esophageal cancer, based on a multinational cohort study.

This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”

That study involved only 11 cases of EAC.

For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.

Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.

SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).

“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.

Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”

Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.

“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”

They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.

Decreased prevalence of Helicobacter pylori infection is not associated with an increased rate of esophageal cancer, based on a multinational cohort study.

This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”

That study involved only 11 cases of EAC.

For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.

Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.

SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).

“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.

Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”

Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.

“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”

They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.

Many patients with eosinophilic esophagitis (EoE) continue to have substantial disease burden despite medical therapy, based on a recent retrospective study.

Challenging patient journeys were common across age groups, with a range of ongoing symptoms and histological abnormalities supporting high unmet need among patients with EoE, lead author Olulade Ayodele, MBBS, MPH, of Takeda Development Center Americas and colleagues reported.

“Recent studies have found that patients with EoE experience a complicated journey to diagnosis and a substantial disease burden, which requires significant healthcare resource utilization,” the investigators wrote in Gastro Hep Advances . “Reasons for this may include delays in diagnosis owing to nonspecific symptoms, adaptive behaviors, progression of silent disease, lack of adequate follow-up or referral, or suboptimal treatment after diagnosis.”Two medications are currently Food and Drug administration approved for EoE: dupilumab, a biologic for patients aged 1 year and older, and budesonide oral suspension, a topical corticosteroid for patients aged 11 years and older.

The investigators noted that “biologic therapies may not always be selected as first-line treatment, and are often associated with high costs”; however, the effects of real-world treatment decisions like these are poorly documented, prompting the present study.

The final dataset comprised 613 patients with newly diagnosed EoE treated in a rural integrated healthcare system, all of whom had at least 12 months of data before and after a predetermined index date. Individuals were stratified by age, including 182 children, 146 adolescents, 244 adults, and 41 older adults.

Signs and symptoms of EoE frequently worsened after the index date, including dysphagia (34.6% before, 49.9% after), abdominal pain (33.0% before, 48.1% after), and nausea/vomiting (20.1% before, 31.5% after).

At baseline, 80.5% of endoscopies were abnormal and 87.9% of patients had more than 15 eosinophils/high-power field. These parameters improved post index; however, 3 years later, 62.3% of patients still had abnormal endoscopic appearance and 51.2% had abnormal histologic activity.

Before and after index, the most prescribed treatments were corticosteroids (47.3% before, 87.9% after) and proton pump inhibitors (51.1% before, 96.1% after).

After index, 44.0% of patients discontinued their first-line treatment, and 13.9% experienced disease progression.

“We found that a substantial portion of patients with EoE received variable medical treatments, and did not report undergoing follow-up care, consulting with specialists, or routinely undergoing endoscopy with biopsy after diagnosis; the reasons for this are unknown, but experiences do not appear to be consistent with current guideline recommendations,” Dr. Ayodele and colleagues wrote.

They also noted substantial healthcare resource utilization; more than half of the patients visited emergency departments, and nearly one in five were admitted as inpatients.

“Our findings outline the persistent disease activity and difficult therapeutic journeys faced by patients with EoE irrespective of their age, as well as the substantial disease burden,” the investigators concluded. “These data highlight the potential unmet medical need of patients with EoE in the United States.”The study was funded by Shire Human Genetic Therapies, a member of the Takeda group of companies. The investigators disclosed additional relationships with RTI Health Solutions and Receptos/Celgene.

Many patients with eosinophilic esophagitis (EoE) continue to have substantial disease burden despite medical therapy, based on a recent retrospective study.

Challenging patient journeys were common across age groups, with a range of ongoing symptoms and histological abnormalities supporting high unmet need among patients with EoE, lead author Olulade Ayodele, MBBS, MPH, of Takeda Development Center Americas and colleagues reported.

“Recent studies have found that patients with EoE experience a complicated journey to diagnosis and a substantial disease burden, which requires significant healthcare resource utilization,” the investigators wrote in Gastro Hep Advances . “Reasons for this may include delays in diagnosis owing to nonspecific symptoms, adaptive behaviors, progression of silent disease, lack of adequate follow-up or referral, or suboptimal treatment after diagnosis.”Two medications are currently Food and Drug administration approved for EoE: dupilumab, a biologic for patients aged 1 year and older, and budesonide oral suspension, a topical corticosteroid for patients aged 11 years and older.

The investigators noted that “biologic therapies may not always be selected as first-line treatment, and are often associated with high costs”; however, the effects of real-world treatment decisions like these are poorly documented, prompting the present study.

The final dataset comprised 613 patients with newly diagnosed EoE treated in a rural integrated healthcare system, all of whom had at least 12 months of data before and after a predetermined index date. Individuals were stratified by age, including 182 children, 146 adolescents, 244 adults, and 41 older adults.

Signs and symptoms of EoE frequently worsened after the index date, including dysphagia (34.6% before, 49.9% after), abdominal pain (33.0% before, 48.1% after), and nausea/vomiting (20.1% before, 31.5% after).

At baseline, 80.5% of endoscopies were abnormal and 87.9% of patients had more than 15 eosinophils/high-power field. These parameters improved post index; however, 3 years later, 62.3% of patients still had abnormal endoscopic appearance and 51.2% had abnormal histologic activity.

Before and after index, the most prescribed treatments were corticosteroids (47.3% before, 87.9% after) and proton pump inhibitors (51.1% before, 96.1% after).

After index, 44.0% of patients discontinued their first-line treatment, and 13.9% experienced disease progression.

“We found that a substantial portion of patients with EoE received variable medical treatments, and did not report undergoing follow-up care, consulting with specialists, or routinely undergoing endoscopy with biopsy after diagnosis; the reasons for this are unknown, but experiences do not appear to be consistent with current guideline recommendations,” Dr. Ayodele and colleagues wrote.

They also noted substantial healthcare resource utilization; more than half of the patients visited emergency departments, and nearly one in five were admitted as inpatients.

“Our findings outline the persistent disease activity and difficult therapeutic journeys faced by patients with EoE irrespective of their age, as well as the substantial disease burden,” the investigators concluded. “These data highlight the potential unmet medical need of patients with EoE in the United States.”The study was funded by Shire Human Genetic Therapies, a member of the Takeda group of companies. The investigators disclosed additional relationships with RTI Health Solutions and Receptos/Celgene.

Many patients with eosinophilic esophagitis (EoE) continue to have substantial disease burden despite medical therapy, based on a recent retrospective study.

Challenging patient journeys were common across age groups, with a range of ongoing symptoms and histological abnormalities supporting high unmet need among patients with EoE, lead author Olulade Ayodele, MBBS, MPH, of Takeda Development Center Americas and colleagues reported.

“Recent studies have found that patients with EoE experience a complicated journey to diagnosis and a substantial disease burden, which requires significant healthcare resource utilization,” the investigators wrote in Gastro Hep Advances . “Reasons for this may include delays in diagnosis owing to nonspecific symptoms, adaptive behaviors, progression of silent disease, lack of adequate follow-up or referral, or suboptimal treatment after diagnosis.”Two medications are currently Food and Drug administration approved for EoE: dupilumab, a biologic for patients aged 1 year and older, and budesonide oral suspension, a topical corticosteroid for patients aged 11 years and older.

The investigators noted that “biologic therapies may not always be selected as first-line treatment, and are often associated with high costs”; however, the effects of real-world treatment decisions like these are poorly documented, prompting the present study.

The final dataset comprised 613 patients with newly diagnosed EoE treated in a rural integrated healthcare system, all of whom had at least 12 months of data before and after a predetermined index date. Individuals were stratified by age, including 182 children, 146 adolescents, 244 adults, and 41 older adults.

Signs and symptoms of EoE frequently worsened after the index date, including dysphagia (34.6% before, 49.9% after), abdominal pain (33.0% before, 48.1% after), and nausea/vomiting (20.1% before, 31.5% after).

At baseline, 80.5% of endoscopies were abnormal and 87.9% of patients had more than 15 eosinophils/high-power field. These parameters improved post index; however, 3 years later, 62.3% of patients still had abnormal endoscopic appearance and 51.2% had abnormal histologic activity.

Before and after index, the most prescribed treatments were corticosteroids (47.3% before, 87.9% after) and proton pump inhibitors (51.1% before, 96.1% after).

After index, 44.0% of patients discontinued their first-line treatment, and 13.9% experienced disease progression.

“We found that a substantial portion of patients with EoE received variable medical treatments, and did not report undergoing follow-up care, consulting with specialists, or routinely undergoing endoscopy with biopsy after diagnosis; the reasons for this are unknown, but experiences do not appear to be consistent with current guideline recommendations,” Dr. Ayodele and colleagues wrote.

They also noted substantial healthcare resource utilization; more than half of the patients visited emergency departments, and nearly one in five were admitted as inpatients.

“Our findings outline the persistent disease activity and difficult therapeutic journeys faced by patients with EoE irrespective of their age, as well as the substantial disease burden,” the investigators concluded. “These data highlight the potential unmet medical need of patients with EoE in the United States.”The study was funded by Shire Human Genetic Therapies, a member of the Takeda group of companies. The investigators disclosed additional relationships with RTI Health Solutions and Receptos/Celgene.

The Fibrosis-4 (FIB-4) index shows high discordance with liver stiffness measurement (LSM) via transient elastography, suggesting that many patients are misclassified, potentially impacting clinical decisions, according to investigators.

These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.

Houston Methodist Hospital

“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Yet the performance of the FIB-4 index in this context remains unclear.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.

All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).

Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.

Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.

“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”

They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.

“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”

The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.

The Fibrosis-4 (FIB-4) index shows high discordance with liver stiffness measurement (LSM) via transient elastography, suggesting that many patients are misclassified, potentially impacting clinical decisions, according to investigators.

These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.

Houston Methodist Hospital

“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Yet the performance of the FIB-4 index in this context remains unclear.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.

All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).

Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.

Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.

“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”

They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.

“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”

The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.

The Fibrosis-4 (FIB-4) index shows high discordance with liver stiffness measurement (LSM) via transient elastography, suggesting that many patients are misclassified, potentially impacting clinical decisions, according to investigators.

These findings call for a cautious interpretation of low-risk FIB-4 results among patients at greatest risk of misclassification, and/or use of alternative assessment strategies, reported Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, and coauthors.

Houston Methodist Hospital

“Currently, the AGA/AASLD Pathways recommends identifying patients at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), then using sequential testing with FIB-4 followed by FibroScan to risk-stratify patients,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Yet the performance of the FIB-4 index in this context remains unclear.

“Previous studies have shown FIB-4 to have low accuracy for screening liver fibrosis, especially among obese and diabetic patients,” the investigators wrote. “Thus, there is a concern that classifying patients with FIB-4 can lead to misclassification and missed diagnosis.”

To explore this concern, Dr. Noureddin and colleagues turned to data from the 2017-2020 National Health and Nutrition Examination Surveys, including 5285 subjects at risk for MASLD. Exclusions were made for those with excessive alcohol intake or other liver diseases, resulting in a final cohort of 3741 individuals.

All subjects were classified as low-, indeterminate-, or high-risk for advanced liver fibrosis based on FIB-4 scores. These scores were then compared with liver stiffness measurements (LSM) obtained through transient elastography (FibroScan).

Out of 2776 subjects classified as low-risk by FIB-4, 277 (10%) were reclassified as higher risk by LSM, including 75 (2.7%) who were found to be at high risk. Out of 879 subjects with indeterminate FIB-4 scores, 37 (4.2%) were at high risk according to LSM. Finally, among the 86 subjects classified as high risk by FIB-4, 68 (79.1%) were reclassified as lower risk by LSM, including 54 (62.8%) who were deemed low risk.

Subjects misclassified as low risk by FIB-4 were typically older and had higher waist circumferences, body mass indices, glycohemoglobin A1c levels, fasting glucose levels, liver enzyme levels, diastolic blood pressures, controlled attenuation parameter scores, white blood cell counts, and alkaline phosphatase levels, but lower high-density lipoprotein and albumin levels (all P less than .05). They were also more likely to have prediabetes or diabetes.

“[I]t is important to acknowledge that 10% of the subjects were misclassified as low risk by FIB-4,” Dr. Noureddin and colleagues wrote, including 2.7% of patients who were actually high risk. “This misclassification of high-risk patients can lead to missed diagnoses, delaying crucial medical treatments or lifestyle interventions.”

They therefore suggested cautious interpretation of low-risk FIB-4 results among patients with factors predicting misclassification, or even use of alternative diagnostic strategies.

“Some possible alternatives to FIB-4 include new serum tests such NIS-2+, MASEF, SAFE score, and machine learning methods,” Dr. Noureddin and colleagues wrote. “However, additional confirmatory and cost-effective studies are required to validate the effectiveness of these tests, including studies conducted on the general population.”

The investigators disclosed relationships with AbbVie, Corcept, Galectin, and others.

Autonomous artificial intelligence (AI) can achieve similar accuracy to AI-assisted humans (AI-H) in the optical diagnosis of diminutive colorectal polyps, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.

These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”

To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.

Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.

The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).

But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).

“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”

Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).

Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.

“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.

Autonomous artificial intelligence (AI) can achieve similar accuracy to AI-assisted humans (AI-H) in the optical diagnosis of diminutive colorectal polyps, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.

These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”

To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.

Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.

The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).

But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).

“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”

Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).

Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.

“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.

Autonomous artificial intelligence (AI) can achieve similar accuracy to AI-assisted humans (AI-H) in the optical diagnosis of diminutive colorectal polyps, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.

These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”

To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.

Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.

The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).

But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).

“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”

Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).

Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.

“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.

Colitis-induced small intestinal hypomotility is closely linked to the loss of enteroendocrine cells (EECs) in mice, revealing a potential therapeutic strategy for patients with inflammatory bowel disease (IBD), according to investigators.

These findings suggest that restoring EEC function could alleviate some of the more general abdominal symptoms associated with IBD, reported lead author Zachariah Raouf, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.

“The symptoms experienced by patients with IBD, especially ulcerative colitis, may include those that are colonic in nature, such as bloody stools, abdominal pain, and weight loss, as well as those that are more general in nature, such as severe nausea and abdominal bloating,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology . “Although the first set of symptoms may be attributable to the effects of colonic inflammation itself, those that are more vague seem to overlap with the symptoms that patients with small intestinal dysmotility experience, such as occur in response to medications, or diabetes.”

Supporting this notion, several previous studies have reported the onset of intestinal dysmotility in experimental models of colitis, which is believed to be caused by impaired enteric nervous system function. But the precise mechanisms behind the impaired intestinal motility observed in colitis patients remain unclear.

To learn more, Dr. Raouf and colleagues conducted experiments involving three groups of mice: wild-type mice, mice genetically engineered to overexpress EECs, and mice lacking EECs.

To induce colitis, the mice were administered dextran sulfate sodium (DSS) in drinking water at concentrations of 2.5% or 5% for 7 days. Small intestinal motility was evaluated by measuring the transit of fluorescein isothiocyanate (FITC)-dextran. Immunohistochemical analyses were conducted to assess EEC number and differentiation, while quantitative reverse-transcriptase polymerase chain reaction was used to examine the expression of genes related to serotonin synthesis and transport.

The researchers examined colon length and signs of colonic inflammation, monitored weight loss, and measured the expression of proinflammatory cytokines. Histological analyses of colon and small intestine tissues were performed to further understand the effects of colitis. The presence and number of EEC cells was evaluated using chromogranin A (ChgA) staining, while apoptosis in EECs was measured via TUNEL staining. The expression of serotonin-related genes was also assessed.

These experiments revealed that DSS-induced colitis led to significant small-bowel hypomotility and a reduction in EEC density. Of note, genetic overexpression of EECs or treatment with prucalopride, a 5-hydroxytryptamine receptor 4 agonist, improved small intestinal motility.

“It is noteworthy that there were no significant changes in the density of other intestinal epithelial cells, or in other cell types that are linked to motility, such as enteric glia and neurons, suggesting the specificity of the effect,” the investigators wrote. “Importantly, treatment with a serotonin agonist ameliorated the colitis-induced, small-bowel hypomotility and attenuated the severity of colitis, providing potential clinical relevance of the current findings. Taken together, these results identify mechanisms to explain the intestinal hypomotility observed in the setting of colitis.”Dr. Raouf and colleagues called for human clinical trials to their findings. Specifically, they suggested exploring therapies targeting enteroendocrine cells or serotonin pathways and examining the role of different EEC types in gut motility during inflammation. The study was supported by the National Institutes of Health. The investigators disclosed no conflicts of interest.

Colitis-induced small intestinal hypomotility is closely linked to the loss of enteroendocrine cells (EECs) in mice, revealing a potential therapeutic strategy for patients with inflammatory bowel disease (IBD), according to investigators.

These findings suggest that restoring EEC function could alleviate some of the more general abdominal symptoms associated with IBD, reported lead author Zachariah Raouf, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.

“The symptoms experienced by patients with IBD, especially ulcerative colitis, may include those that are colonic in nature, such as bloody stools, abdominal pain, and weight loss, as well as those that are more general in nature, such as severe nausea and abdominal bloating,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology . “Although the first set of symptoms may be attributable to the effects of colonic inflammation itself, those that are more vague seem to overlap with the symptoms that patients with small intestinal dysmotility experience, such as occur in response to medications, or diabetes.”

Supporting this notion, several previous studies have reported the onset of intestinal dysmotility in experimental models of colitis, which is believed to be caused by impaired enteric nervous system function. But the precise mechanisms behind the impaired intestinal motility observed in colitis patients remain unclear.

To learn more, Dr. Raouf and colleagues conducted experiments involving three groups of mice: wild-type mice, mice genetically engineered to overexpress EECs, and mice lacking EECs.

To induce colitis, the mice were administered dextran sulfate sodium (DSS) in drinking water at concentrations of 2.5% or 5% for 7 days. Small intestinal motility was evaluated by measuring the transit of fluorescein isothiocyanate (FITC)-dextran. Immunohistochemical analyses were conducted to assess EEC number and differentiation, while quantitative reverse-transcriptase polymerase chain reaction was used to examine the expression of genes related to serotonin synthesis and transport.

The researchers examined colon length and signs of colonic inflammation, monitored weight loss, and measured the expression of proinflammatory cytokines. Histological analyses of colon and small intestine tissues were performed to further understand the effects of colitis. The presence and number of EEC cells was evaluated using chromogranin A (ChgA) staining, while apoptosis in EECs was measured via TUNEL staining. The expression of serotonin-related genes was also assessed.

These experiments revealed that DSS-induced colitis led to significant small-bowel hypomotility and a reduction in EEC density. Of note, genetic overexpression of EECs or treatment with prucalopride, a 5-hydroxytryptamine receptor 4 agonist, improved small intestinal motility.

“It is noteworthy that there were no significant changes in the density of other intestinal epithelial cells, or in other cell types that are linked to motility, such as enteric glia and neurons, suggesting the specificity of the effect,” the investigators wrote. “Importantly, treatment with a serotonin agonist ameliorated the colitis-induced, small-bowel hypomotility and attenuated the severity of colitis, providing potential clinical relevance of the current findings. Taken together, these results identify mechanisms to explain the intestinal hypomotility observed in the setting of colitis.”Dr. Raouf and colleagues called for human clinical trials to their findings. Specifically, they suggested exploring therapies targeting enteroendocrine cells or serotonin pathways and examining the role of different EEC types in gut motility during inflammation. The study was supported by the National Institutes of Health. The investigators disclosed no conflicts of interest.

Colitis-induced small intestinal hypomotility is closely linked to the loss of enteroendocrine cells (EECs) in mice, revealing a potential therapeutic strategy for patients with inflammatory bowel disease (IBD), according to investigators.

These findings suggest that restoring EEC function could alleviate some of the more general abdominal symptoms associated with IBD, reported lead author Zachariah Raouf, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.

“The symptoms experienced by patients with IBD, especially ulcerative colitis, may include those that are colonic in nature, such as bloody stools, abdominal pain, and weight loss, as well as those that are more general in nature, such as severe nausea and abdominal bloating,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology . “Although the first set of symptoms may be attributable to the effects of colonic inflammation itself, those that are more vague seem to overlap with the symptoms that patients with small intestinal dysmotility experience, such as occur in response to medications, or diabetes.”

Supporting this notion, several previous studies have reported the onset of intestinal dysmotility in experimental models of colitis, which is believed to be caused by impaired enteric nervous system function. But the precise mechanisms behind the impaired intestinal motility observed in colitis patients remain unclear.

To learn more, Dr. Raouf and colleagues conducted experiments involving three groups of mice: wild-type mice, mice genetically engineered to overexpress EECs, and mice lacking EECs.

To induce colitis, the mice were administered dextran sulfate sodium (DSS) in drinking water at concentrations of 2.5% or 5% for 7 days. Small intestinal motility was evaluated by measuring the transit of fluorescein isothiocyanate (FITC)-dextran. Immunohistochemical analyses were conducted to assess EEC number and differentiation, while quantitative reverse-transcriptase polymerase chain reaction was used to examine the expression of genes related to serotonin synthesis and transport.

The researchers examined colon length and signs of colonic inflammation, monitored weight loss, and measured the expression of proinflammatory cytokines. Histological analyses of colon and small intestine tissues were performed to further understand the effects of colitis. The presence and number of EEC cells was evaluated using chromogranin A (ChgA) staining, while apoptosis in EECs was measured via TUNEL staining. The expression of serotonin-related genes was also assessed.

These experiments revealed that DSS-induced colitis led to significant small-bowel hypomotility and a reduction in EEC density. Of note, genetic overexpression of EECs or treatment with prucalopride, a 5-hydroxytryptamine receptor 4 agonist, improved small intestinal motility.

“It is noteworthy that there were no significant changes in the density of other intestinal epithelial cells, or in other cell types that are linked to motility, such as enteric glia and neurons, suggesting the specificity of the effect,” the investigators wrote. “Importantly, treatment with a serotonin agonist ameliorated the colitis-induced, small-bowel hypomotility and attenuated the severity of colitis, providing potential clinical relevance of the current findings. Taken together, these results identify mechanisms to explain the intestinal hypomotility observed in the setting of colitis.”Dr. Raouf and colleagues called for human clinical trials to their findings. Specifically, they suggested exploring therapies targeting enteroendocrine cells or serotonin pathways and examining the role of different EEC types in gut motility during inflammation. The study was supported by the National Institutes of Health. The investigators disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

Cleveland Clinic

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

Cleveland Clinic

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

Cleveland Clinic

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.

A new clinical practice guideline by the American Society for Radiation Oncology (ASTRO) steers use of external beam radiation therapy (EBRT) for the palliation of symptomatic bone metastases, including recommendations concerning pain management and quality of life.

The guideline was needed to update previous recommendations and incorporate new high-quality evidence for the management of symptomatic bone metastases, Sara Alcorn, MD, PhD, of the University of Minnesota, Minneapolis, and colleagues wrote in Practical Radiation Oncology.

The focus was on the efficacy of EBRT in reducing pain, improving skeletal function, and enhancing quality of life, they wrote in the clinical practice guideline.

In developing their recommendations, the ASTRO task force reviewed evidence from 53 randomized controlled trials (RCTs) and 31 nonrandomized studies, and considered clinical experience.
 

Indications for Palliative Radiation

EBRT is strongly recommended for reducing pain from osseous metastasis and improving ambulatory status, sphincter function, and reducing pain in patients with spinal metastases causing compression of the spinal cord or cauda equina.

For patients with symptomatic bone metastases and an anticipated life expectancy of at least 4 weeks, EBRT is conditionally recommended to improve quality of life.

Implementation of other Treatments Alongside Palliative Radiation

Instead of RT alone, surgery with postoperative RT is conditionally recommended for patients with compression of the spinal cord or cauda equina.

Postoperative RT is strongly recommended for patients who have undergone surgery for non-spine bone metastases or spine metastases without involving spinal cord or cauda equina compression.

For patients with spinal bone metastases compressing the spinal cord or cauda equina, combining RT with dexamethasone is strongly recommended over RT alone.

Techniques, Dose-Fractionation, and Dose-Constraints for Initial Palliative Radiation

For patients with symptomatic bone metastases undergoing conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 3000 cGy in 10 fractions.

For patients with spinal bone metastases causing compression of the spinal cord or cauda equina who are not candidates for initial surgical decompression and are treated with conventional palliative RT, strongly recommended doses are 800 cGy in 1 fraction, 1600 cGy in 2 fractions, 2000 cGy in 5 fractions, or 3000 cGy in 10 fractions.

When selecting dose-fractionation, consider patient and disease factors such as prognosis and radiosensitivity, the authors wrote.

Highly conformal planning and delivery techniques, such as intensity-modulated radiation therapy, are conditionally recommended for patients with spinal bone metastases compressing the spinal cord or cauda equina who are receiving dose-escalated palliative RT.

The strongly recommended stereotactic body radiotherapy (SBRT) doses for patients with symptomatic bone metastases are 1200 to 1600 cGy in 1 fraction for non-spine metastases and 2400 cGy in 2 fractions for spine metastases. Other established SBRT dose and fractionation regimens with similar biologically effective doses may be considered based on patient tumor characteristics, normal tissue factors, and physician experience.

For patients with symptomatic bone metastases who have an ECOG PS of 0-2, are not undergoing surgical intervention, and have no neurological symptoms, SBRT is conditionally recommended over conventional palliative RT. Other factors to consider include life expectancy, tumor radiosensitivity, and metastatic disease burden, the guideline says.
 

Techniques, Dose-Fractionation, and Dose-Constraints for Palliative Reirradiation

For patients with spinal bone metastases requiring reirradiation to the same site, the strongly recommended conventional palliative RT regimens are 800 cGy in 1 fraction, 2000 cGy in 5 fractions, 2400 cGy in 6 fractions, or 2000 cGy in 8 fractions. When determining the RT dose-fractionation, consider the prior RT dose, time interval, and total spinal cord tolerance, the guideline says.

Treatment with SBRT is conditionally recommended for patients with spinal bone metastases needing reirradiation at the same site. When determining if SBRT is appropriate, consider patient factors such as urgency of treatment, prognosis, and radio-resistance. In addition, consider the prior RT dose, time interval, and total spinal cord tolerance when determining the RT dose-fractionation, the authors say.

The strongly recommended options for patients with symptomatic non-spine bone metastases needing reirradiation at the same site are single-fraction RT (800 cGy in 1 fraction) or multifraction conventional palliative RT (2000 cGy in 5 fractions or 2400 cGy in 6 fractions).
 

Impact of Techniques and Dose-fractionation on Quality of Life and Toxicity

For patients with bone metastases undergoing palliative radiation, it is strongly recommended to use a shared decision-making approach to determine the dose, fractionation, and supportive measures to optimize quality of life.

“Based on published data, the ASTRO task force’s recommendations inform best clinical practices on palliative RT for symptomatic bone metastases,” the guideline panelists said.

Limitations

While the guideline provides comprehensive recommendations, the panelists underscored the importance of individualized treatment approaches. Future research is needed to address gaps in evidence, particularly regarding advanced RT techniques and reirradiation strategies.

Guideline development was funded by ASTRO, with the systematic evidence review funded by the Patient-Centered Outcomes Research Institute. The panelists disclosed relationships with AstraZeneca, Elekta, Teladoc, and others.