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Menopausal Hormone Therapy Lowers Upper GI Cancer Risk
BERLIN — , according to a large population-based study across five Nordic countries. The association appeared strongest for combined estrogen-progestin and systemic formulations.
“This is one of the largest and most comprehensive studies to date supporting the hypothesis of an inverse association between MHT and risk of esophago-gastric cancer,” said Victoria Wocalewski, MD, from the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, who presented the findings at United European Gastroenterology (UEG) Week 2025.
There was a decreased risk for all investigated cancers in MHT users, but the strongest association was observed for esophageal adenocarcinoma (EAC), said Wocalewski. In addition, “there were discrete dose-dependent results for [EAC] and gastric adenocarcinoma (GAC) but not for esophageal squamous cell carcinoma (ESCC).”
Large Population-Based Study
Previous research has suggested that hormonal changes could partly explain the male predominance in esophageal and gastric cancers, but evidence from large, well-controlled datasets has been limited.
“Cancer rates in women increase significantly after age of 60, so it has been hypothesized that this pattern is linked to declined levels of estrogen that comes with menopause,” said Wocalewski, explaining the rationale for the study.
“Some studies looking at MHT use have indicated a possible protective effect, but with some contradictory results and type-specific variations,” Wocalewski noted. “Our study aimed to investigate these previous findings using a larger study sample.”
The population-based case-control study drew on prospectively collected data from the NordGETS database including national prescription, cancer, and population registries in Denmark, Finland, Iceland, Norway, and Sweden spanning 1994-2020. In total, 19,518 women with esophago-gastric cancer were compared with 195,094 controls randomly selected from the general population, and matched for age, calendar year, and country (in a 1:10 ratio). Women were 45 years or over with a diagnosis of EAC, ESCC, or GAC.
In total there were 5000 cases of EAC, 4401 of ESCC, and 10,117 of GAC, with the median ages being 74, 72, and 75 years, respectively; most cases of EAC and ESCC were found in Denmark, and most cases of GAC were in Sweden.
The investigators categorized participants by defined daily doses (DDDs) of MHT into three equal sized categories: low (< 158 DDDs), intermediate (158-848 DDDs), and high (> 848 DDDs). MHT was defined as systemic or local, and estrogen only or combined with progesterone. Odds ratios (ORs) were calculated for three major cancer outcomes of EAC, ESCC, and GAC, adjusted for known confounders such as age, obesity, smoking, alcohol consumption, reflux disease, Helicobacter pylori eradication, and concomitant use of statins or non-steroidal anti-inflammatory drugs (NSAIDs). However, Wocalewski noted that they did not adjust for socio-economic factors.
Significant Reductions Across Esophago-Gastric Cancers
Compared with nonusers, women with any MHT exposure had a markedly reduced risk of EAC with adjusted ORs (aORs) of 0.74 (95% CI, 0.67-0.81) for low-use, 0.68 (95% CI, 0.61-0.75) for intermediate-use, and 0.68 (95% CI, 0.61-0.75) for high-use groups. Various adjustments were made for obesity, reflux, statins, and NSAIDs, as well as smoking, alcohol use, and H pylori eradication.
Similar inverse associations were seen for ESCC with aORs of 0.69 (95% CI, 0.62-0.77), 0.70 (95% CI, 0.62-0.77), and 0.71 (95% CI, 0.64-0.79) across the dose categories, and for GAC where risk decreased progressively from 0.90 (95% CI, 0.84-0.96) to 0.80 (95% CI, 0.74-0.86) across increasing MHT doses.
When stratified by hormone formulation, combined estrogen-progesterone therapy and systemic MHT conferred the strongest risk reduction. For example, systemic MHT use was associated with aORs of 0.67 (95% CI, 0.61-0.74) for EAC and 0.82 (95% CI, 0.76-0.88) for GAC, while local (vaginal) preparations showed slightly weaker associations at 0.72 (95% CI, 0.66-0.78) and 0.87 (95% CI, 0.83-0.92), respectively.
In EAC, combined estrogen-progesterone therapy led to an OR of 0.68 (95% CI, 0.63-0.73) and 0.77 (95% CI, 0.69-0.87) for women on estrogen alone. Similar results were found for ESCC. For GAC, combination resulted in an aOR of 0.85 (95% CI, 0.80-0.89) and 0.88 (95% CI, 0.81-0.97) in estrogen only therapy respectively.
“Our results reinforce the concept that estrogenic signaling may influence tumor development in the upper GI tract,” said Wocalewski. “Understanding these mechanisms could help identify at-risk populations and inform prevention strategies,” she added, noting that, “hormonal effects on epithelial tight junctions and nitric oxide synthesis in the gastrointestinal tract” would have an influence on smooth muscle cells.
Link Between Hormones and GI Pathology
Commenting on the study for GI & Hepatology News, Jan Bornschein, MD, University of Oxford, UK, who was not involved in the research, said the results are “highly relevant.”
“We’ve seen for a long time a link between hormones and GI pathology, however, it has been poorly investigated and the whole mechanisms are not understood, so it’s welcome that this group is moving forward and investigating this in a structured way,” he said.
Another delegate cautioned that MHT was associated with a risk for other non- gastrointestinal cancers. “I think it’s extremely important, because there are data on associations [of MHT] with breast cancer and also endometrial cancer. It’s good to see that it may help and reduce this cancer, but we have to be really careful about the others.”
Wocalewski reports no relevant conflicts of interest. Bornschein has no disclosures relevant to this study. The study was funded by Karolinska Institutet and supported by national cancer and prescription registry data from Denmark, Finland, Iceland, Norway, and Sweden.
A version of this article appeared on Medscape.com.
BERLIN — , according to a large population-based study across five Nordic countries. The association appeared strongest for combined estrogen-progestin and systemic formulations.
“This is one of the largest and most comprehensive studies to date supporting the hypothesis of an inverse association between MHT and risk of esophago-gastric cancer,” said Victoria Wocalewski, MD, from the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, who presented the findings at United European Gastroenterology (UEG) Week 2025.
There was a decreased risk for all investigated cancers in MHT users, but the strongest association was observed for esophageal adenocarcinoma (EAC), said Wocalewski. In addition, “there were discrete dose-dependent results for [EAC] and gastric adenocarcinoma (GAC) but not for esophageal squamous cell carcinoma (ESCC).”
Large Population-Based Study
Previous research has suggested that hormonal changes could partly explain the male predominance in esophageal and gastric cancers, but evidence from large, well-controlled datasets has been limited.
“Cancer rates in women increase significantly after age of 60, so it has been hypothesized that this pattern is linked to declined levels of estrogen that comes with menopause,” said Wocalewski, explaining the rationale for the study.
“Some studies looking at MHT use have indicated a possible protective effect, but with some contradictory results and type-specific variations,” Wocalewski noted. “Our study aimed to investigate these previous findings using a larger study sample.”
The population-based case-control study drew on prospectively collected data from the NordGETS database including national prescription, cancer, and population registries in Denmark, Finland, Iceland, Norway, and Sweden spanning 1994-2020. In total, 19,518 women with esophago-gastric cancer were compared with 195,094 controls randomly selected from the general population, and matched for age, calendar year, and country (in a 1:10 ratio). Women were 45 years or over with a diagnosis of EAC, ESCC, or GAC.
In total there were 5000 cases of EAC, 4401 of ESCC, and 10,117 of GAC, with the median ages being 74, 72, and 75 years, respectively; most cases of EAC and ESCC were found in Denmark, and most cases of GAC were in Sweden.
The investigators categorized participants by defined daily doses (DDDs) of MHT into three equal sized categories: low (< 158 DDDs), intermediate (158-848 DDDs), and high (> 848 DDDs). MHT was defined as systemic or local, and estrogen only or combined with progesterone. Odds ratios (ORs) were calculated for three major cancer outcomes of EAC, ESCC, and GAC, adjusted for known confounders such as age, obesity, smoking, alcohol consumption, reflux disease, Helicobacter pylori eradication, and concomitant use of statins or non-steroidal anti-inflammatory drugs (NSAIDs). However, Wocalewski noted that they did not adjust for socio-economic factors.
Significant Reductions Across Esophago-Gastric Cancers
Compared with nonusers, women with any MHT exposure had a markedly reduced risk of EAC with adjusted ORs (aORs) of 0.74 (95% CI, 0.67-0.81) for low-use, 0.68 (95% CI, 0.61-0.75) for intermediate-use, and 0.68 (95% CI, 0.61-0.75) for high-use groups. Various adjustments were made for obesity, reflux, statins, and NSAIDs, as well as smoking, alcohol use, and H pylori eradication.
Similar inverse associations were seen for ESCC with aORs of 0.69 (95% CI, 0.62-0.77), 0.70 (95% CI, 0.62-0.77), and 0.71 (95% CI, 0.64-0.79) across the dose categories, and for GAC where risk decreased progressively from 0.90 (95% CI, 0.84-0.96) to 0.80 (95% CI, 0.74-0.86) across increasing MHT doses.
When stratified by hormone formulation, combined estrogen-progesterone therapy and systemic MHT conferred the strongest risk reduction. For example, systemic MHT use was associated with aORs of 0.67 (95% CI, 0.61-0.74) for EAC and 0.82 (95% CI, 0.76-0.88) for GAC, while local (vaginal) preparations showed slightly weaker associations at 0.72 (95% CI, 0.66-0.78) and 0.87 (95% CI, 0.83-0.92), respectively.
In EAC, combined estrogen-progesterone therapy led to an OR of 0.68 (95% CI, 0.63-0.73) and 0.77 (95% CI, 0.69-0.87) for women on estrogen alone. Similar results were found for ESCC. For GAC, combination resulted in an aOR of 0.85 (95% CI, 0.80-0.89) and 0.88 (95% CI, 0.81-0.97) in estrogen only therapy respectively.
“Our results reinforce the concept that estrogenic signaling may influence tumor development in the upper GI tract,” said Wocalewski. “Understanding these mechanisms could help identify at-risk populations and inform prevention strategies,” she added, noting that, “hormonal effects on epithelial tight junctions and nitric oxide synthesis in the gastrointestinal tract” would have an influence on smooth muscle cells.
Link Between Hormones and GI Pathology
Commenting on the study for GI & Hepatology News, Jan Bornschein, MD, University of Oxford, UK, who was not involved in the research, said the results are “highly relevant.”
“We’ve seen for a long time a link between hormones and GI pathology, however, it has been poorly investigated and the whole mechanisms are not understood, so it’s welcome that this group is moving forward and investigating this in a structured way,” he said.
Another delegate cautioned that MHT was associated with a risk for other non- gastrointestinal cancers. “I think it’s extremely important, because there are data on associations [of MHT] with breast cancer and also endometrial cancer. It’s good to see that it may help and reduce this cancer, but we have to be really careful about the others.”
Wocalewski reports no relevant conflicts of interest. Bornschein has no disclosures relevant to this study. The study was funded by Karolinska Institutet and supported by national cancer and prescription registry data from Denmark, Finland, Iceland, Norway, and Sweden.
A version of this article appeared on Medscape.com.
BERLIN — , according to a large population-based study across five Nordic countries. The association appeared strongest for combined estrogen-progestin and systemic formulations.
“This is one of the largest and most comprehensive studies to date supporting the hypothesis of an inverse association between MHT and risk of esophago-gastric cancer,” said Victoria Wocalewski, MD, from the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, who presented the findings at United European Gastroenterology (UEG) Week 2025.
There was a decreased risk for all investigated cancers in MHT users, but the strongest association was observed for esophageal adenocarcinoma (EAC), said Wocalewski. In addition, “there were discrete dose-dependent results for [EAC] and gastric adenocarcinoma (GAC) but not for esophageal squamous cell carcinoma (ESCC).”
Large Population-Based Study
Previous research has suggested that hormonal changes could partly explain the male predominance in esophageal and gastric cancers, but evidence from large, well-controlled datasets has been limited.
“Cancer rates in women increase significantly after age of 60, so it has been hypothesized that this pattern is linked to declined levels of estrogen that comes with menopause,” said Wocalewski, explaining the rationale for the study.
“Some studies looking at MHT use have indicated a possible protective effect, but with some contradictory results and type-specific variations,” Wocalewski noted. “Our study aimed to investigate these previous findings using a larger study sample.”
The population-based case-control study drew on prospectively collected data from the NordGETS database including national prescription, cancer, and population registries in Denmark, Finland, Iceland, Norway, and Sweden spanning 1994-2020. In total, 19,518 women with esophago-gastric cancer were compared with 195,094 controls randomly selected from the general population, and matched for age, calendar year, and country (in a 1:10 ratio). Women were 45 years or over with a diagnosis of EAC, ESCC, or GAC.
In total there were 5000 cases of EAC, 4401 of ESCC, and 10,117 of GAC, with the median ages being 74, 72, and 75 years, respectively; most cases of EAC and ESCC were found in Denmark, and most cases of GAC were in Sweden.
The investigators categorized participants by defined daily doses (DDDs) of MHT into three equal sized categories: low (< 158 DDDs), intermediate (158-848 DDDs), and high (> 848 DDDs). MHT was defined as systemic or local, and estrogen only or combined with progesterone. Odds ratios (ORs) were calculated for three major cancer outcomes of EAC, ESCC, and GAC, adjusted for known confounders such as age, obesity, smoking, alcohol consumption, reflux disease, Helicobacter pylori eradication, and concomitant use of statins or non-steroidal anti-inflammatory drugs (NSAIDs). However, Wocalewski noted that they did not adjust for socio-economic factors.
Significant Reductions Across Esophago-Gastric Cancers
Compared with nonusers, women with any MHT exposure had a markedly reduced risk of EAC with adjusted ORs (aORs) of 0.74 (95% CI, 0.67-0.81) for low-use, 0.68 (95% CI, 0.61-0.75) for intermediate-use, and 0.68 (95% CI, 0.61-0.75) for high-use groups. Various adjustments were made for obesity, reflux, statins, and NSAIDs, as well as smoking, alcohol use, and H pylori eradication.
Similar inverse associations were seen for ESCC with aORs of 0.69 (95% CI, 0.62-0.77), 0.70 (95% CI, 0.62-0.77), and 0.71 (95% CI, 0.64-0.79) across the dose categories, and for GAC where risk decreased progressively from 0.90 (95% CI, 0.84-0.96) to 0.80 (95% CI, 0.74-0.86) across increasing MHT doses.
When stratified by hormone formulation, combined estrogen-progesterone therapy and systemic MHT conferred the strongest risk reduction. For example, systemic MHT use was associated with aORs of 0.67 (95% CI, 0.61-0.74) for EAC and 0.82 (95% CI, 0.76-0.88) for GAC, while local (vaginal) preparations showed slightly weaker associations at 0.72 (95% CI, 0.66-0.78) and 0.87 (95% CI, 0.83-0.92), respectively.
In EAC, combined estrogen-progesterone therapy led to an OR of 0.68 (95% CI, 0.63-0.73) and 0.77 (95% CI, 0.69-0.87) for women on estrogen alone. Similar results were found for ESCC. For GAC, combination resulted in an aOR of 0.85 (95% CI, 0.80-0.89) and 0.88 (95% CI, 0.81-0.97) in estrogen only therapy respectively.
“Our results reinforce the concept that estrogenic signaling may influence tumor development in the upper GI tract,” said Wocalewski. “Understanding these mechanisms could help identify at-risk populations and inform prevention strategies,” she added, noting that, “hormonal effects on epithelial tight junctions and nitric oxide synthesis in the gastrointestinal tract” would have an influence on smooth muscle cells.
Link Between Hormones and GI Pathology
Commenting on the study for GI & Hepatology News, Jan Bornschein, MD, University of Oxford, UK, who was not involved in the research, said the results are “highly relevant.”
“We’ve seen for a long time a link between hormones and GI pathology, however, it has been poorly investigated and the whole mechanisms are not understood, so it’s welcome that this group is moving forward and investigating this in a structured way,” he said.
Another delegate cautioned that MHT was associated with a risk for other non- gastrointestinal cancers. “I think it’s extremely important, because there are data on associations [of MHT] with breast cancer and also endometrial cancer. It’s good to see that it may help and reduce this cancer, but we have to be really careful about the others.”
Wocalewski reports no relevant conflicts of interest. Bornschein has no disclosures relevant to this study. The study was funded by Karolinska Institutet and supported by national cancer and prescription registry data from Denmark, Finland, Iceland, Norway, and Sweden.
A version of this article appeared on Medscape.com.
Combining Upper-Lower GI Screening Feasible, Effective
BERLIN — , including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.
“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.
While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.
The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”
Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.
Mixed Rates of GI Cancers Across Europe and the US
These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.
However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”
The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy.
A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.
Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.
Neoplasia and Preneoplasia Found
A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.
A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”
Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.
Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.
Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.
“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.
“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”
PROSPERO: Early Detection of Upper GI Conditions in a UK Population
Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”
“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.
“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”
Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”
TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.
Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.
A version of this article first appeared on Medscape.com.
BERLIN — , including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.
“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.
While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.
The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”
Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.
Mixed Rates of GI Cancers Across Europe and the US
These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.
However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”
The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy.
A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.
Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.
Neoplasia and Preneoplasia Found
A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.
A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”
Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.
Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.
Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.
“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.
“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”
PROSPERO: Early Detection of Upper GI Conditions in a UK Population
Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”
“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.
“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”
Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”
TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.
Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.
A version of this article first appeared on Medscape.com.
BERLIN — , including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.
“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.
While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.
The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”
Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.
Mixed Rates of GI Cancers Across Europe and the US
These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.
However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”
The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy.
A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.
Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.
Neoplasia and Preneoplasia Found
A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.
A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”
Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.
Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.
Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.
“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.
“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”
PROSPERO: Early Detection of Upper GI Conditions in a UK Population
Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”
“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.
“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”
Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”
TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.
Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.
A version of this article first appeared on Medscape.com.
‘At-Need’ Endoscopy Equal to Standard Surveillance in Barrett’s Patients?
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
Old et al report the results of a herculean effort to randomize patients with Barrett’s esophagus (BE) to either scheduled endoscopy at 2-year intervals or endoscopy “at need.” While the intent was to understand the protective effect of endoscopic surveillance, this goal was frustrated by the extensive use of endoscopy in the at-need arm. All told, 59% of at-need patients underwent endoscopy at a median of 25.7 month intervals (compared to the 24.8-month median interval in the surveillance group).
This degree of endoscopy use in at-need patients complicates interpretation, since, as the authors note, such contamination would likely bias the results to the null. Also, only 26% of randomized at-need patients took advantage of the study-end endoscopy. In this group, an additional eight cancers and nine high-grade dysplasia were noted, raising the specter that undiagnosed important disease was present in the at-need group.
Given these concerns, the BOSS results do not provide compelling evidence to change clinical practice. I continue to recommend endoscopic surveillance to my BE patients. However, the trial provides valuable insight. First, it prospectively confirms the low incidence of esophageal adenocarcinoma in low-risk BE, a rate of 0.23%/patient-year. Second, a lot of endoscopy is probably not better than some endoscopy in BE surveillance, and current trends seen in guidelines toward lengthening intervals in low-risk patients are likely merited. Finally, clinicians and patients may overestimate the utility of surveillance, and a patient-centered approach, acknowledging the uncertainties of the utility of endoscopy and the low risk of progression to cancer, is appropriate.
Nicholas J. Shaheen, MD, MPH, AGAF, is the Bozymski-Heizer Distinguished Professor of Medicine and senior associate dean for Clinical Research at the University of North Carolina School of Medicine, Chapel Hill, N.C. He has no conflicts to report.
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
based on results of a randomized controlled trial.
The Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS) showed that surveillance endoscopy did not significantly improve overall survival (OS) or cancer-specific survival, compared with “at-need” endoscopy requested by patients with symptoms, reported Oliver Old, MD, of Gloucestershire Hospitals NHS Foundation Trust, Gloucester, England, and colleagues.
“Surveillance endoscopy at regular intervals is advocated by major gastroenterology societies and practiced in numerous countries worldwide to detect esophageal adenocarcinoma (EAC) early in these high-risk patients,” investigators wrote in Gastroenterology. However, “there are conflicting observational studies on the benefits of Barrett’s esophagus surveillance.”
To address this knowledge gap, Old and colleagues conducted the first randomized study of its kind. The BOSS trial was a multicenter trial conducted at 109 hospitals across the United Kingdom. Adults with an endoscopic and histologic diagnosis of BE were eligible if they were fit for endoscopy and had no history of high-grade dysplasia, esophageal adenocarcinoma, or prior upper gastrointestinal cancer. Patients with low-grade dysplasia were permitted to enroll, consistent with practice guidelines at the time.
A total of 3,453 participants were randomized between 2009 and 2011 to undergo surveillance endoscopy every 2 years or to receive at-need endoscopy triggered only by symptoms. Patients and clinicians were aware of treatment assignment. In the surveillance group, quadrantic biopsies were taken at 2-cm intervals throughout the Barrett’s segment.
The primary endpoint was OS. Secondary outcomes included cancer-specific survival (deaths from any cancer), time to diagnosis of EAC, stage at diagnosis, number of endoscopies performed, and procedure-related adverse events.
Of the 3,453 patients randomized, 1,733 were assigned to surveillance and 1,719 to symptom-driven, at-need endoscopy. Baseline characteristics were similar between groups; the mean age was 63 years, and about 70% were men.
Over the course of the trial, 25% of patients in the surveillance arm, and 9% in the at-need arm, withdrew from the trial back into clinical care, but allowed data collection of their outcomes. After a median of 12.8 years of follow-up, there was no significant difference in overall survival: 333 deaths occurred in the surveillance group (19.2%) and 356 in the at-need group (20.7%; hazard ratio [HR], 0.95; 95% CI, 0.82-1.10). Cancer-specific survival was also similar across groups, with 108 cancer-related deaths in the surveillance arm and 106 in the at-need arm (HR, 1.01; 95% CI, 0.77-1.33).
EAC was diagnosed in 40 patients in the surveillance arm (2.3%) and 31 in the at-need arm (1.8%), a nonsignificant difference (HR, 1.32; 95% CI, 0.82-2.11). Stage at diagnosis did not differ between the two groups.
Endoscopy use was higher in the surveillance arm, with 6,124 procedures compared with 2,424 in the at-need arm. Serious adverse events were rare, reported in 0.5% of surveillance patients and 0.4% of at-need patients, with most related to complications of endoscopy such as bleeding or perforation.
End-of-trial exit endoscopy, offered only to patients in the at-need group (based on data and safety monitoring committee recommendation), detected an additional eight cases of EAC and eight cases of high-grade dysplasia, but these findings were not included in the primary trial analysis.
“These data challenge current clinical practice where surveillance is advocated for all patients with BE,” the investigators wrote. “These results are likely to influence societal guidelines regarding surveillance for nondysplastic BE and inform decision making for individual patients and clinicians.”
The study was supported by the Health Technology Assessment Programme, United Kingdom. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Long-Term Data Support Reduced-Dose Maintenance in EoE
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Simpler Approach Increases Diagnostic Accuracy of Timed Barium Esophagram for Achalasia
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
, according to investigators.
The classification tree offers a practical alternative for evaluating esophagogastric junction (EGJ) outflow disorders when more advanced methods like high-resolution manometry (HRM) or functional lumen imaging probe (FLIP) panometry are unavailable, lead author Ofer Z. Fass, MD, of Northwestern University, Chicago, and colleagues reported.
“[T]here are limited data on normative TBE values,” the investigators wrote in Gastroenterology. “Furthermore, data supporting the accuracy of TBE as a screening test for esophageal motility disorders, as well as clinically relevant test thresholds, remains limited.”
TBE is conventionally interpreted using a handful of single measurements, most often the barium column height at 1, 2, or 5 minutes. Although these metrics are simple to obtain, variability in technique, cutoff values, and interpretation across centers limits reproducibility and weakens diagnostic accuracy, according to the investigators. The role of TBE has therefore been largely confined to adjudicating inconclusive manometry findings, but even in that setting, the absence of validated reference standards constrains its utility as a reliable screening tool.
To address this gap, Fass and colleagues conducted a prospective analysis of 290 patients who underwent TBE at Northwestern Memorial Hospital, Chicago, with HRM and FLIP panometry, interpreted according to the Chicago Classification version 4.0 (CCv4.0), serving as the diagnostic reference standards.
Patients were included if they had both TBE and manometry performed within a short interval, ensuring that the two tests could be meaningfully compared. The study population represented a broad spectrum of esophageal motility presentations, allowing the model to be trained on clinically relevant variation.
Beyond column height, the investigators measured barium height at multiple timepoints, maximal esophageal body width, maximum EGJ diameter, and tablet passage. These variables were incorporated into a recursive partitioning algorithm to build a multimetric classification tree aimed at distinguishing EGJ outflow obstruction from other motility disorders.
The optimal tree incorporated three sequential decision levels. At the top was maximum esophageal body width, followed by EGJ diameter and barium height at the second level, and tablet passage at the third. This stepwise structure allowed the model to refine diagnoses by combining simple, reproducible TBE metrics that are already collected in routine practice.
Among the 290 patients, 121 (42%) had EGJ outflow disorders, 151 (52%) had no outflow disorder, and 18 (6%) had inconclusive manometry findings. Using conventional interpretation with column height and tablet passage, TBE demonstrated a sensitivity of 77.8%, a specificity of 86.0%, and an accuracy of 82.2%. The multimetric classification tree improved diagnostic performance across all parameters, with a sensitivity of 84.2%, a specificity of 92.1%, and an accuracy of 88.3%.
The advantages of multimetric interpretation were most notable in patients with borderline column heights, which single-metric approaches often misclassify, underscoring the value of integrating multiple measurements into a unified model.
“[T]his study demonstrated that TBE can accurately identify achalasia when analyzed using multiple metrics in a classification tree model,” Fass and colleagues wrote. “Future studies should explore the use of TBE metrics and models to identify more specific esophageal motor disorders (such as esophageal spasm and absent contractility), as well as validation in a larger, multicenter cohort.”
Clinical Takeaways
Rishi Naik, MD, of the Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tennessee, said the study represents a step forward in how clinicians can use a widely accessible esophageal imaging test.
“This study is important in that it has updated the way we use a very common, readily available imaging test and compared it to the current gold standard of HRM and FLIP,” he told GI & Hepatology News. “This provides a practical, standardized framework for clinicians evaluating patients with suspected esophageal motility disorders.”
Naik noted that while HRM and FLIP provide highly detailed information, both carry drawbacks that limit their universal adoption.
“Practically, HRM is a transnasal test that can be cumbersome, and FLIP is performed during a sedated procedure,” he said. “From a comfort and cost perspective, the esophagram outcompetes. What the TBE lacked was adequate sensitivity and specificity when just looking at column height, which is how the authors overcame this by leveraging the comparisons using CCv4.0.”
Implementation, however, requires discipline.
“A timed barium esophagram is a protocol, not a single esophagram,” Naik said. “Without proper measurements, you can’t follow the decision tree.”
Still, he pointed to radiology’s increasing adoption of artificial intelligence (AI) as a promising way forward.
“AI has already transformed radiological reads, and I’m optimistic it will eventually allow us to incorporate not only width, height, and tablet clearance but also 3D [three-dimensional] reconstructions of bolus retention and pressure to enhance predictive modeling,” Naik said.
This study was supported by the Public Health Service.
The investigators disclosed having relationships with Takeda, Phathom Pharmaceuticals, Medtronic, and others. Naik is a consultant for Sanofi/Regeneron, Eli Lilly and Company, and Renexxion.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
GLP-1s Increase GERD Risk Over SGLT2 Inhibitors in T2D
in a cohort study of new users.
Risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and patients with gastric comorbidities.
“The findings were not entirely surprising,” principal author Laurent Azoulay, PhD, of McGill University and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada, told GI & Hepatology News. “There is a plausible biological mechanism through which GLP-1 RAs could increase the risk of GERD — namely, by delaying gastric emptying, which can lead to symptoms of reflux. Still, it’s always valuable to see whether the clinical data support what we suspect from a physiological standpoint.”
“As with any medication, it’s about balancing benefits and risks — and being proactive when side effects emerge,” he added.
The study was published online in Annals of Internal Medicine.
Duration of Use, Drug Action
Researchers designed an active comparator new-user cohort study emulating a target trial to estimate the effects of GLP-1 RAs compared with SGLT2 inhibitors on the risk for GERD and its complications among patients with T2D.
The study included 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT2 inhibitors. Participants had a mean age of 56 years, and 55% were men. They initiated treatment with the drugs from January 2013 through December 2021, with follow-up through March 2022.
Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.
Overall, during follow-up, the incidence rate of GERD was 7.9 per 1000 person-years; 138 complications of GERD were observed, with over 90% of them being Barrett’s esophagus.
Over a median follow-up of 3 years, among GLP-1 RA users compared with SGLT2 inhibitor users, the RRs were 1.27 for GERD, with an RD of 0.7 per 100 patients, and 1.55 for complications, with an RD of 0.8 per 1000 patients.
Further analyses found that risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and those with gastric comorbidities associated with gastric motility. The findings remained robust across sensitivity analyses addressing various types of biases.
The widening incidence curves with duration of use may indicate that mucosal injury and symptom severity correlate with reflux frequency and duration of esophageal acid exposure, the authors suggested.
GERD risk also was higher with long-acting GLP-1 RA use, suggesting that long-acting GLP-1 RAs (liraglutide, exenatide once weekly, dulaglutide, and semaglutide) may have more sustained delaying effects, they noted.
“These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD,” the authors concluded.
“Given the mechanism through which these drugs may cause GERD, we can reasonably speculate that a similar effect might be observed in individuals without diabetes,” Azoulay added. “That said, a dedicated study would be needed to confirm that.”
Close Monitoring Advised
Caroline Collins, MD, assistant professor at Emory University School of Medicine in Atlanta, agreed with the findings and said the association between GLP-1s and GERD is consistent with what she has observed in her practice.
“I routinely counsel patients about the potential for GERD symptoms as well as other side effects before initiating GLP-1 therapy,” she told GI & Hepatology News. “Several patients on GLP-1s have reported new or worsening reflux symptoms after initiating therapy. Sometimes, we can lower the dose, and the GERD resolves. Other times initiating GERD treatment or discontinuing the medication is appropriate.”
“Patients with T2D are already at increased risk for delayed gastric emptying, which in itself is a contributor to GERD,” said Collins, who was not involved in the study. “Therefore, adding a GLP-1 RA, which further slows gastric motility, may compound this risk. I consider this when assessing which patients are the best candidates for these medications and often monitor more closely in patients with long-standing diabetes and other predisposing factors to GERD.”
Barrett’s esophagus and esophageal cancer generally occur over many years, she noted. “A median follow-up of 3 years may be insufficient to fully assess the long-term risks of serious complications.”
“Chronic cough, a common but often overlooked manifestation of GERD, was not included in the outcome definitions,” she added. Including chronic cough “may have captured a broader picture of reflux-related symptoms.”
The study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research. Azoulay holds a Distinguished Research Scholar award from the Fonds de recherche du Quebec – Sante and is the recipient of a William Dawson Scholar award from McGill University.
A version of this article appeared on Medscape.com.
in a cohort study of new users.
Risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and patients with gastric comorbidities.
“The findings were not entirely surprising,” principal author Laurent Azoulay, PhD, of McGill University and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada, told GI & Hepatology News. “There is a plausible biological mechanism through which GLP-1 RAs could increase the risk of GERD — namely, by delaying gastric emptying, which can lead to symptoms of reflux. Still, it’s always valuable to see whether the clinical data support what we suspect from a physiological standpoint.”
“As with any medication, it’s about balancing benefits and risks — and being proactive when side effects emerge,” he added.
The study was published online in Annals of Internal Medicine.
Duration of Use, Drug Action
Researchers designed an active comparator new-user cohort study emulating a target trial to estimate the effects of GLP-1 RAs compared with SGLT2 inhibitors on the risk for GERD and its complications among patients with T2D.
The study included 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT2 inhibitors. Participants had a mean age of 56 years, and 55% were men. They initiated treatment with the drugs from January 2013 through December 2021, with follow-up through March 2022.
Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.
Overall, during follow-up, the incidence rate of GERD was 7.9 per 1000 person-years; 138 complications of GERD were observed, with over 90% of them being Barrett’s esophagus.
Over a median follow-up of 3 years, among GLP-1 RA users compared with SGLT2 inhibitor users, the RRs were 1.27 for GERD, with an RD of 0.7 per 100 patients, and 1.55 for complications, with an RD of 0.8 per 1000 patients.
Further analyses found that risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and those with gastric comorbidities associated with gastric motility. The findings remained robust across sensitivity analyses addressing various types of biases.
The widening incidence curves with duration of use may indicate that mucosal injury and symptom severity correlate with reflux frequency and duration of esophageal acid exposure, the authors suggested.
GERD risk also was higher with long-acting GLP-1 RA use, suggesting that long-acting GLP-1 RAs (liraglutide, exenatide once weekly, dulaglutide, and semaglutide) may have more sustained delaying effects, they noted.
“These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD,” the authors concluded.
“Given the mechanism through which these drugs may cause GERD, we can reasonably speculate that a similar effect might be observed in individuals without diabetes,” Azoulay added. “That said, a dedicated study would be needed to confirm that.”
Close Monitoring Advised
Caroline Collins, MD, assistant professor at Emory University School of Medicine in Atlanta, agreed with the findings and said the association between GLP-1s and GERD is consistent with what she has observed in her practice.
“I routinely counsel patients about the potential for GERD symptoms as well as other side effects before initiating GLP-1 therapy,” she told GI & Hepatology News. “Several patients on GLP-1s have reported new or worsening reflux symptoms after initiating therapy. Sometimes, we can lower the dose, and the GERD resolves. Other times initiating GERD treatment or discontinuing the medication is appropriate.”
“Patients with T2D are already at increased risk for delayed gastric emptying, which in itself is a contributor to GERD,” said Collins, who was not involved in the study. “Therefore, adding a GLP-1 RA, which further slows gastric motility, may compound this risk. I consider this when assessing which patients are the best candidates for these medications and often monitor more closely in patients with long-standing diabetes and other predisposing factors to GERD.”
Barrett’s esophagus and esophageal cancer generally occur over many years, she noted. “A median follow-up of 3 years may be insufficient to fully assess the long-term risks of serious complications.”
“Chronic cough, a common but often overlooked manifestation of GERD, was not included in the outcome definitions,” she added. Including chronic cough “may have captured a broader picture of reflux-related symptoms.”
The study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research. Azoulay holds a Distinguished Research Scholar award from the Fonds de recherche du Quebec – Sante and is the recipient of a William Dawson Scholar award from McGill University.
A version of this article appeared on Medscape.com.
in a cohort study of new users.
Risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and patients with gastric comorbidities.
“The findings were not entirely surprising,” principal author Laurent Azoulay, PhD, of McGill University and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada, told GI & Hepatology News. “There is a plausible biological mechanism through which GLP-1 RAs could increase the risk of GERD — namely, by delaying gastric emptying, which can lead to symptoms of reflux. Still, it’s always valuable to see whether the clinical data support what we suspect from a physiological standpoint.”
“As with any medication, it’s about balancing benefits and risks — and being proactive when side effects emerge,” he added.
The study was published online in Annals of Internal Medicine.
Duration of Use, Drug Action
Researchers designed an active comparator new-user cohort study emulating a target trial to estimate the effects of GLP-1 RAs compared with SGLT2 inhibitors on the risk for GERD and its complications among patients with T2D.
The study included 24,708 new users of GLP-1 RAs and 89,096 new users of SGLT2 inhibitors. Participants had a mean age of 56 years, and 55% were men. They initiated treatment with the drugs from January 2013 through December 2021, with follow-up through March 2022.
Three-year risk differences (RDs) and risk ratios (RRs) were estimated and weighted using propensity score fine stratification.
Overall, during follow-up, the incidence rate of GERD was 7.9 per 1000 person-years; 138 complications of GERD were observed, with over 90% of them being Barrett’s esophagus.
Over a median follow-up of 3 years, among GLP-1 RA users compared with SGLT2 inhibitor users, the RRs were 1.27 for GERD, with an RD of 0.7 per 100 patients, and 1.55 for complications, with an RD of 0.8 per 1000 patients.
Further analyses found that risks for GERD were higher overall for each GLP-1 RA type except lixisenatide, and risks for GERD complications were higher in ever-smokers, patients with obesity, and those with gastric comorbidities associated with gastric motility. The findings remained robust across sensitivity analyses addressing various types of biases.
The widening incidence curves with duration of use may indicate that mucosal injury and symptom severity correlate with reflux frequency and duration of esophageal acid exposure, the authors suggested.
GERD risk also was higher with long-acting GLP-1 RA use, suggesting that long-acting GLP-1 RAs (liraglutide, exenatide once weekly, dulaglutide, and semaglutide) may have more sustained delaying effects, they noted.
“These potential risks should be weighed against the established clinical benefits of this drug class, particularly in patients at high risk for gastroparesis and GERD,” the authors concluded.
“Given the mechanism through which these drugs may cause GERD, we can reasonably speculate that a similar effect might be observed in individuals without diabetes,” Azoulay added. “That said, a dedicated study would be needed to confirm that.”
Close Monitoring Advised
Caroline Collins, MD, assistant professor at Emory University School of Medicine in Atlanta, agreed with the findings and said the association between GLP-1s and GERD is consistent with what she has observed in her practice.
“I routinely counsel patients about the potential for GERD symptoms as well as other side effects before initiating GLP-1 therapy,” she told GI & Hepatology News. “Several patients on GLP-1s have reported new or worsening reflux symptoms after initiating therapy. Sometimes, we can lower the dose, and the GERD resolves. Other times initiating GERD treatment or discontinuing the medication is appropriate.”
“Patients with T2D are already at increased risk for delayed gastric emptying, which in itself is a contributor to GERD,” said Collins, who was not involved in the study. “Therefore, adding a GLP-1 RA, which further slows gastric motility, may compound this risk. I consider this when assessing which patients are the best candidates for these medications and often monitor more closely in patients with long-standing diabetes and other predisposing factors to GERD.”
Barrett’s esophagus and esophageal cancer generally occur over many years, she noted. “A median follow-up of 3 years may be insufficient to fully assess the long-term risks of serious complications.”
“Chronic cough, a common but often overlooked manifestation of GERD, was not included in the outcome definitions,” she added. Including chronic cough “may have captured a broader picture of reflux-related symptoms.”
The study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research. Azoulay holds a Distinguished Research Scholar award from the Fonds de recherche du Quebec – Sante and is the recipient of a William Dawson Scholar award from McGill University.
A version of this article appeared on Medscape.com.
How Chronic Stress Disrupts the Gut Microbiome
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Helicobacter pylori May Shift Gastric Cancer Earlier
Helicobacter pylori May Shift Gastric Cancer Earlier
ORLANDO, Fl — , new data suggested.
H pylori infection is a leading risk factor for gastric carcinoma, accounting for as many as 90% of cases. As the new data show, failure to screen routinely for the bacteria could be leading to younger people developing easily preventable forms of gastric cancer, experts said.
“The most concerning and the most interesting finding for us was we found higher prevalence” of gastric cancer linked to H pylori in the younger group, Neel Patel, MD, MPH, with the Department of Pathology at Staten Island University Hospital in Staten Island, New York, told GI & Hepatology News.
“This does not mean most patients are young. Rather, it means H pylori increases the likelihood of gastric cancer appearing earlier in life compared with non-H pylori cases.”
For the study, Patel and his colleagues, who presented their findings at the annual meeting of the College of American Pathologists (CAP) 2025, used 2016-2020 data from the Nationwide Inpatient Sample, which included records for adults with primary diagnoses of gastric cancer. They looked at outcomes of those whose cancer was associated with H pylori compared with the non-H pylori group.
Among 91,670 adult hospitalizations, 1830 (2%) had gastric cancer linked to H pylori (2016-2020). Patel said the low percentage resulted from focusing solely on diagnostic codes for primary diagnoses of gastric cancer and excluding secondary diagnoses.
These cancers were twice as prevalent in patients aged 18-49 years (3.97%) as in those older than 65 years (1.65%).
Septicemia Odds Higher in H pylori Group
Patients in the H pylori group also had a higher burden of comorbidities such as anemia, chronic blood loss, and metastatic cancer, according to the data. The researcher found these patients also had significantly higher odds of septicemia (odds ratio, 1.62; 95% CI, 1.17-2.24; P = .003) and spent an average of 8 days in the hospital — two more than those with cancers not associated with the infection.
Dipti M. Karamchandani, MD, a professor of pathology at the University of Texas Southwestern Medical Center in Dallas, who was not part of the study, said the longer hospital stays and greater risk for septicemia may be related to increased comorbidities among people who get H pylori infection in general. The infection often is caused by unsanitary conditions, and the groups infected may also be more likely to experience malnutrition, anemia, or lower body reserves, for example, she said.
“Also, H pylori often causes gastric ulcers, even before causing cancer, and those patients may be prone to chronic blood loss,” Karamchandani said. “These are all reasons that these patients may be more prone to longer hospital stay.”
US Guidelines Lacking
H pylori infection is a strong predictor of gastric cancer, but it often goes undetected. “Sometimes we ignore the symptoms,” Patel said.
“There are no standard guidelines for screening for H pylori,” he added. “We need to stop the transition from H pylori to gastric cancer.”
“This abstract highlights an important issue: Gastric cancer is rising among younger adults in the US, particularly in noncardia gastric cancer, which is most often associated with Helicobacter pylori infection,” said Chul S. Hyun, MD, PhD, MPH, director of the Gastric Cancer Prevention and Screening Program at Yale School of Medicine in New Haven, Connecticut.
Hyun said the 2% of patients in the study diagnosed with gastric cancer associated with H pylori likely reflected undercoding and “incomplete capture” in the database and noted that subgroup comparisons “become difficult to interpret reliably.” By extension, the findings also underscore, “We are not adequately capturing H pylori in routine US coding and claims.”
“What we do know is that H pylori is the central, modifiable driver of risk, and that prevention efforts should focus on high prevalence populations — including Asian, Hispanic, and immigrant communities — where systematic H pylori screening remains a major unmet need,” said Hyun, who was not involved in the new research.
Currently no US society guideline recommends systematic screening, Hyun said. “Other high-incidence countries, such as Japan and Korea, already incorporate H pylori and gastroscopy screening into national policy,” he said. “For these reasons, guidelines urgently need to evolve to recommend targeted H pylori screening in high prevalence groups.”
Patel, Karamchandani, and Hyun reported having no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
ORLANDO, Fl — , new data suggested.
H pylori infection is a leading risk factor for gastric carcinoma, accounting for as many as 90% of cases. As the new data show, failure to screen routinely for the bacteria could be leading to younger people developing easily preventable forms of gastric cancer, experts said.
“The most concerning and the most interesting finding for us was we found higher prevalence” of gastric cancer linked to H pylori in the younger group, Neel Patel, MD, MPH, with the Department of Pathology at Staten Island University Hospital in Staten Island, New York, told GI & Hepatology News.
“This does not mean most patients are young. Rather, it means H pylori increases the likelihood of gastric cancer appearing earlier in life compared with non-H pylori cases.”
For the study, Patel and his colleagues, who presented their findings at the annual meeting of the College of American Pathologists (CAP) 2025, used 2016-2020 data from the Nationwide Inpatient Sample, which included records for adults with primary diagnoses of gastric cancer. They looked at outcomes of those whose cancer was associated with H pylori compared with the non-H pylori group.
Among 91,670 adult hospitalizations, 1830 (2%) had gastric cancer linked to H pylori (2016-2020). Patel said the low percentage resulted from focusing solely on diagnostic codes for primary diagnoses of gastric cancer and excluding secondary diagnoses.
These cancers were twice as prevalent in patients aged 18-49 years (3.97%) as in those older than 65 years (1.65%).
Septicemia Odds Higher in H pylori Group
Patients in the H pylori group also had a higher burden of comorbidities such as anemia, chronic blood loss, and metastatic cancer, according to the data. The researcher found these patients also had significantly higher odds of septicemia (odds ratio, 1.62; 95% CI, 1.17-2.24; P = .003) and spent an average of 8 days in the hospital — two more than those with cancers not associated with the infection.
Dipti M. Karamchandani, MD, a professor of pathology at the University of Texas Southwestern Medical Center in Dallas, who was not part of the study, said the longer hospital stays and greater risk for septicemia may be related to increased comorbidities among people who get H pylori infection in general. The infection often is caused by unsanitary conditions, and the groups infected may also be more likely to experience malnutrition, anemia, or lower body reserves, for example, she said.
“Also, H pylori often causes gastric ulcers, even before causing cancer, and those patients may be prone to chronic blood loss,” Karamchandani said. “These are all reasons that these patients may be more prone to longer hospital stay.”
US Guidelines Lacking
H pylori infection is a strong predictor of gastric cancer, but it often goes undetected. “Sometimes we ignore the symptoms,” Patel said.
“There are no standard guidelines for screening for H pylori,” he added. “We need to stop the transition from H pylori to gastric cancer.”
“This abstract highlights an important issue: Gastric cancer is rising among younger adults in the US, particularly in noncardia gastric cancer, which is most often associated with Helicobacter pylori infection,” said Chul S. Hyun, MD, PhD, MPH, director of the Gastric Cancer Prevention and Screening Program at Yale School of Medicine in New Haven, Connecticut.
Hyun said the 2% of patients in the study diagnosed with gastric cancer associated with H pylori likely reflected undercoding and “incomplete capture” in the database and noted that subgroup comparisons “become difficult to interpret reliably.” By extension, the findings also underscore, “We are not adequately capturing H pylori in routine US coding and claims.”
“What we do know is that H pylori is the central, modifiable driver of risk, and that prevention efforts should focus on high prevalence populations — including Asian, Hispanic, and immigrant communities — where systematic H pylori screening remains a major unmet need,” said Hyun, who was not involved in the new research.
Currently no US society guideline recommends systematic screening, Hyun said. “Other high-incidence countries, such as Japan and Korea, already incorporate H pylori and gastroscopy screening into national policy,” he said. “For these reasons, guidelines urgently need to evolve to recommend targeted H pylori screening in high prevalence groups.”
Patel, Karamchandani, and Hyun reported having no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
ORLANDO, Fl — , new data suggested.
H pylori infection is a leading risk factor for gastric carcinoma, accounting for as many as 90% of cases. As the new data show, failure to screen routinely for the bacteria could be leading to younger people developing easily preventable forms of gastric cancer, experts said.
“The most concerning and the most interesting finding for us was we found higher prevalence” of gastric cancer linked to H pylori in the younger group, Neel Patel, MD, MPH, with the Department of Pathology at Staten Island University Hospital in Staten Island, New York, told GI & Hepatology News.
“This does not mean most patients are young. Rather, it means H pylori increases the likelihood of gastric cancer appearing earlier in life compared with non-H pylori cases.”
For the study, Patel and his colleagues, who presented their findings at the annual meeting of the College of American Pathologists (CAP) 2025, used 2016-2020 data from the Nationwide Inpatient Sample, which included records for adults with primary diagnoses of gastric cancer. They looked at outcomes of those whose cancer was associated with H pylori compared with the non-H pylori group.
Among 91,670 adult hospitalizations, 1830 (2%) had gastric cancer linked to H pylori (2016-2020). Patel said the low percentage resulted from focusing solely on diagnostic codes for primary diagnoses of gastric cancer and excluding secondary diagnoses.
These cancers were twice as prevalent in patients aged 18-49 years (3.97%) as in those older than 65 years (1.65%).
Septicemia Odds Higher in H pylori Group
Patients in the H pylori group also had a higher burden of comorbidities such as anemia, chronic blood loss, and metastatic cancer, according to the data. The researcher found these patients also had significantly higher odds of septicemia (odds ratio, 1.62; 95% CI, 1.17-2.24; P = .003) and spent an average of 8 days in the hospital — two more than those with cancers not associated with the infection.
Dipti M. Karamchandani, MD, a professor of pathology at the University of Texas Southwestern Medical Center in Dallas, who was not part of the study, said the longer hospital stays and greater risk for septicemia may be related to increased comorbidities among people who get H pylori infection in general. The infection often is caused by unsanitary conditions, and the groups infected may also be more likely to experience malnutrition, anemia, or lower body reserves, for example, she said.
“Also, H pylori often causes gastric ulcers, even before causing cancer, and those patients may be prone to chronic blood loss,” Karamchandani said. “These are all reasons that these patients may be more prone to longer hospital stay.”
US Guidelines Lacking
H pylori infection is a strong predictor of gastric cancer, but it often goes undetected. “Sometimes we ignore the symptoms,” Patel said.
“There are no standard guidelines for screening for H pylori,” he added. “We need to stop the transition from H pylori to gastric cancer.”
“This abstract highlights an important issue: Gastric cancer is rising among younger adults in the US, particularly in noncardia gastric cancer, which is most often associated with Helicobacter pylori infection,” said Chul S. Hyun, MD, PhD, MPH, director of the Gastric Cancer Prevention and Screening Program at Yale School of Medicine in New Haven, Connecticut.
Hyun said the 2% of patients in the study diagnosed with gastric cancer associated with H pylori likely reflected undercoding and “incomplete capture” in the database and noted that subgroup comparisons “become difficult to interpret reliably.” By extension, the findings also underscore, “We are not adequately capturing H pylori in routine US coding and claims.”
“What we do know is that H pylori is the central, modifiable driver of risk, and that prevention efforts should focus on high prevalence populations — including Asian, Hispanic, and immigrant communities — where systematic H pylori screening remains a major unmet need,” said Hyun, who was not involved in the new research.
Currently no US society guideline recommends systematic screening, Hyun said. “Other high-incidence countries, such as Japan and Korea, already incorporate H pylori and gastroscopy screening into national policy,” he said. “For these reasons, guidelines urgently need to evolve to recommend targeted H pylori screening in high prevalence groups.”
Patel, Karamchandani, and Hyun reported having no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Helicobacter pylori May Shift Gastric Cancer Earlier
Helicobacter pylori May Shift Gastric Cancer Earlier
Getting Ahead of Gastrointestinal Cancer
Early-onset gastrointestinal (GI) cancers are climbing among those younger than 50 years, in the US and globally. Although colorectal cancer accounts for approximately half of such cases, rates are also increasing for gastric, esophageal, pancreatic, and several rarer GI malignancies.
Because most in this age group are not included in screening protocols and may present with vague symptoms, diagnosis and treatment is frequently delayed. According to experts in the field, counteracting this trend requires establishing a lower threshold for evaluation, attention to modifiable risk factors, and embracing emerging noninvasive diagnostic tools.
Diagnostic Dilemmas
“Colorectal cancer in particular is often diagnosed later in life,” said Nicholas DeVito, MD, assistant professor at Duke University Medical Center, Durham, North Carolina, and a specialist in GI malignancies. “When the patient is too young for routine screening colonoscopy (< 45 years), they aren’t screened at all, they do not have alarming symptoms, or their symptoms are overlooked.” Other increasingly common GI cancers in young people (esophageal, gastric, pancreatic) lack routine screening guidelines due to limited evidence, he added.
Symptoms such as nausea, weight loss, upset stomach, and abdominal pain are often nonspecific and have many other potential causes, so GI cancers may not be high on the list of possible diagnoses in patients younger than 50 years, said DeVito.
“Insurance coverage, socioeconomic status, appointment availability, and awareness of symptoms and screening methods are all barriers to diagnosis as well, which affect the diagnostic timeline of many cancers,” he added.“While there are multiple factors that contribute to a cancer diagnosis, it seems that obesity, a Western diet, a sedentary lifestyle are all major contributors to the rise in early GI cancers,” DeVito told GI & Hepatology News. “There is no blame or judgement to go around as cancer can happen to anyone at any time, with none of these factors present,” he emphasized.
When counseling patients about GI cancer risk, DeVito recommends keeping advice simple and specific. In general, they should restrict red meat to once a week, emphasize fresh fruits and vegetables, cap alcohol to ≤ 1 serving per day, and limit ultraprocessed foods (e.g., packaged snacks, preprepared meals, and sugary beverages).
Exercise is another pillar. “Find an activity you enjoy and work toward 30 minutes of aerobic exercise three times a week,” he advised. He also encourages finding opportunities to incorporate physical activity in daily lives, such as using a standing desk at work, while keeping patients’ socioeconomic constraints in mind.
Evidence around GI cancer prevention interventions is still evolving. However, a randomized phase 3 trial presented at American Society of Clinical Oncology’s 2025 meeting found significant improvement in disease-free survival among adults with resected stage III or high-risk stage II colon cancer (median age, 61 years) who reported higher intake of anti-inflammatory foods and greater exercise than a comparator group.
“In general, clinicians should be aware of the risk factors, make referrals to physical therapy, weight-loss specialists, endocrinologists, and nutritionists when appropriate, and be consistent and clear with patients about recommendations and what’s achievable,” DeVito said. “Meeting patients where they are can help make incremental progress, as these interventions take time and patience, and we should be understanding of that.”
Identifying at-risk younger adults goes beyond discussing family history and obesity to include diet, exercise, and daily lifestyle, he added.
“Symptoms of potential GI cancer need to be taken seriously in all patients, and there should be a lower threshold in 2025 to get a colonoscopy, endoscopy, or CT scan than in previous years given all that we know today. We then need to establish through clinical studies who needs screening tests and who doesn’t, and what interventions work best to reduce risk.”
Vigilance in the Absence of Screening
“Most GI cancers, unfortunately, can grow a fair amount before symptoms arise, so many patients present with symptoms only when a tumor has grown enough to affect organ function,” said Miguel Burch, MD, chief of minimally invasive and GI surgery at Cedars-Sinai Medical Center, Los Angeles.
Early screening improves outcomes in gastric cancer, Burch noted, and survival benefits are reflected in several East Asian countries that offer gastric cancer screening starting at age 40. In one study from Korea, a single upper endoscopy was associated with an approximate 40% reduction in gastric cancer mortality compared with no screening.
, Burch emphasized. The impact is wide-ranging, contributing to increased morbidity and mortality in younger adults often in their most productive years, leading to lost wages and emotional strains upon patients and their families.Routine endoscopic or imaging screening is not typically performed in the US, and newer blood-based tests such as circulating tumor DNA are not yet sensitive enough to reliably detect very early-stage disease. Nonetheless, there is evidence that noninvasive biomarkers could soon help expand GI cancer screening.
In a study published in JAMA Surgery, Sui and colleagues tested a 10-microRNA signature assay (Destinex) for early detection of gastric cancer and reported robust identification rates above 95%.
“In recent years, the liquid biopsy has gained momentum with the hope of augmenting cancer detection from peripheral blood, even indicating potential as a screening test for healthy populations,” wrote Max R. Coffey, MD, and Vivian E. Strong, MD, both of the Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.
“Early detection is absolutely critical; when gastric cancer is found early, outcomes are dramatically better,” Strong told GI & Hepatology News. Subtle symptoms — reflux, persistent GI discomfort, or unexplained weight loss — should never be ignored, she added.
Early detection should also focus on additional risk factors such as prior Helicobacter pylori infection, smoking, and family history.
“Anyone with a personal or family history of H pylori should have very careful follow-up, and if one household member tests positive, all should be checked,” Strong said. “Just as importantly, if one or more family members have had stomach cancer, that should be discussed with a healthcare provider, as it may warrant higher-level surveillance and genetic testing.”
Individuals concerned about increased risk for GI cancer should proactively ask their doctors whether they might benefit from testing or surveillance, Strong added.
“Lifestyle changes, timely medical evaluation, and tailored surveillance all play a vital role in prevention.”
DeVito disclosed clinical trial funding from the Gateway foundation, Xilio, Phanes, Astellas, GSK, as well as consulting fees/advisory board participation for Guardant, Agenus, and Xilio. Strong disclosed speaking honoraria for Merck and Astra Zeneca.
The study by Sui and colleagues was supported by the National Cancer Institute, National Institutes of Health, as well as by a grant from the American Gastroenterological Association Robert & Sally Funderburg Research Award in Gastric Cancer, and the Stupid Strong Foundation.
Burch had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Early-onset gastrointestinal (GI) cancers are climbing among those younger than 50 years, in the US and globally. Although colorectal cancer accounts for approximately half of such cases, rates are also increasing for gastric, esophageal, pancreatic, and several rarer GI malignancies.
Because most in this age group are not included in screening protocols and may present with vague symptoms, diagnosis and treatment is frequently delayed. According to experts in the field, counteracting this trend requires establishing a lower threshold for evaluation, attention to modifiable risk factors, and embracing emerging noninvasive diagnostic tools.
Diagnostic Dilemmas
“Colorectal cancer in particular is often diagnosed later in life,” said Nicholas DeVito, MD, assistant professor at Duke University Medical Center, Durham, North Carolina, and a specialist in GI malignancies. “When the patient is too young for routine screening colonoscopy (< 45 years), they aren’t screened at all, they do not have alarming symptoms, or their symptoms are overlooked.” Other increasingly common GI cancers in young people (esophageal, gastric, pancreatic) lack routine screening guidelines due to limited evidence, he added.
Symptoms such as nausea, weight loss, upset stomach, and abdominal pain are often nonspecific and have many other potential causes, so GI cancers may not be high on the list of possible diagnoses in patients younger than 50 years, said DeVito.
“Insurance coverage, socioeconomic status, appointment availability, and awareness of symptoms and screening methods are all barriers to diagnosis as well, which affect the diagnostic timeline of many cancers,” he added.“While there are multiple factors that contribute to a cancer diagnosis, it seems that obesity, a Western diet, a sedentary lifestyle are all major contributors to the rise in early GI cancers,” DeVito told GI & Hepatology News. “There is no blame or judgement to go around as cancer can happen to anyone at any time, with none of these factors present,” he emphasized.
When counseling patients about GI cancer risk, DeVito recommends keeping advice simple and specific. In general, they should restrict red meat to once a week, emphasize fresh fruits and vegetables, cap alcohol to ≤ 1 serving per day, and limit ultraprocessed foods (e.g., packaged snacks, preprepared meals, and sugary beverages).
Exercise is another pillar. “Find an activity you enjoy and work toward 30 minutes of aerobic exercise three times a week,” he advised. He also encourages finding opportunities to incorporate physical activity in daily lives, such as using a standing desk at work, while keeping patients’ socioeconomic constraints in mind.
Evidence around GI cancer prevention interventions is still evolving. However, a randomized phase 3 trial presented at American Society of Clinical Oncology’s 2025 meeting found significant improvement in disease-free survival among adults with resected stage III or high-risk stage II colon cancer (median age, 61 years) who reported higher intake of anti-inflammatory foods and greater exercise than a comparator group.
“In general, clinicians should be aware of the risk factors, make referrals to physical therapy, weight-loss specialists, endocrinologists, and nutritionists when appropriate, and be consistent and clear with patients about recommendations and what’s achievable,” DeVito said. “Meeting patients where they are can help make incremental progress, as these interventions take time and patience, and we should be understanding of that.”
Identifying at-risk younger adults goes beyond discussing family history and obesity to include diet, exercise, and daily lifestyle, he added.
“Symptoms of potential GI cancer need to be taken seriously in all patients, and there should be a lower threshold in 2025 to get a colonoscopy, endoscopy, or CT scan than in previous years given all that we know today. We then need to establish through clinical studies who needs screening tests and who doesn’t, and what interventions work best to reduce risk.”
Vigilance in the Absence of Screening
“Most GI cancers, unfortunately, can grow a fair amount before symptoms arise, so many patients present with symptoms only when a tumor has grown enough to affect organ function,” said Miguel Burch, MD, chief of minimally invasive and GI surgery at Cedars-Sinai Medical Center, Los Angeles.
Early screening improves outcomes in gastric cancer, Burch noted, and survival benefits are reflected in several East Asian countries that offer gastric cancer screening starting at age 40. In one study from Korea, a single upper endoscopy was associated with an approximate 40% reduction in gastric cancer mortality compared with no screening.
, Burch emphasized. The impact is wide-ranging, contributing to increased morbidity and mortality in younger adults often in their most productive years, leading to lost wages and emotional strains upon patients and their families.Routine endoscopic or imaging screening is not typically performed in the US, and newer blood-based tests such as circulating tumor DNA are not yet sensitive enough to reliably detect very early-stage disease. Nonetheless, there is evidence that noninvasive biomarkers could soon help expand GI cancer screening.
In a study published in JAMA Surgery, Sui and colleagues tested a 10-microRNA signature assay (Destinex) for early detection of gastric cancer and reported robust identification rates above 95%.
“In recent years, the liquid biopsy has gained momentum with the hope of augmenting cancer detection from peripheral blood, even indicating potential as a screening test for healthy populations,” wrote Max R. Coffey, MD, and Vivian E. Strong, MD, both of the Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.
“Early detection is absolutely critical; when gastric cancer is found early, outcomes are dramatically better,” Strong told GI & Hepatology News. Subtle symptoms — reflux, persistent GI discomfort, or unexplained weight loss — should never be ignored, she added.
Early detection should also focus on additional risk factors such as prior Helicobacter pylori infection, smoking, and family history.
“Anyone with a personal or family history of H pylori should have very careful follow-up, and if one household member tests positive, all should be checked,” Strong said. “Just as importantly, if one or more family members have had stomach cancer, that should be discussed with a healthcare provider, as it may warrant higher-level surveillance and genetic testing.”
Individuals concerned about increased risk for GI cancer should proactively ask their doctors whether they might benefit from testing or surveillance, Strong added.
“Lifestyle changes, timely medical evaluation, and tailored surveillance all play a vital role in prevention.”
DeVito disclosed clinical trial funding from the Gateway foundation, Xilio, Phanes, Astellas, GSK, as well as consulting fees/advisory board participation for Guardant, Agenus, and Xilio. Strong disclosed speaking honoraria for Merck and Astra Zeneca.
The study by Sui and colleagues was supported by the National Cancer Institute, National Institutes of Health, as well as by a grant from the American Gastroenterological Association Robert & Sally Funderburg Research Award in Gastric Cancer, and the Stupid Strong Foundation.
Burch had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Early-onset gastrointestinal (GI) cancers are climbing among those younger than 50 years, in the US and globally. Although colorectal cancer accounts for approximately half of such cases, rates are also increasing for gastric, esophageal, pancreatic, and several rarer GI malignancies.
Because most in this age group are not included in screening protocols and may present with vague symptoms, diagnosis and treatment is frequently delayed. According to experts in the field, counteracting this trend requires establishing a lower threshold for evaluation, attention to modifiable risk factors, and embracing emerging noninvasive diagnostic tools.
Diagnostic Dilemmas
“Colorectal cancer in particular is often diagnosed later in life,” said Nicholas DeVito, MD, assistant professor at Duke University Medical Center, Durham, North Carolina, and a specialist in GI malignancies. “When the patient is too young for routine screening colonoscopy (< 45 years), they aren’t screened at all, they do not have alarming symptoms, or their symptoms are overlooked.” Other increasingly common GI cancers in young people (esophageal, gastric, pancreatic) lack routine screening guidelines due to limited evidence, he added.
Symptoms such as nausea, weight loss, upset stomach, and abdominal pain are often nonspecific and have many other potential causes, so GI cancers may not be high on the list of possible diagnoses in patients younger than 50 years, said DeVito.
“Insurance coverage, socioeconomic status, appointment availability, and awareness of symptoms and screening methods are all barriers to diagnosis as well, which affect the diagnostic timeline of many cancers,” he added.“While there are multiple factors that contribute to a cancer diagnosis, it seems that obesity, a Western diet, a sedentary lifestyle are all major contributors to the rise in early GI cancers,” DeVito told GI & Hepatology News. “There is no blame or judgement to go around as cancer can happen to anyone at any time, with none of these factors present,” he emphasized.
When counseling patients about GI cancer risk, DeVito recommends keeping advice simple and specific. In general, they should restrict red meat to once a week, emphasize fresh fruits and vegetables, cap alcohol to ≤ 1 serving per day, and limit ultraprocessed foods (e.g., packaged snacks, preprepared meals, and sugary beverages).
Exercise is another pillar. “Find an activity you enjoy and work toward 30 minutes of aerobic exercise three times a week,” he advised. He also encourages finding opportunities to incorporate physical activity in daily lives, such as using a standing desk at work, while keeping patients’ socioeconomic constraints in mind.
Evidence around GI cancer prevention interventions is still evolving. However, a randomized phase 3 trial presented at American Society of Clinical Oncology’s 2025 meeting found significant improvement in disease-free survival among adults with resected stage III or high-risk stage II colon cancer (median age, 61 years) who reported higher intake of anti-inflammatory foods and greater exercise than a comparator group.
“In general, clinicians should be aware of the risk factors, make referrals to physical therapy, weight-loss specialists, endocrinologists, and nutritionists when appropriate, and be consistent and clear with patients about recommendations and what’s achievable,” DeVito said. “Meeting patients where they are can help make incremental progress, as these interventions take time and patience, and we should be understanding of that.”
Identifying at-risk younger adults goes beyond discussing family history and obesity to include diet, exercise, and daily lifestyle, he added.
“Symptoms of potential GI cancer need to be taken seriously in all patients, and there should be a lower threshold in 2025 to get a colonoscopy, endoscopy, or CT scan than in previous years given all that we know today. We then need to establish through clinical studies who needs screening tests and who doesn’t, and what interventions work best to reduce risk.”
Vigilance in the Absence of Screening
“Most GI cancers, unfortunately, can grow a fair amount before symptoms arise, so many patients present with symptoms only when a tumor has grown enough to affect organ function,” said Miguel Burch, MD, chief of minimally invasive and GI surgery at Cedars-Sinai Medical Center, Los Angeles.
Early screening improves outcomes in gastric cancer, Burch noted, and survival benefits are reflected in several East Asian countries that offer gastric cancer screening starting at age 40. In one study from Korea, a single upper endoscopy was associated with an approximate 40% reduction in gastric cancer mortality compared with no screening.
, Burch emphasized. The impact is wide-ranging, contributing to increased morbidity and mortality in younger adults often in their most productive years, leading to lost wages and emotional strains upon patients and their families.Routine endoscopic or imaging screening is not typically performed in the US, and newer blood-based tests such as circulating tumor DNA are not yet sensitive enough to reliably detect very early-stage disease. Nonetheless, there is evidence that noninvasive biomarkers could soon help expand GI cancer screening.
In a study published in JAMA Surgery, Sui and colleagues tested a 10-microRNA signature assay (Destinex) for early detection of gastric cancer and reported robust identification rates above 95%.
“In recent years, the liquid biopsy has gained momentum with the hope of augmenting cancer detection from peripheral blood, even indicating potential as a screening test for healthy populations,” wrote Max R. Coffey, MD, and Vivian E. Strong, MD, both of the Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.
“Early detection is absolutely critical; when gastric cancer is found early, outcomes are dramatically better,” Strong told GI & Hepatology News. Subtle symptoms — reflux, persistent GI discomfort, or unexplained weight loss — should never be ignored, she added.
Early detection should also focus on additional risk factors such as prior Helicobacter pylori infection, smoking, and family history.
“Anyone with a personal or family history of H pylori should have very careful follow-up, and if one household member tests positive, all should be checked,” Strong said. “Just as importantly, if one or more family members have had stomach cancer, that should be discussed with a healthcare provider, as it may warrant higher-level surveillance and genetic testing.”
Individuals concerned about increased risk for GI cancer should proactively ask their doctors whether they might benefit from testing or surveillance, Strong added.
“Lifestyle changes, timely medical evaluation, and tailored surveillance all play a vital role in prevention.”
DeVito disclosed clinical trial funding from the Gateway foundation, Xilio, Phanes, Astellas, GSK, as well as consulting fees/advisory board participation for Guardant, Agenus, and Xilio. Strong disclosed speaking honoraria for Merck and Astra Zeneca.
The study by Sui and colleagues was supported by the National Cancer Institute, National Institutes of Health, as well as by a grant from the American Gastroenterological Association Robert & Sally Funderburg Research Award in Gastric Cancer, and the Stupid Strong Foundation.
Burch had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Screening for H. pylori May Reduce Bleeding in Some Patients With MI
Screening for H. pylori May Reduce Bleeding in Some Patients With MI
, according to the HELP-MI SWEDEHEART trial published in JAMA and presented at the European Society of Cardiology (ESC) Congress 2025.
Bleeding in the upper gastrointestinal tract is a common complication after MI. It increases morbidity and mortality itself but can also reduce the effectiveness of antithrombotic treatments and lead to new cardiovascular events. It is often related to infection with H. pylori, the bacterium that can cause stomach inflammation, ulcers, and cancer, said Robin Hofmann, MD, PhD, a cardiologist at the Karolinska Institute in Stockholm, Sweden, who presented the trial results.Hofmann and his colleagues wondered whether screening for the bacterium using a simple urea breath test would help reduce the risk for bleeds. Using Sweden’s national SWEDEHEART registry, researchers performed a cluster-randomized crossover trial of more than 18,000 patients with MI at 35 Swedish hospitals. They found that screening for H. pylori reduced the risk for upper gastrointestinal bleeding by 10%, but the results were not statistically significant.
Several factors may have contributed to the neutral result, noted Hofmann. Just 70% of the people in the screening population were actually screened — though he said that is a fairly good number for a diagnostic test. A relatively small number, around 23%, were positive for H. pylori, a much lower rate than in many other parts of the world, and about 25% of participants in both arms of the trial were already taking proton pump inhibitors to reduce the risk for bleeding.
Signals of Benefit in High-Risk Patients
But in some high-risk subgroups, there was a clearer signal of benefit. Patients with anemia or kidney failure, for example, who are at higher risk for bleeding, saw a relative risk reduction of around 50% in the screening group — though the numbers were too small for formal statistical analysis.
“In unselected patients with myocardial infarction we could not show a significant reduction in bleeding,” said Hofmann. “But it’s very likely that there is a clinical effect, at least in those individuals at increased risk of bleeding.”
Discussant Paul Ridker, MD, a cardiologist at Harvard Medical School, Boston, said he agreed that the trial was technically neutral but clinically positive. He noted that in every subgroup, the trend was in the direction of benefit, with only the top end of the cardiac indices crossing over into no benefit. And the benefit appeared larger among high-risk patients with anemia or kidney failure.
“These are the very patients I’m most concerned about and don’t want to bleed,” he said.Because the urea breath test and eradication therapy are simple, safe, and inexpensive, Hofmann said he thinks there is “good evidence to recommend H. pylori screening in patients at higher risk of bleeding.”
“I’m very sure from a clinical perspective that we will be able to identify the groups that are low-hanging fruit,” he said. “But the guideline committees will have to decide if this evidence is enough.”
Hofmann and Ridker reported having no financial conflicts of interest.
A version of this article appeared on Medscape.com.
, according to the HELP-MI SWEDEHEART trial published in JAMA and presented at the European Society of Cardiology (ESC) Congress 2025.
Bleeding in the upper gastrointestinal tract is a common complication after MI. It increases morbidity and mortality itself but can also reduce the effectiveness of antithrombotic treatments and lead to new cardiovascular events. It is often related to infection with H. pylori, the bacterium that can cause stomach inflammation, ulcers, and cancer, said Robin Hofmann, MD, PhD, a cardiologist at the Karolinska Institute in Stockholm, Sweden, who presented the trial results.Hofmann and his colleagues wondered whether screening for the bacterium using a simple urea breath test would help reduce the risk for bleeds. Using Sweden’s national SWEDEHEART registry, researchers performed a cluster-randomized crossover trial of more than 18,000 patients with MI at 35 Swedish hospitals. They found that screening for H. pylori reduced the risk for upper gastrointestinal bleeding by 10%, but the results were not statistically significant.
Several factors may have contributed to the neutral result, noted Hofmann. Just 70% of the people in the screening population were actually screened — though he said that is a fairly good number for a diagnostic test. A relatively small number, around 23%, were positive for H. pylori, a much lower rate than in many other parts of the world, and about 25% of participants in both arms of the trial were already taking proton pump inhibitors to reduce the risk for bleeding.
Signals of Benefit in High-Risk Patients
But in some high-risk subgroups, there was a clearer signal of benefit. Patients with anemia or kidney failure, for example, who are at higher risk for bleeding, saw a relative risk reduction of around 50% in the screening group — though the numbers were too small for formal statistical analysis.
“In unselected patients with myocardial infarction we could not show a significant reduction in bleeding,” said Hofmann. “But it’s very likely that there is a clinical effect, at least in those individuals at increased risk of bleeding.”
Discussant Paul Ridker, MD, a cardiologist at Harvard Medical School, Boston, said he agreed that the trial was technically neutral but clinically positive. He noted that in every subgroup, the trend was in the direction of benefit, with only the top end of the cardiac indices crossing over into no benefit. And the benefit appeared larger among high-risk patients with anemia or kidney failure.
“These are the very patients I’m most concerned about and don’t want to bleed,” he said.Because the urea breath test and eradication therapy are simple, safe, and inexpensive, Hofmann said he thinks there is “good evidence to recommend H. pylori screening in patients at higher risk of bleeding.”
“I’m very sure from a clinical perspective that we will be able to identify the groups that are low-hanging fruit,” he said. “But the guideline committees will have to decide if this evidence is enough.”
Hofmann and Ridker reported having no financial conflicts of interest.
A version of this article appeared on Medscape.com.
, according to the HELP-MI SWEDEHEART trial published in JAMA and presented at the European Society of Cardiology (ESC) Congress 2025.
Bleeding in the upper gastrointestinal tract is a common complication after MI. It increases morbidity and mortality itself but can also reduce the effectiveness of antithrombotic treatments and lead to new cardiovascular events. It is often related to infection with H. pylori, the bacterium that can cause stomach inflammation, ulcers, and cancer, said Robin Hofmann, MD, PhD, a cardiologist at the Karolinska Institute in Stockholm, Sweden, who presented the trial results.Hofmann and his colleagues wondered whether screening for the bacterium using a simple urea breath test would help reduce the risk for bleeds. Using Sweden’s national SWEDEHEART registry, researchers performed a cluster-randomized crossover trial of more than 18,000 patients with MI at 35 Swedish hospitals. They found that screening for H. pylori reduced the risk for upper gastrointestinal bleeding by 10%, but the results were not statistically significant.
Several factors may have contributed to the neutral result, noted Hofmann. Just 70% of the people in the screening population were actually screened — though he said that is a fairly good number for a diagnostic test. A relatively small number, around 23%, were positive for H. pylori, a much lower rate than in many other parts of the world, and about 25% of participants in both arms of the trial were already taking proton pump inhibitors to reduce the risk for bleeding.
Signals of Benefit in High-Risk Patients
But in some high-risk subgroups, there was a clearer signal of benefit. Patients with anemia or kidney failure, for example, who are at higher risk for bleeding, saw a relative risk reduction of around 50% in the screening group — though the numbers were too small for formal statistical analysis.
“In unselected patients with myocardial infarction we could not show a significant reduction in bleeding,” said Hofmann. “But it’s very likely that there is a clinical effect, at least in those individuals at increased risk of bleeding.”
Discussant Paul Ridker, MD, a cardiologist at Harvard Medical School, Boston, said he agreed that the trial was technically neutral but clinically positive. He noted that in every subgroup, the trend was in the direction of benefit, with only the top end of the cardiac indices crossing over into no benefit. And the benefit appeared larger among high-risk patients with anemia or kidney failure.
“These are the very patients I’m most concerned about and don’t want to bleed,” he said.Because the urea breath test and eradication therapy are simple, safe, and inexpensive, Hofmann said he thinks there is “good evidence to recommend H. pylori screening in patients at higher risk of bleeding.”
“I’m very sure from a clinical perspective that we will be able to identify the groups that are low-hanging fruit,” he said. “But the guideline committees will have to decide if this evidence is enough.”
Hofmann and Ridker reported having no financial conflicts of interest.
A version of this article appeared on Medscape.com.
Screening for H. pylori May Reduce Bleeding in Some Patients With MI
Screening for H. pylori May Reduce Bleeding in Some Patients With MI