Pancreas and Biliary Tract

Could oral microbiome profiling help spot people at risk for pancreatic cancer?

It may be possible, according to a recent analysis published in JAMA Oncology.

Researchers found that a microbial risk score derived from oral wash samples may help identify people at an increased risk for pancreatic cancer, which could be a step toward earlier detection of the deadly malignancy.

“We identified 27 individual bacterial and fungal species significantly associated with pancreatic cancer development,” said Jiyoung Ahn, PhD, of NYU Grossman School of Medicine in New York City.

“If validated, oral microbiome profiling could serve as a noninvasive biomarker to identify individuals at elevated risk who might benefit from enhanced surveillance,” Ahn told GI & Hepatology News by email.

Rates of pancreatic cancer are on the rise. But detecting the disease before it becomes unresectable has remained an elusive goal, and the US Preventive Services Task Force discourages screening of asymptomatic adults.

For their study, Ahn and her colleagues analyzed data from 122,000 participants who provided oral wash samples as part of two cohort studies conducted in the US. The researchers used whole-genome shotgun sequencing and internal transcribed spacer sequencing to identity the bacterial and fungal species in the samples, respectively.

Over a median follow-up of nearly 9 years, 445 people developed pancreatic cancer and were matched with 445 who did not. Three oral bacterial periodontal pathogens — Porphyromonas gingivalis (odds ratio [OR], 1.27), Eubacterium nodatum (OR, 1.42), and Parvimonas micra (OR, 1.36) — as well as the fungal genus Candida were all linked to significantly increased odds of developing pancreatic cancer.

In a bacteriome-wide scan, the researchers pinpointed another 20 oral bacteria associated with pancreatic cancer — eight with a decreased risk and 13 with an increased risk for the disease.

The researchers also calculated a microbial risk score, which was the weighted sum of the relative abundance of bacterial and fungal species. In a meta-analysis of data from the two cohorts, the microbial risk score derived from 23 bacterial species and four fungal species, including various Candida species, was associated with pancreatic cancer (multivariate OR per 1-SD increase in the score, 3.44; 95% CI, 2.63-4.51).

“The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention,” Ahn and her colleagues concluded.

But Gil Welch, MD, of Brigham and Women’s Hospital in Boston, who has written about screening for decades, isn’t so sure.

Given the “impressive volume of information” included in the analysis, “it is not surprising that the investigators are able to create a microbial risk score (based on 27 species of bacteria and fungi) that is highly related to pancreatic cancer,” Welch said. “The authors are careful to emphasize these are associations, not causal relationships.”

But even if the relationship were causal, finding more people with the malignancy can also have downsides, said Welch.

In a study out last year, Welch and colleagues found that while the incidence of pancreatic cancer among young Americans has been rising, mortality rates in this demographic haven’t budged, suggesting a potential for overdiagnosis.

“Screening for pancreatic cancer has never been shown to reduce pancreatic cancer mortality,” Welch told GI & Hepatology News. “Why screen large swaths of the population simply to enumerate ‘risk factors’ for an unproven benefit that, at best, could help only a few? Meanwhile, the burdens for everyone else are real: the mental and financial strains of ‘high risk’ labels, false alarms, and endless follow-ups. It’s a recipe to make us all worried sick — and poorer.”

Ahn reported having no disclosures. Welch reported receiving royalties from three books including “Should I be tested for cancer?”

A version of this article appeared on Medscape.com.

Could oral microbiome profiling help spot people at risk for pancreatic cancer?

It may be possible, according to a recent analysis published in JAMA Oncology.

Researchers found that a microbial risk score derived from oral wash samples may help identify people at an increased risk for pancreatic cancer, which could be a step toward earlier detection of the deadly malignancy.

“We identified 27 individual bacterial and fungal species significantly associated with pancreatic cancer development,” said Jiyoung Ahn, PhD, of NYU Grossman School of Medicine in New York City.

“If validated, oral microbiome profiling could serve as a noninvasive biomarker to identify individuals at elevated risk who might benefit from enhanced surveillance,” Ahn told GI & Hepatology News by email.

Rates of pancreatic cancer are on the rise. But detecting the disease before it becomes unresectable has remained an elusive goal, and the US Preventive Services Task Force discourages screening of asymptomatic adults.

For their study, Ahn and her colleagues analyzed data from 122,000 participants who provided oral wash samples as part of two cohort studies conducted in the US. The researchers used whole-genome shotgun sequencing and internal transcribed spacer sequencing to identity the bacterial and fungal species in the samples, respectively.

Over a median follow-up of nearly 9 years, 445 people developed pancreatic cancer and were matched with 445 who did not. Three oral bacterial periodontal pathogens — Porphyromonas gingivalis (odds ratio [OR], 1.27), Eubacterium nodatum (OR, 1.42), and Parvimonas micra (OR, 1.36) — as well as the fungal genus Candida were all linked to significantly increased odds of developing pancreatic cancer.

In a bacteriome-wide scan, the researchers pinpointed another 20 oral bacteria associated with pancreatic cancer — eight with a decreased risk and 13 with an increased risk for the disease.

The researchers also calculated a microbial risk score, which was the weighted sum of the relative abundance of bacterial and fungal species. In a meta-analysis of data from the two cohorts, the microbial risk score derived from 23 bacterial species and four fungal species, including various Candida species, was associated with pancreatic cancer (multivariate OR per 1-SD increase in the score, 3.44; 95% CI, 2.63-4.51).

“The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention,” Ahn and her colleagues concluded.

But Gil Welch, MD, of Brigham and Women’s Hospital in Boston, who has written about screening for decades, isn’t so sure.

Given the “impressive volume of information” included in the analysis, “it is not surprising that the investigators are able to create a microbial risk score (based on 27 species of bacteria and fungi) that is highly related to pancreatic cancer,” Welch said. “The authors are careful to emphasize these are associations, not causal relationships.”

But even if the relationship were causal, finding more people with the malignancy can also have downsides, said Welch.

In a study out last year, Welch and colleagues found that while the incidence of pancreatic cancer among young Americans has been rising, mortality rates in this demographic haven’t budged, suggesting a potential for overdiagnosis.

“Screening for pancreatic cancer has never been shown to reduce pancreatic cancer mortality,” Welch told GI & Hepatology News. “Why screen large swaths of the population simply to enumerate ‘risk factors’ for an unproven benefit that, at best, could help only a few? Meanwhile, the burdens for everyone else are real: the mental and financial strains of ‘high risk’ labels, false alarms, and endless follow-ups. It’s a recipe to make us all worried sick — and poorer.”

Ahn reported having no disclosures. Welch reported receiving royalties from three books including “Should I be tested for cancer?”

A version of this article appeared on Medscape.com.

Could oral microbiome profiling help spot people at risk for pancreatic cancer?

It may be possible, according to a recent analysis published in JAMA Oncology.

Researchers found that a microbial risk score derived from oral wash samples may help identify people at an increased risk for pancreatic cancer, which could be a step toward earlier detection of the deadly malignancy.

“We identified 27 individual bacterial and fungal species significantly associated with pancreatic cancer development,” said Jiyoung Ahn, PhD, of NYU Grossman School of Medicine in New York City.

“If validated, oral microbiome profiling could serve as a noninvasive biomarker to identify individuals at elevated risk who might benefit from enhanced surveillance,” Ahn told GI & Hepatology News by email.

Rates of pancreatic cancer are on the rise. But detecting the disease before it becomes unresectable has remained an elusive goal, and the US Preventive Services Task Force discourages screening of asymptomatic adults.

For their study, Ahn and her colleagues analyzed data from 122,000 participants who provided oral wash samples as part of two cohort studies conducted in the US. The researchers used whole-genome shotgun sequencing and internal transcribed spacer sequencing to identity the bacterial and fungal species in the samples, respectively.

Over a median follow-up of nearly 9 years, 445 people developed pancreatic cancer and were matched with 445 who did not. Three oral bacterial periodontal pathogens — Porphyromonas gingivalis (odds ratio [OR], 1.27), Eubacterium nodatum (OR, 1.42), and Parvimonas micra (OR, 1.36) — as well as the fungal genus Candida were all linked to significantly increased odds of developing pancreatic cancer.

In a bacteriome-wide scan, the researchers pinpointed another 20 oral bacteria associated with pancreatic cancer — eight with a decreased risk and 13 with an increased risk for the disease.

The researchers also calculated a microbial risk score, which was the weighted sum of the relative abundance of bacterial and fungal species. In a meta-analysis of data from the two cohorts, the microbial risk score derived from 23 bacterial species and four fungal species, including various Candida species, was associated with pancreatic cancer (multivariate OR per 1-SD increase in the score, 3.44; 95% CI, 2.63-4.51).

“The oral microbiota holds promise as a biomarker to identify individuals at high risk of pancreatic cancer, potentially enabling personalized pancreatic cancer prevention,” Ahn and her colleagues concluded.

But Gil Welch, MD, of Brigham and Women’s Hospital in Boston, who has written about screening for decades, isn’t so sure.

Given the “impressive volume of information” included in the analysis, “it is not surprising that the investigators are able to create a microbial risk score (based on 27 species of bacteria and fungi) that is highly related to pancreatic cancer,” Welch said. “The authors are careful to emphasize these are associations, not causal relationships.”

But even if the relationship were causal, finding more people with the malignancy can also have downsides, said Welch.

In a study out last year, Welch and colleagues found that while the incidence of pancreatic cancer among young Americans has been rising, mortality rates in this demographic haven’t budged, suggesting a potential for overdiagnosis.

“Screening for pancreatic cancer has never been shown to reduce pancreatic cancer mortality,” Welch told GI & Hepatology News. “Why screen large swaths of the population simply to enumerate ‘risk factors’ for an unproven benefit that, at best, could help only a few? Meanwhile, the burdens for everyone else are real: the mental and financial strains of ‘high risk’ labels, false alarms, and endless follow-ups. It’s a recipe to make us all worried sick — and poorer.”

Ahn reported having no disclosures. Welch reported receiving royalties from three books including “Should I be tested for cancer?”

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.

In the US, lack of funding for GI cancer screening remains a barrier to early identification, 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.

In the US, lack of funding for GI cancer screening remains a barrier to early identification, 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.

In the US, lack of funding for GI cancer screening remains a barrier to early identification, 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.

Purpose

The aim of this study is to quantify the frequency of Memorial Sloan Kettering (MSK) Precision Oncology Knowledge Base (OncoKB) Level 1 genetic alterations in Veterans with various solid organ malignancies and evaluate the clinical benefit and impact of testing on treatment of these patients.

Background

The VA National Precision Oncology Program (NPOP) facilitates comprehensive genomic profiling (CGP) testing of Veterans with advanced cancer. While CGP is increasingly utilized and routinely ordered in patients with advanced solid organ malignancies, the clinical utility and value has not been proven in certain cancers. We present data from 5,979 patients with head and neck (H&N), pancreatic, hepatocellular (HCC), esophageal and kidney cancers who underwent CGP.

Methods

Our cohort consists of Veterans that received CGP testing to identify somatic variants between 1/1/2019 and 4/2/2025. Identified variants and biomarkers were formatted for use with oncoKB-annotator, a publicly available tool to annotate genomic variants with FDA approved drug recommendations stored as Level 1 annotations in OncoKB, and prescribed drugs were extracted from the Veteran Health Administration’s (VHA) Corporate Data Warehouse (CDW). Cancers were grouped by MSK’s OncoTree codes, and summary counts of Veterans tested, Veterans recommended, Veterans prescribed recommended FDA approved drugs were determined. Percentages were calculated using the total number of Veterans tested as the denominator.

Results

Level 1 OncoKB alterations were infrequent in H&N (0.94%), kidney (0.45%), HCC(0.28%), and pancreatic adenocarcinomas (1%). The frequency of Level 1 alterations in esophageal adenocarcinomas (EAC) was 20%. Approximately 98% of the Level 1 alterations in EAC patients were HER2 positivity or MSI-High status, which can be determined by other diagnostic methodologies such as IHC. The remaining 2% of EAC patients with level 1 alterations had BRAF V600E or NTRK rearrangements.

Conclusions

The incidence of level 1 genetic variants in H&N, kidney, HCC and pancreatic adenocarcinoma is very low and would very uncommonly result in clinical benefit. Although there is an expanding number of precision oncology-based therapies available, the proportion of patients with the aforementioned solid organ malignancies who benefitted from CGP was low, suggesting CGP has minimal impact on the treatment of Veterans with these malignancies.

Purpose

The aim of this study is to quantify the frequency of Memorial Sloan Kettering (MSK) Precision Oncology Knowledge Base (OncoKB) Level 1 genetic alterations in Veterans with various solid organ malignancies and evaluate the clinical benefit and impact of testing on treatment of these patients.

Background

The VA National Precision Oncology Program (NPOP) facilitates comprehensive genomic profiling (CGP) testing of Veterans with advanced cancer. While CGP is increasingly utilized and routinely ordered in patients with advanced solid organ malignancies, the clinical utility and value has not been proven in certain cancers. We present data from 5,979 patients with head and neck (H&N), pancreatic, hepatocellular (HCC), esophageal and kidney cancers who underwent CGP.

Methods

Our cohort consists of Veterans that received CGP testing to identify somatic variants between 1/1/2019 and 4/2/2025. Identified variants and biomarkers were formatted for use with oncoKB-annotator, a publicly available tool to annotate genomic variants with FDA approved drug recommendations stored as Level 1 annotations in OncoKB, and prescribed drugs were extracted from the Veteran Health Administration’s (VHA) Corporate Data Warehouse (CDW). Cancers were grouped by MSK’s OncoTree codes, and summary counts of Veterans tested, Veterans recommended, Veterans prescribed recommended FDA approved drugs were determined. Percentages were calculated using the total number of Veterans tested as the denominator.

Results

Level 1 OncoKB alterations were infrequent in H&N (0.94%), kidney (0.45%), HCC(0.28%), and pancreatic adenocarcinomas (1%). The frequency of Level 1 alterations in esophageal adenocarcinomas (EAC) was 20%. Approximately 98% of the Level 1 alterations in EAC patients were HER2 positivity or MSI-High status, which can be determined by other diagnostic methodologies such as IHC. The remaining 2% of EAC patients with level 1 alterations had BRAF V600E or NTRK rearrangements.

Conclusions

The incidence of level 1 genetic variants in H&N, kidney, HCC and pancreatic adenocarcinoma is very low and would very uncommonly result in clinical benefit. Although there is an expanding number of precision oncology-based therapies available, the proportion of patients with the aforementioned solid organ malignancies who benefitted from CGP was low, suggesting CGP has minimal impact on the treatment of Veterans with these malignancies.

Purpose

The aim of this study is to quantify the frequency of Memorial Sloan Kettering (MSK) Precision Oncology Knowledge Base (OncoKB) Level 1 genetic alterations in Veterans with various solid organ malignancies and evaluate the clinical benefit and impact of testing on treatment of these patients.

Background

The VA National Precision Oncology Program (NPOP) facilitates comprehensive genomic profiling (CGP) testing of Veterans with advanced cancer. While CGP is increasingly utilized and routinely ordered in patients with advanced solid organ malignancies, the clinical utility and value has not been proven in certain cancers. We present data from 5,979 patients with head and neck (H&N), pancreatic, hepatocellular (HCC), esophageal and kidney cancers who underwent CGP.

Methods

Our cohort consists of Veterans that received CGP testing to identify somatic variants between 1/1/2019 and 4/2/2025. Identified variants and biomarkers were formatted for use with oncoKB-annotator, a publicly available tool to annotate genomic variants with FDA approved drug recommendations stored as Level 1 annotations in OncoKB, and prescribed drugs were extracted from the Veteran Health Administration’s (VHA) Corporate Data Warehouse (CDW). Cancers were grouped by MSK’s OncoTree codes, and summary counts of Veterans tested, Veterans recommended, Veterans prescribed recommended FDA approved drugs were determined. Percentages were calculated using the total number of Veterans tested as the denominator.

Results

Level 1 OncoKB alterations were infrequent in H&N (0.94%), kidney (0.45%), HCC(0.28%), and pancreatic adenocarcinomas (1%). The frequency of Level 1 alterations in esophageal adenocarcinomas (EAC) was 20%. Approximately 98% of the Level 1 alterations in EAC patients were HER2 positivity or MSI-High status, which can be determined by other diagnostic methodologies such as IHC. The remaining 2% of EAC patients with level 1 alterations had BRAF V600E or NTRK rearrangements.

Conclusions

The incidence of level 1 genetic variants in H&N, kidney, HCC and pancreatic adenocarcinoma is very low and would very uncommonly result in clinical benefit. Although there is an expanding number of precision oncology-based therapies available, the proportion of patients with the aforementioned solid organ malignancies who benefitted from CGP was low, suggesting CGP has minimal impact on the treatment of Veterans with these malignancies.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Below are some selections from what I am reading in the AGA journals, highlighting clinically applicable and possibly practice-changing expert reviews and studies.

Esophagus/Motility

Nguyen AD, et al. AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.05.011.

Hartnett DA, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.06.032.

Gyawali CP, et al. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 May. doi: 10.1016/j.cgh.2025.02.032.

Stomach

Wiklund AK, et al. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.239.

Sonaiya S, et al. Over-the-Scope Clip versus Standard Endoscopic Therapy as First-Line Intervention for Nonvariceal Upper Gastrointestinal Bleeding: A Cost-Effectiveness Analysis. Tech Innov Gastrointest. 2025 Jun. doi: 10.1016/j.tige.2025.250935.

Colon

Hassan C, et al. Colon Cancer Screening, Surveillance, and Treatment: Novel Artificial Intelligence Driving Strategies in the Management of Colon Lesions. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.021.

Pancreas

Wilcox CM, et al; US Pancreatic Disease Study Group. Management of the Disconnected Pancreatic Duct in Pancreatic Necrosis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.05.024.

Ghimire C, et al. The effect of advances in pancreatic cancer treatment in population mortality: A SEER-based study. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100739.

Hepatology

Canivet CM, et al. Validation of the AASLD/EASL Multi-Step Screening Strategies for MASLD. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100747.

Miscellaneous

Chang L, et al. Gut Feelings: The Critical Role of Interoception in Obesity and Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.04.002.

Bashiri K, et al. Advancing Hemostatic Powder Technologies for Management of Gastrointestinal Bleeding: Challenges and Solutions. Tech Innov Gastrointest. 2025 Jul. doi: 10.1016/j.tige.2025.250940.

Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.

Below are some selections from what I am reading in the AGA journals, highlighting clinically applicable and possibly practice-changing expert reviews and studies.

Esophagus/Motility

Nguyen AD, et al. AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.05.011.

Hartnett DA, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.06.032.

Gyawali CP, et al. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 May. doi: 10.1016/j.cgh.2025.02.032.

Stomach

Wiklund AK, et al. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.239.

Sonaiya S, et al. Over-the-Scope Clip versus Standard Endoscopic Therapy as First-Line Intervention for Nonvariceal Upper Gastrointestinal Bleeding: A Cost-Effectiveness Analysis. Tech Innov Gastrointest. 2025 Jun. doi: 10.1016/j.tige.2025.250935.

Colon

Hassan C, et al. Colon Cancer Screening, Surveillance, and Treatment: Novel Artificial Intelligence Driving Strategies in the Management of Colon Lesions. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.021.

Pancreas

Wilcox CM, et al; US Pancreatic Disease Study Group. Management of the Disconnected Pancreatic Duct in Pancreatic Necrosis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.05.024.

Ghimire C, et al. The effect of advances in pancreatic cancer treatment in population mortality: A SEER-based study. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100739.

Hepatology

Canivet CM, et al. Validation of the AASLD/EASL Multi-Step Screening Strategies for MASLD. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100747.

Miscellaneous

Chang L, et al. Gut Feelings: The Critical Role of Interoception in Obesity and Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.04.002.

Bashiri K, et al. Advancing Hemostatic Powder Technologies for Management of Gastrointestinal Bleeding: Challenges and Solutions. Tech Innov Gastrointest. 2025 Jul. doi: 10.1016/j.tige.2025.250940.

Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.

Below are some selections from what I am reading in the AGA journals, highlighting clinically applicable and possibly practice-changing expert reviews and studies.

Esophagus/Motility

Nguyen AD, et al. AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.05.011.

Hartnett DA, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.06.032.

Gyawali CP, et al. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 May. doi: 10.1016/j.cgh.2025.02.032.

Stomach

Wiklund AK, et al. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.239.

Sonaiya S, et al. Over-the-Scope Clip versus Standard Endoscopic Therapy as First-Line Intervention for Nonvariceal Upper Gastrointestinal Bleeding: A Cost-Effectiveness Analysis. Tech Innov Gastrointest. 2025 Jun. doi: 10.1016/j.tige.2025.250935.

Colon

Hassan C, et al. Colon Cancer Screening, Surveillance, and Treatment: Novel Artificial Intelligence Driving Strategies in the Management of Colon Lesions. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.021.

Pancreas

Wilcox CM, et al; US Pancreatic Disease Study Group. Management of the Disconnected Pancreatic Duct in Pancreatic Necrosis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.05.024.

Ghimire C, et al. The effect of advances in pancreatic cancer treatment in population mortality: A SEER-based study. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100739.

Hepatology

Canivet CM, et al. Validation of the AASLD/EASL Multi-Step Screening Strategies for MASLD. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100747.

Miscellaneous

Chang L, et al. Gut Feelings: The Critical Role of Interoception in Obesity and Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.04.002.

Bashiri K, et al. Advancing Hemostatic Powder Technologies for Management of Gastrointestinal Bleeding: Challenges and Solutions. Tech Innov Gastrointest. 2025 Jul. doi: 10.1016/j.tige.2025.250940.

Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.

Acute pancreatitis can be associated with multiorgan system failure, including respiratory failure, which has a high mortality rate. Acute respiratory distress syndrome (ARDS) is a known complication of severe, acute pancreatitis, and is fatal in up to 40% of cases. Mortality rates exceed 80% in patients with PaO₂/FiO₂ < 100 mm Hg.² Although ARDS is typically associated with bilateral pulmonary infiltrates, severe hypoxemia in pancreatitis may not be visible in radiography in up to 50% of cases.¹

Hypertriglyceridemia is the third-most common cause of acute pancreatitis, with an incidence of 2% to 10% among patients diagnosed with acute pancreatitis.^3.4 Elevated serum triglycerides have been proposed to trigger acute pancreatitis by increasing plasma viscosity, which leads to ischemia and inflammation of the pancreas.⁴ In severe cases of hypertriglyceridemia-induced acute pancreatitis, plasmapheresis is used to rapidly reduce serum chylomicron and triglyceride levels.³    

This case report discusses a patient with acute pancreatitis whose hypoxemia coincided with the severity of hypertriglyceridemia, but without radiographic evidence of pulmonary infiltrates or other known pulmonary causes.

Case Presentation

A 60-year-old male presented to the emergency department with several hours of diffuse abdominal pain, nausea, and vomiting. The patient reported that his symptoms began after eating fried chicken. He reported no dyspnea, fever, chills, or other symptoms. His medical history included type 2 diabetes (hemoglobin A_1c, 11.1%), Hashimoto hypothyroidism, severe obstructive sleep apnea not on continuous positive airway pressure (apnea-hypoxia index, 59/h), and obesity (body mass index, 52). Initial vital signs were afebrile, heart rate of 90 beats/min, and oxygen saturation (SpO₂) of 85% on 6L oxygen via nasal cannula. He was admitted to the intensive care unit and quickly maximized on high flow nasal cannula, ultimately requiring endotracheal intubation and mechanical ventilation.

Initial laboratory studies were remarkable for serum sodium of 120 mmol/L (reference range, 136-146 mmol/L), creatinine of 1.65 mg/dL (reference range, 0.52-1.28 mg/dL), anion gap of 18 mEq/L (reference range, 3-11 mEq/L), lipase level of 1115 U/L (reference range, 11-82 U/L), glucose level of 334 mg/dL (reference range, 70-110 mg/dL), white blood count of 13.1 K/uL (reference range, 4.5-11.0 K/uL), lactate level of 3.8 mmol/L (reference range, 0.5-2.2 mmol/L), triglyceride level of 1605 mg/dL (reference range, 40-160 mg/dL), cholesterol level of 565 mg/dL (reference range, < 200 mg/dL), aminotransferase of 21 U/L (reference range, 13-36 U/L), alanine aminotransferase of < 3 U/L (reference range, 7-45 U/L), and total bilirubin level of 1.6 mg/dL (reference range, 0.2-1 mg/dL).     

The patient had an initial arterial blood gas pH of 7.26, partial pressure of CO₂ and O₂ of 64.1 mm Hg and 74.1 mm Hg, respectively, on volume control with a tidal volume of 500 mL, positive end-expiratory pressure of 10 cm H₂O, respiratory rate of 26 breaths/min, and FiO₂ was 100%, which yielded a PaO₂/FiO₂ of 74 mm Hg. The patient was maintained in steep reverse-Trendelenburg position with moderate improvement in his SpO₂.    

Chest X-ray and computed tomography angiogram did not reveal pleural effusions, pulmonary infiltrates, or pulmonary embolism (Figure 1). Computed tomography of the abdomen and pelvis demonstrated severe acute interstitial edematous pancreatitis with no evidence of pancreatic necrosis or evidence of gallstones (Figure 2). A transthoracic echocardiogram with bubble was negative for intracardiac right to left shunting.    

The leading diagnosis was ARDS secondary to acute pancreatitis with hypoxemia exacerbated by morbid obesity and untreated obstructive sleep apnea leading to hypoventilation.

Treatment

The patient was intubated and restricted to nothing by mouth and provided fluid resuscitation with crystalloids. On hospital day 1, he remained intubated and on mechanical ventilation, started on plasmapheresis and continued insulin infusion for severe hypertriglyceridemia. The patient’s PaO₂/FiO₂ ratio remained persistently < 100 mm Hg despite maximal ventilatory support. After 3 sessions of plasmapheresis, the serum triglyceride levels and oxygen requirements improved (Figure 3).

Due to prolonged intubation, the patient ultimately required a tracheostomy. By hospital day 48, the patient was successfully weaned off mechanical ventilation. His tracheostomy was decannulated uneventfully on hospital day 55 and the stoma was closed. The patient was discharged to a skilled nursing home for rehabilitation and received intensive physical therapy for deconditioning from prolonged hospitalization.

Discussion

Respiratory insufficiency is a common and potentially lethal complication observed in one-third of patients with acute pancreatitis.¹ Radiographic evidence of pleural effusions, atelectasis and pulmonary infiltrates are often present. Acute lung injury (ALI) and ARDS are the most severe pulmonary complications of acute pancreatitis.⁵ It has been proposed that ALI and ARDS are driven by a hyperinflammatory state, which has multiple downstream effects. Pulmonary parenchymal and vascular damage has been associated with activated proinflammatory cytokines, trypsin, phospholipase A, and free fatty acids (Figure 4).¹

Hypoxemia secondary to acute pancreatitis may occur without initial radiographic findings and has been observed in up to half of patients.¹ Hypoxemia in ARDS occurs due to ventilation-perfusion defects causing gas exchange impairments which may be worsened further by high distending volumes and pressures on mechanical ventilation, dyssynchronous breathing, and/or lung derecruitment.⁶ Patients who require intubation for pancreatitis-associated ALI or ARDS eventually exhibit imaging findings consistent with their disease.¹ The patient in this case exhibited severe hypoxemia for several days despite persistently negative radiographic studies. His history of obstructive sleep apnea and a body mass index of 52 may have contributed to respiratory failure; however, assessment of other contributors to the acute and profound hypoxemia yielded largely unremarkable results. The patient did not have a history or evidence of heart failure and his hypoxemia did not improve with diuresis. He tested positive for COVID-19 on admission and was briefly treated with remdesivir and dexamethasone, but it was determined that the test was likely a false positive due to negative subsequent tests and elevated cycle thresholds (> 40). A concomitant COVID-19 infection likely did not contribute to his symptoms.    

Ventilation-perfusion mismatch is a well-recognized complication of pancreatitis, which results in right-to-left shunting.⁵ While we considered whether an intracardiac shunt may have contributed to the patient’s hypoxemia, a transthoracic echocardiogram with bubble contrast was negative.    

The patient had a peak serum triglyceride of > 6000 mg/dl, which meets the criteria for very severe hypertriglyceridemia.⁷ As observed in prior reports, the extent of the hypertriglyceridemia in this patient resulted in pronounced lipemic blood, which was appreciable by the eye and necessitated several rounds of centrifugation to analyze the laboratory studies.⁸ In this case, plasmapheresis was used to rapidly treat the hypertriglyceridemia, thereby reducing inflammation and further damage to the pancreas.⁹    

It is possible the patient’s hypertriglyceridemia may have been associated with his hypoxemia. His hypoxemia was most pronounced approximately 24 hours postadmission, which coincided with the peak of the hypertriglyceridemia. It remains unclear whether the severity of triglyceride elevation could accurately predict the severity of respiratory insufficiency. Hypoxemia is thought to modulate triglyceride metabolism through stimulation of intracellular lipolysis, upregulation of very low-density lipoproteins production in the liver, and inhibition of triglyceride-rich lipoprotein metabolism.¹⁰ Evidence from rodent studies supports the idea that acute hypoxemia increases triglycerides, and the degree of hypoxemia correlates with the elevated triglyceride levels.¹¹ However, this has not been consistently observed in humans and may vary by prandial state.^12,13 Thus, dysfunction of lipid metabolism may be a relevant clinical indicator of hypoxemia; further work is needed to elucidate this association.

Patient Perspective

The patient continues to undergo extensive rehabilitation following his prolonged illness and hospitalization. He expressed gratitude for the care received. However, he has limited and distorted recollection of the events during his hospitalization and stated that it felt “like an extraterrestrial state.”

Conclusions

This report describes a case of marked hypoxemia in the setting of acute pancreatitis. Pulmonary insufficiency in acute pancreatitis is commonly associated with imaging findings such as atelectasis, pleural effusions, and pulmonary infiltrates; however, up to half of cases initially lack any radiographic findings. Plasmapheresis is an effective treatment for hypertriglyceridemia-induced pancreatitis to both directly reduce circulating triglycerides and inflammation. Plasmapheresis also represents a promising therapy for the prevention of further episodes of pancreatitis in patients with recurrent pancreatitis. We propose a feedback mechanism through which pancreatitis induces severe hypoxemia, which may modulate lipid metabolism and severe hypertriglyceridemia correlates with respiratory failure.

Acute pancreatitis can be associated with multiorgan system failure, including respiratory failure, which has a high mortality rate. Acute respiratory distress syndrome (ARDS) is a known complication of severe, acute pancreatitis, and is fatal in up to 40% of cases. Mortality rates exceed 80% in patients with PaO₂/FiO₂ < 100 mm Hg.² Although ARDS is typically associated with bilateral pulmonary infiltrates, severe hypoxemia in pancreatitis may not be visible in radiography in up to 50% of cases.¹

Hypertriglyceridemia is the third-most common cause of acute pancreatitis, with an incidence of 2% to 10% among patients diagnosed with acute pancreatitis.^3.4 Elevated serum triglycerides have been proposed to trigger acute pancreatitis by increasing plasma viscosity, which leads to ischemia and inflammation of the pancreas.⁴ In severe cases of hypertriglyceridemia-induced acute pancreatitis, plasmapheresis is used to rapidly reduce serum chylomicron and triglyceride levels.³    

This case report discusses a patient with acute pancreatitis whose hypoxemia coincided with the severity of hypertriglyceridemia, but without radiographic evidence of pulmonary infiltrates or other known pulmonary causes.

Case Presentation

A 60-year-old male presented to the emergency department with several hours of diffuse abdominal pain, nausea, and vomiting. The patient reported that his symptoms began after eating fried chicken. He reported no dyspnea, fever, chills, or other symptoms. His medical history included type 2 diabetes (hemoglobin A_1c, 11.1%), Hashimoto hypothyroidism, severe obstructive sleep apnea not on continuous positive airway pressure (apnea-hypoxia index, 59/h), and obesity (body mass index, 52). Initial vital signs were afebrile, heart rate of 90 beats/min, and oxygen saturation (SpO₂) of 85% on 6L oxygen via nasal cannula. He was admitted to the intensive care unit and quickly maximized on high flow nasal cannula, ultimately requiring endotracheal intubation and mechanical ventilation.

Initial laboratory studies were remarkable for serum sodium of 120 mmol/L (reference range, 136-146 mmol/L), creatinine of 1.65 mg/dL (reference range, 0.52-1.28 mg/dL), anion gap of 18 mEq/L (reference range, 3-11 mEq/L), lipase level of 1115 U/L (reference range, 11-82 U/L), glucose level of 334 mg/dL (reference range, 70-110 mg/dL), white blood count of 13.1 K/uL (reference range, 4.5-11.0 K/uL), lactate level of 3.8 mmol/L (reference range, 0.5-2.2 mmol/L), triglyceride level of 1605 mg/dL (reference range, 40-160 mg/dL), cholesterol level of 565 mg/dL (reference range, < 200 mg/dL), aminotransferase of 21 U/L (reference range, 13-36 U/L), alanine aminotransferase of < 3 U/L (reference range, 7-45 U/L), and total bilirubin level of 1.6 mg/dL (reference range, 0.2-1 mg/dL).     

The patient had an initial arterial blood gas pH of 7.26, partial pressure of CO₂ and O₂ of 64.1 mm Hg and 74.1 mm Hg, respectively, on volume control with a tidal volume of 500 mL, positive end-expiratory pressure of 10 cm H₂O, respiratory rate of 26 breaths/min, and FiO₂ was 100%, which yielded a PaO₂/FiO₂ of 74 mm Hg. The patient was maintained in steep reverse-Trendelenburg position with moderate improvement in his SpO₂.    

Chest X-ray and computed tomography angiogram did not reveal pleural effusions, pulmonary infiltrates, or pulmonary embolism (Figure 1). Computed tomography of the abdomen and pelvis demonstrated severe acute interstitial edematous pancreatitis with no evidence of pancreatic necrosis or evidence of gallstones (Figure 2). A transthoracic echocardiogram with bubble was negative for intracardiac right to left shunting.    

The leading diagnosis was ARDS secondary to acute pancreatitis with hypoxemia exacerbated by morbid obesity and untreated obstructive sleep apnea leading to hypoventilation.

Treatment

The patient was intubated and restricted to nothing by mouth and provided fluid resuscitation with crystalloids. On hospital day 1, he remained intubated and on mechanical ventilation, started on plasmapheresis and continued insulin infusion for severe hypertriglyceridemia. The patient’s PaO₂/FiO₂ ratio remained persistently < 100 mm Hg despite maximal ventilatory support. After 3 sessions of plasmapheresis, the serum triglyceride levels and oxygen requirements improved (Figure 3).

Due to prolonged intubation, the patient ultimately required a tracheostomy. By hospital day 48, the patient was successfully weaned off mechanical ventilation. His tracheostomy was decannulated uneventfully on hospital day 55 and the stoma was closed. The patient was discharged to a skilled nursing home for rehabilitation and received intensive physical therapy for deconditioning from prolonged hospitalization.

Discussion

Respiratory insufficiency is a common and potentially lethal complication observed in one-third of patients with acute pancreatitis.¹ Radiographic evidence of pleural effusions, atelectasis and pulmonary infiltrates are often present. Acute lung injury (ALI) and ARDS are the most severe pulmonary complications of acute pancreatitis.⁵ It has been proposed that ALI and ARDS are driven by a hyperinflammatory state, which has multiple downstream effects. Pulmonary parenchymal and vascular damage has been associated with activated proinflammatory cytokines, trypsin, phospholipase A, and free fatty acids (Figure 4).¹

Hypoxemia secondary to acute pancreatitis may occur without initial radiographic findings and has been observed in up to half of patients.¹ Hypoxemia in ARDS occurs due to ventilation-perfusion defects causing gas exchange impairments which may be worsened further by high distending volumes and pressures on mechanical ventilation, dyssynchronous breathing, and/or lung derecruitment.⁶ Patients who require intubation for pancreatitis-associated ALI or ARDS eventually exhibit imaging findings consistent with their disease.¹ The patient in this case exhibited severe hypoxemia for several days despite persistently negative radiographic studies. His history of obstructive sleep apnea and a body mass index of 52 may have contributed to respiratory failure; however, assessment of other contributors to the acute and profound hypoxemia yielded largely unremarkable results. The patient did not have a history or evidence of heart failure and his hypoxemia did not improve with diuresis. He tested positive for COVID-19 on admission and was briefly treated with remdesivir and dexamethasone, but it was determined that the test was likely a false positive due to negative subsequent tests and elevated cycle thresholds (> 40). A concomitant COVID-19 infection likely did not contribute to his symptoms.    

Ventilation-perfusion mismatch is a well-recognized complication of pancreatitis, which results in right-to-left shunting.⁵ While we considered whether an intracardiac shunt may have contributed to the patient’s hypoxemia, a transthoracic echocardiogram with bubble contrast was negative.    

The patient had a peak serum triglyceride of > 6000 mg/dl, which meets the criteria for very severe hypertriglyceridemia.⁷ As observed in prior reports, the extent of the hypertriglyceridemia in this patient resulted in pronounced lipemic blood, which was appreciable by the eye and necessitated several rounds of centrifugation to analyze the laboratory studies.⁸ In this case, plasmapheresis was used to rapidly treat the hypertriglyceridemia, thereby reducing inflammation and further damage to the pancreas.⁹    

It is possible the patient’s hypertriglyceridemia may have been associated with his hypoxemia. His hypoxemia was most pronounced approximately 24 hours postadmission, which coincided with the peak of the hypertriglyceridemia. It remains unclear whether the severity of triglyceride elevation could accurately predict the severity of respiratory insufficiency. Hypoxemia is thought to modulate triglyceride metabolism through stimulation of intracellular lipolysis, upregulation of very low-density lipoproteins production in the liver, and inhibition of triglyceride-rich lipoprotein metabolism.¹⁰ Evidence from rodent studies supports the idea that acute hypoxemia increases triglycerides, and the degree of hypoxemia correlates with the elevated triglyceride levels.¹¹ However, this has not been consistently observed in humans and may vary by prandial state.^12,13 Thus, dysfunction of lipid metabolism may be a relevant clinical indicator of hypoxemia; further work is needed to elucidate this association.

Patient Perspective

The patient continues to undergo extensive rehabilitation following his prolonged illness and hospitalization. He expressed gratitude for the care received. However, he has limited and distorted recollection of the events during his hospitalization and stated that it felt “like an extraterrestrial state.”

Conclusions

This report describes a case of marked hypoxemia in the setting of acute pancreatitis. Pulmonary insufficiency in acute pancreatitis is commonly associated with imaging findings such as atelectasis, pleural effusions, and pulmonary infiltrates; however, up to half of cases initially lack any radiographic findings. Plasmapheresis is an effective treatment for hypertriglyceridemia-induced pancreatitis to both directly reduce circulating triglycerides and inflammation. Plasmapheresis also represents a promising therapy for the prevention of further episodes of pancreatitis in patients with recurrent pancreatitis. We propose a feedback mechanism through which pancreatitis induces severe hypoxemia, which may modulate lipid metabolism and severe hypertriglyceridemia correlates with respiratory failure.

Acute pancreatitis can be associated with multiorgan system failure, including respiratory failure, which has a high mortality rate. Acute respiratory distress syndrome (ARDS) is a known complication of severe, acute pancreatitis, and is fatal in up to 40% of cases. Mortality rates exceed 80% in patients with PaO₂/FiO₂ < 100 mm Hg.² Although ARDS is typically associated with bilateral pulmonary infiltrates, severe hypoxemia in pancreatitis may not be visible in radiography in up to 50% of cases.¹

Hypertriglyceridemia is the third-most common cause of acute pancreatitis, with an incidence of 2% to 10% among patients diagnosed with acute pancreatitis.^3.4 Elevated serum triglycerides have been proposed to trigger acute pancreatitis by increasing plasma viscosity, which leads to ischemia and inflammation of the pancreas.⁴ In severe cases of hypertriglyceridemia-induced acute pancreatitis, plasmapheresis is used to rapidly reduce serum chylomicron and triglyceride levels.³    

This case report discusses a patient with acute pancreatitis whose hypoxemia coincided with the severity of hypertriglyceridemia, but without radiographic evidence of pulmonary infiltrates or other known pulmonary causes.

Case Presentation

A 60-year-old male presented to the emergency department with several hours of diffuse abdominal pain, nausea, and vomiting. The patient reported that his symptoms began after eating fried chicken. He reported no dyspnea, fever, chills, or other symptoms. His medical history included type 2 diabetes (hemoglobin A_1c, 11.1%), Hashimoto hypothyroidism, severe obstructive sleep apnea not on continuous positive airway pressure (apnea-hypoxia index, 59/h), and obesity (body mass index, 52). Initial vital signs were afebrile, heart rate of 90 beats/min, and oxygen saturation (SpO₂) of 85% on 6L oxygen via nasal cannula. He was admitted to the intensive care unit and quickly maximized on high flow nasal cannula, ultimately requiring endotracheal intubation and mechanical ventilation.

Initial laboratory studies were remarkable for serum sodium of 120 mmol/L (reference range, 136-146 mmol/L), creatinine of 1.65 mg/dL (reference range, 0.52-1.28 mg/dL), anion gap of 18 mEq/L (reference range, 3-11 mEq/L), lipase level of 1115 U/L (reference range, 11-82 U/L), glucose level of 334 mg/dL (reference range, 70-110 mg/dL), white blood count of 13.1 K/uL (reference range, 4.5-11.0 K/uL), lactate level of 3.8 mmol/L (reference range, 0.5-2.2 mmol/L), triglyceride level of 1605 mg/dL (reference range, 40-160 mg/dL), cholesterol level of 565 mg/dL (reference range, < 200 mg/dL), aminotransferase of 21 U/L (reference range, 13-36 U/L), alanine aminotransferase of < 3 U/L (reference range, 7-45 U/L), and total bilirubin level of 1.6 mg/dL (reference range, 0.2-1 mg/dL).     

The patient had an initial arterial blood gas pH of 7.26, partial pressure of CO₂ and O₂ of 64.1 mm Hg and 74.1 mm Hg, respectively, on volume control with a tidal volume of 500 mL, positive end-expiratory pressure of 10 cm H₂O, respiratory rate of 26 breaths/min, and FiO₂ was 100%, which yielded a PaO₂/FiO₂ of 74 mm Hg. The patient was maintained in steep reverse-Trendelenburg position with moderate improvement in his SpO₂.    

Chest X-ray and computed tomography angiogram did not reveal pleural effusions, pulmonary infiltrates, or pulmonary embolism (Figure 1). Computed tomography of the abdomen and pelvis demonstrated severe acute interstitial edematous pancreatitis with no evidence of pancreatic necrosis or evidence of gallstones (Figure 2). A transthoracic echocardiogram with bubble was negative for intracardiac right to left shunting.    

The leading diagnosis was ARDS secondary to acute pancreatitis with hypoxemia exacerbated by morbid obesity and untreated obstructive sleep apnea leading to hypoventilation.

Treatment

The patient was intubated and restricted to nothing by mouth and provided fluid resuscitation with crystalloids. On hospital day 1, he remained intubated and on mechanical ventilation, started on plasmapheresis and continued insulin infusion for severe hypertriglyceridemia. The patient’s PaO₂/FiO₂ ratio remained persistently < 100 mm Hg despite maximal ventilatory support. After 3 sessions of plasmapheresis, the serum triglyceride levels and oxygen requirements improved (Figure 3).

Due to prolonged intubation, the patient ultimately required a tracheostomy. By hospital day 48, the patient was successfully weaned off mechanical ventilation. His tracheostomy was decannulated uneventfully on hospital day 55 and the stoma was closed. The patient was discharged to a skilled nursing home for rehabilitation and received intensive physical therapy for deconditioning from prolonged hospitalization.

Discussion

Respiratory insufficiency is a common and potentially lethal complication observed in one-third of patients with acute pancreatitis.¹ Radiographic evidence of pleural effusions, atelectasis and pulmonary infiltrates are often present. Acute lung injury (ALI) and ARDS are the most severe pulmonary complications of acute pancreatitis.⁵ It has been proposed that ALI and ARDS are driven by a hyperinflammatory state, which has multiple downstream effects. Pulmonary parenchymal and vascular damage has been associated with activated proinflammatory cytokines, trypsin, phospholipase A, and free fatty acids (Figure 4).¹

Hypoxemia secondary to acute pancreatitis may occur without initial radiographic findings and has been observed in up to half of patients.¹ Hypoxemia in ARDS occurs due to ventilation-perfusion defects causing gas exchange impairments which may be worsened further by high distending volumes and pressures on mechanical ventilation, dyssynchronous breathing, and/or lung derecruitment.⁶ Patients who require intubation for pancreatitis-associated ALI or ARDS eventually exhibit imaging findings consistent with their disease.¹ The patient in this case exhibited severe hypoxemia for several days despite persistently negative radiographic studies. His history of obstructive sleep apnea and a body mass index of 52 may have contributed to respiratory failure; however, assessment of other contributors to the acute and profound hypoxemia yielded largely unremarkable results. The patient did not have a history or evidence of heart failure and his hypoxemia did not improve with diuresis. He tested positive for COVID-19 on admission and was briefly treated with remdesivir and dexamethasone, but it was determined that the test was likely a false positive due to negative subsequent tests and elevated cycle thresholds (> 40). A concomitant COVID-19 infection likely did not contribute to his symptoms.    

Ventilation-perfusion mismatch is a well-recognized complication of pancreatitis, which results in right-to-left shunting.⁵ While we considered whether an intracardiac shunt may have contributed to the patient’s hypoxemia, a transthoracic echocardiogram with bubble contrast was negative.    

The patient had a peak serum triglyceride of > 6000 mg/dl, which meets the criteria for very severe hypertriglyceridemia.⁷ As observed in prior reports, the extent of the hypertriglyceridemia in this patient resulted in pronounced lipemic blood, which was appreciable by the eye and necessitated several rounds of centrifugation to analyze the laboratory studies.⁸ In this case, plasmapheresis was used to rapidly treat the hypertriglyceridemia, thereby reducing inflammation and further damage to the pancreas.⁹    

It is possible the patient’s hypertriglyceridemia may have been associated with his hypoxemia. His hypoxemia was most pronounced approximately 24 hours postadmission, which coincided with the peak of the hypertriglyceridemia. It remains unclear whether the severity of triglyceride elevation could accurately predict the severity of respiratory insufficiency. Hypoxemia is thought to modulate triglyceride metabolism through stimulation of intracellular lipolysis, upregulation of very low-density lipoproteins production in the liver, and inhibition of triglyceride-rich lipoprotein metabolism.¹⁰ Evidence from rodent studies supports the idea that acute hypoxemia increases triglycerides, and the degree of hypoxemia correlates with the elevated triglyceride levels.¹¹ However, this has not been consistently observed in humans and may vary by prandial state.^12,13 Thus, dysfunction of lipid metabolism may be a relevant clinical indicator of hypoxemia; further work is needed to elucidate this association.

Patient Perspective

The patient continues to undergo extensive rehabilitation following his prolonged illness and hospitalization. He expressed gratitude for the care received. However, he has limited and distorted recollection of the events during his hospitalization and stated that it felt “like an extraterrestrial state.”

Conclusions

This report describes a case of marked hypoxemia in the setting of acute pancreatitis. Pulmonary insufficiency in acute pancreatitis is commonly associated with imaging findings such as atelectasis, pleural effusions, and pulmonary infiltrates; however, up to half of cases initially lack any radiographic findings. Plasmapheresis is an effective treatment for hypertriglyceridemia-induced pancreatitis to both directly reduce circulating triglycerides and inflammation. Plasmapheresis also represents a promising therapy for the prevention of further episodes of pancreatitis in patients with recurrent pancreatitis. We propose a feedback mechanism through which pancreatitis induces severe hypoxemia, which may modulate lipid metabolism and severe hypertriglyceridemia correlates with respiratory failure.