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Bringing HCC Patients Hope Through Trials, Advanced Treatments
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
For Reena Salgia, MD, the most rewarding part about working with patients with hepatocellular carcinoma is being there for their entire journey, thanks to advancements in treatment. “It brings a smile to my face just to think about it,” says Dr. Salgia, medical director of Henry Ford Health’s Liver Cancer Clinic in Detroit.
Hepatocellular carcinoma accounts for 80% of all liver cancer. When she first entered the field, Dr. Salgia often heard that survival rates 5 years after diagnosis were less than 10%. Over the last decade however, “I’ve seen an expansion in the procedural options that we offer these patients. We have an array of options both surgically as well as procedurally,” she said.
Especially over the last three to four years, “we’ve seen meaningful responses for patients with medications that we previously didn’t have in our toolbox. That’s really been exciting, along with continued involvement in clinical trials and being able to offer patients a number of different approaches to their care of liver cancer,” said Dr. Salgia.
A regular attendee and presenter at national GI meetings, Dr. Salgia participated in AGA’s Women’s Executive Leadership Conference in 2023. Her academic resume includes a long list of clinical trials to assess treatments for patients at different stages of hepatocellular carcinoma.
In an interview, she discussed the highlights of her career as a researcher and mentor of fellows, and how she guides and supports her transplant patients.
What drove you to pursue the field of hepatology and transplant hepatology?
I came across this field during my fourth year of medical school. I didn’t know anything about hepatology when I reached that stage and had the opportunity to do an elective. I just fell in love with the specialty. I liked the complex pathophysiology of liver disease, the long-term follow-up and care of patients. It appealed to the type of science that I had enjoyed back in college.
As I went into my GI fellowship training, I got to learn more about the field of transplant medicine. For instance, how you can take these patients who are incredibly ill, really at a very vulnerable point of their illness, and then offer them great hope and see their lives turn around afterwards. When I had the opportunity to see patients go from end stage liver disease to such significant improvement in their quality of life, and restoring their physical functioning beyond what we would’ve ever imagined when they were ill, it reaffirmed my interest in both hepatology as well as in transplant medicine.
How do you help those patients waiting on transplant lists for a liver?
We are intimately involved in their care all the way through their journey with liver disease, up until the time of physically getting the liver transplant, which is performed by our colleagues in transplant surgery. From the time they are transplanted, we are involved in their inpatient and outpatient post-transplant care. We’ve helped to get them on the transplant list with the work of the multidisciplinary team. If there are opportunities to help them understand their position on the list or obtaining exceptions—though that is done in a very objective fashion through the regulatory system—we help to guide them through that journey.
You’ve worked on many studies that involve treatments for hepatocellular carcinoma. Can you highlight a paper that yielded clinically significant benefits?
What really stands out the most to me was our site’s involvement in the IMbrave150 trial, which was published in 2020. This multicenter study made a big difference in the outcomes and treatments for patients, as it brought the adoption of first-line immunotherapy (atezolizumab plus bevacizumab) for patients with advanced hepatocellular carcinoma. I remember vividly the patients we had the opportunity to enroll in that trial – some who we continue to care for today. This stands out as one of the trials that I was involved in that had a lasting impact.
What were the clinical endpoints and key results of that trial?
The endpoint was to see an improvement in overall survival utilizing immunotherapy, compared with the prior standard of care then available, oral therapy. The results led to the adoption and FDA approval of immunotherapy in the first line setting for advanced unresectable hepatocellular carcinoma patients.
What are some of the highlights of serving as director of Henry Ford’s fellowship program?
Education is my passion. I went into medical training feeling that at some point I would love to blend in teaching in a formal role. Becoming program director of the gastroenterology and hepatology fellowship at Henry Ford in 2018 was one of the most meaningful things that I’ve had the opportunity to do in my career. I get to see trainees who are at a very impressionable point of their journey go on to become gastroenterologists and then launch into their first job and really develop in this field. Seeing them come in day one, not knowing how to hold a scope or do a procedure on a patient of this nature, then quickly evolve over the first year and grow over three years to achieve this specialty training [is rewarding]. I’ve learned a lot from the fellows along the way. I think of them as an extension of my family. We have 15 fellows currently in our program and we’ll be growing this summer. So that’s really been a highlight of my career thus far.
What fears did you have to push past to get to where you are in your career?
I think that there have been a few. One is certainly the fear of making the wrong choice with your first career opportunity. I did choose to leave my comfort zone from where I had done my training. I met that with some fear, but also excitement for new opportunities of personal and professional growth.
Another fear is: Am I going to be able to be ambitious in this field? Can I pursue research, become a program director, and do things that my role models and mentors were able to achieve? There’s also the fear of being able to balance a busy work life with a busy home life and figuring out how to do both well and minimize the guilt on both sides. I have a family with two girls. They are definitely a top priority.
What teacher or mentor had the greatest impact on you?
Helen Te, MD, a hepatologist at the University of Chicago. When I was a medical student there, I had the opportunity to work with her and saw her passion for this field. She really had so much enthusiasm for teaching and was a big part of why I started to fall in love with liver disease.
Karen Kim, MD, now the dean of Penn State College of Medicine, was one of my assigned mentors as a medical student. She helped me explore the fields where there were opportunities for residency and helped me make the decision to go into internal medicine, which often is a key deciding point for medical students. She was also a very influential teacher. The other individual who stands out is my fellowship program director, Hari Sree Conjeevaram, MD, MSc, at University of Michigan Health. He exhibited the qualities as an educator and program director that helped me recognize that education was something that I wanted to pursue in a formal fashion once I moved on in my career.
Describe how you would spend a free Saturday afternoon.
Likely taking a hike or go to a park with my family, enjoying the outdoors and spending time with them.
Lightning Round
If you weren’t a gastroenterologist, what would you be?
Philanthropist
Favorite city in U.S. besides the one you live in?
Chicago
Place you most want to travel?
New Zealand
Favorite breakfast?
Avocado toast
Favorite ice cream flavor?
Cookies and cream
How many cups of coffee do you drink per day?
Two…or more
Cat person or dog person?
Dog
Texting or talking?
Talk
Favorite season?
Autumn
Favorite type of music?
Pop
Favorite movie genre?
Action
Endoscopist Brings Cutting-Edge Tech to Asia-Pacific Region
As the COVID-19 crisis unfolded in early 2020, Tossapol Kerdsirichairat, MD, faced another challenge: his mother’s ovarian cancer diagnosis.
“She chose to remain in Thailand, so I decided to relocate to care for her,” said Dr. Kerdsirichairat, an interventional endoscopist who completed fellowships at the University of Michigan, Ann Arbor, and Johns Hopkins University in Baltimore. The move to Bangkok turned out to be one of the best decisions of his life, he said, as he could support his mother while introducing advanced endoscopic techniques and devices to the region.
“Bangkok is a hub for medical innovation in Asia, offering opportunities to work with a diverse patient population and access to cutting-edge technology,” said Dr. Kerdsirichairat, who works at Bumrungrad International Hospital as a clinical associate professor.
The program is the first of its kind in Thailand and one of the few in the Asia-Pacific region.
“I guide patients and families through understanding their risks and implementing preventive strategies, collaborating with multidisciplinary teams to ensure comprehensive care. It’s incredibly rewarding to see the impact of early tumor detection,” said Dr. Kerdsirichairat, an international member of AGA who was a participant in the AGA Young Delegates Program.
He has set several records in Thailand for the smallest tumor detected, including a 0.3-millimeter (mm) esophageal tumor, a 0.8-mm tumor for stomach cancer, a 5-mm pancreatic tumor, and a 1-mm tumor for colon cancer.
“These were detected through high-standard screening programs, as patients often do not develop symptoms from these subtle lesions,” said Dr. Kerdsirichairat, who discussed in an interview the unique challenges of practicing overseas.
Why did you choose GI?
Gastroenterology is a specialty that uniquely integrates procedural skill, clinical decision making, and a deep understanding of complex biological systems. I was drawn especially to the ability to make a direct and meaningful impact in patients’ lives through advanced endoscopic procedures, while also addressing both acute and chronic diseases, and focusing on cancer prevention. It is incredibly rewarding to perform an endoscopic retrograde cholangiopancreatography (ERCP) for cholangitis and see a patient return to normal the very next day, or to perform an endoscopic ultrasound (EUS) for pancreatic cancer screening in high-risk individuals and detect a sub-centimeter pancreatic tumor.
Realizing that early detection can improve survival by threefold after surgery is a powerful reminder of the difference we can make in patients’ lives. This specialty requires a delicate balance of precision and empathy, which perfectly aligns with my strengths and values as a physician.
You have a wide variety of clinical interests, from endoscopic procedures to cancer research to GERD. What’s your key subspecialty and why?
My primary specialty is advanced endoscopy, which includes techniques such as EUS, ERCP, and endoscopic resection of precancerous and early cancerous lesions. I also focus on cutting-edge, evidence-based techniques recently included in clinical guidelines, such as Transoral Incisionless Fundoplication (TIF). These minimally invasive options allow me to diagnose and treat conditions that once required surgery. The precision and innovation involved in advanced endoscopy enable me to effectively manage complex cases—from diagnosing early cancers to managing bile duct obstructions and resecting precancerous lesions.
Can you describe your work in cancer genetics and screening?
I am deeply committed to the early detection of gastrointestinal cancers, particularly through screening for precancerous conditions and hereditary syndromes. During my general GI training at the University of Michigan, I had the privilege of working with Grace Elta, MD, AGAF, and Michelle Anderson, MD, MSc, renowned experts in pancreatic cancer management. I was later trained by Anne Marie Lennon, PhD, AGAF, who pioneered the liquid biopsy technique for cancer screening through the CancerSEEK project, and Marcia (Mimi) Canto, MD, MHS, who initiated the Cancer of the Pancreas Screening project for high-risk individuals of pancreatic cancer.
I also had the distinction of being the first at Bumrungrad International Hospital to perform endoscopic drainage for pancreatic fluid collections in the setting of multi-organ failure. This endoscopic approach has been extensively validated in the medical literature as significantly improving survival rates compared to surgical drainage. My training in this specialized procedure was conducted under the guidance of the premier group for necrotizing pancreatitis, led by Martin Freeman, MD, at the University of Minnesota.
Later, I contributed to overseeing the Inherited Gastrointestinal Malignancy Clinic of MyCode, a large-scale population-based cohort program focused on cancer screening in Pennsylvania. By December 2024, MyCode had collected blood samples from over 258,000 individuals, analyzed DNA sequences from over 184,000, and provided clinical data that benefits over 142,000 patients. It’s not uncommon for healthy 25-year-old patients to come to our clinic for colon cancer screening after learning from the program that they carry a cancer syndrome, and early screening can potentially save their lives.
What are the key differences between training and practicing medicine in the United States and in an Asian country?
The U.S. healthcare system is deeply rooted in evidence-based protocols and multidisciplinary care, driven by an insurance-based model. In contrast, many Asian countries face challenges such as the dependency on government approval for certain treatments and insurance limitations. Practicing in Asia requires navigating unique cultural, economic, and systemic differences, including varying resource availability and disease prevalence.
What specific challenges have you faced as a GI in Thailand?
As an advanced endoscopist, one of the biggest challenges I faced initially was the difficulty in obtaining the same devices I used in the U.S. for use in Thailand. With support from device companies and mentors in the U.S., I was able to perform groundbreaking procedures, such as the TIF in Southeast Asia and the first use of a full-thickness resection device in Thailand. I am also proud to be part of one of the first few centers worldwide performing the combination of injectable semaglutide and endoscopic sleeve gastroplasty, resulting in a remarkable weight reduction of 44%, comparable to surgical gastric bypass.
In addition, Bumrungrad International Hospital, where I practice, sees over 1.1 million visits annually from patients from more than 190 countries. This offers a unique opportunity to engage with a global patient base and learn from diverse cultures. Over time, although the hospital has professional interpreters for all languages, I have become able to communicate basic sentences with international patients in their preferred languages, including Chinese, Japanese, and Arabic, which has enriched my practice.
What’s your favorite thing to do when you’re not practicing GI?
I enjoy traveling, exploring new cuisines, and spending quality time with family and friends. These activities help me recharge and offer fresh perspectives on life.
Lightning Round
Texting or talking?
Talking. It’s more personal and meaningful.
Favorite city in the U.S.?
Ann Arbor, Michigan
Cat or dog person?
Dog person
Favorite junk food?
Pizza
How many cups of coffee do you drink per day?
Two – just enough to stay sharp, but not jittery.
If you weren’t a GI, what would you be?
Architect
Best place you went on vacation?
Kyoto, Japan
Favorite sport?
Skiing
Favorite ice cream?
Matcha green tea
What song do you have to sing along with when you hear it?
“Everybody” by Backstreet Boys
Favorite movie or TV show?
Forrest Gump and Friends
Optimist or pessimist?
Optimist. I believe in focusing on solutions and possibilities.
As the COVID-19 crisis unfolded in early 2020, Tossapol Kerdsirichairat, MD, faced another challenge: his mother’s ovarian cancer diagnosis.
“She chose to remain in Thailand, so I decided to relocate to care for her,” said Dr. Kerdsirichairat, an interventional endoscopist who completed fellowships at the University of Michigan, Ann Arbor, and Johns Hopkins University in Baltimore. The move to Bangkok turned out to be one of the best decisions of his life, he said, as he could support his mother while introducing advanced endoscopic techniques and devices to the region.
“Bangkok is a hub for medical innovation in Asia, offering opportunities to work with a diverse patient population and access to cutting-edge technology,” said Dr. Kerdsirichairat, who works at Bumrungrad International Hospital as a clinical associate professor.
The program is the first of its kind in Thailand and one of the few in the Asia-Pacific region.
“I guide patients and families through understanding their risks and implementing preventive strategies, collaborating with multidisciplinary teams to ensure comprehensive care. It’s incredibly rewarding to see the impact of early tumor detection,” said Dr. Kerdsirichairat, an international member of AGA who was a participant in the AGA Young Delegates Program.
He has set several records in Thailand for the smallest tumor detected, including a 0.3-millimeter (mm) esophageal tumor, a 0.8-mm tumor for stomach cancer, a 5-mm pancreatic tumor, and a 1-mm tumor for colon cancer.
“These were detected through high-standard screening programs, as patients often do not develop symptoms from these subtle lesions,” said Dr. Kerdsirichairat, who discussed in an interview the unique challenges of practicing overseas.
Why did you choose GI?
Gastroenterology is a specialty that uniquely integrates procedural skill, clinical decision making, and a deep understanding of complex biological systems. I was drawn especially to the ability to make a direct and meaningful impact in patients’ lives through advanced endoscopic procedures, while also addressing both acute and chronic diseases, and focusing on cancer prevention. It is incredibly rewarding to perform an endoscopic retrograde cholangiopancreatography (ERCP) for cholangitis and see a patient return to normal the very next day, or to perform an endoscopic ultrasound (EUS) for pancreatic cancer screening in high-risk individuals and detect a sub-centimeter pancreatic tumor.
Realizing that early detection can improve survival by threefold after surgery is a powerful reminder of the difference we can make in patients’ lives. This specialty requires a delicate balance of precision and empathy, which perfectly aligns with my strengths and values as a physician.
You have a wide variety of clinical interests, from endoscopic procedures to cancer research to GERD. What’s your key subspecialty and why?
My primary specialty is advanced endoscopy, which includes techniques such as EUS, ERCP, and endoscopic resection of precancerous and early cancerous lesions. I also focus on cutting-edge, evidence-based techniques recently included in clinical guidelines, such as Transoral Incisionless Fundoplication (TIF). These minimally invasive options allow me to diagnose and treat conditions that once required surgery. The precision and innovation involved in advanced endoscopy enable me to effectively manage complex cases—from diagnosing early cancers to managing bile duct obstructions and resecting precancerous lesions.
Can you describe your work in cancer genetics and screening?
I am deeply committed to the early detection of gastrointestinal cancers, particularly through screening for precancerous conditions and hereditary syndromes. During my general GI training at the University of Michigan, I had the privilege of working with Grace Elta, MD, AGAF, and Michelle Anderson, MD, MSc, renowned experts in pancreatic cancer management. I was later trained by Anne Marie Lennon, PhD, AGAF, who pioneered the liquid biopsy technique for cancer screening through the CancerSEEK project, and Marcia (Mimi) Canto, MD, MHS, who initiated the Cancer of the Pancreas Screening project for high-risk individuals of pancreatic cancer.
I also had the distinction of being the first at Bumrungrad International Hospital to perform endoscopic drainage for pancreatic fluid collections in the setting of multi-organ failure. This endoscopic approach has been extensively validated in the medical literature as significantly improving survival rates compared to surgical drainage. My training in this specialized procedure was conducted under the guidance of the premier group for necrotizing pancreatitis, led by Martin Freeman, MD, at the University of Minnesota.
Later, I contributed to overseeing the Inherited Gastrointestinal Malignancy Clinic of MyCode, a large-scale population-based cohort program focused on cancer screening in Pennsylvania. By December 2024, MyCode had collected blood samples from over 258,000 individuals, analyzed DNA sequences from over 184,000, and provided clinical data that benefits over 142,000 patients. It’s not uncommon for healthy 25-year-old patients to come to our clinic for colon cancer screening after learning from the program that they carry a cancer syndrome, and early screening can potentially save their lives.
What are the key differences between training and practicing medicine in the United States and in an Asian country?
The U.S. healthcare system is deeply rooted in evidence-based protocols and multidisciplinary care, driven by an insurance-based model. In contrast, many Asian countries face challenges such as the dependency on government approval for certain treatments and insurance limitations. Practicing in Asia requires navigating unique cultural, economic, and systemic differences, including varying resource availability and disease prevalence.
What specific challenges have you faced as a GI in Thailand?
As an advanced endoscopist, one of the biggest challenges I faced initially was the difficulty in obtaining the same devices I used in the U.S. for use in Thailand. With support from device companies and mentors in the U.S., I was able to perform groundbreaking procedures, such as the TIF in Southeast Asia and the first use of a full-thickness resection device in Thailand. I am also proud to be part of one of the first few centers worldwide performing the combination of injectable semaglutide and endoscopic sleeve gastroplasty, resulting in a remarkable weight reduction of 44%, comparable to surgical gastric bypass.
In addition, Bumrungrad International Hospital, where I practice, sees over 1.1 million visits annually from patients from more than 190 countries. This offers a unique opportunity to engage with a global patient base and learn from diverse cultures. Over time, although the hospital has professional interpreters for all languages, I have become able to communicate basic sentences with international patients in their preferred languages, including Chinese, Japanese, and Arabic, which has enriched my practice.
What’s your favorite thing to do when you’re not practicing GI?
I enjoy traveling, exploring new cuisines, and spending quality time with family and friends. These activities help me recharge and offer fresh perspectives on life.
Lightning Round
Texting or talking?
Talking. It’s more personal and meaningful.
Favorite city in the U.S.?
Ann Arbor, Michigan
Cat or dog person?
Dog person
Favorite junk food?
Pizza
How many cups of coffee do you drink per day?
Two – just enough to stay sharp, but not jittery.
If you weren’t a GI, what would you be?
Architect
Best place you went on vacation?
Kyoto, Japan
Favorite sport?
Skiing
Favorite ice cream?
Matcha green tea
What song do you have to sing along with when you hear it?
“Everybody” by Backstreet Boys
Favorite movie or TV show?
Forrest Gump and Friends
Optimist or pessimist?
Optimist. I believe in focusing on solutions and possibilities.
As the COVID-19 crisis unfolded in early 2020, Tossapol Kerdsirichairat, MD, faced another challenge: his mother’s ovarian cancer diagnosis.
“She chose to remain in Thailand, so I decided to relocate to care for her,” said Dr. Kerdsirichairat, an interventional endoscopist who completed fellowships at the University of Michigan, Ann Arbor, and Johns Hopkins University in Baltimore. The move to Bangkok turned out to be one of the best decisions of his life, he said, as he could support his mother while introducing advanced endoscopic techniques and devices to the region.
“Bangkok is a hub for medical innovation in Asia, offering opportunities to work with a diverse patient population and access to cutting-edge technology,” said Dr. Kerdsirichairat, who works at Bumrungrad International Hospital as a clinical associate professor.
The program is the first of its kind in Thailand and one of the few in the Asia-Pacific region.
“I guide patients and families through understanding their risks and implementing preventive strategies, collaborating with multidisciplinary teams to ensure comprehensive care. It’s incredibly rewarding to see the impact of early tumor detection,” said Dr. Kerdsirichairat, an international member of AGA who was a participant in the AGA Young Delegates Program.
He has set several records in Thailand for the smallest tumor detected, including a 0.3-millimeter (mm) esophageal tumor, a 0.8-mm tumor for stomach cancer, a 5-mm pancreatic tumor, and a 1-mm tumor for colon cancer.
“These were detected through high-standard screening programs, as patients often do not develop symptoms from these subtle lesions,” said Dr. Kerdsirichairat, who discussed in an interview the unique challenges of practicing overseas.
Why did you choose GI?
Gastroenterology is a specialty that uniquely integrates procedural skill, clinical decision making, and a deep understanding of complex biological systems. I was drawn especially to the ability to make a direct and meaningful impact in patients’ lives through advanced endoscopic procedures, while also addressing both acute and chronic diseases, and focusing on cancer prevention. It is incredibly rewarding to perform an endoscopic retrograde cholangiopancreatography (ERCP) for cholangitis and see a patient return to normal the very next day, or to perform an endoscopic ultrasound (EUS) for pancreatic cancer screening in high-risk individuals and detect a sub-centimeter pancreatic tumor.
Realizing that early detection can improve survival by threefold after surgery is a powerful reminder of the difference we can make in patients’ lives. This specialty requires a delicate balance of precision and empathy, which perfectly aligns with my strengths and values as a physician.
You have a wide variety of clinical interests, from endoscopic procedures to cancer research to GERD. What’s your key subspecialty and why?
My primary specialty is advanced endoscopy, which includes techniques such as EUS, ERCP, and endoscopic resection of precancerous and early cancerous lesions. I also focus on cutting-edge, evidence-based techniques recently included in clinical guidelines, such as Transoral Incisionless Fundoplication (TIF). These minimally invasive options allow me to diagnose and treat conditions that once required surgery. The precision and innovation involved in advanced endoscopy enable me to effectively manage complex cases—from diagnosing early cancers to managing bile duct obstructions and resecting precancerous lesions.
Can you describe your work in cancer genetics and screening?
I am deeply committed to the early detection of gastrointestinal cancers, particularly through screening for precancerous conditions and hereditary syndromes. During my general GI training at the University of Michigan, I had the privilege of working with Grace Elta, MD, AGAF, and Michelle Anderson, MD, MSc, renowned experts in pancreatic cancer management. I was later trained by Anne Marie Lennon, PhD, AGAF, who pioneered the liquid biopsy technique for cancer screening through the CancerSEEK project, and Marcia (Mimi) Canto, MD, MHS, who initiated the Cancer of the Pancreas Screening project for high-risk individuals of pancreatic cancer.
I also had the distinction of being the first at Bumrungrad International Hospital to perform endoscopic drainage for pancreatic fluid collections in the setting of multi-organ failure. This endoscopic approach has been extensively validated in the medical literature as significantly improving survival rates compared to surgical drainage. My training in this specialized procedure was conducted under the guidance of the premier group for necrotizing pancreatitis, led by Martin Freeman, MD, at the University of Minnesota.
Later, I contributed to overseeing the Inherited Gastrointestinal Malignancy Clinic of MyCode, a large-scale population-based cohort program focused on cancer screening in Pennsylvania. By December 2024, MyCode had collected blood samples from over 258,000 individuals, analyzed DNA sequences from over 184,000, and provided clinical data that benefits over 142,000 patients. It’s not uncommon for healthy 25-year-old patients to come to our clinic for colon cancer screening after learning from the program that they carry a cancer syndrome, and early screening can potentially save their lives.
What are the key differences between training and practicing medicine in the United States and in an Asian country?
The U.S. healthcare system is deeply rooted in evidence-based protocols and multidisciplinary care, driven by an insurance-based model. In contrast, many Asian countries face challenges such as the dependency on government approval for certain treatments and insurance limitations. Practicing in Asia requires navigating unique cultural, economic, and systemic differences, including varying resource availability and disease prevalence.
What specific challenges have you faced as a GI in Thailand?
As an advanced endoscopist, one of the biggest challenges I faced initially was the difficulty in obtaining the same devices I used in the U.S. for use in Thailand. With support from device companies and mentors in the U.S., I was able to perform groundbreaking procedures, such as the TIF in Southeast Asia and the first use of a full-thickness resection device in Thailand. I am also proud to be part of one of the first few centers worldwide performing the combination of injectable semaglutide and endoscopic sleeve gastroplasty, resulting in a remarkable weight reduction of 44%, comparable to surgical gastric bypass.
In addition, Bumrungrad International Hospital, where I practice, sees over 1.1 million visits annually from patients from more than 190 countries. This offers a unique opportunity to engage with a global patient base and learn from diverse cultures. Over time, although the hospital has professional interpreters for all languages, I have become able to communicate basic sentences with international patients in their preferred languages, including Chinese, Japanese, and Arabic, which has enriched my practice.
What’s your favorite thing to do when you’re not practicing GI?
I enjoy traveling, exploring new cuisines, and spending quality time with family and friends. These activities help me recharge and offer fresh perspectives on life.
Lightning Round
Texting or talking?
Talking. It’s more personal and meaningful.
Favorite city in the U.S.?
Ann Arbor, Michigan
Cat or dog person?
Dog person
Favorite junk food?
Pizza
How many cups of coffee do you drink per day?
Two – just enough to stay sharp, but not jittery.
If you weren’t a GI, what would you be?
Architect
Best place you went on vacation?
Kyoto, Japan
Favorite sport?
Skiing
Favorite ice cream?
Matcha green tea
What song do you have to sing along with when you hear it?
“Everybody” by Backstreet Boys
Favorite movie or TV show?
Forrest Gump and Friends
Optimist or pessimist?
Optimist. I believe in focusing on solutions and possibilities.
Three Sisters Embrace ‘Collaborative Spirit’ of GI Science
They all share the same genes—and job title.
Each has her own lab, working in different specialties. But if one sister needs the others, it’s reassuring to know they’re not far away.
“We have very different points of view. I’m interested in microbes. Amy’s really interested in myosin mediated trafficking and Kristen’s interested in viruses and purinergic signaling. It’s awesome that we can all work in the same field but have very different questions. And there’s so many questions that we can tackle,” said Mindy Engevik, the oldest of the trio.
If Mindy’s students need help with staining, she sends them to Amy’s lab. If they need help with calcium signaling and live cell imaging, she’ll send them to Kristen’s lab. “We interchange our expertise a lot,” said Mindy.
It’s nice to have a sister down the hall at work who can advise you on RNA sequencing analysis or immunofluorescence imaging, noted Amy Engevik. “You can ask them: ‘Can you just walk my student through this for a minute?’ Or, could they help with organoid cultures you don’t have time for right now?”
Kristen, who joined her older sisters at MUSC in 2024, observed that “having a little bit of the variety with our backgrounds and training really helps bring out the collaborative spirit of science.”
In an interview, the Engevik sisters spoke more about their familial network, their shared love of gastroenterology (GI) science, and how they’ve parlayed their expertise into other critical areas of research.
Growing up, did you ever think that you would choose similar career paths? How did you all become interested in GI research?
Mindy Engevik: As kids we were all interested in nature and the world around us. We all liked being outside. Amy and I were obsessed with rocks and classifying plants and rocks. We all had a general interest in science. But I personally didn’t think that all three of us would go into the same thing and that we’d be working together as adults.
Amy Engevik: Once we got into high school and college, we all became very close and we all majored in biology. That set the stage for our interest in science and our love of science. Then, we all kind of fell in love with the GI tract and chose postdocs that were GI focused. Since Mindy and I graduated a year apart, ultimately our goal was to form a lab and work together.
Kristen Engevik: I was interested in science when my sisters were both at college studying for biology and talking about the things they were learning in microbiology and physiology. But I don’t think until I joined the PhD program that I was ever like: ‘Oh yeah, we’re all going to be in science and it’s all going to be one big giant collaborative multi-lab collaboration.’
What do each of you love about the field of gastroenterology?
Mindy Engevik: At our heart, we’re all people that love problem solving. A fun fact about us is on Thursdays once a month, we do a puzzle competition here in Charleston. We’re really into it. But I think we genuinely like the problem-solving nature of the GI tract, and there’s so many diverse questions that you can answer.
Amy Engevik: I love that the scientific community in the GI community is so wonderful. They are very kind, helpful people. Some other fields are more competitive and more cutthroat. I feel like I have such a great network of people to reach out to if I have problems or questions. And I think other fields don’t have such a wonderful welcoming community that is very inclusive and dynamic.
Kristen Engevik: The nice thing with studying the GI tract is all things essentially lead to the gut. You can collaborate with other scientists and go into the gut-brain axis, or there’s the cardiovascular-gut axis and all these different places that you can also go, or different diseases that don’t necessarily seem to originate at the gut but have a lot of effects on the gut. There’s a lot of variation that we can do within GI.
Each of you has focused on a different area of digestive disease. Can each of you briefly discuss your areas of study and any findings or discoveries you’d like to highlight?
Mindy Engevik: My research focuses on microbial-host interactions. We’re really interested in how microbes colonize the gastrointestinal tract, how they interact with mucus – which I think is an important aspect of the gut that sometimes is overlooked – and how their metabolites really impact host health. One thing that I’m particularly proud of is we’ve really been starting to understand the neurotransmitters that bacteria generate and how they influence specific cells within the gut. It’s an exciting time to be doing both microbiology and gut physiology.
Amy Engevik: I study the host side of things; the gastric or the GI epithelium, and how a specific molecular motor contributes to trafficking in the GI tract. Recently, I’ve been going back to some of my PhD work in the stomach. In a high fat diet model, we’re finding that there are early metaplastic changes in the stomach. I think the stomach is very often overlooked within the GI tract. And I think it really sets the stage for the lower GI tract for the microbiome that colonizes the colon and the small intestine. I think that changes in the stomach really should come to the forefront of GI. Those changes have profound impacts on things like colorectal cancer and inflammatory bowel disease.
Kristen Engevik: I’m also more on the epithelial side with Amy. My new lab’s work is going to be focusing on understanding cell communications, specifically through extracellular purines, which is known as purinergic signaling, and understanding what the effects are during both homeostasis and disease, since it hasn’t been studied within the gut itself. From my work in postdoctoral training, we found that this communication is important for a lot of aspects, specifically during viral infection. But I have some preliminary data that shows it may also have an important role during disease, like colitis. My lab is interested in understanding what this epithelial communication is and are there ways to increase or decrease the signaling depending on the disease.
You’re all skilled in analyzing bioinformatics data. How do you apply this skill in your GI research?
Mindy Engevik: We all got our PhDs in systems biology and physiology, so we were forced to take computational analysis classes. I remember at the time thinking, ‘Oh, I’m probably not going to use a bunch of this.’ And then it really captured our attention. We realized how valuable it was and how much information you could glean.
We do a lot of work using publicly available data sets. I think there’s a wealth of information out there now with single cell sequencing data and bulk RNA sequencing data of different sites in the GI tract. It’s been a very valuable time to data mine and look especially at inflammatory bowel disease and colorectal cancer. We’ve been really focused on all our favorite genes of interest. I’ve been looking at a lot of the mucins and IBD (inflammatory bowel disease) and cancer. Amy’s been looking at Myosin-Vb and other myosin and binding partners like Rabs, and Kristen has been looking at purinergic signaling receptors.
All three of you recently worked together to identify a possible genetic driver of uterine corpus endometrial cancer, the fourth deadliest cancer in women. Where are you in the research process right now?
Mindy Engevik: Our mom was diagnosed with cancer, so we took quite a bit of time off to go to California to help her with her chemotherapy, surgery, and radiation. While we were there, we decided to do some computational analyses of cancers that affect women as our way to deal with this devastating disease. We were really fascinated to find that Myosin-Vb, which is Amy’s favorite gene of interest, was highly up-regulated in tumors from uterine and corpus endometrial cancer.
This was independent of the age of the patient, the stage of the cancer, the grade of the tumors. We figured out that the promoter region of the gene was hypomethylated, so it was having a higher expression. And that led to changes in metabolism and it linked very closely with what we were seeing in the gut, what Myosin-Vb was doing. We have some uterine cancer tumor cells in the lab that we’ve been growing and we’re going to really prove that it’s Myosin-Vb that’s driving some of these metabolism phenotypes. And the nice thing is at least there is a Myosin-Vb inhibitor available.
We also have a paper under review, identifying what Myosin-Vb is doing in cancer in the colon. So we’re excited to continue both the uterine cancer part but then also the colorectal cancer part using our same processes.
Amy Engevik: We’re going to be generating a mouse model that I think will be helpful since it’s in vivo. Sometimes things in vivo behave very differently than they do in vitro, so I think it’ll be a nice coupling of in vitro data with in vivo, taking that computational base and expanding it into more mechanistic studies and more experimental approaches where we can actually develop uterine cancer in the mice and then see if we can knock out Myosin-Vb specifically in that tissue and prevent it from either happening in the first place or decrease its pathogenesis.
What challenges have you faced in your career? How do you offer each other support?
Mindy Engevik: I think for any female scientists trying to have an independent career, there are some hurdles. An article in Nature recently stated that women receive less credit than their male counterparts and another article in Science demonstrated that women who are last authors on publications are cited less. That’s something that all women must deal with everywhere. I think it’s been incredibly helpful for us since there’s three of us. I think it gives us extra visibility in the field.
Amy Engevik: There’s a lot of microaggressions and things that can hinder your career success. I think that we’ve definitely had that. And I think the academic landscape is changing a little bit now that more women are becoming principal investigators and then rising through the ranks of academia. So I think there’s a lot of hope for the future women, but I think it’s still quite challenging.
Kristen Engevik: Things do seem to be getting better as there are more women as faculty members in certain departments. Science is getting better as things progress. However, there are still a lot of difficulties in trying to get credit for what you do, and getting the promotions.
Mindy Engevik: We have a built-in sisterhood, if you will. So I’m always going to champion Amy or Kristen. If there’s an award that I can nominate them for, I’m always going to do it. If there’s something that I think they should apply for that maybe they hadn’t seen, I’m going to make sure I put it on the radar. I think that’s just incredibly helpful, having people that have your best interest in mind.
Every project we have is basically a big collaboration. We have a lot of papers from our postdocs where we are coauthors. Now, as principal investigators, we have a lot of papers together. And I think in the future you’ll be seeing a lot of coauthored publications from our group as well.
Lightning Round
Texting or talking?
KE: Talking
Favorite city in US besides the one you live in?
AE: Boston
Favorite breakfast?
ME: Biscuits and grits
Place you most want to travel?
KE: Antarctica
Favorite junk food?
AE: French fries
Favorite season?
ME: Fall
Favorite ice cream flavor?
KE: Black raspberry chip
Number of cups of coffee you drink per day?
AE: None, I like Diet Coke
Last movie you watched?
ME: Inside Out 2
If you weren’t a gastroenterologist, what would you be?
KE: National Park ranger
Best Halloween costume you ever wore?
AE: Princess Leia
Favorite type of music?
ME: ABBA
Favorite movie genre?
KE: Romantic comedies
Cat person or dog person?
AE: Neither, I like rabbits
Favorite sport?
ME: Surfing
What song do you have to sing along with when you hear it?
KE: Mama Mia
Introvert or extrovert?
AE: Introvert
Favorite holiday?
ME: Halloween
They all share the same genes—and job title.
Each has her own lab, working in different specialties. But if one sister needs the others, it’s reassuring to know they’re not far away.
“We have very different points of view. I’m interested in microbes. Amy’s really interested in myosin mediated trafficking and Kristen’s interested in viruses and purinergic signaling. It’s awesome that we can all work in the same field but have very different questions. And there’s so many questions that we can tackle,” said Mindy Engevik, the oldest of the trio.
If Mindy’s students need help with staining, she sends them to Amy’s lab. If they need help with calcium signaling and live cell imaging, she’ll send them to Kristen’s lab. “We interchange our expertise a lot,” said Mindy.
It’s nice to have a sister down the hall at work who can advise you on RNA sequencing analysis or immunofluorescence imaging, noted Amy Engevik. “You can ask them: ‘Can you just walk my student through this for a minute?’ Or, could they help with organoid cultures you don’t have time for right now?”
Kristen, who joined her older sisters at MUSC in 2024, observed that “having a little bit of the variety with our backgrounds and training really helps bring out the collaborative spirit of science.”
In an interview, the Engevik sisters spoke more about their familial network, their shared love of gastroenterology (GI) science, and how they’ve parlayed their expertise into other critical areas of research.
Growing up, did you ever think that you would choose similar career paths? How did you all become interested in GI research?
Mindy Engevik: As kids we were all interested in nature and the world around us. We all liked being outside. Amy and I were obsessed with rocks and classifying plants and rocks. We all had a general interest in science. But I personally didn’t think that all three of us would go into the same thing and that we’d be working together as adults.
Amy Engevik: Once we got into high school and college, we all became very close and we all majored in biology. That set the stage for our interest in science and our love of science. Then, we all kind of fell in love with the GI tract and chose postdocs that were GI focused. Since Mindy and I graduated a year apart, ultimately our goal was to form a lab and work together.
Kristen Engevik: I was interested in science when my sisters were both at college studying for biology and talking about the things they were learning in microbiology and physiology. But I don’t think until I joined the PhD program that I was ever like: ‘Oh yeah, we’re all going to be in science and it’s all going to be one big giant collaborative multi-lab collaboration.’
What do each of you love about the field of gastroenterology?
Mindy Engevik: At our heart, we’re all people that love problem solving. A fun fact about us is on Thursdays once a month, we do a puzzle competition here in Charleston. We’re really into it. But I think we genuinely like the problem-solving nature of the GI tract, and there’s so many diverse questions that you can answer.
Amy Engevik: I love that the scientific community in the GI community is so wonderful. They are very kind, helpful people. Some other fields are more competitive and more cutthroat. I feel like I have such a great network of people to reach out to if I have problems or questions. And I think other fields don’t have such a wonderful welcoming community that is very inclusive and dynamic.
Kristen Engevik: The nice thing with studying the GI tract is all things essentially lead to the gut. You can collaborate with other scientists and go into the gut-brain axis, or there’s the cardiovascular-gut axis and all these different places that you can also go, or different diseases that don’t necessarily seem to originate at the gut but have a lot of effects on the gut. There’s a lot of variation that we can do within GI.
Each of you has focused on a different area of digestive disease. Can each of you briefly discuss your areas of study and any findings or discoveries you’d like to highlight?
Mindy Engevik: My research focuses on microbial-host interactions. We’re really interested in how microbes colonize the gastrointestinal tract, how they interact with mucus – which I think is an important aspect of the gut that sometimes is overlooked – and how their metabolites really impact host health. One thing that I’m particularly proud of is we’ve really been starting to understand the neurotransmitters that bacteria generate and how they influence specific cells within the gut. It’s an exciting time to be doing both microbiology and gut physiology.
Amy Engevik: I study the host side of things; the gastric or the GI epithelium, and how a specific molecular motor contributes to trafficking in the GI tract. Recently, I’ve been going back to some of my PhD work in the stomach. In a high fat diet model, we’re finding that there are early metaplastic changes in the stomach. I think the stomach is very often overlooked within the GI tract. And I think it really sets the stage for the lower GI tract for the microbiome that colonizes the colon and the small intestine. I think that changes in the stomach really should come to the forefront of GI. Those changes have profound impacts on things like colorectal cancer and inflammatory bowel disease.
Kristen Engevik: I’m also more on the epithelial side with Amy. My new lab’s work is going to be focusing on understanding cell communications, specifically through extracellular purines, which is known as purinergic signaling, and understanding what the effects are during both homeostasis and disease, since it hasn’t been studied within the gut itself. From my work in postdoctoral training, we found that this communication is important for a lot of aspects, specifically during viral infection. But I have some preliminary data that shows it may also have an important role during disease, like colitis. My lab is interested in understanding what this epithelial communication is and are there ways to increase or decrease the signaling depending on the disease.
You’re all skilled in analyzing bioinformatics data. How do you apply this skill in your GI research?
Mindy Engevik: We all got our PhDs in systems biology and physiology, so we were forced to take computational analysis classes. I remember at the time thinking, ‘Oh, I’m probably not going to use a bunch of this.’ And then it really captured our attention. We realized how valuable it was and how much information you could glean.
We do a lot of work using publicly available data sets. I think there’s a wealth of information out there now with single cell sequencing data and bulk RNA sequencing data of different sites in the GI tract. It’s been a very valuable time to data mine and look especially at inflammatory bowel disease and colorectal cancer. We’ve been really focused on all our favorite genes of interest. I’ve been looking at a lot of the mucins and IBD (inflammatory bowel disease) and cancer. Amy’s been looking at Myosin-Vb and other myosin and binding partners like Rabs, and Kristen has been looking at purinergic signaling receptors.
All three of you recently worked together to identify a possible genetic driver of uterine corpus endometrial cancer, the fourth deadliest cancer in women. Where are you in the research process right now?
Mindy Engevik: Our mom was diagnosed with cancer, so we took quite a bit of time off to go to California to help her with her chemotherapy, surgery, and radiation. While we were there, we decided to do some computational analyses of cancers that affect women as our way to deal with this devastating disease. We were really fascinated to find that Myosin-Vb, which is Amy’s favorite gene of interest, was highly up-regulated in tumors from uterine and corpus endometrial cancer.
This was independent of the age of the patient, the stage of the cancer, the grade of the tumors. We figured out that the promoter region of the gene was hypomethylated, so it was having a higher expression. And that led to changes in metabolism and it linked very closely with what we were seeing in the gut, what Myosin-Vb was doing. We have some uterine cancer tumor cells in the lab that we’ve been growing and we’re going to really prove that it’s Myosin-Vb that’s driving some of these metabolism phenotypes. And the nice thing is at least there is a Myosin-Vb inhibitor available.
We also have a paper under review, identifying what Myosin-Vb is doing in cancer in the colon. So we’re excited to continue both the uterine cancer part but then also the colorectal cancer part using our same processes.
Amy Engevik: We’re going to be generating a mouse model that I think will be helpful since it’s in vivo. Sometimes things in vivo behave very differently than they do in vitro, so I think it’ll be a nice coupling of in vitro data with in vivo, taking that computational base and expanding it into more mechanistic studies and more experimental approaches where we can actually develop uterine cancer in the mice and then see if we can knock out Myosin-Vb specifically in that tissue and prevent it from either happening in the first place or decrease its pathogenesis.
What challenges have you faced in your career? How do you offer each other support?
Mindy Engevik: I think for any female scientists trying to have an independent career, there are some hurdles. An article in Nature recently stated that women receive less credit than their male counterparts and another article in Science demonstrated that women who are last authors on publications are cited less. That’s something that all women must deal with everywhere. I think it’s been incredibly helpful for us since there’s three of us. I think it gives us extra visibility in the field.
Amy Engevik: There’s a lot of microaggressions and things that can hinder your career success. I think that we’ve definitely had that. And I think the academic landscape is changing a little bit now that more women are becoming principal investigators and then rising through the ranks of academia. So I think there’s a lot of hope for the future women, but I think it’s still quite challenging.
Kristen Engevik: Things do seem to be getting better as there are more women as faculty members in certain departments. Science is getting better as things progress. However, there are still a lot of difficulties in trying to get credit for what you do, and getting the promotions.
Mindy Engevik: We have a built-in sisterhood, if you will. So I’m always going to champion Amy or Kristen. If there’s an award that I can nominate them for, I’m always going to do it. If there’s something that I think they should apply for that maybe they hadn’t seen, I’m going to make sure I put it on the radar. I think that’s just incredibly helpful, having people that have your best interest in mind.
Every project we have is basically a big collaboration. We have a lot of papers from our postdocs where we are coauthors. Now, as principal investigators, we have a lot of papers together. And I think in the future you’ll be seeing a lot of coauthored publications from our group as well.
Lightning Round
Texting or talking?
KE: Talking
Favorite city in US besides the one you live in?
AE: Boston
Favorite breakfast?
ME: Biscuits and grits
Place you most want to travel?
KE: Antarctica
Favorite junk food?
AE: French fries
Favorite season?
ME: Fall
Favorite ice cream flavor?
KE: Black raspberry chip
Number of cups of coffee you drink per day?
AE: None, I like Diet Coke
Last movie you watched?
ME: Inside Out 2
If you weren’t a gastroenterologist, what would you be?
KE: National Park ranger
Best Halloween costume you ever wore?
AE: Princess Leia
Favorite type of music?
ME: ABBA
Favorite movie genre?
KE: Romantic comedies
Cat person or dog person?
AE: Neither, I like rabbits
Favorite sport?
ME: Surfing
What song do you have to sing along with when you hear it?
KE: Mama Mia
Introvert or extrovert?
AE: Introvert
Favorite holiday?
ME: Halloween
They all share the same genes—and job title.
Each has her own lab, working in different specialties. But if one sister needs the others, it’s reassuring to know they’re not far away.
“We have very different points of view. I’m interested in microbes. Amy’s really interested in myosin mediated trafficking and Kristen’s interested in viruses and purinergic signaling. It’s awesome that we can all work in the same field but have very different questions. And there’s so many questions that we can tackle,” said Mindy Engevik, the oldest of the trio.
If Mindy’s students need help with staining, she sends them to Amy’s lab. If they need help with calcium signaling and live cell imaging, she’ll send them to Kristen’s lab. “We interchange our expertise a lot,” said Mindy.
It’s nice to have a sister down the hall at work who can advise you on RNA sequencing analysis or immunofluorescence imaging, noted Amy Engevik. “You can ask them: ‘Can you just walk my student through this for a minute?’ Or, could they help with organoid cultures you don’t have time for right now?”
Kristen, who joined her older sisters at MUSC in 2024, observed that “having a little bit of the variety with our backgrounds and training really helps bring out the collaborative spirit of science.”
In an interview, the Engevik sisters spoke more about their familial network, their shared love of gastroenterology (GI) science, and how they’ve parlayed their expertise into other critical areas of research.
Growing up, did you ever think that you would choose similar career paths? How did you all become interested in GI research?
Mindy Engevik: As kids we were all interested in nature and the world around us. We all liked being outside. Amy and I were obsessed with rocks and classifying plants and rocks. We all had a general interest in science. But I personally didn’t think that all three of us would go into the same thing and that we’d be working together as adults.
Amy Engevik: Once we got into high school and college, we all became very close and we all majored in biology. That set the stage for our interest in science and our love of science. Then, we all kind of fell in love with the GI tract and chose postdocs that were GI focused. Since Mindy and I graduated a year apart, ultimately our goal was to form a lab and work together.
Kristen Engevik: I was interested in science when my sisters were both at college studying for biology and talking about the things they were learning in microbiology and physiology. But I don’t think until I joined the PhD program that I was ever like: ‘Oh yeah, we’re all going to be in science and it’s all going to be one big giant collaborative multi-lab collaboration.’
What do each of you love about the field of gastroenterology?
Mindy Engevik: At our heart, we’re all people that love problem solving. A fun fact about us is on Thursdays once a month, we do a puzzle competition here in Charleston. We’re really into it. But I think we genuinely like the problem-solving nature of the GI tract, and there’s so many diverse questions that you can answer.
Amy Engevik: I love that the scientific community in the GI community is so wonderful. They are very kind, helpful people. Some other fields are more competitive and more cutthroat. I feel like I have such a great network of people to reach out to if I have problems or questions. And I think other fields don’t have such a wonderful welcoming community that is very inclusive and dynamic.
Kristen Engevik: The nice thing with studying the GI tract is all things essentially lead to the gut. You can collaborate with other scientists and go into the gut-brain axis, or there’s the cardiovascular-gut axis and all these different places that you can also go, or different diseases that don’t necessarily seem to originate at the gut but have a lot of effects on the gut. There’s a lot of variation that we can do within GI.
Each of you has focused on a different area of digestive disease. Can each of you briefly discuss your areas of study and any findings or discoveries you’d like to highlight?
Mindy Engevik: My research focuses on microbial-host interactions. We’re really interested in how microbes colonize the gastrointestinal tract, how they interact with mucus – which I think is an important aspect of the gut that sometimes is overlooked – and how their metabolites really impact host health. One thing that I’m particularly proud of is we’ve really been starting to understand the neurotransmitters that bacteria generate and how they influence specific cells within the gut. It’s an exciting time to be doing both microbiology and gut physiology.
Amy Engevik: I study the host side of things; the gastric or the GI epithelium, and how a specific molecular motor contributes to trafficking in the GI tract. Recently, I’ve been going back to some of my PhD work in the stomach. In a high fat diet model, we’re finding that there are early metaplastic changes in the stomach. I think the stomach is very often overlooked within the GI tract. And I think it really sets the stage for the lower GI tract for the microbiome that colonizes the colon and the small intestine. I think that changes in the stomach really should come to the forefront of GI. Those changes have profound impacts on things like colorectal cancer and inflammatory bowel disease.
Kristen Engevik: I’m also more on the epithelial side with Amy. My new lab’s work is going to be focusing on understanding cell communications, specifically through extracellular purines, which is known as purinergic signaling, and understanding what the effects are during both homeostasis and disease, since it hasn’t been studied within the gut itself. From my work in postdoctoral training, we found that this communication is important for a lot of aspects, specifically during viral infection. But I have some preliminary data that shows it may also have an important role during disease, like colitis. My lab is interested in understanding what this epithelial communication is and are there ways to increase or decrease the signaling depending on the disease.
You’re all skilled in analyzing bioinformatics data. How do you apply this skill in your GI research?
Mindy Engevik: We all got our PhDs in systems biology and physiology, so we were forced to take computational analysis classes. I remember at the time thinking, ‘Oh, I’m probably not going to use a bunch of this.’ And then it really captured our attention. We realized how valuable it was and how much information you could glean.
We do a lot of work using publicly available data sets. I think there’s a wealth of information out there now with single cell sequencing data and bulk RNA sequencing data of different sites in the GI tract. It’s been a very valuable time to data mine and look especially at inflammatory bowel disease and colorectal cancer. We’ve been really focused on all our favorite genes of interest. I’ve been looking at a lot of the mucins and IBD (inflammatory bowel disease) and cancer. Amy’s been looking at Myosin-Vb and other myosin and binding partners like Rabs, and Kristen has been looking at purinergic signaling receptors.
All three of you recently worked together to identify a possible genetic driver of uterine corpus endometrial cancer, the fourth deadliest cancer in women. Where are you in the research process right now?
Mindy Engevik: Our mom was diagnosed with cancer, so we took quite a bit of time off to go to California to help her with her chemotherapy, surgery, and radiation. While we were there, we decided to do some computational analyses of cancers that affect women as our way to deal with this devastating disease. We were really fascinated to find that Myosin-Vb, which is Amy’s favorite gene of interest, was highly up-regulated in tumors from uterine and corpus endometrial cancer.
This was independent of the age of the patient, the stage of the cancer, the grade of the tumors. We figured out that the promoter region of the gene was hypomethylated, so it was having a higher expression. And that led to changes in metabolism and it linked very closely with what we were seeing in the gut, what Myosin-Vb was doing. We have some uterine cancer tumor cells in the lab that we’ve been growing and we’re going to really prove that it’s Myosin-Vb that’s driving some of these metabolism phenotypes. And the nice thing is at least there is a Myosin-Vb inhibitor available.
We also have a paper under review, identifying what Myosin-Vb is doing in cancer in the colon. So we’re excited to continue both the uterine cancer part but then also the colorectal cancer part using our same processes.
Amy Engevik: We’re going to be generating a mouse model that I think will be helpful since it’s in vivo. Sometimes things in vivo behave very differently than they do in vitro, so I think it’ll be a nice coupling of in vitro data with in vivo, taking that computational base and expanding it into more mechanistic studies and more experimental approaches where we can actually develop uterine cancer in the mice and then see if we can knock out Myosin-Vb specifically in that tissue and prevent it from either happening in the first place or decrease its pathogenesis.
What challenges have you faced in your career? How do you offer each other support?
Mindy Engevik: I think for any female scientists trying to have an independent career, there are some hurdles. An article in Nature recently stated that women receive less credit than their male counterparts and another article in Science demonstrated that women who are last authors on publications are cited less. That’s something that all women must deal with everywhere. I think it’s been incredibly helpful for us since there’s three of us. I think it gives us extra visibility in the field.
Amy Engevik: There’s a lot of microaggressions and things that can hinder your career success. I think that we’ve definitely had that. And I think the academic landscape is changing a little bit now that more women are becoming principal investigators and then rising through the ranks of academia. So I think there’s a lot of hope for the future women, but I think it’s still quite challenging.
Kristen Engevik: Things do seem to be getting better as there are more women as faculty members in certain departments. Science is getting better as things progress. However, there are still a lot of difficulties in trying to get credit for what you do, and getting the promotions.
Mindy Engevik: We have a built-in sisterhood, if you will. So I’m always going to champion Amy or Kristen. If there’s an award that I can nominate them for, I’m always going to do it. If there’s something that I think they should apply for that maybe they hadn’t seen, I’m going to make sure I put it on the radar. I think that’s just incredibly helpful, having people that have your best interest in mind.
Every project we have is basically a big collaboration. We have a lot of papers from our postdocs where we are coauthors. Now, as principal investigators, we have a lot of papers together. And I think in the future you’ll be seeing a lot of coauthored publications from our group as well.
Lightning Round
Texting or talking?
KE: Talking
Favorite city in US besides the one you live in?
AE: Boston
Favorite breakfast?
ME: Biscuits and grits
Place you most want to travel?
KE: Antarctica
Favorite junk food?
AE: French fries
Favorite season?
ME: Fall
Favorite ice cream flavor?
KE: Black raspberry chip
Number of cups of coffee you drink per day?
AE: None, I like Diet Coke
Last movie you watched?
ME: Inside Out 2
If you weren’t a gastroenterologist, what would you be?
KE: National Park ranger
Best Halloween costume you ever wore?
AE: Princess Leia
Favorite type of music?
ME: ABBA
Favorite movie genre?
KE: Romantic comedies
Cat person or dog person?
AE: Neither, I like rabbits
Favorite sport?
ME: Surfing
What song do you have to sing along with when you hear it?
KE: Mama Mia
Introvert or extrovert?
AE: Introvert
Favorite holiday?
ME: Halloween
Searching for the Optimal CRC Surveillance Test
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
Alarming Rise in Early-Onset GI Cancers Calls for Early Screening, Lifestyle Change
, said the authors of a JAMA review.
In the US, early-onset GI cancers are increasing faster than any other type of early-onset cancer, including breast cancer. The trend is not limited to colorectal cancer (CRC). Gastric, pancreatic, esophageal, as well as many biliary tract and appendix cancers, are also on the rise in young adults, Kimmie Ng, MD, MPH, and Thejus Jayakrishnan, MD, both with Dana-Farber Cancer Institute, Boston, noted in their article.
The increase in early-onset GI cancers follows a “birth cohort effect,” with generational variation in risk, suggesting a potential association with changes in environmental exposures, Ng explained in an accompanying JAMA podcast.
All these GI cancers link strongly to multiple modifiable risk factors, and it is a “top area of investigation to determine exactly what environmental exposures are at play,” Ng added.
For many of these GI cancers, obesity has been the “leading hypothesis” given that rising rates seem to parallel the increase in incidence of these early-onset GI cancers, Ng explained.
“But we also have evidence, particularly strong for colorectal cancer, that dietary patterns, such as consuming a Western diet, as well as sedentary behavior and lifestyles seem to be associated with a significantly higher risk of developing these cancers at an age under 50,” Ng said.
Rising Incidence
Globally, among early-onset GI cancers reported in 2022, CRC was the most common (54%), followed by gastric cancer (24%), esophageal cancer (13%), and pancreatic cancer (9%).
In the US in 2022, 20,805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric cancer, 2657 with early-onset pancreatic cancer, and 875 with early-onset esophageal cancer.
Since the mid-1990s, CRC among adults of all ages in the US declined by 1.3%-4.2% annually but early-onset CRC increased by roughly 2% per year in both men and women, and currently makes up about 14% of all CRC cases.
Early-onset pancreatic cancer and esophageal cancer each currently make up about 5% of all cases of these cancers in the US.
Between 2010 and 2019, the number of newly diagnosed cases of early-onset GI cancers rose by nearly about 15%, with Black, Hispanic, Indigenous ancestry, and women disproportionately affected, Ng and coauthors noted in a related review published in the British Journal of Surgery.
Modifiable and Nonmodifiable Risk Factors
Along with obesity and poor diet, other modifiable risk factors for early-onset GI cancers include sedentary lifestyle, cigarette smoking, and alcohol consumption.
Nonmodifiable risk factors include family history, hereditary cancer syndromes such as Lynch syndrome and inflammatory bowel disease.
Roughly 15%-30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2.
All individuals with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk, Ng and Jayakrishnan advised.
Treatment Challenges
Treatment for early-onset GI cancers is generally similar to later-onset GI cancers and prognosis for patients with early-onset GI cancers is “similar to or worse” than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection, the authors said.
Ng noted that younger cancer patients often face more challenges after diagnosis than older patients and benefit from multidisciplinary care, including referral for fertility counseling and preservation if appropriate, and psychosocial support.
“It is very difficult and challenging to receive a cancer diagnosis no matter what age you are, but when a person is diagnosed in their 20s, 30s, or 40s, there are unique challenges,” Ng said.
Studies have documented “much higher levels of psychosocial distress, depression and anxiety” in early-onset cancer patients, “and they also often experience more financial toxicity, disruptions in their education as well as their career and there may be fertility concerns,” Ng added.
Diagnostic Delays and Screening
Currently, screening is not recommended for most early-onset GI cancers — with the exception of CRC, with screening recommended for average-risk adults in the US starting at age 45.
Yet, despite this recommendation, fewer than 1 in 5 (19.7%) US adults aged 45-49 years were screened in 2021, indicating a significant gap in early detection efforts.
High-risk individuals, such as those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma, should begin CRC screening earlier, at an age determined by the specific risk factor.
“Studies have shown significant delays in diagnosis among younger patients. It’s important that prompt diagnosis happens so that these patients do not end up being diagnosed with advanced or metastatic stages of cancer, as they often are,” Ng said.
“Screening adherence is absolutely critical,” co-author Jayakrishnan added in a news release.
“We have strong evidence that colorectal cancer screening saves lives by reducing both the number of people who develop colorectal cancer and the number of people who die from it. Each missed screening is a lost opportunity to detect cancer early when it is more treatable, or to prevent cancer altogether by identifying and removing precancerous polyps,” Jayakrishnan said.This research had no funding. Ng reported receipt of nonfinancial support from Pharmavite, institutional grants from Janssen, and personal fees from Bayer, Seagen, GlaxoSmithKline, Pfizer, CytomX, Jazz Pharmaceuticals, Revolution Medicines, Redesign Health, AbbVie, Etiome, and CRICO. Ng is an associate editor of JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Jayakrishnan had no disclosures.
A version of this article appeared on Medscape.com.
, said the authors of a JAMA review.
In the US, early-onset GI cancers are increasing faster than any other type of early-onset cancer, including breast cancer. The trend is not limited to colorectal cancer (CRC). Gastric, pancreatic, esophageal, as well as many biliary tract and appendix cancers, are also on the rise in young adults, Kimmie Ng, MD, MPH, and Thejus Jayakrishnan, MD, both with Dana-Farber Cancer Institute, Boston, noted in their article.
The increase in early-onset GI cancers follows a “birth cohort effect,” with generational variation in risk, suggesting a potential association with changes in environmental exposures, Ng explained in an accompanying JAMA podcast.
All these GI cancers link strongly to multiple modifiable risk factors, and it is a “top area of investigation to determine exactly what environmental exposures are at play,” Ng added.
For many of these GI cancers, obesity has been the “leading hypothesis” given that rising rates seem to parallel the increase in incidence of these early-onset GI cancers, Ng explained.
“But we also have evidence, particularly strong for colorectal cancer, that dietary patterns, such as consuming a Western diet, as well as sedentary behavior and lifestyles seem to be associated with a significantly higher risk of developing these cancers at an age under 50,” Ng said.
Rising Incidence
Globally, among early-onset GI cancers reported in 2022, CRC was the most common (54%), followed by gastric cancer (24%), esophageal cancer (13%), and pancreatic cancer (9%).
In the US in 2022, 20,805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric cancer, 2657 with early-onset pancreatic cancer, and 875 with early-onset esophageal cancer.
Since the mid-1990s, CRC among adults of all ages in the US declined by 1.3%-4.2% annually but early-onset CRC increased by roughly 2% per year in both men and women, and currently makes up about 14% of all CRC cases.
Early-onset pancreatic cancer and esophageal cancer each currently make up about 5% of all cases of these cancers in the US.
Between 2010 and 2019, the number of newly diagnosed cases of early-onset GI cancers rose by nearly about 15%, with Black, Hispanic, Indigenous ancestry, and women disproportionately affected, Ng and coauthors noted in a related review published in the British Journal of Surgery.
Modifiable and Nonmodifiable Risk Factors
Along with obesity and poor diet, other modifiable risk factors for early-onset GI cancers include sedentary lifestyle, cigarette smoking, and alcohol consumption.
Nonmodifiable risk factors include family history, hereditary cancer syndromes such as Lynch syndrome and inflammatory bowel disease.
Roughly 15%-30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2.
All individuals with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk, Ng and Jayakrishnan advised.
Treatment Challenges
Treatment for early-onset GI cancers is generally similar to later-onset GI cancers and prognosis for patients with early-onset GI cancers is “similar to or worse” than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection, the authors said.
Ng noted that younger cancer patients often face more challenges after diagnosis than older patients and benefit from multidisciplinary care, including referral for fertility counseling and preservation if appropriate, and psychosocial support.
“It is very difficult and challenging to receive a cancer diagnosis no matter what age you are, but when a person is diagnosed in their 20s, 30s, or 40s, there are unique challenges,” Ng said.
Studies have documented “much higher levels of psychosocial distress, depression and anxiety” in early-onset cancer patients, “and they also often experience more financial toxicity, disruptions in their education as well as their career and there may be fertility concerns,” Ng added.
Diagnostic Delays and Screening
Currently, screening is not recommended for most early-onset GI cancers — with the exception of CRC, with screening recommended for average-risk adults in the US starting at age 45.
Yet, despite this recommendation, fewer than 1 in 5 (19.7%) US adults aged 45-49 years were screened in 2021, indicating a significant gap in early detection efforts.
High-risk individuals, such as those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma, should begin CRC screening earlier, at an age determined by the specific risk factor.
“Studies have shown significant delays in diagnosis among younger patients. It’s important that prompt diagnosis happens so that these patients do not end up being diagnosed with advanced or metastatic stages of cancer, as they often are,” Ng said.
“Screening adherence is absolutely critical,” co-author Jayakrishnan added in a news release.
“We have strong evidence that colorectal cancer screening saves lives by reducing both the number of people who develop colorectal cancer and the number of people who die from it. Each missed screening is a lost opportunity to detect cancer early when it is more treatable, or to prevent cancer altogether by identifying and removing precancerous polyps,” Jayakrishnan said.This research had no funding. Ng reported receipt of nonfinancial support from Pharmavite, institutional grants from Janssen, and personal fees from Bayer, Seagen, GlaxoSmithKline, Pfizer, CytomX, Jazz Pharmaceuticals, Revolution Medicines, Redesign Health, AbbVie, Etiome, and CRICO. Ng is an associate editor of JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Jayakrishnan had no disclosures.
A version of this article appeared on Medscape.com.
, said the authors of a JAMA review.
In the US, early-onset GI cancers are increasing faster than any other type of early-onset cancer, including breast cancer. The trend is not limited to colorectal cancer (CRC). Gastric, pancreatic, esophageal, as well as many biliary tract and appendix cancers, are also on the rise in young adults, Kimmie Ng, MD, MPH, and Thejus Jayakrishnan, MD, both with Dana-Farber Cancer Institute, Boston, noted in their article.
The increase in early-onset GI cancers follows a “birth cohort effect,” with generational variation in risk, suggesting a potential association with changes in environmental exposures, Ng explained in an accompanying JAMA podcast.
All these GI cancers link strongly to multiple modifiable risk factors, and it is a “top area of investigation to determine exactly what environmental exposures are at play,” Ng added.
For many of these GI cancers, obesity has been the “leading hypothesis” given that rising rates seem to parallel the increase in incidence of these early-onset GI cancers, Ng explained.
“But we also have evidence, particularly strong for colorectal cancer, that dietary patterns, such as consuming a Western diet, as well as sedentary behavior and lifestyles seem to be associated with a significantly higher risk of developing these cancers at an age under 50,” Ng said.
Rising Incidence
Globally, among early-onset GI cancers reported in 2022, CRC was the most common (54%), followed by gastric cancer (24%), esophageal cancer (13%), and pancreatic cancer (9%).
In the US in 2022, 20,805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric cancer, 2657 with early-onset pancreatic cancer, and 875 with early-onset esophageal cancer.
Since the mid-1990s, CRC among adults of all ages in the US declined by 1.3%-4.2% annually but early-onset CRC increased by roughly 2% per year in both men and women, and currently makes up about 14% of all CRC cases.
Early-onset pancreatic cancer and esophageal cancer each currently make up about 5% of all cases of these cancers in the US.
Between 2010 and 2019, the number of newly diagnosed cases of early-onset GI cancers rose by nearly about 15%, with Black, Hispanic, Indigenous ancestry, and women disproportionately affected, Ng and coauthors noted in a related review published in the British Journal of Surgery.
Modifiable and Nonmodifiable Risk Factors
Along with obesity and poor diet, other modifiable risk factors for early-onset GI cancers include sedentary lifestyle, cigarette smoking, and alcohol consumption.
Nonmodifiable risk factors include family history, hereditary cancer syndromes such as Lynch syndrome and inflammatory bowel disease.
Roughly 15%-30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2.
All individuals with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk, Ng and Jayakrishnan advised.
Treatment Challenges
Treatment for early-onset GI cancers is generally similar to later-onset GI cancers and prognosis for patients with early-onset GI cancers is “similar to or worse” than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection, the authors said.
Ng noted that younger cancer patients often face more challenges after diagnosis than older patients and benefit from multidisciplinary care, including referral for fertility counseling and preservation if appropriate, and psychosocial support.
“It is very difficult and challenging to receive a cancer diagnosis no matter what age you are, but when a person is diagnosed in their 20s, 30s, or 40s, there are unique challenges,” Ng said.
Studies have documented “much higher levels of psychosocial distress, depression and anxiety” in early-onset cancer patients, “and they also often experience more financial toxicity, disruptions in their education as well as their career and there may be fertility concerns,” Ng added.
Diagnostic Delays and Screening
Currently, screening is not recommended for most early-onset GI cancers — with the exception of CRC, with screening recommended for average-risk adults in the US starting at age 45.
Yet, despite this recommendation, fewer than 1 in 5 (19.7%) US adults aged 45-49 years were screened in 2021, indicating a significant gap in early detection efforts.
High-risk individuals, such as those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma, should begin CRC screening earlier, at an age determined by the specific risk factor.
“Studies have shown significant delays in diagnosis among younger patients. It’s important that prompt diagnosis happens so that these patients do not end up being diagnosed with advanced or metastatic stages of cancer, as they often are,” Ng said.
“Screening adherence is absolutely critical,” co-author Jayakrishnan added in a news release.
“We have strong evidence that colorectal cancer screening saves lives by reducing both the number of people who develop colorectal cancer and the number of people who die from it. Each missed screening is a lost opportunity to detect cancer early when it is more treatable, or to prevent cancer altogether by identifying and removing precancerous polyps,” Jayakrishnan said.This research had no funding. Ng reported receipt of nonfinancial support from Pharmavite, institutional grants from Janssen, and personal fees from Bayer, Seagen, GlaxoSmithKline, Pfizer, CytomX, Jazz Pharmaceuticals, Revolution Medicines, Redesign Health, AbbVie, Etiome, and CRICO. Ng is an associate editor of JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Jayakrishnan had no disclosures.
A version of this article appeared on Medscape.com.
Colonoscopy Costs Rise When Private Equity Acquires GI Practices, but Quality Does Not
Price increases ranged from about 5% to about 7%.
In view of the growing trend to such acquisitions, policy makers should monitor the impact of PE investment in medical practices, according to researchers led by health economist Daniel R. Arnold, PhD, of the Department of Health Services, Policy & Practice in the School of Public Health at Brown University in Providence, Rhode Island. “In a previous study of ours, gastroenterology stood out as a particularly attractive specialty to private equity,” Arnold told GI & Hepatology News.
Published in JAMA Health Forum, the economic evaluation of more than 1.1 million patients and 1.3 million colonoscopies concluded that PE acquisitions of GI sites are difficult to justify.
The Study
This difference-in-differences event study and economic evaluation analyzed data from US GI practices acquired by PE firms from 2015 to 2021. Commercial insurance claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021, with all data analyzed from April to September 2024.
The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality, as defined by polyp detection, incomplete colonoscopies, and four adverse event measures: cardiovascular, serious and nonserious GI events, and any other adverse events.
The mean age of patients was 47.1 years, and 47.8% were men. The sample included 718, 851 colonoscopies conducted by 1494 physicians in 590, 900 patients across 1240 PE-acquired practice sites and 637, 990 control colonoscopies conducted by 2550 physicians in 527,380 patients across 2657 independent practice sites.
Among the findings:
- Colonoscopy prices at PE-acquired sites increased by 4.5% (95% CI, 2.5-6.6; P < .001) vs independent practices. That increase was much lower than that reported by Singh and colleagues for .
- The estimated price increase was 6.7% (95% CI, 4.2-9.3; P < .001) when only colonoscopies at PE practices with market shares above the 75th percentile (24.4%) in 2021 were considered. Both increases were in line with other research, Arnold said.
- Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3-19.4; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively. These measures, however, were already increasing before PE acquisition.
- No statistically significant associations were detected for the six quality measures analyzed.
Could such cost-raising acquisitions potentially be blocked by concerned regulators?
“No. Generally the purchases are at prices below what would require notification to federal authorities,” Arnold said. “The Department of Justice/Federal Trade Commission hinted at being willing to look at serial acquisitions in their 2023 Merger Guidelines, but until that happens, these will likely continue to fly under the radar.”
Still, as evidence of PE-associated poorer quality outcomes as well as clinician burnout continues to emerge, Arnold added, “I would advise physicians who get buyout offers from PE to educate themselves on what could happen to patients and staff if they choose to sell.”
Offering an outsider’s perspective on the study, health economist Atul Gupta, PhD, an assistant professor of healthcare management in the Wharton School at the University of Pennsylvania in Philadelphia, called it an “excellent addition to the developing literature examining the effects of private equity ownership of healthcare providers.” Very few studies have examined the effects on prices and quality for the same set of deals and providers. “This is important because we want to be able to do an apples-to-apples comparison of the effects on both outcomes before judging PE ownership,” he told GI & Hepatology News.
In an accompanying editorial , primary care physician Jane M. Zhu, MD, an associate professor of medicine at Oregon Health & Science University in Portland, Oregon, and not involved in the commercial-insurance-based study, said one interpretation of the findings may be that PE acquisition focuses on reducing inefficiencies, improving access by expanding practice capacity, and increasing throughput. “Another interpretation may be that PE acquisition is focused on the strategic exploitation of market and pricing power. The latter may have less of an impact on clinical measures like quality of care, but potentially, both strategies could be at play.”
Since this analysis focused on the commercial population, understanding how patient demographics may change after PE acquisition is a future avenue for exploration. “For instance, a potential explanation for both the price and utilization shifts might be if payer mix shifted toward more commercially insured patients at the expense of Medicaid or Medicare patients,” she wrote.
Zhu added that the impact of PE on prices and spending, by now replicated across different settings and specialties, is far clearer than the effect of PE on access and quality. “The analysis by Arnold et al is a welcome addition to the literature, generating important questions for future study and transparent monitoring as investor-owners become increasingly influential in healthcare.”
Going forward, said Gupta, an open question is whether the harmful effects of PE ownership of practices are differentially worse than those of other corporate entities such as insurers and hospital systems.
“There are reasons to believe that PE could be worse in theory. For example, their short-term investment horizon may force them to take measures that others will not as well as avoid investing into capital improvements that have a long-run payoff,” he said. “Their uniquely high dependence on debt and unbundling of real estate can severely hurt financial solvency of providers.” But high-quality evidence is lacking to compare the effects from these two distinct forms of corporatization.
The trend away from individual private practice is a reality, Arnold said. “The administrative burden on solo docs is becoming too much and physicians just seem to want to treat patients and not deal with it. So the options at this point really become selling to a hospital system or private equity.”
This study was funded by a grant from the philanthropic foundation Arnold Ventures (no family relation to Daniel Arnold).
Arnold reported receiving grants from Arnold Ventures during the conduct of the study. Gupta had no competing interests to declare. Zhu reported receiving grants from the Agency for Healthcare Research and Quality during the submitted work and from the National Institutes of Health, National Institute for Health Care Management Foundation, and American Psychological Association, as well as personal fees from Cambia outside the submitted work.
A version of this article appeared on Medscape.com.
Price increases ranged from about 5% to about 7%.
In view of the growing trend to such acquisitions, policy makers should monitor the impact of PE investment in medical practices, according to researchers led by health economist Daniel R. Arnold, PhD, of the Department of Health Services, Policy & Practice in the School of Public Health at Brown University in Providence, Rhode Island. “In a previous study of ours, gastroenterology stood out as a particularly attractive specialty to private equity,” Arnold told GI & Hepatology News.
Published in JAMA Health Forum, the economic evaluation of more than 1.1 million patients and 1.3 million colonoscopies concluded that PE acquisitions of GI sites are difficult to justify.
The Study
This difference-in-differences event study and economic evaluation analyzed data from US GI practices acquired by PE firms from 2015 to 2021. Commercial insurance claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021, with all data analyzed from April to September 2024.
The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality, as defined by polyp detection, incomplete colonoscopies, and four adverse event measures: cardiovascular, serious and nonserious GI events, and any other adverse events.
The mean age of patients was 47.1 years, and 47.8% were men. The sample included 718, 851 colonoscopies conducted by 1494 physicians in 590, 900 patients across 1240 PE-acquired practice sites and 637, 990 control colonoscopies conducted by 2550 physicians in 527,380 patients across 2657 independent practice sites.
Among the findings:
- Colonoscopy prices at PE-acquired sites increased by 4.5% (95% CI, 2.5-6.6; P < .001) vs independent practices. That increase was much lower than that reported by Singh and colleagues for .
- The estimated price increase was 6.7% (95% CI, 4.2-9.3; P < .001) when only colonoscopies at PE practices with market shares above the 75th percentile (24.4%) in 2021 were considered. Both increases were in line with other research, Arnold said.
- Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3-19.4; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively. These measures, however, were already increasing before PE acquisition.
- No statistically significant associations were detected for the six quality measures analyzed.
Could such cost-raising acquisitions potentially be blocked by concerned regulators?
“No. Generally the purchases are at prices below what would require notification to federal authorities,” Arnold said. “The Department of Justice/Federal Trade Commission hinted at being willing to look at serial acquisitions in their 2023 Merger Guidelines, but until that happens, these will likely continue to fly under the radar.”
Still, as evidence of PE-associated poorer quality outcomes as well as clinician burnout continues to emerge, Arnold added, “I would advise physicians who get buyout offers from PE to educate themselves on what could happen to patients and staff if they choose to sell.”
Offering an outsider’s perspective on the study, health economist Atul Gupta, PhD, an assistant professor of healthcare management in the Wharton School at the University of Pennsylvania in Philadelphia, called it an “excellent addition to the developing literature examining the effects of private equity ownership of healthcare providers.” Very few studies have examined the effects on prices and quality for the same set of deals and providers. “This is important because we want to be able to do an apples-to-apples comparison of the effects on both outcomes before judging PE ownership,” he told GI & Hepatology News.
In an accompanying editorial , primary care physician Jane M. Zhu, MD, an associate professor of medicine at Oregon Health & Science University in Portland, Oregon, and not involved in the commercial-insurance-based study, said one interpretation of the findings may be that PE acquisition focuses on reducing inefficiencies, improving access by expanding practice capacity, and increasing throughput. “Another interpretation may be that PE acquisition is focused on the strategic exploitation of market and pricing power. The latter may have less of an impact on clinical measures like quality of care, but potentially, both strategies could be at play.”
Since this analysis focused on the commercial population, understanding how patient demographics may change after PE acquisition is a future avenue for exploration. “For instance, a potential explanation for both the price and utilization shifts might be if payer mix shifted toward more commercially insured patients at the expense of Medicaid or Medicare patients,” she wrote.
Zhu added that the impact of PE on prices and spending, by now replicated across different settings and specialties, is far clearer than the effect of PE on access and quality. “The analysis by Arnold et al is a welcome addition to the literature, generating important questions for future study and transparent monitoring as investor-owners become increasingly influential in healthcare.”
Going forward, said Gupta, an open question is whether the harmful effects of PE ownership of practices are differentially worse than those of other corporate entities such as insurers and hospital systems.
“There are reasons to believe that PE could be worse in theory. For example, their short-term investment horizon may force them to take measures that others will not as well as avoid investing into capital improvements that have a long-run payoff,” he said. “Their uniquely high dependence on debt and unbundling of real estate can severely hurt financial solvency of providers.” But high-quality evidence is lacking to compare the effects from these two distinct forms of corporatization.
The trend away from individual private practice is a reality, Arnold said. “The administrative burden on solo docs is becoming too much and physicians just seem to want to treat patients and not deal with it. So the options at this point really become selling to a hospital system or private equity.”
This study was funded by a grant from the philanthropic foundation Arnold Ventures (no family relation to Daniel Arnold).
Arnold reported receiving grants from Arnold Ventures during the conduct of the study. Gupta had no competing interests to declare. Zhu reported receiving grants from the Agency for Healthcare Research and Quality during the submitted work and from the National Institutes of Health, National Institute for Health Care Management Foundation, and American Psychological Association, as well as personal fees from Cambia outside the submitted work.
A version of this article appeared on Medscape.com.
Price increases ranged from about 5% to about 7%.
In view of the growing trend to such acquisitions, policy makers should monitor the impact of PE investment in medical practices, according to researchers led by health economist Daniel R. Arnold, PhD, of the Department of Health Services, Policy & Practice in the School of Public Health at Brown University in Providence, Rhode Island. “In a previous study of ours, gastroenterology stood out as a particularly attractive specialty to private equity,” Arnold told GI & Hepatology News.
Published in JAMA Health Forum, the economic evaluation of more than 1.1 million patients and 1.3 million colonoscopies concluded that PE acquisitions of GI sites are difficult to justify.
The Study
This difference-in-differences event study and economic evaluation analyzed data from US GI practices acquired by PE firms from 2015 to 2021. Commercial insurance claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021, with all data analyzed from April to September 2024.
The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality, as defined by polyp detection, incomplete colonoscopies, and four adverse event measures: cardiovascular, serious and nonserious GI events, and any other adverse events.
The mean age of patients was 47.1 years, and 47.8% were men. The sample included 718, 851 colonoscopies conducted by 1494 physicians in 590, 900 patients across 1240 PE-acquired practice sites and 637, 990 control colonoscopies conducted by 2550 physicians in 527,380 patients across 2657 independent practice sites.
Among the findings:
- Colonoscopy prices at PE-acquired sites increased by 4.5% (95% CI, 2.5-6.6; P < .001) vs independent practices. That increase was much lower than that reported by Singh and colleagues for .
- The estimated price increase was 6.7% (95% CI, 4.2-9.3; P < .001) when only colonoscopies at PE practices with market shares above the 75th percentile (24.4%) in 2021 were considered. Both increases were in line with other research, Arnold said.
- Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3-19.4; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively. These measures, however, were already increasing before PE acquisition.
- No statistically significant associations were detected for the six quality measures analyzed.
Could such cost-raising acquisitions potentially be blocked by concerned regulators?
“No. Generally the purchases are at prices below what would require notification to federal authorities,” Arnold said. “The Department of Justice/Federal Trade Commission hinted at being willing to look at serial acquisitions in their 2023 Merger Guidelines, but until that happens, these will likely continue to fly under the radar.”
Still, as evidence of PE-associated poorer quality outcomes as well as clinician burnout continues to emerge, Arnold added, “I would advise physicians who get buyout offers from PE to educate themselves on what could happen to patients and staff if they choose to sell.”
Offering an outsider’s perspective on the study, health economist Atul Gupta, PhD, an assistant professor of healthcare management in the Wharton School at the University of Pennsylvania in Philadelphia, called it an “excellent addition to the developing literature examining the effects of private equity ownership of healthcare providers.” Very few studies have examined the effects on prices and quality for the same set of deals and providers. “This is important because we want to be able to do an apples-to-apples comparison of the effects on both outcomes before judging PE ownership,” he told GI & Hepatology News.
In an accompanying editorial , primary care physician Jane M. Zhu, MD, an associate professor of medicine at Oregon Health & Science University in Portland, Oregon, and not involved in the commercial-insurance-based study, said one interpretation of the findings may be that PE acquisition focuses on reducing inefficiencies, improving access by expanding practice capacity, and increasing throughput. “Another interpretation may be that PE acquisition is focused on the strategic exploitation of market and pricing power. The latter may have less of an impact on clinical measures like quality of care, but potentially, both strategies could be at play.”
Since this analysis focused on the commercial population, understanding how patient demographics may change after PE acquisition is a future avenue for exploration. “For instance, a potential explanation for both the price and utilization shifts might be if payer mix shifted toward more commercially insured patients at the expense of Medicaid or Medicare patients,” she wrote.
Zhu added that the impact of PE on prices and spending, by now replicated across different settings and specialties, is far clearer than the effect of PE on access and quality. “The analysis by Arnold et al is a welcome addition to the literature, generating important questions for future study and transparent monitoring as investor-owners become increasingly influential in healthcare.”
Going forward, said Gupta, an open question is whether the harmful effects of PE ownership of practices are differentially worse than those of other corporate entities such as insurers and hospital systems.
“There are reasons to believe that PE could be worse in theory. For example, their short-term investment horizon may force them to take measures that others will not as well as avoid investing into capital improvements that have a long-run payoff,” he said. “Their uniquely high dependence on debt and unbundling of real estate can severely hurt financial solvency of providers.” But high-quality evidence is lacking to compare the effects from these two distinct forms of corporatization.
The trend away from individual private practice is a reality, Arnold said. “The administrative burden on solo docs is becoming too much and physicians just seem to want to treat patients and not deal with it. So the options at this point really become selling to a hospital system or private equity.”
This study was funded by a grant from the philanthropic foundation Arnold Ventures (no family relation to Daniel Arnold).
Arnold reported receiving grants from Arnold Ventures during the conduct of the study. Gupta had no competing interests to declare. Zhu reported receiving grants from the Agency for Healthcare Research and Quality during the submitted work and from the National Institutes of Health, National Institute for Health Care Management Foundation, and American Psychological Association, as well as personal fees from Cambia outside the submitted work.
A version of this article appeared on Medscape.com.
Eradicating H Pylori Cuts Long-Term Gastric Cancer Risk
Helicobacter pylori (HP) eradication reduced the risk of gastric noncardia adenocarcinoma in five Scandinavian countries, a population-based study in Gastroenterology reported. Risk became virtually similar to the background population from 11 years after treatment onward.
HP infection of the stomach is the main established risk factor for this tumor, but not much was known about the impact of eradication on long-term risk, particularly in Western populations, noted investigators led by Jesper Lagengren, MD, a gastrointestinal surgeon and professor at the Karolinksa Institutet in Stockholm, Sweden. Research with longer follow-up has reported contradictory results.
The study cohort included all adults treated for HP from 1995 to 2019 in Denmark, Finland, Iceland, Norway, and Sweden. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by comparing the gastric noncardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country.
The 659,592 treated participants were 54.3% women, 61.5% age 50 or younger, and had no serious comorbidities. They contributed to 5,480,873 person-years at risk with a mean follow-up of 8.3 years. Treatment consisted of a minimum one-week antibiotic regimen with two of amoxicillin, clarithromycin, or metronidazole, in combination with a proton pump inhibitor. This is the recommended regimen in the Nordic countries, where it achieves successful eradication in 90% of infected individuals.
Among these patients, 1311 developed gastric noncardia adenocarcinoma. Over as many as 24 years of follow-up, the SIR in treated HP patients was initially significantly higher than in the background population at 2.27 (95% confidence interval [CI], 2.10-2.44) at 1 to 5 years after treatment. By 6 to 10 years the SIR had dropped to 1.34 (1.21-1.48) and by 11 to 24 years it further fell to 1.11 (.98-1.27). In terms of observed vs expected cases, that translated to 702 vs 310 at 1 to 5 years, 374 vs 270 at 6 to 10 years, and 235 vs 211 from 11 to 24 years.
The results of the Nordic study align with systematic reviews from Asian populations indicating that eradication reduces the risk of gastric cancer, the authors said.
They noted gastric HP infection is the most prevalent bacterial infection worldwide, found in approximately 50% of the global population but with striking geographical variations in prevalence and virulence. The highest prevalence (>80%) and virulence are found in countries with low socioeconomic status and sanitation standards such as regions in Africa and Western Asia.
Gastric adenocarcinoma is the fourth-commonest cause of cancer-related death globally, leading to 660,000 deaths in 2022.
Lagergren and colleagues cited the need for research to delineate high-risk individuals who would benefit rom HP screening and eradication.
This study was supported by the Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, and Stockholm Cancer Society. The authors had no conflicts of interest to disclose.
Helicobacter pylori (HP) eradication reduced the risk of gastric noncardia adenocarcinoma in five Scandinavian countries, a population-based study in Gastroenterology reported. Risk became virtually similar to the background population from 11 years after treatment onward.
HP infection of the stomach is the main established risk factor for this tumor, but not much was known about the impact of eradication on long-term risk, particularly in Western populations, noted investigators led by Jesper Lagengren, MD, a gastrointestinal surgeon and professor at the Karolinksa Institutet in Stockholm, Sweden. Research with longer follow-up has reported contradictory results.
The study cohort included all adults treated for HP from 1995 to 2019 in Denmark, Finland, Iceland, Norway, and Sweden. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by comparing the gastric noncardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country.
The 659,592 treated participants were 54.3% women, 61.5% age 50 or younger, and had no serious comorbidities. They contributed to 5,480,873 person-years at risk with a mean follow-up of 8.3 years. Treatment consisted of a minimum one-week antibiotic regimen with two of amoxicillin, clarithromycin, or metronidazole, in combination with a proton pump inhibitor. This is the recommended regimen in the Nordic countries, where it achieves successful eradication in 90% of infected individuals.
Among these patients, 1311 developed gastric noncardia adenocarcinoma. Over as many as 24 years of follow-up, the SIR in treated HP patients was initially significantly higher than in the background population at 2.27 (95% confidence interval [CI], 2.10-2.44) at 1 to 5 years after treatment. By 6 to 10 years the SIR had dropped to 1.34 (1.21-1.48) and by 11 to 24 years it further fell to 1.11 (.98-1.27). In terms of observed vs expected cases, that translated to 702 vs 310 at 1 to 5 years, 374 vs 270 at 6 to 10 years, and 235 vs 211 from 11 to 24 years.
The results of the Nordic study align with systematic reviews from Asian populations indicating that eradication reduces the risk of gastric cancer, the authors said.
They noted gastric HP infection is the most prevalent bacterial infection worldwide, found in approximately 50% of the global population but with striking geographical variations in prevalence and virulence. The highest prevalence (>80%) and virulence are found in countries with low socioeconomic status and sanitation standards such as regions in Africa and Western Asia.
Gastric adenocarcinoma is the fourth-commonest cause of cancer-related death globally, leading to 660,000 deaths in 2022.
Lagergren and colleagues cited the need for research to delineate high-risk individuals who would benefit rom HP screening and eradication.
This study was supported by the Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, and Stockholm Cancer Society. The authors had no conflicts of interest to disclose.
Helicobacter pylori (HP) eradication reduced the risk of gastric noncardia adenocarcinoma in five Scandinavian countries, a population-based study in Gastroenterology reported. Risk became virtually similar to the background population from 11 years after treatment onward.
HP infection of the stomach is the main established risk factor for this tumor, but not much was known about the impact of eradication on long-term risk, particularly in Western populations, noted investigators led by Jesper Lagengren, MD, a gastrointestinal surgeon and professor at the Karolinksa Institutet in Stockholm, Sweden. Research with longer follow-up has reported contradictory results.
The study cohort included all adults treated for HP from 1995 to 2019 in Denmark, Finland, Iceland, Norway, and Sweden. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by comparing the gastric noncardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country.
The 659,592 treated participants were 54.3% women, 61.5% age 50 or younger, and had no serious comorbidities. They contributed to 5,480,873 person-years at risk with a mean follow-up of 8.3 years. Treatment consisted of a minimum one-week antibiotic regimen with two of amoxicillin, clarithromycin, or metronidazole, in combination with a proton pump inhibitor. This is the recommended regimen in the Nordic countries, where it achieves successful eradication in 90% of infected individuals.
Among these patients, 1311 developed gastric noncardia adenocarcinoma. Over as many as 24 years of follow-up, the SIR in treated HP patients was initially significantly higher than in the background population at 2.27 (95% confidence interval [CI], 2.10-2.44) at 1 to 5 years after treatment. By 6 to 10 years the SIR had dropped to 1.34 (1.21-1.48) and by 11 to 24 years it further fell to 1.11 (.98-1.27). In terms of observed vs expected cases, that translated to 702 vs 310 at 1 to 5 years, 374 vs 270 at 6 to 10 years, and 235 vs 211 from 11 to 24 years.
The results of the Nordic study align with systematic reviews from Asian populations indicating that eradication reduces the risk of gastric cancer, the authors said.
They noted gastric HP infection is the most prevalent bacterial infection worldwide, found in approximately 50% of the global population but with striking geographical variations in prevalence and virulence. The highest prevalence (>80%) and virulence are found in countries with low socioeconomic status and sanitation standards such as regions in Africa and Western Asia.
Gastric adenocarcinoma is the fourth-commonest cause of cancer-related death globally, leading to 660,000 deaths in 2022.
Lagergren and colleagues cited the need for research to delineate high-risk individuals who would benefit rom HP screening and eradication.
This study was supported by the Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, and Stockholm Cancer Society. The authors had no conflicts of interest to disclose.
FROM GASTROENTEROLOGY
Can Modulation of the Microbiome Improve Cancer Immunotherapy Tolerance and Efficacy?
WASHINGTON — For years, oncologist Jonathan Peled, MD, PhD, and his colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City have been documenting gut microbiota disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its role in frequent and potentially fatal bloodstream infections (BSIs) in the first 100 days after transplant.
, and at the Gut Microbiota for Health (GMFH) World Summit 2025, Peled shared two new findings.
In one study, his team found that sucrose can exacerbate antibiotic-induced microbiome injury in patients undergoing allo-HSCT — a finding that “raises the question of whether our dietary recommendations [for] allo-HSCT patients are correct,” said Peled, assistant attending at MSKCC, during a session on the gut microbiome and oncology.
And in another study, they found that a rationally designed probiotic formulation may help lower the incidence of bacterial BSIs. In December 2024, the probiotic formulation (SER-155, Seres Therapeutics, Inc.) was granted breakthrough therapy designation by the FDA.
With immunotherapies more broadly, researchers are increasingly looking at diet and modulation of the microbiome to improve both treatment tolerance and efficacy, experts said at the meeting convened by the AGA and the European Society of Neurogastroenterology and Motility.
“Cancer patients and caregivers are asking, ‘What should I eat?’” said Carrie Daniel-MacDougall, PhD, MPH, a nutritional epidemiologist at the University of Texas MD Anderson Cancer Center in Houston. “They’re not just focused on side effects — they want a good outcome for their treatment, and they’re exploring a lot of dietary strategies [for which there] is not a lot of evidence.”
Clinicians are challenged by the fact that “we don’t typically collect dietary data in clinical trials of cancer drugs,” leaving them to extrapolate from evidence-based diet guidelines for cancer prevention, Daniel-MacDougall said.
But “I think that’s starting to shift,” she said, with the microbiome being increasingly recognized for its potential influences on therapeutic response and clinical trials underway looking at “a healthy dietary pattern not just for prevention but survival.”
Diet and Probiotics After allo-HSCT
The patterns of microbiota disruption during allo-HSCT — a procedure that includes antibiotic administration, chemotherapy, and sometimes irradiation — are characterized by loss of diversity and the expansion of potentially pathogenic organisms, most commonly Enterococcus, said Peled.
This has been demonstrated across transplantation centers. In a multicenter, international study published in 2020, the patterns of microbiota disruption and their impact on mortality were similar across MSK and other transplantation centers, with higher diversity of intestinal microbiota associated with lower mortality.
Other studies have shown that Enterococcus domination alone (defined arbitrarily as > 30% of fecal microbial composition) is associated with graft vs host disease and higher mortality after allo-HSCT and that intestinal domination by Proteobacteria coincides temporally with BSIs, he said.
Autologous fecal microbiota transplantation (FMT) has been shown to largely restore the microbiota composition the patient had before antibiotic treatment and allo-HSCT, he said, making fecal sample banking and posttreatment FMT a potential approach for reconstituting the gut microbiome and improving outcomes.
But “lately we’ve been very interested in diet for modulating [harmful] patterns” in the microbiome composition, Peled said.
In the new study suggesting a role for sugar avoidance, published last year as a bioRxiv preprint, Peled and his colleagues collected real-time dietary intake data (40,702 food entries) from 173 patients hospitalized for several weeks for allo-HSCT at MSK and analyzed it alongside longitudinally collected fecal samples. They used a Bayesian mixed-effects model to identify dietary components that may correlate with microbial disruption.
“What jumped out as very predictive of a low diversity fecal sample [and expansion of Enterococcus] in the 2 days prior to collection was the interaction between antibiotics and the consumption of sweets” — foods rich in simple sugars, Peled said. The relationship between sugar and the microbiome occurred only during periods of antibiotic exposure.
“And it was particularly perplexing because the foods that fall into the ‘sweets’ category are foods we encourage people to eat clinically when they’re not feeling well and food intake drops dramatically,” he said. This includes foods like nutritional drinks or shakes, Italian ice, gelatin dessert, and sports drinks.
(In a mouse model of post-antibiotic Enterococcus expansion, Peled and his co-investigators then validated the findings and ruled out the impact of any reductions in fiber.)
In addition to possibly revising dietary recommendations for patients undergoing allo-HSCT, the findings raise the question of whether avoiding sugar intake while on antibiotics, in general, is a way to mitigate antibiotic-induced dysbiosis, he said.
To test the role of probiotics, Peled and colleagues collaborated with Seres Therapeutics on a phase 1b trial of an oral combination (SER-155) of 16 fermented strains “selected rationally,” he said, for their ability to decolonize gut pathogens, improve gut barrier function (in vitro), and reduce gut inflammation and local immune activation.
After a safety lead-in, patients were randomized to receive SER-155 (20) or placebo (14) three times — prior to transplant, upon neutrophil engraftment (with vancomycin “conditioning”), and after transplant. “The strains succeeded in grafting in the [gastrointestinal] GI tract…and some of them persisted all the way through to day 100,” Peled said.
The incidence of pathogen domination was substantially lower in the probiotic recipients compared to an MSK historical control cohort, and the incidence of BSIs was significantly lower compared to the placebo arm (10% vs 43%, respectively, representing a 77% relative risk reduction), he said.
Diet and Immunotherapy Response: Trials at MD Anderson
One of the first trials Daniel-MacDougall launched at MD Anderson on diet and the microbiome randomized 55 patients who were obese and had a history of colorectal cancer or precancerous polyps to add a cup of beans to their usual diet or to continue their usual diet without beans. There was a crossover at 8 weeks in the 16-week BE GONE trial; stool and fasting blood were collected every 4 weeks.
“Beans are a prebiotic super-house in my opinion, and they’re also something this population would avoid,” said Daniel-MacDougall, associate professor in the department of epidemiology at MD Anderson and faculty director of the Bionutrition Research Core and Research Kitchen.
“We saw a modest increase in alpha diversity [in the intervention group] and similar trends with microbiota-derived metabolites” that regressed when patients returned to their usual diet, she said. The researchers also documented decreases in proteomic biomarkers of intestinal and systemic immune and inflammatory response.
The impact of diet on cancer survival was shown in subsequent research, including an observational study published in Science in 2021 of patients with melanoma receiving immune checkpoint blockade (ICB) treatment. “Patients who consumed insufficient dietary fiber at the start of therapy tended to do worse [than those reporting sufficient fiber intake],” with significantly lower progression-free survival, Daniel-MacDougall said.
“And interestingly, when we looked at dietary fiber [with and without] probiotic use, patients who had sufficient fiber but did not take probiotics did the best,” she said. [The probiotics were not endorsed or selected by their physicians.]
Now, the researchers at MD Anderson are moving into “precision nutrition” research, Daniel-MacDougall said, with a phase 2 randomized, double-blind trial of high dietary fiber intake (a target of 50 g/d from whole foods) vs a healthy control diet (20 g/d of fiber) in patients with melanoma receiving ICB.
The study, which is underway, is a fully controlled feeding study, with all meals and snacks provided by MD Anderson and macronutrients controlled. Researchers are collecting blood, stool, and tumor tissue (if available) to answer questions about the microbiome, changes in systemic and tissue immunity, disease response and immunotherapy toxicity, and other issues.
Peled disclosed IP licensing and research support from Seres Therapeutics; consulting with Da Volterra, MaaT Pharma, and CSL Behring; and advisory/equity with Postbiotics + Research LLC and Prodigy Biosciences. Daniel-MacDougall reported having no disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON — For years, oncologist Jonathan Peled, MD, PhD, and his colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City have been documenting gut microbiota disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its role in frequent and potentially fatal bloodstream infections (BSIs) in the first 100 days after transplant.
, and at the Gut Microbiota for Health (GMFH) World Summit 2025, Peled shared two new findings.
In one study, his team found that sucrose can exacerbate antibiotic-induced microbiome injury in patients undergoing allo-HSCT — a finding that “raises the question of whether our dietary recommendations [for] allo-HSCT patients are correct,” said Peled, assistant attending at MSKCC, during a session on the gut microbiome and oncology.
And in another study, they found that a rationally designed probiotic formulation may help lower the incidence of bacterial BSIs. In December 2024, the probiotic formulation (SER-155, Seres Therapeutics, Inc.) was granted breakthrough therapy designation by the FDA.
With immunotherapies more broadly, researchers are increasingly looking at diet and modulation of the microbiome to improve both treatment tolerance and efficacy, experts said at the meeting convened by the AGA and the European Society of Neurogastroenterology and Motility.
“Cancer patients and caregivers are asking, ‘What should I eat?’” said Carrie Daniel-MacDougall, PhD, MPH, a nutritional epidemiologist at the University of Texas MD Anderson Cancer Center in Houston. “They’re not just focused on side effects — they want a good outcome for their treatment, and they’re exploring a lot of dietary strategies [for which there] is not a lot of evidence.”
Clinicians are challenged by the fact that “we don’t typically collect dietary data in clinical trials of cancer drugs,” leaving them to extrapolate from evidence-based diet guidelines for cancer prevention, Daniel-MacDougall said.
But “I think that’s starting to shift,” she said, with the microbiome being increasingly recognized for its potential influences on therapeutic response and clinical trials underway looking at “a healthy dietary pattern not just for prevention but survival.”
Diet and Probiotics After allo-HSCT
The patterns of microbiota disruption during allo-HSCT — a procedure that includes antibiotic administration, chemotherapy, and sometimes irradiation — are characterized by loss of diversity and the expansion of potentially pathogenic organisms, most commonly Enterococcus, said Peled.
This has been demonstrated across transplantation centers. In a multicenter, international study published in 2020, the patterns of microbiota disruption and their impact on mortality were similar across MSK and other transplantation centers, with higher diversity of intestinal microbiota associated with lower mortality.
Other studies have shown that Enterococcus domination alone (defined arbitrarily as > 30% of fecal microbial composition) is associated with graft vs host disease and higher mortality after allo-HSCT and that intestinal domination by Proteobacteria coincides temporally with BSIs, he said.
Autologous fecal microbiota transplantation (FMT) has been shown to largely restore the microbiota composition the patient had before antibiotic treatment and allo-HSCT, he said, making fecal sample banking and posttreatment FMT a potential approach for reconstituting the gut microbiome and improving outcomes.
But “lately we’ve been very interested in diet for modulating [harmful] patterns” in the microbiome composition, Peled said.
In the new study suggesting a role for sugar avoidance, published last year as a bioRxiv preprint, Peled and his colleagues collected real-time dietary intake data (40,702 food entries) from 173 patients hospitalized for several weeks for allo-HSCT at MSK and analyzed it alongside longitudinally collected fecal samples. They used a Bayesian mixed-effects model to identify dietary components that may correlate with microbial disruption.
“What jumped out as very predictive of a low diversity fecal sample [and expansion of Enterococcus] in the 2 days prior to collection was the interaction between antibiotics and the consumption of sweets” — foods rich in simple sugars, Peled said. The relationship between sugar and the microbiome occurred only during periods of antibiotic exposure.
“And it was particularly perplexing because the foods that fall into the ‘sweets’ category are foods we encourage people to eat clinically when they’re not feeling well and food intake drops dramatically,” he said. This includes foods like nutritional drinks or shakes, Italian ice, gelatin dessert, and sports drinks.
(In a mouse model of post-antibiotic Enterococcus expansion, Peled and his co-investigators then validated the findings and ruled out the impact of any reductions in fiber.)
In addition to possibly revising dietary recommendations for patients undergoing allo-HSCT, the findings raise the question of whether avoiding sugar intake while on antibiotics, in general, is a way to mitigate antibiotic-induced dysbiosis, he said.
To test the role of probiotics, Peled and colleagues collaborated with Seres Therapeutics on a phase 1b trial of an oral combination (SER-155) of 16 fermented strains “selected rationally,” he said, for their ability to decolonize gut pathogens, improve gut barrier function (in vitro), and reduce gut inflammation and local immune activation.
After a safety lead-in, patients were randomized to receive SER-155 (20) or placebo (14) three times — prior to transplant, upon neutrophil engraftment (with vancomycin “conditioning”), and after transplant. “The strains succeeded in grafting in the [gastrointestinal] GI tract…and some of them persisted all the way through to day 100,” Peled said.
The incidence of pathogen domination was substantially lower in the probiotic recipients compared to an MSK historical control cohort, and the incidence of BSIs was significantly lower compared to the placebo arm (10% vs 43%, respectively, representing a 77% relative risk reduction), he said.
Diet and Immunotherapy Response: Trials at MD Anderson
One of the first trials Daniel-MacDougall launched at MD Anderson on diet and the microbiome randomized 55 patients who were obese and had a history of colorectal cancer or precancerous polyps to add a cup of beans to their usual diet or to continue their usual diet without beans. There was a crossover at 8 weeks in the 16-week BE GONE trial; stool and fasting blood were collected every 4 weeks.
“Beans are a prebiotic super-house in my opinion, and they’re also something this population would avoid,” said Daniel-MacDougall, associate professor in the department of epidemiology at MD Anderson and faculty director of the Bionutrition Research Core and Research Kitchen.
“We saw a modest increase in alpha diversity [in the intervention group] and similar trends with microbiota-derived metabolites” that regressed when patients returned to their usual diet, she said. The researchers also documented decreases in proteomic biomarkers of intestinal and systemic immune and inflammatory response.
The impact of diet on cancer survival was shown in subsequent research, including an observational study published in Science in 2021 of patients with melanoma receiving immune checkpoint blockade (ICB) treatment. “Patients who consumed insufficient dietary fiber at the start of therapy tended to do worse [than those reporting sufficient fiber intake],” with significantly lower progression-free survival, Daniel-MacDougall said.
“And interestingly, when we looked at dietary fiber [with and without] probiotic use, patients who had sufficient fiber but did not take probiotics did the best,” she said. [The probiotics were not endorsed or selected by their physicians.]
Now, the researchers at MD Anderson are moving into “precision nutrition” research, Daniel-MacDougall said, with a phase 2 randomized, double-blind trial of high dietary fiber intake (a target of 50 g/d from whole foods) vs a healthy control diet (20 g/d of fiber) in patients with melanoma receiving ICB.
The study, which is underway, is a fully controlled feeding study, with all meals and snacks provided by MD Anderson and macronutrients controlled. Researchers are collecting blood, stool, and tumor tissue (if available) to answer questions about the microbiome, changes in systemic and tissue immunity, disease response and immunotherapy toxicity, and other issues.
Peled disclosed IP licensing and research support from Seres Therapeutics; consulting with Da Volterra, MaaT Pharma, and CSL Behring; and advisory/equity with Postbiotics + Research LLC and Prodigy Biosciences. Daniel-MacDougall reported having no disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON — For years, oncologist Jonathan Peled, MD, PhD, and his colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City have been documenting gut microbiota disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its role in frequent and potentially fatal bloodstream infections (BSIs) in the first 100 days after transplant.
, and at the Gut Microbiota for Health (GMFH) World Summit 2025, Peled shared two new findings.
In one study, his team found that sucrose can exacerbate antibiotic-induced microbiome injury in patients undergoing allo-HSCT — a finding that “raises the question of whether our dietary recommendations [for] allo-HSCT patients are correct,” said Peled, assistant attending at MSKCC, during a session on the gut microbiome and oncology.
And in another study, they found that a rationally designed probiotic formulation may help lower the incidence of bacterial BSIs. In December 2024, the probiotic formulation (SER-155, Seres Therapeutics, Inc.) was granted breakthrough therapy designation by the FDA.
With immunotherapies more broadly, researchers are increasingly looking at diet and modulation of the microbiome to improve both treatment tolerance and efficacy, experts said at the meeting convened by the AGA and the European Society of Neurogastroenterology and Motility.
“Cancer patients and caregivers are asking, ‘What should I eat?’” said Carrie Daniel-MacDougall, PhD, MPH, a nutritional epidemiologist at the University of Texas MD Anderson Cancer Center in Houston. “They’re not just focused on side effects — they want a good outcome for their treatment, and they’re exploring a lot of dietary strategies [for which there] is not a lot of evidence.”
Clinicians are challenged by the fact that “we don’t typically collect dietary data in clinical trials of cancer drugs,” leaving them to extrapolate from evidence-based diet guidelines for cancer prevention, Daniel-MacDougall said.
But “I think that’s starting to shift,” she said, with the microbiome being increasingly recognized for its potential influences on therapeutic response and clinical trials underway looking at “a healthy dietary pattern not just for prevention but survival.”
Diet and Probiotics After allo-HSCT
The patterns of microbiota disruption during allo-HSCT — a procedure that includes antibiotic administration, chemotherapy, and sometimes irradiation — are characterized by loss of diversity and the expansion of potentially pathogenic organisms, most commonly Enterococcus, said Peled.
This has been demonstrated across transplantation centers. In a multicenter, international study published in 2020, the patterns of microbiota disruption and their impact on mortality were similar across MSK and other transplantation centers, with higher diversity of intestinal microbiota associated with lower mortality.
Other studies have shown that Enterococcus domination alone (defined arbitrarily as > 30% of fecal microbial composition) is associated with graft vs host disease and higher mortality after allo-HSCT and that intestinal domination by Proteobacteria coincides temporally with BSIs, he said.
Autologous fecal microbiota transplantation (FMT) has been shown to largely restore the microbiota composition the patient had before antibiotic treatment and allo-HSCT, he said, making fecal sample banking and posttreatment FMT a potential approach for reconstituting the gut microbiome and improving outcomes.
But “lately we’ve been very interested in diet for modulating [harmful] patterns” in the microbiome composition, Peled said.
In the new study suggesting a role for sugar avoidance, published last year as a bioRxiv preprint, Peled and his colleagues collected real-time dietary intake data (40,702 food entries) from 173 patients hospitalized for several weeks for allo-HSCT at MSK and analyzed it alongside longitudinally collected fecal samples. They used a Bayesian mixed-effects model to identify dietary components that may correlate with microbial disruption.
“What jumped out as very predictive of a low diversity fecal sample [and expansion of Enterococcus] in the 2 days prior to collection was the interaction between antibiotics and the consumption of sweets” — foods rich in simple sugars, Peled said. The relationship between sugar and the microbiome occurred only during periods of antibiotic exposure.
“And it was particularly perplexing because the foods that fall into the ‘sweets’ category are foods we encourage people to eat clinically when they’re not feeling well and food intake drops dramatically,” he said. This includes foods like nutritional drinks or shakes, Italian ice, gelatin dessert, and sports drinks.
(In a mouse model of post-antibiotic Enterococcus expansion, Peled and his co-investigators then validated the findings and ruled out the impact of any reductions in fiber.)
In addition to possibly revising dietary recommendations for patients undergoing allo-HSCT, the findings raise the question of whether avoiding sugar intake while on antibiotics, in general, is a way to mitigate antibiotic-induced dysbiosis, he said.
To test the role of probiotics, Peled and colleagues collaborated with Seres Therapeutics on a phase 1b trial of an oral combination (SER-155) of 16 fermented strains “selected rationally,” he said, for their ability to decolonize gut pathogens, improve gut barrier function (in vitro), and reduce gut inflammation and local immune activation.
After a safety lead-in, patients were randomized to receive SER-155 (20) or placebo (14) three times — prior to transplant, upon neutrophil engraftment (with vancomycin “conditioning”), and after transplant. “The strains succeeded in grafting in the [gastrointestinal] GI tract…and some of them persisted all the way through to day 100,” Peled said.
The incidence of pathogen domination was substantially lower in the probiotic recipients compared to an MSK historical control cohort, and the incidence of BSIs was significantly lower compared to the placebo arm (10% vs 43%, respectively, representing a 77% relative risk reduction), he said.
Diet and Immunotherapy Response: Trials at MD Anderson
One of the first trials Daniel-MacDougall launched at MD Anderson on diet and the microbiome randomized 55 patients who were obese and had a history of colorectal cancer or precancerous polyps to add a cup of beans to their usual diet or to continue their usual diet without beans. There was a crossover at 8 weeks in the 16-week BE GONE trial; stool and fasting blood were collected every 4 weeks.
“Beans are a prebiotic super-house in my opinion, and they’re also something this population would avoid,” said Daniel-MacDougall, associate professor in the department of epidemiology at MD Anderson and faculty director of the Bionutrition Research Core and Research Kitchen.
“We saw a modest increase in alpha diversity [in the intervention group] and similar trends with microbiota-derived metabolites” that regressed when patients returned to their usual diet, she said. The researchers also documented decreases in proteomic biomarkers of intestinal and systemic immune and inflammatory response.
The impact of diet on cancer survival was shown in subsequent research, including an observational study published in Science in 2021 of patients with melanoma receiving immune checkpoint blockade (ICB) treatment. “Patients who consumed insufficient dietary fiber at the start of therapy tended to do worse [than those reporting sufficient fiber intake],” with significantly lower progression-free survival, Daniel-MacDougall said.
“And interestingly, when we looked at dietary fiber [with and without] probiotic use, patients who had sufficient fiber but did not take probiotics did the best,” she said. [The probiotics were not endorsed or selected by their physicians.]
Now, the researchers at MD Anderson are moving into “precision nutrition” research, Daniel-MacDougall said, with a phase 2 randomized, double-blind trial of high dietary fiber intake (a target of 50 g/d from whole foods) vs a healthy control diet (20 g/d of fiber) in patients with melanoma receiving ICB.
The study, which is underway, is a fully controlled feeding study, with all meals and snacks provided by MD Anderson and macronutrients controlled. Researchers are collecting blood, stool, and tumor tissue (if available) to answer questions about the microbiome, changes in systemic and tissue immunity, disease response and immunotherapy toxicity, and other issues.
Peled disclosed IP licensing and research support from Seres Therapeutics; consulting with Da Volterra, MaaT Pharma, and CSL Behring; and advisory/equity with Postbiotics + Research LLC and Prodigy Biosciences. Daniel-MacDougall reported having no disclosures.
A version of this article appeared on Medscape.com.
Journal Highlights: January-April 2025
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.
Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.
Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.
Small Bowel
Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.
Colon
Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.
Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.
Inflammatory Bowel Disease
Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.
Pancreas
Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.
Hepatology
Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.
Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.
Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.
Miscellaneous
Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.
Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.
Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
MASH Driving Global Epidemic of Primary Liver Cancer
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY