Feature

Dear colleagues,

Since our last Perspectives feature on artificial intelligence (AI) in gastroenterology and hepatology, the field has experienced remarkable growth in both innovation and clinical adoption. AI tools that were once conceptual are now entering everyday practice, with many more on the horizon poised to transform how we diagnose, treat, and manage patients. In this issue of Perspectives, we present two timely essays that explore how AI is reshaping clinical care—while also emphasizing the need for caution, thoughtful integration, and ongoing oversight.

Dr. Yuvaraj Singh, Dr. Alessandro Colletta, and Dr. Neil Marya discuss how purpose-built AI models can reduce diagnostic uncertainty in advanced endoscopy. From cholangioscopy systems that outperform standard ERCP sampling in distinguishing malignant biliary strictures to EUS-based platforms that differentiate autoimmune pancreatitis from pancreatic cancer, they envision a near-term future in which machine intelligence enhances accuracy, accelerates decision-making, and refines interpretation—without replacing the clinician’s expertise.

Complementing this, Dr. Dennis Shung takes a broader view across the endoscopy unit and outpatient clinic. He highlights the promise of AI for polyp detection, digital biopsy, and automated reporting, while underscoring the importance of human oversight, workflow integration, and safeguards against misinformation. Dr. Shung also emphasizes the pivotal role professional societies can play in establishing clear standards, ethical boundaries, and trusted frameworks for AI deployment in GI practice.

We hope these perspectives spark practical conversations about when—and how—to integrate AI in your own practice. As always, we welcome your feedback and real-world experience. Join the conversation on X at @AGA_GIHN.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

AI Models in Advanced Endoscopy

BY YUVARAJ SINGH, MD; ALESSANDRO COLLETTA, MD; NEIL MARYA, MD

As the adage goes, “if tumor is the rumor, then tissue is the issue, because cancer may be the answer.”

Establishing an accurate diagnosis is the essential first step toward curing or palliating malignancy. From detecting an early neoplastic lesion, to distinguishing between malignant and benign pathology, or to determining when and where to obtain tissue, endoscopists are frequently faced with the challenge of transforming diagnostic suspicion into certainty.

Artificial intelligence (AI), designed to replicate human cognition such as pattern recognition and decision-making, has emerged as a technology to assist gastroenterologists in addressing a variety of different tasks during endoscopy. AI research in gastrointestinal endoscopy has initially focused on computer-aided detection (CADe) of colorectal polyps. More recently, however, there has been increased emphasis on developing AI to assist advanced endoscopists.

For instance, in biliary endoscopy, AI is being explored to improve the notoriously challenging diagnosis of cholangiocarcinoma, where conventional tissue sampling often falls short of providing a definitive diagnosis. Similarly, in the pancreas, AI models are showing potential to differentiate autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), a distinction with profound therapeutic implications. Even pancreatic cysts are beginning to benefit from AI models that refine risk stratification and guide management. Together, these advances underscore how AI is not merely an adjunct but a potentially massive catalyst for reimagining the diagnostic role of advanced endoscopists.

Classifying biliary strictures (MBS) accurately remains a challenge. Standard ERCP-based sampling techniques (forceps biopsy and brush cytology) are suboptimal diagnostic tools with false negative rates for detecting MBS of less than 50%. The diagnostic uncertainty related to biliary stricture classification carries significant consequences for patients. For example, patients with biliary cancer without positive cytology have treatments delayed until a malignant diagnosis is established. 

Ancillary technologies to enhance ERCP-based tissue acquisition are still weighed down by low sensitivity and accuracy; even with ancillary use of fluorescent in situ hybridization (FISH), diagnostic yield remains limited. EUS-FNA can help with distal biliary strictures, but this technique risks needle-tract seeding in cases of perihilar disease. Cholangioscopy allows for direct visualization and targeted sampling; however, cholangioscopy-guided forceps biopsies are burdened by low sensitivities.¹ Additionally, physician interpretation of visual findings during cholangioscopy often suffers from poor interobserver agreement and poor accuracy.²

To improve the classification of biliary strictures, several groups have studied the application of AI for cholangioscopy footage of biliary pathology. In our lab, we trained an AI incorporating over 2.3 million cholangioscopy still images and nearly 20,000 expert-annotated frames to enhance its development. The AI closely mirrored expert labeling of cholangioscopy images of malignant pathology and, when tested on full cholangioscopy videos of indeterminate biliary strictures, the AI achieved a diagnostic accuracy of 91%—outperforming both brush cytology (63%) and forceps biopsy (61%).³

The results from this initial study were later validated across multiple centers. AI-assisted cholangioscopy could thus offer a reproducible, real-world solution to one of the most persistent diagnostic dilemmas advanced endoscopists face—helping clinicians act earlier and with greater confidence when evaluating indeterminate strictures.

Moving from the biliary tree to the pancreas, autoimmune pancreatitis (AIP) is a benign fibro-inflammatory disease that often frustrates advanced endoscopists as it closely mimics the appearance of pancreatic ductal adenocarcinoma (PDAC). The stakes are high: despite modern diagnostic techniques, including advanced imaging, some patients with pancreatic resections for “suspected PDAC” are still found to have AIP on final pathology. Conventional tools to distinguish AIP from PDAC have gaps: serum IgG4 and EUS-guided biopsies are both specific but insensitive.

Using EUS videos and images of various pancreas pathologies at Mayo Clinic, we developed an AI to tackle this dilemma. After intensive training, the EUS AI achieved a greater accuracy for distinguishing AIP from PDAC than a group of expert Mayo clinic endosonographers.⁵ In practice, an EUS-AI can identify AIP patterns in real-time, guiding clinicians toward steroid trials or biopsies and reducing the need for unnecessary surgeries.

Looking ahead, there are multiple opportunities for integration of AI into advanced endoscopy practices. Ongoing research suggests that AI could soon assist with identification of pancreas cysts most at risk for malignant transformation, classification of high risk Barrett’s esophagus, and even help with rapid on-site assessment of cytologic specimens obtained during EUS. Beyond diagnosis, AI could likely play an important role in guiding therapeutic interventions. For example, an ERCP AI in the future may be able to provide cannulation assistance or an AI assistant could help endosonographers during deployments of lumen apposing metal stents.

By enhancing image interpretation and procedural consistency, AI has the potential to uphold the fundamental principle of primum non nocere, enabling us to intervene with precision while minimizing harm. AI can also bridge grey zones in clinical practice and narrow diagnostic uncertainty in real time. Importantly, these systems can help clinicians achieve expertise in a fraction of the time it traditionally takes to acquire comparable human proficiency, while offering wider availability across practice settings and reducing interobserver variability that has long challenged endoscopic interpretation.

Currently, adoption is limited by high bias risk, lack of external validation, and interpretability Still, the trajectory of AI suggests a future where these computer technologies will not only support but also elevate human expertise, reshaping the standards of care of diseases managed by advanced endoscopists.

Dr. Singh, Dr. Colletta, and Dr. Marya are based at the Division of Gastroenterology and Hepatology, UMass Chan Medical School, Worcester, Massachusetts. Dr. Marya is a consultant for Boston Scientific, and has no other disclosures. Dr. Singh and Dr. Colletta have no disclosures.

References

1. Navaneethan U, et al. Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc. 2015 Jan. doi: 10.1016/j.gie.2014.09.017.

2. Stassen PMC, et al. Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures. Gastrointest Endosc 2021 Dec. doi: 10.1016/j.gie.2021.06.027.

3. Marya NB, et al. Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video). Gastrointest Endosc. 2023 Feb. doi: 10.1016/j.gie.2022.08.021.

4. Marya NB, et al. Multicenter validation of a cholangioscopy artificial intelligence system for the evaluation of biliary tract disease. Endoscopy. 2025 Aug. doi: 10.1055/a-2650-0789.

5. Marya NB, et al. Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis. Gut. 2021 Jul. doi: 10.1136/gutjnl-2020-322821.

AI in General GI and Endoscopy

BY DENNIS L. SHUNG, MD, MHS, PHD

The practice of gastroenterology is changing, but much of it will be rooted in the same – careful, focused attention on endoscopic procedures, and compassionate, attentive care in clinic. Artificial intelligence (AI), like the Industrial Revolution before, is going to transform our practice. This comes with upsides and downsides, and highlights the need for strong leadership from our societies to safeguard the technology for practitioners and patients.

What are the upsides? 

AI has the potential to serve as a second set of eyes in detecting colon polyps, increasing the adenoma detection rate (ADR).¹ AI can be applied to all areas of the gastrointestinal tract, providing digital biopsies, guiding resection, and ensuring quality, which are all now possible with powerful new endoscopy foundation models, such as GastroNet-5M.²

Additionally. the advent of automating the collection of data into reports may herald the end of our days as data entry clerks. Generative AI also has the potential to give us all the best information at our fingertips, suggesting guideline-based care, providing the most up to date evidence, and guiding the differential diagnosis. The potential for patient-facing AI systems could lead to better health literacy, more meaningful engagement, and improved patient satisfaction.³

What are the downsides? 

For endoscopy, AI cannot make up for poor technique to ensure adequate mucosal exposure by the endoscopist, and an increase in AI-supported ADR does not yet convincingly translate into concrete gains in colorectal cancer-related mortality. For the foreseeable future, AI cannot make a connection with the patient in front of us, which is critical in diagnosing and treating patients.

Currently, AI appears to worsen loneliness⁴, and does not necessarily deepen the bonds or provide the positive touch that can heal, and which for many of us, was the reason we became physicians. Finally, as information proliferates, the information risk to patients and providers is growing – in the future, trusted sources to monitor, curate, and guide AI will be ever more important.

 

Black Swans

As AI begins to mature, there are risks that lurk beneath the surface. When regulatory bodies begin to look at AI-assisted diagnostics or therapeutics as the new standard of care, reimbursement models may adjust, and providers may be left behind. The rapid proliferation and haphazard adoption of AI could lead to overdependence and deskilling or result in weird and as yet unknown errors that are difficult to troubleshoot.

What is the role of the GI societies? 

Specialty societies like AGA are taking leadership roles in determining the bounds of where AIs may tread, not just in providing information to their membership but also in digesting evidence and synthesizing recommendations. Societies must balance the real promise of AI in endoscopy with the practice realities for members, and provide living guidelines that reflect the consensus of members regarding scope of practice with the ability to update as new data become available.⁵

Societies also have a role as advocates for safety, taking ownership of high-quality content to prevent misinformation. AGA recently announced the development of a chat interface that will be focused on providing its members the highest quality information, and serve as a portal to identify and respond to its members’ information needs. By staying united rather than fragmenting, societies can maintain bounds to protect its members and their patients and advance areas where there is clinical need, together.

Dr. Shung is senior associate consultant, Division of Gastroenterology and Hepatology, and director of clinical generative artificial intelligence and informatics, Department of Medicine, at Mayo Clinic Rochester, Minnesota. He has no disclosures in regard to this article.

References

1. Soleymanjahi S, et al. Artificial Intelligence-Assisted Colonoscopy for Polyp Detection : A Systematic Review and Meta-analysis. Ann Intern Med. 2024 Dec. doi:10.7326/annals-24-00981.

2. Jong MR, et al. GastroNet-5M: A Multicenter Dataset for Developing Foundation Models in Gastrointestinal Endoscopy. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.07.030.

3. Soroush A, et al. Generative Artificial Intelligence in Clinical Medicine and Impact on Gastroenterology. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.03.038.

4. Mengying Fang C, et al. How AI and Human Behaviors Shape Psychosocial Effects of Extended Chatbot Use: A Longitudinal Randomized Controlled Study. arXiv e-prints. 2025 Mar. doi: 10.48550/arXiv.2503.17473.

5. Sultan S, et al. AGA Living Clinical Practice Guideline on Computer-Aided Detection-Assisted Colonoscopy. Gastroenterology. 2025 Apr. doi:10.1053/j.gastro.2025.01.002.

Dear colleagues,

Since our last Perspectives feature on artificial intelligence (AI) in gastroenterology and hepatology, the field has experienced remarkable growth in both innovation and clinical adoption. AI tools that were once conceptual are now entering everyday practice, with many more on the horizon poised to transform how we diagnose, treat, and manage patients. In this issue of Perspectives, we present two timely essays that explore how AI is reshaping clinical care—while also emphasizing the need for caution, thoughtful integration, and ongoing oversight.

Dr. Yuvaraj Singh, Dr. Alessandro Colletta, and Dr. Neil Marya discuss how purpose-built AI models can reduce diagnostic uncertainty in advanced endoscopy. From cholangioscopy systems that outperform standard ERCP sampling in distinguishing malignant biliary strictures to EUS-based platforms that differentiate autoimmune pancreatitis from pancreatic cancer, they envision a near-term future in which machine intelligence enhances accuracy, accelerates decision-making, and refines interpretation—without replacing the clinician’s expertise.

Complementing this, Dr. Dennis Shung takes a broader view across the endoscopy unit and outpatient clinic. He highlights the promise of AI for polyp detection, digital biopsy, and automated reporting, while underscoring the importance of human oversight, workflow integration, and safeguards against misinformation. Dr. Shung also emphasizes the pivotal role professional societies can play in establishing clear standards, ethical boundaries, and trusted frameworks for AI deployment in GI practice.

We hope these perspectives spark practical conversations about when—and how—to integrate AI in your own practice. As always, we welcome your feedback and real-world experience. Join the conversation on X at @AGA_GIHN.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

AI Models in Advanced Endoscopy

BY YUVARAJ SINGH, MD; ALESSANDRO COLLETTA, MD; NEIL MARYA, MD

As the adage goes, “if tumor is the rumor, then tissue is the issue, because cancer may be the answer.”

Establishing an accurate diagnosis is the essential first step toward curing or palliating malignancy. From detecting an early neoplastic lesion, to distinguishing between malignant and benign pathology, or to determining when and where to obtain tissue, endoscopists are frequently faced with the challenge of transforming diagnostic suspicion into certainty.

Artificial intelligence (AI), designed to replicate human cognition such as pattern recognition and decision-making, has emerged as a technology to assist gastroenterologists in addressing a variety of different tasks during endoscopy. AI research in gastrointestinal endoscopy has initially focused on computer-aided detection (CADe) of colorectal polyps. More recently, however, there has been increased emphasis on developing AI to assist advanced endoscopists.

For instance, in biliary endoscopy, AI is being explored to improve the notoriously challenging diagnosis of cholangiocarcinoma, where conventional tissue sampling often falls short of providing a definitive diagnosis. Similarly, in the pancreas, AI models are showing potential to differentiate autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), a distinction with profound therapeutic implications. Even pancreatic cysts are beginning to benefit from AI models that refine risk stratification and guide management. Together, these advances underscore how AI is not merely an adjunct but a potentially massive catalyst for reimagining the diagnostic role of advanced endoscopists.

Classifying biliary strictures (MBS) accurately remains a challenge. Standard ERCP-based sampling techniques (forceps biopsy and brush cytology) are suboptimal diagnostic tools with false negative rates for detecting MBS of less than 50%. The diagnostic uncertainty related to biliary stricture classification carries significant consequences for patients. For example, patients with biliary cancer without positive cytology have treatments delayed until a malignant diagnosis is established. 

Ancillary technologies to enhance ERCP-based tissue acquisition are still weighed down by low sensitivity and accuracy; even with ancillary use of fluorescent in situ hybridization (FISH), diagnostic yield remains limited. EUS-FNA can help with distal biliary strictures, but this technique risks needle-tract seeding in cases of perihilar disease. Cholangioscopy allows for direct visualization and targeted sampling; however, cholangioscopy-guided forceps biopsies are burdened by low sensitivities.¹ Additionally, physician interpretation of visual findings during cholangioscopy often suffers from poor interobserver agreement and poor accuracy.²

To improve the classification of biliary strictures, several groups have studied the application of AI for cholangioscopy footage of biliary pathology. In our lab, we trained an AI incorporating over 2.3 million cholangioscopy still images and nearly 20,000 expert-annotated frames to enhance its development. The AI closely mirrored expert labeling of cholangioscopy images of malignant pathology and, when tested on full cholangioscopy videos of indeterminate biliary strictures, the AI achieved a diagnostic accuracy of 91%—outperforming both brush cytology (63%) and forceps biopsy (61%).³

The results from this initial study were later validated across multiple centers. AI-assisted cholangioscopy could thus offer a reproducible, real-world solution to one of the most persistent diagnostic dilemmas advanced endoscopists face—helping clinicians act earlier and with greater confidence when evaluating indeterminate strictures.

Moving from the biliary tree to the pancreas, autoimmune pancreatitis (AIP) is a benign fibro-inflammatory disease that often frustrates advanced endoscopists as it closely mimics the appearance of pancreatic ductal adenocarcinoma (PDAC). The stakes are high: despite modern diagnostic techniques, including advanced imaging, some patients with pancreatic resections for “suspected PDAC” are still found to have AIP on final pathology. Conventional tools to distinguish AIP from PDAC have gaps: serum IgG4 and EUS-guided biopsies are both specific but insensitive.

Using EUS videos and images of various pancreas pathologies at Mayo Clinic, we developed an AI to tackle this dilemma. After intensive training, the EUS AI achieved a greater accuracy for distinguishing AIP from PDAC than a group of expert Mayo clinic endosonographers.⁵ In practice, an EUS-AI can identify AIP patterns in real-time, guiding clinicians toward steroid trials or biopsies and reducing the need for unnecessary surgeries.

Looking ahead, there are multiple opportunities for integration of AI into advanced endoscopy practices. Ongoing research suggests that AI could soon assist with identification of pancreas cysts most at risk for malignant transformation, classification of high risk Barrett’s esophagus, and even help with rapid on-site assessment of cytologic specimens obtained during EUS. Beyond diagnosis, AI could likely play an important role in guiding therapeutic interventions. For example, an ERCP AI in the future may be able to provide cannulation assistance or an AI assistant could help endosonographers during deployments of lumen apposing metal stents.

By enhancing image interpretation and procedural consistency, AI has the potential to uphold the fundamental principle of primum non nocere, enabling us to intervene with precision while minimizing harm. AI can also bridge grey zones in clinical practice and narrow diagnostic uncertainty in real time. Importantly, these systems can help clinicians achieve expertise in a fraction of the time it traditionally takes to acquire comparable human proficiency, while offering wider availability across practice settings and reducing interobserver variability that has long challenged endoscopic interpretation.

Currently, adoption is limited by high bias risk, lack of external validation, and interpretability Still, the trajectory of AI suggests a future where these computer technologies will not only support but also elevate human expertise, reshaping the standards of care of diseases managed by advanced endoscopists.

Dr. Singh, Dr. Colletta, and Dr. Marya are based at the Division of Gastroenterology and Hepatology, UMass Chan Medical School, Worcester, Massachusetts. Dr. Marya is a consultant for Boston Scientific, and has no other disclosures. Dr. Singh and Dr. Colletta have no disclosures.

References

1. Navaneethan U, et al. Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc. 2015 Jan. doi: 10.1016/j.gie.2014.09.017.

2. Stassen PMC, et al. Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures. Gastrointest Endosc 2021 Dec. doi: 10.1016/j.gie.2021.06.027.

3. Marya NB, et al. Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video). Gastrointest Endosc. 2023 Feb. doi: 10.1016/j.gie.2022.08.021.

4. Marya NB, et al. Multicenter validation of a cholangioscopy artificial intelligence system for the evaluation of biliary tract disease. Endoscopy. 2025 Aug. doi: 10.1055/a-2650-0789.

5. Marya NB, et al. Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis. Gut. 2021 Jul. doi: 10.1136/gutjnl-2020-322821.

AI in General GI and Endoscopy

BY DENNIS L. SHUNG, MD, MHS, PHD

The practice of gastroenterology is changing, but much of it will be rooted in the same – careful, focused attention on endoscopic procedures, and compassionate, attentive care in clinic. Artificial intelligence (AI), like the Industrial Revolution before, is going to transform our practice. This comes with upsides and downsides, and highlights the need for strong leadership from our societies to safeguard the technology for practitioners and patients.

What are the upsides? 

AI has the potential to serve as a second set of eyes in detecting colon polyps, increasing the adenoma detection rate (ADR).¹ AI can be applied to all areas of the gastrointestinal tract, providing digital biopsies, guiding resection, and ensuring quality, which are all now possible with powerful new endoscopy foundation models, such as GastroNet-5M.²

Additionally. the advent of automating the collection of data into reports may herald the end of our days as data entry clerks. Generative AI also has the potential to give us all the best information at our fingertips, suggesting guideline-based care, providing the most up to date evidence, and guiding the differential diagnosis. The potential for patient-facing AI systems could lead to better health literacy, more meaningful engagement, and improved patient satisfaction.³

What are the downsides? 

For endoscopy, AI cannot make up for poor technique to ensure adequate mucosal exposure by the endoscopist, and an increase in AI-supported ADR does not yet convincingly translate into concrete gains in colorectal cancer-related mortality. For the foreseeable future, AI cannot make a connection with the patient in front of us, which is critical in diagnosing and treating patients.

Currently, AI appears to worsen loneliness⁴, and does not necessarily deepen the bonds or provide the positive touch that can heal, and which for many of us, was the reason we became physicians. Finally, as information proliferates, the information risk to patients and providers is growing – in the future, trusted sources to monitor, curate, and guide AI will be ever more important.

 

Black Swans

As AI begins to mature, there are risks that lurk beneath the surface. When regulatory bodies begin to look at AI-assisted diagnostics or therapeutics as the new standard of care, reimbursement models may adjust, and providers may be left behind. The rapid proliferation and haphazard adoption of AI could lead to overdependence and deskilling or result in weird and as yet unknown errors that are difficult to troubleshoot.

What is the role of the GI societies? 

Specialty societies like AGA are taking leadership roles in determining the bounds of where AIs may tread, not just in providing information to their membership but also in digesting evidence and synthesizing recommendations. Societies must balance the real promise of AI in endoscopy with the practice realities for members, and provide living guidelines that reflect the consensus of members regarding scope of practice with the ability to update as new data become available.⁵

Societies also have a role as advocates for safety, taking ownership of high-quality content to prevent misinformation. AGA recently announced the development of a chat interface that will be focused on providing its members the highest quality information, and serve as a portal to identify and respond to its members’ information needs. By staying united rather than fragmenting, societies can maintain bounds to protect its members and their patients and advance areas where there is clinical need, together.

Dr. Shung is senior associate consultant, Division of Gastroenterology and Hepatology, and director of clinical generative artificial intelligence and informatics, Department of Medicine, at Mayo Clinic Rochester, Minnesota. He has no disclosures in regard to this article.

References

1. Soleymanjahi S, et al. Artificial Intelligence-Assisted Colonoscopy for Polyp Detection : A Systematic Review and Meta-analysis. Ann Intern Med. 2024 Dec. doi:10.7326/annals-24-00981.

2. Jong MR, et al. GastroNet-5M: A Multicenter Dataset for Developing Foundation Models in Gastrointestinal Endoscopy. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.07.030.

3. Soroush A, et al. Generative Artificial Intelligence in Clinical Medicine and Impact on Gastroenterology. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.03.038.

4. Mengying Fang C, et al. How AI and Human Behaviors Shape Psychosocial Effects of Extended Chatbot Use: A Longitudinal Randomized Controlled Study. arXiv e-prints. 2025 Mar. doi: 10.48550/arXiv.2503.17473.

5. Sultan S, et al. AGA Living Clinical Practice Guideline on Computer-Aided Detection-Assisted Colonoscopy. Gastroenterology. 2025 Apr. doi:10.1053/j.gastro.2025.01.002.

Dear colleagues,

Since our last Perspectives feature on artificial intelligence (AI) in gastroenterology and hepatology, the field has experienced remarkable growth in both innovation and clinical adoption. AI tools that were once conceptual are now entering everyday practice, with many more on the horizon poised to transform how we diagnose, treat, and manage patients. In this issue of Perspectives, we present two timely essays that explore how AI is reshaping clinical care—while also emphasizing the need for caution, thoughtful integration, and ongoing oversight.

Dr. Yuvaraj Singh, Dr. Alessandro Colletta, and Dr. Neil Marya discuss how purpose-built AI models can reduce diagnostic uncertainty in advanced endoscopy. From cholangioscopy systems that outperform standard ERCP sampling in distinguishing malignant biliary strictures to EUS-based platforms that differentiate autoimmune pancreatitis from pancreatic cancer, they envision a near-term future in which machine intelligence enhances accuracy, accelerates decision-making, and refines interpretation—without replacing the clinician’s expertise.

Complementing this, Dr. Dennis Shung takes a broader view across the endoscopy unit and outpatient clinic. He highlights the promise of AI for polyp detection, digital biopsy, and automated reporting, while underscoring the importance of human oversight, workflow integration, and safeguards against misinformation. Dr. Shung also emphasizes the pivotal role professional societies can play in establishing clear standards, ethical boundaries, and trusted frameworks for AI deployment in GI practice.

We hope these perspectives spark practical conversations about when—and how—to integrate AI in your own practice. As always, we welcome your feedback and real-world experience. Join the conversation on X at @AGA_GIHN.

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

AI Models in Advanced Endoscopy

BY YUVARAJ SINGH, MD; ALESSANDRO COLLETTA, MD; NEIL MARYA, MD

As the adage goes, “if tumor is the rumor, then tissue is the issue, because cancer may be the answer.”

Establishing an accurate diagnosis is the essential first step toward curing or palliating malignancy. From detecting an early neoplastic lesion, to distinguishing between malignant and benign pathology, or to determining when and where to obtain tissue, endoscopists are frequently faced with the challenge of transforming diagnostic suspicion into certainty.

Artificial intelligence (AI), designed to replicate human cognition such as pattern recognition and decision-making, has emerged as a technology to assist gastroenterologists in addressing a variety of different tasks during endoscopy. AI research in gastrointestinal endoscopy has initially focused on computer-aided detection (CADe) of colorectal polyps. More recently, however, there has been increased emphasis on developing AI to assist advanced endoscopists.

For instance, in biliary endoscopy, AI is being explored to improve the notoriously challenging diagnosis of cholangiocarcinoma, where conventional tissue sampling often falls short of providing a definitive diagnosis. Similarly, in the pancreas, AI models are showing potential to differentiate autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), a distinction with profound therapeutic implications. Even pancreatic cysts are beginning to benefit from AI models that refine risk stratification and guide management. Together, these advances underscore how AI is not merely an adjunct but a potentially massive catalyst for reimagining the diagnostic role of advanced endoscopists.

Classifying biliary strictures (MBS) accurately remains a challenge. Standard ERCP-based sampling techniques (forceps biopsy and brush cytology) are suboptimal diagnostic tools with false negative rates for detecting MBS of less than 50%. The diagnostic uncertainty related to biliary stricture classification carries significant consequences for patients. For example, patients with biliary cancer without positive cytology have treatments delayed until a malignant diagnosis is established. 

Ancillary technologies to enhance ERCP-based tissue acquisition are still weighed down by low sensitivity and accuracy; even with ancillary use of fluorescent in situ hybridization (FISH), diagnostic yield remains limited. EUS-FNA can help with distal biliary strictures, but this technique risks needle-tract seeding in cases of perihilar disease. Cholangioscopy allows for direct visualization and targeted sampling; however, cholangioscopy-guided forceps biopsies are burdened by low sensitivities.¹ Additionally, physician interpretation of visual findings during cholangioscopy often suffers from poor interobserver agreement and poor accuracy.²

To improve the classification of biliary strictures, several groups have studied the application of AI for cholangioscopy footage of biliary pathology. In our lab, we trained an AI incorporating over 2.3 million cholangioscopy still images and nearly 20,000 expert-annotated frames to enhance its development. The AI closely mirrored expert labeling of cholangioscopy images of malignant pathology and, when tested on full cholangioscopy videos of indeterminate biliary strictures, the AI achieved a diagnostic accuracy of 91%—outperforming both brush cytology (63%) and forceps biopsy (61%).³

The results from this initial study were later validated across multiple centers. AI-assisted cholangioscopy could thus offer a reproducible, real-world solution to one of the most persistent diagnostic dilemmas advanced endoscopists face—helping clinicians act earlier and with greater confidence when evaluating indeterminate strictures.

Moving from the biliary tree to the pancreas, autoimmune pancreatitis (AIP) is a benign fibro-inflammatory disease that often frustrates advanced endoscopists as it closely mimics the appearance of pancreatic ductal adenocarcinoma (PDAC). The stakes are high: despite modern diagnostic techniques, including advanced imaging, some patients with pancreatic resections for “suspected PDAC” are still found to have AIP on final pathology. Conventional tools to distinguish AIP from PDAC have gaps: serum IgG4 and EUS-guided biopsies are both specific but insensitive.

Using EUS videos and images of various pancreas pathologies at Mayo Clinic, we developed an AI to tackle this dilemma. After intensive training, the EUS AI achieved a greater accuracy for distinguishing AIP from PDAC than a group of expert Mayo clinic endosonographers.⁵ In practice, an EUS-AI can identify AIP patterns in real-time, guiding clinicians toward steroid trials or biopsies and reducing the need for unnecessary surgeries.

Looking ahead, there are multiple opportunities for integration of AI into advanced endoscopy practices. Ongoing research suggests that AI could soon assist with identification of pancreas cysts most at risk for malignant transformation, classification of high risk Barrett’s esophagus, and even help with rapid on-site assessment of cytologic specimens obtained during EUS. Beyond diagnosis, AI could likely play an important role in guiding therapeutic interventions. For example, an ERCP AI in the future may be able to provide cannulation assistance or an AI assistant could help endosonographers during deployments of lumen apposing metal stents.

By enhancing image interpretation and procedural consistency, AI has the potential to uphold the fundamental principle of primum non nocere, enabling us to intervene with precision while minimizing harm. AI can also bridge grey zones in clinical practice and narrow diagnostic uncertainty in real time. Importantly, these systems can help clinicians achieve expertise in a fraction of the time it traditionally takes to acquire comparable human proficiency, while offering wider availability across practice settings and reducing interobserver variability that has long challenged endoscopic interpretation.

Currently, adoption is limited by high bias risk, lack of external validation, and interpretability Still, the trajectory of AI suggests a future where these computer technologies will not only support but also elevate human expertise, reshaping the standards of care of diseases managed by advanced endoscopists.

Dr. Singh, Dr. Colletta, and Dr. Marya are based at the Division of Gastroenterology and Hepatology, UMass Chan Medical School, Worcester, Massachusetts. Dr. Marya is a consultant for Boston Scientific, and has no other disclosures. Dr. Singh and Dr. Colletta have no disclosures.

References

1. Navaneethan U, et al. Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc. 2015 Jan. doi: 10.1016/j.gie.2014.09.017.

2. Stassen PMC, et al. Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures. Gastrointest Endosc 2021 Dec. doi: 10.1016/j.gie.2021.06.027.

3. Marya NB, et al. Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video). Gastrointest Endosc. 2023 Feb. doi: 10.1016/j.gie.2022.08.021.

4. Marya NB, et al. Multicenter validation of a cholangioscopy artificial intelligence system for the evaluation of biliary tract disease. Endoscopy. 2025 Aug. doi: 10.1055/a-2650-0789.

5. Marya NB, et al. Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis. Gut. 2021 Jul. doi: 10.1136/gutjnl-2020-322821.

AI in General GI and Endoscopy

BY DENNIS L. SHUNG, MD, MHS, PHD

The practice of gastroenterology is changing, but much of it will be rooted in the same – careful, focused attention on endoscopic procedures, and compassionate, attentive care in clinic. Artificial intelligence (AI), like the Industrial Revolution before, is going to transform our practice. This comes with upsides and downsides, and highlights the need for strong leadership from our societies to safeguard the technology for practitioners and patients.

What are the upsides? 

AI has the potential to serve as a second set of eyes in detecting colon polyps, increasing the adenoma detection rate (ADR).¹ AI can be applied to all areas of the gastrointestinal tract, providing digital biopsies, guiding resection, and ensuring quality, which are all now possible with powerful new endoscopy foundation models, such as GastroNet-5M.²

Additionally. the advent of automating the collection of data into reports may herald the end of our days as data entry clerks. Generative AI also has the potential to give us all the best information at our fingertips, suggesting guideline-based care, providing the most up to date evidence, and guiding the differential diagnosis. The potential for patient-facing AI systems could lead to better health literacy, more meaningful engagement, and improved patient satisfaction.³

What are the downsides? 

For endoscopy, AI cannot make up for poor technique to ensure adequate mucosal exposure by the endoscopist, and an increase in AI-supported ADR does not yet convincingly translate into concrete gains in colorectal cancer-related mortality. For the foreseeable future, AI cannot make a connection with the patient in front of us, which is critical in diagnosing and treating patients.

Currently, AI appears to worsen loneliness⁴, and does not necessarily deepen the bonds or provide the positive touch that can heal, and which for many of us, was the reason we became physicians. Finally, as information proliferates, the information risk to patients and providers is growing – in the future, trusted sources to monitor, curate, and guide AI will be ever more important.

 

Black Swans

As AI begins to mature, there are risks that lurk beneath the surface. When regulatory bodies begin to look at AI-assisted diagnostics or therapeutics as the new standard of care, reimbursement models may adjust, and providers may be left behind. The rapid proliferation and haphazard adoption of AI could lead to overdependence and deskilling or result in weird and as yet unknown errors that are difficult to troubleshoot.

What is the role of the GI societies? 

Specialty societies like AGA are taking leadership roles in determining the bounds of where AIs may tread, not just in providing information to their membership but also in digesting evidence and synthesizing recommendations. Societies must balance the real promise of AI in endoscopy with the practice realities for members, and provide living guidelines that reflect the consensus of members regarding scope of practice with the ability to update as new data become available.⁵

Societies also have a role as advocates for safety, taking ownership of high-quality content to prevent misinformation. AGA recently announced the development of a chat interface that will be focused on providing its members the highest quality information, and serve as a portal to identify and respond to its members’ information needs. By staying united rather than fragmenting, societies can maintain bounds to protect its members and their patients and advance areas where there is clinical need, together.

Dr. Shung is senior associate consultant, Division of Gastroenterology and Hepatology, and director of clinical generative artificial intelligence and informatics, Department of Medicine, at Mayo Clinic Rochester, Minnesota. He has no disclosures in regard to this article.

References

1. Soleymanjahi S, et al. Artificial Intelligence-Assisted Colonoscopy for Polyp Detection : A Systematic Review and Meta-analysis. Ann Intern Med. 2024 Dec. doi:10.7326/annals-24-00981.

2. Jong MR, et al. GastroNet-5M: A Multicenter Dataset for Developing Foundation Models in Gastrointestinal Endoscopy. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.07.030.

3. Soroush A, et al. Generative Artificial Intelligence in Clinical Medicine and Impact on Gastroenterology. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.03.038.

4. Mengying Fang C, et al. How AI and Human Behaviors Shape Psychosocial Effects of Extended Chatbot Use: A Longitudinal Randomized Controlled Study. arXiv e-prints. 2025 Mar. doi: 10.48550/arXiv.2503.17473.

5. Sultan S, et al. AGA Living Clinical Practice Guideline on Computer-Aided Detection-Assisted Colonoscopy. Gastroenterology. 2025 Apr. doi:10.1053/j.gastro.2025.01.002.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Even though older adults are more likely to be diagnosed with colorectal cancer (CRC), there is a concerning rise in diagnoses among younger adults, making it essential for healthcare providers to educate adult patients of all ages about the lifestyle-related risk factors associated with the disease.

Many are familiar with the modifiable risk factors of obesity, smoking, and alcohol consumption, but the impact of processed meat — a common element of the Western diet —often remains underappreciated.

But the data are clear: Processed meat, defined as meat that has been altered through methods such as salting, curing, fermentation, or smoking to enhance flavor or preservation, has been linked to an increased risk for CRC.

The International Agency for Research on Cancer, part of the World Health Organization, analyzed over 800 global studies and classified processed meats as carcinogenic to humans, whereas red meat was deemed “probably” carcinogenic. Their findings were later published in The Lancet Oncology, confirming that the strongest epidemiological evidence linked processed meat consumption to CRC.

“While I routinely counsel my patients about lifestyle and dietary risk factors for CRC, including processed meat, I’m not sure how often this is specifically mentioned by physicians in practice,” Peter S. Liang, MD, MPH, an assistant professor and researcher focused on CRC prevention at NYU Langone Health in New York City, and an AGA spokesperson, told GI & Hepatology News.

David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University, both in Norfolk, Virginia, concurred.

Many healthcare providers may not fully recognize the risks posed by processed meat in relation to CRC to counsel their patients, Johnson said. “In my experience, there is not a widespread awareness.”

 

Understanding the Carcinogenic Risks 

The excess risk for CRC per gram of intake is higher for processed meat than for red meat. However, the threshold for harmful consumption varies among studies, and many group red and processed meat together in their analyses.

For example, a 2020 prospective analysis of UK Biobank data reported that a 70 g/d higher intake of red and processed meat was associated with a 32% and 40% greater risk for CRC and colon cancer, respectively.

More recently, a 2025 prospective study examined the associations between CRC and 97 dietary factors in 542,778 women. Investigators found that, aside from alcohol, red and processed meat were the only other dietary factors positively associated with CRC, with a 30 g/d intake increasing the risk for CRC by 8%.

Although the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) recommend limiting red meat consumption to no more than three portions a week, their guidance on processed meat is simpler and more restrictive: Consume very little, if any.

The risk for CRC associated with processed meats is likely due to a naturally occurring element in the meat and carcinogenic compounds that are added or created during its preparation, Johnson said.

Large bodies of evidence support the association between certain compounds in processed meat and cancer, added Ulrike Peters, PhD, MPH, professor and associate director of the Public Health Sciences Division at the Fred Hutchinson Cancer Center in Seattle.

These compounds include:

• Heterocyclic amines: Prevalent in charred and well-done meat, these chemicals are created from the reaction at high temperatures between creatine/creatinine, amino acids, and sugars.
• Nitrates/nitrites: Widely used in the curing of meat (eg, sausages, ham, bacon) to give products their pink coloring and savory flavor, these inorganic compounds bind with amines to produce N-nitrosamines, among the most potent genotoxic carcinogens.
• Polycyclic aromatic hydrocarbons: Generated during high-temperature cooking and smoking, these compounds can induce DNA damage in the colon.
• Heme iron: This type of iron, abundant in red and processed meats, promotes formation of carcinogenic N-nitroso compounds and oxidative damage to intestinal tissue.

Peters said that the compounds may work synergistically to increase the risk for CRC through various mechanisms, including DNA damage, inflammation, and altered gut microbiota.

While it would be useful to study whether the different meat-processing methods — for example, smoking vs salting — affect CRC risk differently, “practically, this is difficult because there’s so much overlap,” Liang noted.

 

Risk Mitigation

Lifestyle factors likely play a crucial role in the risk for CRC. For example, a study of European migrants to Australia found that those from countries with lower CRC incidences tended to develop a higher risk for CRC the longer they resided in Australia due to the dietary change.

Understanding how to mitigate these risk factors is becoming increasingly important with the rates of early-onset CRC projected to double by 2030 in the United States, a trend that is also being observed globally.

“With early-onset CRC, it’s becoming quite clear that there’s no single risk factor that’s driving this increase,” Liang said. “We need to look at the risk factors that we know cause CRC in older adults and see which have become more common over time.”

The consumption of processed meats is one such factor that’s been implicated, particularly for early-onset CRC. The average global consumption of all types of meat per capita has increased significantly over the last 50 years. A 2022 report estimated that global mean processed meat consumption was 17 g/d, with significantly higher rates in high-income regions. This number is expected to rise, with the global processed meat market projected to grow from $318 billion in 2023 to $429 billion by 2029. Given this, the importance of counseling patients to reduce their meat intake is further underscored.

Another strategy for mitigating the risks around processed meat is specifically identifying those patients who may be most vulnerable.

In 2024, Peters and colleagues published findings from their genome-wide gene-environment interaction analysis comparing a large population with CRC and healthy control individuals. The research identified two novel biomarkers that support the role of red and processed meat with an increased risk for CRC and may explain the higher risk in certain population subgroups. They are working on genetic risk prediction models that will incorporate these genetic markers but must first ensure robust validation through larger studies.

“This approach aligns with precision medicine principles, allowing for more personalized prevention strategies, though we’re not quite there yet in terms of clinical application,” Peters said.

Another knowledge gap that future research efforts could address is how dietary factors influence survival outcomes after a diagnosis of CRC.

“The existing guidelines primarily focus on cancer prevention, with strong evidence linking processed meat consumption to increased CRC risk. However, the impact of dietary choices on survival after CRC diagnosis remains poorly understood,” Peters said. “This distinction between prevention and survival is crucial, as biological mechanisms and optimal dietary interventions may differ significantly between these two contexts.”

Well-designed studies investigating the relationship between dietary patterns and CRC survival outcomes would enable the development of evidence-based nutritional recommendations specifically tailored for CRC survivors, Peters said. In addition, she called for well-designed studies that compare levels of processed meat consumption between cohorts of patients with early-onset CRC and healthy counterparts.

“This would help establish whether there’s a true causal relationship rather than just correlation,” Peters said.

 

Simple Strategies to Dietary Changes

With a 2024 study finding that greater adherence to WCRF/AICR Cancer Prevention Recommendations, including reducing processed meat consumption, was linked to a 14% reduction in CRC risk, physicians should emphasize the benefits of adopting dietary and lifestyle recommendations to patients.

Johnson advised simple strategies to encourage any needed dietary changes.

“Pay attention to what you eat, proportions, and variation of meal menus. Those are good starter points,” he told GI & Hepatology News. “None of these recommendations related to meats should be absolute, but reduction can be the target.”

Liang stressed the importance of repeated, nonjudgmental discussions.

“Research shows that physician recommendation is one of the strongest motivators in preventive health, so even if it doesn’t work the first few times, we have to continue delivering the message that can improve our patients’ health.”

A version of this article appeared on Medscape.com.

Even though older adults are more likely to be diagnosed with colorectal cancer (CRC), there is a concerning rise in diagnoses among younger adults, making it essential for healthcare providers to educate adult patients of all ages about the lifestyle-related risk factors associated with the disease.

Many are familiar with the modifiable risk factors of obesity, smoking, and alcohol consumption, but the impact of processed meat — a common element of the Western diet —often remains underappreciated.

But the data are clear: Processed meat, defined as meat that has been altered through methods such as salting, curing, fermentation, or smoking to enhance flavor or preservation, has been linked to an increased risk for CRC.

The International Agency for Research on Cancer, part of the World Health Organization, analyzed over 800 global studies and classified processed meats as carcinogenic to humans, whereas red meat was deemed “probably” carcinogenic. Their findings were later published in The Lancet Oncology, confirming that the strongest epidemiological evidence linked processed meat consumption to CRC.

“While I routinely counsel my patients about lifestyle and dietary risk factors for CRC, including processed meat, I’m not sure how often this is specifically mentioned by physicians in practice,” Peter S. Liang, MD, MPH, an assistant professor and researcher focused on CRC prevention at NYU Langone Health in New York City, and an AGA spokesperson, told GI & Hepatology News.

David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University, both in Norfolk, Virginia, concurred.

Many healthcare providers may not fully recognize the risks posed by processed meat in relation to CRC to counsel their patients, Johnson said. “In my experience, there is not a widespread awareness.”

 

Understanding the Carcinogenic Risks 

The excess risk for CRC per gram of intake is higher for processed meat than for red meat. However, the threshold for harmful consumption varies among studies, and many group red and processed meat together in their analyses.

For example, a 2020 prospective analysis of UK Biobank data reported that a 70 g/d higher intake of red and processed meat was associated with a 32% and 40% greater risk for CRC and colon cancer, respectively.

More recently, a 2025 prospective study examined the associations between CRC and 97 dietary factors in 542,778 women. Investigators found that, aside from alcohol, red and processed meat were the only other dietary factors positively associated with CRC, with a 30 g/d intake increasing the risk for CRC by 8%.

Although the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) recommend limiting red meat consumption to no more than three portions a week, their guidance on processed meat is simpler and more restrictive: Consume very little, if any.

The risk for CRC associated with processed meats is likely due to a naturally occurring element in the meat and carcinogenic compounds that are added or created during its preparation, Johnson said.

Large bodies of evidence support the association between certain compounds in processed meat and cancer, added Ulrike Peters, PhD, MPH, professor and associate director of the Public Health Sciences Division at the Fred Hutchinson Cancer Center in Seattle.

These compounds include:

• Heterocyclic amines: Prevalent in charred and well-done meat, these chemicals are created from the reaction at high temperatures between creatine/creatinine, amino acids, and sugars.
• Nitrates/nitrites: Widely used in the curing of meat (eg, sausages, ham, bacon) to give products their pink coloring and savory flavor, these inorganic compounds bind with amines to produce N-nitrosamines, among the most potent genotoxic carcinogens.
• Polycyclic aromatic hydrocarbons: Generated during high-temperature cooking and smoking, these compounds can induce DNA damage in the colon.
• Heme iron: This type of iron, abundant in red and processed meats, promotes formation of carcinogenic N-nitroso compounds and oxidative damage to intestinal tissue.

Peters said that the compounds may work synergistically to increase the risk for CRC through various mechanisms, including DNA damage, inflammation, and altered gut microbiota.

While it would be useful to study whether the different meat-processing methods — for example, smoking vs salting — affect CRC risk differently, “practically, this is difficult because there’s so much overlap,” Liang noted.

 

Risk Mitigation

Lifestyle factors likely play a crucial role in the risk for CRC. For example, a study of European migrants to Australia found that those from countries with lower CRC incidences tended to develop a higher risk for CRC the longer they resided in Australia due to the dietary change.

Understanding how to mitigate these risk factors is becoming increasingly important with the rates of early-onset CRC projected to double by 2030 in the United States, a trend that is also being observed globally.

“With early-onset CRC, it’s becoming quite clear that there’s no single risk factor that’s driving this increase,” Liang said. “We need to look at the risk factors that we know cause CRC in older adults and see which have become more common over time.”

The consumption of processed meats is one such factor that’s been implicated, particularly for early-onset CRC. The average global consumption of all types of meat per capita has increased significantly over the last 50 years. A 2022 report estimated that global mean processed meat consumption was 17 g/d, with significantly higher rates in high-income regions. This number is expected to rise, with the global processed meat market projected to grow from $318 billion in 2023 to $429 billion by 2029. Given this, the importance of counseling patients to reduce their meat intake is further underscored.

Another strategy for mitigating the risks around processed meat is specifically identifying those patients who may be most vulnerable.

In 2024, Peters and colleagues published findings from their genome-wide gene-environment interaction analysis comparing a large population with CRC and healthy control individuals. The research identified two novel biomarkers that support the role of red and processed meat with an increased risk for CRC and may explain the higher risk in certain population subgroups. They are working on genetic risk prediction models that will incorporate these genetic markers but must first ensure robust validation through larger studies.

“This approach aligns with precision medicine principles, allowing for more personalized prevention strategies, though we’re not quite there yet in terms of clinical application,” Peters said.

Another knowledge gap that future research efforts could address is how dietary factors influence survival outcomes after a diagnosis of CRC.

“The existing guidelines primarily focus on cancer prevention, with strong evidence linking processed meat consumption to increased CRC risk. However, the impact of dietary choices on survival after CRC diagnosis remains poorly understood,” Peters said. “This distinction between prevention and survival is crucial, as biological mechanisms and optimal dietary interventions may differ significantly between these two contexts.”

Well-designed studies investigating the relationship between dietary patterns and CRC survival outcomes would enable the development of evidence-based nutritional recommendations specifically tailored for CRC survivors, Peters said. In addition, she called for well-designed studies that compare levels of processed meat consumption between cohorts of patients with early-onset CRC and healthy counterparts.

“This would help establish whether there’s a true causal relationship rather than just correlation,” Peters said.

 

Simple Strategies to Dietary Changes

With a 2024 study finding that greater adherence to WCRF/AICR Cancer Prevention Recommendations, including reducing processed meat consumption, was linked to a 14% reduction in CRC risk, physicians should emphasize the benefits of adopting dietary and lifestyle recommendations to patients.

Johnson advised simple strategies to encourage any needed dietary changes.

“Pay attention to what you eat, proportions, and variation of meal menus. Those are good starter points,” he told GI & Hepatology News. “None of these recommendations related to meats should be absolute, but reduction can be the target.”

Liang stressed the importance of repeated, nonjudgmental discussions.

“Research shows that physician recommendation is one of the strongest motivators in preventive health, so even if it doesn’t work the first few times, we have to continue delivering the message that can improve our patients’ health.”

A version of this article appeared on Medscape.com.

Even though older adults are more likely to be diagnosed with colorectal cancer (CRC), there is a concerning rise in diagnoses among younger adults, making it essential for healthcare providers to educate adult patients of all ages about the lifestyle-related risk factors associated with the disease.

Many are familiar with the modifiable risk factors of obesity, smoking, and alcohol consumption, but the impact of processed meat — a common element of the Western diet —often remains underappreciated.

But the data are clear: Processed meat, defined as meat that has been altered through methods such as salting, curing, fermentation, or smoking to enhance flavor or preservation, has been linked to an increased risk for CRC.

The International Agency for Research on Cancer, part of the World Health Organization, analyzed over 800 global studies and classified processed meats as carcinogenic to humans, whereas red meat was deemed “probably” carcinogenic. Their findings were later published in The Lancet Oncology, confirming that the strongest epidemiological evidence linked processed meat consumption to CRC.

“While I routinely counsel my patients about lifestyle and dietary risk factors for CRC, including processed meat, I’m not sure how often this is specifically mentioned by physicians in practice,” Peter S. Liang, MD, MPH, an assistant professor and researcher focused on CRC prevention at NYU Langone Health in New York City, and an AGA spokesperson, told GI & Hepatology News.

David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University, both in Norfolk, Virginia, concurred.

Many healthcare providers may not fully recognize the risks posed by processed meat in relation to CRC to counsel their patients, Johnson said. “In my experience, there is not a widespread awareness.”

 

Understanding the Carcinogenic Risks 

The excess risk for CRC per gram of intake is higher for processed meat than for red meat. However, the threshold for harmful consumption varies among studies, and many group red and processed meat together in their analyses.

For example, a 2020 prospective analysis of UK Biobank data reported that a 70 g/d higher intake of red and processed meat was associated with a 32% and 40% greater risk for CRC and colon cancer, respectively.

More recently, a 2025 prospective study examined the associations between CRC and 97 dietary factors in 542,778 women. Investigators found that, aside from alcohol, red and processed meat were the only other dietary factors positively associated with CRC, with a 30 g/d intake increasing the risk for CRC by 8%.

Although the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) recommend limiting red meat consumption to no more than three portions a week, their guidance on processed meat is simpler and more restrictive: Consume very little, if any.

The risk for CRC associated with processed meats is likely due to a naturally occurring element in the meat and carcinogenic compounds that are added or created during its preparation, Johnson said.

Large bodies of evidence support the association between certain compounds in processed meat and cancer, added Ulrike Peters, PhD, MPH, professor and associate director of the Public Health Sciences Division at the Fred Hutchinson Cancer Center in Seattle.

These compounds include:

• Heterocyclic amines: Prevalent in charred and well-done meat, these chemicals are created from the reaction at high temperatures between creatine/creatinine, amino acids, and sugars.
• Nitrates/nitrites: Widely used in the curing of meat (eg, sausages, ham, bacon) to give products their pink coloring and savory flavor, these inorganic compounds bind with amines to produce N-nitrosamines, among the most potent genotoxic carcinogens.
• Polycyclic aromatic hydrocarbons: Generated during high-temperature cooking and smoking, these compounds can induce DNA damage in the colon.
• Heme iron: This type of iron, abundant in red and processed meats, promotes formation of carcinogenic N-nitroso compounds and oxidative damage to intestinal tissue.

Peters said that the compounds may work synergistically to increase the risk for CRC through various mechanisms, including DNA damage, inflammation, and altered gut microbiota.

While it would be useful to study whether the different meat-processing methods — for example, smoking vs salting — affect CRC risk differently, “practically, this is difficult because there’s so much overlap,” Liang noted.

 

Risk Mitigation

Lifestyle factors likely play a crucial role in the risk for CRC. For example, a study of European migrants to Australia found that those from countries with lower CRC incidences tended to develop a higher risk for CRC the longer they resided in Australia due to the dietary change.

Understanding how to mitigate these risk factors is becoming increasingly important with the rates of early-onset CRC projected to double by 2030 in the United States, a trend that is also being observed globally.

“With early-onset CRC, it’s becoming quite clear that there’s no single risk factor that’s driving this increase,” Liang said. “We need to look at the risk factors that we know cause CRC in older adults and see which have become more common over time.”

The consumption of processed meats is one such factor that’s been implicated, particularly for early-onset CRC. The average global consumption of all types of meat per capita has increased significantly over the last 50 years. A 2022 report estimated that global mean processed meat consumption was 17 g/d, with significantly higher rates in high-income regions. This number is expected to rise, with the global processed meat market projected to grow from $318 billion in 2023 to $429 billion by 2029. Given this, the importance of counseling patients to reduce their meat intake is further underscored.

Another strategy for mitigating the risks around processed meat is specifically identifying those patients who may be most vulnerable.

In 2024, Peters and colleagues published findings from their genome-wide gene-environment interaction analysis comparing a large population with CRC and healthy control individuals. The research identified two novel biomarkers that support the role of red and processed meat with an increased risk for CRC and may explain the higher risk in certain population subgroups. They are working on genetic risk prediction models that will incorporate these genetic markers but must first ensure robust validation through larger studies.

“This approach aligns with precision medicine principles, allowing for more personalized prevention strategies, though we’re not quite there yet in terms of clinical application,” Peters said.

Another knowledge gap that future research efforts could address is how dietary factors influence survival outcomes after a diagnosis of CRC.

“The existing guidelines primarily focus on cancer prevention, with strong evidence linking processed meat consumption to increased CRC risk. However, the impact of dietary choices on survival after CRC diagnosis remains poorly understood,” Peters said. “This distinction between prevention and survival is crucial, as biological mechanisms and optimal dietary interventions may differ significantly between these two contexts.”

Well-designed studies investigating the relationship between dietary patterns and CRC survival outcomes would enable the development of evidence-based nutritional recommendations specifically tailored for CRC survivors, Peters said. In addition, she called for well-designed studies that compare levels of processed meat consumption between cohorts of patients with early-onset CRC and healthy counterparts.

“This would help establish whether there’s a true causal relationship rather than just correlation,” Peters said.

 

Simple Strategies to Dietary Changes

With a 2024 study finding that greater adherence to WCRF/AICR Cancer Prevention Recommendations, including reducing processed meat consumption, was linked to a 14% reduction in CRC risk, physicians should emphasize the benefits of adopting dietary and lifestyle recommendations to patients.

Johnson advised simple strategies to encourage any needed dietary changes.

“Pay attention to what you eat, proportions, and variation of meal menus. Those are good starter points,” he told GI & Hepatology News. “None of these recommendations related to meats should be absolute, but reduction can be the target.”

Liang stressed the importance of repeated, nonjudgmental discussions.

“Research shows that physician recommendation is one of the strongest motivators in preventive health, so even if it doesn’t work the first few times, we have to continue delivering the message that can improve our patients’ health.”

A version of this article appeared on Medscape.com.

Pancreatic cancer remains one of the most challenging cancers to diagnose early, with almost half of patients presenting with metastatic disease. Now, a growing body of evidence indicates that this deadly cancer has been steadily on the rise, particularly in younger individuals who may not even realize they are at risk.

A recent survey, for instance, found that 33% of 1000 respondents younger than 50 years believe that only older adults are at risk for pancreatic cancer, and more than half said they wouldn’t even recognize the early signs and symptoms, which include unexplained weight loss, fatigue, jaundice, abdominal pain that radiates to the back, nausea, and vomiting.

These survey findings allude to a bigger challenge: Identifying the disease remains elusive against a backdrop of these increasing rates and nonspecific risks and symptoms.

Currently, only about 15% of pancreatic cancers are caught at a localized, resectable stage, when 5-year survival rates are highest at 44%. But most are found later, after symptoms arise, and at this point, the 5-year survival odds plummet —16% for regional disease, 3% for distant, and 1% for stage IV.

 

“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages,” said survey coauthor Zobeida Cruz-Monserrate, PhD, in the division of gastroenterology, hepatology and nutrition at Ohio State University Medical Center, Columbus.

 

Rising Rates

Since 2001, rates of pancreatic cancer have steadily increased by about 1% annually, and this increase appears greater among younger individuals, especially women.

A recent study in Gastroenterology, for instance, found that, while overall rates of pancreatic cancer among people aged 15-34 years remained low (0.3% in women and 0.2% in men) between 2001 and 2018, the average annual percent change in this age group was considerably higher than that for older individuals — 6.45% for women and 2.97% for men compared with 1.11% for women aged 55 years and 1.17% for men aged 55 years. Another recent analysis, published in Annals of Internal Medicine, reported similar increased rates in men and women aged 15-39 years between 2011 and 2019.

Although more than 90% of cases do occur in those 55 years or older, “we’re now seeing this disease in people who are in their 40s much more regularly,” Cruz-Monserrate said. “This is a concerning trend — and more research is needed to learn why.”

But it’s early days. Studies so far indicate that early onset pancreatic cancer tends to be even more aggressive, but the “underlying reason is not yet clear,” researcher wrote in a 2025 review.

Some evidence indicates younger individuals may have distinct molecular characteristics, whereas other research shows younger and older patients have similar genetic profiles. Younger patients may also be more likely to smoke, drink more, and delay seeking medical attention as well as experience delays in being diagnosed by physicians, the authors explained.

 

Catching It Early

Given the rising rates, early detection is especially important.

There are some known genetic and medical risk factors for pancreatic cancer. About 10% of these cancers are linked to heredity risk or genetic markers, including BRCA1 and BRCA2 or Lynch syndrome. People with chronic pancreatitis, type 2 diabetes, obesity, or with a family history of pancreatic cancer face an elevated risk.

Lifestyle factors can play a role as well. Alcohol consumption, a poor diet that includes red or processed meat, and smoking increase people’s risk for pancreatic cancer. In fact, smoking leads to a twofold higher risk, compared with not smoking.

 

However, uncovering pancreatic cancer from these factors alone can be like “finding a needle in a haystack,” said Srinivas Gaddam, MD, head of the pancreatic cancer screening and early detection program at Cedars-Sinai Medical Center in Los Angeles.

One strategy to help detect the disease earlier would be to screen more.

The latest guidance from the American Cancer Society suggests that people with a genetic predisposition or a family history of pancreatic cancer could benefit from annual surveillance with endoscopic ultrasound or MRI.

But the US Preventive Services Task Force currently recommends against routine screening of average-risk asymptomatic adults (JAMA. 2019;322[5]:438-444). The task force found no evidence that screening for pancreatic cancer improves disease-specific morbidity or mortality or all-cause mortality.

“The absolute incidence in younger people is far too small to make screening beneficial,” explained The Lancet Gastroenterology & Hepatology editors in a 2023 editorial.

In fact, more screening could lead to overdiagnosis, a concern reinforced by the recent study in Annals of Internal Medicine. That analysis found that much of the observed increase in early-onset pancreatic cancer stemmed from the detection of more small, early-stage endocrine cancer, rather than pancreatic adenocarcinoma, whereas mortality from the disease remained stable over the study period.

Recent findings do “suggest the potential for overdiagnosis and overtreatment, particularly in cases of indolent pancreatic neuroendocrine tumors,” Gaddam said.

Gaddam has observed an increase in both adenocarcinoma and neuroendocrine tumors in the clinic and in his research, especially in women younger than 50 years, but he noted these early onset diagnoses do remain rare.

 

Staying Vigilant

As the understanding of pancreatic cancer risks and symptoms evolves, ensuring that patients, especially younger individuals, recognize the warning signs, without causing alarm, remains a challenge.

The disease “presents more advanced in younger patients, but symptoms are so nonspecific,” said Randall Brand, MD, AGAF, director of the gastrointestinal malignancy early detection, diagnosis, and prevention program at the University of Pittsburgh Medical Center, Pennsylvania. Given that, “I am not sure how to best highlight a communication approach that would not cause undue stress to the patient and our healthcare resources.”

Gaddam agreed that it’s tough to pinpoint or communicate straightforward risks or symptoms to the general public without potentially leading to unnecessary screening.

At a minimum, however, clinicians can share more general risk-mitigating strategies with their patients.

Communicating such strategies may be especially important for younger patients, given that the recent survey found almost 40% of younger adults believe there’s nothing they can do to change their risk for pancreatic cancer.

However, Cruz-Monserrate explained, adults of all ages can lower their risks through regular exercise, limited alcohol and tobacco use, and a healthy diet with less red meat or processed meat.

Ultimately, for clinicians, given how difficult it is now to identify pancreatic cancer early, we have to “follow their good clinical judgment when alarming features, such as weight loss or nuances of pancreatic pain arise, and then get good imaging,” Gaddam said.

Cruz-Monserrate, Brand, and Gaddam reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Pancreatic cancer remains one of the most challenging cancers to diagnose early, with almost half of patients presenting with metastatic disease. Now, a growing body of evidence indicates that this deadly cancer has been steadily on the rise, particularly in younger individuals who may not even realize they are at risk.

A recent survey, for instance, found that 33% of 1000 respondents younger than 50 years believe that only older adults are at risk for pancreatic cancer, and more than half said they wouldn’t even recognize the early signs and symptoms, which include unexplained weight loss, fatigue, jaundice, abdominal pain that radiates to the back, nausea, and vomiting.

These survey findings allude to a bigger challenge: Identifying the disease remains elusive against a backdrop of these increasing rates and nonspecific risks and symptoms.

Currently, only about 15% of pancreatic cancers are caught at a localized, resectable stage, when 5-year survival rates are highest at 44%. But most are found later, after symptoms arise, and at this point, the 5-year survival odds plummet —16% for regional disease, 3% for distant, and 1% for stage IV.

 

“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages,” said survey coauthor Zobeida Cruz-Monserrate, PhD, in the division of gastroenterology, hepatology and nutrition at Ohio State University Medical Center, Columbus.

 

Rising Rates

Since 2001, rates of pancreatic cancer have steadily increased by about 1% annually, and this increase appears greater among younger individuals, especially women.

A recent study in Gastroenterology, for instance, found that, while overall rates of pancreatic cancer among people aged 15-34 years remained low (0.3% in women and 0.2% in men) between 2001 and 2018, the average annual percent change in this age group was considerably higher than that for older individuals — 6.45% for women and 2.97% for men compared with 1.11% for women aged 55 years and 1.17% for men aged 55 years. Another recent analysis, published in Annals of Internal Medicine, reported similar increased rates in men and women aged 15-39 years between 2011 and 2019.

Although more than 90% of cases do occur in those 55 years or older, “we’re now seeing this disease in people who are in their 40s much more regularly,” Cruz-Monserrate said. “This is a concerning trend — and more research is needed to learn why.”

But it’s early days. Studies so far indicate that early onset pancreatic cancer tends to be even more aggressive, but the “underlying reason is not yet clear,” researcher wrote in a 2025 review.

Some evidence indicates younger individuals may have distinct molecular characteristics, whereas other research shows younger and older patients have similar genetic profiles. Younger patients may also be more likely to smoke, drink more, and delay seeking medical attention as well as experience delays in being diagnosed by physicians, the authors explained.

 

Catching It Early

Given the rising rates, early detection is especially important.

There are some known genetic and medical risk factors for pancreatic cancer. About 10% of these cancers are linked to heredity risk or genetic markers, including BRCA1 and BRCA2 or Lynch syndrome. People with chronic pancreatitis, type 2 diabetes, obesity, or with a family history of pancreatic cancer face an elevated risk.

Lifestyle factors can play a role as well. Alcohol consumption, a poor diet that includes red or processed meat, and smoking increase people’s risk for pancreatic cancer. In fact, smoking leads to a twofold higher risk, compared with not smoking.

 

However, uncovering pancreatic cancer from these factors alone can be like “finding a needle in a haystack,” said Srinivas Gaddam, MD, head of the pancreatic cancer screening and early detection program at Cedars-Sinai Medical Center in Los Angeles.

One strategy to help detect the disease earlier would be to screen more.

The latest guidance from the American Cancer Society suggests that people with a genetic predisposition or a family history of pancreatic cancer could benefit from annual surveillance with endoscopic ultrasound or MRI.

But the US Preventive Services Task Force currently recommends against routine screening of average-risk asymptomatic adults (JAMA. 2019;322[5]:438-444). The task force found no evidence that screening for pancreatic cancer improves disease-specific morbidity or mortality or all-cause mortality.

“The absolute incidence in younger people is far too small to make screening beneficial,” explained The Lancet Gastroenterology & Hepatology editors in a 2023 editorial.

In fact, more screening could lead to overdiagnosis, a concern reinforced by the recent study in Annals of Internal Medicine. That analysis found that much of the observed increase in early-onset pancreatic cancer stemmed from the detection of more small, early-stage endocrine cancer, rather than pancreatic adenocarcinoma, whereas mortality from the disease remained stable over the study period.

Recent findings do “suggest the potential for overdiagnosis and overtreatment, particularly in cases of indolent pancreatic neuroendocrine tumors,” Gaddam said.

Gaddam has observed an increase in both adenocarcinoma and neuroendocrine tumors in the clinic and in his research, especially in women younger than 50 years, but he noted these early onset diagnoses do remain rare.

 

Staying Vigilant

As the understanding of pancreatic cancer risks and symptoms evolves, ensuring that patients, especially younger individuals, recognize the warning signs, without causing alarm, remains a challenge.

The disease “presents more advanced in younger patients, but symptoms are so nonspecific,” said Randall Brand, MD, AGAF, director of the gastrointestinal malignancy early detection, diagnosis, and prevention program at the University of Pittsburgh Medical Center, Pennsylvania. Given that, “I am not sure how to best highlight a communication approach that would not cause undue stress to the patient and our healthcare resources.”

Gaddam agreed that it’s tough to pinpoint or communicate straightforward risks or symptoms to the general public without potentially leading to unnecessary screening.

At a minimum, however, clinicians can share more general risk-mitigating strategies with their patients.

Communicating such strategies may be especially important for younger patients, given that the recent survey found almost 40% of younger adults believe there’s nothing they can do to change their risk for pancreatic cancer.

However, Cruz-Monserrate explained, adults of all ages can lower their risks through regular exercise, limited alcohol and tobacco use, and a healthy diet with less red meat or processed meat.

Ultimately, for clinicians, given how difficult it is now to identify pancreatic cancer early, we have to “follow their good clinical judgment when alarming features, such as weight loss or nuances of pancreatic pain arise, and then get good imaging,” Gaddam said.

Cruz-Monserrate, Brand, and Gaddam reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Pancreatic cancer remains one of the most challenging cancers to diagnose early, with almost half of patients presenting with metastatic disease. Now, a growing body of evidence indicates that this deadly cancer has been steadily on the rise, particularly in younger individuals who may not even realize they are at risk.

A recent survey, for instance, found that 33% of 1000 respondents younger than 50 years believe that only older adults are at risk for pancreatic cancer, and more than half said they wouldn’t even recognize the early signs and symptoms, which include unexplained weight loss, fatigue, jaundice, abdominal pain that radiates to the back, nausea, and vomiting.

These survey findings allude to a bigger challenge: Identifying the disease remains elusive against a backdrop of these increasing rates and nonspecific risks and symptoms.

Currently, only about 15% of pancreatic cancers are caught at a localized, resectable stage, when 5-year survival rates are highest at 44%. But most are found later, after symptoms arise, and at this point, the 5-year survival odds plummet —16% for regional disease, 3% for distant, and 1% for stage IV.

 

“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages,” said survey coauthor Zobeida Cruz-Monserrate, PhD, in the division of gastroenterology, hepatology and nutrition at Ohio State University Medical Center, Columbus.

 

Rising Rates

Since 2001, rates of pancreatic cancer have steadily increased by about 1% annually, and this increase appears greater among younger individuals, especially women.

A recent study in Gastroenterology, for instance, found that, while overall rates of pancreatic cancer among people aged 15-34 years remained low (0.3% in women and 0.2% in men) between 2001 and 2018, the average annual percent change in this age group was considerably higher than that for older individuals — 6.45% for women and 2.97% for men compared with 1.11% for women aged 55 years and 1.17% for men aged 55 years. Another recent analysis, published in Annals of Internal Medicine, reported similar increased rates in men and women aged 15-39 years between 2011 and 2019.

Although more than 90% of cases do occur in those 55 years or older, “we’re now seeing this disease in people who are in their 40s much more regularly,” Cruz-Monserrate said. “This is a concerning trend — and more research is needed to learn why.”

But it’s early days. Studies so far indicate that early onset pancreatic cancer tends to be even more aggressive, but the “underlying reason is not yet clear,” researcher wrote in a 2025 review.

Some evidence indicates younger individuals may have distinct molecular characteristics, whereas other research shows younger and older patients have similar genetic profiles. Younger patients may also be more likely to smoke, drink more, and delay seeking medical attention as well as experience delays in being diagnosed by physicians, the authors explained.

 

Catching It Early

Given the rising rates, early detection is especially important.

There are some known genetic and medical risk factors for pancreatic cancer. About 10% of these cancers are linked to heredity risk or genetic markers, including BRCA1 and BRCA2 or Lynch syndrome. People with chronic pancreatitis, type 2 diabetes, obesity, or with a family history of pancreatic cancer face an elevated risk.

Lifestyle factors can play a role as well. Alcohol consumption, a poor diet that includes red or processed meat, and smoking increase people’s risk for pancreatic cancer. In fact, smoking leads to a twofold higher risk, compared with not smoking.

 

However, uncovering pancreatic cancer from these factors alone can be like “finding a needle in a haystack,” said Srinivas Gaddam, MD, head of the pancreatic cancer screening and early detection program at Cedars-Sinai Medical Center in Los Angeles.

One strategy to help detect the disease earlier would be to screen more.

The latest guidance from the American Cancer Society suggests that people with a genetic predisposition or a family history of pancreatic cancer could benefit from annual surveillance with endoscopic ultrasound or MRI.

But the US Preventive Services Task Force currently recommends against routine screening of average-risk asymptomatic adults (JAMA. 2019;322[5]:438-444). The task force found no evidence that screening for pancreatic cancer improves disease-specific morbidity or mortality or all-cause mortality.

“The absolute incidence in younger people is far too small to make screening beneficial,” explained The Lancet Gastroenterology & Hepatology editors in a 2023 editorial.

In fact, more screening could lead to overdiagnosis, a concern reinforced by the recent study in Annals of Internal Medicine. That analysis found that much of the observed increase in early-onset pancreatic cancer stemmed from the detection of more small, early-stage endocrine cancer, rather than pancreatic adenocarcinoma, whereas mortality from the disease remained stable over the study period.

Recent findings do “suggest the potential for overdiagnosis and overtreatment, particularly in cases of indolent pancreatic neuroendocrine tumors,” Gaddam said.

Gaddam has observed an increase in both adenocarcinoma and neuroendocrine tumors in the clinic and in his research, especially in women younger than 50 years, but he noted these early onset diagnoses do remain rare.

 

Staying Vigilant

As the understanding of pancreatic cancer risks and symptoms evolves, ensuring that patients, especially younger individuals, recognize the warning signs, without causing alarm, remains a challenge.

The disease “presents more advanced in younger patients, but symptoms are so nonspecific,” said Randall Brand, MD, AGAF, director of the gastrointestinal malignancy early detection, diagnosis, and prevention program at the University of Pittsburgh Medical Center, Pennsylvania. Given that, “I am not sure how to best highlight a communication approach that would not cause undue stress to the patient and our healthcare resources.”

Gaddam agreed that it’s tough to pinpoint or communicate straightforward risks or symptoms to the general public without potentially leading to unnecessary screening.

At a minimum, however, clinicians can share more general risk-mitigating strategies with their patients.

Communicating such strategies may be especially important for younger patients, given that the recent survey found almost 40% of younger adults believe there’s nothing they can do to change their risk for pancreatic cancer.

However, Cruz-Monserrate explained, adults of all ages can lower their risks through regular exercise, limited alcohol and tobacco use, and a healthy diet with less red meat or processed meat.

Ultimately, for clinicians, given how difficult it is now to identify pancreatic cancer early, we have to “follow their good clinical judgment when alarming features, such as weight loss or nuances of pancreatic pain arise, and then get good imaging,” Gaddam said.

Cruz-Monserrate, Brand, and Gaddam reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Dear colleagues,

 

We now have the ability to remove almost any large colon polyp endoscopically using a variety of techniques — from the widely used endoscopic mucosal resection to the increasingly prevalent endoscopic submucosal dissection. Yet, in this new era, are there specific polyps for which we should exercise caution and consult a surgeon first?

In this issue of Perspectives, Dr. Jeffrey Mosko and Dr. Moamen Gabr discuss the importance of careful polyp selection and argue that almost all polyps can be safely removed endoscopically, with low recurrence rates. In contrast, Dr. Ira Leeds from colorectal surgery offers a counterpoint, urging caution when managing polyps in the cecum and rectum while highlighting the role of minimally invasive surgical approaches. We hope these discussions provide valuable insights to support your approach to managing large colorectal polyps, especially in an era of increasing colon cancer screening. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Advantages of Endoscopic Resection for Large Colon Polyps

BY MOAMEN GABR, MD, MSC, AND JEFFREY D. MOSKO MD, MSC

General Advantages

Endoscopy has revolutionized the management of large colorectal polyps, offering a minimally invasive alternative to surgical resection. The dawn of endoscopic resection in the late 20th century, particularly the evolution of endoscopic mucosal resection (EMR) in Japan, marked a paradigm shift in the treatment of colonic lesions by enabling the removal of lesions that would otherwise necessitate surgery.

Endoscopic resection of colorectal polyps is generally performed in an outpatient setting, allowing patients to recover at home the same day. This not only minimizes disruption to daily life but also significantly enhances patient satisfaction.

Most procedures are performed under moderate or deep sedation eliminating the need for general anesthesia. This represents a critical benefit, particularly for older or medically frail patients who are at higher risk of anesthesia-related complications.

From an economic perspective, endoscopic resection reduces healthcare costs by eliminating prolonged hospital stays and complex perioperative care. Additionally, preserving the colon’s structure and function avoids long-term consequences such as altered bowel habits or ostomy dependence, common with surgical interventions.

The advantages of endoscopic intervention are clear: safety, cost-effectiveness, organ preservation, and convenience for patients.

 

Lesion Selection

The superiority of endoscopic resection relies on selecting lesions appropriately, specifically those with a low risk of lymph node metastases. This meticulous process should include assessing a lesion’s size, location, morphology, granularity, microvascular and surface pit pattern using a combination of high-definition white light endoscopy, virtual chromoendoscopy and image magnification (when available).

Gross morphologic assessment utilizes the Paris and LST classifications. Combining the Paris classification, lesion granularity and location is both straightforward and revealing. Ulcerated/excavated lesions (0-III) are concerning for deep invasion. Depressed (0-IIc) morphologies are strongly associated with T1 CRC. Nodular lesions (0-Is or IIa + Is) have a higher risk of T1 colorectal cancer (CRC), compared with flat lesions (0-IIa or 0-IIb). Non-granular lesions (0-Is and 0-IIa + Is) have a higher risk of covert cancer. Finally, the rectosigmoid location is associated with an increased risk of T1 CRC (vs. proximal locations).

Endoscopic surface pattern assessment increases one’s diagnostic accuracy. There are three primary endoscopic surface pattern classifications: NBI International Colorectal Endoscopic (NICE), Japanese NBI expert team (JNET), and Kudo pit pattern classifications. Colonic lesions that have a NICE Type 3, JNET 3, or Kudo type Vn pattern should be referred promptly for surgical resection. Lesions with a JNET 2B or Kudo type VI carry a higher risk of superficial T1 CRC but can still be removed endoscopically (see below) in expert centers. All other lesions should undergo endoscopic resection. 

 

Endoscopic Resection Techniques

Endoscopic resection of large colorectal polyps encompasses two primary techniques: EMR and endoscopic submucosal dissection (ESD), each tailored to specific lesion characteristics and operator expertise.

EMR, the technique of choice for the vast majority of lesions, relies on injecting a submucosal cushion to lift the lesion before excision. Recent advances, including enhanced snare designs and underwater EMR, have improved en-bloc resection rates, significantly reducing recurrence and enhancing the efficacy of this technique.

ESD offers unparalleled precision for en-bloc resection of complex lesions, particularly those with fibrosis or high-risk features. Cutting-edge innovations, such as traction devices, have streamlined the procedure, addressing the traditional challenges of ESD. Despite being more time intensive, ESD minimizes recurrence and provides complete histopathological evaluation, critical for the management of malignant or pre-malignant lesions.

For non-lifting polyps, newer techniques such as endoscopic full-thickness resection (eFTR), using tools like the Full-Thickness Resection Device (FTRD), enable resection of up to 2-3 cm of the colonic or rectal wall. This ensures complete removal of any lesion and its underlying tissue, effectively preventing recurrence.

These advancements demonstrate how endoscopy can tackle even the most challenging colorectal polyps, reinforcing its position as the preferred treatment modality.

 

Perceived Limitations 

With ongoing refinement over the last 2 decades, many of the perceived limitations (below) of endoscopic resection have now been overcome.

• Difficult locations/access: Historically lesions at the anorectal junction, ileocecal valve, appendiceal orifice and anastomoses were preferentially sent for surgery. In spite of unique technical challenges at each of these locations, there is now compelling data supporting EMR for these scenarios. We now also have techniques aimed at enabling the resection of lesions with poor access including patient repositioning, distal attachments, variable endoscope diameter/flexibility, traction and overtube devices.
• Recurrence: In the past, recurrence after endoscopic resection of lesions > 20 mm has been reported to be as high as 20%. With our current systematic approach to complete resection, meticulous examination of the post-resection defect for residual polyp tissue, adjunctive techniques to address submucosal fibrosis (hot avulsion, CAST, submucosal release) and thermal ablation to the resection margin (EMR-T), the risk of recurrence for piecemeal resections can be decreased to < 5%. In fact, some groups argue for the en-bloc resection of all large colorectal lesions based on the extremely low (< 1%) recurrence rates and potential for decreased follow-up.
• Post-resection bleeding: Post-resection bleeding is no longer a major limitation of any endoscopic approach because of the combination of improved intra-procedural hemostatic and resection techniques, optimized electrosurgical technology, and enhanced defect closure capabilities and devices (with prophylactic defect closure now supported by randomized control trial level data).
• Perforation: Deep mural injury, once an endoscopists’ worst fear during resection, is no longer a surgical emergency. It can now be predicted, identified (Sydney classification) and successfully managed. In spite of more widespread aggressive resection strategies, the risk of emergency surgery in patients undergoing EMR and even ESD (where the risk of DMI is significantly higher) is extremely low.

Endoscopic resection for large colorectal polyps is effective, available, minimally invasive and organ sparing making it the standard of care for the management of colonic polyps. With ongoing iteration in techniques, more invasive surgical approaches can be avoided in almost all patients with benign and low-risk T1 colorectal cancers.

Dr. Gabr is associate GI division director at the University of Cincinnati, Ohio. Dr. Mosko is based in the division of gastroenterology at St. Michael’s Hospital, Toronto, Ontario, Canada. The authors declare no conflicts of interest.

Blurred Lines: Polyp Needing Surgical versus Endoscopic Excision

BY IRA LEEDS, MD

I am grateful for the invitation to join in discussion with Dr. Gabr and Dr. Mosko on the ever-increasing role of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, as a surgeon, I do carry at least mild trepidation entering one of the literary “safe spaces” of my gastroenterology colleagues.

With the increasing evidentiary support of EMR approaches and the increasing experience of those performing ESD, these two techniques are quickly becoming the options of choice. As these practices become ubiquitous, it is important to recognize both their advantages and limitations, compared with available surgical options. The decision to proceed with EMR and ESD is essentially a turning point away from early surgical referral for a complex lesion. In this discussion, I intend to highlight when EMR and ESD have a clear advantage to early surgical referral, why I believe that early surgical referral is still superior to advanced endoscopic techniques in the rectum, and why the approach for right-sided lesions should hinge on careful shared decision-making. 

 

Endoscopic approaches nearly always beat surgical approaches when considering short-term risks. Even in the best surgical series, colorectal surgery typically leads to complications in 10%-15% of patients, 1%-5% being serious. Moreover, transabdominal surgical interventions (ie, colectomy) require considerable recovery involving at least a few days in the inpatient setting and over a month of activity restrictions. Finally, there is a minority of chronically unwell patients who cannot tolerate surgical intervention but may be fortunate enough to have a lesion that with enhanced attention can be endoscopically resectioned. While EMR and ESD also contribute a disproportionate burden of complications to endoscopy practice, overall complication rates are still favorable when compared with surgical resection.

Moreover, the most feared short-term complication of EMR and ESD, perforation, has the added benefit of a “controlled failure” to colectomy. Advanced endoscopic approaches already require a prepared colon, and patients are given strict return instructions. Hence, the yearly handful of postprocedural perforations that I get called upon to assist with typically tolerate a routine surgical exploration, repair or resection, and recover at rates equal to or better than elective colon resections. For these reasons, lesions that can be endoscopically removed within appropriate risk tolerances, can and should be considered for EMR or ESD at time of diagnosis.

There are two clinical scenarios where this consideration for up-front EMR or ESD requires further caution. First, any rectal lesion considered for advanced endoscopic techniques really needs to be done in multidisciplinary conference with a colorectal surgeon. In the modern era of colorectal surgery, surgeons now have numerous approaches to reach the rectum that bridge the gap between traditional endoscopy and transabdominal resection. For many rectal lesions, transanal laparoscopic and robotic approaches offer the opportunity for local excision. The most commonly practiced approach, transanal minimally invasive microsurgery (TAMIS), provides many of the benefits of endoscopy (eg, same-day discharge, no activity restrictions, limited periprocedural physiologic stress, low complication rates) while providing the surgical precision, repair strategies, and specimen orientation of conventional surgery. Anecdotally, the time it takes to do a high-quality TAMIS excision in the rectum can be substantially less than that required for a comparable ESD.

For rectal lesions in particular, specimen quality is paramount for oncologic prognosis. Regardless of any intrinsic favorable histopathology or deft hand of the endoscopist, a TAMIS approach will typically provide for a deeper partial thickness or even full thickness excision. More times each year than I would like, I find myself at a multidisciplinary tumor board discussing an endoscopically removed rectal lesion done in a piecemeal fashion or insufficient deep ESD where appropriate risk stratification is impossible and we end up offering patients a likely overly aggressive proctectomy or a potentially oncologically unsound re-excision. Consideration of EMR/ESD vs TAMIS up front would allow better sorting of which technique is most suited to which lesion and avoid these diagnostic dilemmas that only seem to be more common as EMR and ESD practices proliferate.

For a different set of reasons, an advanced cecal adenoma may also be more suited to upfront surgical considerations. Right colon lesions can be more challenging for surveillance for a host of reasons. Procedurally, right colon lesions are undeniably more difficult. The thin-walled cecum can be unforgiving for repeated polypectomies. Despite it being an uncomfortable subject for colonoscopists, the evidence suggests that getting to the cecum is not consistent or 100% expected. Finally, patients can be unwilling to undergo serial bowel preparation and endoscopic examination. In contrast, a laparoscopic right colectomy avoids these issues while also attributing little additional risk. Laparoscopic right-colon operations have overall complication rates of less than 10% and major complications of less than 1%. Hospital stays for laparoscopic right colectomy are typically 3 days or less. Finally, surgery reduces both the frequency of surveillance, and a shortened colon makes surveillance easier.

Advanced polypectomy techniques broaden our ability to address even difficult lesions under the ideally aligned degree of invasive procedure. However, like any procedure, these techniques have their own advantages and limitations. There will always be a minority of premalignant colon lesions that are best suited to surgery-first approaches to treatment. In my practice, maintaining open lines of communication and regular interaction with my endoscopy colleagues naturally leads to polyps being addressed in their most suitable fashion.

Dr. Leeds is assistant professor of surgery at the Yale School of Medicine and a staff surgeon at the VA Connecticut Healthcare System. He declares no conflicts of interest.

Dear colleagues,

 

We now have the ability to remove almost any large colon polyp endoscopically using a variety of techniques — from the widely used endoscopic mucosal resection to the increasingly prevalent endoscopic submucosal dissection. Yet, in this new era, are there specific polyps for which we should exercise caution and consult a surgeon first?

In this issue of Perspectives, Dr. Jeffrey Mosko and Dr. Moamen Gabr discuss the importance of careful polyp selection and argue that almost all polyps can be safely removed endoscopically, with low recurrence rates. In contrast, Dr. Ira Leeds from colorectal surgery offers a counterpoint, urging caution when managing polyps in the cecum and rectum while highlighting the role of minimally invasive surgical approaches. We hope these discussions provide valuable insights to support your approach to managing large colorectal polyps, especially in an era of increasing colon cancer screening. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Advantages of Endoscopic Resection for Large Colon Polyps

BY MOAMEN GABR, MD, MSC, AND JEFFREY D. MOSKO MD, MSC

General Advantages

Endoscopy has revolutionized the management of large colorectal polyps, offering a minimally invasive alternative to surgical resection. The dawn of endoscopic resection in the late 20th century, particularly the evolution of endoscopic mucosal resection (EMR) in Japan, marked a paradigm shift in the treatment of colonic lesions by enabling the removal of lesions that would otherwise necessitate surgery.

Endoscopic resection of colorectal polyps is generally performed in an outpatient setting, allowing patients to recover at home the same day. This not only minimizes disruption to daily life but also significantly enhances patient satisfaction.

Most procedures are performed under moderate or deep sedation eliminating the need for general anesthesia. This represents a critical benefit, particularly for older or medically frail patients who are at higher risk of anesthesia-related complications.

From an economic perspective, endoscopic resection reduces healthcare costs by eliminating prolonged hospital stays and complex perioperative care. Additionally, preserving the colon’s structure and function avoids long-term consequences such as altered bowel habits or ostomy dependence, common with surgical interventions.

The advantages of endoscopic intervention are clear: safety, cost-effectiveness, organ preservation, and convenience for patients.

 

Lesion Selection

The superiority of endoscopic resection relies on selecting lesions appropriately, specifically those with a low risk of lymph node metastases. This meticulous process should include assessing a lesion’s size, location, morphology, granularity, microvascular and surface pit pattern using a combination of high-definition white light endoscopy, virtual chromoendoscopy and image magnification (when available).

Gross morphologic assessment utilizes the Paris and LST classifications. Combining the Paris classification, lesion granularity and location is both straightforward and revealing. Ulcerated/excavated lesions (0-III) are concerning for deep invasion. Depressed (0-IIc) morphologies are strongly associated with T1 CRC. Nodular lesions (0-Is or IIa + Is) have a higher risk of T1 colorectal cancer (CRC), compared with flat lesions (0-IIa or 0-IIb). Non-granular lesions (0-Is and 0-IIa + Is) have a higher risk of covert cancer. Finally, the rectosigmoid location is associated with an increased risk of T1 CRC (vs. proximal locations).

Endoscopic surface pattern assessment increases one’s diagnostic accuracy. There are three primary endoscopic surface pattern classifications: NBI International Colorectal Endoscopic (NICE), Japanese NBI expert team (JNET), and Kudo pit pattern classifications. Colonic lesions that have a NICE Type 3, JNET 3, or Kudo type Vn pattern should be referred promptly for surgical resection. Lesions with a JNET 2B or Kudo type VI carry a higher risk of superficial T1 CRC but can still be removed endoscopically (see below) in expert centers. All other lesions should undergo endoscopic resection. 

 

Endoscopic Resection Techniques

Endoscopic resection of large colorectal polyps encompasses two primary techniques: EMR and endoscopic submucosal dissection (ESD), each tailored to specific lesion characteristics and operator expertise.

EMR, the technique of choice for the vast majority of lesions, relies on injecting a submucosal cushion to lift the lesion before excision. Recent advances, including enhanced snare designs and underwater EMR, have improved en-bloc resection rates, significantly reducing recurrence and enhancing the efficacy of this technique.

ESD offers unparalleled precision for en-bloc resection of complex lesions, particularly those with fibrosis or high-risk features. Cutting-edge innovations, such as traction devices, have streamlined the procedure, addressing the traditional challenges of ESD. Despite being more time intensive, ESD minimizes recurrence and provides complete histopathological evaluation, critical for the management of malignant or pre-malignant lesions.

For non-lifting polyps, newer techniques such as endoscopic full-thickness resection (eFTR), using tools like the Full-Thickness Resection Device (FTRD), enable resection of up to 2-3 cm of the colonic or rectal wall. This ensures complete removal of any lesion and its underlying tissue, effectively preventing recurrence.

These advancements demonstrate how endoscopy can tackle even the most challenging colorectal polyps, reinforcing its position as the preferred treatment modality.

 

Perceived Limitations 

With ongoing refinement over the last 2 decades, many of the perceived limitations (below) of endoscopic resection have now been overcome.

• Difficult locations/access: Historically lesions at the anorectal junction, ileocecal valve, appendiceal orifice and anastomoses were preferentially sent for surgery. In spite of unique technical challenges at each of these locations, there is now compelling data supporting EMR for these scenarios. We now also have techniques aimed at enabling the resection of lesions with poor access including patient repositioning, distal attachments, variable endoscope diameter/flexibility, traction and overtube devices.
• Recurrence: In the past, recurrence after endoscopic resection of lesions > 20 mm has been reported to be as high as 20%. With our current systematic approach to complete resection, meticulous examination of the post-resection defect for residual polyp tissue, adjunctive techniques to address submucosal fibrosis (hot avulsion, CAST, submucosal release) and thermal ablation to the resection margin (EMR-T), the risk of recurrence for piecemeal resections can be decreased to < 5%. In fact, some groups argue for the en-bloc resection of all large colorectal lesions based on the extremely low (< 1%) recurrence rates and potential for decreased follow-up.
• Post-resection bleeding: Post-resection bleeding is no longer a major limitation of any endoscopic approach because of the combination of improved intra-procedural hemostatic and resection techniques, optimized electrosurgical technology, and enhanced defect closure capabilities and devices (with prophylactic defect closure now supported by randomized control trial level data).
• Perforation: Deep mural injury, once an endoscopists’ worst fear during resection, is no longer a surgical emergency. It can now be predicted, identified (Sydney classification) and successfully managed. In spite of more widespread aggressive resection strategies, the risk of emergency surgery in patients undergoing EMR and even ESD (where the risk of DMI is significantly higher) is extremely low.

Endoscopic resection for large colorectal polyps is effective, available, minimally invasive and organ sparing making it the standard of care for the management of colonic polyps. With ongoing iteration in techniques, more invasive surgical approaches can be avoided in almost all patients with benign and low-risk T1 colorectal cancers.

Dr. Gabr is associate GI division director at the University of Cincinnati, Ohio. Dr. Mosko is based in the division of gastroenterology at St. Michael’s Hospital, Toronto, Ontario, Canada. The authors declare no conflicts of interest.

Blurred Lines: Polyp Needing Surgical versus Endoscopic Excision

BY IRA LEEDS, MD

I am grateful for the invitation to join in discussion with Dr. Gabr and Dr. Mosko on the ever-increasing role of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, as a surgeon, I do carry at least mild trepidation entering one of the literary “safe spaces” of my gastroenterology colleagues.

With the increasing evidentiary support of EMR approaches and the increasing experience of those performing ESD, these two techniques are quickly becoming the options of choice. As these practices become ubiquitous, it is important to recognize both their advantages and limitations, compared with available surgical options. The decision to proceed with EMR and ESD is essentially a turning point away from early surgical referral for a complex lesion. In this discussion, I intend to highlight when EMR and ESD have a clear advantage to early surgical referral, why I believe that early surgical referral is still superior to advanced endoscopic techniques in the rectum, and why the approach for right-sided lesions should hinge on careful shared decision-making. 

 

Endoscopic approaches nearly always beat surgical approaches when considering short-term risks. Even in the best surgical series, colorectal surgery typically leads to complications in 10%-15% of patients, 1%-5% being serious. Moreover, transabdominal surgical interventions (ie, colectomy) require considerable recovery involving at least a few days in the inpatient setting and over a month of activity restrictions. Finally, there is a minority of chronically unwell patients who cannot tolerate surgical intervention but may be fortunate enough to have a lesion that with enhanced attention can be endoscopically resectioned. While EMR and ESD also contribute a disproportionate burden of complications to endoscopy practice, overall complication rates are still favorable when compared with surgical resection.

Moreover, the most feared short-term complication of EMR and ESD, perforation, has the added benefit of a “controlled failure” to colectomy. Advanced endoscopic approaches already require a prepared colon, and patients are given strict return instructions. Hence, the yearly handful of postprocedural perforations that I get called upon to assist with typically tolerate a routine surgical exploration, repair or resection, and recover at rates equal to or better than elective colon resections. For these reasons, lesions that can be endoscopically removed within appropriate risk tolerances, can and should be considered for EMR or ESD at time of diagnosis.

There are two clinical scenarios where this consideration for up-front EMR or ESD requires further caution. First, any rectal lesion considered for advanced endoscopic techniques really needs to be done in multidisciplinary conference with a colorectal surgeon. In the modern era of colorectal surgery, surgeons now have numerous approaches to reach the rectum that bridge the gap between traditional endoscopy and transabdominal resection. For many rectal lesions, transanal laparoscopic and robotic approaches offer the opportunity for local excision. The most commonly practiced approach, transanal minimally invasive microsurgery (TAMIS), provides many of the benefits of endoscopy (eg, same-day discharge, no activity restrictions, limited periprocedural physiologic stress, low complication rates) while providing the surgical precision, repair strategies, and specimen orientation of conventional surgery. Anecdotally, the time it takes to do a high-quality TAMIS excision in the rectum can be substantially less than that required for a comparable ESD.

For rectal lesions in particular, specimen quality is paramount for oncologic prognosis. Regardless of any intrinsic favorable histopathology or deft hand of the endoscopist, a TAMIS approach will typically provide for a deeper partial thickness or even full thickness excision. More times each year than I would like, I find myself at a multidisciplinary tumor board discussing an endoscopically removed rectal lesion done in a piecemeal fashion or insufficient deep ESD where appropriate risk stratification is impossible and we end up offering patients a likely overly aggressive proctectomy or a potentially oncologically unsound re-excision. Consideration of EMR/ESD vs TAMIS up front would allow better sorting of which technique is most suited to which lesion and avoid these diagnostic dilemmas that only seem to be more common as EMR and ESD practices proliferate.

For a different set of reasons, an advanced cecal adenoma may also be more suited to upfront surgical considerations. Right colon lesions can be more challenging for surveillance for a host of reasons. Procedurally, right colon lesions are undeniably more difficult. The thin-walled cecum can be unforgiving for repeated polypectomies. Despite it being an uncomfortable subject for colonoscopists, the evidence suggests that getting to the cecum is not consistent or 100% expected. Finally, patients can be unwilling to undergo serial bowel preparation and endoscopic examination. In contrast, a laparoscopic right colectomy avoids these issues while also attributing little additional risk. Laparoscopic right-colon operations have overall complication rates of less than 10% and major complications of less than 1%. Hospital stays for laparoscopic right colectomy are typically 3 days or less. Finally, surgery reduces both the frequency of surveillance, and a shortened colon makes surveillance easier.

Advanced polypectomy techniques broaden our ability to address even difficult lesions under the ideally aligned degree of invasive procedure. However, like any procedure, these techniques have their own advantages and limitations. There will always be a minority of premalignant colon lesions that are best suited to surgery-first approaches to treatment. In my practice, maintaining open lines of communication and regular interaction with my endoscopy colleagues naturally leads to polyps being addressed in their most suitable fashion.

Dr. Leeds is assistant professor of surgery at the Yale School of Medicine and a staff surgeon at the VA Connecticut Healthcare System. He declares no conflicts of interest.

Dear colleagues,

 

We now have the ability to remove almost any large colon polyp endoscopically using a variety of techniques — from the widely used endoscopic mucosal resection to the increasingly prevalent endoscopic submucosal dissection. Yet, in this new era, are there specific polyps for which we should exercise caution and consult a surgeon first?

In this issue of Perspectives, Dr. Jeffrey Mosko and Dr. Moamen Gabr discuss the importance of careful polyp selection and argue that almost all polyps can be safely removed endoscopically, with low recurrence rates. In contrast, Dr. Ira Leeds from colorectal surgery offers a counterpoint, urging caution when managing polyps in the cecum and rectum while highlighting the role of minimally invasive surgical approaches. We hope these discussions provide valuable insights to support your approach to managing large colorectal polyps, especially in an era of increasing colon cancer screening. 

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Advantages of Endoscopic Resection for Large Colon Polyps

BY MOAMEN GABR, MD, MSC, AND JEFFREY D. MOSKO MD, MSC

General Advantages

Endoscopy has revolutionized the management of large colorectal polyps, offering a minimally invasive alternative to surgical resection. The dawn of endoscopic resection in the late 20th century, particularly the evolution of endoscopic mucosal resection (EMR) in Japan, marked a paradigm shift in the treatment of colonic lesions by enabling the removal of lesions that would otherwise necessitate surgery.

Endoscopic resection of colorectal polyps is generally performed in an outpatient setting, allowing patients to recover at home the same day. This not only minimizes disruption to daily life but also significantly enhances patient satisfaction.

Most procedures are performed under moderate or deep sedation eliminating the need for general anesthesia. This represents a critical benefit, particularly for older or medically frail patients who are at higher risk of anesthesia-related complications.

From an economic perspective, endoscopic resection reduces healthcare costs by eliminating prolonged hospital stays and complex perioperative care. Additionally, preserving the colon’s structure and function avoids long-term consequences such as altered bowel habits or ostomy dependence, common with surgical interventions.

The advantages of endoscopic intervention are clear: safety, cost-effectiveness, organ preservation, and convenience for patients.

 

Lesion Selection

The superiority of endoscopic resection relies on selecting lesions appropriately, specifically those with a low risk of lymph node metastases. This meticulous process should include assessing a lesion’s size, location, morphology, granularity, microvascular and surface pit pattern using a combination of high-definition white light endoscopy, virtual chromoendoscopy and image magnification (when available).

Gross morphologic assessment utilizes the Paris and LST classifications. Combining the Paris classification, lesion granularity and location is both straightforward and revealing. Ulcerated/excavated lesions (0-III) are concerning for deep invasion. Depressed (0-IIc) morphologies are strongly associated with T1 CRC. Nodular lesions (0-Is or IIa + Is) have a higher risk of T1 colorectal cancer (CRC), compared with flat lesions (0-IIa or 0-IIb). Non-granular lesions (0-Is and 0-IIa + Is) have a higher risk of covert cancer. Finally, the rectosigmoid location is associated with an increased risk of T1 CRC (vs. proximal locations).

Endoscopic surface pattern assessment increases one’s diagnostic accuracy. There are three primary endoscopic surface pattern classifications: NBI International Colorectal Endoscopic (NICE), Japanese NBI expert team (JNET), and Kudo pit pattern classifications. Colonic lesions that have a NICE Type 3, JNET 3, or Kudo type Vn pattern should be referred promptly for surgical resection. Lesions with a JNET 2B or Kudo type VI carry a higher risk of superficial T1 CRC but can still be removed endoscopically (see below) in expert centers. All other lesions should undergo endoscopic resection. 

 

Endoscopic Resection Techniques

Endoscopic resection of large colorectal polyps encompasses two primary techniques: EMR and endoscopic submucosal dissection (ESD), each tailored to specific lesion characteristics and operator expertise.

EMR, the technique of choice for the vast majority of lesions, relies on injecting a submucosal cushion to lift the lesion before excision. Recent advances, including enhanced snare designs and underwater EMR, have improved en-bloc resection rates, significantly reducing recurrence and enhancing the efficacy of this technique.

ESD offers unparalleled precision for en-bloc resection of complex lesions, particularly those with fibrosis or high-risk features. Cutting-edge innovations, such as traction devices, have streamlined the procedure, addressing the traditional challenges of ESD. Despite being more time intensive, ESD minimizes recurrence and provides complete histopathological evaluation, critical for the management of malignant or pre-malignant lesions.

For non-lifting polyps, newer techniques such as endoscopic full-thickness resection (eFTR), using tools like the Full-Thickness Resection Device (FTRD), enable resection of up to 2-3 cm of the colonic or rectal wall. This ensures complete removal of any lesion and its underlying tissue, effectively preventing recurrence.

These advancements demonstrate how endoscopy can tackle even the most challenging colorectal polyps, reinforcing its position as the preferred treatment modality.

 

Perceived Limitations 

With ongoing refinement over the last 2 decades, many of the perceived limitations (below) of endoscopic resection have now been overcome.

• Difficult locations/access: Historically lesions at the anorectal junction, ileocecal valve, appendiceal orifice and anastomoses were preferentially sent for surgery. In spite of unique technical challenges at each of these locations, there is now compelling data supporting EMR for these scenarios. We now also have techniques aimed at enabling the resection of lesions with poor access including patient repositioning, distal attachments, variable endoscope diameter/flexibility, traction and overtube devices.
• Recurrence: In the past, recurrence after endoscopic resection of lesions > 20 mm has been reported to be as high as 20%. With our current systematic approach to complete resection, meticulous examination of the post-resection defect for residual polyp tissue, adjunctive techniques to address submucosal fibrosis (hot avulsion, CAST, submucosal release) and thermal ablation to the resection margin (EMR-T), the risk of recurrence for piecemeal resections can be decreased to < 5%. In fact, some groups argue for the en-bloc resection of all large colorectal lesions based on the extremely low (< 1%) recurrence rates and potential for decreased follow-up.
• Post-resection bleeding: Post-resection bleeding is no longer a major limitation of any endoscopic approach because of the combination of improved intra-procedural hemostatic and resection techniques, optimized electrosurgical technology, and enhanced defect closure capabilities and devices (with prophylactic defect closure now supported by randomized control trial level data).
• Perforation: Deep mural injury, once an endoscopists’ worst fear during resection, is no longer a surgical emergency. It can now be predicted, identified (Sydney classification) and successfully managed. In spite of more widespread aggressive resection strategies, the risk of emergency surgery in patients undergoing EMR and even ESD (where the risk of DMI is significantly higher) is extremely low.

Endoscopic resection for large colorectal polyps is effective, available, minimally invasive and organ sparing making it the standard of care for the management of colonic polyps. With ongoing iteration in techniques, more invasive surgical approaches can be avoided in almost all patients with benign and low-risk T1 colorectal cancers.

Dr. Gabr is associate GI division director at the University of Cincinnati, Ohio. Dr. Mosko is based in the division of gastroenterology at St. Michael’s Hospital, Toronto, Ontario, Canada. The authors declare no conflicts of interest.

Blurred Lines: Polyp Needing Surgical versus Endoscopic Excision

BY IRA LEEDS, MD

I am grateful for the invitation to join in discussion with Dr. Gabr and Dr. Mosko on the ever-increasing role of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, as a surgeon, I do carry at least mild trepidation entering one of the literary “safe spaces” of my gastroenterology colleagues.

With the increasing evidentiary support of EMR approaches and the increasing experience of those performing ESD, these two techniques are quickly becoming the options of choice. As these practices become ubiquitous, it is important to recognize both their advantages and limitations, compared with available surgical options. The decision to proceed with EMR and ESD is essentially a turning point away from early surgical referral for a complex lesion. In this discussion, I intend to highlight when EMR and ESD have a clear advantage to early surgical referral, why I believe that early surgical referral is still superior to advanced endoscopic techniques in the rectum, and why the approach for right-sided lesions should hinge on careful shared decision-making. 

 

Endoscopic approaches nearly always beat surgical approaches when considering short-term risks. Even in the best surgical series, colorectal surgery typically leads to complications in 10%-15% of patients, 1%-5% being serious. Moreover, transabdominal surgical interventions (ie, colectomy) require considerable recovery involving at least a few days in the inpatient setting and over a month of activity restrictions. Finally, there is a minority of chronically unwell patients who cannot tolerate surgical intervention but may be fortunate enough to have a lesion that with enhanced attention can be endoscopically resectioned. While EMR and ESD also contribute a disproportionate burden of complications to endoscopy practice, overall complication rates are still favorable when compared with surgical resection.

Moreover, the most feared short-term complication of EMR and ESD, perforation, has the added benefit of a “controlled failure” to colectomy. Advanced endoscopic approaches already require a prepared colon, and patients are given strict return instructions. Hence, the yearly handful of postprocedural perforations that I get called upon to assist with typically tolerate a routine surgical exploration, repair or resection, and recover at rates equal to or better than elective colon resections. For these reasons, lesions that can be endoscopically removed within appropriate risk tolerances, can and should be considered for EMR or ESD at time of diagnosis.

There are two clinical scenarios where this consideration for up-front EMR or ESD requires further caution. First, any rectal lesion considered for advanced endoscopic techniques really needs to be done in multidisciplinary conference with a colorectal surgeon. In the modern era of colorectal surgery, surgeons now have numerous approaches to reach the rectum that bridge the gap between traditional endoscopy and transabdominal resection. For many rectal lesions, transanal laparoscopic and robotic approaches offer the opportunity for local excision. The most commonly practiced approach, transanal minimally invasive microsurgery (TAMIS), provides many of the benefits of endoscopy (eg, same-day discharge, no activity restrictions, limited periprocedural physiologic stress, low complication rates) while providing the surgical precision, repair strategies, and specimen orientation of conventional surgery. Anecdotally, the time it takes to do a high-quality TAMIS excision in the rectum can be substantially less than that required for a comparable ESD.

For rectal lesions in particular, specimen quality is paramount for oncologic prognosis. Regardless of any intrinsic favorable histopathology or deft hand of the endoscopist, a TAMIS approach will typically provide for a deeper partial thickness or even full thickness excision. More times each year than I would like, I find myself at a multidisciplinary tumor board discussing an endoscopically removed rectal lesion done in a piecemeal fashion or insufficient deep ESD where appropriate risk stratification is impossible and we end up offering patients a likely overly aggressive proctectomy or a potentially oncologically unsound re-excision. Consideration of EMR/ESD vs TAMIS up front would allow better sorting of which technique is most suited to which lesion and avoid these diagnostic dilemmas that only seem to be more common as EMR and ESD practices proliferate.

For a different set of reasons, an advanced cecal adenoma may also be more suited to upfront surgical considerations. Right colon lesions can be more challenging for surveillance for a host of reasons. Procedurally, right colon lesions are undeniably more difficult. The thin-walled cecum can be unforgiving for repeated polypectomies. Despite it being an uncomfortable subject for colonoscopists, the evidence suggests that getting to the cecum is not consistent or 100% expected. Finally, patients can be unwilling to undergo serial bowel preparation and endoscopic examination. In contrast, a laparoscopic right colectomy avoids these issues while also attributing little additional risk. Laparoscopic right-colon operations have overall complication rates of less than 10% and major complications of less than 1%. Hospital stays for laparoscopic right colectomy are typically 3 days or less. Finally, surgery reduces both the frequency of surveillance, and a shortened colon makes surveillance easier.

Advanced polypectomy techniques broaden our ability to address even difficult lesions under the ideally aligned degree of invasive procedure. However, like any procedure, these techniques have their own advantages and limitations. There will always be a minority of premalignant colon lesions that are best suited to surgery-first approaches to treatment. In my practice, maintaining open lines of communication and regular interaction with my endoscopy colleagues naturally leads to polyps being addressed in their most suitable fashion.

Dr. Leeds is assistant professor of surgery at the Yale School of Medicine and a staff surgeon at the VA Connecticut Healthcare System. He declares no conflicts of interest.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.