User login
Virtual Chromoendoscopy Beats Other Modalities at Neoplasia Detection in IBD
BERLIN —
The research, presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress, also found “significant variability in IBD surveillance practice in the real world,” said study presenter Chandni Radia, MD, Department of Gastroenterology, King’s College Hospital NHS Foundation Trust, London, England.
Although dye chromoendoscopy with targeted biopsies traditionally was considered the gold standard for neoplasia detection in patients with IBD, randomized trials have challenged its superiority over virtual chromoendoscopy and high-definition white-light endoscopy, the researchers noted. They hypothesized that the modality used would not affect the neoplasia detection rate.
To investigate, they conducted a retrospective observational cohort study of adults with ulcerative colitis, Crohn’s disease or primary sclerosing cholangitis (PSC) who underwent routine clinical IBD surveillance at one of five centers in the United Kingdom between 2019 and 2023. They examined data from the endoscopy reporting software, alongside endoscopy reports, endoscopy images, and electronic patient records.
In all, 2673 colonoscopies performed on 2050 patients were included, with 1032 procedures using dye chromoendoscopy, 366 using virtual chromoendoscopy, and 1275 using high-definition white-light endoscopy.
The overall neoplasia detection rate was 11.4%, “which is very similar to what has previously been seen in the literature,” Radia said.
However, the detection rate varied significantly by procedure: 19% in virtual chromoendoscopy, 12% in dye chromoendoscopy, and 9% in white-light endoscopy (P < .001). After accounting for a range of potential confounding factors, virtual chromoendoscopy still had the highest neoplasia detection rate.
Dye chromoendoscopy had a “prolonged withdrawal time and increased need for targeted biopsies without improving their neoplasia yield, which goes against our aspirations of sustainability,” Radia noted.
“It was interesting to see that the procedures with the most dye chromoendoscopy seem to have the longest withdrawal time, and those with the most white-light endoscopy seem to have the shortest,” she said. The difference remained significant even after controlling for procedures with polypectomy, “which has a significantly longer withdrawal time compared to procedures without.”
Results Varied by Center
There was wide variability between the five centers on several findings. The neoplasia detection rate ranged from 7.4% to 17.2%, depending on the center.
The surveillance method also varied. One center, for example, used white-light endoscopy in 82% of cases and dye chromoendoscopy in the other 18%. At another center, 61% of patients had dye chromoendoscopy, 36% white-light endoscopy, and 3% virtual chromoendoscopy. In a third center, 48% had virtual chromoendoscopy, 46% white-light endoscopy, and 6% dye chromoendoscopy.
The centers had varying proportions of patients with each of the three conditions, with ulcerative colitis ranging from 46% to 63%, Crohn’s disease from 9% to 39%, and PSC from 14% to 45%.
The heterogeneity of patients between the modality groups is one of the study’s limitations, Radia said. Others are the shorter withdrawal time with white-light endoscopy and the lack of standardized withdrawal time for the procedures.
The research team’s analyses are ongoing and include examination of the types of neoplasia detected, as well as accounting for endoscopist experience and patients who underwent two procedures with different modalities, Radia said.
Reflection of ‘Real-Life Practice’
Because the study was a retrospective analysis, it contains inherent biases and other issues, Raf Bisschops, MD, PhD, director of endoscopy, University of Leuven, Belgium, who co-chaired the session, said in an interview.
However, it was a “thorough analysis” that reflects “real-life practice,” he said. As such, it lends “huge support” to virtual chromoendoscopy, which “actually goes against the new [British Society of Gastroenterology] guideline that is about to come out.” The society plans to recommend in favor of dye chromoendoscopy, but the new study findings could be still incorporated into the upcoming guidelines so as to also endorse virtual chromoendoscopy.
Whatever the modality used, clinicians need to make sure they “pay attention” when looking for small neoplastic lesions, and “anything that can help you do that, that draws your attention to cell lesions ... can be helpful,” Bisschops said.
Performing targeted biopsies, as with dye chromoendoscopy, can be problematic, as “people don’t pay attention anymore to those cell lesions; they just focus on taking the 32 biopsies, which is a huge endeavor and it’s a pain to do it,” he added.
Radia has received a Research Training Fellowship Award from the UK patient organization PSC Support. No other funding was declared. Radia declared relationships with Abbvie, Galapogos, and Dr. Falk Pharma.
A version of this article appeared on Medscape.com.
BERLIN —
The research, presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress, also found “significant variability in IBD surveillance practice in the real world,” said study presenter Chandni Radia, MD, Department of Gastroenterology, King’s College Hospital NHS Foundation Trust, London, England.
Although dye chromoendoscopy with targeted biopsies traditionally was considered the gold standard for neoplasia detection in patients with IBD, randomized trials have challenged its superiority over virtual chromoendoscopy and high-definition white-light endoscopy, the researchers noted. They hypothesized that the modality used would not affect the neoplasia detection rate.
To investigate, they conducted a retrospective observational cohort study of adults with ulcerative colitis, Crohn’s disease or primary sclerosing cholangitis (PSC) who underwent routine clinical IBD surveillance at one of five centers in the United Kingdom between 2019 and 2023. They examined data from the endoscopy reporting software, alongside endoscopy reports, endoscopy images, and electronic patient records.
In all, 2673 colonoscopies performed on 2050 patients were included, with 1032 procedures using dye chromoendoscopy, 366 using virtual chromoendoscopy, and 1275 using high-definition white-light endoscopy.
The overall neoplasia detection rate was 11.4%, “which is very similar to what has previously been seen in the literature,” Radia said.
However, the detection rate varied significantly by procedure: 19% in virtual chromoendoscopy, 12% in dye chromoendoscopy, and 9% in white-light endoscopy (P < .001). After accounting for a range of potential confounding factors, virtual chromoendoscopy still had the highest neoplasia detection rate.
Dye chromoendoscopy had a “prolonged withdrawal time and increased need for targeted biopsies without improving their neoplasia yield, which goes against our aspirations of sustainability,” Radia noted.
“It was interesting to see that the procedures with the most dye chromoendoscopy seem to have the longest withdrawal time, and those with the most white-light endoscopy seem to have the shortest,” she said. The difference remained significant even after controlling for procedures with polypectomy, “which has a significantly longer withdrawal time compared to procedures without.”
Results Varied by Center
There was wide variability between the five centers on several findings. The neoplasia detection rate ranged from 7.4% to 17.2%, depending on the center.
The surveillance method also varied. One center, for example, used white-light endoscopy in 82% of cases and dye chromoendoscopy in the other 18%. At another center, 61% of patients had dye chromoendoscopy, 36% white-light endoscopy, and 3% virtual chromoendoscopy. In a third center, 48% had virtual chromoendoscopy, 46% white-light endoscopy, and 6% dye chromoendoscopy.
The centers had varying proportions of patients with each of the three conditions, with ulcerative colitis ranging from 46% to 63%, Crohn’s disease from 9% to 39%, and PSC from 14% to 45%.
The heterogeneity of patients between the modality groups is one of the study’s limitations, Radia said. Others are the shorter withdrawal time with white-light endoscopy and the lack of standardized withdrawal time for the procedures.
The research team’s analyses are ongoing and include examination of the types of neoplasia detected, as well as accounting for endoscopist experience and patients who underwent two procedures with different modalities, Radia said.
Reflection of ‘Real-Life Practice’
Because the study was a retrospective analysis, it contains inherent biases and other issues, Raf Bisschops, MD, PhD, director of endoscopy, University of Leuven, Belgium, who co-chaired the session, said in an interview.
However, it was a “thorough analysis” that reflects “real-life practice,” he said. As such, it lends “huge support” to virtual chromoendoscopy, which “actually goes against the new [British Society of Gastroenterology] guideline that is about to come out.” The society plans to recommend in favor of dye chromoendoscopy, but the new study findings could be still incorporated into the upcoming guidelines so as to also endorse virtual chromoendoscopy.
Whatever the modality used, clinicians need to make sure they “pay attention” when looking for small neoplastic lesions, and “anything that can help you do that, that draws your attention to cell lesions ... can be helpful,” Bisschops said.
Performing targeted biopsies, as with dye chromoendoscopy, can be problematic, as “people don’t pay attention anymore to those cell lesions; they just focus on taking the 32 biopsies, which is a huge endeavor and it’s a pain to do it,” he added.
Radia has received a Research Training Fellowship Award from the UK patient organization PSC Support. No other funding was declared. Radia declared relationships with Abbvie, Galapogos, and Dr. Falk Pharma.
A version of this article appeared on Medscape.com.
BERLIN —
The research, presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress, also found “significant variability in IBD surveillance practice in the real world,” said study presenter Chandni Radia, MD, Department of Gastroenterology, King’s College Hospital NHS Foundation Trust, London, England.
Although dye chromoendoscopy with targeted biopsies traditionally was considered the gold standard for neoplasia detection in patients with IBD, randomized trials have challenged its superiority over virtual chromoendoscopy and high-definition white-light endoscopy, the researchers noted. They hypothesized that the modality used would not affect the neoplasia detection rate.
To investigate, they conducted a retrospective observational cohort study of adults with ulcerative colitis, Crohn’s disease or primary sclerosing cholangitis (PSC) who underwent routine clinical IBD surveillance at one of five centers in the United Kingdom between 2019 and 2023. They examined data from the endoscopy reporting software, alongside endoscopy reports, endoscopy images, and electronic patient records.
In all, 2673 colonoscopies performed on 2050 patients were included, with 1032 procedures using dye chromoendoscopy, 366 using virtual chromoendoscopy, and 1275 using high-definition white-light endoscopy.
The overall neoplasia detection rate was 11.4%, “which is very similar to what has previously been seen in the literature,” Radia said.
However, the detection rate varied significantly by procedure: 19% in virtual chromoendoscopy, 12% in dye chromoendoscopy, and 9% in white-light endoscopy (P < .001). After accounting for a range of potential confounding factors, virtual chromoendoscopy still had the highest neoplasia detection rate.
Dye chromoendoscopy had a “prolonged withdrawal time and increased need for targeted biopsies without improving their neoplasia yield, which goes against our aspirations of sustainability,” Radia noted.
“It was interesting to see that the procedures with the most dye chromoendoscopy seem to have the longest withdrawal time, and those with the most white-light endoscopy seem to have the shortest,” she said. The difference remained significant even after controlling for procedures with polypectomy, “which has a significantly longer withdrawal time compared to procedures without.”
Results Varied by Center
There was wide variability between the five centers on several findings. The neoplasia detection rate ranged from 7.4% to 17.2%, depending on the center.
The surveillance method also varied. One center, for example, used white-light endoscopy in 82% of cases and dye chromoendoscopy in the other 18%. At another center, 61% of patients had dye chromoendoscopy, 36% white-light endoscopy, and 3% virtual chromoendoscopy. In a third center, 48% had virtual chromoendoscopy, 46% white-light endoscopy, and 6% dye chromoendoscopy.
The centers had varying proportions of patients with each of the three conditions, with ulcerative colitis ranging from 46% to 63%, Crohn’s disease from 9% to 39%, and PSC from 14% to 45%.
The heterogeneity of patients between the modality groups is one of the study’s limitations, Radia said. Others are the shorter withdrawal time with white-light endoscopy and the lack of standardized withdrawal time for the procedures.
The research team’s analyses are ongoing and include examination of the types of neoplasia detected, as well as accounting for endoscopist experience and patients who underwent two procedures with different modalities, Radia said.
Reflection of ‘Real-Life Practice’
Because the study was a retrospective analysis, it contains inherent biases and other issues, Raf Bisschops, MD, PhD, director of endoscopy, University of Leuven, Belgium, who co-chaired the session, said in an interview.
However, it was a “thorough analysis” that reflects “real-life practice,” he said. As such, it lends “huge support” to virtual chromoendoscopy, which “actually goes against the new [British Society of Gastroenterology] guideline that is about to come out.” The society plans to recommend in favor of dye chromoendoscopy, but the new study findings could be still incorporated into the upcoming guidelines so as to also endorse virtual chromoendoscopy.
Whatever the modality used, clinicians need to make sure they “pay attention” when looking for small neoplastic lesions, and “anything that can help you do that, that draws your attention to cell lesions ... can be helpful,” Bisschops said.
Performing targeted biopsies, as with dye chromoendoscopy, can be problematic, as “people don’t pay attention anymore to those cell lesions; they just focus on taking the 32 biopsies, which is a huge endeavor and it’s a pain to do it,” he added.
Radia has received a Research Training Fellowship Award from the UK patient organization PSC Support. No other funding was declared. Radia declared relationships with Abbvie, Galapogos, and Dr. Falk Pharma.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
Surgical vs Endoscopic Excision of Large Colon Polyps
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,
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,
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,
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.
Colorectal Cancer Awareness Month is Here!
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Happy Colorectal Cancer (CRC) Awareness Month! Today, CRC is the third-most common cancer in men and women in the United States. But there’s good news: We know that screening saves lives. That’s why
We have a variety of resources for both physicians and patients to navigate the CRC screening process.
Clinical Guidance
AGA’s clinical guidelines and clinical practice updates provide evidence-based recommendations to guide your clinical practice decisions. Visit AGA’s new toolkit on CRC for the latest guidance on topics including colonoscopy follow-up, liquid biopsy, appropriate and tailored polypectomy, and more.
Patient Resources
AGA’s GI Patient Center can help your patients understand the need for CRC screening, colorectal cancer symptoms and risks, available screening tests, and the importance of preparing for a colonoscopy. Visit patient.gastro.org to access patient education materials.
Join the Conversation
We’ll be sharing resources and encouraging screenings on social media all month long. Join us as we remind everyone that 45 is the new 50.
Fecal Hemoglobin Levels From Negative FITs Signal CRC Risk
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
, according to a large international dose-response meta-analysis.
Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the Department of Public Health at Erasmus MC, University Medical Center in Rotterdam, the Netherlands.
Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”
Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.
According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.
Study Details
The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.
All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.
With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I2 = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.
“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the US report as a qualitative positive-negative result.”
The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.
Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.
Feasibility of Implementation
In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.
“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.
Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.
The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.
This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing.
The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Random Biopsy Improves IBD Dysplasia Detection, With Caveats
according to a recent review and meta-analysis.
Random biopsies collected in studies after 2011 provided limited additional yield, suggesting that high-definition equipment alone may be sufficient to achieve a high detection rate, lead author Li Gao, MD, of Air Force Medical University, Xi’an, China, and colleagues reported. In contrast, patients with primary sclerosing cholangitis (PSC) consistently benefited from random biopsy, offering clearer support for use in this subgroup.
“Random biopsy has been proposed as a strategy that may detect dysplastic lesions that cannot be identified endoscopically, thus minimizing the occurrence of missed colitis-associated dysplasia during colonoscopy,” the investigators wrote in Clinical Gastroenterology and Hepatology. However, the role of random biopsies in colonoscopic surveillance for patients with IBD remains a topic of ongoing debate.”
The SCENIC guidelines remain inconclusive on the role of random biopsy in IBD surveillance, the investigators noted, while other guidelines recommend random biopsy with high-definition white light endoscopy, but not chromoendoscopy.
The present meta-analysis aimed to characterize the impact of random biopsy on dysplasia detection. The investigators aggregated prospective and retrospective studies published in English through September 2023, all of which compared random biopsy with other surveillance techniques and reported the proportion of dysplasia detected exclusively through random biopsy.
“To the best of our knowledge, this systematic review and meta-analysis was the first comprehensive summary of the additional yield of random biopsy during colorectal cancer surveillance in patients with IBD,” Dr. Gao and colleagues noted.
The final dataset comprised 37 studies with 9,051 patients undergoing colorectal cancer surveillance for IBD. Patients had diverse baseline characteristics, including different proportions of ulcerative colitis and Crohn’s disease, as well as varying prevalence of PSC, a known risk factor for colorectal neoplasia.
The pooled additional yield of random biopsy was 10.34% in per-patient analysis and 16.20% in per-lesion analysis, meaning that approximately 1 in 10 patients and 1 in 6 lesions were detected exclusively through random biopsy. Despite these benefits, detection rates were relatively low: 1.31% per patient and 2.82% per lesion.
Subgroup analyses showed a decline in random biopsy additional yield over time. Studies conducted before 2011 reported an additional yield of 14.43% in per-patient analysis, compared to just 0.42% in studies conducted after 2011. This decline coincided with the widespread adoption of high-definition endoscopy.
PSC status strongly influenced detection rates throughout the study period. In patients without PSC (0%-10% PSC prevalence), the additional yield of random biopsy was 4.83% in per-patient analysis and 11.23% in per-lesion analysis. In studies where all patients had PSC, the additional yield increased dramatically to 56.05% and 45.22%, respectively.
“These findings highlight the incremental benefits of random biopsy and provide valuable insights into the management of endoscopic surveillance in patients with IBD,” the investigators wrote. “Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating random biopsy in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.”This study was supported by the National Key R&D Program of China, the Key Research and Development Program of Shaanxi Province, and the Nanchang High-Level Scientific and Technological Innovation Talents “Double Hundred Plan” project. The investigators disclosed no conflicts of interest.
Patients with inflammatory bowel diseases (IBD) with colonic involvement are at two- to threefold increased risk of colorectal cancer (CRC), compared with the general population. The development and progression of dysplasia in these patients with IBD does not follow the typical adenoma-carcinoma sequence; rather, patients with IBD at increased risk of colorectal cancer may have field cancerization changes. Historically, these mucosal changes have been difficult to visualize endoscopically, at least with standard definition endoscopes. As a result, systematic, four-quadrant, random biopsies — 8 in each segment of the colon, totaling to 32 biopsies — are recommended for dysplasia detection. The practice has been adopted and accepted widely. Over time, there have been significant advancements in the management of IBD, with improved colonoscopic resolution, adjunct surveillance techniques, focus on quality of colonoscopic exams and evolution of treatments and treatment targets, and these have resulted in a reduction in the risk of CRC in patients with IBD. The value of random biopsies for dysplasia surveillance in patients with colonic IBD has been questioned.
In this context, the systematic review and meta-analysis from Gao and colleagues provides critical insights into the yield of random biopsies for dysplasia surveillance in patients with IBD. Through a detailed analysis of 37 studies published between 2003 to 2023, with 9051 patients who underwent dysplasia surveillance with random biopsies, they ascertained the incremental yield of random biopsies. Overall, 1.3% of patients who underwent random biopsies were detected to have dysplasia. Of these, 1 in 10 patients were detected to have dysplasia only on random biopsies. On per-lesion analysis, one in six dysplastic lesions were only detected on random biopsies. Interestingly, this yield of random biopsies varied markedly depending on the era, as a surrogate for quality of colonoscopies. In studies that fully enrolled and published before 2011 (majority of patients recruited in the 1990s to early 2000s), the per-patient incremental yield of random biopsies was 14%; this dropped precipitously to 0.4% in studies published after 2011 (majority of patients recruited in late 2000s to 2010s). The incremental yield of random biopsies remained markedly high in studies with a high proportion of patients with primary sclerosing cholangitis (PSC), a condition consistently associated with a four- to sixfold higher risk of CRC in patients with IBD.
These findings lend support to the notion that improvements in endoscopy equipment with wide adoption of high-definition white-light colonoscopes and an emphasis on quality of endoscopic examination may be leading to better endoscopic detection of previously “invisible” dysplastic lesions, leading to a markedly lower incremental yield of random biopsies in the current era. This questions the utility of routinely collecting 32 random biopsies during a surveillance exam for a patient with IBD at increased risk of CRC (as long as a thorough high-quality exam is being performed), though there may be subpopulations such as patients with PSC where there may be benefit. Large ongoing trials comparing the yield of targeted biopsies vs random and targeted biopsies in patients with IBD undergoing dysplasia surveillance with high-definition colonoscopes will help to definitively address this question.
Siddharth Singh, MD, MS, is associate professor of medicine and director of the UCSD IBD Center in the division of gastroenterology, University of California, San Diego. He declares no conflicts of interest relative to this article.
Patients with inflammatory bowel diseases (IBD) with colonic involvement are at two- to threefold increased risk of colorectal cancer (CRC), compared with the general population. The development and progression of dysplasia in these patients with IBD does not follow the typical adenoma-carcinoma sequence; rather, patients with IBD at increased risk of colorectal cancer may have field cancerization changes. Historically, these mucosal changes have been difficult to visualize endoscopically, at least with standard definition endoscopes. As a result, systematic, four-quadrant, random biopsies — 8 in each segment of the colon, totaling to 32 biopsies — are recommended for dysplasia detection. The practice has been adopted and accepted widely. Over time, there have been significant advancements in the management of IBD, with improved colonoscopic resolution, adjunct surveillance techniques, focus on quality of colonoscopic exams and evolution of treatments and treatment targets, and these have resulted in a reduction in the risk of CRC in patients with IBD. The value of random biopsies for dysplasia surveillance in patients with colonic IBD has been questioned.
In this context, the systematic review and meta-analysis from Gao and colleagues provides critical insights into the yield of random biopsies for dysplasia surveillance in patients with IBD. Through a detailed analysis of 37 studies published between 2003 to 2023, with 9051 patients who underwent dysplasia surveillance with random biopsies, they ascertained the incremental yield of random biopsies. Overall, 1.3% of patients who underwent random biopsies were detected to have dysplasia. Of these, 1 in 10 patients were detected to have dysplasia only on random biopsies. On per-lesion analysis, one in six dysplastic lesions were only detected on random biopsies. Interestingly, this yield of random biopsies varied markedly depending on the era, as a surrogate for quality of colonoscopies. In studies that fully enrolled and published before 2011 (majority of patients recruited in the 1990s to early 2000s), the per-patient incremental yield of random biopsies was 14%; this dropped precipitously to 0.4% in studies published after 2011 (majority of patients recruited in late 2000s to 2010s). The incremental yield of random biopsies remained markedly high in studies with a high proportion of patients with primary sclerosing cholangitis (PSC), a condition consistently associated with a four- to sixfold higher risk of CRC in patients with IBD.
These findings lend support to the notion that improvements in endoscopy equipment with wide adoption of high-definition white-light colonoscopes and an emphasis on quality of endoscopic examination may be leading to better endoscopic detection of previously “invisible” dysplastic lesions, leading to a markedly lower incremental yield of random biopsies in the current era. This questions the utility of routinely collecting 32 random biopsies during a surveillance exam for a patient with IBD at increased risk of CRC (as long as a thorough high-quality exam is being performed), though there may be subpopulations such as patients with PSC where there may be benefit. Large ongoing trials comparing the yield of targeted biopsies vs random and targeted biopsies in patients with IBD undergoing dysplasia surveillance with high-definition colonoscopes will help to definitively address this question.
Siddharth Singh, MD, MS, is associate professor of medicine and director of the UCSD IBD Center in the division of gastroenterology, University of California, San Diego. He declares no conflicts of interest relative to this article.
Patients with inflammatory bowel diseases (IBD) with colonic involvement are at two- to threefold increased risk of colorectal cancer (CRC), compared with the general population. The development and progression of dysplasia in these patients with IBD does not follow the typical adenoma-carcinoma sequence; rather, patients with IBD at increased risk of colorectal cancer may have field cancerization changes. Historically, these mucosal changes have been difficult to visualize endoscopically, at least with standard definition endoscopes. As a result, systematic, four-quadrant, random biopsies — 8 in each segment of the colon, totaling to 32 biopsies — are recommended for dysplasia detection. The practice has been adopted and accepted widely. Over time, there have been significant advancements in the management of IBD, with improved colonoscopic resolution, adjunct surveillance techniques, focus on quality of colonoscopic exams and evolution of treatments and treatment targets, and these have resulted in a reduction in the risk of CRC in patients with IBD. The value of random biopsies for dysplasia surveillance in patients with colonic IBD has been questioned.
In this context, the systematic review and meta-analysis from Gao and colleagues provides critical insights into the yield of random biopsies for dysplasia surveillance in patients with IBD. Through a detailed analysis of 37 studies published between 2003 to 2023, with 9051 patients who underwent dysplasia surveillance with random biopsies, they ascertained the incremental yield of random biopsies. Overall, 1.3% of patients who underwent random biopsies were detected to have dysplasia. Of these, 1 in 10 patients were detected to have dysplasia only on random biopsies. On per-lesion analysis, one in six dysplastic lesions were only detected on random biopsies. Interestingly, this yield of random biopsies varied markedly depending on the era, as a surrogate for quality of colonoscopies. In studies that fully enrolled and published before 2011 (majority of patients recruited in the 1990s to early 2000s), the per-patient incremental yield of random biopsies was 14%; this dropped precipitously to 0.4% in studies published after 2011 (majority of patients recruited in late 2000s to 2010s). The incremental yield of random biopsies remained markedly high in studies with a high proportion of patients with primary sclerosing cholangitis (PSC), a condition consistently associated with a four- to sixfold higher risk of CRC in patients with IBD.
These findings lend support to the notion that improvements in endoscopy equipment with wide adoption of high-definition white-light colonoscopes and an emphasis on quality of endoscopic examination may be leading to better endoscopic detection of previously “invisible” dysplastic lesions, leading to a markedly lower incremental yield of random biopsies in the current era. This questions the utility of routinely collecting 32 random biopsies during a surveillance exam for a patient with IBD at increased risk of CRC (as long as a thorough high-quality exam is being performed), though there may be subpopulations such as patients with PSC where there may be benefit. Large ongoing trials comparing the yield of targeted biopsies vs random and targeted biopsies in patients with IBD undergoing dysplasia surveillance with high-definition colonoscopes will help to definitively address this question.
Siddharth Singh, MD, MS, is associate professor of medicine and director of the UCSD IBD Center in the division of gastroenterology, University of California, San Diego. He declares no conflicts of interest relative to this article.
according to a recent review and meta-analysis.
Random biopsies collected in studies after 2011 provided limited additional yield, suggesting that high-definition equipment alone may be sufficient to achieve a high detection rate, lead author Li Gao, MD, of Air Force Medical University, Xi’an, China, and colleagues reported. In contrast, patients with primary sclerosing cholangitis (PSC) consistently benefited from random biopsy, offering clearer support for use in this subgroup.
“Random biopsy has been proposed as a strategy that may detect dysplastic lesions that cannot be identified endoscopically, thus minimizing the occurrence of missed colitis-associated dysplasia during colonoscopy,” the investigators wrote in Clinical Gastroenterology and Hepatology. However, the role of random biopsies in colonoscopic surveillance for patients with IBD remains a topic of ongoing debate.”
The SCENIC guidelines remain inconclusive on the role of random biopsy in IBD surveillance, the investigators noted, while other guidelines recommend random biopsy with high-definition white light endoscopy, but not chromoendoscopy.
The present meta-analysis aimed to characterize the impact of random biopsy on dysplasia detection. The investigators aggregated prospective and retrospective studies published in English through September 2023, all of which compared random biopsy with other surveillance techniques and reported the proportion of dysplasia detected exclusively through random biopsy.
“To the best of our knowledge, this systematic review and meta-analysis was the first comprehensive summary of the additional yield of random biopsy during colorectal cancer surveillance in patients with IBD,” Dr. Gao and colleagues noted.
The final dataset comprised 37 studies with 9,051 patients undergoing colorectal cancer surveillance for IBD. Patients had diverse baseline characteristics, including different proportions of ulcerative colitis and Crohn’s disease, as well as varying prevalence of PSC, a known risk factor for colorectal neoplasia.
The pooled additional yield of random biopsy was 10.34% in per-patient analysis and 16.20% in per-lesion analysis, meaning that approximately 1 in 10 patients and 1 in 6 lesions were detected exclusively through random biopsy. Despite these benefits, detection rates were relatively low: 1.31% per patient and 2.82% per lesion.
Subgroup analyses showed a decline in random biopsy additional yield over time. Studies conducted before 2011 reported an additional yield of 14.43% in per-patient analysis, compared to just 0.42% in studies conducted after 2011. This decline coincided with the widespread adoption of high-definition endoscopy.
PSC status strongly influenced detection rates throughout the study period. In patients without PSC (0%-10% PSC prevalence), the additional yield of random biopsy was 4.83% in per-patient analysis and 11.23% in per-lesion analysis. In studies where all patients had PSC, the additional yield increased dramatically to 56.05% and 45.22%, respectively.
“These findings highlight the incremental benefits of random biopsy and provide valuable insights into the management of endoscopic surveillance in patients with IBD,” the investigators wrote. “Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating random biopsy in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.”This study was supported by the National Key R&D Program of China, the Key Research and Development Program of Shaanxi Province, and the Nanchang High-Level Scientific and Technological Innovation Talents “Double Hundred Plan” project. The investigators disclosed no conflicts of interest.
according to a recent review and meta-analysis.
Random biopsies collected in studies after 2011 provided limited additional yield, suggesting that high-definition equipment alone may be sufficient to achieve a high detection rate, lead author Li Gao, MD, of Air Force Medical University, Xi’an, China, and colleagues reported. In contrast, patients with primary sclerosing cholangitis (PSC) consistently benefited from random biopsy, offering clearer support for use in this subgroup.
“Random biopsy has been proposed as a strategy that may detect dysplastic lesions that cannot be identified endoscopically, thus minimizing the occurrence of missed colitis-associated dysplasia during colonoscopy,” the investigators wrote in Clinical Gastroenterology and Hepatology. However, the role of random biopsies in colonoscopic surveillance for patients with IBD remains a topic of ongoing debate.”
The SCENIC guidelines remain inconclusive on the role of random biopsy in IBD surveillance, the investigators noted, while other guidelines recommend random biopsy with high-definition white light endoscopy, but not chromoendoscopy.
The present meta-analysis aimed to characterize the impact of random biopsy on dysplasia detection. The investigators aggregated prospective and retrospective studies published in English through September 2023, all of which compared random biopsy with other surveillance techniques and reported the proportion of dysplasia detected exclusively through random biopsy.
“To the best of our knowledge, this systematic review and meta-analysis was the first comprehensive summary of the additional yield of random biopsy during colorectal cancer surveillance in patients with IBD,” Dr. Gao and colleagues noted.
The final dataset comprised 37 studies with 9,051 patients undergoing colorectal cancer surveillance for IBD. Patients had diverse baseline characteristics, including different proportions of ulcerative colitis and Crohn’s disease, as well as varying prevalence of PSC, a known risk factor for colorectal neoplasia.
The pooled additional yield of random biopsy was 10.34% in per-patient analysis and 16.20% in per-lesion analysis, meaning that approximately 1 in 10 patients and 1 in 6 lesions were detected exclusively through random biopsy. Despite these benefits, detection rates were relatively low: 1.31% per patient and 2.82% per lesion.
Subgroup analyses showed a decline in random biopsy additional yield over time. Studies conducted before 2011 reported an additional yield of 14.43% in per-patient analysis, compared to just 0.42% in studies conducted after 2011. This decline coincided with the widespread adoption of high-definition endoscopy.
PSC status strongly influenced detection rates throughout the study period. In patients without PSC (0%-10% PSC prevalence), the additional yield of random biopsy was 4.83% in per-patient analysis and 11.23% in per-lesion analysis. In studies where all patients had PSC, the additional yield increased dramatically to 56.05% and 45.22%, respectively.
“These findings highlight the incremental benefits of random biopsy and provide valuable insights into the management of endoscopic surveillance in patients with IBD,” the investigators wrote. “Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating random biopsy in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.”This study was supported by the National Key R&D Program of China, the Key Research and Development Program of Shaanxi Province, and the Nanchang High-Level Scientific and Technological Innovation Talents “Double Hundred Plan” project. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Suboptimal Diets Tied to Global Doubling of GI Cancer Cases
according to a recent study.
Writing in Gastroenterology, researchers led by Li Liu, PhD, of the department of epidemiology and biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported that excessive consumption of processed meats (the biggest culprit), insufficient fruit intake, and insufficient whole grain intake were the leading dietary risk factors. In addition, the number of diet-related cases doubled from 1990 to 2018.
“In regions with limited access to healthy foods, policy interventions like taxing unhealthy foods and subsidizing nutritious options may help shift dietary patterns and reduce cancer risk,” Liu said in an interview.
The study examined meta-analyses from 184 countries in seven regions for the period 1990-2018 looking at rates of six major GI cancers: colorectal, liver, esophageal, pancreatic, and gallbladder/biliary tract. Among these, the age-standardized incidence of liver, pancreatic, and colorectal increased significantly over the past 3 decades.
The research team used a comparative risk assessment model to estimate the impact of diet on GI cancer independent of energy intake and adiposity. Although the principal dietary risk factors varied across individual cancers, suboptimal intake of the three aforementioned components was responsible for 66.51% of all diet-attributable GI cancers in 2018. The global mean processed meat consumption was 17 g/d in 2018, falling to a low in South Asia of 3 g/d.
The investigators also found diet-linked cancer incidence positively correlated with the Sociodemographic Index (SDI), an integrated measure of national development, income, and fertility. Incidence varied across world regions, with the highest proportion of cases in Central and Eastern Europe, Central Asia, Latin America, the Caribbean, and in high-income countries. The findings support the development of targeted diet-related public health interventions in various regions and nations to reduce GI cancer incidence, the authors wrote.
Among the study’s specific findings:
- In 2018, 21.5% (95% uncertainty interval [UI], 19.1-24.5) of incident GI cancer cases globally were attributable to suboptimal diets, a relatively stable proportion since 1990 (22.4%; 95% UI, 19.7-25.6).
- Absolute diet-attributable cases doubled from 580,862 (95% UI, 510,658-664,076) in 1990 to 1,039,877 (95% UI, 923,482-1,187,244) in 2018.
- Excessive processed meat consumption (5.9%; 95% UI, 4.2%-7.9%), insufficient fruit intake (4.8%; 95% UI, 3.8%-5.9%), and insufficient whole grain intake (3.6%; 95% UI, 2.8%-5.1%) were the most significant dietary risk factors in 2018 — a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake.
Given the well-established link between diet and GI cancers, the incidence findings came as no surprise. “However, the dramatic doubling of diet-attributable cases over the past few decades was truly unexpected,” Liu said. “This increase can likely be attributed to global population growth and aging. While aging is an irreversible process, we can still reduce the growing burden of diet-related GI cancers by focusing on modifiable behaviors, particularly through targeted dietary interventions.”
A Modifiable Risk Factor
Commenting on the analysis but not involved in it, Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston, noted that his own group’s studies also support the association of diet with an increased risk for GI cancers, particularly colorectal cancers.
“Although much work needs to be done to clarify the precise mechanisms underlying this association, there are substantial data that diet may cause changes in the gut microbiome, which in turn promotes cancer,” Chan said in an interview. “Going forward, we are working to develop strategies in which diet is modified to mitigate the risk of cancer associated with suboptimal diets.”
In other study findings, Liu’s group observed that two regional groups, Central and Eastern Europe, Central Asia, Latin America, and the Caribbean, as well as high-income countries, bore the top three diet-attributable burdens worldwide in 2018, all driven mostly by an upward-trending excess of processed meat.
By regions, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in 1990 (31.6%; UI, 27.0%-37.4%) and 2018 (31.6%; UI, 27.3%-36.5%).
As for the impact of the SDI, the authors explained that diet-attributable GI cancer burden was higher among adults with higher education and living in urban areas than among those with lower education and rural residency. “Some dietary habits tended to be worse in higher-SDI countries, specifically, higher consumption of processed meats,” they wrote.
Although the proportional attributable GI incidence remains relatively stable, they added, the doubling of absolute cases from 1990 to 2018, along with the discrepancies between urbanicity and countries/regions, supports more targeted preventive measures.
And while the diet-GI cancer connection is clear, they agreed with Chan in that “the precise pathogenesis from suboptimal diets to these cancers remains unclear and requires further basic studies to clarify the mechanism.”
In the meantime, the findings “underscore the urgent need for proactive public health interventions. Diet, as a modifiable risk factor, still offers substantial potential for improvement,” Liu said.
This study was funded by the National Natural Science Foundation of China and the American Cancer Society. The authors and Chan disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
according to a recent study.
Writing in Gastroenterology, researchers led by Li Liu, PhD, of the department of epidemiology and biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported that excessive consumption of processed meats (the biggest culprit), insufficient fruit intake, and insufficient whole grain intake were the leading dietary risk factors. In addition, the number of diet-related cases doubled from 1990 to 2018.
“In regions with limited access to healthy foods, policy interventions like taxing unhealthy foods and subsidizing nutritious options may help shift dietary patterns and reduce cancer risk,” Liu said in an interview.
The study examined meta-analyses from 184 countries in seven regions for the period 1990-2018 looking at rates of six major GI cancers: colorectal, liver, esophageal, pancreatic, and gallbladder/biliary tract. Among these, the age-standardized incidence of liver, pancreatic, and colorectal increased significantly over the past 3 decades.
The research team used a comparative risk assessment model to estimate the impact of diet on GI cancer independent of energy intake and adiposity. Although the principal dietary risk factors varied across individual cancers, suboptimal intake of the three aforementioned components was responsible for 66.51% of all diet-attributable GI cancers in 2018. The global mean processed meat consumption was 17 g/d in 2018, falling to a low in South Asia of 3 g/d.
The investigators also found diet-linked cancer incidence positively correlated with the Sociodemographic Index (SDI), an integrated measure of national development, income, and fertility. Incidence varied across world regions, with the highest proportion of cases in Central and Eastern Europe, Central Asia, Latin America, the Caribbean, and in high-income countries. The findings support the development of targeted diet-related public health interventions in various regions and nations to reduce GI cancer incidence, the authors wrote.
Among the study’s specific findings:
- In 2018, 21.5% (95% uncertainty interval [UI], 19.1-24.5) of incident GI cancer cases globally were attributable to suboptimal diets, a relatively stable proportion since 1990 (22.4%; 95% UI, 19.7-25.6).
- Absolute diet-attributable cases doubled from 580,862 (95% UI, 510,658-664,076) in 1990 to 1,039,877 (95% UI, 923,482-1,187,244) in 2018.
- Excessive processed meat consumption (5.9%; 95% UI, 4.2%-7.9%), insufficient fruit intake (4.8%; 95% UI, 3.8%-5.9%), and insufficient whole grain intake (3.6%; 95% UI, 2.8%-5.1%) were the most significant dietary risk factors in 2018 — a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake.
Given the well-established link between diet and GI cancers, the incidence findings came as no surprise. “However, the dramatic doubling of diet-attributable cases over the past few decades was truly unexpected,” Liu said. “This increase can likely be attributed to global population growth and aging. While aging is an irreversible process, we can still reduce the growing burden of diet-related GI cancers by focusing on modifiable behaviors, particularly through targeted dietary interventions.”
A Modifiable Risk Factor
Commenting on the analysis but not involved in it, Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston, noted that his own group’s studies also support the association of diet with an increased risk for GI cancers, particularly colorectal cancers.
“Although much work needs to be done to clarify the precise mechanisms underlying this association, there are substantial data that diet may cause changes in the gut microbiome, which in turn promotes cancer,” Chan said in an interview. “Going forward, we are working to develop strategies in which diet is modified to mitigate the risk of cancer associated with suboptimal diets.”
In other study findings, Liu’s group observed that two regional groups, Central and Eastern Europe, Central Asia, Latin America, and the Caribbean, as well as high-income countries, bore the top three diet-attributable burdens worldwide in 2018, all driven mostly by an upward-trending excess of processed meat.
By regions, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in 1990 (31.6%; UI, 27.0%-37.4%) and 2018 (31.6%; UI, 27.3%-36.5%).
As for the impact of the SDI, the authors explained that diet-attributable GI cancer burden was higher among adults with higher education and living in urban areas than among those with lower education and rural residency. “Some dietary habits tended to be worse in higher-SDI countries, specifically, higher consumption of processed meats,” they wrote.
Although the proportional attributable GI incidence remains relatively stable, they added, the doubling of absolute cases from 1990 to 2018, along with the discrepancies between urbanicity and countries/regions, supports more targeted preventive measures.
And while the diet-GI cancer connection is clear, they agreed with Chan in that “the precise pathogenesis from suboptimal diets to these cancers remains unclear and requires further basic studies to clarify the mechanism.”
In the meantime, the findings “underscore the urgent need for proactive public health interventions. Diet, as a modifiable risk factor, still offers substantial potential for improvement,” Liu said.
This study was funded by the National Natural Science Foundation of China and the American Cancer Society. The authors and Chan disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
according to a recent study.
Writing in Gastroenterology, researchers led by Li Liu, PhD, of the department of epidemiology and biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, reported that excessive consumption of processed meats (the biggest culprit), insufficient fruit intake, and insufficient whole grain intake were the leading dietary risk factors. In addition, the number of diet-related cases doubled from 1990 to 2018.
“In regions with limited access to healthy foods, policy interventions like taxing unhealthy foods and subsidizing nutritious options may help shift dietary patterns and reduce cancer risk,” Liu said in an interview.
The study examined meta-analyses from 184 countries in seven regions for the period 1990-2018 looking at rates of six major GI cancers: colorectal, liver, esophageal, pancreatic, and gallbladder/biliary tract. Among these, the age-standardized incidence of liver, pancreatic, and colorectal increased significantly over the past 3 decades.
The research team used a comparative risk assessment model to estimate the impact of diet on GI cancer independent of energy intake and adiposity. Although the principal dietary risk factors varied across individual cancers, suboptimal intake of the three aforementioned components was responsible for 66.51% of all diet-attributable GI cancers in 2018. The global mean processed meat consumption was 17 g/d in 2018, falling to a low in South Asia of 3 g/d.
The investigators also found diet-linked cancer incidence positively correlated with the Sociodemographic Index (SDI), an integrated measure of national development, income, and fertility. Incidence varied across world regions, with the highest proportion of cases in Central and Eastern Europe, Central Asia, Latin America, the Caribbean, and in high-income countries. The findings support the development of targeted diet-related public health interventions in various regions and nations to reduce GI cancer incidence, the authors wrote.
Among the study’s specific findings:
- In 2018, 21.5% (95% uncertainty interval [UI], 19.1-24.5) of incident GI cancer cases globally were attributable to suboptimal diets, a relatively stable proportion since 1990 (22.4%; 95% UI, 19.7-25.6).
- Absolute diet-attributable cases doubled from 580,862 (95% UI, 510,658-664,076) in 1990 to 1,039,877 (95% UI, 923,482-1,187,244) in 2018.
- Excessive processed meat consumption (5.9%; 95% UI, 4.2%-7.9%), insufficient fruit intake (4.8%; 95% UI, 3.8%-5.9%), and insufficient whole grain intake (3.6%; 95% UI, 2.8%-5.1%) were the most significant dietary risk factors in 2018 — a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake.
Given the well-established link between diet and GI cancers, the incidence findings came as no surprise. “However, the dramatic doubling of diet-attributable cases over the past few decades was truly unexpected,” Liu said. “This increase can likely be attributed to global population growth and aging. While aging is an irreversible process, we can still reduce the growing burden of diet-related GI cancers by focusing on modifiable behaviors, particularly through targeted dietary interventions.”
A Modifiable Risk Factor
Commenting on the analysis but not involved in it, Andrew T. Chan, MD, MPH, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston, noted that his own group’s studies also support the association of diet with an increased risk for GI cancers, particularly colorectal cancers.
“Although much work needs to be done to clarify the precise mechanisms underlying this association, there are substantial data that diet may cause changes in the gut microbiome, which in turn promotes cancer,” Chan said in an interview. “Going forward, we are working to develop strategies in which diet is modified to mitigate the risk of cancer associated with suboptimal diets.”
In other study findings, Liu’s group observed that two regional groups, Central and Eastern Europe, Central Asia, Latin America, and the Caribbean, as well as high-income countries, bore the top three diet-attributable burdens worldwide in 2018, all driven mostly by an upward-trending excess of processed meat.
By regions, Central and Eastern Europe and Central Asia experienced the highest attributable burden across regions in 1990 (31.6%; UI, 27.0%-37.4%) and 2018 (31.6%; UI, 27.3%-36.5%).
As for the impact of the SDI, the authors explained that diet-attributable GI cancer burden was higher among adults with higher education and living in urban areas than among those with lower education and rural residency. “Some dietary habits tended to be worse in higher-SDI countries, specifically, higher consumption of processed meats,” they wrote.
Although the proportional attributable GI incidence remains relatively stable, they added, the doubling of absolute cases from 1990 to 2018, along with the discrepancies between urbanicity and countries/regions, supports more targeted preventive measures.
And while the diet-GI cancer connection is clear, they agreed with Chan in that “the precise pathogenesis from suboptimal diets to these cancers remains unclear and requires further basic studies to clarify the mechanism.”
In the meantime, the findings “underscore the urgent need for proactive public health interventions. Diet, as a modifiable risk factor, still offers substantial potential for improvement,” Liu said.
This study was funded by the National Natural Science Foundation of China and the American Cancer Society. The authors and Chan disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Promising New Blood Test for Colorectal Cancer Screening
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Low-Dose Aspirin Cuts CRC Recurrence
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Quality, Not Type, of Diet Linked to Microbiome Health
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
FROM NATURE MICROBIOLOGY
Obesity Linked with Malignant Progression of Barrett’s Esophagus
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY