Preliminary Work: A Vaccine to Prevent Colon Cancer and A Blood Test to Detect Colon Cancer

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D’Alise, A.M., Willis, J., Duzagac, F. et al. Nat Med (2026). https://doi.org/10.1038/s41591-025-04182-9. Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial. (Open Access!)

Background: “Lynch syndrome (LS) is a prevalent hereditary cancer syndrome affecting ~1 in 300 individuals, with an overall lifetime cancer risk as high as 80%. LS is caused by germline mutations in the DNA mismatch repair genes, leading to microsatellite instability (MSI) and accumulation of shared mutations. When these occur in coding regions, they generate frameshift peptides (FSPs). Nous-209 is a neoantigen-directed immunotherapy” against these FSPS. These are “the results from cohort 1 of a phase 1b/2 single-arm trial of Nous-209 for cancer interception in LS carriers (n = 45).”

Key findings:

  • Neoantigen-specific immune responses were observed after vaccination in 100% of evaluable participants (n = 37), with induction of potent T cell immunity
  • The immune response was durable and detectable at 1 year in 85% of participants
  • Both CD8+ and CD4+ T cells were induced, recognizing multiple FSPs
  • Peptide–human leukocyte antigen predictions allowed the identification of >100 immunogenic FSPs with demonstration of cytotoxic activity in vitro
Colorectal neoplasia burden observed at end-of-study colonoscopy inversely correlates with breadth of immune response. a, Number of participants who underwent screening colonoscopy at baseline and end of study (EoS; n = 43) who had no adenomas (adenomas absent), at least one adenoma (adenomas present) and advanced adenomas (advanced adenomas present) detected.
b, Number of adenomas per trial participant at baseline and end of study; comparison of baseline versus EoS was performed using a two-tailed Mann–Whitney U-test; NS, not significant. c, Number of reactive pools measured at 6 months (n = 34 evaluable subjects) between the participants with and without adenomas. Data are shown as the mean ± s.e.m.

My take (borrowed in part from authors): “Overall, this clinical trial provides important proof-of-concept data of the safety and the robustness of induced immunogenicity of
Nous-209 in LS carriers…and supporting its clinical development as a valuable intervention for cancer immune interception.” Vaccines have a long history in reducing cancer (for Hepatitis B, Cervical Cancer (due to HPV), Anal Cancer, Leukemia (by boosting immunity) and Others). Until recently, this has been by preventing viral infections that increase the risk of cancer. This is a new approach.

Related article: Blood test for colorectal cancer: A Mannucci et al. Gastroenterol 2026; 170: 330-343. An Exosome-Based Liquid Biopsy for the Detection of Early-Onset Colorectal Cancer: The ENCODER Multicenter Study Methods: A panel of 6 cell-free and exosome-based circulating biomarkers were identified through small RNA sequencing from a biomarker discovery cohort (blood test). Key finding: “This study developed and independently tested a blood-based test with 97.3% sensitivity for screening-relevant CRC stages I–III and 61.5% for the noninvasive detection of high-grade dysplasia.”

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More Pediatric Data Supporting GLP-1 RA Efficacy for MASLD

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AM Tou et al. J Pediatr Gastroenterol Nutr. 2026;82:146–155. Glucagon‐like peptide‐1 receptor agonists in pediatric metabolic dysfunction‐associated steatotic liver disease

Methods: Retrospective study in patients ≤18 years old with a diagnosis of MASLD, who were prescribed a GLP-1RA from January 2, 2018 and January 10, 2024 at the Children’s Hospital of Philadelphia. 42 patients met inclusion criteria (out of a cohort of 111 that had received GLP-1RA with diagnosis of MASLD). Of the GLP-1RA medications, liraglutide was most frequently prescribed (44%), followed by semaglutide (27%), dulaglutide (25%), and exenatide (4%).

Key findings:

  • ALT improved by a mean of 56 U/L at 6 months (p = 0.04), and by 37 U/L at end of treatment (p = 0.004)
  •  71% of patients had a therapeutic indication for T2DM and 29% for obesity
  • “Improvements were also observed in aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), glycated hemoglobin (HbA1C), and triglycerides. Body mass index (BMI) percentile and z-score showed no significant changes, but BMI stabilization was observed”

My take: While Semaglutide has an FDA indication for MASLD treatment, there is limited pediatric data. This study indicates that GLP1-RAs are likely to have similar efficacy in adolescents. The lack of weight loss in this study is likely related partly to use in T2DM which has a lower response and the use of GLP-1RAs known to have lower response with regard to weight loss.

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Have You Read the New “Dietary Guidelines for Americans, 2025-2030”?

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Here’s a link to the new 10-page guidelines: Dietary Guidelines for Americans

Here are critiques:

What’s Good About This Guidance:

  1. Short enough to read and understand
  2. The emphasis of reducing unprocessed foods and clear language
  3. Encouraging early introduction of potential allergens at 6 months of life. This lowers the risk of developing food allergies later.

Some of the questionable advice:

  1. Increasing the protein recommendation to 1.2-1.6 gm per day, up to double prior recommendations. The reason why this level of protein is not a good idea for everyone is noted in a prior blog post: Is a High Protein Diet Beneficial and Safe?. And from the AJC critique: “Pushing protein higher can also crowd out vegetables and fiber, which play a major role in heart health, digestion and overall wellness.”
  2. Backing away from previous advice about alcohol. The current guidance states to “consume less alcohol.” From NY Times: “It is the first time in decades that the government has omitted the daily caps on drinking that define moderate consumption. The guidelines no longer warn of risks like cancer.”
  3. Encouraged changes (more red meat, full-fat dairy) may increase saturated fat intake above stated goal of less than 10%.

The NY Times article on conflicts of interests notes that “Robert F. Kennedy Jr. had promised that his panel, which released new guidelines this week, would have no “conflicts of interest”….Some parts of the guidelines represent such a departure from previous versions that it seems like the administration “handpicked” scientists likely to support those conclusions, “versus undertaking a neutral review of the science,” said Lindsey Smith Taillie, a professor of nutrition at the U.N.C. Gillings School of Global Public Health.”

My take: Overall, the focus on reducing processed foods and decreasing added sugar are worthwhile. The brevity of the guidelines make them accessible. At the same time, the guidelines appear to continue a pattern of RFK Jr of selecting advisers, whether with diet recommendations or with vaccine policy, to support a desired outcome.

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Gastroenterology and the Rise of Private Equity Investments

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TA Brenner et al. Clin Gastroenterol Hepatol 2026: 24: 7-9. Geodemographic Trends in Private Equity Acquisitions of US Gastroenterology Practices: An Analysis of Transactions From 2013 to 2023

An excerpt:

“The combination of high-volume procedures, strong ancillary revenue streams, and opportunities for outpatient consolidation has made gastroenterology a prime target for PE-backed investment. For many gastroenterologists, this trend is no longer theoretical—it is local, visible, and shaping the landscape of everyday practice.”

“Between 2013 and 2023, PE firms acquired 114 outpatient gastroenterology practices, encompassing 1169 clinical sites nationwide…That includes 854 clinics, 266 endoscopy centers, and 49 infusion centers. Collectively, these sites employed approximately 2675 physicians and advanced practice providers. In total, around 14% of all gastroenterology clinical sites nationwide are now affiliated with PE-backed platforms.”

 (A) Trend in private equity acquisitions of gastroenterology practices (red)
and gastroenterology clinical sites (blue) by year.

“PE firms are less likely to invest in gastroenterology practices located in the poorest communities… Practices in zip codes with the lowest income levels were about 60% less likely to be acquired than those in wealthier areas (aRR, 0.37; 95% CI, 0.31–0.45; P < .001)…PE firms tend to prioritize markets with strong commercial payer mixes and higher rates of elective procedures, steering clear of areas with high Medicaid penetration or large numbers of uninsured patients.”

Key Points:

  • “First, consolidation is accelerating…Even if you are not interested in selling, you may need to compete with PE-backed groups that have more capital, better tech infrastructure, and stronger payer contracts”
  • “Second, staying independent may become more difficult. As regional consolidation increases, remaining unaffiliated could put independent practices at a disadvantage. PE-backed platforms often negotiate better rates with commercial insurers and have the scale to invest in centralized billing, marketing, and compliance.”
  • “Third…If PE firms avoid lower-income or rural areas, gastroenterology access could become more uneven and more challenging to sustain in underserved regions.”
  • “Studies in other specialties suggest that practices owned by PE firms often face changes in staffing, autonomy, and productivity expectations. Physicians may experience higher pressure to perform more procedures, see more patients, or adopt system-wide workflows they did not design.”

My take: PE acquisitions are affecting broad areas of healthcare. However, they do not seem to result in improvement in patient care or physician satisfaction.

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Updated Data on PPI Effectiveness For Eosinophilic Esophagitis

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AJ Lucendo et al. Clin Gastroenterol Hepatol 2025; 23: 2115-2127. Proton Pump Inhibitors for Inducing and Maintaining Remission in Eosinophilic Esophagitis: An Updated Systematic Review and Meta-Analysis

Background/Methods: This systematic review aimed to update the response/remission rates of PPI therapy for eosinophilic esophagitis. Compared to review in 2016, the current review covers a 10-fold increase in population (from 619 to 7304 patients), with a more balanced distribution between children (41%) and adults, and with a geographical representation from several continents.

Key findings:

  • PPI therapy led to clinical response in 65% (95% confidence interval [CI], 57.2–72.4)) and histological remission (<15 eos/hpf) in 45.4% (95% CI, 41.6%–49.3%) of patients, without differences between children and adults (41.4% vs 48%; P = .17)
  • Overall, 34.1% (95% CI, 27.9%–40.5%) achieved <5 eosinophils per high-power field
  • Maintenance half-doses led to sustained histological remission in 68.2% (95% CI, 63.7%–72.6%) of patients
  • Clinical and histological remission (<15 eos/hpf) was achieved in 45% of patients
  • Histological remission was significantly higher with double PPI doses compared with standard (51.7% vs 28.3%; P < .005)

In the discussion, it was noted that Japanese cohorts had a better response to PPI therapy with a histological remission (67.9%). This could be related to more favorable metabolism of PPI. “CYP2C19∗17 haplotype (related to ultrarapid and rapid PPI metabolizers), is the least prevalent (<3%) in patients with Asian ancestry.”

My take: This study reinforces previous data showing a 40-50% remission rate with PPI therapy for EoE. Twice a day PPI therapy is significantly more effective than once a day.

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#5000: Simple Rule for Deciding When pH Impedance Testing Should Be Done While on Therapy

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Editor’s note: This is the 5000th post on this blog! The first post was on December 7th, 2011.

Iguazu Falls

CP Gyawali et al. Clin Gastroenterol Hepatol 2025; 23: 2459-2467. Open Access! pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but Not in Unproven GERD

Methods: Prospective 2-center study enrolled adult patients (n=79) with typical reflux symptoms with incomplete PPI response; they were studied both off PPI (wireless pH monitoring) and on PPI (pH-impedance monitoring)

Key findings:

  •  In 60 patients with proven GERD off-PPI, 56.7% had no ongoing GERD on PPI (despite reflux symptoms)
  • In unproven GERD, pH-impedance monitoring on acid suppressive therapy is unable to differentiate non-GERD symptoms from controlled GERD in the majority of patients, or identify patients who could benefit from discontinuation of acid suppression

Discussion points:

  • “Only a small proportion of PPI nonresponders have true GERD, and most have either no GERD or overlap between inconclusive GERD and a non-GERD process such as an esophageal disorder of gut-brain interaction (E-DGBI).10,11“
  • “On-therapy pH-impedance monitoring can identify refractory GERD in patients with previously proven GERD.”
  • “Definitive GERD evidence and persisting symptoms despite optimized PPI therapy is an indication for escalation of management.20… potassium competitive acid blockers provide better healing of advanced grade esophagitis21 as well as faster symptom response in nonerosive reflux disease,22,23 and could be an option”

My take:

  1. Simple rule: Only perform on-therapy pH-impedance monitoring in patients with proven GERD
  2. Many patients with GERD symptoms do not have GERD (see posts below)
  3. In patients with documented GERD, on therapy pH monitoring can be helpful in proving refractory GERD which may benefit from alternative treatments

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Nahuel Huapi Lake (near Bariloche, Argentina)

Etrasimod for Ulcerative Colitis (2026)

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AJ Yarur et al. Clinical Gastroenterology and Hepatology 2026; 24: 210 – 220. Open Access! Efficacy of Etrasimod in Ulcerative Colitis: Analysis of ELEVATE UC 52 and ELEVATE UC 12 by Baseline Endoscopic Severity.

Methods: Efficacy end points were evaluated at Weeks 12 (pooled population) and 52 (ELEVATE UC 52)

Key findings:

  • Clinical remission in the moderate group compared to placebo: Week 12: 38.3% vs 17.9%; Week 52: 36.5% vs 14.3%
  • Clinical remission in the severe group compared to placebo: Week 12: 18.2% vs 6.1%; Week 52: 29.4% vs 3.4%
  • “Our findings were consistent with those for other UC treatments…with efficacy improvements generally being greater among patients who were naive rather than experienced with biologics and/or JAKi.12–17“

My take: Etrasimod demonstrated significant induction and maintenance efficacy over placebo in both moderate and severe endoscopic disease. Its role remains limited as there are other treatments with improved likelihood of response, especially in those with prior advanced therapies. However, it is notable that recent AGA guidelines promote etrasimod as one of the higher efficacy agents in patients naive to advanced therapies.

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Increased Mortality with Achalasia

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A Forss et al. Clin Gastroenterol Hepatol 2025: 23: 2468-2476. Open Access! All-cause and Cause-specific Mortality in Achalasia: A Nationwide Matched Cohort Study

Methods: This study was a nationwide, population-based, matched cohort study using the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort which included all adults in Sweden with incident achalasia (n = 704; 1969–2017; follow-up until December 31, 2021) without any other prior esophageal conditions. Individuals with achalasia were matched by age, sex, birth year, and county to up to 5 reference individuals (n = 3348) from the general population. The median follow-up was 9.1 years. Medians age in the study was 60 years.

Key findings:

  • There were 270 deaths in individuals with achalasia, and 1023 in reference individuals (IR, 69.4 vs 51.9/1000 person-years)
  • Thus, there was a 42% increase in the risk of death. This translated into 1 extra death per every 6 individuals with achalasia followed for 10 years
  • Risk increases were seen for death from any cancer (aHR, 1.65), esophageal cancer (aHR, 23.19), and respiratory disease (aHR, 2.22)

Discussion point: “The sibling comparison (aHR for all-cause mortality, 1.78; 95% CI, 1.13–2.81) confirmed our findings in the main analysis (aHR, 1.42; 95% CI, 1.21–1.65). The similar risk estimates suggest that shared early-life exposures do not play any major role for mortality in achalasia. In all, we are confident that the observed elevated mortality is unlikely to be fully explained by environmental exposures or comorbidities, because the risk estimates remained largely unchanged in the sibling comparison as well as after adjustment for a wide range of comorbidities (through CCI).”

My take: This study is in agreement with others which have sown that achalasia is associated with an increased mortality risk.

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Big Study: Total Pancreatectomy with Islet Autotransplantation (TPIAT) for Chronic Pancreatitis

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T Guru et al. Gastroenterology 2025: 169:1499 – 1509. Total Pancreatectomy With Islet Autotransplantation for Chronic Pancreatitis

This prospective multicenter study included 384 patients with a mean age of 30 years (34% pediatric).

Key findings:

  • Daily abdominal pain decreased from 65% to 23%, whereas the mean pain score decreased from 4.9 (SD, 2.3) to 2.3 (SD, 2.5; both P < .001)
  • Opioid use decreased (assessed over a 14-day interval) from 61% before to 24% at 1 year after TPIAT (P < .001)
  • Improved physical and mental health: Physical component summary and mental component summary scores improved by ≥10 points in 58% and 35%, respectively
  • Mean hemoglobin A1c was 7% (SD, 1.9%) with 20% insulin independent at 1 year
  • Young age was associated with better outcomes, whereas duration and etiology of disease did not predict response to TPIAT

In their discussion, the authors note that it had been “widely hypothesized that after several years of pain, mechanism shift to solely neuropathic pain, such that surgery would be unlikely to offer benefit. Our results suggest this is not true.”

My take: This study provides robust data supporting TPIAT as average pain scores declined by more than 50%, the need for opioid analgesics decreased substantially, and mental health/physical health/QOL all improved. Most maintained glycemic control.

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Humor (from 2009): YouTube Link: Brain Surgeon – That Mitchell & Webb Look (2:09 min)

    Lower Expectations for Outcomes After Botox for Retrograde Cricopharyngeus Dysfunction (aka Abelchia)

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    K Raymenants et al. Clin Gastroenterol Hepatol 2026; 24: 81-91. Diagnosis of Retrograde Cricopharyngeus Dysfunction Using High Resolution Impedance Manometry and Comparison With Control Subjects

    Methods: Retrospective analysis of High Resolution Impedance Manometry
    (HRiM) with belch provocation was performed between May 2021 and April 2024 in 55 patients with R-CPD, 30 control patients, and 15 healthy volunteers. Age of patients with R-CPD was 22-35 years.

    Key findings:

    • During belching, we saw higher UES pressures in R-CPD patients vs controls, leading to incomplete air clearance and air oscillating in the esophagus (P < .0001)
    •  After BT injection, median UES pressures during belching decreased (56 vs 3 mmHg), and air clearance improved (P < .0001)
    • A maximum UES pressure during belching >31 mmHg adequately discriminated patients from controls
    • Interestingly, the authors did not include one of the major findings in their abstract: “Symptom improvement of at least 50% was present in 57% of patients, which is lower than reported up to now”
    • R-CPD patients had inability to belch in 100%, gurgling chest noises in 100%, bloating in 92%, chest pain in 67%, nausea in 59%, and heartburn (at least weekly) in 65%

    My take: Recognition of this treatable disorder is important. However, the lower improvement rate in this study is useful for counseling patients. My suspicion is that this finding likely reflects more widespread results as initial studies could have more selection or reporting bias.

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