Tag Archives: adenoma

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.”

Related blog posts:

Sugary Diet and Colonic Adenomas

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H-K Joh et al. Gastroenterol 2021; 161: 128-142. Full text: Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors

Methods: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses’ Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015.

Key Findings:

  • High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions.
  • Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05–1.31) for total and 1.30 (95% CI, 1.06–1.60) for high-risk adenoma

Full text (editorial, pg 27): JK Lee et al: Sugary Truth of Early-Onset Colorectal Neoplasia—Not So Sweet After All

Key points:

  • “In the United States, SSB [sugar-sweetened beverage] consumption has increased by nearly 5-fold over time, from 10.8 gallons per person in 1950 to 49.3 gallons per person in 2000.8 In adolescents, SSB consumption has more than doubled since the 1960s and comprises the largest source of simple sugar and calories in their diets”
  • “Recent studies, including several from the Nurses’ Health Study, have identified lifestyle factors from early adulthood, including Western diet,13,14 alcohol,15 tobacco,16 sedentary television viewing,11 diabetes,17 and obesity12 as risk factors for early-onset CRC or adenoma. Other studies report no association between sugar, fruit juice, and SSB consumption during adulthood and risk of CRC in older adults”

My take (borrowed from editorial): “Increasing fructose and SSB consumption, particularly among adolescents and young adults, is troublesome because substantial evidence links consumption to various health outcomes, including obesity, type 2 diabetes, cardiovascular disease, some cancers, all-cause mortality, and now early-onset high-risk adenoma…. clinicians should continue to support public health policies discouraging or reducing consumption of simple sugars and SSBs in adolescents, for whom exposure might have lifelong consequences.”

Consensus guidelines after polypectomy

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The US Multi-Society Task Force (MSTF) on colorectal cancer has updated their recommendations and provided an update on the literature as well (Gastroenterol 2012; 143: 844-57).

Their recommendations are summarized in Table 1 of this article.  In brief, repeat colonoscopy is recommended at the following interval:

  • 10 years –If no polyps or small (<10 mm) hyperplastic polyps in rectum/sigmoid
  • 5-10 years –if 1-2 small (<10 mm) tubular adenomas
  • 3 years –if 3-10 tubular adenomas or if adenoma with high-grade dysplasia
  • ❤ years –if >10 adenomas
  • 1 year  –if serrated polyposis syndrome

Other important points include the recommendation of adopting split-dose bowel preparations and avoiding interval fecal testing within 5 years after colonoscopy.  If the bowel preparation is poor, the MSTF recommends that in most cases colonoscopy should be repeated within 1 year.  Newer techniques like chromoendoscopy, narrow band imaging, and magnification endoscopy have not been adequately studied to recommend them as part of  a surveillance strategy.

Related blog entries:

Colonoscopy, Split-dosing bowel preps, and Ottawa scores

Aspirin prophylaxis for colorectal cancer?

Additional references:

  • -Gastroenterol 2010; 138: 73, 27 (ed). Overutilization of colon screening in low risk situations and underutilization in high risk situations in clinical practice.
  • -Clin Gastro & Hep 2010; 8: 795. Juvenile Polyps. Describes frequent rate of recurrence (3 of 18 among single polyps) & 45% overall. n=257. 39% with at least 2 polyps. Among those with multiple polyps, 7 had mutations in either SMAD4 (mothers against decpentaplegic drosophilia), BMPR1A (bone morphogenetic protein), or PTEN (phosphatase & tensin homolog). Their recs: recheck with scope in 1-3 years depending on polyp burden and presence of dysplasia.
  • -Clin Gastro & Hep 2009; 7: 1217. Fewer polyps detected as day progresses at a VA hospital n=477 pts. 27% decline in polyp detection.
  • -NEJM 2009; 361: 1179. Review of screening for colorectal cancer.
  • -Gastroenterol 2009; 137: 792. Use of CT colonography -current appraisal.
  • -Ann Intern Med 2009; 150: 1-8. Says endoscopists miss most cancers on right side & colonosopy reduces cancer by ~60% primarily due to left-sided cancers.  Most, 73%, of colonoscopies not done by GI/colorectal surgery.
  • -Gastroenterol 2008; 134: 1570. Update recommendations from ACS, ACR, US Multi-society task force.
  • -Clin Gastro & Hep 2005; 3: 633.  Inherited polyposis syndromes & genetic testing.
  • -Clin Perspectives in Gastro 2002; 5: 329.  Polyp techniques & complications. If entrapped snare, consider cutting off snare handle & pulling on 1 wire. Alternative us to use snare as guidewire & push scope beyond wire. For large stalks, consider using snare as tourniquet for 5 min. Consider pure (or blended) coagulation at settings 20-30W.
    Injection of fluid into the submucosa beneath the polyp increases the distance between the polyp and the deeper layers of the colon. Using a sclerotherapy needle normal saline is injected at the edge of the polyp raising a bleb. No specific volume of normal saline is used. The objective is to raise a large bleb with marked elevation of the polyp. The snare is then placed around the base of the polyp and it can be removed with electrocautery. If bleeding is a consideration then a solution of epinephrine can be used at a 1:10,000 concentration. The advantage of cautery is that residual tissue is usually destroyed although this is usually not a consideration when removing juvenile polyps.Hot biopsy forceps are usually used to ablate diminutive polyps (< 5 mm in diameter). The coagulation current applied should be low. 10-15 watts applied for 1-2 seconds. The technique is generally safe but serious complications including bleeding or perforation have been reported.The cold snare technique is safe in small polyps. (< 5 mm) The rationale is that the vessels feeding the polyp are small and the risk of bleeding is low. The advantage is that without cautery there is not deep tissue damage. Submucosal injection may make the procedure safer.