Inflammation severity at cancer diagnosis tied to outcomes in ulcerative colitis
Nationwide Japanese study finds colorectal cancers within UC-affected mucosa linked to lower recurrence-free and cancer-specific survival.
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02/18/2026
A nationwide, multicenter retrospective study published in the Journal of Crohn’s and Colitis investigated the relationship between background mucosal inflammation and oncologic outcomes in patients with ulcerative colitis (UC) who developed colorectal cancer (CRC). The study was conducted by Hiroki Ishii, MD, PhD, of the University of Tokyo, and colleagues, and included contributions from 43 institutions across Japan, analyzing patient data collected over nearly four decades, from 1983 to 2020.
The study cohort consisted of 723 patients with histologically confirmed UC-associated CRC. Patients were categorized based on tumor location relative to the UC-involved mucosa as documented by endoscopy at the time of cancer diagnosis. Of these, 683 patients were classified as having CRC within the UC-involved area (“within-area”), while 40 patients had CRC outside this area (“outside-area”).
Baseline demographic and clinical characteristics differed between the two groups. Patients with within-area tumors were younger on average (mean age 51.8 years) compared with those in the outside-area group (mean age 61.1 years). The extent of UC involvement also varied, with 81.3% of the within-area group having extensive colitis, while left-sided colitis and proctitis predominated in the outside-area group. Tumor location was predominantly in the left colon and rectum among within-area patients, whereas right-sided colon tumors were more frequent in the outside-area group.
Five-year recurrence-free survival (RFS) rates were 75.1% for patients with within-area CRC compared with 87.6% for those with outside-area CRC, a statistically significant difference (P = .022). Similarly, cancer-specific survival (CSS) was lower in the within-area group at 81.1% versus 94.3% in the outside-area group (P = .038). Multivariable Cox proportional hazards modeling showed that tumor location relative to UC involvement remained an independent prognostic factor, with a hazard ratio of 2.99 (95% confidence interval, 1.09–8.18; P = .030), alongside pathological stage and histological tumor type.
As Ishii and colleagues wrote in the Discussion section, “Patients with CRC within the UC-involved area had significantly worse outcomes in terms of both RFS and CSS compared with CRC outside the UC-involved area.” They further reported that, in multivariable analysis, this classification “remained an independent prognostic factor alongside pathological stage and histological type.”
Within the within-area group, severity of background mucosal inflammation was assessed by the Mayo Endoscopic Score (MES) applied to non-neoplastic mucosa at cancer diagnosis. The MES categorizes inflammation as inactive (0), mild to moderate (1–2), or severe (3). A stepwise decrease in 5-year CSS was observed with increasing MES severity: 89.0% for inactive, 84.8% for mild–moderate, and 73.8% for severe inflammation (P = .048). Recurrence-free survival also showed a similar trend, although this did not reach statistical significance. Importantly, pathological stage and histological subtype did not significantly differ across MES strata, indicating that inflammation severity was independently associated with prognosis.
The authors concluded that “greater background mucosal inflammation shows a graded association with poorer prognosis that is not simply explained by stage or histology,” reinforcing the potential clinical importance of assessing inflammation severity at the time of cancer diagnosis.
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7 Key Takeaways
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Developed a paper-based colorimetric sensor array for chemical threat detection.
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Can detect 12 chemical agents, including industrial toxins.
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Production cost is under 20 cents per chip.
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Utilizes dye-loaded silica particles on self-adhesive paper.
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Provides rapid, simultaneous identification through image analysis.
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Inspired by the mammalian olfactory system for pattern recognition.
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Future developments include a machine learning-enabled reader device.
The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.