Long-standing inflammatory bowel disease (IBD) increases the risk of dysplasia and colorectal cancer (CRC), particularly in patients with extensive disease or coexisting primary sclerosing cholangitis (PSC). Several non-conventional dysplasia subtypes have been identified. Hypermucinous dysplasia was first formally proposed in 2020, and it arises predominantly in patients with long-standing ulcerative colitis, frequently in extensive disease and concomitant PSC. Histologically, hypermucinous dysplasia is characterized by a tubulovillous or villous architecture lined by tall, prominent, mucin-rich epithelial cells comprising more than 50% of the lesion, with minimal-to-mild cytologic atypia. Although often classified as low-grade dysplasia according to previously established criteria, hypermucinous dysplasia is disproportionately associated with advanced neoplasia, including high-grade dysplasia and CRC, and frequently coexists with both conventional and other non-conventional dysplasias. Molecular alterations commonly include aneuploidy and occasional TP53 mutation. Emerging evidence suggests that non-dysplastic, mucin-rich epithelial proliferation, such as hypermucinous mucosa and foveolar metaplasia, may represent putative precursor lesions within a broader metaplasia–dysplasia sequence. This review provides the first comprehensive synthesis focusing exclusively on hypermucinous dysplasia, highlighting the consistency in histopathologic definitions, proposed precursor lesions, clinicopathological associations, molecular features, and diagnostic reproducibility. Increased awareness of hypermucinous dysplasia is essential for accurate diagnosis, risk stratification, high-risk IBD population screening, and optimal management of patients with IBD.

Objectives: Diagnosis of undifferentiated-type-predominant mixed-type early gastric cancer (UM-EGC) remains challenging due to its complex histological features and overlapping characteristics with other gastric cancer types. We aimed to develop a novel nomogram based on clinicopathological and endoscopic features and validate its performance in predicting UM-EGC prior to endoscopic treatment.

Methods: In this retrospective single-center study, 808 patients with early gastric cancer (EGC) who underwent curative endoscopic submucosal dissection were included. Among them, 493 were assigned to the training cohort and 84 to the external validation cohort. Clinicopathological characteristics and endoscopic features were compared between differentiated EGC and UM-EGC using logistic regression analysis. A predictive nomogram was constructed and evaluated.

Results: Multivariable regression analysis identified open-type atrophic gastritis (O1–O3) (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.08–0.82), IIb (OR 9.72, 95% CI 3.01–31.35), IIc (OR 7.75, 95% CI 2.81–21.39), discolored lesion (OR 4.12, 95% CI 1.57–10.80), horizontal location at the greater curvature (OR 2.98, 95% CI 1.15–7.75) or anterior wall (OR 2.91, 95% CI 1.26–6.74), and previous H. pylori eradication (OR 0.23, 95% CI 0.09–0.55) as independently associated with UM-EGC. UM-EGC was also more susceptible to metachronous cancer (OR 5.50, 95% CI 1.30–23.21). The nomogram demonstrated good discriminative ability with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.77–0.87) in the training cohort and 0.82 (95% CI 0.69–0.98) in the external validation cohort.

Conclusion: This nomogram comprising clinicopathological and endoscopic features may assist in the preoperative prediction of UM-EGC risk.

Trial Registration: The clinical trial registration number for patient source in this study is ChiCTR1800017117

Objective: To explore the involvement of neutrophil dysregulation in Cronkhite–Canada syndrome (CCS) and to identify serum biomarkers for its diagnosis and disease activity assessment.

Methods: We performed comprehensive serum proteomic analysis using data-independent acquisition (DIA) on samples from patients with active CCS (aCCS) and healthy controls (HCs). Candidate proteins were further evaluated by parallel reaction monitoring (PRM). An independent validation cohort including cases with aCCS, remitting CCS (rCCS), and HCs was then assessed using enzyme-linked immunosorbent assay (ELISA). In addition, previously generated transcriptomic data and immunofluorescence staining of colonic polyps were used to assess local neutrophil extracellular trap (NET)-related immune changes in intestinal tissues.

Results: Proteomic screening identified 362 differentially expressed proteins, and bioinformatic analysis consistently highlighted pathways related to neutrophil activation, acute inflammation, and NET formation. Key neutrophil-associated proteins, including myeloperoxidase (MPO), lipocalin-2 (LCN2), and matrix metalloproteinase-9 (MMP-9), were significantly upregulated. PRM validated seven upregulated candidate proteins. In the independent validation cohort, compared with HCs, serum MPO-DNA complexes, LCN2, and MMP-9 were significantly elevated in aCCS patients, whereas MPO-DNA complexes and MMP-9 were significantly reduced in rCCS cases. Tissue-level transcriptomic and immunofluorescence analyses further supported NET-related immune activation in CCS colonic polyps. Receiver operating characteristic curve analysis demonstrated favorable diagnostic performance for these biomarkers.

Conclusions: Our findings support the involvement of neutrophil dysregulation and NET-associated pathways in CCS pathobiology. Serum MPO-DNA complexes, LCN2, and MMP-9 may serve as promising non-invasive biomarkers for diagnosis and disease activity monitoring. Further studies incorporating disease control cohorts and mechanistic validation are warranted.

Objectives: Despite the relatively comprehensive understanding of esophageal high-grade intraepithelial neoplasia (HGIN), clinical characteristics of HGIN dominated by cytological atypia after endoscopic submucosal dissection (ESD) remain unclear. We aimed to investigate the postoperative features and adverse events of patients with this pathological feature after ESD.

Methods: We retrospectively analyzed the data of 160 patients who underwent ESD for HGIN from 2018 to 2019. The patient cohort was divided into two groups based on the histopathology of the resected lesions: dominated by architectural atypia (HGINa) and cytological atypia (HGINc). Information on postoperative adverse events (fever, perforation, hemorrhage, and esophageal stricture) and second-stage endoscopic treatments was collected. Follow-up was conducted until December 2024 to analyze postoperative new-onset neoplasia between the two groups. Binary logistic regression analyses were used to assess risk factors for postoperative adverse events.

Results: Among all included patients, 43 (26.88%) and 117 (73.12%) were classified as having HGINc and HGINa, respectively. The rates of postoperative fever and new-onset neoplasia were significantly higher in the HGINc group than in the HGINa group (both p < 0.05), and HGINc emerged as an independent risk factor for these outcomes. Muscularis propria injury and mucosal defect exceeding 75% of the circumference were associated with postoperative esophageal stricture.

Conclusion: Post-ESD management should focus on fever and new-onset neoplasia in patients with HGINc.

Objectives: Vonoprazan was approved in China for reflux esophagitis (RE) in 2019; however, its real-world safety and effectiveness remain undetermined. We aimed to evaluate the safety of vonoprazan in patients and its effectiveness in patients with RE in a real-world setting.

Methods: In this prospective, non-interventional, real-world study, vonoprazan 20 mg was administered orally daily for 4 or 8 weeks. Primary endpoints were incidence rates of adverse events (AEs), serious AEs (SAEs), and adverse drug reactions (ADRs). Secondary endpoints included proportions of patients with RE without typical gastroesophageal reflux disease (GERD) symptoms (complete symptom relief) at baseline and Week 4, relief of heartburn/regurgitation symptoms (all day/nighttime) during Week 1, and mean change in GERD Questionnaire (GERDQ) score at Week 4.

Results: Of the 2829 patients with safety data, 488 (17.2%) reported ≥ 1 AE; 29 (1.0%) reported ≥ 1 SAE; and 129 (4.6%) reported ≥ 1 ADR. Of 1796 patients with RE and effectiveness data, the proportion without typical symptoms of GERD increased from 20.1% (95% confidence interval [CI] 18.29–22.05) at baseline to 55.2% (95% CI 52.63–57.79) at Week 4 (change: 35.1%, 95% CI 31.95–38.25). Complete relief from heartburn, nighttime heartburn, regurgitation, and nighttime regurgitation was observed in 32.3% (314/971), 43.8% (427/975), 27.0% (262/971), and 40.5% (395/976) patients, respectively, during Week 1. Mean change in GERDQ score (n = 1464) improved by Week 4 (−1.70).

Conclusion: Vonoprazan is well tolerated through 8 weeks in patients and improves symptoms in patients with RE in the real-world setting in China (VIEW; NCT04501627).

Objectives: Comparative data on infliximab (IFX) and tacrolimus as salvage therapies for intravenous glucocorticoid (ivGC)-refractory acute severe ulcerative colitis (ASUC) are limited. We aimed to evaluate the effectiveness and safety of IFX versus tacrolimus in hospitalized patients with ivGC-refractory ASUC.

Methods: This retrospective study was conducted between 2017 and 2024 at a tertiary medical center, including inpatients with ASUC who failed ivGC and received IFX or tacrolimus. The primary outcome was colectomy-free clinical response at discharge.

Results: Thirty-seven patients received IFX (median age 27 years; 32.4% males), and 24 received tacrolimus (median age 32 years; 41.7% males). Compared with the patients who received IFX, those receiving tacrolimus had a longer disease duration (4 years vs. 1 year, p = 0.031) and a higher rate of prior exposure to advanced therapy (anti-tumor necrosis factor agent: 58.3% vs. 2.7%, p = 1.05 × 10⁻⁶; Janus kinase inhibitors: 20.8% vs. 0%, p = 0.007). The length of hospitalization was significantly longer among those receiving tacrolimus (median 19.5 days vs. 11.0 days, p = 0.019). Colectomy-free clinical response rate at discharge (81.1% vs. 83.3%, multivariate analysis p = 0.956) and total colectomy rate in the following year (12.5% vs. 14.3%, p = 0.851) did not significantly differ between the IFX and tacrolimus groups. Safety profile during hospitalization was comparable between groups.

Conclusions: In ivGC-refractory ASUC cases, IFX and tacrolimus showed comparable effectiveness and safety. Similar outcomes were observed despite a more treatment-refractory profile in the tacrolimus group. These findings support the use of either agent as a feasible salvage option in this clinical setting.