Colorectal cancer (CRC) occurs with higher frequency in patients with inflammatory bowel disease (IBD) and has increased morbidity and mortality compared with CRC in patients in the general population. STAT3 has been implicated in CRC development, but strategies to target it have yet to be employed to prevent its occurrence in groups at high risk for CRC. Our group developed TTI-101, a small-molecule STAT3 inhibitor, which was effective in treating colitis in the dextran sodium sulfate (DSS) mouse model. In the current study, we examined the ability of TTI-101 to prevent CRC in the azoxymethane (AOM)-DSS mouse model of CRC. Mice received AOM followed by DSS and were treated with either TTI-101 or vehicle control for 10 weeks. While vehicle-treated AOM-DSS mice developed polyps and adenocarcinomas, TTI-101-treated AOM-DSS mice did not. Levels of activated STAT3 (pY-STAT3) were increased in both the epithelial and stromal compartments of adenocarcinomas vs. normal colon mucosa and correlated with adenocarcinoma burden. Pharmacologically relevant concentrations of TTI-101 were detected in plasma and colon; plasma levels correlated with colon levels and correlated inversely with adenocarcinoma number. Transcriptomic analyses revealed that TTI-101 normalized expression of AOM-DSS-induced CRC-associated genes in the colon, many of which are regulated by STAT3. The addition of DSS to AOM resulted in a distinct cecal microbiome diversity and composition that was muted by the addition of TTI-101. Thus, TTI-101 prevented colitis-associated CRC in the AOM-DSS model through targeting STAT3's pro-oncogenic effects on the colon transcriptome and modulating colitis-associated dysbiosis; targeting STAT3 in patients with IBD merits consideration for CRC prevention, as well as IBD treatment.

Crohn's disease (CD) is a subtype of inflammatory bowel disease characterized by discontinuous lesions and transmural inflammation. Delayed diagnosis may lead to fistula formation between the intestine and adjacent organs. However, most CD-associated fistulas are enteroenteric or perianal, and abdominal wall abscesses are rarely reported in pediatric patients. We report a case of CD presenting as an abdominal wall abscess in a 15-year-old girl with autism spectrum disorder. Contrast-enhanced computed tomography revealed a fistulous communication between the abscess cavity and the transverse colon. Percutaneous drainage and antibiotic therapy were performed to control the infection. Colonoscopy demonstrated skip lesions with longitudinal ulcers, cobblestone-like mucosa, and inflammatory polyps. Histopathological examination showed active chronic colitis compatible with inflammatory bowel disease. Remission induction therapy consisting of elemental diet, 5-aminosalicylic acid, and corticosteroids was initiated after infection control. Her clinical condition gradually improved, and she was discharged on hospital Day 37. During follow-up, her appetite improved and she gradually gained weight. At 18 months after discharge, contrast-enhanced computed tomography showed no recurrence of the abdominal wall fistula, and her clinical condition remained stable. In pediatric patients, CD may present with nonspecific systemic symptoms, which can delay diagnosis. In patients with autism spectrum disorder, communication difficulties may further obscure gastrointestinal symptoms. Clinicians should consider underlying inflammatory bowel disease when children present with unexplained abdominal wall abscesses accompanied by systemic symptoms such as growth failure or malnutrition.

Enterococcus faecalis bacteremia presents a diagnostic challenge, particularly in elderly patients with multiple comorbidities and cardiac implantable electronic devices. We present the case of an 88-year-old woman with atrial fibrillation on anticoagulation, pacemaker placement, hypertension, hypothyroidism, and anxiety who presented with five days of abdominal pain, nausea, vomiting, and upper back/right shoulder pain. Initial evaluation raised concern for pneumonia due to the patient's chest X-ray and elevated temperature, and she was admitted for further management. Blood cultures at 48 hours grew Gram-positive cocci in pairs and chains and Enterococcus faecalis, prompting treatment with ceftriaxone and ampicillin and an extensive search for an infectious source. Transthoracic and transesophageal echocardiography showed no evidence of infective endocarditis or pacemaker-associated infection. Abdominal imaging was unrevealing. During hospitalization, the patient developed a declining hemoglobin and reported melena, prompting gastrointestinal evaluation. Colonoscopy revealed multiple colonic polyps, including tubular adenomas in the cecum and rectum, without evidence of malignancy. These adenomas were considered the most plausible portal of entry for bacteremia. Repeat blood cultures cleared, and the patient was transitioned to oral amoxicillin on discharge with outpatient follow-up. This case highlights the importance of considering gastrointestinal sources, including colorectal neoplasia, in patients with E. faecalis bacteremia of unclear origin. It also supports the role of multidisciplinary evaluation, including infectious disease, cardiology, and gastroenterology, in guiding workup and management.

Accurate segmentation of colorectal polyps is important for colorectal cancer prevention. However, domain shifts across medical centers and blurred boundaries of diminutive lesions remain major challenges for robust polyp segmentation. We propose FreqPolyp, a frequency-domain polyp segmentation framework designed for single-source domain generalization. At the input stage, the frequency domain augmentation module perturbs amplitude-related appearance statistics while preserving phase-related structural information, thereby reducing dependence on source-domain photometric styles without using target-domain data. At the decoding stage, the wavelet dual-stream fusion module uses discrete wavelet transform to extract high-frequency boundary cues and semantic-guided cross-attention to refine low-contrast lesion boundaries. In addition, a hybrid spatial-frequency supervision strategy combines amplitude-domain spectral consistency with phase-aware structural consistency. Experiments on five public benchmarks show that FreqPolyp achieves mDice/mIoU scores of 0.849/0.738 on ColonDB and 0.831/0.711 on ETIS, with an average unseen-domain mDice/mIoU of 0.865/0.765 across ColonDB, ETIS, and CVC-300. Under the tested RTX 3090 setting, FreqPolyp contains 26.2 M parameters and reaches 58 FPS. These results suggest that FreqPolyp provides a favorable accuracy-efficiency trade-off under public benchmark and controlled GPU evaluation settings.

PTEN Hamartoma Tumor Syndrome (PHTS) is a rare condition characterized by a complex phenotype including gastrointestinal hamartomas and increased lifetime malignancy risk. To characterize the clinical phenotype, genetic landscape, and spectrum of malignancies within a large cohort of adult PHTS carriers. A retrospective cohort study of adult patients (≥ 18 years) followed at specialized high-risk clinics who met PHTS diagnostic criteria based on either: (1) identification of a germline PTEN pathogenic/likely pathogenic variant, or (2) fulfillment of clinical criteria according to National Comprehensive Cancer Network (NCCN) guidelines. A total of 62 individuals were included (62.9% male; median age at inclusion 39.5, IQR, 28-52). All fulfilled diagnostic criteria for PHTS. PTEN pathogenic or likely pathogenic variant were identified in 50 individuals (80.6%). Colonic polyps were present in 40 patients. Malignancies were reported in 61% (n = 38), most frequently breast (n=13) and thyroid (n=7). Three individuals (4.8%) had rare soft tissue tumors: one with a desmoid tumor at age 18, one with concurrent axillary osteosarcoma and bilateral chest liposarcoma, and one with a skull-base sarcoma. Macrocephaly was observed in 33.8% (n = 21), and developmental delay, including autism spectrum disorder, in 8 patients (12.9%). One case of PTEN mosaicism was identified through tumor sequencing after negative blood genetic testing. Five individuals (8%) were treated with Sirolimus. This large cohort highlights the broad clinical spectrum and substantial cancer burden in PHTS, including rare soft tissue tumors. Constitutional mosaicism should be considered when clinical suspicion persists despite negative germline testing.

Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, ovary, stomach, small bowel, urinary tract, biliary tract, brain (usually glioblastoma), skin (sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas), pancreas, and prostate. Cancer risks and age of onset vary depending on the associated gene. Several other cancer types have been reported to occur in individuals with Lynch syndrome (e.g., breast, sarcomas, adrenocortical carcinoma). However, the data are not sufficient to demonstrate that the risk of developing these cancers is increased in individuals with Lynch syndrome.

Juvenile colorectal polyps (JP) are the most common polypoid lesions of the colon in children and the leading cause of lower gastrointestinal bleeding in pediatric patients. Although histologically classified as benign hamartomatous lesions, they arise in a context of allergic sensitization and IgE-mediated inflammation, suggesting that the epithelial compartment may play an active role in their pathogenesis. To date, most studies have focused on the immune cell infiltrate, leaving the molecular programs operating within the epithelium largely unexplored. Whole-transcriptome RNA sequencing (RNA-seq) was performed on epithelial cells isolated from pediatric JP (n = 8) and paired tissue circumjacent to polyp (TCP) (n = 7) obtained from children with a history of rectal bleeding and IgE sensitization to food allergens. Differential expression, functional enrichment (GO, KEGG, GSEA), and cross-dataset comparison with TCGA colorectal adenocarcinoma (CRC) was conducted. Candidate genes were validated by RT-qPCR in independent samples, including colorectal cancer (CRC) and inflammatory bowel disease (IBD) tissue. Differential expression analysis identified 3273 differentially expressed genes (2342 upregulated, 931 downregulated in JP vs. TCP), with 220 genes exceeding 32-fold change, including SERPINB3 (log2FC = 12.16), MMP1 (log2FC = 10.19), NMUR2 (log2FC = 10.08) and CHI3L1 (log2FC = 8.87). JP epithelium displayed a coherent type 2 inflammatory signature, encompassing upregulation of the alarmin IL33, eosinophil-attracting chemokines (CCL11, CCL24), IgE receptor subunits (FCER1A, FCER1G), and a coordinately activated leukotriene and prostaglandin biosynthetic program (ALOX5, ALOX5AP, PTGS2). Concurrent alterations in epithelial identity were observed, including downregulation of absorptive enterocyte and intestinal stem cell markers (CDX2, LGR5, ASCL2) alongside upregulation of secretory and regenerative programs, including the ectopic gastric-type mucin MUC5AC. Tight junction dysregulation-notably upregulation of the pore-forming claudin CLDN2 and loss of barrier-sealing claudins (CLDN3, CLDN4, CLDN23)-was consistent with impaired epithelial permeability. Pathway analyses confirmed activation of type 2 immune and extracellular matrix remodeling programs, with concurrent suppression of mitochondrial oxidative phosphorylation. Cross-dataset comparison with TCGA CRC data identified 381 co-upregulated and 87 co-downregulated genes shared between JP and CRC, including SERPINE1, CXCL8, ICAM1, and MMP3, several of which were associated with poorer disease-specific survival in CRC patients. RT-qPCR validation confirmed elevation of CHI3L1 and SERPINE1 in both JP and CRC, while SERPINB4 appeared JP-specific. Epithelial cells from pediatric juvenile colorectal polyps associated with allergic sensitization display a comprehensive type 2 inflammatory transcriptome alongside profound alterations in lineage identity, barrier integrity, and metabolic programming. Partial convergence with CRC-associated gene expression programs-in the absence of histological dysplasia-suggests that chronic allergic inflammation activates conserved epithelial remodeling pathways shared across mucosal tissues. CHI3L1, SERPINE1, and SERPINB4 are candidate biomarkers warranting validation in larger cohorts.

Colonoscopy is a key screening method for colorectal cancer (CRC), but its effectiveness is limited. Computer-aided detection (CADe) and computer-aided diagnostics (CADx), as part of an artificial intelligence (AI) system, improve the detection and optical characterization of lesions. This review maps and analyzes the evidence on the application of AI in colonoscopy, with a focus on the detection, segmentation, and characterization of colon neoplasms, available platforms, architectural models and implementation. The review was conducted in accordance with JBI and PRISMA-ScR guidelines, using the PCC framework. Meta-analyses, randomized controlled trials, systematic and narrative reviews, observational studies, guidelines, and consensus documents on the use of AI systems in different phases of colonoscopy were searched. CADe significantly improves adenoma detection and reduces the number of missed lesions. CADx, segmentation, depth of invasion assessment, and detection of learned lesions remain limited and heterogeneous. CADe has strong evidence for improving ADR, whereas current evidence for CADx remains insufficient to support a "resect-and-discard" strategy. Further cost-effectiveness studies are needed. Commercial platforms vary in their features and level of clinical validation. Colonoscopy using AI is a current topic with rapid development. This scoping review comprises heterogeneous literature covering clinical applications, technical aspects, the potential benefits and limitations of AI in improving colonoscopy performance and reducing the burden of colorectal cancer. Further trials involving diverse patient populations across different countries are needed to validate and extend the current evidence.