Globally, colon cancer remains one of the leading causes of mortality. Multidrug resistance, systemic toxicity, and poor tumor selectivity significantly limit conventional chemotherapy. This review highlights the need for localized therapy to increase efficacy and minimize systemic side effects. Colon-targeted drug delivery systems (CDDS) are designed and developed to overcome these challenges. Both natural and synthetic polysaccharides act as carriers in CDDS because of their biodegradability, biocompatibility, pH- and enzyme-responsiveness, and mucoadhesive properties. Polysaccharides such as chitosan, dextran, pectin, alginate, and hyaluronic acid have been formulated into nanoparticles, microparticles, and hydrogels, enabling controlled and site-specific delivery. These carriers deliver chemotherapeutics, nucleic acids, and immunotherapeutics, as well as theranostic agents that combine imaging and therapy. Preclinical evidence demonstrates significant translational potential for polysaccharide-based CDDS. However, clinical trials remain limited, which highlights the gap between laboratory findings and clinical applications. Major challenges in colon-targeted drug delivery include variability in polysaccharide sources and quality, difficulties in large-scale manufacturing, and regulatory challenges. Addressing these challenges will be essential to move towards commercialization and clinical adoption. Personalized therapy through microbiome profiling, integration with nanotechnology and bioinformatics, and smart, biosensor-responsive carriers will be the focus going forward. Polysaccharide-based CDDS provide safer, more effective, and more personalized treatment with continued research to optimize delivery and overcome existing limitations.

Collision tumours are uncommon lesions in which two histologically distinct neoplasms coexist at one anatomical site, creating diagnostic difficulty when one component predominates clinically or histologically. A 70-year-old man presented with a large exophytic pigmented tumour on the lower abdomen that had been present for approximately 20 years and had enlarged rapidly during the preceding 5 years. He was brought to the emergency department because of tumour bleeding, progressive anaemia, poor nutritional status, and difficulty with mobilisation. Contrast-enhanced computed tomography during emergency systemic assessment revealed multiple pulmonary, hepatic, and bilateral lymph node lesions suspicious for distant metastases. Because urgent local control was required, no preoperative incisional biopsy was performed, and complete excision with immediate reconstruction was undertaken as a therapeutic excisional biopsy. Initial histopathological and immunohistochemical evaluation showed basal cell carcinoma with BerEP4 positivity. However, the metastatic pattern was inconsistent with basal cell carcinoma, prompting biopsy of a pulmonary nodule, which demonstrated malignant melanoma. Because primary pulmonary melanoma is extremely rare, the abdominal lesion was re-evaluated. Additional sampling from previously unsampled areas identified a MelanA-positive atypical melanocytic component adjacent to and partially intermingled with the basal cell carcinoma, confirming a cutaneous collision tumour. The distant lesions were interpreted as metastases from the melanoma component. BRAF V600 mutation analysis was negative, and nivolumab plus ipilimumab was initiated. However, the disease progressed rapidly, further systemic therapy was discontinued, and the patient died shortly thereafter from cancer-related complications. This case highlights how sampling bias and clinicopathological discordance can obscure aggressive malignant components in cutaneous collision tumours. In large, heterogeneous, or clinically aggressive cutaneous tumours, systematic multi-site sampling and prompt clinicopathological reassessment are essential when the initial pathological diagnosis does not fully explain the clinical behaviour.

Retinoblastoma (RB) is a treatable tumor that arises in the retina, mainly affecting children under 2 years old. It results from a mutation on the long arm of chromosome 13, specifically of the RB1 gene (13q14). Patients with the hereditary form of RB have a higher incidence of metastases and secondary cancer development. These cancers, including metastasis, secondary malignant neoplasms, and radiation-associated sarcomas, are rare and typically occur in advanced stages. Although the overall prognosis for RB is generally favorable, it declines significantly when metastases develop. While rare, the most common sites of RB metastasis are the brain, osseous structures, cervical nodes, central nervous system, lungs, and liver. Here, we present the clinical and radiologic features of three patients with osseous metastasis from RB and review current literature, including the development of secondary malignant neoplasms, radiation-associated sarcomas, prognosis, and treatment options.

 Small intestinal cavernous hemangiomas are rare vascular malformations that present diagnostic and therapeutic challenges due to their deep location and propensity for recurrent bleeding. This report aims to describe a case with a sequential management approach and to synthesize existing evidence through a narrative literature review.

A 74-year-old female presented with recurrent melena for five months. Initial imaging (gastroscopy, colonoscopy, computed tomography angiography, and computed tomography enterography) revealed no bleeding source. Balloon-assisted enteroscopy identified a 0.6 cm mucosal protrusion 520 cm distal to the pylorus, with active oozing. Endoscopic hemostasis was achieved using metal clip occlusion and lauromacrogol sclerotherapy, following which a biopsy was performed safely to confirm the diagnosis of hemangioma. Six months later, melena recurred, and the patient underwent surgical resection of the same lesion. Pathological examination confirmed a cavernous hemangioma. At two-year follow-up, the patient remained free from recurrent gastrointestinal bleeding.

 This case highlights the value of balloon-assisted enteroscopy for localizing obscure small intestinal bleeding and achieving temporary hemostasis. While endoscopic intervention facilitates diagnosis and acute bleeding control, surgical resection remains the definitive treatment for selected cases. Close follow-up may be considered to monitor for potential recurrence. A narrative review of the literature supports the rarity of this condition and the limited evidence base for treatment standardization.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer-related mortality. The gut microbiome has attracted growing attention because of its involvement in CRC initiation and progression, early detection, prognostic evaluation, and therapeutic response. However, CRC microbiome studies continue to face inconsistent findings and limited reproducibility, partly because of differences in specimen type. Directly comparing microbial signals from fecal, mucosal, and intratumoral samples may therefore bias mechanistic interpretation and mislead clinical translation. From a spatial-niche perspective, this review summarizes the distinct characteristics, formation mechanisms, interrelationships, and clinical implications of fecal, mucosal, and intratumoral microbiota during CRC progression. We further propose a "seed bank-colonizers-specialized populations" model to conceptualize the continuous but non-equivalent hierarchy among these niches. By providing a clearer spatially stratified framework, this review aims to help move CRC microbiome research beyond descriptive associations toward precision-oriented applications supported by mechanistic interpretability, reproducible evidence, and clinical translatability.

Thyroid cancer (TC) and colorectal cancer are common malignancies of the endocrine and gastrointestinal systems, respectively, and continue to impose a substantial global disease burden. The tumor immune microenvironment (TIME) plays a central role in tumor initiation, progression, and therapeutic response; however, the cellular composition and intercellular communication networks within the TIME exhibit marked heterogeneity between these two malignancies. Recent advances in single-cell sequencing and spatial transcriptomics have revealed complex and dynamic alterations in immune cell subsets, stromal cell functions, cytokine networks, and metabolic programs within the TIME. In particular, bidirectional communication between tumor cells and immune cells has emerged as a critical determinant of immune evasion and therapeutic resistance. Nevertheless, most existing studies have focused on individual tumor types, and systematic comparisons of the shared and distinct features of the TIME in thyroid cancer and colorectal cancer remain limited. Moreover, combination therapeutic strategies targeting the TIME are still under active investigation. This review systematically compares the immune microenvironments of thyroid cancer (TC) and colorectal cancer (CRC), highlighting the development of more precise and effective immunotherapeutic strategies for thyroid cancer and colorectal cancer.

Colorectal cancer (CRC) remains a major cause of cancer mortality, with up to 26% of adenomas missed on conventional colonoscopy. Artificial intelligence (AI)-based computer-aided detection (CADe) systems may reduce these miss rates. We aimed to validate the iIDEAS-C CADe module in a prospective cohort, with co-primary endpoints of adenomas per colonoscopy (APC) and lesion-level miss rate.

In this prospective, nonrandomized, single-center study (NCT05784935), consecutive adults (18-75 years) undergoing screening, surveillance, or diagnostic colonoscopy were enrolled between February and May 2023. Each colon segment was inspected twice: an initial blinded withdrawal without CADe, followed by a second inspection with iIDEAS-C. Missed lesions were those identified by CADe during the second inspection and confirmed endoscopically. Secondary outcomes included PDR, ADR, PPC, lesion characteristics, and procedural times.Two hundred patients (mean age 44.1 ± 12.7 years; 64% male) were included. Eighty-two polyps were detected across 42 patients (PDR = 21%). Endoscopists detected 61/82 polyps (74.4%), yielding a per-polyp miss rate of 25.6%. The iIDEAS-C module detected all 82 lesions, achieving 0% per-polyp and per-adenoma miss rate. Missed lesions were mostly diminutive and proximal. PPC increased from 0.305 to 0.410 (p < 0.0001), PDR from 17.5% to 21.0% (p = 0.016), and APC from 0.115 to 0.140 (p = 0.029). No adverse events occurred.

The iIDEAS-C module demonstrated a 0% lesion-level miss rate and significantly improved key detection metrics, especially for small proximal lesions. Larger multicenter studies are warranted to confirm these findings and assess long-term outcomes. ClinicalTrials.gov: NCT05784935. Trial Registration: ClinicalTrials.gov identifier: NCT05784935.

Chronic pancreatitis (CP) creates an inflammatory pancreatic microenvironment and is an established risk factor for pancreatic cancer (PC). However, immune-inflammatory links between CP and PC remain unclear. Isorhamnetin (ISO), a natural flavonoid with anti-inflammatory and antitumor activities, may influence pancreatic inflammatory signaling. This study investigated ISO-associated molecular networks shared by CP and PC, examined the relationships between prioritized targets and transcriptome-estimated immune-cell infiltration, and evaluated the effects of ISO in pancreatic cancer cells.

CP- and PC-associated targets were collected from disease databases, and ISO targets were obtained from drug-target prediction platforms. Disease- and ISO-related targets were analyzed using protein-protein interaction networks, functional enrichment, and hub-gene screening. The expression, prognostic relevance, diagnostic performance, and immune infiltration associations of hub genes were evaluated using TCGA-PAAD, GTEx, Kaplan-Meier Plotter, ROC analysis, and CIBERSORTx. Molecular docking and 100 ns molecular dynamics simulations assessed ISO-target binding stability. Two-sample Mendelian randomization (MR) explored potential causal associations between genetically proxied circulating levels of the six hub proteins and CP or PC risk. The effects of ISO on proliferation, wound closure, apoptosis, and target protein expression were examined in PANC-1 and BXPC-3 cells.

372 overlapping CP- and PC-associated targets and 48 ISO-related targets were identified. EGFR, AKT1, MMP9, BCL2, TNF, and IL6 were screened as hub genes. Functional enrichment indicated targets were involved in inflammatory responses, cytokine-related signaling, apoptosis regulation, epithelial proliferation, pancreatic cancer-related pathways, and PI3K-Akt signaling. Hub-gene expression was correlated with CIBERSORTx-estimated immune-cell fractions, including activated natural killer cells and several T-cell subsets. Molecular docking and molecular dynamics simulations provided preliminary support for ISO-target interactions and complex stability. Across the 12 prespecified protein-outcome combinations, MMP9-CP was the only nominal IVW association. In vitro, ISO reduced the viability and wound closure of PANC-1 and BXPC-3 cells, promoted apoptosis, and decreased EGFR, AKT1, BCL2, and TNF-α protein expression in a concentration-dependent manner.

ISO may influence CP- and PC-associated molecular networks through multitarget regulation involving EGFR, AKT1, MMP9, BCL2, TNF, and IL6. These findings provide hypothesis-generating computational, genetic, and cellular evidence supporting investigation of ISO in pancreatic inflammation-associated tumor biology. However, immune regulatory effects, MMP9/IL6 protein modulation, and EGFR/AKT pathway activation require further experimental validation.

Clear cell renal cell carcinoma (ccRCC) is a major subtype of renal cell carcinoma and characterized by metabolic reprogramming, especially glycolysis. Neurexophilin 4 (NXPH4) is associated with malignancy of several cancers. However, its function in ccRCC remains unclear. In the current study, several online bioinformatics databases confirmed that NXPH4 was highly expressed in ccRCC tissues and was correlated with poor prognosis in patients with ccRCC. Notably, inhibition of NXPH4 suppressed cell viability, invasion and migration of ccRCC cells, and promoted cell apoptosis; while its overexpression produced the opposite effects. Further online database revealed a positive correlation between NXPH4 expression and glycolysis-related genes LDHA and HK2 in ccRCC tissues. Suppression of NXPH4 obviously decreased protein expression of LDHA and HK2 in ccRCC cells. Importantly, knockdown of NXPH4 attenuated glycolysis by inhibiting glucose uptake, lactate, ATP levels, extracellular acidification rate (ECAR) and increasing oxygen consumption rate (OCR); however, NXPH4 up-regulation promoted glycolysis. Intriguingly, the pro-tumor effects of NXPH4 were reversed by the glycolysis antagonist 2-DG. Additionally, NXPH4 elevation activated the PI3K/AKT pathway, while blocking this pathway significantly offset NXPH4-driven glycolysis, viability, invasion and migration. Collectively, NXPH4 may contribute to cancer cell growth and metastatic potential in ccRCC by activating the PI3K/AKT-evoked glycolysis, supporting it as a promising therapeutic target for ccRCC.

The recruitment of immune cells to the tumor microenvironment (TME) is an important component of immune regulation and tumor progression. Studying the spatial and temporal relationships between immune and tumor cells in vivo can provide insight into interactions within the TME. However, visualizing and quantifying these interactions in intact organisms remains challenging using conventional imaging and histological approaches. Zebrafish provide a valuable model for cancer research owing to their genetic tractability, rapid development, and optical transparency during early developmental stages, enabling visualization of fluorescently labeled cells in vivo. Here, we present a protocol to generate, identify, image, and quantify immune and tumor cells that are differentially labeled with fluorescent markers in a zebrafish model of neuroblastoma. The protocol includes breeding and screening of compound transgenic zebrafish, live imaging of larvae, preparation and imaging of adult tumor-bearing fish, and quantification of immune cells surrounding and within tumor regions. Using transgenic reporter lines, CD4⁺ immune cells and MYCN-driven neuroblastoma cells can be visualized and analyzed at different developmental stages. The workflow enables assessment of immune cell localization relative to tumors in both larval and adult fish and can be used to compare immune cell abundance across disease stages. This protocol provides a reproducible approach for imaging and quantifying immune cells within the TME in vivo using zebrafish and may facilitate studies of immune-tumor interactions in other cancer models.