Search Results (2,439)

Background: The introduction of tyrosine kinase inhibitors has revolutionised the treatment of gastrointestinal stromal tumours (GISTs), yet the role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal GISTosis remains controversial. Methods: A retrospective analysis was conducted on patients with peritoneal GISTosis who underwent CRS plus HIPEC in an 18-year period. We analysed the clinicopathological characteristics and evaluated the perioperative and long-term outcomes based on the extent of disease (peritoneal cancer index, PCI), the resection (completeness of cytoreduction score) and the IM-administration. The survival factors were also analysed and the Kaplan–Meier estimator to model and estimate overall (OS) and progression-free survival (PFS). The median follow-up period was 72 months (range, 12–146). Results: A total of 25 patients (M:F = 15:10) with a median age of 57 years (range, 32–69) underwent CRS with HIPEC for peritoneal GIST metastases, detected either synchronously (n = 11) or metachronously (n = 14). The media PCI score was 9 (range, 4–20) and complete cytoreduction was achieved in 80%. Grade III complications were observed in two patients, whereas there was no postoperative mortality. Neoadjuvant imatinib-mesylate (IM) therapy was administered in 60% of patients who detected with metachronous metastases (n = 8/14), whereas adjuvant IM therapy was administered in 19 of 25 patients. Median OS was 62 months (95% CI = 22.8–101.2). Median OS and DFS for patients with PCI scores ≤ 10 were significantly longer compared to those with PCI scores > 10 (p = 0.009 and p = 0.024, respectively). Patients with CC scores of 0–1 had a significantly longer OS compared to those with CC scores of 2 (p = 0.005) and 3 (p = 0.002) and longer PFS compared to those with CC scores of 3 (p = 0.005). The need for imatinib did not significantly impact OS (p = 0.240) or PFS (p = 0.243). Conclusions: CRS combined with HIPEC shows promising results in peritoneal GISTosis, especially in patients with lower PCI and CC scores. Until larger studies validate its safety and efficacy, it should be primarily performed in expert hands in specialised peritoneal surface oncology centres. Full article

Background: Gastric signet-ring cell carcinoma (GSRCC) is a distinct subtype of gastric cancer characterized by unique biological features, leading to low rates of early diagnosis, poor prognosis, and limited response to chemotherapy and immunotherapy. Effective targeted therapies for GSRCC remain scarce. Given these treatment challenges and the potential efficacy of antibody-drug conjugates (ADCs) in clinical settings, this study focuses on identifying novel ADCs with significant potential to improve the treatment outcomes of GSRCC. Methods: We conducted a comprehensive bioinformatics analysis of GSRCC using multi-omics data (including transcriptomics and proteomics) and identified the poliovirus receptor (PVR) as a potential therapeutic target for GSRCC. We selected deruxtecan (DXd) as an effective carrier for developing an ADC targeting GSRCC. The synthesized PVR monoclonal antibody-DXd complex (PVR-DXd) has a drug-to-antibody ratio (DAR) of 4. Results: PVR-DXd demonstrated potent antitumor activity in a human GSRCC xenograft model, effectively eliminating tumors while sparing normal tissue, highlighting its potential as a novel and impactful targeted therapy for this aggressive subtype of gastric signet ring cell carcinoma. Conclusions: This preliminary study supports the further development of PVR-DXd as a candidate therapy for advanced GSRCC. Full article

Background/Objectives: Endoscopic submucosal dissection (ESD) is a state-of-the-art en bloc resection for early gastro-intestinal cancers and precursors developed and validated in Japan. Western expertise with this complex technique remains limited. Tutored training might be optimal for patients and ESD learning. We established ESD tutoring courses led by experienced Japanese experts to provide (i) optimal long-term curative outcomes and low complication rates for patients and (ii) hands-on training on difficult lesions for European endoscopists under direct expert supervision. Methods: Prospective data from 2011 to 2015 (follow-up to 12/2024) were analyzed. A total of 118 neoplasms (50% HGIEN and cancer) in 101 patients (median age 68 [37–91] years; 38% with significant comorbidities) were treated with expert or tutored ESD. Japanese experts performed 28 ESDs, while 22 trained beginners conducted 90 supervised procedures on difficult lesions during 5 live and 20 tutoring events (1–4 days each). Results: Analysis of the complete data showed curative and en bloc resection rates of 88% and 95%, respectively, with no recurrence after R0 resections during a median follow-up of 9.8 [1.5–14.9] years. Long-term survival remained recurrence-free after endoscopic resection of 3 recurrent adenomas (at R1/Rx) and curative surgery/2nd ESD for 5 non-curative ESDs. Adverse events occurred in 9.3% without emergency surgery or 30-day mortality. Comparing expert-only vs. tutored ESD procedures, beginners correctly applied curative ESD indications in 94% of 118 neoplasms. Experts resected larger lesions (22 cm²) at a rate of 9.3 cm²/h in 121 min. Tutored beginners achieved a 75% [25–100] self-completion rate on 33% smaller lesions in 112 min. Conclusions: ESD tutoring courses led by Japanese experts ensure excellent patient outcomes and standardized procedural training. This model may foster professional ESD performance across European referral centers. Full article

A key function of naturally occurring antibodies is to control pathologically altered cells, such as those with aberrant glycosylation. Age-related diminution in the pool of B cells producing these immunoglobulins is linked to impaired anti-tumor immunity. In this study, the levels of antibodies against tumor-associated carbohydrate antigens (TACAs)—common in gastric cancer (GC) and other malignancies—were analyzed in 235 treatment-naïve GC patients (stages I–IV) and 76 healthy donors using a printed glycan array (PGA). We found that anti-glycan IgM levels, but not IgG, reduced with age in both patients and donors. Crucially, IgM levels against most glycans were significantly lower in the GC cohort compared with healthy donors, a trend that remained after age adjustment. Furthermore, an immunohistochemical analysis revealed that human anti-GalNAcα (Tn) antibodies—a well-characterized TACA in gastrointestinal cancers—bound to tumor cells and exhibited perinuclear and membrane staining in non-tumor surface cells within the same organ. These data support the hypothesis that gastric cancer patients have reduced levels of anti-glycan IgMs, which are responsible for the early recognition of transformed cells. This specific immunodeficiency may contribute to a permissive environment for tumor development. Full article

Background and Clinical significance: Cowden syndrome is an autosomal dominant disorder caused by germline loss-of-function mutations in the PTEN tumor suppressor gene. It is characterized by multiple hamartomas and an increased lifetime risk of malignancies affecting the breast, thyroid, endometrium, and gastrointestinal (GI) tract. Pediatric presentations may include macrocephaly, scrotal tongue, and intellectual disability. Gastrointestinal involvement is frequent, with juvenile-like hamartomatous polyps occurring in at least half of patients and distributed throughout the GI tract, posing a risk for malignant transformation. Early diagnosis and surveillance are crucial for improving patient outcomes. Case Presentation: We report a case of a 10-year-old Caucasian female with Cowden syndrome, with a history of a malignant germ cell tumor of the ovary consisting of a yolk sac tumor and low-grade immature teratoma diagnosed at age six, and thyroidectomy at age nine. The patient has mild intellectual disability. Routine radiological surveillance revealed a right colon intraluminal mass, prompting referral for pediatric gastroenterology evaluation. Endoscopy identified multiple polyps throughout the colon, stomach, and small intestine. Polypectomy of larger lesions was performed, and histopathology confirmed juvenile-like hamartomatous polyps without dysplasia or malignancy. This case highlights the necessity of comprehensive gastrointestinal evaluation in pediatric Cowden syndrome patients. Endoscopic surveillance is essential for early detection and management of polyps. Conclusions: Given the multisystem involvement and elevated cancer risk associated with PTEN mutations, a multidisciplinary approach that includes genetic counseling, dermatologic evaluation, and ongoing oncologic monitoring is recommended. Increased awareness of gastrointestinal manifestations enables timely intervention and may reduce morbidity and mortality in this high-risk population. Full article

The mesenchymal–epithelial transition (MET) receptor is a tyrosine kinase activated by its sole known ligand, hepatocyte growth factor (HGF). MET signaling regulates key cellular processes, including proliferation, survival, migration, motility, and angiogenesis. Dysregulation and hyperactivation of this pathway are implicated in multiple malignancies, including lung, breast, colorectal, and gastrointestinal cancers. In non–small cell lung cancer (NSCLC), aberrant activation of the MET proto-oncogene contributes to 1% of known oncogenic drivers and is associated with poor clinical outcomes. Several mechanisms can induce MET hyperactivation, including MET gene amplification, transcriptional upregulation of MET or HGF, MET fusion genes, and MET exon 14 skipping mutations. Furthermore, MET pathway activation represents a frequent mechanism of acquired resistance to EGFR- and ALK-targeted tyrosine kinase inhibitors (TKIs) in EGFR- and ALK-driven NSCLCs. Although MET has long been recognized as a promising therapeutic target in NSCLC, the clinical efficacy of MET-targeted therapies has historically lagged behind that of EGFR and ALK inhibitors. Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. They have also demonstrated potential in overcoming MET-driven resistance to EGFR TKIs or ALK TKIs. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC. Full article

Cisplatin, a platinum-based compound, is a cornerstone of modern chemotherapy and remains widely used against a variety of solid tumors, including testicular, ovarian, lung, bladder, and head and neck cancers. Its anticancer activity is primarily attributed to the formation of DNA crosslinks, which obstruct replication and repair, ultimately leading to apoptosis. However, the clinical value of cisplatin is constrained by two major challenges: its toxic profile and the development of resistance. Cisplatin toxicity arises from its interaction not only with tumor DNA but also with proteins and nucleic acids in healthy tissues, resulting in a range of adverse effects, including, but not limited to, nephrotoxicity, ototoxicity, neurotoxicity, and gastrointestinal injury. In pediatric patients, permanent hearing loss represents a particularly debilitating complication. On the other hand, tumor cells can evade cisplatin cytotoxicity through diverse mechanisms, including reduced intracellular drug accumulation, enhanced DNA repair, detoxification by thiol-containing molecules, and alterations in apoptotic signaling. These resistance pathways severely compromise treatment outcomes and often necessitate alternative or combination strategies. This review examines the chemical structure of cisplatin, the molecular mechanisms of cisplatin cytotoxicity and cisplatin-induced resistance, as well as the main applications in cancer management and the complications associated with its clinical use. Full article

Introduction: The increasing global interest in plant-based diets has led to the development of innovative meat analogs that not only mimic the sensory properties of traditional products but may also offer potential health benefits. In this study, we investigated the nutritional characteristics and biological activity of potato protein-based vegan burgers (PBBs) enriched with plant-derived iron and fiber sources. Methods: The burgers were subjected to in vitro gastrointestinal digestion, followed by evaluation of their cytotoxic potential against human intestinal cancer cell lines (Caco-2 and HT-29) and normal colon epithelial cells (CCD 841 CoN). Additionally, their influence on the intestinal microbiota composition and enzymatic activity of β-glucosidase and β-glucuronidase was assessed. Results: PBBs demonstrated favorable nutritional profiles, high protein and fiber contents, and a balanced fatty acid ratio (n-6/n-3). After digestion, bioaccessible fractions showed selective cytotoxicity toward cancer cells, while maintaining safety for normal intestinal cells. Furthermore, PBBs modulated the gut microbiota by promoting the growth of beneficial genera (Lactobacillus, Bifidobacterium) and reducing potentially harmful Enterobacteriaceae, accompanied by decreased β-glucuronidase activity. Conclusions: These findings suggest that potato protein-based burgers could represent a functional plant-based alternative to conventional meat products, contributing to intestinal health and potentially reducing colorectal cancer risk. Full article

Colorectal cancer (CRC) has a high mortality rate worldwide. Oral and intestinal microbiota members may have an effect on gastrointestinal tumors’ pathogenesis, particularly in CRC. Designed as a pilot study, this study’s aim was to investigate the relationship between CRC and oral microbiota and to identify potential biomarkers for CRC diagnosis. Saliva samples were collected from recently diagnosed CRC patients (n = 14) and healthy controls (n = 14) between March 2023 and December 2023. Microbiota (16S rRNA) analyses were conducted on these saliva samples using a next-generation sequencing method. Phylogenetic analyses, including alpha diversity, principal component analysis (PCA), principal coordinate analysis (PCoA), beta diversity, biomarker, and phenotype analyses, were conducted using the Qiime2 (Quantitative Insights Into Microbial Ecology) platform. Alpha diversity indices (Shannon: p = 0.78, Cho1: p = 0.28, Simpson: p = 0.81) showed no significant difference between CRC and control groups. Beta diversity analysis using Bray–Curtis PCoA indicated significant differences in the microbial community between the two groups (p = 0.003). Examination of OTU distributions revealed that the Mycoplasmatota phylum was undetectable in the oral microbiota of healthy controls but was significantly elevated in CRC patients (CRC: 0.13 ± 0.30, Control: 0.00 ± 0.00, p < 0.05). Additionally, Metamycoplasma salivarium, Bacteroides intestinalis, and Pseudoprevotella muciniphila were undetectable in healthy controls but significantly more prevalent in CRC patients (p < 0.05 for all three species). LEfSe analysis identified eight species with an LDA score > 2, Granulicatella adiacens, Streptococcus thermophilus, Streptococcus gwangjuense, Capnocytophaga sp. FDAARGOS_737, Capnocytophaga gingivalis, Granulicatella elegans, Bacteroides intestinalis, and Pseudoprevotella muciniphila, as potential biomarkers. The results of this study contribute critical evidence of the role of oral microbiota in the pathogenesis of colorectal cancer. Alterations in the microbiota suggest potential biomarkers in understanding the biological mechanisms underlying CRC and developing diagnostic and therapeutic strategies. Full article

Microgravity (µg)-generated three-dimensional (3D) multicellular aggregates can serve as models of tissue and disease development. They are relevant in the fields of cancer and in vitro metastasis or regenerative medicine (tissue engineering). Driven by the 3R concept—replacement, reduction, and refinement of animal testing—µg-exposure of human cells represents a new alternative method that avoids animal experiments entirely. New Approach Methodologies (NAMs) are used in biomedical research, pharmacology, toxicology, cancer research, radiotherapy, and translational regenerative medicine. Various types of human cells grow as 3D spheroids or organoids when exposed to µg-conditions provided by µg simulating instruments on Earth. Examples for such µg-simulators are the Rotating Wall Vessel, the Random Positioning Machine, and the 2D or 3D clinostat. This review summarizes the most recent literature focusing on µg-engineered tissues. We are discussing all reports examining different tumor cell types from breast, lung, thyroid, prostate, and gastrointestinal cancers. Moreover, we are focusing on µg-generated spheroids and organoids derived from healthy cells like chondrocytes, stem cells, bone cells, endothelial cells, and cardiovascular cells. The obtained data from NAMs and µg-experiments clearly imply that they can support translational medicine on Earth. Full article

In this study, dextran-based hydrogels were synthesized in dimethyl sulfoxide via free-radical polymerization with three structurally different crosslinking agents: divinyl benzene (DVB), diethylene glycol diacrylate (DEGDA), and 4,4′-di(methacryloylamino)azobenzene (DMAAazoB). Their morphology, swelling ability, mechanical properties, and potential for controlled release of the model substance (uracil) were examined, with the results showing that the chemical structure and chain length of the crosslinking agents significantly influence the structural and functional properties of hydrogels. Hydrogels crosslinked with DMAAazoB showed the highest swelling ability at pH 3 and pH 6 (2552 and 1696%, respectively), associated with protonation effects and sponge-like morphology, while simultaneously showing the lowest mechanical strength (20 and 47 MPa). In vitro simulations of gastrointestinal digestion showed that uracil was not released in the gastric phase, while in the intestinal environment, the release was significant, especially in Dex-DMAAzoB hydrogels (88.52%). The absence of azoreductases in the simulated system indicates that the release of the drug in real conditions would likely be even more pronounced. The Dex-DAAazoB hydrogel exhibited a slight antibacterial effect, producing inhibition zones of 8 and 7 mm against Escherichia coli ATCC 8739 and Staphylococcus epidermidis ATCC 12228, respectively. In contrast, the remaining hydrogel formulations showed no detectable antibacterial activity toward either bacterial strain, indicating their microbiological inertness and supporting their suitability as carrier matrices for antitumor drug delivery in colorectal cancer therapy. The obtained results confirm that azo-crosslinked dextran hydrogels, with an optimized amount of crosslinking agent, are promising carriers for the targeted and controlled delivery of antitumor drugs to the colorectal region. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide, underscoring the need for diagnostic tools that early, accurate, and clinically interpretable. Current artificial intelligence (AI) models are predominantly unimodal and lack sufficient interpretability, which restricts their clinical adoption. Methods: We propose IDF-Net, an interpretable dynamic fusion framework that integrates endoscopy, computed tomography (CT), and histopathology using modality-specific encoders, a dual-stage adaptive gating mechanism, and cross-modal attention. We conducted stratified 5-fold cross-validation and assessed interpretability using spatial heatmaps and modality attribution. We also quantified the results using the intersection-over-union metric for saliency alignment. Results: IDF-Net achieved a state-of-the-art accuracy of 0.920 (0.907–0.936) and area under the curve (AUC) of 0.991 (95% CI: 0.965–0.997), significantly outperforming unimodal and static-fusion baselines (p < 0.05). Interpretability analysis of IDF-Net demonstrated a strong alignment between Gradient-weighted Class Activation Mapping++ heatmaps and expert-annotated lesions, as well as case-specific modality contributions via SHapley Additive exPlanations values. Ablation studies confirmed the contribution of each component, with dynamic routing and cross-attention fusion improving AUC by 0.038 and 0.046, respectively. Conclusions: IDF-Net introduces a dynamically fused, multimodal diagnostic framework with integrated quantitative interpretability, demonstrating superior accuracy and strong potential for clinical translation in CRC diagnosis. The model’s adaptive design allows it to function robustly even when CT data is unavailable, aligning with common clinical pathways while leveraging additional imaging when present for comprehensive staging. Full article

The interaction between LC and active TB has been known for many years. The first description of ‘cancerous phthisis’ was reported by Bayle in 1810. The results of subsequent attempts to establish an etiological correlation between the two clinical entities have ranged from insignificant—even antagonistic—to a direct causal relationship. This narrative review explores the relationship between tuberculosis and LC assessing overall and site-specific malignancy risks in individuals with TB compared with the general population. We also examine the timing of cancer development following TB, highlighting periods of elevated risk. Chronic inflammation, immune dysregulation, and metabolic changes associated with TB may contribute to tumor initiation and progression, with organ-specific factors influencing susceptibility to cancers such as lung, head and neck, gastrointestinal, and hematologic malignancies. Clinically, awareness of these interactions supports targeted TB screening in high-risk cancer patients, careful monitoring for TB reactivation during cancer therapy, and consideration of immunological and metabolic factors when planning treatment. Full article

Background/Objectives: Incidence of malnutrition varies greatly among gastrointestinal (GI) cancer patients and has a major impact on prognosis. We performed a meta-analysis to identify risk factors for malnutrition risk, malnutrition diagnosis, and cachexia in patients with GI cancer. Methods: A systematic search was performed on 31 October 2025 on the PubMed (Medline), Embase, and Cochrane Library databases. Eligible studies reported on risk factors for malnutrition risk, malnutrition diagnosis, malnutrition-related complication risk and cachexia in adult patients with GI cancer. Articles on neuroendocrine tumours, primary cancer outside the GI tract, and the paediatric population were excluded. The random-effects model yielded the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the investigated risk factors. Results: A total of 37,624 records were identified. Data from 262,525 patients from 578 articles were included in the analysis. Older age (≥65) was associated with higher odds for malnutrition risk across all GI cancers. In gastric cancer, males had a lower odds for malnutrition risk (OR 0.84; 95% CI 0.75–0.95); however, the sex difference across other cancer types was heterogeneous, and mostly not significant. Tumour location influenced the odds for malnutrition-related complication risk in pancreatic ductal adenocarcinoma (head vs. body/tail—OR 1.48; 95% CI 0.98–2.23) and colorectal cancer (colon vs. rectal—OR 1.39; 95% CI 1.07–1.81; right-sided vs. left-sided—OR 1.54; 95% CI 1.34–1.77). Increased C-reactive protein alone indicated higher odds for malnutrition risk at baseline. Conclusions: Inflammatory biomarkers and tumour characteristics may indicate malnutrition risk in GI cancer at baseline. There is a great need for standardised and harmonised approaches in nutritional status assessment in GI cancer. Full article