Search Results (9,736)

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-associated mortality worldwide. The current therapeutic interventions are heavily constrained by the development of resistance and severe systemic toxicity. To address these challenges, this study integrated a multi-disciplinary framework involving high-throughput in silico screening followed by in vitro experimental validation to identify novel genetic targets of CRC and evaluate the efficacy of FDA-approved drugs. The primary objective was to identify safe and selective therapeutic agents capable of modulating their effect. Methods: The methodology employed a systematic screening of recent large-scale Genome-Wide Association Studies (GWASs) to pinpoint novel targets, followed by in silico pathogenicity prediction, homology modelling and high-throughput virtual screening of over 1615 FDA-approved drugs. The prioritized candidates were validated in vitro using MTT cytotoxicity assays and differential gene expression analysis across CRC cell lines (HCT116 and HT29) and a non-tumorigenic control, Human embryonic kidney cell line HEK293. Results: In silico analysis identified CLUH, CLSTN3 and SLC11A2 as novel potential targets. Based on in silico predicted deleterious mutations and subsequent molecular docking-based virtual screening, Telmisartan, Dutasteride and Venetoclax were prioritized. This prioritization was supported by their high binding affinity and dose-dependent cytotoxicity in MTT assays; thus, suggesting their repurposing potential for CRC treatment. Telmisartan exhibited a superior therapeutic profile not only in terms of the statistically significant cytotoxicity (p < 0.01), but also its selective effect on HCT116 and HT29 when compared to high safety profile in HEK293. This was further validated when Telmisartan selectively downregulated CLUH and SLC11A2 in CRC cell lines, HCT116 and HT29 while maintaining expression levels in the non-cancerous HEK293 cell line remained significantly unaffected. Furthermore, a 100 ns molecular dynamics simulation confirmed the stable binding conformation and structural reliability of the SLC11A2 (Trp179Ser)–Telmisartan complex. Conclucions: Our findings conclude that Telmisartan is a promising candidate for drug repurposing for CRC treatment and capable of modulating selected novel biomarkers CLUH and SLC11A2. However, further multi-omics-based confirmatory studies and pre-clinical validation studies are needed in the future to confirm the long-term efficacy of this repositioning strategy. Full article

The role of adamalysins (ADAMs) has been widely described in many processes related to carcinogenesis, angiogenesis, inflammation, metastasis, and metabolic disorders. Despite numerous studies, their role in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the expression of selected ADAM genes in colorectal cancer tissue and corresponding surgical margins. In addition, for a subgroup of patients, the expression of selected proteins from the ADAM family was assessed. The final study group consisted of 67 patients who underwent elective surgery for colorectal cancer. The relative expression of the ADAM10, 12, 17, and 28 genes was expressed as relative quantification (RQ) and determined by real-time quantitative PCR (RT-qPCR) in tumor tissue and surgical margins. In addition, for a subgroup of 45 patients, the expression of ADAM10, 12, and 17 proteins was assessed by ELISA. Associations between ADAM expression and clinicopathological parameters were analyzed statistically. ADAM12 gene expression was significantly higher in tumor than in margin tissue (median RQ: 0.995 vs. 0.251; p = 0.003), whereas ADAM28 RQ was significantly higher in the margin (median RQ: 0.400 vs. 0.204; p = 0.021). No significant differences were observed in the expression of the ADAM10, ADAM12, ADAM17, or ADAM28 genes based on tumor stage, sex, substance use, BMI, or age, except for nominally higher ADAM12 gene expression in patients over 65 years of age (p = 0.033). Among patients under 65 years of age with cardiovascular disease (CVD), ADAM28 RQ in tumor tissue was significantly higher than in those without CVD (p < 0.05). In obese patients with CVD, a markedly increased expression of ADAM28 in tumor tissue was observed, regardless of age (1.469 vs. 0.132; p < 0.005). Significant positive correlations were observed between the ADAM10 and ADAM17 RQ, and between the ADAM10 and ADAM28 RQ, in both tumor and marginal tissues (all adjusted p < 0.01). No significant correlations were found between gene expression and corresponding protein levels for ADAM10, ADAM12, or ADAM17. ADAM10, 12, 17, and 28 are poor biomarkers for colorectal cancer, but their significance may increase in patients with comorbid metabolic disorders. The lack of correlation between protein expression and gene expression suggests the contribution of post-transcriptional and post-translational regulatory mechanisms, which justifies further research. Full article

Background: The prognostic nutritional index (PNI) is an inexpensive marker derived from serum albumin and peripheral lymphocyte count. Although low PNI has been associated with adverse surgical outcomes, its incremental value beyond basic clinical variables and the stability of commonly used thresholds remain uncertain in heterogeneous colorectal surgical populations. We evaluated the association between preoperative PNI and postoperative complications and examined whether adding PNI improved a basic clinical model. Methods: This retrospective single-center cohort included 205 consecutive adults undergoing colorectal surgery between January 2024 and March 2026. PNI was calculated as albumin (g/L) + 5 × lymphocyte count (10⁹/L). PNI was modeled primarily as a continuous predictor; PNI < 45 was examined secondarily. ROC analysis, multivariable logistic regression, nested-model comparison, calibration assessment, bootstrap internal validation, complete-case sensitivity analysis, and exploratory subgroup analyses were performed. Results: Fifty-six patients (27.3%) had PNI < 45. Postoperative complications occurred in 67 patients (32.7%) overall and were more frequent with PNI < 45 (51.8% vs. 25.5%; RR 2.03, 95% CI 1.40–2.95; OR 3.14, 95% CI 1.65–5.95; Fisher p < 0.001). PNI alone showed modest discrimination (AUC 0.659); the Youden cutoff was 45.45 (sensitivity 50.7%, specificity 78.3%). In the complete-case multivariable model (n = 191), each 5-point decrease in PNI was associated with higher odds of complications (OR 1.52, 95% CI 1.22–1.90; p < 0.001). Adding continuous PNI to age, BMI, and operative approach increased AUC from 0.663 to 0.711 and improved model fit (likelihood-ratio χ² = 15.89, p < 0.001). Bootstrap resampling showed substantial cutoff variability (95% percentile interval 32.05–52.00). Conclusions: Lower preoperative PNI was associated with postoperative complications and added discriminatory information to a basic clinical model. However, its stand-alone discrimination was modest, the data-derived cutoff was unstable on bootstrap resampling, and residual confounding and clinical heterogeneity limit causal or treatment-directed interpretation. PNI should therefore be considered a risk marker rather than a stand-alone decision rule. Prospective interventional studies in well-defined patient groups are needed to determine whether PNI-guided nutritional optimization improves outcomes. Full article

Background/Objectives: Liver metastasis develops in approximately 50% of patients with colorectal cancer. Invasion of the biliary tract from colorectal liver metastasis (CRLM) is rarely reported. Preoperative diagnosis remains elusive, prohibiting optimal surgical management. The objective of this systematic review was to summarize the clinical, radiological, pathological, and treatment characteristics of ibCRLM and describe the reported outcomes. Methods: A systematic literature search of the Medline, Embase, Web of Science, CENTRAL, and CINAHL databases was undertaken for studies reporting clinical outcomes of patients with ibCRLM, up to May 2026. An individual patient data analysis approach was utilized. Results: Thirty-eight case reports and 10 case-series, incorporating 228 patients with biliary involvement from CRLM, were identified. Mean age was 62.4 ± 10.9 years, with a male-to-female ratio of 3.2:1. The majority of metastatic lesions were metachronous in 71.1% and solitary in 59.1% of patients. Surgical treatment was implemented in 89.2% of patients. Major hepatectomy was the most common procedure, being performed in 46.2% of patients, followed by minor hepatectomy in 38.7% and pancreatoduodenectomy in 4.3%. After a median follow-up of 52.5 months (range 2–164 months), the survival rate was 60.5%. Non-survivors were found to have significantly more synchronous CRLM (50% versus 0, p = 0.008), while a single patient did not receive any curative-intent treatment and died 20 days following CRLM presentation. Conclusions: IbCRLM is a distinct clinicopathological presentation of CRLM with characteristic radiological and pathological features. The available evidence suggests that selected patients may achieve favorable long-term outcomes following complete surgical resection, although these findings should be interpreted with caution given the limitations of the available literature. Full article

Background: In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 (TIMP1) gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. Methods: To probe how TIMP1 acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan–Meier survival assessment. We also investigated the connection between the expression abundance of TIMP1 and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how TIMP1 gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high-TIMP1 and low-TIMP1 cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with TIMP1. We constructed the protein–protein interaction map for TIMP1-interacting partners via the STRING repository. To further explore TIMP1-correlated genes, we performed Venn diagram intersection analysis combined with Spearman’s correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect TIMP1 messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. Results: According to outcome data, TIMP1 transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated TIMP1 expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29–0.64, p < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22–0.68, p = 0.001) among colorectal-carcinoma patients. TIMP1-high and TIMP1-low groups exhibited notable differences in immune cell infiltration (CD8⁺ T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4⁺ T cells). TIMP1 expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., CD274 [PD-L1] and CTLA4), and immunomodulatory chemokines (e.g., CCL3 and CCL5). Twelve TIMP1-interacting DEGs were selected: COL5A1, FN1, PRG4, and a cluster of nine MMPs (MMP1/2/3/7/8/9/11/13/14), all of which showed significant positive correlations with TIMP1 (r = 0.31–0.63, all p < 0.001). Conclusions: TIMP1 expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that TIMP1 shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation. Full article

Cancer metastasis, characterized by the dissemination of malignant cells from the primary tumor to distant organs, remains the leading cause of cancer-related mortality in solid tumors. In colorectal cancer (CRC), increasing attention has been directed toward therapeutic strategies aimed at suppressing cancer cell migration and invasion rather than solely reducing tumor mass, giving rise to the concept of migrastatic therapies. In the present study, green-synthesized silver nanoparticles (AgNPs), previously obtained using aqueous extracts of Filipendula ulmaria (L.) Maxim. and Salvia verticillata L., were evaluated for their antimigratory and anti-inflammatory potential in human colorectal carcinoma HCT-116 cells. Treatment with AgNPs induced considerable perturbations in cellular redox homeostasis, as evidenced by increased intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), glutathione (GSH), and nitric oxide (NO) levels. These redox alterations were accompanied by a significant inhibition of cancer cell migration, together with reduced expression of matrix metalloproteinases MMP-2 and MMP-9, key mediators of extracellular matrix remodeling associated with tumor progression. AgNP exposure was associated with activation of the cytoprotective transcription factor Nrf-2 and suppression of the pro-inflammatory NF-κB/COX-2 signaling axis, indicating coordinated modulation of redox-sensitive pathways linked to tumor cell motility and inflammatory responses. Collectively, these findings demonstrate that green-synthesized AgNPs derived from F. ulmaria and S. verticillata exert multi-level regulatory effects on redox balance, inflammatory signaling, and migration-associated molecular markers in colorectal cancer cells. This study supports their potential as promising migrastatic nanocarriers for further investigation in colorectal cancer research. Full article

Background/Objectives: Metastatic colorectal cancer (mCRC) remains difficult to treat, largely due to chemotherapy resistance. Mutations in TP53 impair apoptosis and are associated with poor response to irinotecan. This study aimed to determine whether targeting Survivin, a key inhibitor of apoptosis, and using the disulfiram-derived compound CuET could restore apoptotic signaling and improve irinotecan efficacy. Methods: Human CRC cell lines with varying TP53 status and murine tumor models were treated with irinotecan (or its active metabolite SN-38), the Survivin inhibitor YM-155, and CuET, alone or in combination. Cell viability, clonogenic survival, and apoptotic signaling were assessed using cytotoxicity assays, flow cytometry, confocal microscopy, and Western blotting. In vivo efficacy was evaluated in xenograft and syngeneic mouse models through tumor growth measurements and histological analyses. Results: Inhibition of Survivin with YM-155 enhanced irinotecan-induced cytotoxicity and promoted caspase-dependent apoptosis in CRC cells. Irinotecan treatment induced Survivin expression, suggesting an adaptive resistance mechanism that was reversed by YM-155. CuET demonstrated potent cytotoxic activity independent of TP53 status and partially suppressed Survivin expression. Importantly, CuET restored sensitivity to irinotecan in TP53-deficient models and significantly enhanced antitumor efficacy in vivo, leading to reduced tumor growth, decreased proliferation, and increased apoptosis. Conclusions: These findings identify Survivin-mediated apoptotic resistance as a key determinant of irinotecan response in CRC. Targeting this pathway, either directly through Survivin inhibition or through CuET-induced stress responses, restores apoptotic sensitivity and enhances chemotherapy efficacy. This study supports the development of combination strategies incorporating CuET to overcome resistance in TP53-mutant CRC. Full article

The present study investigated the anticancer effects of irinotecan (IR) combined with the acid ceramidase inhibitor Ceranib-2 in HT-29 human colorectal cancer cells. Cell viability was assessed using the MTT assay, apoptosis was evaluated by Annexin V flow cytometry, and morphological alterations were examined by fluorescence microscopy. Both irinotecan and Ceranib-2 significantly reduced cell viability in a dose-dependent manner. Notably, the combination treatment produced greater growth inhibition than either agent alone (p < 0.01). Morphological analysis revealed pronounced apoptotic features, including nuclear condensation, membrane blebbing, and cytoskeletal disruption, particularly in the combination-treated cells. Annexin V analysis further demonstrated that combined treatment markedly increased apoptotic cell populations compared with single-agent treatments (p < 0.01). These findings suggest that Ceranib-2 enhances the anticancer activity of irinotecan and that this combination may represent a promising therapeutic strategy for colorectal cancer. Full article

Background: Risk stratification after colorectal cancer surgery remains challenging. We evaluated whether a perioperative ratio combining immediate postoperative lactate with preoperative albumin is associated with in-hospital mortality after elective colorectal resection. Methods: In this single-center retrospective cohort, 282 patients underwent open elective colorectal resection. The perioperative lactate-to-albumin ratio (LAR) was calculated as arterial lactate (mmol/L) divided by serum albumin (g/dL), and discrimination was assessed by receiver operating characteristic (ROC) analysis with age-adjusted association by Firth’s penalized logistic regression and fixed-model bootstrap validation. Results: Seventeen patients (6.0%) died in hospital, and mortality rose across LAR tertiles (2.1%, 5.3%, and 10.6%; p = 0.014). LAR showed moderate discrimination (AUC 0.73; 95% CI 0.58–0.87; optimism-corrected AUC 0.78), with no evidence of better discrimination than lactate or albumin alone. At the Youden threshold of 0.555, sensitivity was 76.5% and specificity 61.1%. The age-adjusted Firth odds ratio was 1.19 per 0.1-unit increase (95% CI 1.09–1.29). Conclusions: The perioperative lactate-to-albumin ratio was associated with in-hospital mortality after age adjustment in this single-center cohort. Given the small number of deaths and absence of external validation, LAR should be regarded as a candidate marker requiring prospective multicenter validation before clinical application. Full article

Background: Family caregivers play a central role in supporting people with colorectal cancer (CRC) and often manage complex physical, emotional, and practical demands. However, evidence regarding their experiences and supportive care needs in Kazakhstan remains limited. This qualitative study explored caregiving experiences, caregiving burden, caregivers’ needs, and coping strategies. Methods: A qualitative descriptive design was used, involving semi-structured interviews with 21 family caregivers caring for patients with CRC. Participants were recruited purposively from the Medical Center of West Kazakhstan Marat Ospanov Medical University and outpatient clinics in Aktobe between December 2025 and March 2026. Interviews were audio-recorded, transcribed verbatim, and analyzed using inductive reflexive thematic analysis. Results: Most family caregivers of patients with colorectal cancer were women (95.2%). Five main themes developed: emotional challenges, transformation of daily life, caregiving tasks, caregivers’ needs and support gaps, and coping strategies and resilience. Diagnosis was described as a distressing experience characterized by shock, fear, and uncertainty. Caregiving substantially disrupted employment, financial stability, and family roles, often requiring work adjustment or leaving the workforce. Caregivers reported insufficient preparation for stoma care and expressed a strong need for structured training. Social isolation was common, as both caregivers and patients experienced a shrinking of their social support networks. Despite substantial burden, caregivers described adaptive responses to ongoing emotional and practical demands, and resilience was a prominent theme. Conclusions: Family caregivers of patients with colorectal cancer in Kazakhstan face interconnected emotional, informational, physical, and system-level challenges, while also drawing on resilience. The findings highlight priorities for support, including structured stoma care education, psychological services, recognition of caregivers’ roles, and improved discharge and transitional care. Full article

Gastrointestinal (GI) cancers represent a diverse group of malignancies that remain a major cause of cancer-related morbidity and mortality worldwide. Their management is increasingly complex, reflecting differences in tumor biology, anatomical location, stage, and molecular profile. In recent years, advances in molecular diagnostics, immunotherapy, and targeted treatment have moved clinical decision-making beyond a purely organ- and stage-based approach toward more individualized, biomarker-guided care. This narrative review summarizes established and emerging biological and targeted therapies used in esophageal, gastric and gastroesophageal junction, colorectal, pancreatic, hepatocellular, and biliary tract cancers. It focuses on immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4; HER2-directed monoclonal antibodies and antibody–drug conjugates; antiangiogenic and anti-EGFR therapies; and newer strategies involving CLDN18.2, FGFR2b, and tumor-agnostic alterations such as NTRK fusions. The review also considers the predictive biomarkers used to guide treatment selection and the growing integration of systemic therapy with surgery in neoadjuvant, perioperative, adjuvant, and conversion settings. However, clinical efficacy alone does not determine whether new treatments become part of routine practice. Regulatory approval, reimbursement, access to molecular testing, and the availability of specialized multidisciplinary care are equally important. The rapidly evolving treatment landscape for GI cancers therefore requires clinical decisions that account for tumor biology, anatomical resectability, molecular eligibility, expected benefit, treatment-related toxicity, and local access to therapy. Expanding access to comprehensive biomarker testing and effective molecularly guided treatments will be essential to translate progress in precision oncology into more personalized and equitable care for patients with GI cancers. Full article

Cancer remains one of the leading causes of global mortality, with its incidence continuing to rise due to population growth, aging, lifestyle factors, and environmental exposures. Despite significant advances in early diagnosis and therapeutic strategies, the clinical management of cancer is still hindered by drug resistance, limited selectivity, and treatment-related toxicity. Consequently, increasing attention has been directed toward natural products as sources of novel anticancer agents with improved efficacy and reduced adverse effects. Pogostemon cablin (patchouli), a medicinal plant widely used in traditional medicine, has emerged as a promising candidate owing to its diverse bioactive constituents and broad pharmacological properties. This review systematically summarizes and critically evaluates current evidence on the anticancer potential of patchouli leaves, with particular emphasis on molecular mechanisms and translational relevance. Based on available experimental and preclinical studies, patchouli and its major phytochemicals exhibit notable anticancer activity against a wide range of malignancies, including endometrial, ovarian, liver, skin, nasopharyngeal, prostate, hematological, colorectal, and lung cancers. Mechanistically, these effects are primarily associated with the modulation of apoptosis, cell cycle regulation, oxidative stress, and key oncogenic signaling pathways, as well as potential synergistic interactions with conventional chemotherapeutic agents. Overall, this review highlights the therapeutic promise of patchouli leaves as a source of anticancer agents, identifies current knowledge gaps, and outlines future research directions to facilitate their development and clinical translation. Full article

Metastatic colorectal cancer remains associated with poor prognosis despite major therapeutic advances, highlighting the need for robust biomarkers to refine treatment selection and monitor disease dynamics. This review summarizes emerging predictive and prognostic biomarkers in metastatic colorectal cancer across molecular and cellular layers, encompassing both tissue and circulating biomarkers. At the tissue level, we discuss genomic alterations and mutational signatures, transcriptomic classification systems and immune-related gene expression tools, protein-level immune checkpoint markers, and cellular determinants including immune infiltrates, cancer-associated fibroblasts and microbiome features. At the circulating level, we review biomarkers derived from liquid biopsy and peripheral blood, including circulating tumor DNA kinetics, T-cell receptor repertoire diversity, soluble cytokines and proteins, immune cell phenotyping, and circulating tumor cells. We highlight major challenges limiting clinical translation, including tumor heterogeneity, methodological variability, and the absence of standardized analytical pipelines and thresholds. Finally, we discuss future perspectives, emphasizing the integration of multi-omics biomarkers and artificial intelligence-driven strategies to improve biomarker validation and enable more precise management of metastatic colorectal cancer, particularly for patients with microsatellite-stable tumors who derive limited benefit from immune checkpoint inhibition. Full article

High-amylose starch (HAS) is composed predominantly of linear α-1,4-linked glucose units and is high in resistant starch content. Its unique physicochemical properties and gut fermentation dynamics confer multiple health benefits. This review summarizes HAS digestion, its interactions with gut microbes, and its systemic effects. HAS intake can reshape the gut microbiota by enriching beneficial taxa such as Bifidobacterium, Faecalibacterium, and Akkermansia, while suppressing harmful bacteria like Escherichia coli and Clostridium difficile. These microbial shifts enhance short-chain fatty acid production, improve gut barrier integrity, and reduce inflammation. HAS also demonstrates therapeutic potential in obesity, type 2 diabetes, chronic kidney disease, and colorectal cancer by improving insulin sensitivity, reducing glycemic variability, and modulating oncogenic pathways. Collectively, dietary incorporation of HAS represents a promising functional strategy to support gut and systemic health across diverse physiological contexts. Full article

Background: Emergency surgery for complicated colorectal cancer (CRC) presenting with obstruction, perforation, or uncontrolled bleeding has high postoperative mortality, especially in older patients. However, age-related risk and the roles of radical versus palliative treatment are not fully understood. This study aimed to measure 90-day and 36-month mortality after emergency CRC surgery and to analyze whether the relationship between age and mortality is nonlinear and influenced by operative intent. Methods: Retrospective cohort of consecutive adults undergoing emergency surgery for complicated CRC (2015–2024). The outcome was 90-day and 36-month all-cause mortality. Cox regression provided adjusted hazard ratios (HR) using two models: a primary whole-cohort model omitting pathological T/N stage, and a secondary resection-only model including pathological stage. Age was modeled with restricted cubic splines and predicted 90-day and 36-month mortality were plotted by operative intent. Results: In 496 patients, 90-day mortality was 19.7% (98/496), while 36-month mortality was 37.3% (185/496). In the primary whole-cohort Cox model, independent predictors of 36-month mortality included age ≥75 years (HR 2.09, 95% CI 1.48–2.95, p < 0.001), Charlson Comorbidity Index (HR 1.02, 95% CI 0.98–1.06, p = 0.31), obstruction (HR 1.69, 95% CI 1.18–2.42, p = 0.004), perforation (HR 2.05, 95% CI 1.24–3.39, p = 0.005), and metastatic disease (HR 2.30, 95% CI 1.62–3.27, p < 0.001); radical operative intent was independently associated with lower 36-month mortality (HR 0.461, 95% CI 0.30–0.71, p = 0.001). In a secondary resection-only model additionally adjusting for pathological T/N stage (n = 426 with available pathology), the association for radical intent was attenuated and no longer statistically significant (HR 0.67, 95% CI 0.43–1.03, p = 0.067). The 36-month mortality spline estimate indicated an increasing risk with advancing age; a likelihood-ratio test did not show that the spline model fit significantly better than a linear age term (χ² = 1.43, df = 1, p = 0.233), so this pattern is interpreted descriptively rather than as formal evidence of nonlinearity, and no formal interaction between age and operative intent was demonstrated. Conclusions: Ninety-day mortality after emergency colon cancer surgery remains significant. Age-related risk shows a predominantly monotonic, descriptive pattern and should not be assumed to vary by operative intent without formal interaction testing, emphasizing individualized risk assessment and shared decision-making. Full article