Search Results (9,720)

Background/Objectives: Chemerin is an adipokine implicated in metabolic regulation, inflammation and cancer biology, but its value as a circulating biomarker in colorectal neoplasia remains uncertain. We investigated serum chemerin concentrations in patients with colorectal cancer (CRC), patients with colorectal polyps and colonoscopy-negative controls, and explored chemerin immunoreactivity in available polyp and tumour tissue. Methods: This exploratory observational case–control study included 41 patients with CRC, 20 patients with colorectal polyps and 29 colonoscopy-negative controls. Serum chemerin was measured by ELISA. Tissue specimens underwent routine histopathology and qualitative immunohistochemical staining for chemerin. Between-group comparisons were performed using non-parametric tests; subgroup analyses were exploratory and unadjusted. Results: Serum chemerin concentrations did not differ significantly between CRC and controls (median 144.0 vs. 135.7 ng/mL; p = 0.41), CRC and polyp groups (144.0 vs. 97.4 ng/mL; p = 0.24), or polyp and control groups (97.4 vs. 135.7 ng/mL; p = 0.94). Chemerin immunostaining was absent in CRC tissue (0/41) and conventional adenomatous polyps (0/15), whereas all available hyperplastic/serrated lesions showed epithelial cytoplasmic and/or stromal immunoreactivity (5/5); in lesions containing dysplasia, dysplastic glands showed no detectable staining. In controls, higher chemerin concentrations were associated with hyperglycaemia, hypertension, body weight and bilirubin, but these exploratory findings were not adjusted for multiplicity or metabolic confounding. Conclusions: In this exploratory cohort, serum chemerin did not discriminate CRC or colorectal adenoma from colonoscopy-negative controls. Together with the absence of staining in CRC and conventional adenomas, the findings argue against chemerin as a standalone circulating or commonly expressed tissue biomarker for these lesions under the assay conditions used. Immunoreactivity in the non-dysplastic epithelial and/or stromal compartments of hyperplastic/serrated lesions remains preliminary and requires prospective confirmation with standardised pre-analytics, quantitative pathology scoring and adjustment for metabolic confounders. Full article

The immune checkpoint blockade (ICB) has changed the way many solid tumors are treated; yet, only a minority of patients respond durably. The biomarkers that guide therapy (the PD-L1 expression, tumor mutational burden, and microsatellite status) read only fixed molecular features and miss the shifting tumor–immune exchange. Patient-derived tumor organoids reproduce the tumor epithelium and predict the chemotherapy responses, but, in their usual form, they omit the immune compartment on which the ICB acts. This review asks how immune-competent organoids can close that gap, and how well they predict the response. One idea organizes the field: how a model is built determines what it can predict. Two complementary construction routes have been developed. One preserves endogenous immunity through an air–liquid interface culture; the other rebuilds it by a co-culture with defined effector populations. Both now incorporate microenvironmental reconstruction and quantitative functional readouts. The most developed examples are in colorectal cancer, with breast cancer applications only beginning to appear. Evidence for the ICB response prediction, graded on a four-level scale, remains at the proof-of-concept stage. Organoid functional assays complement rather than replace molecular biomarkers. Their clinical translation requires progress on four fronts: standardized protocols, longer immune cell viability, spatial and multi-omic integration, and prospective paired validation. Full article

The incidence of neoplastic disorders worldwide has steadily increased, and Romania is no exception, showing a substantial rise in active oncologic surveillance cases. Family physicians are essential to the multidisciplinary team, providing screening, early diagnosis, care during and after cancer treatment, comorbidity management, and palliative care. Primary prevention through lifestyle behavioral changes and early detection in the asymptomatic phase remain the most effective strategies to reduce cancer morbidity and mortality. However, structural barriers within the Romanian primary healthcare system, specifically fragmented digital infrastructure, administrative workloads and limited patient health literacy, frequently restrict these preventive activities. The aim of this narrative review is to analyze cancer prevention and management within Romania’s current demographic and socio-economic context, comparing the national system to models from the UK, the Netherlands, and Spain. The analysis highlights operational gaps, including low breast, cervical, and colorectal screening uptake in Romania. We concluded that optimizing patient care requires transitioning to an integrated pathway, supported by practical reforms like digital fast-track scheduling modules managed directly by family physicians. Full article

Background: Anastomotic leakage remains the most feared complication after colorectal cancer surgery, and reliable preoperative risk stratification is still evolving. The skeletal muscle index (SMI), derived from routine computed tomography, offers an objective, widely available measure of muscle mass. This study evaluated whether a low preoperative SMI predicts anastomotic leakage after colorectal cancer resection. Methods: We retrospectively screened 550 consecutive patients who underwent colorectal cancer resection with primary anastomosis at a single tertiary referral centre between 2018 and 2024, of whom 468 satisfied the eligibility criteria and formed the analytic cohort. Skeletal muscle area was measured on preoperative axial computed tomography at the third lumbar vertebra and normalised to the height squared to obtain the SMI. Anastomotic leakage was defined according to the International Study Group of Rectal Cancer criteria. Receiver operating characteristic analysis identified a single pragmatic SMI cut-off. Group comparisons used Mann–Whitney U and chi-square tests, and independent predictors were assessed by multivariable logistic regression. Results: Anastomotic leakage occurred in 33 of 468 patients (7.1%). Patients who developed leakage had a significantly lower mean SMI than those who did not (40.0 cm²/m² vs. 46.8 cm²/m², p = 0.005). An SMI below 48.6 cm2/m2 predicted leakage with 90.9% sensitivity, 38.2% specificity, and a 98.2% negative predictive value (area under the curve 0.646). Because specificity (38.2%) and positive predictive value (10.0%) were low, the index performed as a rule-out marker: a preserved SMI identified a low-risk subgroup, whereas a low-SMI had limited positive predictive value. The leakage rate reached 10.0% in the low SMI group versus 1.8% in the high-SMI group (p = 0.0008). Following multivariable analysis, low SMI was the only independent predictor of anastomotic leakage (adjusted odds ratio: 5.67, 95% confidence interval: 1.69 to 19.01, p = 0.005). Conclusions: A low preoperative SMI independently increased the odds of anastomotic leakage almost six-fold after colorectal cancer surgery, while its high negative predictive value identified a large group of patients at very low risk. Routine SMI assessment on existing staging computed tomography may strengthen preoperative risk stratification at no additional cost or radiation. Full article

Perioperative treatment for colorectal cancer (CRC) is undergoing a paradigm shift from uniform cytotoxic regimens toward strategies guided by tumor location, microsatellite instability (MSI)/mismatch repair (MMR) status, and recurrence risk. Four clinically relevant subgroups now shape decision-making: microsatellite stable (MSS)/proficient MMR (pMMR) colon cancer, microsatellite instability-high (MSI-H)/deficient MMR (dMMR) colon cancer, MSS/pMMR rectal cancer, and MSI-H/dMMR rectal cancer. In MSS/pMMR colon cancer, adjuvant therapy is being refined through risk-adapted treatment duration and selective use of neoadjuvant chemotherapy. In MSS/pMMR rectal cancer, total neoadjuvant therapy, selective omission of pelvic radiotherapy, and watch-and-wait strategies are redefining treatment sequencing and organ preservation. In MSI-H/dMMR colon cancer, immune checkpoint inhibitor (ICI) therapy has shown marked activity in both adjuvant and neoadjuvant settings. In MSI-H/dMMR rectal cancer, neoadjuvant ICI therapy is being explored as a non-operative organ preservation strategy. In parallel, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assessment is emerging as a tool for postoperative escalation, de-escalation, and surveillance. Across these settings, the maturity of the evidence varies widely, ranging from established phase III standards to guideline-endorsed but still single-arm approaches and investigational strategies that require prospective validation before routine adoption. This review summarizes the current evidence and remaining challenges in biology-, site-, and risk-adapted perioperative management of CRC. Full article

Fusobacterium nucleatum has been implicated in colorectal cancer, but its role in adenomas remains unclear. We applied an RNA-based detection of F. nucleatum in formalin-fixed paraffin-embedded adenoma tissue and explored the mutational landscape and transcriptomic profile of F. nucleatum+ patients in comparison to F. nucleatum- patients. Bespoke F. nucleatum probes successfully detected F. nucleatum in 11% of adenomas. F. nucleatum+ patients exhibited a positively enriched anti-bacterial defence response and immune-related transcriptomic signatures, as well as a proliferative profile. These findings suggest that F. nucleatum positivity is associated with immune and proliferative transcriptomic signatures in colorectal adenomas, but this requires validation in larger, longitudinal cohorts. Full article

Fenjiu distillers’ grains are a major by-product of Fenjiu production and contain various bioactive components derived from cereal raw materials and microbial fermentation. Colorectal cancer (CRC) remains a global health challenge, and the development of safe and effective therapeutic agents is urgently needed. In this study, we successfully obtained DGAE-1 (distillers’ grains ethanol extract fraction 1), an ethanol-extracted bioactive fraction derived from Fenjiu distillers’ grains, with anti-colorectal cancer activity. LC-MS analysis tentatively annotated the chemical constituents of DGAE-1 fraction based on MS/MS fragmentation patterns and database similarity matching, with the major annotated compounds belonging to carboxylic acids and derivatives, organic nitrogen compounds, organic phosphoric acid derivatives, and other chemical classes. These annotated compounds may contribute to the biological activity of DGAE-1 fraction, although the specific active constituents remain to be further clarified. DGAE-1 fraction inhibited colorectal cancer cell proliferation and induced autophagy. Further studies indicated that the PI3K/AKT pathway is involved in DGAE-1 fraction-induced autophagy. The results of this study demonstrate that DGAE-1 fraction exerts anti-colorectal cancer activity in both cellular and animal models. These findings provide new insights into the development and utilization of Fenjiu distillers’ grains and highlight their potential as a source of bioactive compounds for health-related applications. Full article

Background: Greater familiarity between surgeons and anaesthetists is associated with better teamwork and patient safety. We investigated whether the volume of major UGI cancer resections the same surgeon and anaesthetist perform together influences post-operative outcomes at our tertiary specialist cancer centre. Methods: A 10-year retrospective cohort study was conducted via propensity score matching analysis (PSM). Consecutive adults undergoing elective surgical resection for primary UGI carcinoma and colorectal liver metastases from January 2014 to December 2024 were included. Cases were performed by surgeon–anaesthetist dyads composed of five Consultant Surgeons and 34 Consultant Anaesthetists. The primary Consultant Surgeon and Consultant Anaesthetist, the Charlson co-morbidity (CCM) score, and Clavien–Dindo (CD) complications were recorded. Cases were matched for age and CCM score. Results: A total of n = 792 cases were included, which became n = 546 after PSM. The median number of cases performed per dyad was 23, and the median CCM score = 5. Dyads were stratified into high (≥23 cases/dyad) and low volume (<23 cases/dyad), and cases into high (CCM ≥ 5) and low risk (CCM < 5). High-volume dyads had a lower incidence of post-operative complications when adjusted for PSM (35.2%) compared to low-volume dyads (42.8%) (p = 0.829). Probability of CD grade III complications among low-volume dyads increased with a rise in CCM (p = 0.224), but not in high-volume dyads. Conclusions: Greater familiarity between surgeons and anaesthetists may develop by operating on more cases together. This study has highlighted a trend suggesting that high-volume dyads could safely perform UGI resections on higher-risk cases without significant increases in post-operative complications. Dyad volume should be considered in operative scheduling for UGI cancer surgery. Full article

Since the discovery of truncated mutations of adenomatous polyposis coli proteins in familial adenoma patients in 1991, the mechanism of cytosolic β-catenin regulation has been intensively studied, and now it is very well known that the central role of the canonical Wnt/β-catenin is in colorectal cancer. However, Wnt signaling is very complicated because of the presence of almost 20 Wnt ligand genes, six Frizzled seven-transmembrane receptors, and three LRP co-receptors. In addition, research in the past two decades illuminated the existence of the other Wnt signaling—non-canonical Wnt signaling (Wnt/PCP and Wnt/Ca²⁺ pathways), and an increasing number of studies have shown the potential role of non-canonical Wnt signaling in cancer recently. One of the well-studied Wnt ligands in non-canonical Wnt signaling is Wnt-5a. However, the role of Wnt-5a and non-canonical pathways in cancer is mosaic—i.e., it may involve tumor-promoting or suppressing pathways. In certain cancers, non-canonical Wnt signaling may mainly act as a tumor promoter, yet the results are very controversial in colorectal cancer. Elucidating the role of non-canonical Wnt signaling in colorectal cancer may be very important to further reduce the risk of colorectal cancer, especially in patients who do not carry truncated mutations of adenomatous polyposis coli. In this review, I would like to mainly discuss the apparent controversy surrounding non-canonical Wnt signaling in colorectal cancer, and I would like to point out a few potential reasons contributing to the mysterious roles of Wnt5a-initiated non-canonical signaling in colorectal cancer. Full article

Background/Objectives: Colorectal cancer (CRC) remains a major contributor to the global oncological burden, with marked disparities in mortality and survival between Western and Eastern European countries. Romania continues to report unfavorable CRC outcomes, driven by delayed diagnosis, limited screening uptake, and heterogeneous care pathways. This study aimed to assess the 15-year institutional description of colorectal cancer case-mix in South-West Oltenia, Romania, using real-world data from a high-volume oncology referral center. Methods: We conducted a retrospective observational study including 3497 patients with newly diagnosed CRC registered between 2011 and 2025. Sociodemographic characteristics, tumor localization, stage at diagnosis, and histopathological grade were analyzed. Temporal patterns were assessed across three five-year intervals. Results: The institutional CRC case volume increased, with 434 cases recorded in 2011–2015, 1015 in 2016–2020, and 2048 in 2021–2025. Male patients accounted for 60.5% and urban residents for 60.3% of cases. Early-onset CRC was identified in 12.0% of patients, with no significant temporal trend. Rectosigmoid junction/rectal cancers represented the largest anatomical group, followed by left-sided cancers, with stable distribution across periods. Advanced stage disease was frequent, with 77.1% of patients diagnosed in stage III–IV, increasing from 67.7% to 82.0% across study intervals (p < 0.001). Histopathological grade changed significantly (p < 0.001), due to a progressive increase in unspecified grade, from 16.1% to 45.5%. Conclusions: Colorectal cancer represents a substantial institutional workload at this regional referral center, emphasizing the need for strengthened early detection strategies, optimized referral system, improved diagnostic access, and standardized pathological reporting practices. Full article

In colorectal cancer (CRC), tumor progression is influenced by immunosuppressive tumor microenvironment (TME), in which innate immunity and adaptive immunity play an important role. CD47 is one of the key molecules in the process. It sends a “don’t eat me” signal to macrophages by binding to signal regulatory protein alpha (SIRPα), thus helping tumor cells escape immune clearance. Forkhead box P3 (FOXP3)⁺ regulatory immune cells further suppress antitumor T-cell responses. Here, based on a review of the literature and publicly available transcriptomic data, we propose that CD47 expression and FOXP3⁺ regulatory T cells in CRC are interconnected components of a broader myeloid–regulatory immunosuppressive phenotype, rather than a simple linear CD47–FOXP3 pathway. Evidence from cancer studies and exploratory GEPIA3/TIMER3.0 analyses supports a weak and method-dependent association between CD47 expression, FOXP3 transcripts, and estimated Treg infiltration. Hippo/Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) signaling serves as a potential upstream program contributing to this immune context. Full article

Histopathology foundation models (FMs) have become widely used as patch-level feature extractors in computational pathology (CPath), where domain shift is a central challenge, yet their generalization ability across acquisition centers and scanning platforms remains insufficiently studied. In this work, we evaluate the domain generalization of ten state-of-the-art FMs on two multi-source datasets with different supervision settings: SemiCOL, a colorectal cancer cohort of 499 whole-slide images (WSIs) for weakly labeled slide-level binary tumor classification, and BEETLE, a breast cancer cohort of 583 WSIs for patch-level four-class tissue classification. In an ablation-style setting, FMs are used as patch-level feature extractors, with patch embeddings mean-pooled into slide-level representations for SemiCOL, and a lightweight multi-layer perceptron trained for slide-level and patch-level classification on SemiCOL and BEETLE, respectively. To test FM domain generalization, we use three evaluation protocols: a Baseline source-mixed 5-fold cross-validation (CV) and two leave-source-out CV settings that assess cross-center and cross-scanner performance. On SemiCOL, all FMs achieve near-saturated performance, indicating stable performance under acquisition-source domain shift for slide-level Tumor vs. Benign classification. In contrast, BEETLE reveals clear generalization gaps, with scanner-induced domain shift more challenging than center-induced domain shift, and class-wise results showing that performance losses concentrate in epithelial discrimination. Overall, Virchow2 shows the strongest robustness across all evaluated protocols. These findings show that standard source-mixed CV can overestimate domain generalization across centers and scanners, and that FM choice matters in multi-source cohorts, especially for more challenging CPath tasks, where cross-domain failures are more visible. Full article

Objectives: This study evaluated the association between maintenance therapy and survival outcomes following first-line bevacizumab-based combination chemotherapy in metastatic colorectal cancer (mCRC) using real-world data. Methods: This retrospective study included 94 mCRC patients achieving disease control, defined as complete response (CR), partial response (PR), or stable disease (SD), after first-line bevacizumab-based chemotherapy (2015–2025). Patients were divided into maintenance (fluoropyrimidine ± bevacizumab, n = 44) and active surveillance (n = 50) groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using a landmark approach, Kaplan–Meier methods, and Cox regression models. Results: The overall patient cohort (n = 94) had a median age of 62 years and a male predominance of 61.7%. Median OS was significantly longer with maintenance therapy than surveillance (24.8 vs. 18.0 months; p = 0.045); PFS differences were not statistically significant (11.3 vs. 6.7 months; p = 0.077). In multivariable analysis, maintenance was not independently associated with OS or PFS. Male sex, comorbidities, multiple metastases, and non-resected primary tumors independently predicted worse OS. No statistically significant treatment-by-subgroup interactions were identified in the exploratory analyses. Conclusions: These real-world data suggest a potential survival advantage associated with maintenance therapy following first-line bevacizumab-based combination chemotherapy in patients with mCRC who achieve disease control. However, this association was not maintained after multivariable adjustment, suggesting that baseline differences may have contributed to the observed findings. Trial Registration: This retrospective observational study was not prospectively registered. Full article

Colorectal cancer progression and therapeutic response are determined not only by tumor-intrinsic programs but also by neural, stromal, and immune components of the tumor microenvironment. However, biologically interpretable transcriptomic scores that jointly capture neural/stromal remodeling and immune activation remain limited. We developed a neuro-immune score (NIS), defined as the neural/stromal module score minus the immune activation module score. NIS was constructed using the combined TCGA-COAD/READ colorectal cancer cohort and externally evaluated in independent Gene Expression Omnibus (GEO) datasets. Single-cell RNA sequencing, focused ligand–receptor analysis, and spatial transcriptomics were further integrated to characterize the cellular origins, spatial organization, and potential mechanisms underlying NIS-associated biology. A high NIS (NIS-high) was associated with adverse prognosis in bulk transcriptomic cohorts. External validation demonstrated that a high NIS was significantly associated with worse disease-free survival/relapse-free survival (DFS/RFS) in GSE39582 and worse overall survival in GSE17536. A multi-cohort meta-analysis further supported a consistent association between NIS-high and poor clinical outcomes. Single-cell analysis localized the NIS-high signal mainly to glial-like cells, fibroblasts, pericytes, endothelial cells, and malignant epithelial cells, whereas CD8+ T cells and natural killer cells exhibited low NIS. Focused ligand–receptor analysis suggested that NIS-high cellular compartments may communicate with immune and tumor compartments through MIF-CD74/CXCR4, SPP1-CD44, extracellular matrix (ECM)–integrin, TGF-β, and immune checkpoint-related axes. Spatial transcriptomics further demonstrated that NIS-high regions were enriched in stromal, neural/glial-like, vascular/pericyte, and tumor–stromal niches, whereas NIS-low regions were associated with immune-activated and cytotoxic T/NK cell-rich areas. NIS captures a spatially organized state of the colorectal cancer microenvironment characterized by neural/stromal remodeling, activation of ECM and vascular/pericyte niches, and relatively reduced or spatially segregated immune activation. NIS may serve as a biologically interpretable microenvironment stratification score associated with adverse outcomes. It also provides a framework for future studies targeting stromal remodeling, myeloid-mediated immune regulation, neural-associated signaling, and antitumor immunity. Full article

Background: Surgical site infection (SSI) is a common complication after colorectal cancer (CRC) surgery. We evaluated routinely available perioperative biomarkers for early prediction of superficial SSI after curative CRC surgery. Methods: This retrospective study included 488 patients undergoing elective curative CRC resection. Preoperative and postoperative day (POD) 1 laboratory parameters were evaluated using receiver operating characteristic curve analysis and multivariable logistic regression. Results: Superficial SSI developed in 66 patients (13.5%). In the perioperative multivariable association model, preoperative serum albumin ≤ 3.70 g/dL (odds ratio [OR], 1.918; 95% confidence interval [CI], 1.066–3.449; p = 0.030) and WBC count ≥ 6.30 × 10³/µL (OR, 1.970; 95% CI, 1.123–3.458; p = 0.018) were independently associated with superficial SSI. On POD1, serum albumin ≤ 2.80 g/dL (OR, 3.447; 95% CI, 1.993–5.963; p < 0.001) and WBC count ≥ 10.50 × 10³/µL (OR, 2.822; 95% CI, 1.600–4.976; p < 0.001) remained independently associated with SSI. Although lower POD1 lymphocyte-to-monocyte ratio was associated with SSI in univariable analysis, it was not significant after adjustment. A combined model incorporating dichotomized preoperative and POD1 albumin and WBC counts showed modest discrimination (AUC, 0.731; 95% CI, 0.663–0.800), with 47.0% sensitivity and 89.3% specificity. Conclusions: Perioperative albumin and WBC counts were independently associated with superficial SSI. POD1 assessment may aid early risk stratification; however, the modest performance indicates that these biomarkers should complement rather than replace clinical surveillance. Prospective external validation is required. Full article