Search Results (278)

Human colorectal cancer (CRC) encompasses tumors affecting a segment of the large intestine (colon) and rectum. It is the third most commonly diagnosed malignancy and the second leading cause of cancer deaths worldwide. It is a multifactorial disease, whose carcinogenesis process involves genetic and epigenetic alterations in oncogenes and tumor suppressor genes, including genes related to DNA repair. The pathogenic mechanisms are described based on the pathways of chromosomal instability, microsatellite instability, and CpG island methylator phenotype. When detected early, CRC is potentially curable, and its treatment is based on the pathological characteristics of the tumor and factors related to the patient, as well as on drug efficacy and toxicity studies. Therefore, the aim of this study was to review the pathogenesis and molecular subtypes of CRC and to describe the main targets of disease-directed therapy used in patients refractory to current treatments. Full article

Background/Objectives: Although numerous prognostic biomarkers have been proposed for colorectal cancer (CRC), their longitudinal evaluation remains limited. The aim of this study was to investigate longitudinal changes in biomarkers calculated from routinely used laboratory markers and their relationships to common chronic diseases (comorbidities). Methods: A retrospective longitudinal observational study was completed with the inclusion of 817 CRC patients and a total of 4542 measurement points. Pan-immune inflammation value (PIV), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated based on complete blood count and albumin measurement data. Results: Longitudinal data analyses confirmed the different values and slopes of the parameters tested at the different endpoints. Survivors had the lowest and most constant PIVs and SII values, and the highest and most slowly decreasing PNI values. Those patients with non-cancerous death had similar values to the previous cohort, but an increase/decrease occurred towards the death event. Patients with CRC-related death had significantly higher PIVs and SII values and significantly lower PNI values (p < 0.0001), and a significant increase/decrease was observed at the early observational periods. The presence of lymph node and/or distant metastases, adjuvant chemotherapy, and hypertension significantly affected PIVs and SII and/or PNI values. The changes in PIVs and SII and PNI values toward pathological values are poor prognostic signs (p < 0.0001). Conclusions: Each of the three calculated markers demonstrates suitability for longitudinal patient follow-up, and their pathological alterations over time serve as valuable prognostic indicators. They may also be useful to detect certain clinicopathological parameters early. Full article

Background/Objectives: Colorectal cancer (CRC) is among the most prevalent malignant neoplasms globally. Chemotherapeutic treatment strategies have demonstrated minimal improvement over the past decade. Combination therapies, including those with nutraceuticals, are currently being investigated as promising alternatives to enhance therapeutic efficacy. The organosulfur garlic extract diallyl disulfide (DADS) has demonstrated anti-tumoral activity in several types of cancer. This study aimed to investigate the effects of DADS and 5-fluorouracil (5-FU), both individually and in combination, on the human CRC cell lines Caco-2 and HT-29. Methods: Caco-2, HT-29, and non-tumoral human umbilical vein endothelial cells (HUVEC) were exposed to DADS (25–600 µM) and 5-FU (5–100 µM), either individually or in simultaneous combination (DADS 100 µM + 5-FU 100 µM), for 24 h. Cytotoxicity was evaluated in all three cell lines. In addition, the effects of these treatments on oxidative stress, cell migration, genotoxicity, cell death, global DNA methylation, and gene–nutraceutical interactions were assessed in both tumor cell lines. Results: DADS demonstrated cytotoxic effects at high concentrations in Caco-2, HT-29, and HUVECs and induced DNA damage in both colorectal cancer cell lines. The combination of DADS and 5-FU significantly promoted apoptotic cell death, increased genotoxicity, elevated global DNA methylation, and inhibited cell migration, with these effects being particularly pronounced in HT-29 cells. Conclusions: We provide evidence that DADS combined with 5-FU is potentially useful in the therapy of CRC. However the combination of nutraceuticals and chemotherapy must consider the distinct molecular and phenotypic characteristics of each tumor cell line. Full article

Background/Objectives: This study evaluates the performance of a large language model (lLm) in providing geographically tailored colorectal cancer screening and surveillance recommendations to gastrointestinal surgeons. Methods: Fifty-four patient cases, varying by age and family history, were developed based on colorectal cancer guidelines. Standardized prompts with predefined query terms were used to query ChatGPT-4.5 on 18 April 2025, from four locations: Canada, Italy, Romania, and the United Kingdom. Responses were classified as “Correct,” “Partially Correct,” or “Incorrect” based on clinical guidelines and expert recommendations for each country. Outcomes were analyzed using descriptive statistics. Results: ChatGPT provided recommendations on screening eligibility, test interpretation, the management of positive results, and surveillance intervals. Correct recommendations were given for 50.0% (27/54) of cases in Canada, 63.0% (34/54) of cases in Italy, 40.7% (22/54) of cases in Romania, and 55.6% (30/54) of cases in the United Kingdom. Queries in Italian yielded correct guidance for 64.8% (35/54) of cases, while Romanian queries were accurate for 40.7% (22/54) of cases. Notably, Romania and Italy lacked detailed guidelines for polyp management and post-test surveillance. A key finding was the inconsistency between ChatGPT-generated titles and corresponding recommendations, which may impact its reliability in clinical decision-making. Conclusions: ChatGPT-4.5’s performance varies by country and language, highlighting inconsistencies in geographically tailored recommendations. This study highlights limitations associated with the training data cutoff and the potential biases introduced by model-generated responses. Healthcare professionals should recognize these limitations and the possible gaps in guideline availability, particularly for high-risk screening, polyp management, and surveillance in certain European countries. Full article

In this study, we investigated the expression of TIM-3 and Galectin-9 (Gal-9) in colorectal cancer (CRC) and their associations with oncogenic mutations, MSI status, cytokine profiles, and transcriptional data. TIM-3 and Gal-9 protein levels were significantly increased in CRC tissues compared to matched non-tumor margins (p < 0.05 and p < 0.001, respectively). TIM-3 protein concentration was notably higher in PIK3CA-mutated tumors (p < 0.05), while no associations were found with KRAS, NRAS, BRAF, AKT1, or MSI status. Multiplex cytokine profiling revealed strong correlations between TIM-3 and Gal-9 levels and key immunomodulatory pathways, including IL-10, IL-17, and chemokine signaling. We also observed significant associations with cytokine subsets involved in protumor activity and immune regulation. Gene set enrichment analysis (GSEA) demonstrated that high TIM-3 and Gal-9 expression was associated with upregulation of cell cycle-related pathways, and downregulation of immune signatures, such as interferon responses and TNF-α/NFκB signaling. These findings suggest that increased TIM-3 and Gal-9 expression reflects a shift toward proliferative activity and immune suppression in the CRC tumor microenvironment, highlighting their potential as biomarkers of immunoevasive tumor phenotypes, especially in PIK3CA-mutant CRC tumors. Full article

Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article

Colorectal cancer (CRC) is one of the most prevalent and deadly neoplasms globally; this fact puts emphasis on the need for accurate molecular biomarkers for early detection and accurate prognosis. Circular RNAs (circRNAs) have recently emerged as very promising cancer biomarkers. In this study, we thoroughly examined whether the expression levels of circular transcripts of the protein arginine methyltransferase 1 (PRMT1) gene can predict the prognosis of patients diagnosed with colorectal adenocarcinoma, the most frequent type of CRC. Hence, a highly sensitive quantitative PCR (qPCR) assay was developed and applied to quantify circ-PRMT1 expression in cDNAs from 210 primary colorectal adenocarcinoma tissue specimens and 86 paired normal colorectal mucosae. Extensive biostatistical analysis was then performed to assess the potential prognostic power of circ-PRMT1. Significant overexpression of this molecule was observed in colorectal adenocarcinoma tissue samples in contrast to their non-cancerous counterparts. Moreover, higher circ-PRMT1 expression was correlated with poorer disease-free survival (DFS) and worse overall survival (OS) in colorectal adenocarcinoma patients. Interestingly, multivariate Cox regression analysis revealed that the prognostic value of the expression of this circRNA does not depend on other established prognostic factors included in the prognostic model. Furthermore, the stratification of patients based on TNM staging revealed that higher circ-PRMT1 levels were significantly related to shorter DFS and OS intervals, particularly in patients with colorectal adenocarcinoma of TNM stage II or III. In summary, this original research study provides evidence that circ-PRMT1 overexpression represents a promising molecular biomarker of poor prognosis in colorectal adenocarcinoma, not depending on other established prognostic factors such as TNM staging. Full article

Background/Objectives: TTF-1 and Napsin A are immunohistochemical markers that are widely used for the diagnosis of lung adenocarcinomas or thyroid carcinomas, as well as the characterization of metastases. However, several publications have reported the aberrant expression of one or both markers in extrathoracic malignancies, including gastrointestinal adenocarcinomas. The goal of our study was to determine the frequency of TTF-1- and Napsin A-positive neoplasms in cohorts consisting of esophageal, gastric and colorectal adenocarcinomas. Methods: Buffered formalin-fixed paraffin-embedded tumor tissues from 854 patients with primary resected gastrointestinal and esophageal carcinomas were placed in tissue microarrays (TMAs) for investigation. Between two and six tumor cores were analyzed for each case. For immunohistochemical staining, we used TTF-1 (SPT24 clone) and Napsin A (IP64 clone). Tumors were considered positive if at least 5% of their tumor cells showed weak nuclear (TTF-1) or cytoplasmic (Napsin A) staining. Results: In total, 16 cases showed positive staining for TTF-1, alongside 7 cases for Napsin A. The greatest proportion of TTF-1- and/or Napsin A-positive tumors was found among esophageal adenocarcinomas (5/125 cases; 4%). Co-expression of TTF-1 and Napsin A was found in five cases, including three esophageal and two gastric adenocarcinomas. In colorectal carcinomas, co-expression of these markers was not detected. Conclusions: TTF-1 and Napsin A are useful immunohistochemical makers for establishing the diagnosis of pulmonary adenocarcinoma. Additionally, knowing that a proportion of gastrointestinal neoplasms express these markers can help to avoid diagnostic misinterpretations. Full article

Objective: Although prior research developed an artificial intelligence (AI)-based classification system predicting colorectal lesion histology, the heavy computational demands limited its practical application. Recent advancements in medical AI emphasize decentralized architectures using edge computing devices, enhancing accessibility and real-time performance. This study aims to construct and evaluate a deep learning-based colonoscopy image classification model for automatic histologic categorization for real-time use on edge computing hardware. Design: We retrospectively collected 2418 colonoscopic images, subsequently dividing them into training, validation, and internal test datasets at a ratio of 8:1:1. Primary evaluation metrics included (1) classification accuracy across four histologic categories (advanced colorectal cancer, early cancer/high-grade dysplasia, tubular adenoma, and nonneoplasm) and (2) binary classification accuracy differentiating neoplastic from nonneoplastic lesions. Additionally, an external test was conducted using an independent dataset of 269 colonoscopic images. Results: For the internal-test dataset, the model achieved an accuracy of 83.5% (95% confidence interval: 78.8–88.2%) for the four-category classification. In binary classification (neoplasm vs. nonneoplasm), accuracy improved significantly to 94.6% (91.8–97.4%). The external test demonstrated an accuracy of 82.9% (78.4–87.4%) in the four-category task and a notably higher accuracy of 95.5% (93.0–98.0%) for binary classification. The inference speed of lesion classification was notably rapid, ranging from 2–3 ms/frame in GPU mode to 5–6 ms/frame in CPU mode. During real-time colonoscopy examinations, expert endoscopists reported no noticeable latency or interference from AI model integration. Conclusions: This study successfully demonstrates the feasibility of a deep learning-powered colonoscopy image classification system designed for the rapid, real-time histologic categorization of colorectal lesions on edge computing platforms. This study highlights how nature-inspired frameworks can improve the diagnostic capacities of medical AI systems by aligning technological improvements with biomimetic concepts. Full article

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by perivascular epithelioid cell proliferation. They can occur in various organs, but colonic PEComas are exceptionally rare, showing diagnostic challenges due to their nonspecific clinical presentation and similar features to those of other colorectal tumors. We present a case of a 61-year-old female with defecation accompanied by blood clots, initially diagnosed with a suspected tumor in the sigmoid colon. Despite initial biopsy yielding non-informative material, repeat colonoscopy and imaging studies revealed a malignant tumor with multinucleated giant (osteoclast-like) cells and probable p53 mutation, most likely of mesenchymal origin. Robotic surgical resection was performed, and ultimately pathological examination refined the diagnosis as a malignant PEComa of the colon. This case demonstrates the importance of considering PEComa in the differential diagnosis of colonic tumors. Further research is needed to ascertain the clinical behavior and optimal treatment for colonic PEComas. Full article

Background and Objectives: Serrated adenocarcinoma (SAC) is a distinctive neoplasm that is histopathologically characterized by the presence of epithelial serration, an eosinophilic cytoplasm, and a vesicular nucleus. However, the literature data concerning somatic mutations in SACs remain extremely limited. Materials and Methods: A total of 159 colon resection cases diagnosed with adenocarcinoma whose DNA mutations were analyzed by next-generation sequencing (NGS) were retrospectively reviewed. In 23 cases, the SAC area exceeded 50%. A chi-square test was used to evaluate histopathologic characteristics and somatic mutations in SACs and non-serrated adenocarcinomas (non-SACs). Results: A significant difference was found in histological grade (p = 0.019) between SACs and non-SACs. TP53, KRAS, and PIK3CA genes have been identified as the most frequently mutated genes in both SACs and non-SACs. No statistically significant difference in somatic mutations was observed between the two groups (p > 0.05). Conclusions: In the present study, a higher prevalence of KRAS mutations was observed in SACs compared to BRAF mutations (KRAS: 39.1%, BRAF: 4.3%). This finding is consistent with the recent literature reporting a higher prevalence of KRAS mutations in colorectal SACs, in contrast to previous studies. The somatic mutation results of our study and the previous literature data suggest the potential importance of epigenetic alterations documented in the literature in the development of SACs. Full article

Background/Objectives: Colorectal neoplasms rank as the third most prevalent cancer globally and stand as the second leading cause of cancer-related mortality. Its etiology is multifaceted, pointing to the role of microorganisms within the human microbiota in its development. Notably, the high prevalence of oral pathogens like Fusobacterium nucleatum and Parvimonas micra is implicated in inducing gut dysbiosis and stimulating the proliferation and metastasis of cancer cells. Therefore, this study aimed to evaluate in vitro the biological effects of extracts from Juglans regia and Pfaffia paniculata. Methods: Phytochemical analysis was carried out by HPLC, and the antioxidant effect was determined by DPPH. Antimicrobial activity was investigated on F. nucleatum and P. micra planktonic and biofilms. Metabolic activity and genotoxicity were performed. Results:J. regia and P. paniculata expressed CE50 37.26 and 1367.57 mcg, respectively. The extracts exhibited a minimum bactericidal concentration of 1.73 and 0.48 mg/mL for J. regia and P. paniculata, respectively. Reduction superiorly 90% of P. micra biofilms. Metabolic activity was varied proportionally to the extract concentration, and no genotoxic effects were observed. Conclusions: The J. regia extract has great antioxidant activity and could be used as an alternative in combating pathogens associated with the onset of dysbiosis and tumor progression in colorectal neoplasms. Nevertheless, further studies are needed to validate their clinical applicability. Full article

Background/Objectives: This population-based study examined epidemiological trends of primary cancers in adolescents and young adults (AYAs) to enhance the understanding of the specific spectrum of cancers impacting AYAs in Belgium. Methods: Data on incidence, prevalence, mortality, and survival were obtained from the Belgian Cancer Registry (2004–2020, N = 43,535). (A)APC statistics were compared with children (5–14 years) and adults (40–49 years). Results: Cancer incidence increased by 0.4% annually from 66 to 80 per 100,000 person-years (ESR2013) but stabilised after 2015, except for Hodgkin lymphoma, chronic myeloid neoplasms, and testicular and breast cancer, which continued to rise. Mortality decreased by 1% annually, from 10 to 7 per 100,000 person-years (2004–2019). Five-year relative survival (RS) was 87% but remained low for certain cancers, including ovary (78%), central nervous system (67%), precursor haematopoietic neoplasms (64%), gastrointestinal (excl. colorectal) (49%), and lung-bronchus-trachea cancers (42%). Conclusions: From 2004–2020, the cancer burden among AYAs in Belgium increased due to improved survival, while incidence stabilised after 2015. Five-year RS exceeds 80% overall but remains lower for some cancers compared to children (e.g., precursor haematopoietic neoplasms) or older adults (e.g., breast cancer, sarcoma). The Belgian epidemiological trends align with those in neighbouring countries (Netherlands, France, Germany). Full article

Background: An unhealthy diet is a major risk factor for colorectal cancer (CRC). This study assessed the diet-related CRC burden from 1990 to 2021 in Organisation for Economic Co-operation and Development (OECD) nations and estimated the burden until 2050. Methods: Data for OECD countries on diet-related CRC disability-adjusted life years (DALYs) and deaths were obtained from the Global Burden of Disease 2021 study. The estimated annual percent change (EAPC) was calculated to analyse the CRC burden attributable to dietary factors. A generalised additive model with a negative binomial distribution was used to predict the future burden of CRC attributable to dietary factors from 2021 to 2050. Results: In 2021, the age-standardised percentages of diet-related CRC DALYs and deaths were 39.1% (95% uncertainty interval (UI): 9.3, 61.3) and 39.0% (95% UI: 9.7, 60.9), respectively, in the OECD countries. Between 1990 and 2021, the age-standardised DALYs decreased from 185 to 129 per 100,000, and deaths decreased from 8 to 6 per 100,000 population for OECD countries. Similarly, the EAPC in the rates showed a downward trend (EAPC_deaths = −1.26 and EAPC_DALYs = −1.20). The estimated diet-related CRC DALYs and deaths are projected to increase to 4.1 million DALYs and 0.2 million deaths by 2050. There is a downward trend in CRC deaths (EAPC = 1.33 for both sexes) and in DALYs (−0.90 for males and −1.0 for females) from 1990 to 2050. Conclusions: The diet-related CRC burden remains significant. Implementing nutrition intervention programmes is necessary to promote access to affordable and nutritious foods and raise awareness about the importance of a healthy diet in reducing CRC risk. Full article

Research undertaken over the past few years has brought attention to the role of oxidative stress in the development of neoplasms by damaging nucleic acids, lipids, and proteins, thereby altering their normal function. In general, the levels of antioxidant enzymes are low in patients with neoplasms, and the biomarkers used to quantify oxidative stress have increased levels. Elevated levels of 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), as well as decreased levels of antioxidant enzymes, have been observed in patients diagnosed with colorectal cancer (CRC) at various stages of evolution, but further research is needed on the correlation between these biomarkers and disease progression. Inflammation enhances the production of reactive oxygen species and plays an important role in CRC development. Studies in the field of metabolomics have suggested that changes in serum metabolites might be indicators of the progression from adenoma to colorectal carcinoma, particularly those resulting from lipid metabolism. The role of lipidomics in the pathogenesis of CRC warrants further investigation, as these combinations of metabolites (metabolic fingerprints) may have the potential to become clinically useful markers. In this article, we review our current understanding of the interplay between oxidative stress, inflammatory markers and lipidomic products in the pathogenesis of CRC. Full article