Synchronous multiple colorectal cancers (SMCRC) are rare and defined as distinct malignant tumors occurring simultaneously in the colon and rectum without evidence of metastasis from one tumor to another. This case report presents a 69 year-old Tibetan male admitted with acute abdominal pain, abdominal distension, nausea, and vomiting. Imaging studies and colonoscopy revealed synchronous cancers in the rectum, sigmoid colon, and transverse colon, all pathologically confirmed as moderately differentiated adenocarcinomas. The patient underwent a multisegment colectomy with complete resection of all tumors. Postoperative recovery was uneventful, and no recurrence was reported during follow-up. This case underscores the importance of thorough diagnostic and surgical strategies for SMCRC, particularly in emergency presentations where limited diagnostic modalities may pose challenges.

The introduction of self-expandable metal stent (SEMS) insertion in obstructive colorectal cancer (CRC) has been associated with an increased risk of tumor perforation, potentially leading to peritoneal dissemination, tumor cell spread via lymphatic vessels, perineural invasion, and peripheral bloodstream. The objective of this study was to assess the impact of SEMS placement on CRC lymph node metastasis.

We retrospectively reviewed 48 patients with malignant colorectal obstruction treated with a temporary SEMS before elective surgery, and 51 patients with malignant colorectal obstruction who underwent elective surgery without prior SEMS placement.

No significant differences were found in the lymph node ratio (LNR) or in the results obtained from the logarithm of the ratio between positive and negative nodes (LODDS). Regarding recurrence, patients without SEMS had a fourfold higher risk of local recurrence compared to those with SEMS (19.6% vs. 6.3%), and a twofold higher risk of distant recurrence (31.4% vs. 14.6%). These differences were statistically significant for overall recurrence and for each local and distant recurrence individually (P = 0.02, P = 0.05, and P = 0.04, respectively).

SEMS placement in obstructive CRC not only shows the potential to suppress tumor growth, but also reduce nodal spread, as no differences in LNR and LODDS values were observed when comparing preoperative SEMS placement in patients with advanced left CRC.

Automated colorectal cancer (CRC) segmentation in medical imaging is the key to achieving automation of CRC detection, staging, and treatment response monitoring. Compared with magnetic resonance imaging (MRI) and computed tomography colonography (CTC), conventional computed tomography (CT) has enormous potential because of its broad implementation, superiority for the hollow viscera (colon), and convenience without needing bowel preparation. However, the segmentation of CRC in conventional CT is more challenging due to the difficulties presenting with the unprepared bowel, such as distinguishing the colorectum from other structures with similar appearance and distinguishing the CRC from the contents of the colorectum. To tackle these challenges, we introduce DeepCRC-SL, the first automated segmentation algorithm for CRC and colorectum in conventional contrast-enhanced CT scans. We propose a topology-aware deep learning-based approach, which builds a novel 1-D colorectal coordinate system and encodes each voxel of the colorectum with a relative position along the coordinate system. We then induce an auxiliary regression task to predict the colorectal coordinate value of each voxel, aiming to integrate global topology into the segmentation network and thus improve the colorectum's continuity. Self-attention layers are utilized to capture global contexts for the coordinate regression task and enhance the ability to differentiate CRC and colorectum tissues. Moreover, a coordinate-driven self-learning (SL) strategy is introduced to leverage a large amount of unlabeled data to improve segmentation performance. We validate the proposed approach on a dataset including 227 labeled and 585 unlabeled CRC cases by fivefold cross-validation. Experimental results demonstrate that our method outperforms some recent related segmentation methods and achieves the segmentation accuracy in DSC for CRC of 0.669 and colorectum of 0.892, reaching to the performance (at 0.639 and 0.890, respectively) of a medical resident with two years of specialized CRC imaging fellowship.

Endoscopic submucosal dissection (ESD) is a standardized therapeutic approach for early carcinoma of the digestive tracts. In this regard, the process of histopathological diagnosis requires standardization. However, the uneven development of healthcare in China, especially in eastern and western China, creates challenges for sharing a standardized diagnostic process.

To optimize the process of ESD specimen sampling, embedding and slide production, and to provide complete and accurate pathological reports.

We established a practical process of specimen sampling, created standardized reporting templates, and trained pathologists from neighboring hospitals and those in the western region. A training effectiveness survey was conducted, and the collected data were assessed by the corresponding percentages.

A total of 111 valid feedback forms have been received, among which 58% of the participants obtained photographs during specimen collection, whereas the percentage increased to 79% after training. Only 58% and 62% of the respondents ensured the mucosal tissue strips were flat and their order remained unchanged; after training, these two proportions increased to 95% and 92%, respectively. Approximately half the participants measured the depth of the submucosal infiltration, which significantly increased to 95% after training. The percentage of pathologists who did not evaluate lymphovascular invasion effectively reduced. Only 22% of the participants had fixed clinic-pathological meetings before training, which increased to 49% after training. The number of participants who had a thorough understanding of endoscopic diagnosis also significantly increased.

There have been significant improvements in the process of specimen collection, section quality, and pathology reporting in trained hospitals. Therefore, our study provides valuable insights for others facing similar challenges.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, necessitating the continuous evolution of therapeutic approaches. Despite advancements in early detection and localized treatments, metastatic colorectal cancer (mCRC) poses significant challenges due to low survival rates and resistance to conventional therapies. This review highlights the current landscape of CRC treatment, focusing on chemotherapy and targeted therapies. Chemotherapeutic agents, including 5-fluorouracil, irinotecan, and oxaliplatin, have significantly improved survival but face limitations such as systemic toxicity and resistance. Targeted therapies, leveraging mechanisms like VEGF, EGFR, and Hedgehog pathway inhibition, offer promising alternatives, minimizing damage to healthy tissues while enhancing therapeutic precision. Furthermore, future directions in CRC treatment include exploring innovative targets such as Wnt/β-catenin, Notch, and TGF-β pathways, alongside IGF/IGF1R inhibition. These emerging strategies aim to address drug resistance and improve patient outcomes. This review emphasizes the importance of integrating molecular insights into drug development, advocating for a more personalized approach to combat CRC's complexity and heterogeneity.

Colonoscopy, a crucial procedure for detecting and removing colorectal polyps, has seen transformative advancements through the integration of artificial intelligence, specifically in computer-aided detection (CADe) and diagnosis (CADx). These tools enhance real-time detection and characterization of lesions, potentially reducing human error, and standardizing the quality of colonoscopy across endoscopists. CADe has proven effective in increasing adenoma detection rate, potentially reducing long-term colorectal cancer incidence. However, CADe's benefits are accompanied by challenges, such as potentially longer procedure times, increased non-neoplastic polyp resections, and a higher surveillance burden. CADx, although promising in differentiating neoplastic and non-neoplastic diminutive polyps, encounters limitations in accuracy, particularly in the proximal colon. Real-world data also revealed gaps between trial efficacy and practical outcomes, emphasizing the need for further research in uncontrolled settings. Moreover, CADx limited specificity and binary output underscore the necessity for explainable artificial intelligence to gain endoscopists' trust. This review aimed to explore the benefits, harms, and limitations of artificial intelligence for colon cancer screening, surveillance, and treatment focusing on CADe and CADx systems for lesion detection and characterization, respectively, while addressing challenges in integrating these technologies into clinical practice.

Background: The use of adjuvant chemotherapy in patients with stage T3N0 rectal cancer following total mesorectal excision (TME) is debated. This study is aimed at investigating the clinical significance of negative lymph node (NLN) counts in patients with T3N0 rectal cancer, particularly in relation to adjuvant chemotherapy. Methods: This retrospective analysis examined 311 patients with T3N0 rectal cancer who underwent radical resection at the Sixth Affiliated Hospital of Sun Yat-sen University between August 2014 and December 2021. The optimal cutoff for NLN counts was determined using receiver operating characteristic (ROC) curves. Clinicopathological characteristics and clinical outcomes were compared between the high and low NLN groups. Overall survival (OS) and disease-free survival (DFS) were used to evaluate the efficacy of adjuvant chemotherapy. Results: The optimal cutoff for NLNs was 21. Of the 311 patients, 141 were categorized into the high NLN group and 170 into the low NLN group. Patients with NLNs ≥ 21 had significantly better 5-year OS (99.3% vs. 88.2%, p < 0.05) and 5-year DFS (92.2% vs. 79.4%, p < 0.05) compared to those with low NLNs. Multivariate Cox analysis revealed that NLN count was an independent prognostic factor for OS (hazard ratio (HR) = 0.078, 95% confidence interval (CI): 0.011-0.582, p = 0.013) and DFS (HR = 0.417, 95% CI: 0.213-0.815, p = 0.011). Subgroup analysis indicated that adjuvant chemotherapy significantly improved OS (p < 0.05) and DFS (p < 0.05) in the low NLN group. Conclusion: NLN count is an independent prognostic factor in patients with T3N0 rectal cancer. Patients with low NLN counts (NLN < 21) may benefit from adjuvant chemotherapy.

Inaccurate prediction of lymph node metastasis (LNM) may lead to unnecessary surgery following endoscopic resection of T1 colorectal cancer (CRC). We aimed to validate the usefulness of artificial intelligence (AI) models for predicting LNM in patients with T1 CRC.

We analyzed the clinical data, laboratory results, pathological reports, and endoscopic findings of patients who underwent radical surgery for T1 CRC. We developed AI models to predict LNM using four algorithms: regularized logistic regression classifier (RLRC), random forest classifier (RFC), CatBoost classifier (CBC), and the voting classifier (VC). Four histological factors and four endoscopic findings were included to develop AI models. Areas under the receiver operating characteristics curves (AUROCs) were measured to distinguish AI model performance in accordance with the Japanese Society for Cancer of the Colon and Rectum guidelines.

Among 1,386 patients with T1 CRC, 173 patients (12.5%) had LNM. The AUROC values of the RLRC, RFC, CBC, and VC models for LNM prediction were significantly higher (0.673, 0.640, 0.679, and 0.677, respectively) than the 0.525 suggested in accordance with the Japanese Society for Cancer of the Colon and Rectum guidelines (vs RLRC, p<0.001; vs RFC, p=0.001; vs CBC, p<0.001; vs VC, p<0.001). The AUROC value was similar between T1 colon versus T1 rectal cancers (0.718 vs 0.615, p=0.700). The AUROC value was also similar between the initial endoscopic resection and initial surgery groups (0.581 vs 0.746, p=0.845).

AI models trained on the basis of endoscopic findings and pathological features performed well in predicting LNM in patients with T1 CRC regardless of tumor location and initial treatment method.

The poor prognosis of colorectal cancer (CRC) contributes to a yearly increase in CRC mortality, while microRNAs (miRNAs) were found to play a regulatory function in diversiform cancers, including CRC. The objective of this research was to evaluate the clinical value and possible regulatory mechanisms of miR-767-5p in CRC. The expression level of miR-767-5p in CRC tissues and cells was examined. The Kaplan-Meier curve was utilized to analyse the function of miR-767-5p in CRC prognosis. The independent prognostic factors in CRC were assessed by a multivariate COX regression analysis. Additionally, the regulatory mechanism of miR-767-5p in CRC was determined through an in vitro cell experiment. The miR-767-5p expression was down-regulated in CRC tumour tissues and CRC cells. Indicators such as tumour differentiation, TNM, LNM and miR-767-5p were identified as independent prognostic factors for a poor CRC prognosis. The regulatory relationship between miR-767-5p and nuclear factor I A (NFIA) was verified by the dual-luciferase reporter assay, and the NFIA expression level was significantly suppressed by over-expressed miR-767-5p. The proliferation, migration and invasion of CRC cells were inhibited by over-expressing miR-767-5p, while the inhibition effect could be reversed by over-expressing NFIA. The over-expressed miR-767-5p could serve as a tumour suppressor to inhibit the progression of CRC by suppressing the expression level of NFIA.

Colorectal cancer represents a significant health challenge as one of the deadliest forms of malignancy. Manual examination methods are subjective, leading to inconsistent interpretations among different examiners and compromising reliability. Additionally, process is time-consuming and labor-intensive, necessitating the development of computer-aided diagnostic systems. This study investigates the segmentation of colorectal cancer regions of normal tissue, polyps, high-grade intraepithelial neoplasia, low-grade intraepithelial neoplasia, adenocarcinoma, and serrated Adenoma, using proposed segmentation models: VGG16-UNet, ResNet50-UNet, MobileNet-UNet, and MobileViT-UNet. This is the first study to integrate MobileViT as a UNet encoder. Each model was trained with two distinct loss functions, binary cross-entropy and dice loss, and evaluated using metrics including Dice ratio, Jaccard index, precision, and recall. The MobileViT-UNet+Dice loss emerged as the leading model in colorectal histopathology segmentation, consistently achieving high scores across all evaluation metrics. Specifically, it achieved a Dice ratio of 0.944 ± 0.030 and a Jaccard index of 0.897 ± 0.049, with precision at 0.955 ± 0.046 and Recall at 0.939 ± 0.038 across all classes. To further obtain the best performing model, we employed multi-criteria decision analysis (MCDA) using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). This analysis revealed that the MobileViT-UNet+Dice model achieved the highest TOPSIS scores of 1, thereby attaining the highest ranking among all models. Our comparative analysis includes benchmarking with existing works, the results highlight that our best-performing model (MobileViT-UNet+Dice) significantly outperforms existing models, showcasing its potential to enhance the accuracy and efficiency of colorectal cancer segmentation.

The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration showed no significant clinical difference in outcomes in patients with stage III colon cancer (CC) treated with 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy (O-ACT). We aimed to assess change in real-world practice patterns before and after publication of the IDEA study.

This retrospective cohort study included patients age ≥18 years with stage III CC diagnosed between January 1, 2012, and December 31, 2020. Eligible patients received >1 dose of ACT between March 20, 2012, and May 10, 2021 inclusive. They were categorized into pre-IDEA (diagnosed before March 31, 2018) and post-IDEA (diagnosed on or after April 1, 2018) groups. The primary outcome was the median duration and type of ACT and factors associated with a shorter duration. Secondary outcomes were 2-year overall survival (OS) and cancer-specific survival (CSS).

In total, 740 patients were included (median age, 64 years, range, 27-90; 52.7% male). 48.8% had pT4 and/or pN2 disease. 77% received O-ACT. In the post-IDEA era, capecitabine plus oxaliplatin (CAPOX) ACT use increased (22.8%-50.7%, P < .001), and median duration of treatment was significantly shorter (2.7 v 4.8 months, P < .001). Factors associated with shorter O-ACT duration included diagnosis in the post-IDEA era (odds ratio, 2.08, P = .002), absence of pT4 and/or pN2 disease (hazard ratio [HR], 1.71, P = .01), and receipt of CAPOX (HR, 2.58, P < .001). Two-year OS and CSS were comparable between pre- and post-IDEA eras (OS 95% v 94%; CSS 96% v 96%).

Our study shows that the results of the IDEA trial have been largely adopted in clinical practice with shorter duration of ACT in low-risk stage III CC.

Accurate stratification of the risk of lymph node metastasis (LNM) following endoscopic resection of submucosal invasive (T1) colorectal cancer (CRC) is imperative for determining the necessity for additional surgery. In this systematic review, we evaluated the efficacy of prediction of LNM by artificial intelligence (AI) models utilizing whole slide image (WSI) in patients with T1 CRC.

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted through searches in PubMed (MEDLINE), Embase, and the Cochrane Library for relevant studies published up to December 2023. The inclusion criteria were studies assessing the accuracy of hematoxylin and eosin-stained WSI-based AI models for predicting LNM in patients with T1 CRC.

Four studies met the criteria for inclusion in this systematic review. The area under the receiver operating characteristic curve for these AI models ranged from 0.57 to 0.76. In the three studies in which AI performance was compared directly with current treatment guidelines, AI consistently exhibited a higher area under the receiver operating characteristic curve. At a fixed sensitivity of 100%, specificities ranged from 18.4% to 45.0%.

Artificial intelligence models based on WSI can potentially address the issue of diagnostic variability between pathologists and exceed the predictive accuracy of current guidelines. However, these findings require confirmation by larger studies that incorporate external validation.

This study investigated the incidence of lymph node metastasis and long-term outcomes in patients with T1 colorectal cancer where endoscopic submucosal dissection (ESD) resulted in noncurative treatment. It is focused on those with deep submucosal invasion, a factor considered a weak predictor of lymph node metastasis in the absence of other risk factors.

This nationwide, multicenter, prospective study conducted a post-hoc analysis of 141 patients with T1 colorectal cancer ≥20 mm where ESD of the lesion resulted in noncurative outcomes, characterized by poor differentiation, deep submucosal invasion (≥1000 μm), lymphovascular invasion, high-grade tumor budding, or positive vertical margins. Clinicopathologic features and patient prognoses focusing on lesion sites and additional surgery requirements were evaluated. Lymph node metastasis incidence in the low-risk T1 group, identified by deep submucosal invasion as the sole high-risk histological feature, was assessed.

Lymph node metastasis occurred in 14% of patients undergoing additional surgery post-noncurative endoscopic submucosal dissection for T1 colorectal cancer. In the low-risk T1 group, in the absence of other risk factors, the frequency was 9.7%. The lymph node metastasis rates in patients with T1 colon and rectal cancers did not differ significantly (14% vs. 16%). Distant recurrence was observed in one patient (2.3%) in the ESD only group and in one (1.0%) in the additional surgery group, both of whom had had rectal cancer removed.

The risk of lymph node metastasis or distant occurrence was not negligible, even in the low-risk T1 group. The findings suggest the need for considering additional surgery, particularly for rectal lesions (Clinical Trial Registration: UMIN000010136).

Endoscopic procedures and surgery are common treatments for early colorectal cancer (CRC). However, only approximately 10% of patients who undergo surgery have lymph node metastases (LNM) detected on postoperative pathology, which often leads to overtreatment. This study aims to comprehensively analyze the risk factors for LNM in early CRC patients, establishing a predictive model to aid in treatment decisions.

This study reviewed the clinicopathologic data of patients with early CRC who underwent surgery from January 2015 to June 2023. Univariate and multivariate logistic regression analyses were employed to identify LNM risk factors. The receiver operating characteristic (ROC) analysis and calibration curves were also constructed to verify the model's discrimination and calibration. A simplified scale was calculated to promote the risk stratification for LNM.

The study analyzed medical records of 375 patients. Of these, 37 (9.9%) cases had LNM. Univariate analysis identified age, nerve invasion, depth of submucosal invasion, histologic grade, LVI, and tumor budding as risk factors. The multivariate analysis confirmed histologic grade (OR, 13.403; 95% CI, 1.415-126.979; P = 0.024), LVI (OR, 6.703; 95% CI, 2.600-17.284; P < 0.001), and tumor budding (OR, 3.090; 95% CI, 1.082-8.820; P = 0.035) as independent predictors. The optimal nomogram, incorporating six risk factors, demonstrated strong predictability with an area under the ROC curve (AUC) of 0.837 (95% CI, 0.762-0.912). A simplified risk assessment scale with a total score of 19 points was developed.

The study developed a nomogram and a simplified risk assessment scale to predict LNM risk, potentially optimizing the management of early CRC patients.

APRIL (A proliferation-inducing ligand) is a member of the tumor necrosis factor superfamily that is overexpressed in a variety of malignant tumors, including colorectal cancer (CRC). Its key physiological roles include inducing the immunoglobulin switch and ensuring plasmocyte survival. In terms of pathological roles, APRIL antagonism has been identified as a key target in autoimmune diseases and immunoglobulin disorders. As previously demonstrated, several inflammatory processes occur at the site of neoplastic initial stages, and their local symptoms are difficult to detect, particularly in the early stages. That is why we chose to study the current literature on APRIL's role in the development of colorectal cancer. The main objective of our research was to investigate the role of APRIL in cancer initiation and its usefulness in the detection and therapy of CRC. Interestingly, the findings conducted so far show that the selected protein has a significant potential as a CRC biomarker and treatment target. Importantly, based on its concentration, it is possible to identify CRC patients, but whether the lesion has a benign or malignant nature, indicating the possibility of rapid detection of an ongoing disease process.

Colorectal cancer (CRC) ranks second in incidence and third in cancer mortality worldwide. This situation, together with the understanding of the heterogeneity of the disease, has highlighted the need to develop a more individualised approach to its prevention, diagnosis and treatment through personalised medicine. This approach aims to stratify patients according to risk, predict disease progression and determine the most appropriate treatment. It is essential to identify patients who may respond adequately to treatment and those who may be resistant to treatment to avoid unnecessary therapies and minimise adverse side effects. Current research is focused on identifying biomarkers such as specific mutated genes, the type of mutations and molecular profiles critical for the individualisation of CRC diagnosis, prognosis and treatment guidance. In addition, the study of the intestinal microbiota as biomarkers is being incorporated due to the growing scientific evidence supporting its influence on this disease. This article comprehensively addresses the use of current and emerging diagnostic, prognostic and predictive biomarkers in precision medicine against CRC. The effects of host genetics and gut microbiota composition on new approaches to treating this disease are discussed. How the gut microbiota could mitigate the side effects of treatment is reviewed. In addition, strategies to modulate the gut microbiota, such as dietary interventions, antibiotics, and transplantation of faecal microbiota and phages, are discussed to improve CRC prevention and treatment. These findings provide a solid foundation for future research and improving the care of CRC patients.

Submucosal invasive (T1) colorectal cancer is a significant clinical management challenge, with an estimated 10% of patients developing extraintestinal lymph node metastasis. This condition necessitates surgical resection along with lymph node dissection to achieve a curative outcome. Thus, the precise preoperative assessment of lymph node metastasis risk is crucial to guide treatment decisions after endoscopic resection. Contemporary clinical guidelines strive to identify a low-risk cohort for whom endoscopic resection will suffice, applying stringent criteria to maximize patient safety. Those failing to meet these criteria are often recommended for surgical resection, with its associated mortality risks although it may still include patients with a low risk of metastasis. In the quest to enhance the precision of preoperative lymph node metastasis risk prediction, innovative models leveraging artificial intelligence or nomograms are being developed. Nevertheless, the debate over the ideal sensitivity and specificity for such models persists, with no consensus on target metrics. This review puts forth postoperative mortality rates as a practical benchmark for the sensitivity of predictive models. We underscore the importance of this method and advocate for research to amass data on surgical mortality in T1 colorectal cancer. Establishing specific benchmarks for predictive accuracy in lymph node metastasis risk assessment will hopefully optimize the treatment of T1 colorectal cancer.

The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established.

This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency.

This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines.

The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.

Due to its decade-long progression, colorectal cancer (CRC) is most suitable for population screening to achieve a significant reduction in its incidence and mortality. DNA methylation has emerged as a potential marker for the early detection of CRC. However, the current mainstream methylation detection method represented by bisulfite conversion has issues such as tedious operation, DNA damage, and unsatisfactory sensitivity. Herein, a new high-performance CRC screening tool based on the promising specific terminal-mediated polymerase chain reaction (STEM-PCR) strategy is developed. CRC-related methylation-specific candidate CpG sites are first prescreened through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases using self-developed bioinformatics. Next, 9 homebrew colorectal cancer DNA methylated STEM‒PCR assays (ColoC-mSTEM) with high sensitivity (0.1%) and high specificity are established to identify candidate sites. The clinical diagnostic performance of these selected methylation sites is confirmed and validated by a case-control study. The optimized diagnostic model has an overall sensitivity of 94.8% and a specificity of 95.0% for detecting early-stage CRC. Taken together, ColoC-mSTEM, based on a single methylation-specific site, is a promising diagnostic approach for the early detection of CRC which is perfectly suitable for the screening needs of CRC in primary healthcare institutions.

Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients.

The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, microsatellite instability status, tumor locations, recurrence risk factors, preoperative carcinoembryonic antigen levels, and adjuvant treatments were systematically evaluated.

In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index of 25.1 kg/m2. In the patient group without risk factors, no statistically significant difference was detected in disease-free survival (DFS) rates between those who received treatment and those who did not (p = 0.546). DFS rates of patients with >1 risk factor were statistically significantly lower than those with a single risk factor (p = 0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p < 0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was significantly higher in the group receiving capecitabine (p = 0.01).

The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity.

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.

While the overwhelming majority of colorectal carcinomas (CRC) are diagnosed as adenocarcinoma not otherwise specified, there are numerous under-recognised morphologic patterns of CRC. These patterns are recognised by the WHO, appear in reporting manuals for the American Joint Committee of Cancer, and/or are listed on synoptic reports, while many other variants have either fallen out of favour or are emerging as future bona fide patterns. Herein, we discuss 13 variants: serrated adenocarcinoma, micropapillary adenocarcinoma, medullary carcinoma, neuroendocrine carcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, adenosquamous carcinoma, adenoma-like adenocarcinoma, lymphoglandular complex-like CRC, carcinoma with sarcomatoid components, cribriform-comedo-type adenocarcinoma, undifferentiated carcinoma and low-grade tubuloglandular adenocarcinoma. The purpose of this review is to scrutinise these variants by assessing their clinical characteristics, morphologic cues, as well as pitfalls, and address their prognostic significance. Our analysis aims to bring clarity and updated understanding to these variants, offering valuable insights for pathologists. This contributes to more nuanced CRC diagnosis and treatment strategies, highlighting the importance of recognising a broad spectrum of morphologic patterns in CRC.

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.

Venous invasion (VI) in colorectal carcinoma influences treatment strategies, especially in early stages. Despite elastin staining effectiveness in detecting VI, guidelines for its routine application, including the optimal number of slides for staining, are limited.

Elastin staining was performed for VI assessment in patients with colorectal adenocarcinoma. Patients were categorised into two groups: single elastin stain group (SEG, n=248) and multiple elastin stain group (MEG, n=204).

The average number of elastin-stained blocks was 2±1.7, increasing to 3.3±1.9 in MEG. VI detection was significantly higher in patients in MEG (50.5%) compared with SEG (37.0%) (p=0.004). VI detection rate was higher in MEG (63.7%) than in SEG (46.0%) among patients with stage III-IV disease (p=0.011), but did not significantly differ among patients with stage I-II disease. Staining two blocks improved VI detection without additional gains from more stains. Compared with elastin performed on a single block, VI detected by elastin stain on two or more blocks did not significantly impact progression-free or disease-free survival with stage II patients.

Employing two elastin stains on separate blocks significantly enhances VI detection in colorectal carcinoma without additional benefits from more extensive staining. This study suggests that while increasing sensitivity for VI detection, staining beyond two blocks may not benefit prognostication and could be counterproductive, warranting further research. We emphasise the need for strategic use of the elastin stain and cautious interpretation of the increased detection sensitivity of multiple elastin stains.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value.

Colorectal cancer is an enormous health concern since it is among the most lethal types of malignancy. The manual examination has its limitations, including subjectivity and data overload. To overcome these challenges, computer-aided diagnostic systems focusing on image segmentation and abnormality classification have been developed. This study presents a two-stage approach for the automatic detection of five types of colorectal abnormalities in addition to a control group: polyp, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, serrated adenoma, adenocarcinoma. In the first stage, UNet3+ was used for image segmentation to locate the anomalies, while in the second stage, the Cross-Attention Multi-Scale Vision Transformer deep learning model was used to predict the type of anomaly after highlighting the anomaly on the raw images. In anomaly segmentation, UNet3+ achieved values of 0.9872, 0.9422, 0.9832, and 0.9560 for Dice Coefficient, Jaccard Index, Sensitivity, Specificity respectively. In anomaly detection, the Cross-Attention Multi-Scale Vision Transformer model attained a classification performance of 0.9340, 0.9037, 0.9446, 0.8723, 0.9102, 0.9849 for accuracy, F1 score, precision, recall, Matthews correlation coefficient, and specificity, respectively. The proposed approach proves its capacity to alleviate the overwhelm of pathologists and enhance the accuracy of colorectal cancer diagnosis by achieving high performance in both the identification of anomalies and the segmentation of regions.

Increased cancer survival leads to more patients requiring oncological follow-up. Debate about how best to coordinate this care has led to the proposed involvement of general practitioners (GPs) rather than continued reliance on hospital care. However, we still require patient opinions to inform this debate.

This qualitative interview study explored opinions about organization of follow-up care of patients treated curatively for breast and colorectal cancer. Thematic analysis was applied.

We interviewed 29 patients and identified three themes concerning care substitution: "benefits and barriers," "requirements," and "suitable patient groups." Benefits included accessibility, continuity, contextual knowledge, and psychosocial support. Barriers included concerns about cancer-specific expertise of GPs and longer waiting times. Requirements were sufficient time and remuneration, sufficient training, clear protocols, and shared-care including efficient communication with specialists.

According to patients with cancer, formal GP involvement appears feasible, although important barriers must be overcome before instituting care substitution. A possible solution are personalized follow-up plans based on three-way conversations with the specialist and the GP after the initial hospital care.

With adequate training, time, and remuneration, formal GP involvement could ensure more comprehensive care, possibly starting with less complex cases.

This purpose of this study was to evaluate the effect of pelvic floor muscle exercises (PFMEs) on bowel evacuation problems and health-related quality of life (HRQOL) following ostomy closure.

Randomized controlled trial.

Forty individuals following ostomy closure consented to participate in the study; 6 participants (15%) did not complete the trial (2 died and 2 required a second ostomy) yielding a study sample of 34. Participants were randomly allocated to an Exercise Group (EG, n = 17) and Control Group (CG, n = 17). The mean age of the EG was 55.7 (SD 12.6) years, whereas the mean age of the CG was 62.0 (SD 12.1) years. The study setting was the surgery clinic of 4 hospitals in Ankara, Turkey. Data were collected between December 2018 and May 2020.

The study intervention, PFME training by a clinician, was administered to participants in the EG; CG participants received no information regarding PFME. Data were collected during face-to-face interviews on the day before discharge and by phone at the first, second, third, and sixth months after surgery. A questionnaire was used for data collection that queried a demographic and pertinent clinical questions, along with the Assessment Form for Bowel Evacuation Habits and Psychosocial Problems, Wexner Scale, and the Short Form (SF-36) Health-related Quality of Life Scale. Descriptive statistics and Mann-Whitney U test, t-test, Pearson-χ2 test, Fisher's Exact test, Friedman test, and Cochran-Q test statistical analysis according to normal distribution were used in data evaluation.

The number of defecations in the EG was statistically significantly lower than the CG at the second, third, and sixth months (P = .002, P = .002, P = .001, respectively). In addition, the number of individuals experiencing night defecation was statistically significantly less in the EG compared to the CG at the second-, third-, and sixth-month follow-ups (P = .001, P = .001, P = .028, respectively). HRQOL scores were also significantly higher in the EG.

Pelvic floor exercises applied after ostomy closure are effective in reducing bowel evacuation and increasing quality of life. Given these findings, PFMEs are recommended for patients after ostomy closure.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths. The hippo pathway works as a regulator of organ growth and is often a target for mutations in cancer. Ferm domain containing protein 6 (FRMD6) is an activator of the hippo pathway. This study aimed to explore the role of FRMD6 in CRC and to determine how well it works as a prognostic factor among CRC patients.

The tumor expression of FRMD6 was evaluated using immunohistochemistry in 538 colorectal patients operated on at Helsinki University Hospital. We assessed FRMD6 expression with clinicopathological parameters and the impact of FRMD6 expression on survival.

Patients with a high FRMD6 expression exhibited a better prognosis (univariable hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81), with a 5-year disease-specific survival (DSS) of 66.3%. By contrast, patients with a low FRMD6 expression had a 5-year DSS of 52.8%. A high FRMD6 expression level served as an independent predictor for better survival in the Cox multivariable survival analysis (HR 0.53, 95% CI 0.33-0.86).

To our knowledge, this is the first study to show that a high FRMD6 expression is an independent marker for a better prognosis in CRC and could help determine the prognosis for CRC patients.

The disease burden of colorectal cancer in East Asia has been at a high level. However, the epidemiological characteristics of the disease burden in this region have not been systematically studied.

Data were obtained from the Global Burden of Disease 2019 program. Joinpoint analysis was used to identify long-term trends in mortality of colorectal cancer. Independent effects of age, period, and cohort were detected by the age-period-cohort model. The Bayesian age-period-cohort model was performed to predict the burden of colorectal cancer across East Asia by 2030.

From 1990 to 2019, the average annual percentage change (AAPC) showed upward trends in mainland China (1.05 [95% confidence interval (CI)], 0.82, 1.28) as well as Taiwan Province of China (1.81 [95% CI], 1.51, 2.10) but downward in Japan (-0.60 [95% CI], -0.70, -0.49) (P < 0.05). Attributable risk factors for colorectal cancer in East Asia remained stable over 30 years, while the risk of metabolic factors is noteworthy in the future. In the next decade, the age-standardized death rate (ASDR) of colorectal cancer in China was predicted to surpass that of Japan and South Korea in expectation.

The mortality of colorectal cancer is escalating in developing countries, while it is gradually declining in high-income countries across East Asia. Nonetheless, the disease burden of colorectal cancer in high-income countries remains substantial level.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant's methanolic root extract (BVR) against colon cancer cells. Studies were conducted in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3, 46.1, and 50.2 µg/mL for the LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of the cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. Nuclear double staining revealed the great proapoptotic BVR properties in HT-29 cells and subtle effect in LS180 cells. RT-qPCR with the relative quantification method showed significant changes in the expression of genes related to apoptosis in both the LS180 and HT-29 cells. The genes BCL2L1 (126.86-421.43%), BCL2L2 (240-286.02%), CASP3 (177.19-247.83%), and CASP9 (157.99-243.75%) had a significantly elevated expression, while BCL2 (25-52.03%) had a reduced expression compared to the untreated control. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93 ± 0.01, 122.92 ± 0.01, and 220.29 ± 0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+, and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62.60 ± 0.87% of enzyme inhibition. The chemical composition of BVR was determined using a UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). The results are very promising and encourage the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer, and were widely discussed alongside data from the literature.

Colorectal cancer (CRC) is a complex disease with diverse etiologies and clinical outcomes. Despite considerable progress in development of CRC therapeutics, challenges remain regarding the diagnosis and management of advanced stage metastatic CRC (mCRC). In particular, the five-year survival rate is very low since mCRC is currently rarely curable. Over the past decade, cancer treatment has significantly improved with the introduction of cancer immunotherapies, specifically immune checkpoint inhibitors. Therapies aimed at blocking immune checkpoints such as PD-1, PD-L1, and CTLA-4 target inhibitory pathways of the immune system, and thereby enhance anti-tumor immunity. These therapies thus have shown promising results in many clinical trials alone or in combination. The efficacy and safety of immunotherapy, either alone or in combination with CRC, have been investigated in several clinical trials. Clinical trials, including KEYNOTE-164 and CheckMate 142, have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab, respectively, for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC. Unfortunately, these drugs benefit only a small percentage of patients, with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients. To this end, primary and secondary resistance to immunotherapy remains a significant issue, and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response. This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC. The underlying rationale, challenges faced, and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Lymph node metastasis (LNM) is a crucial factor that determines the prognosis of T1 colorectal cancer (CRC) patients. We aimed to develop a practical prediction model for LNM in T1 CRC.

We conducted a retrospective analysis of data from 825 patients with T1 CRC who underwent radical resection at a single center in China. All enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3 using R software. Risk factors for LNM were identified through multivariate logistic regression analyses. Subsequently, a prediction model was developed using the selected variables.

The lymph node metastasis (LNM) rate was 10.1% in the training cohort and 9.3% in the validation cohort. In the training set, risk factors for LNM in T1 CRC were identified, including depressed endoscopic gross appearance, sex, submucosal invasion combined with tumor grade (DSI-TG), lymphovascular invasion (LVI), and tumor budding. LVI emerged as the most potent predictor for LNM. The prediction model based on these factors exhibited good discrimination ability in the validation sets (AUC: 79.3%). Compared to current guidelines, the model could potentially reduce over-surgery by 48.9%. Interestingly, we observed that sex had a differential impact on LNM between early-onset and late-onset CRC patients.

We developed a clinical prediction model for LNM in T1 CRC using five factors that are easily accessible in clinical practice. The model has better predictive performance and practicality than the current guidelines and can assist clinicians in making treatment decisions for T1 CRC patients.

Over the past few decades, substantial advancements have been achieved in the early detection and treatment of gastrointestinal oncological diseases. The survival rates of patients have significantly improved due to the expansion and enhancement of therapeutic and diagnostic options, leading to modifications in (neo-)adjuvant, perioperative, and palliative strategies, as well as the advent of personalized molecular therapy. Noteworthy progress has also been observed in primary, secondary, and tertiary prevention domains.Despite these advancements, gastrointestinal tumours continue to be a global health burden, with approximately 4 million new cases diagnosed annually. These constitute over a quarter of all tumour cases, with nearly one-third of all global tumour-related mortalities attributed to gastrointestinal tumours.Emerging evidence implicates aberrant differentiation of stem or progenitor cells in the pathogenesis of gastrointestinal tumour diseases. A confluence of clinically recognized risk factors, including high-fat diet, bile acid, microbiome alterations, and host factors, can instigate chronic inflammation. This disrupts stem cell homeostasis and precipitates malignant transformation. Consequently, environmental inflammation emerges as a critical risk factor warranting consideration in clinical cancer prevention and surveillance strategies.This review encapsulates the current understanding and recommendations in the prevention of selected gastrointestinal tumours, aiming to facilitate their integration into clinical practice. It underscores the need for continued research to further refine diagnostic and therapeutic strategies and improve patient outcomes.

Risk evaluation of lymph node metastasis for early-stage (T1 and T2) colorectal cancers is critical for determining therapeutic strategies. Traditional methods of lymph node metastasis prediction have limited accuracy. This systematic review aimed to review the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers.

A comprehensive search was performed of papers that evaluated the potential of artificial intelligence in predicting lymph node metastasis in early-stage colorectal cancers. Studies were appraised using the Joanna Briggs Institute tools. The primary outcome was summarizing artificial intelligence models and their accuracy. Secondary outcomes included influential variables and strategies to address challenges.

Of 3190 screened manuscripts, 11 were included, involving 8648 patients from 1996 to 2023. Due to diverse artificial intelligence models and varied metrics, no data synthesis was performed. Models included random forest algorithms, support vector machine, deep learning, artificial neural network, convolutional neural network and least absolute shrinkage and selection operator regression. Artificial intelligence models' area under the curve values ranged from 0.74 to 0.9993 (slide level) and 0.9476 to 0.9956 (single-node level), outperforming traditional clinical guidelines.

Artificial intelligence models show promise in predicting lymph node metastasis in early-stage colorectal cancers, potentially refining clinical decisions and improving outcomes.

CRD42023409094.

As a major public health issue, colorectal cancer causes 9.4% of total cancer-related deaths and comprises 10% of new cancer diagnoses worldwide. In the year 2023, an estimated 153,020 people are expected to receive an identification of colorectal cancer (CRC), resulting in roughly 52,550 fatalities anticipated as a result of this illness. Among those impacted, approximately 19,550 cases and 3750 deaths are projected to occur in individuals under the age of 50. Irinotecan (IRN) is a compound derived from the chemical structure of camptothecin, a compound known for its action in inhibiting DNA topoisomerase I. It is employed in the treatment strategy for CRC therapies. Comprehensive in vivo and in vitro studies have robustly substantiated the anticancer efficacy of these compounds against colon cancer cell lines. Blending irinotecan in conjunction with other therapeutic cancer agents such as oxaliplatin, imiquimod, and 5 fluorouracil enhanced cytotoxicity and improved chemotherapeutic efficacy. Nevertheless, it is linked to certain serious complications and side effects. Utilizing nano-formulated prodrugs within "all-in-one" carrier-free self-assemblies presents an effective method to modify the pharmacokinetics and safety portfolio of cytotoxic chemotherapeutics. This review focuses on elucidating the mechanism of action, exploring synergistic effects, and innovating novel delivery approaches to enhance the therapeutic efficacy of irinotecan.

Colorectal cancer (CRC) poses a significant threat to many human lives worldwide and survival following resection is predominantly stage dependent. For early-stage cancer, patients are not routinely advised to undergo additional post-operative adjuvant chemotherapy. Acceptable clinical management guidelines are well established for patients in pTNM stages I, III and IV. However, recommendations for managing CRC stage II patients remain controversial and many studies have been conducted to segregate stage II patients into low- and high-risk of recurrence using genomic, transcriptomic and proteomic molecular markers. As proteins provide valuable insights into cellular functions and disease state and have a relatively easy translation to the clinic, this review aims to discuss potential prognostic protein biomarkers proposed for predicting tumour relapse in early-stage II CRC. It is suggested that a panel of markers may be more effective than a single marker and further evaluation is required to translate these into clinical practice.

By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance.

Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test.

In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001).

Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer.

Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer.

• The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-κB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.