We interrogated two large national databases to explore the underlying mechanisms and institutional effects of the known association of enhanced survival with a higher lymph node yield (LNY) in non-metastatic colon cancer.

Clinical and pathological data for stage I-III colon adenocarcinomas were extracted from the CORECT-R (England, 2010-2020) and SEER database (USA, 2000-2020). A lymph node (LN) cut-off for the lack of clinically significant increase in nodal positivity was identified. A multivariable Cox-regression model was developed to study the effect of LNY on overall survival. Furthermore, institutional variations in LNY and their impact on survival were explored.

Patients were retrospectively included from the CORECT-R (n = 84,116) and SEER (n = 287,974) databases. No significant increase in nodal positivity was noted after a LN cut-off of 9. However, improved survival was noted in node-negative and node-positive cancers beyond this cut-off. A 1% risk-reduction concerning overall survival was reported for every node counted. We identified ten outlying institutions across England with an observed LNY greater or less than the expected, with no impact on overall survival.

We advocate incorporating LNY into patient and clinician discussions as a surrogate marker of tumour biology and prognosis rather than using LNY as a quality indicator.

Lymphadenectomy for rectal cancer is clearly defined by total mesorectal excision (TME). The analogous surgical strategy for the colon, the complete mesocolic excision (CME), follows the same principles of dissection in embryologically predefined planes.

This narrative review initially identified key issues related to lymphadenectomy of rectal and colon cancer. The subsequent search was based on PubMed and focused on meta-analyses. The endpoints for rectal cancer were the benefit of high tie versus low tie and the indications for lateral pelvic lymphadenectomy. For colon cancer the evidence for CME, for the longitudinal extent of resection, for the dissection of infrapyloric and gastroepiploic lymph nodes, for the number of lymph nodes and for the sentinel lymph node technique were used as endpoints.

An oncological benefit of the high tie cannot be derived from the current data. Lateral pelvic lymphadenectomy should only be selectively performed after chemoradiotherapy (CRT) in cases of remaining lymph nodes with suspected metastases. In most studies CME proved to be oncologically superior, especially in stage III. The longitudinal extent of resection should be at least 10 cm in both directions if the principles of CME are observed. Infrapyloric and gastroepiploic lymph node involvement is to be expected in 0.7-22% of cases, depending on patient selection, which justifies dissection, particularly in carcinomas of both flexure and the transverse colon. The minimum number of lymph nodes to be removed cannot be clearly derived from the available studies. Precisely performed CME and an optimal pathological work-up are important. The sentinel lymph node technique cannot currently be used as a criterion for limiting the extent of resection.

Both TME and CME are reliable standards for the lymphadenectomy in colorectal carcinomas. A lymphadenectomy that goes beyond this is reserved for selected cases and is partly the subject of currently ongoing studies.

Nonenlarged lymph node metastasis (NELNM) of rectal cancer is easily overlooked because these apparently normal lymph nodes are sometimes too small to measure directly using imaging techniques. Radiomic-based multiparametric imaging sequences could predict NELNM based on the primary lesion of rectal cancer. We aimed to study the performance of magnetic resonance imaging (MRI) radiomics derived from reduced field-of-view diffusion-weighted imaging (rDWI) and conventional DWI (cDWI) for the prediction of NELNM.

A total of 86 rectal cancer patients (60 and 26 patients in training and test cohorts, respectively), underwent multiparametric MRI. Radiomic features were extracted from the whole primary lesion of rectal cancer segmented on T2-weighted imaging (T2WI), rDWI, and cDWI, both with b-value of 800 s/mm2 and apparent diffusion coefficient (ADC) maps from both DWI sequences (rADC and cADC). The radiomic models based on the above imaging methods were built for the assessment of NELNM status. Their diagnostic performances were evaluated in comparison with subjective evaluation by radiologists.

rADC demonstrated a significant advantage over subjective assessment in predicting NELNM in both training and test cohorts (p ≤ 0.002). In the test cohort, rADC exhibited a significantly higher area under the receiver operating characteristics curve than cADC, cDWIb800, and T2WI (p ≤ 0.020) in assessing NELNM for region-of-interest (ROI) delineation while excelling over rDWIb800 for prediction of NELNM (p = 0.0498).

Radiomic features based on rADC outperformed those derived from T2WI and fDWI in predicting the NELNM status of rectal cancer, rADC was more advantageous than rDWIb800 in assessing NELNM.

Advanced rDWI excelled over cDWI in radiomic assessment of NELNM of rectal cancer, with the best performance observed for rADC, in contrast to rDWIb800, cADC, cDWIb800, and T2WI.

rDWI, cDWI, and T2WI radiomics could help assess NELNM of rectal cancer. Radiomic features based on rADC outperformed those based on rDWIb800, cADC, cDWIb800, and T2WI in predicting NELNM. For rDWI radiomics, the ADC map was more accurate and reliable than DWI to assess NELNM for region of interest delineation.

Colon cancer remains a major cause of cancer-related deaths worldwide, with recurrence post-surgery, posing a significant challenge. Accurate lymph node (LN) staging is critical for prognosis and treatment decisions, but traditional systems, such as the AJCC TNM, often fail to predict recurrence. This study compares the prognostic performance of three LN staging systems Lymph Node Ratio (LNR), Log Odds of Metastatic Lymph Nodes (LODDS), and pN in colon cancer.

We retrospectively analyzed data from 812 colon cancer patients who underwent radical surgery at two tertiary hospitals (2010-2019). LNR, LODDS, and pN were calculated, and their ability to predict postoperative recurrence was assessed using C-index, AIC, BIC, and ROC curves. Machine learning models (LASSO, Random Forest, XGBoost) identified the most predictive staging system. A nomogram was developed integrating the best staging system with clinical factors to predict postoperative recurrence.

The study identified LNR as the most predictive staging system for colon cancer. The nomogram based on LNR, along with other variables such as T stage and tumor grade, demonstrated superior predictive performance compared to individual staging systems. In the training cohort, the nomogram achieved an AUC of 0.791 at 1 year, 0.815 at 3 years, and 0.789 at 5 years. The C-index for the nomogram was 0.788, higher than that of LNR (C-index = 0.694) and tumor stage (C-index = 0.665). The nomogram successfully stratified patients into high- and low-risk groups, with higher risk scores correlating with poorer survival outcomes. The validation cohort confirmed the robustness of the model, showing that patients with lower risk scores had better prognoses.

LNR is an effective predictor of recurrence and prognosis in colon cancer. The nomogram developed from LNR and other clinical factors offers superior prognostication and can aid in personalized treatment strategies.

Lymph node (LN) examination is important for staging colorectal cancer. Examining < 12 LN has been associated with a poor prognosis. However, surgical and pathological advances have led to increase examined LN, necessitating the reassessment of the best cutoff for prognosis.

We reviewed patients with stage II-III colon cancer from the Yonsei Cancer Center Registry (YCC) database and the Netherlands Cancer Registry (NCR). The optimal LN cutoff was determined by comparison with hazard ratio (HR) in 12 LN. We compared higher vs. lower LN cutoff effects on a 6-year overall survival (OS).

From 2005 to 2015, the proportion with < 12 LN decreased significantly (P < .001). There was no significant association between 6-year OS and LN yield in all stages II-III patients (HR = 1.21, P = .116), stage II (HR = 1.39, P = .068), and stage III (HR = 1.18, P = .297) colon cancer based on the standard 12 LN examined, whereas the 20 LN cutoff examined was associated with a significant increase in 6-year OS in all patients (HR = 1.51, P < .001). Multivariate regression revealed a significant decrease in 6-year OS in stage II (HR = 1.39, P = .026) and stage III (HR = 1.47, P < .001) with < 20 LN yield. In the NCR, < 20 LN was associated with poorer 6-year OS in stage II-III patients (HR = 1.25, P < .001), stage II (HR = 1.43, P < .001), and stage III (HR = 1.13, P = .007).

Over the past decade, inadequate LN examinations have significantly decreased. Compared to < 12 LN, < 20 LN examined is more associated with a worse prognosis in patients who underwent surgery.

Analysis of existing literature on lymph node yield (LNY) in neck dissection (ND) for head and neck squamous cell carcinomas (HNSCC) used as a prognostic factor and an indication of treatment adequacy.

PubMed, EMBASE and Web of Science databases were systematically searched from January 2010 to June 2023. Inclusion criteria encompassed studies on mucosal HNSCC patients undergoing ND with data on LNY and its association with survival outcomes. The quality assessment followed the REMARK guidelines.

Among 29 included studies, minimum LNY tresholds associated with improved survival outcomes ranged from 10 to 36.5 nodes. The heterogeneity in subsite involvement and cN0/cN + status constituted a challenge in establishing a consensus cutoff. The review highlights the need for standardized surgical techniques and pathological assessments to ensure data comparability.

LNY is a prognostic indicator and could reflect ND quality in HNSCC.

Lateral lymph node dissection (LLND) is getting global attention as an a surgical option to reduce local recurrence in locally advanced rectal cancer. As the transanal total mesorectal excision (TaTME) is gaining popularity worldwide, a novel LLND approach was established adopting a two-team approach that combines the transabdominal and transanal approaches using the TaTME technique. This narrative review describes the advantages, anatomical landmarks, surgical techniques, and pitfalls of transanal LLND (TaLLND). The advantages of TaLLND include a magnified view and enhanced maneuverability of the laparoscopic instruments in the deep pelvis. TaLLND is also beneficial for LLND in patients with a history of pelvic surgery because surgeons can have access to the areas unaffected by previous surgery. To master the TaLLND technique, the procedure should be understood according to the following steps: S4 nerve identification, lateral space entry, lateral dissection, obturator vein, artery, and nerve identification, dissection along the external iliac vein, medial dissection, median and bottom dissection, dissection along the internal iliac artery, and dissection along the obturator nerve. TaLLND can be applied to highly advanced disease that requires combined resection of the major internal iliac vessels, pelvic nerves, or adjacent organs. In such cases, simultaneous transanal and transabdomiinal LLND utilizing a two team approach has advantages as these approaches can provide mutual complementary roles. TaLLND is expected to overcome the difficulty of transabdominal LLND and improve the quality of LLND.

Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, with colon cancer accounting for approximately 60% of all CRC cases. Surgery remains the primary and most effective treatment. Robotic-assisted surgery (RAS) has emerged as a promising approach for colon cancer resection. This retrospective study compares RAS and laparoscopic-assisted surgery (LSS) for stage I-III colon cancer resections at a single medical center in East Asia. Methods: Between 1 January 2018, and 29 February 2024, patients undergoing colectomy were classified into right-side and left-side colectomies. Propensity score matching was conducted based on age group, gender, ASA score, and BMI to ensure comparability between groups. After matching, there were 50 RAS and 200 LSS cases for right colectomy (RC), and 129 RAS and 258 LSS cases for left colectomy (LC). Perioperative outcomes were compared between the two surgical approaches. The primary outcomes were recovery milestones, while secondary outcomes included complications and postoperative pain scores. Results: RAS demonstrated faster recovery milestones compared to LSS (hospital stay: 6.5 vs. 10.2 days, p = 0.005 for RC; 5.5 vs. 8.2 days, p < 0.001 for LC). RAS also resulted in lower rates of ileus (14% vs. 26%, p = 0.064 for RC; 6.2% vs. 15.9%, p = 0.007 for LC) and higher lymph node yields (31.4 vs. 26.8, p = 0.028 for RC; 25.8 vs. 23.9, p = 0.066 for LC). Major complication rates showed no significant difference between RAS and LSS (4.0% vs. 7.0%, p = 0.746 for RC; 4.7% vs. 3.1%, p = 0.563 for LC). Patients in the RAS group experienced earlier diuretic phases and reported significantly lower postoperative pain scores (3.0 vs. 4.1, p = 0.011 for RC; 2.9 vs. 4.1, p < 0.001 for LC). Conclusions: Robotic-assisted surgery is associated with faster recovery, lower rates of ileus (LC), higher lymph node yield (RC) and reduced postoperative pain compared to laparoscopic-assisted surgery for colon cancer resection.

The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of the Node-RADS classification of staging computed tomography (CT) images to categorize and stage lymph nodes in patients with colon cancer.

All patients were surgically resected and the lymph nodes were histopathological analyzed. All investigated lymph nodes were scored in accordance to the Node-RADS classification by two experienced radiologists. Interreader variability was assessed with Cohen's kappa analysis, discrimination analysis was performed with Mann-Whitney-U test and diagnostic accuracy was assessed with receiver-operating characteristics (ROC) curve analysis.

Overall, 108 patients (n = 49 females, 45.3%) with a mean age of 70.08 ± 14.34 years were included. In discrimination analysis, the total Node-RADS score showed statistically significant differences between N- and N + stage (for reader 1: mean 1.89 ± 1.09 score for N- versus 2.93 ± 1.62 score for N+, for reader 2: 1.33 ± 0.48 score for N- versus 3.65 ± 0.94 score for N+, p = 0.001, respectively). ROC curve analysis for lymph node discrimination showed an area under the curve of 0.68. A threshold value of 2 resulted in a sensitivity of 0.62 and a specificity of 0.71.

Node-RADS score derived from staging CT shows only limited diagnostic accuracy to correctly predict nodal positivity in colon cancer. The interreader variability seems to be high and should question the clinical translation for this tumour entity.

The number of lymph nodes (LNs) dissected during surgery has become an interesting topic. Simple intuition always leads us to believe that dissecting more LNs will result in more accurate pathological staging and assurance of surgical quality. However, when the number of LNs dissected reaches a certain threshold, the patient's prognosis does not continue to improve as the number of dissected nodes increases. Instead, an increase in the number of dissected LNs may be accompanied by a higher incidence of complications. Currently, there are only less than 40% of colorectal cancer patients undergoing adequate LN evaluation. Therefore, obtaining a sufficient number of LNs in clinical practice is extremely challenging. How to further address the insufficiency of LN dissection due to various reasons, which results in concerns of surgeons about patient prognosis, is currently a critical focus.

To investigate the effect of preoperative carbon nanoparticle tracing technique via colonoscopy on the five-year overall survival and disease-free survival rates in patients undergoing radical resection for colorectal cancer.

A retrospective cohort study was conducted to collect data from patients diagnosed with colorectal cancer who underwent radical resection with complete postoperative pathological information at the First Affiliated Hospital of Chongqing Medical University from March 2013 to February 2017. Patients with multiple primary cancers were excluded, resulting in 2,237 eligible patients in the study. Of these, 368 patients were lost to follow-up within five years after surgery, resulting in a final sample of 1,869 patients. These patients were then divided into two groups: 758 patients who underwent preoperative carbon nanoparticle tracing technique via colonoscopy (CAS group) and 1,111 patients who did not undergo carbon nanoparticle tracing (non-CAS group). Survival curves for both overall survival and disease-free survival were plotted for both groups based on follow-up results. Univariate and multivariate analyses were performed to investigate the effect of carbon nanoparticle tracing technique on the 5-year overall survival and disease-free survival rates in patients, as well as to explore the factors influencing these outcomes.

The results showed that the total number of lymph nodes detected in the tracing group 15(11,19) was significantly higher than that in the non-tracing group 11(7,15), with a statistically significant difference (p<0.05). The 5-year overall survival rates were 90.8% in the CAS group and 87.4% in the non-CAS group, and, while the disease-free survival rate were 88.5% and 83.4%, respectively. However, the differences between 5-year overall survival and disease-free survival between the two groups were not statistically significant (p>0.05). Both univariate and multivariate cox regression analyses demonstrated that patient age, tumor stage, postoperative chemoradiotherapy, postoperative radiotherapy, and postoperative tumor recurrence were independent factors influencing the 5-year overall survival and disease-free survival rates in colorectal cancer patients.

Carbon nanoparticle tracing technique can effectively increase the total detected number of lymph nodes in patients with radical resection for colorectal cancer, but it does not significantly impact the 5-year overall survival and disease-free survival rates in these patients.

The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system.

We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database.

This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00 months (95%CI 46.97-63.03), 48.00 months (95%CI 40.65-55.35), and 68.00 months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N stage, presence of perineural infiltration, number of tumor deposits and number of positive regional lymph nodes were identified as independent prognostic risk variables (p < 0.05). In comparison to the conventional TNM staging model, the Cox proportional risk regression model exhibited a higher C-index. After controlling for competing risk events, age, N stage, presence of perineural infiltration, number of tumor deposits, number of regional lymph nodes examined, and number of positive regional lymph nodes were independent predictors of the risk of cancer-specific mortality (p < 0.05).

We have developed a prognostic model to predict the survival of patients with synchronous CRLM who undergo preoperative chemotherapy and surgery. This model has been tested internally and externally, confirming its accuracy and reliability.

Colorectal cancer (CRC) remains a significant global health burden, necessitating a thorough understanding of prognostic and predictive factors to enhance patient outcomes. This systematic review aims to comprehensively evaluate prognostic and predictive determinants in CRC, encompassing both traditional and emerging biomarkers. A systematic search of major electronic databases was conducted to identify relevant studies published from 1995 up to 2024. Eligible articles were critically appraised, and data extraction was performed according to predefined criteria. The prognostic determinants examined included clinicopathological features such as tumor stage, grade, and lymph node involvement, as well as molecular biomarkers including RAS, BRAF, and MSI status. Predictive determinants encompassed biomarkers influencing response to targeted therapies and immunotherapy, such as HER2 and Immunoscore. The review also explores novel prognostic and predictive markers, including tumor microenvironment characteristics and liquid biopsy-based biomarkers. Synthesizing evidence from diverse studies, this review provides insights into the prognostic and predictive landscape of CRC, highlighting the potential clinical implications of identified determinants. Understanding the multifaceted nature of prognostic and predictive factors in CRC is imperative for the advancement of personalized treatment strategies and improvement of patient outcomes.

Lymph node status is a well-established prognostic factor for colon cancer, but the optimal number of nodes for accurate staging remains unclear. This study explored the relationship between lymph node yield (LNY) and 5-year mortality rates in colon cancer patients in New Zealand.

Data from the New Zealand Cancer Registry were retrospectively analyzed for patients with TNM stage I, II, and III colon cancer between August 2003 and December 2021, with follow-up until January 2024. The primary outcome was the 5-year all-cause mortality rate, with LNY, age, sex, ethnicity, tumor site, district health board (DHB), and the number of positive nodes as covariates. Statistical analyses included univariate analysis, Cox regression modeling, and chi-squared tests.

LNY was a significant predictor of 5-year mortality risk (hazard ratio 0.985, p < 0.0001), adjusted for age, sex, ethnicity, tumor site, and DHB. The strongest association between LNY and mortality rate was observed at 12 nodes. Further increases in LNY beyond 22 nodes did not lead to statistically significant differences in mortality rates. Lymph node ratio (LNR) was strongly associated with survival in stage III colon cancer, independent of LNY and the number of positive nodes.

Higher LNY is significantly associated with reduced 5-year mortality rates in stage I-III colon cancer up to the 22-node mark. The strong correlation between LNR and mortality highlights its potential value for improving treatment planning in future clinical practice.

The main purpose of the study is to comprehensively evaluate population-level survival disparities stage-by-stage, according to specific anatomical colon segments, and based on prognosis as defined by lymph nodes among patients who have undergone curative resection for non-metastatic colon cancer.

The study was conducted from the Surveillance Epidemiology and End Result (SEER) program from the USA. Patients who underwent surgery for colon adenocarcinoma between 2000 and 2019 were identified. Demographics and clinical and pathologic factors were compared amongst each other according to different colon segments, stages, and time periods.

A total of 482,672 patients were identified and 195,105 of them met the inclusion criteria. Patients with proximal cancers were significantly older, more likely to be female, had a higher number of lymph nodes, and node positivity (p < 0.001). During the study period, an almost 10% improvement in overall survival rate was observed at 3 and 5 years for each colon site and stage (p < 0.05).

The study's findings revealed a notable improvement in overall and cancer-specific survival rates across all colon segments and stages in patients who underwent curative treatment for non-metastatic primary colon cancer from a nationwide database.

Colorectal cancer (CRC) has a 5-year overall survival rate of over 60%. The decrease in the rate of metastatic disease is due to screening programs and the population's awareness of healthy lifestyle. Similarly, advancements in surgical methods and the use of adjuvant chemotherapy have contributed to a decrease in the recurrence of resected disease. Before evaluating a patient's treatment, it is recommended to be discussed in a multidisciplinary tumor board. In stage II tumors, the pathologic characteristics of poor prognosis must be known (T4, number of lymph nodes analyzed less than 12, lymphovascular or perineural invasion, obstruction or perforation, poor histologic grade, presence of tumor budding) and it is mandatory to determine the MSI/MMR status for avoiding administering fluoropyridimidines in monotherapy to patients with MSI-H/dMMR tumors. In stage III tumors, the standard treatment consists of a combination of fluoropyrimidine (oral or intravenous) with oxaliplatin for 6 months although the administration of CAPOX can be considered for 3 months in low-risk tumors. Neoadjuvant treatment is not consolidated yet although immunotherapy is achieving very good preliminary results in MSI-H patients. The use of ctDNA to define the treatment and monitoring of resected tumors is only recommended within studies. These guidelines are intended to help decision-making to offer the best management of patients with non-metastatic colon cancer.

Poly(lactide-co-glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA (Mw = 13,900) was synthesized by ring-opening polymerization in the presence of a biocompatible zinc-proline initiator through a green route. Irinotecan (Ir) loaded with efficient PLGA core-lipid shell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin, by a nanoprecipitation method, and the fabricated LPs were designated as P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were further validated for their physicochemical properties and biological potential for colon cancer application. The potential delivery of a poorly water-soluble chemotherapeutic drug (Ir) was studied for the treatment of colon cancer. LPs were successfully prepared, providing controlled size (80-120 nm) and surface charge (∼ -35 mV), and the sustained release properties and cytotoxicity against CT-26 colon cancer cells were studied. The in vivo biodistribution and tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice showed promising results for tumor uptake and retention for a prolonged time period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant tumor growth delay as compared to untreated and blank formulation-treated groups in CT-26 (subcutaneous tumor model) after 4 treatments of 10 mg irinotecan/kg dose. The biocompatibility and safety of the LPs were confirmed by an acute toxicity study of the optimized formulation. Overall, this proof-of-concept study demonstrates that the PLGA-based LPs improve the efficacy and bioavailability and decrease neutropenia of Ir to combat colon cancer.

To develop and evaluate a nomogram that integrates clinical parameters with deep learning radiomics (DLR) extracted from Magnetic Resonance Imaging (MRI) data to enhance the predictive accuracy for preoperative lymph node (LN) metastasis in rectal cancer.

A retrospective analysis was conducted on 356 patients diagnosed with rectal cancer. Of these, 286 patients were allocated to the training set, and 70 patients comprised the external validation cohort. Preprocessed T2-weighted and diffusion-weighted imaging performed preoperatively facilitated the extraction of DLR features. Five machine learning algorithms-k-nearest neighbor, light gradient boosting machine, logistic regression, random forest, and support vector machine-were utilized to develop DLR models. The most effective algorithm was identified and used to establish a clinical DLR (CDLR) nomogram specifically designed to predict LN metastasis in rectal cancer. The performance of the nomogram was evaluated using receiver operating characteristic curve analysis.

The logistic regression classifier demonstrated significant predictive accuracy using the DLR signature, achieving an Area Under the Curve (AUC) of 0.919 in the training cohort and 0.778 in the external validation cohort. The integrated CDLR nomogram exhibited robust predictive performance across both datasets, with AUC values of 0.921 in the training cohort and 0.818 in the external validation cohort. Notably, it outperformed both the clinical model, which had AUC values of 0.770 and 0.723 in the training and external validation cohorts, respectively, and the stand-alone DLR model.

The nomogram derived from multiparametric MRI data, referred to as the CDLR model, demonstrates strong predictive efficacy in forecasting LN metastasis in rectal cancer.

The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features.

In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis.

The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884-0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769-1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673-0.998) in the test cohort.

We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients.

The effect of the number of lymph node dissections (LNDs) during radical resection for colorectal cancer (CRC) on overall survival (OS) remains controversial.

To investigate the association between the number of LNDs and OS in patients with tumor node metastasis (TNM) stage I-II CRC undergoing radical resection.

Patients who underwent radical resection for CRC at a single-center hospital between January 2011 and December 2021 were retrospectively analyzed. Cox regression analyses were performed to identify the independent predictors of OS at different T stages.

A total of 2850 patients who underwent laparoscopic radical resection for CRC were enrolled. At stage T1, age [P < 0.01, hazard ratio (HR) = 1.075, 95% confidence interval (CI): 1.019-1.134] and tumour size (P = 0.021, HR = 3.635, 95%CI: 1.210-10.917) were independent risk factors for OS. At stage T2, age (P < 0.01, HR = 1.064, 95%CI: 1.032-1.098) and overall complications (P = 0.012, HR = 2.297, 95%CI: 1.200-4.397) were independent risk factors for OS. At stage T3, only age (P < 0.01, HR = 1.047, 95%CI: 1.027-1.066) was an independent risk factor for OS. At stage T4, age (P < 0.01, HR = 1.057, 95%CI: 1.039-1.075) and body mass index (P = 0. 034, HR = 0.941, 95%CI: 0.890-0.995) were independent risk factors for OS. However, there was no association between LNDs and OS in stages I and II.

The number of LDNs did not affect the survival of patients with TNM stages I and II CRC. Therefore, insufficient LNDs should not be a cause for alarm during the surgery.

Background and Objectives: Colorectal cancer (CRC) poses a major global health challenge, with high incidence rates and ongoing treatment debates. Adjuvant chemotherapy benefits for high-risk subgroups, particularly stage II disease, remain controversial. This study seeks to clarify this issue by specifically examining the impact of adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS) in patients diagnosed with T4 colon cancer. Materials and Methods: This retrospective study analyzed patients undergoing radical surgery for T4 colon cancer between 2002 and 2023. Results: Our study of 184 pT4 pN0 colon cancer patients revealed that 79.3% received adjuvant chemotherapy. Multivariate analysis demonstrated significant DFS improvement: a 60% reduction in risk for those who received adjuvant therapy (0.40 95% CI: 0.25-0.62, p < 0.001). Lymphovascular invasion (LVI) and adjuvant treatment were also significantly associated with OS. Adjuvant treatment reduced mortality by 60% (HR: 0.40, 95% CI: 0.23-0.68, p = 0.001). Patients with LVI had a 1.9-fold increase in mortality (HR: 1.94, 95% CI: 1.17-3.20, p = 0.011). These findings underscore the potential value of adjuvant chemotherapy and highlight the importance of treatment completion in managing T4 colon cancer. Conclusions: Our study identifies LVI and adjuvant chemotherapy as key prognostic factors in T4 colon cancer patients. These results support the consideration of adjuvant chemotherapy in this patient population.

Cancer dissemination to lymph nodes (LN) is associated with a worse prognosis, increased incidence of distant metastases and reduced response to therapy. The LN microenvironment puts selective pressure on cancer cells, creating cells that can survive in LN as well as providing survival advantages for distant metastatic spread. Additionally, the presence of cancer cells leads to an immunosuppressive LN microenvironment, favoring the evasion of anti-cancer immune surveillance. However, recent studies have also characterized previously unrecognized roles for tumor-draining lymph nodes (TDLNs) in cancer immunotherapy response, including acting as a reservoir for pre-exhausted CD8+ T cells and stem-like CD8+ T cells. In this review, we will discuss the spread of cancer cells through the lymphatic system, the roles of TDLNs in metastasis and anti-cancer immune responses, and the therapeutic opportunities and challenges in targeting LN metastasis.

Radiomics has been used in the diagnosis of tumor lymph node metastasis (LNM). However, to date, most studies have been based on intratumoral radiomics. Few studies have focused on the use of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) peritumoral radiomics for the diagnosis of LNM in colorectal cancer (CRC).

Determining the value of radiomics features extracted from 18F-FDG PET/CT images of the peritumoral region in predicting LNM in patients with CRC.

The clinical data and preoperative 18F-FDG PET/CT images of 244 CRC patients were retrospectively analyzed. Intratumoral and peritumoral radiomics features were screened using the mutual information method, and least absolute shrinkage and selection operator regression. Based on the selected radiomics features, a radiomics score (Rad-score) was calculated, and independent risk factors obtained from univariate and multivariate logistic regression analyses were used to construct clinical and combined (Radiomics + Clinical) models. The performance of these models was evaluated using the DeLong test, while their clinical utility was assessed by decision curve analysis. Finally, a nomogram was constructed to visualize the predictive model.

The most optimal set of features retained by the feature filtering process were all peritumoral radiomic features. Carcinoembryonic antigen levels, PET/CT-reported lymph node status and Rad-score were found to be independent risk factors for LNM. All three LNM risk assessment models exhibited good predictive performance, with the combined model showing the best classification results, with areas under the curve of 0.85 and 0.76 in the training and validation groups, respectively. The DeLong test revealed that the performance of the combined model was superior to that of the clinical and radiomics models in both the training and validation groups, although this difference was only statistically significant in the training group. DCA indicated that the combined model displayed better clinical utility.

18F-FDG PET/CT peritumoral radiomics is uniquely suited to predict the presence of LNM in patients with CRC. In particular, the predictive efficacy of LNM for precision therapy and individualized patient management can be improved by using a combination of clinical risk factors.

To prospectively determine the influence of variations of surgical radicality and surgical quality on long-term outcome in patients with stage I-III colon cancer.

From a prospective multicenter cohort study including 1040 patients undergoing surgery for colorectal cancer from 09/2001 to 06/2005 in nine Swiss and one German hospital, 423 patients with stage I-III colon cancer were selected and analyzed. Surgeons and pathologists filled in standardized forms prospectively assessing items of oncosurgical radicality and quality. Patients had standardized follow-up according to national guidelines.

Follow-up was median 6.2 years (range 0.3-10.4) showing a 5-year disease-free survival/overall survival of 83 %/87 % in stage I (n = 85), 69 %/77 % in stage II (n = 187), and 53 %/61 % in stage III (n = 151) colon cancer. Despite remarkable variations of oncosurgical radicality and quality, the multivariate model revealed that mainly quality items correlated significantly with disease-free survival (surgical tumor lesion HR 2.12, p = 0.036, perioperative blood transfusion HR 1.67, p = 0.018, emergency resection HR 1.74, p = 0.035) and overall survival (early venous ligation HR 0.66, p = 0.023, surgical tumor lesion HR 2.28, p = 0.027, perioperative blood transfusion HR1.79, p = 0.010, emergency resection HR 1.88, p = 0.026), while radicality parameters (length of specimen, distance of the tumor to nearest bowel resection site, number of lymph nodes, height of resected mesocolon and of central vascular dissection) did not.

Surgical quality seems to have a stronger impact on oncologic long-term outcome in stage I - III colon cancer than surgical radicality.

Australia's National Bowel Cancer Screening Program consists of an immunohistochemical faecal occult blood test, targeting adults aged 50-74. Existing literature supports the principle of early detection of colorectal cancer (CRC) via national screening, but little is known about the association between colonoscopy or polypectomy rates and CRC stage over time. The aim of this study is to identify the longitudinal change to colonoscopy and polypectomy rates, and any stage shift associated with this screening program.

A retrospective data-linkage study was performed using the Australian national health database (Medicare) to obtain colonoscopy and polypectomy rates between 1998 and 2017. A second prospective database of CRC resection specimens was analysed for this period. The cohort was divided based on time intervals related to the National Bowel Cancer Screening Program: pre-commencement 1998-2006 (Period A), immediately post-commencement 2007-2011 (Period B), and subsequent years 2012-2017 (Period C). Linear regression was used to test relation between annualized predictor and response variables.

Annual colonoscopy rates doubled, and polypectomy rates tripled during the study (P < 0.001). Annual colonoscopy rate correlated to a lower T-stage (P = 0.038) and lower N-stage (P = 0.026), and there was a 7% increase in early CRC (stage I-II) in Period C (P < 0.001). Across the study period there was also a significant increase in right-sided tumours, and concurrent MMR deficiency and BRAF mutation.

Polypectomy and colonoscopy rates increased after the introduction of the National Bowel Cancer screening program. There was a clinically significant shift to earlier CRC stage which manifested 5 years after its implementation.

In the context of an increasing older population, knowing the surgical outcomes of older patients is of paramount importance to define a comprehensive strategy for colon cancer treatment in these patients. This study aimed to analyze the surgical outcomes and survival of patients over 80 years old undergoing surgery for colon cancer.

This is an observational retrospective longitudinal study of patients over 80 years old with colon cancer diagnosis who underwent surgery for this condition, between 2018 and 2021, in a Portuguese hospital. Demographic and clinical features were characterized. Kaplan-Meier method was used for survival analysis.

Out of 90 patients in the study, 41.1% were female. The majority (56.7%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0, with a median Charlson Comorbidity Index of 7.0. Tumors were primarily located in the right colon (52.2%) and sigmoid colon (25.6%), with most patients having stage II (35.6%) or stage III (25.5%) disease. Elective surgeries accounted for 73% of procedures, and 80.0% had curative intent, with laparoscopic surgery performed in 66.7% of cases. Only 8.3% of those undergoing curative-intent procedures received adjuvant chemotherapy. Emergent admissions were associated with more advanced cancer stages, higher rates of palliative intent procedures (45.8% versus 10.6%, p < 0.001), and more open surgeries (75.0% versus 9.1%, p < 0.001) when compared to elective procedures. Postoperative mortality was higher in the emergent group (20.8% versus 10.6%), though there was no association between the type of admission and postoperative complications. Median overall survival for all patients was 36.7 (95% CI 28.1 to 45.3) months, with significant differences between curative-intent and palliative surgeries (median of 39.8 (95% CI 32.6 to 47.0) versus 10.6 (95% CI 0.67 to 20.5) months, p = 0.015). The elective group of patients had significantly better overall survival compared to the emergent group (median of 36.7 (95% CI 30.7 to 42.7) versus 11.9 (95% CI 6.0 to 17.8) months, p = 0.01). Among the patients who underwent curative-intent procedures, there were no significant differences in overall or disease-free survival between elective and emergent groups.

Despite the increased complexity of managing older patients, particularly in emergent cases, these findings emphasize the importance of elective, curative-intent surgeries to optimize overall survival. Effective treatment strategies and perioperative management tailored to this age group are essential for improving surgical outcomes and extending survival in elderly colon cancer patients.

In patients with stage II colon cancer (CC) undergoing minimally invasive surgery, the association between the clinical significance of lymph node yield and tumor localization remains unknown. We aimed to determine the optimal number of lymph nodes to be retrieved based on tumor localization in patients with stage II CC undergoing minimally invasive surgery.

This was a multicenter retrospective study. Overall, 263 patients with stage II CC who underwent laparoscopic surgery between January 1, 2008 and December 31 were enrolled. The primary outcome was the optimal number of lymph nodes retrieved based on tumor localization.

The median number of retrieved lymph nodes was 30 and 26 in the right-(n = 125) and left-sided (n = 138) CC groups, respectively (p = .0007). Inadequate dissection (<12 nodes) occurred in 4.2% of patients: 1.6% in the right-sided CC group and 6.5% in the left-sided CC group. Multivariate Cox regression analysis showed a decreasing trend in adjusted hazard ratios with increasing nodes, with an optimal cutoff of 15 lymph nodes in the left-sided CC group (adjusted hazard ratio, 5.868; 95% confidence interval, 1.247-27.62; p = .02). Lymph node yield was not independently associated with survival in the right-sided CC group.

For patients with left-sided stage II CC undergoing laparoscopic surgery, aiming for at least 15 retrieved lymph nodes may be optimal for accurate staging and prognostic assessment. The optimal lymph node yield likely varies based on tumor location, requiring further investigation in right-sided CC.

To construct and validate multiparametric MR-based radiomic models based on primary tumors for predicting lymph node metastasis (LNM) following neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) patients.

A total of 150 LARC patients from two independent centers were enrolled. The training cohort comprised 100 patients from center A. Fifty patients from center B were included in the external validation cohort. Radiomic features were extracted from the manually segmented volume of interests of the primary tumor before and after nCRT. Feature selection was performed using multivariate logistic regression analysis. The clinical risk factors were selected via the least absolute shrinkage and selection operator method. The radiologist's assessment of LNM was performed. Eight models were constructed using random forest classifiers, including four single-sequence models, three combined-sequence models, and a clinical model. The models' discriminative performance was assessed via receiver operating characteristic curve analysis quantified by the area under the curve (AUC).

The AUCs of the radiologist's assessment, the clinical model, and the single-sequence models ranged from 0.556 to 0.756 in the external validation cohort. Among the single-sequence models, modelpost_DWI exhibited superior predictive power, with an AUC of 0.756 in the external validation set. In combined-sequence models, modelpre_T2_DWI_post had the best diagnostic performance in predicting LNM after nCRT, with a significantly higher AUC (0.831) than those of the clinical model, modelpre_T2_DWI, and the single-sequence models (all p < 0.05).

A multiparametric model that incorporates MR radiomic features before and after nCRT is optimal for predicting LNM after nCRT in LARC.

This study enrolled 150 LARC patients from two independent centers and constructed multiparametric MR-based radiomic models based on primary tumors for predicting LNM following nCRT, which aims to guide therapeutic decisions and predict prognosis for LARC patients.

The biological characteristics of primary tumors and metastatic LNs are similar in rectal cancer. Radiomics features and clinical data before and after nCRT provide complementary tumor information. Preoperative prediction of LN status after nCRT contributes to clinical decision-making.

The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood.

This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the "limma" package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration.

Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment.

The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.

As a natural nonflavonoid polyphenol compound, resveratrol is the main functional component of Reynoutria japonica and has anti-inflammatory, antioxidant, antiviral, and other physiological activities. In this study, the effect of resveratrol on the viability of RAW264.7 cells was examined, and murine norovirus (MNV-1) was used as a surrogate for human norovirus to evaluate the inhibitory effect of resveratrol. The concentrations of resveratrol resulting in 50% cytotoxicity (CC50) for RAW264.7 cells were 21.32 and 24.97 μg/mL after 24 and 48 h of incubation, respectively, and resveratrol at a concentration lower than the half-effective inhibitory concentration (EC50) could not damage cell DNA. The EC50 of resveratrol on MNV-1 in infected RAW264.7 cells was determined to equal 5.496 μg/mL. After RAW264.7 cells, virus, and a fresh mixture of virus and RAW264.7 cells were treated with resveratrol solution for 1 h (denoted cell pre-treatment, virus pre-treatment, and mixture coprocessing), the RAW264.7 cells obtained after cell pre-treatment exhibited lower virus infection, and MNV-1 obtained after virus pre-treatment and mixture coprocessing showed a decreased infectious capacity. The inhibition ratio of resveratrol on MNV-1 did not significantly differ between the treatments at 4 and 25 °C or among the various pH values except for the lower acidic condition (pH 2). TEM revealed significant changes in the morphology of MNV-1 after treatment with resveratrol, and molecular docking indicated that resveratrol strongly binds to the viral capsid protein of MNV-1. In addition, resveratrol regulated the expression of cytokine that protects against MNV-1 infection. Therefore, at a lower concentration, resveratrol, a natural component from Reynoutria japonica, exerts an inhibitory effect on MNV-1 growth and could be used as a safe additive in food products to improve the nutritional status and control norovirus.

Lymph node dissection has been a long-standing diagnostic and therapeutic strategy for metastatic cancers. However, questions over myriad related complications and survival outcomes are continuously debated. Immunotherapy, particularly neoadjuvant immunotherapy, has revolutionized the conventional paradigm of cancer treatment, yet has benefited only a fraction of patients. Emerging evidence has unveiled the role of lymph nodes as pivotal responders to immunotherapy, whose absence may contribute to drastic impairment in treatment efficacy, again posing challenges over excessive lymph node dissection. Hence, centering around this theme, we concentrate on the mechanisms of immune activation in lymph nodes and provide an overview of minimally invasive lymph node metastasis diagnosis, current best practices for activating lymph nodes, and the prognostic outcomes of omitting lymph node dissection. In particular, we discuss the potential for future comprehensive cancer treatment with effective activation of immunotherapy driven by lymph node preservation and highlight the challenges ahead to achieve this goal.

The aim was to investigate whether the stem cell marker LGR6 has prognostic value in colon cancer, alone or in combination with the prognostic biomarkers CEA and CXCL16.

LGR6 mRNA levels were determined in 370 half lymph nodes of 121 colon cancer patients. Ability to predict relapse after curative surgery was estimated by Kaplan-Meier survival model and Cox regression analyses.

Patients with high LGR6 levels [LGR6(+)] had a decreased mean survival time of 11 months at 5-year follow-up and 47 months at 12-year follow-up, respectively, with hazard ratios of 3.2 and 2.8. LGR6 mRNA analysis added prognostic value to CEA and CXCL16 mRNA analysis. In the poor prognosis groups CEA(+) and CXCL16(+), further division was achieved by LGR6 analysis. LGR6(+) patients had a very poor prognosis. LGR6 also identified a small number of CEA(-), TNM stage I patients who relapsed suggesting stem cell origin of these tumors. LGR6 and LGR5 levels correlated strongly in lymph nodes of stage I and IV patients but not in stage II patients, suggesting that these stem cell markers are differentially regulated.

This study highlights LGR6 as a useful prognostic biomarker independently and in combination with CEA, CXCL16 or LGR5 identifying different risk groups.

Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer.

A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis.

One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS.

CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

Lymph node ratio (LNR) may offer superior prognostic stratification in colorectal adenocarcinoma compared with N stage. However, candidate cutoff ratios require validation. We aimed to study the prognostic significance of LNR and its optimal cutoff ratio.

We reviewed the pathology records of all patients with stage III colorectal adenocarcinoma who were managed at the King Hussein Cancer Center between January 2014 and December 2019. We then studied the clinical characteristics of the patients, correlates of lymph node count, prognostic significance of positive lymph nodes, and value of sampling additional lymph nodes.

Among 226 included patients, 94.2% had ≥ 12 lymph nodes sampled, while 5.8% had < 12 sampled lymph nodes. The median number of lymph nodes sampled varied according to tumor site, neoadjuvant therapy, and the grossing pathologist's level of training. According to the TNM system, 142 cases were N1 (62.8%) and 84 were N2 (37.2%). Survival distributions differed according to LNR at 10% (p = 0.022), and 16% (p < 0.001), but not the N stage (p = 0.065). Adjusted Cox-regression analyses demonstrated that both N stage and LNR at 10% and 16% predicted overall survival (p = 0.044, p = 0.010, and p = 0.001, respectively).

LNR is a robust predictor of overall survival in patients with stage III colorectal adenocarcinoma. At a cutoff ratio of 0.10 and 0.16, LNR offers better prognostic stratification in comparison with N stage and is less susceptible to variation introduced by the number of lymph nodes sampled, which is influenced both by clinical variables and grossing technique.

Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.

One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.

Due to the impact of nodal metastasis on colon cancer prognosis, adequate regional lymph node resection and accurate pathological evaluation are required. The ratio of metastatic to examined nodes may bring an additional prognostic value to the actual staging system. This study analyzes the identification of factors influencing a high lymph node yield and its impact on survival. The lymph node ratio was determined in patients with fewer than 12 or at least 12 evaluated nodes. The study included patients after radical colon cancer resection in UICC stages II and III. For the lymph node ratio (LNR) analysis, node-positive patients were divided into four categories: i.e., LNR 1 (<0.05), LNR 2 (≥0.05; <0.2), LNR 3 (≥0.2; <0.4), and LNR 4 (≥0.4), and classified into two groups: i.e., those with <12 and ≥12 evaluated nodes. The study was conducted on 7012 patients who met the set criteria and were included in the data analysis. The mean number of examined lymph nodes was 22.08 (SD 10.64, median 20). Among the study subjects, 94.5% had 12 or more nodes evaluated. These patients were more likely to be younger, women, with a lower ASA classification, pT3 and pN2 categories. Also, they had no risk factors and frequently had a right-sided tumor. In the multivariate analysis, a younger age, ASA classification of II and III, high pT and pN categories, absence of risk factors, and right-sided location remained independent predictors for a lymph node yield ≥12. The univariate survival analysis of the entire cohort demonstrated a better five-year overall survival (OS) in patients with at least 12 lymph nodes examined (68% vs. 63%, p = 0.027). The LNR groups showed a significant association with OS, reaching from 75.5% for LNR 1 to 33.1% for LNR 4 (p < 0.001) in the ≥12 cohort, and from 74.8% for LNR2 to 49.3% for LNR4 (p = 0.007) in the <12 cohort. This influence remained significant and independent in multivariate analyses. The hazard ratios ranged from 1.016 to 2.698 for patients with less than 12 nodes, and from 1.248 to 3.615 for those with at least 12 nodes. The LNR allowed for a more precise estimation of the OS compared with the pN classification system. The metastatic lymph node ratio is an independent predictor for survival and should be included in current staging and therapeutic decision-making processes.