Node-negative Colorectal Cancer Research Articles

A commentary on the article entitled 'finding the minimum number of retrieved lymph nodes in Node-negative colorectal Cancer using Real-world data and the SEER database'.

A commentary on the article entitled 'finding the minimum number of retrieved lymph nodes in Node-negative colorectal Cancer using Real-world data and the SEER database'.

Finding the minimum number of retrieved lymph nodes in node-negative colorectal cancer using Real-world Data and the SEER database.

Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients. A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables. The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9-18) in 2013 to 17 (IQR: 15-20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P =0.009), with a threshold ( N =16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan-Meier curves revealed that N0 limited patients who received chemotherapy exhibited better outcomes than those who did not. Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy.

The effect of adjuvant chemotherapy on survival in node negative colorectal cancer with or without perineural invasion: a systematic review and meta-analysis.

It was aimed at assessing the benefits of adjuvant chemotherapy (ACT) for patients with node-negative colorectal cancer (CRC) either with or without perineural invasion (PNI). We systematically searched PubMed, Cochrane Library, Embase, and Web of Science from database inception through October 1, 2023. Survival outcomes were analyzed using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Heterogeneity for the descriptive meta-analyses was quantified using the I2 statistic. Ten studies included in this review. ACT improved overall survival (OS) (HR 0.52, 95% CI 0.40-0.69) and disease-free survival (DFS) (HR 0.53, 95% CI 0.35-0.82) in PNI + patients but did not affect DFS (HR 1.13, 95% CI 0.72-1.77) in PNI- patients. A disease-specific survival (DSS) benefit with chemotherapy was observed in PNI + (HR 0.76, 95% CI 0.58-0.99) and PNI- patients (HR 0.76, 95% CI 0.57-1.00). And PNI decreased DFS (HR 1.94, 95% CI 1.52-2.47) and OS (HR 1.75, 95% CI 0.96-3.17) in node-negative CRC. In conclusion, chemotherapy appears most beneficial for survival outcomes in node-negative patients with PNI, but may also confer some advantage in those without PNI. Identifier INPLASY2021120103.

Septin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer

BackgroundMolecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. MethodsWe analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). ResultsOf the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). ConclusionOur data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.

Prognostic Value of Mesorectal Lymph Node Micrometastases in ypN0 Rectal Cancer After Chemoradiation.

More than 25% of patients with node-negative colorectal cancer experience a recurrent disease even after curative surgery. This suggests the existence and oncologic influence of micrometastasis in regional lymph nodes or in distant organs. The objective of this study was to identify mesorectal lymph node micrometastases using an immunohistochemical analysis and to determine its prognostic value in node-negative rectal cancer after neoadjuvant chemoradiation. A total of 91 patients who received preoperative chemoradiation and radical resection for rectal cancer were included. Based on conventional hematoxylin and eosin staining, all patients had a node-negative disease. Mesorectal lymph nodes from resected specimens were re-evaluated to detect micrometastases by immunohistochemistry using anticytokeratin antibody AE1/AE3. The clinicopathologic data were collected from a prospectively maintained database of colorectal cancer patients and analyzed retrospectively. Micrometastases of mesorectal lymph nodes were detected in nine patients (9.9%). The three-year overall survival was similar regardless of micrometastasis (88.9% in the positive group versus 90.7% in the negative group, P=0.681); however, the three-year disease-free survival was significantly poorer in the patients with micrometastases (40.0% versus 84.2%, P=0.001). In the multivariate analysis, the advanced pT category (ypT3/T4 versus ypT0: hazard ratio [HR] 10.477, 95% confidence interval [CI] 1.102-99.594, P=0.041) and micrometastases in mesorectal lymph nodes (HR 5.655, 95% CI 1.837-17.409, P=0.003) were independent prognostic factors for disease-free survival. In node-negative rectal cancer after preoperative chemoradiation, immunohistochemically detected micrometastases of mesorectal lymph nodes were significantly correlated with poor disease-free survival.

Selection Factors for Treatment and Stratification of Rare Abdominal or Pelvic Tumors with Peritoneal Metastases.

To maximize the results of treatments for peritoneal metastases for rare abdominal or pelvic tumors, selection of patients with a possibility for long-term success is necessary. Because these malignancies are rare, data from which these selection factors can be extracted do not exist. In order to facilitate knowledgeable patient selection for treatment, the well established clinical and histopathologic features of the common malignancies treated for peritoneal metastases were reviewed. The potential application of selection factors for common diagnoses was explored in an attempt to provide selection factors for rare tumors. The histopathologic grade, the lymph node status, the Ki-67 proliferation index, prior surgical score (PSS), preoperative radiologic imaging, preoperative laparoscopic assessment, response to neoadjuvant chemotherapy, peritoneal cancer index (PCI), and completeness of cytoreduction score were all included in this search for relevant selection factors for a rare disease. To facilitate the use of selection factors from common peritoneal metastases diagnoses, these diseases were divided into four groups. Placement of the rare cause of peritoneal metastases into one of these four groups will allow knowledgeable selection for treatment. Rare diseases with a natural history resembling low-grade appendiceal neoplasms are in group 1, diseases resembling lymph node negative colorectal cancer are in group 2, diseases resembling lymph node positive colorectal peritoneal metastases in group 3, and diseases resembling gastric cancer in group 4.

Abstract 5546: Inflamed lymph nodes mark active tumor immune response in colorectal cancer patients

Abstract Background Tumor-infiltrating lymphocytes (TILs) can be used to predict immune response in multiple tumors. Currently, the evaluation of TILs relies on pathological and molecular examine on resected tumor samples. Enlarged regional lymph nodes could be attributed to tumor involvement or local inflammation with active immune response. We therefore aimed to investigate the role of inflamed lymph nodes in distinguishing the hot tumor from cold tumor. Methods Fresh-frozen tumor samples from pathologically-confirmed node-negative colorectal cancer patients with inflamed nodes (n= 22) and non-inflamed nodes (n= 23) were used to generate the genome-wide DNA methylation profile using Infinium Methylation EPIC BeadChip. The inflamed and non-inflamed nodes were defined as the pathologically-confirmed negative regional lymph nodes with enlarged size (≥ 5mm) and normal size (&amp;lt; 5mm) in radiological imaging, respectively. A MeTIL algorithm that integrates CD3+ T cell-specific differentially methylated positions was constructed and validated by immunohistochemical assay to evaluate TIL-based tumor immune response in bulk tumor samples. Results The baseline characteristics were balanced between patients with inflamed and non-inflamed nodes. The high abundance of TILs was significantly associated with inflamed nodes (P= 0.025). In addition, we identified a subgroup of superhot tumors characterized by inflamed nodes, enriched TILs and favorable overall survival outcomes (HR 0.53, 95% CI: 0.36-0.97; P = 0.032). Conclusions Inflamed regional lymph nodes in radiological imaging indicate potential active immune response in tumor. Our findings provide an easily accessible biomarker for cancer immunotherapy. Citation Format: Dingcheng Shen, Xiaolin Wang, Meijin Huang, Yanxin Luo, Huichuan Yu. Inflamed lymph nodes mark active tumor immune response in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5546.

Micrometastasis in lymph nodes of colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide. Postoperative adjuvant chemotherapy is recommended for node‐positive stage III patients. A systematic meta‐analysis reported that the presence of micrometastases in regional lymph nodes (LNs) was associated with poor survival in patients with node‐negative CRC. Because most data employed in the meta‐analysis were based on retrospective studies, we conducted a prospective clinical trial and concluded that stage II is a transitional zone between stage I and stage III, where CRC tumors continuously increase the micrometastasis volume in LNs and proportionally raise the risk for tumor recurrence. The one‐step nucleic acid amplification (OSNA) assay is a simple and rapid technique to detect CK19 mRNA using the reverse‐transcription loop‐mediated isothermal amplification (RT‐LAMP) method. Using the OSNA assay, we and colleagues reported that the upstaging rates of pStages I, IIA, IIB, and IIC were 2.0%, 17.7%, 12.5%, and 25%, respectively, in 124 node‐negative patients. Survival analysis indicated that OSNA positive stage II CRC patients had a shorter 3‐y disease‐free survival rate than OSNA negative stage II CRC patients. In 2017, AJCC TNM staging (the 8th version) revised the definition of LN metastasis in colon cancer and it is stated that micrometastasis should be considered as a standard LN metastasis. To our surprise, this revision was based on a meta‐analysis to which our previous study on micrometastasis largely contributed. The remaining questions to be addressed are how to find micrometastases efficiently and whether postadjuvant chemotherapy is effective to prevent disease recurrence and to contribute to longer survival.

Analysis of risk factors and prognosis of 253 lymph node metastasis in colorectal cancer patients

BackgroundThis study aimed to explore potential risk factors for 253 lymph node metastasis, and to identify the prognostic impact of 253 lymph node metastasis in colorectal cancer patients.MethodsA retrospective study was conducted of 391 colorectal cancer patients who underwent surgical treatments that included 253 lymph node dissection. Clinicopathological features, molecular indexes and 1-year overall survival rates were analyzed.ResultsUnivariate analyses revealed the following risk factors for 253 lymph node metastasis: high preoperative levels of CEA, large tumour max diameters, and numbers of harvested lymph nodes, presence of vessel carcinoma emboli, low level of MSH6 and MLH1 immunohistochemical staining intensity. Multivariate analysis showed that elevated MLH1 immunohistochemical staining intensity was an independent protective factor for 253 lymph node metastasis (OR: 0.969, 95% CI 0.945, 0.994, P = 0.015). A significant difference was found in 1-year overall survival rate between 253 lymph node-positive and lymph node-negative colorectal cancer patients (88.9% vs.75.0%, P < 0.001).Conclusions253 lymph node-positive colorectal cancer patients had a worse prognosis than the 253 lymph node-negative patients. 253 lymph node dissection may improve the prognosis of colorectal cancer patients with high risk factors for 253 lymph node metastasis.

CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly correlated with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. In conclusion, the circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

Correlation between CT Texture Analysis and Synchronous Distant Metastasis in Patients with Lymph Node-negative Colorectal Cancer

Objective To investigate the correlation between CT texture analysis and synchronous distant metastasis in patients with lymph node-negative colorectal cancer. Methods The preoperative CT images of 82 patients with lymph node-negative colorectal cancer were analyzed retrospectively.There were 12 patients with simultaneous distant metastasis and 70 patients without simultaneous distant metastasis.The maximum plane of the lesion on plain scan and portal CT images was analyzed by TexRAD software.When the spatial scaling factor(SSF)was 0 and 2-6,six texture parameters were obtained,and the differences of texture parameters between the two groups were compared.The counting data were analyzed by chi-square test and the measurement data by Mann-Whitney test. Results There was a significant difference in the skewness of SSF=3 between the simultaneous distant metastasis group and the non-synchronous metastasis group on plain CT scan(P=0.031).On contrast-enhanced CT images,the entropy values of SSF=2,3,5,and 6 were statistically significant(P=0.048,P=0.027,P=0.016,P=0.017),and the peak values of SSF=2 were statistically significant(P=0.026).According to the comprehensive analysis of the texture parameters of the six groups,when the boundary value was 0.636,the sensitivity and specificity for the diagnosis of simultaneous distant metastasis were 75% and 89%,respectively. Conclusion CT texture analysis is useful in the diagnosis of synchronous distant metastasis in patients with lymph node-negative colorectal cancer.

The advantage of one-step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients.

Generally, the postoperative examination of lymph nodes (LNs) is based on a microscopic examination of one hematoxylin and eosin (HE)‐stained slide; however, an examination of only one part of the LN might lead to incorrect staging of the tumor due to tissue allocation bias. Although multilevel sectioning and the use of immunohistochemistry (IHC) have improved the detection of micrometastases in LNs, this approach is laborious, time‐consuming, and costly. A novel molecular technique for the detection of LN metastases of tumors, called one‐step nucleic acid amplification (OSNA), is a rapid and semi‐quantitative examination quantifying the number of cytokeratin 19 (CK‐19) mRNA copies derived from a tumor. OSNA is already in clinical use for the diagnosis of LN metastasis in breast cancer patients; however, the use of OSNA is under investigation with promising results for colorectal cancer (CRC). The present review assessed recent studies on OSNA vs a histopathological examination and its implications for CRC staging and treatment. A total of 16 studies of OSNA in CRC yielded by a PubMed search were reviewed. Among them, seven studies evaluating the diagnostic performance revealed that OSNA had a high specificity (96.8%), high concordance rate (96.0%), and negative predictive value (98.6%) in a pooled assessment. In addition, four studies examining the utility of OSNA in sentinel LNs (SLNs) and two studies focusing on upstaging in pathologically node‐negative CRC patients were also reviewed. Multicenter prospective studies with a large cohort of CRC patients are warranted to reveal the benefits of OSNA in the future.

Node negative colorectal cancer patients: assesment of high-risk features on recurrence

BackgroundThe introduction of population-based screening programs for colorectal cancer (CRC) results in less patients with advanced disease. There is an increase in the amount of node negative CRC, which makes adequate risk stratification for this particular group of patients necessary. The addition of more risk factors to the conventional histological high-risk factors is investigated in this retrospective study. Patients and MethodsA cohort of 227 node negative (stage I and II) CRC patients who were not treated with adjuvant chemotherapy were selected from two previously conducted cohort studies. Detailed histopathological examination was performed by two independent observers and molecular background (BRAF/RAS mutations, microsatellite status (MSI)) was studied. Univariate analyses were used to analyse differences in histological and mutational characteristics between patients with and without recurrence. P-values below 0.05 were considered statistically significant. ResultsPoorly differentiated histology (p:0.002), BRAF mutation (p:0.002) and MSI status (p:0.006) were found significant relevant risk factors that were related to recurrent disease. Poorly differentiated histology was associated with intermediate/high tumor budding (TB) (p:0.001), a BRAF mutation (p:0.001) and MSI status (p:0.001). A combination of all three features (poorly differentiated histology, BRAF and MSI) was more often present in the recurrence group. ConclusionsRecurrence in node negative CRC patients could be better predicted when molecular features such as, BRAF mutation and MSI status are incorporated into a model with poorly differentiated CRC. Therefore, these features might help in the selection of patients who possibly will benefit from adjuvant treatment.

Histogram Analysis of Diffusion-Weighted MR Imaging as a Biomarker to Predict Survival of Surgically Treated Colorectal Cancer Patients.

Structural abnormality is a well-recognized feature of malignancy. On the other hand, diffusion-weighted MRI (DWI) has been reported as a tool that can reflect tumor biology. The purpose of this study is to apply histogram analysis to DWI to quantify structural abnormality of colorectal cancer, and evaluate its biomarker value. This is a retrospective study of 80 (46 men and 34 women; median age: 68.0years) colorectal cancer patients who underwent DWI followed by curative surgery at the Chiba University Hospital between 2009 and 2011. Median follow-up time was 62.2months. Histogram parameters including signal intensity of kurtosis and skewness of the tumor were measured on DWI at b = 1000, and mean apparent diffusion coefficient value (ADC) of the tumor was also measured on ADC map generated by DWIs at b = 0 and 1000. Associations of tumor parameters (kurtosis, skewness, and ADC) with pathological features were analyzed, and these parameters were also compared with overall survival (OS) and relapse-free survival (RFS) using Cox regression and Kaplan-Meier analysis. ADC of the tumor did not have significant associations with any pathological factors, but kurtosis and skewness of signal intensity in the tumor was significantly different between tumors with distant metastases and those without (4.23 ± 1.31 vs. 3.24 ± 1.32, p = 0.04; 1.09 ± 0.39 vs. 0.57 ± 0.58, p = 0.03). Kurtosis of the tumor was significantly correlated with OS and RFS (p = 0.04, p = 0.03, respectively), and skewness was significantly correlated with OS (p = 0.03) in Cox regression analysis. Higher kurtosis or higher skewness of the tumor was associated with worse OS in Kaplan-Meier analysis (p = 0.01, p = 0.009, log-rank). In subset analysis, there were 50 patients (32 men and 18 women) of lymph node-negative colorectal cancers (≤ stage II); skewness of signal intensity in the tumor was associated with OS using univariate Cox regression analysis (p = 0.04). Histogram analysis of DWI can be a prognostic biomarker for colorectal cancer.

Oncological outcomes analysis of colorectal cancer with unfavorable histological features

Objective: To explore the effect of unfavorable histological features on the clinical outcomes of patients receiving radical resection of colorectal cancer. Methods: A retrospective analysis of patients with colorectal cancer who received radical surgery between January 2013 and December 2015 at Department of General Surgery, Peking Union Medical College Hospital was performed. The impact of unfavorable histological features on the oncological outcomes of patients with lymph node-negative colorectal cancer were analyzed.A total of 167 patients were enrolled, including 98 males and 69 females with age of (63.6±11.6) years. Observation indicators included age, T stage, lymphovascular invasion, perineural invasion, tumor deposits, number of lymph node dissection, degree of differentiation, tissue type, and circumferential margin. Univariate analysis was performed with χ(2) test and multivariate analysis was performed with Cox regression model. Results: Univariate analysis showed that positive circumferential margins (CRM), tumor deposits and age were associated with disease free survival (DFS) rate; positive CRM, age, tumor deposits, and lymph nodes dissection less than 12 were significantly associated with overall survival (OS) rate (all P<0.05). Multivariate analysis showed that over 70 years of age (HR=1.053, 95% CI: 1.013 to 1.095, P=0.009), poorly differentiated adenocarcinoma (HR=7.572, 95%CI: 1.815 to 31.587, P=0.005), tumor deposits (HR=4.711, 95% CI: 1.809 to 12.264, P=0.002), mucinous adenocarcinoma (HR=3.063, 95% CI: 1.003 to 9.354, P=0.049), lymphovascular invasion (HR=2.885, 95% CI: 1.062 to 7.832, P=0.038), and nerve infiltration (HR=6.610, 95% CI: 1.037 to 42.122, P=0.046) were adverse prognostic factors of DFS rate; poorly differentiated adenocarcinoma (HR=12.200, 95% CI: 1.985 to 74.972, P=0.007), tumor nodules (HR=5.379, 95% CI: 1.636 to 17.685, P=0.006), over 70 years of age (HR=1.062, 95% CI: 1.013 to 1.114, P=0.013), and perineural invasion (HR=8.043, 95% CI: 1.026 to 63.055, P=0.047) were adverse prognostic factors of OS rate. There was no significant difference in the 3-year DFS rate and 3-year OS rate between T1-2 group and T3-4 group (P>0.05). Conclusion: Over 70 years of age, poorly differentiated adenocarcinoma, mucinous adenocarcinoma, tumor nodules, lymphovascular invasion, and perineural invasion are independent adverse prognostic factors of lymph node-negative colorectal cancer.

Epigenetic silencing of tumor suppressor candidate 3 confers adverse prognosis in early colorectal cancer.

Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 (TUSC3/N33) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins. However, the consequences of TUSC3 loss are largely unknown. Thus, the aim of the study was to characterize the functional and clinical relevance of TUSC3 expression in CRC patients’ tissues (n=306 cases) and cell lines. TUSC3 mRNA expression was silenced by promoter methylation in 85 % of benign adenomas (n=46 cases) and 35 % of CRCs (n =74 cases). Epidermal growth factor receptor (EGFR) was selected as one exemplary ER-derived target protein of TUSC3-mediated posttranslational modification. We found that TUSC3 inhibited EGFR-signaling and promoted apoptosis in human CRC cells, whereas TUSC3 siRNA knock-down increased EGFR-signaling. Accordingly, in stage I/II node negative CRC patients (n=156 cases) loss of TUSC3 protein expression was associated with poor overall survival. In sum, our data suggested that epigenetic silencing of TUSC3 may be useful as a molecular marker for progression of early CRC.

Perioperative Hepatic Arterial Infusion Pump Chemotherapy Is Associated With Longer Survival After Resection of Colorectal Liver Metastases: A Propensity Score Analysis.

Purpose To investigate whether perioperative hepatic arterial infusion pump chemotherapy (HAI) was associated with overall survival (OS) in patients who had a complete resection of colorectal liver metastases (CLM). Methods Patients who underwent a complete resection of CLM between 1992 and 2012 were included from a single-center prospectively maintained database. All patients who received HAI also received perioperative systemic chemotherapy. Propensity score analysis was used to match patients for seven known prognostic factors. Results A total of 2,368 consecutive patients underwent a complete resection of CLM, with a median follow-up of 55 months. The median OS for patients with HAI (n = 785) was 67 months versus 44 months without HAI (n = 1,583; P < .001), despite more advanced disease in the HAI group. OS at 10 years was 38.0% versus 23.8% without HAI. For patients who received modern systemic chemotherapy (n = 1,442), the median OS was 67 months with HAI and 47 months without HAI ( P < .001). The hazard ratio adjusted by propensity score demonstrated longer OS with HAI: 0.67 (95% CI, 0.59 to 0.76; P < .001). A pronounced difference in median OS was found for patients with node-negative colorectal cancer (129 months with HAI v 51 months without; P < .001) and a low clinical risk score of 0 to 2 points (89 months with HAI v 53 months without; P < .001). Conclusion Patients who received HAI had a median OS of approximately 2 years longer than patients without HAI. The strong association was independent of the use of modern systemic chemotherapy and remained in propensity score analysis. Patients with node-negative primary tumors or a low clinical risk score seemed to benefit most from HAI.

Correlation between quantitative expression of T lymphoma invasion and metastasis inducing factor 1 mRNA and lymph node micrometastasis and prognosis in patients with colorectal cancer

Objective To investigate the relationship between the changes of expression of T lymphoma invasion and metastasis inducing factor 1(Tiam1) mRNA and lymph node micrometastasis and prognosis in patients with node-negative colorectal cancer(CRC). Methods From June 2008 to August 2010, a total of 63 patients with lymph node-negative CRC, 20 patients with lymph node-positive CRC and 25 patients with colorectal benign lesions were enrolled. The relative quantity expression (RQ) of Tiam1 mRNA in CRC cancer tissues and colorectal benign lesions were detected by real-time quantitative polymerase chain reaction (PCR). The lymph node micrometastasis was determined by cytokeratin 20 detection in lymph nodes tissues. The five-year postoperative prognosis was evaluated by followed-up in the patients with lymph node-negative CRC. The correlation between the expression of Tiam1 mRNA and lymph node micrometastasis and prognosis was analyzed. The t-test, univariate analysis, multivariate analysis and Log-rank test were performed for statistical analysis. Results Lymphnode micrometastasis occurred in 33 from 63 patients with lymph node-negative CRC. The RQ of Tiam1 mRNA in the patients with lymph node-positive CRC was 9.84±2.36, which was higher than that of patients with lymph node-negative CRC (5.15±3.58), and the difference was statistically significant (t=5.479, P<0.01). The RQ of Tiam1 mRNA of these two groups were both higher than that of colorectal benign lesion (0.30±0.21), and the difference was statistically significant(t=20.169, 6.745; both P<0.01). The RQ of Tiam1 mRNA of positive lymph node micrometastasis group was 6.30±1.95, which was higher than that of negative lymph node micrometastasis group (3.88±1.63), and the difference was statistically significant (t=5.330, P<0.01). In the patients with lymph node-negative CRC, the lower degree of tumor difference, the deeper invasion, the shorter survival time after surgery and postoperative recurrence and metastasis were related with the higher RQ of Tiam1 mRNA in tumor tissues (t=2.536, 3.112, 3.213, 2.676; all P<0.05). Univariate analysis revealed that the expression of Tiam1 mRNA in cancer tissues was correlated with lymph node micrometastases(χ2 =11.878, P=0.001). Multivariate analysis showed that it was an independent risk factors of lymph node micrometastases in CRC(relative risk: 9.782). The five-year postoperative cumulative survival rate of high Tiam1 mRNA expression group was 75.8%, which was lower than that of low expression group (97.1%) , and the difference was statistically significant (χ2 =4.575, P<0.05). Conclusions Tiam1 may participate in the regulation of lymph node metastasis in CRC. Elevated expression of Tiam1 promotes lymph node metastasis and is closely relatived with poor prognosis of node-negative CRC, and which can be considered as an indicator of prognosis. Key words: Tiam1 mRNA; Colorectal cancer; Lymph node micrometastases; Prognosis

What is the likelihood of colorectal cancer when surgery for ulcerative-colitis-associated dysplasia is deferred?

Surgery aims to prevent cancer-related morbidity for patients with ulcerative colitis (UC) associated dysplasia. The literature varies widely regarding the likelihood of dysplastic progression to higher grades of dysplasia or cancer. The aim of this study was to characterize the likelihood of the development of colorectal cancer (CRC) of patients with UC-associated dysplasia who chose to defer surgery. A retrospective review was carried out of patients undergoing surgery for UC at the Mayo Clinic, who were diagnosed to have dysplasia between August 1993 and July 2012. The relationships between grade of dysplasia, time to surgery and the detection of unsuspected carcinoma were investigated. In all, 175 patients underwent surgery at a median of 4.9 (interquartile range 2.5-8.9) months after a diagnosis of dysplasia. Their median age was 52 (interquartile range 43-59) years. An initial diagnosis of indeterminate dysplasia was not associated with CRC [0/23; 17.7 (8.1-29.6) months]. Thirty-six patients who had an initial diagnosis of dysplasia progressed from indeterminate to low-grade dysplasia [24.2 (11.0-30.4) months]. Low-grade dysplasia was associated with a 2% (1/56; T2N0M0) risk of CRC when present in random surveillance biopsies and a 3% (2/61; T1N0M0, T4N0M0) risk if detected in endoscopically visible lesions [7.4 (5.2-33.3) months]. Eighteen patients progressed from indeterminate to high-grade dysplasia [19.1 (9.2-133.9) months]. Seventeen patients progressed from low to high-grade dysplasia [11.0 (5.8-30.1) months]. None of the patients with high-grade dysplasia (0/35) progressed to CRC [4.5 (1.7-9.9) months]. Dysplasia was associated with a low incidence of node negative CRC if surgery was deferred for up to 5years. These findings may help inform the decision-making process for asymptomatic patients who are having to decide between intensive surveillance or surgery for UC-associated dysplasia.

Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review and Pooled Analysis

Tumour budding is defined as the presence of isolated or small clusters of malignant cells at the invasive edge of the tumour. It is considered a negative prognostic factor in colorectal cancer (CRC) and is associated with a poor outcome and adverse pathological features. Here, we report a meta-analysis of the association of tumour budding and survival in stage II CRC patients. PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that assessed the relationship between tumour budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to compute odds ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst patients with respect to the extent of tumour budding, using multivariate analysis. Data were pooled using the Mantel-Haenszel random effect model. We analysed 12 studies that included a total of 1652 patients. High-grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 % confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5-year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly noteworthy that the presence of high-grade budding was associated with an increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001). Tumour budding is associated with worse survival in stage II CRC, in particular in pT3N0M0 patients. It could therefore potentially be used when deciding whether to administer adjuvant chemotherapy in high-risk node negative CRC patients.