Non-metastatic Colorectal Cancer Research Articles

Clinicopathological characteristics and prognosis of patients according to recurrence time after curative resection for colorectal cancer.

To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.

Prevalence and correlates of patient symptom burden at initiation of curative chemotherapy.

176 Background: Side effects of curative chemotherapy regimens are highly prevalent and can lead to unplanned oncology clinic visits or hospital-level care. The current study aim was to examine physical symptoms among patients at their first chemotherapy visit, even prior to receiving their first infusion, in order to characterize symptom burden and unmet needs at this early stage of care. Methods: The current study utilized baseline data from a larger health services research trial for consecutive patients initiating chemotherapy for non-metastatic breast (48.0%), colorectal (28.0%), or lung (24.0%) cancer (n=75). Patients were invited to complete a self-report survey at their first chemotherapy visit, including demographics and measures of physical symptoms (Memorial Symptom Assessment Scale) and psychological distress (Patient Health Questionnaire-4; score ≥ 3 indicates positive anxiety or depression screen). Results: Among participants (M age=55.3 [SD=13.3]; female=70.7%), more than half (54.7%) endorsed at least one physical symptom -- primarily fatigue (34.7%) and constipation (29.3%). Additionally, one-fourth (25.3%) screened positive for anxiety (22.7%) and/or depression (9.3%). There were no differences in physical symptom bother or likelihood of fatigue or constipation, by factors including patient age, gender, marital status, work status, disease type, recent surgery, or concurrent radiotherapy. However, patients with positive anxiety and/or depression screens reported greater symptom bother and were more likely to endorse fatigue relative to those with negative screens (Mbother=4.5 vs. 1.3; fatigue=78.9% vs. 19.6%, p’s&lt;.01). There was no difference in constipation between these groups. Conclusions: Symptom frequency was markedly high among patients initiating curative chemotherapy, with at least half reporting physical symptoms prior to their first infusion, and psychological distress clustered with general symptom bother and fatigue. Future work should explore 1) the extent to which physical and psychological symptoms at chemotherapy initiation may be associated with longitudinal symptom profiles, and 2) strategies for addressing symptom burden early on in outpatient care.

Expression and Significance of Interleukin 1α mRNA in Colorectal Cancer

Quantitative analysis for the relative mRNA expression of interleukin 1α (IL-1α) in colorectal cancer and cancer-adjacent tissues, the clinical significance of which will be investigated. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the relative mRNA levels of IL-1α in 42 colorectal cancer tissues and corresponding cancer-adjacent tissues, statistically analyzing the co-relation of IL-1α mRNA levels with the differentiation, clinical stages and metastatic status of cancer. The relative content of IL-1α mRNA in colorectal tissues was 1.18 ± 0.80, and that in cancer-adjacent tissues was 0.74 ± 0.49, with a significant difference between the two groups (t=-3.12, P=0.003). The relative content of IL-1α mRNA in advance-staged (stage III-IV) colorectal cancer tissues was 1.50 ± 0.93, which was significantly higher than that in early-staged colorectal cancer tissues (1.50 ± 0.93 vs. 0.89 ± 0.52, t=-2.67, P=0.01). The relative content of IL-1α mRNA in metastatic colorectal cancer tissues was 1.59 ± 0.90, which was significantly higher than that in non-metastatic colorectal cancer tissues (1.59 ± 0.90 vs. 0.84 ± 0.50, P=0.002). Expression of IL-1α mRNA in colorectal cancer tissues is significantly elevated, and has a positive co-relation with the clinical stages and metastatic status, suggesting IL-1α might play a role in the initiation and progression of colorectal cancer.

Abstract 2824: Circulating tumor cells (CTCs) can predict survival and response to treatment in non-metastatic colorectal cancer (CRC): Correlation between flowcytometry, quantitative real-time pcr (qPCR) and cytomorphology

Abstract Background: Circulating tumor cells (CTCs) were detected in patients with metastatic epithelial malignancies using different methodologies. The number of CTCs before and during treatment of advanced CRC is an independent predictor of poor response to treatment, progression-free (PFS) and overall survival (OS). We investigated 1) whether CTC count can predict outcome in patients with CRC and 2) the utility of FCM supplemented with PCR and/or cyto-morphology (CM) in enumerating CTCs. Methodology: CTCs were enumerated in 56 CRC cases and 20 normal controls (NC) by flowcytometry (FCM), and quantitative real time PCR (qPCR) using CK19, MUC, CD44, CD133 and ALDH1after immune-magnetic separation. Results were correlated to cytomorphology, standard prognostic factors, overall and progression free survival (OS&amp;PFS). Results: CTCs &amp;lt; 3 were detected in 45% of the cases compared to 55% with ≥3 CTCs. CK19, MUC1, CD44, CD133 and ALDH1-RNA expression was detected in (55.4%, 44.6%, 53.6%, 43.6%, 46.4%; respectively). The concordance between FCM&amp; qPCR, FCM&amp;CM, qPCR&amp; CM ranged from 82% to 96%. Significant correlations were reported between CTCs and tumor stage and grade (p&amp;lt;0.01). OS was significantly associated with pathological tumor type, T stage, lymph nodes involvement, CTC, CK, MUC1, CD44 and CD133. PFS was significantly associated with pathological tumor type, disease stage, N stage, CTC, CK, MUC1, CD44 and CD133 (p=). Conclusions:1)enumeration of CTCs, pre- and after initial treatment, can predict outcome in CRC patients, 2)FCM is a sensitive, rapid and easy technique for enumeration of CTCs, especially if supplemented with qPCR for detection of CRC cells biomarkers (CK19), MUC, CD44, CD133 and ALDH1). Citation Format: Abeer Bahnassy, Abdel-Rahman N. Zekri, Salem E. Salem, Marwa Mohamad, Marwa Mohanad. Circulating tumor cells (CTCs) can predict survival and response to treatment in non-metastatic colorectal cancer (CRC): Correlation between flowcytometry, quantitative real-time pcr (qPCR) and cytomorphology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2824. doi:10.1158/1538-7445.AM2014-2824

Abstract 3064: Importance of circulating tumor cells in newly diagnosed colorectal cancer

Abstract Background: The presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). This study was conducted to determine if the presence of CTC prior to surgery and during follow-up in patients with newly diagnosed non-metastatic CRC identifies patients who are at risk for disease recurrence. Methods: In a prospective single center study 183 patients with newly diagnosed non-disseminated CRC scheduled for surgery were enrolled from 2003 till 2008 and followed up for a median of 5.1 years. CTC were enumerated with the CellSearch System in 4 aliquots of 7.5 ml of peripheral blood before and after surgery (1-26 weeks), after adjuvant therapy and 1, 2, 3 and 4 years after surgery. Findings: ≥1 CTC/ 30ml of blood were detected in 44 (24%) patients before surgery. CTC frequency did not change significantly at the time points after surgery. Patients with CTC before surgery had a significant decrease in Recurrence Free Survival (RFS, logrank test p=0.014) and Colon Cancer Related Survival (CCRS, p=0.002). Five year RFS dropped from 75% to 61% and five year CCRS from 83% to 69% for patients with CTC before surgery. In a multivariate analysis of CTC, T-Stage and N-stage, the presence of CTC and N-stage remained as significant factors for RFS and CCRS. Surprisingly the presence of CTC after surgery was not significantly associated with RFS and CCRS whereas CTC 2-3 years after surgery was again significantly associated with RFS and CCRS. Interpretation: The presence of CTC in patients with stage I-III CRC before surgery is associated with a significant reduction RFS and CCRS. Although similar amounts of CTC were detected within 3 months after surgery they were not associated with RFS or CCRS. In contrast CTC were again highly significant for RFS and CCRS 2-3 years after surgery. These findings suggest a role of CTC detection, to assess which patients need adjuvant treatment. To implement CTC detection in the non-metastatic setting a validated CTC detection technology is needed with increased sensitivity and specificity. Citation Format: Guus van Dalum, Marco R. de Groot, Gerrit-Jan Stam, Loes F.A. Scholten, Walter J.B. Mastboom, Istvan Vermes, Arjan G.J. Tibbe, Leon W.M.M. Terstappen. Importance of circulating tumor cells in newly diagnosed colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3064. doi:10.1158/1538-7445.AM2014-3064

Prognostic value of preoperative D-dimer and carcinoembryonic antigen levels in patients undergoing intended curative resection for colorectal cancer: a prospective cohort study.

Carcinoembryonic antigen (CEA) has limited value as an isolated predictor for survival among colorectal cancer (CRC) patients. D-dimer (DD) is a strong predictor of survival among metastatic CRC patients, but the prognostic value in non-metastatic CRC patients remains controversial. We examined the prognostic value of preoperative DD levels in relation to CEA levels in non-metastatic, resectable CRC patients. Between October 2003 and November 2005, 166 patients were included. We used the Kaplan-Meier method to compute 5-year mortality rates, stratified by preoperative DD and CEA levels. Adjusted Cox regression analysis was used to compute mortality rate ratios (MRRs) during postoperative years 0-1 and 1-5 based on the preoperative CEA and DD levels. The cumulative 5-year mortality rate was 15 % (95 % confidence interval [CI], 9-25 %) in patients with normal DD and CEA levels, 30 % (CI, 16-53 %) in patients with isolated elevated CEA levels, 37 % (CI, 25-53 %) in patients with isolated elevated DD levels, and 60 % (CI, 37-83 %) in patients with elevated CEA and DD levels. Elevated CEA was associated with an approximately ten-fold increase in mortality within the first postoperative year (adjusted MRR 9.8, CI 2.5-38.3); this association was lost during postoperative years 1-5 (adjusted MRR 1.1, CI 0.5-2.7). Elevated DD was associated with a greater than two-fold increase in mortality during postoperative years 0-1 (adjusted MRR 2.8, CI 0.7-11.0) and 1-5 (adjusted MRR 2.2, CI 1.1-4.8). DD is a strong predictor of survival among non-metastatic curatively resected CRC patients, particularly in combination with CEA.

Mean platelet volume as a prognostic marker in metastatic colorectal cancer patients treated with bevacizumab-combined chemotherapy.

Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC (7.895±1.060 versus 7.322±1.136, p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy.

A Preoperative Neutrophil to Lymphocyte Ratio of 3 Predicts Disease-Free Survival After Curative Elective Colorectal Cancer Surgery

This study aims to determine the role of the neutrophil to lymphocyte ratio (NLR) as a prognostic marker for patients with nonmetastatic colorectal cancer undergoing curative resection. An NLR reflects a systematic inflammatory response, with some evidence suggesting that an elevated preoperative NLR of more than 5.0 is associated with poorer survival in patients with colorectal cancer. Data from 506 consecutive patients with a diagnosis of nonmetastatic colorectal adenocarcinoma undergoing surgical resection between 2006 and 2011 were included. Receiver operating characteristic curve analysis was used to identify the optimal value for NLR in relation to disease-free and overall survival. Univariate and multivariate Cox regression models were used to determine the role of NLR after stratification by several clinicopathological factors. Patients were followed by a standardized protocol until February 2013. Median follow-up was 45 months [interquartile range, 21-65]. Multivariate Cox regression analysis identified an NLR of more than 3 as an independent prognostic factor for disease-free survival (odds ratio = 2.41; 95% confidence interval = 1.12-5.15; P = 0.024) but not for overall survival (odds ratio = 1.23; 95% confidence interval = 0.80-1.90; P = 0.347). A high NLR was significantly associated with older age, higher T and N stages, the presence of microvascular invasion, low preoperative albumin levels, and higher ASA (American Society of Anesthesiologists) status of the patient. For patients with colorectal cancer, a preoperative NLR of more than 3.0 may be an independent prognostic factor for disease-free survival. Considering this in addition to well-established prognostic variables may improve the processes of identifying patients at higher risk of recurrence who would benefit from adjuvant therapies or more frequent surveillance, thereby providing more personalized cancer care.

Introducing a Novel and Robust Technique for Determining Lymph Node Status in Colorectal Cancer

This study aims to harness the potential of public gene expression repositories, to develop gene expression profiles that could accurately determine nodal status in colorectal cancer. Currently, techniques that determine lymph node positivity (before resection) have poor sensitivity and specificity. The ability to determine lymph node status, based on preoperative biopsies, would greatly assist in planning treatment in colorectal cancer. This is particularly relevant in polyp-detected cancers. Public gene expression repositories were screened for experiments comparing metastatic and nonmetastatic colorectal cancer. A customized graphic user interface was developed to extract genes dysregulated across most identified studies (ie, consensus profiles). The utility of consensus profiles was tested by determining whether classifiers could be derived that determined nodal positivity or negativity. Consensus profiles-derived classifiers were tested on separate Affymetrix- and Illumina-based experiments, and collated outputs were compiled in summary receiver operator curve characteristic format, with area under the curve (AUC) reflecting accuracy. The association between classification and oncologic outcome was determined using an additional, independent data set. Final validation was conducted using the Ingenuity network-linkage environment. Four consensus profiles were generated from which classifiers were derived that accurately determined node positive and negative status (pooled AUC were 0.79 ± 0.04 and 0.8 ± 0.03 for nodal positivity and negativity, respectively). Overall AUC ranged from 0.73 to 0.86, demonstrating high accuracy across consensus profile type, classification technique, and array platform used. As consensus profile enabled classification of nodal status, survival outcomes could be compared for those predicted node negative or positive. Patterns of disease-free and overall survival were identical to those observed for standard histopathologic nodal status. Genes contained within consensus profiles were strongly linked to the metastatic process and included (among others) FYN, WNT5A, COL8A1, BMP, and SMAD family members. Microarray expression data available in public gene expression repositories can be harnessed to generate consensus profiles. The latter are a source of classifiers that have prognostic and predictive properties.

Impact of hyperglycemia on survival and infection-related adverse events in patients with metastatic colorectal cancer who were receiving palliative chemotherapy.

PurposeNon-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC.Materials and MethodsWe reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results.ResultsThe mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). ConclusionHyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.

Calcium, vitamin D, dairy products, and mortality among colorectal cancer survivors: the Cancer Prevention Study-II Nutrition Cohort.

Higher calcium, vitamin D, and dairy product intakes are associated with lower colorectal cancer incidence, but their impacts on colorectal cancer survival are unclear. We evaluated associations of calcium, vitamin D, and dairy product intakes before and after colorectal cancer diagnosis with all-cause and colorectal cancer-specific mortality among colorectal cancer patients. This analysis included 2,284 participants in a prospective cohort who were diagnosed with invasive, nonmetastatic colorectal cancer after baseline (1992 or 1993) and up to 2009. Mortality follow-up was through 2010. Prediagnosis risk factor information was collected on the baseline questionnaire. Postdiagnosis information was collected via questionnaires in 1999 and 2003 and was available for 1,111 patients. A total of 949 participants with colorectal cancer died during follow-up, including 408 from colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, postdiagnosis total calcium intake was inversely associated with all-cause mortality (relative risk [RR] for those in the highest relative to the lowest quartiles, 0.72; 95% CI, 0.53-0.98; Ptrend = .02) and associated with marginally statistically significant reduced colorectal cancer-specific mortality (RR, 0.59; 95% CI, 0.33 to 1.05; Ptrend = .01). An inverse association with all-cause mortality was also observed for postdiagnosis milk intake (RR, 0.72; 95% CI, 0.55 to 0.94; Ptrend = .02), but not vitamin D intake. Prediagnosis calcium, vitamin D, and dairy product intakes were not associated with any mortality outcomes. Higher postdiagnosis intakes of total calcium and milk may be associated with lower risk of death among patients with nonmetastatic colorectal cancer.

Low expression of novel lncRNA RP11-462C24.1 suggests a biomarker of poor prognosis in colorectal cancer.

Long noncoding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules, which were involved in a broad range of biological processes and complex diseases. Research on lncRNAs may shed light on tumorigenesis and progression of colorectal cancer (CRC). The purpose of the present study was to identify lncRNAs correlated with CRC and then investigate their potential functions. We selected 92 patients for this prospective study and then collected the tumor samples and clinical records. First, the global lncRNA expression profiles in tumor and adjacent normal tissues of patients with non-metastatic CRC and patients with metastatic CRC were measured by microarray assay. Then, a noteworthy lncRNAs RP11-462C24.1 whose function was previously unknown was explored in detail on the aspect of the association of its expression level and clinicopathological features of CRC and patients’ survival. We found that RP11-462C24.1 expression level was lower in cancer tissues compared with adjacent normal samples (P < 0.001). Furthermore, its expression level was lower in CRC patients with metastasis than those without metastasis (P = 0.049). That is, RP11-462C24.1 expression level decreased as the malignant degree of CRC increased. In addition, low expression of RP11-462C24.1 significantly correlated with more distant metastasis (P = 0.011). The areas under ROC curves were 0.78 and 0.65 for RP11-462C24.1, distinguishing CRC from normal tissue and distinguishing CRC without metastasis from CRC with metastasis, respectively. Multivariate analysis identified that RP11-462C24.1 was an independent predictor for patients prognosis (P = 0.005). Furthermore, Kaplan–Meier analysis showed that patients with low expression of RP11-462C24.1 had a poor disease-free survival (P < 0.001). This is the first study that correlates RP11-462C24.1 expression profile with malignancy grade in human CRC. Our results showed that RP11-462C24.1 could be a potential novel prognostic marker for CRC, and thus, provided a new strategy for CRC diagnosis. Meanwhile, our findings indicated the potential roles of RP11-462C24.1 in tumorigenesis and progression of CRC, which gave a clue for future studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s12032-014-0031-7) contains supplementary material, which is available to authorized users.

The association between American Indian/Alaska Native race and time to treatment initiation for nonmetastatic breast, colorectal, and lung cancer patients in Medicare.

6573 Background: Early initiation of treatment following a cancer diagnosis is associated with better patient outcomes. Therefore, we compared time to treatment initiation in American Indian/Alaska...

Diagnostic and prognostic value of miR-205 in colorectal cancer.

Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial cell processes such as the epithelial-mesenchymal transition (EMT) and aberrant expression with tumorigenesis in many types of human malignancy. This prospective study characterized the contribution of miR-205 to the colorectal cancer (CRC) tumorigenesis. The real-time reverse transcription-polymerase chain reaction was used to examine miR-205 levels prospectively in 36 pairs of samples of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). In addition, the relationship between miR-205 levels and clinicopathological features was explored. The capability of miR-205 to function as a tumor marker was also examined. miR-205 expression levels did not show significant changes overall. However, miR-205 was significantly downregulated in a group of CRC samples compared with matched noncancerous tissue samples. Moreover, decreased miR-205 correlated significantly with lymphatic metastasis. A receiver operating characteristic (ROC) curve also showed an optimum cut off point of 1.4?10-3 to distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we found lymphatic metastasis in almost 80% of the depressed samples. This study suggested that miR-205 could be reduced in the majority of metastatic CRCs and the risk of CRC metastasis may be predicted by monitoring miR-205 in patient samples collected at the time of the initial diagnosis. Therefore, targeting miR-205 and its potential environmental activators might be a promising therapeutic option to prevent malignant progression toward metastasis.

Quality of colorectal cancer care among veterans: a 10-year retrospective cohort.

Nearly 5,000 patients within Veterans Health Administration (VHA) are diagnosed with colorectal cancer (CRC) annually. However, the link between performance on CRC practice guidelines and outcomes is unclear. The purpose of this study was to evaluate quality of CRC care by assessing adherence to National Comprehensive Cancer Network (NCCN) guidelines and to determine if receipt of these metrics was associated with improvement in mortality. We performed a retrospective cohort study of all patients who underwent resection for nonmetastatic CRC at VHA Tennessee Valley Healthcare System from 2001 to 2010. We defined "excellent" care as receipt of at least 75% of eligible NCCN metrics. We also examined time to treatment and the relationship between excellent care and mortality. A total of 331 patients underwent resection for CRC within the study period. Only 47% of patients received excellent care, and 9% received 100% of eligible metrics. The median time from diagnosis to definitive treatment was 22days [interquartile range (IQR) 12, 41] and 37days (IQR 24, 56) among colon and rectal cancer patients, respectively. The likelihood of receiving excellent care increased significantly over time. However, there was no association between receipt of excellent care and 5-year all-cause mortality [hazard ratio (HR) 0.85; 95% CI 0.53-1.36]. Although patients received timely care overall, fewer than half of CRC patients received at least 75% of eligible NCCN metrics. Although receipt of excellent care was not associated with reduction in all-cause mortality, further research is necessary to identify quality metrics likely to influence patient outcomes.

Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival

Multicentre randomized trials have demonstrated equivalent long-term outcomes for open and laparoscopic resection of colon cancer. Some studies have indicated a possible survival advantage in certain patients undergoing laparoscopic resection. Patients who receive adjuvant chemotherapy in <8weeks following surgery can have an improved survival. Data were collated for patients having an elective laparoscopic or open resection for non-metastatic colorectal cancer between October 2003 and December 2010 and subsequently having adjuvant chemotherapy. Survival analysis was conducted. In all, 209 patients received adjuvant chemotherapy following open (n=76) or laparoscopic (n=133) surgery. Median length of stay was 3days with laparoscopic resection and 6days with open resection (P<0.0005). Median number of days to initiation of adjuvant chemotherapy was 52 with laparoscopic resection and 58 with open resection (P=0.008). The 5-year overall survival was 89.6% in patients receiving chemotherapy in <8weeks after surgery, compared with 73.5% who started the treatment over 8weeks (P=0.016). The 5-year overall survival for those patients with a laparoscopic resection was 82.3% compared with 80.3% with an open resection (P=0.049). There is an overall survival advantage when patients receive adjuvant chemotherapy <8weeks after surgery. Laparoscopic resection allows earlier discharge and, subsequently, earlier initiation of adjuvant chemotherapy.

Better Long-Term Survival in Young Patients with Non-Metastatic Colorectal Cancer after Surgery, an Analysis of 69,835 Patients in SEER Database

ObjectiveTo compare the long-term survival of colorectal cancer (CRC) in young patients with elderly ones.MethodsUsing Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 69,835 patients with non-metastatic colorectal cancer diagnosed between January 1, 1988 and December 31, 2003 treated with surgery. Patients were divided into young (40 years and under) and elderly groups (over 40 years of age). Five-year cancer specific survival data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.ResultsYoung patients showed significantly higher pathological grading (p<0.001), more cases of mucinous and signet-ring histological type (p<0.001), later AJCC stage (p<0.001), more lymph nodes (≥12 nodes) dissected (p<0.001) and higher metastatic lymph node ratio (p<0.001). The 5-year colorectal cancer specific survival rates were 78.6% in young group and 75.3% in elderly group, which had significant difference in both univariate and multivariate analysis (P<0.001). Further analysis showed this significant difference only existed in stage II and III patients.ConclusionsCompared with elderly patients, young patients with colorectal cancer treated with surgery appear to have unique characteristics and a higher cancer specific survival rate although they presented with higher proportions of unfavorable biological behavior as well as advanced stage disease.

A novel and robust technique for determining lymph node status in colorectal cancer.

483 Background: Currently, techniques that determine lymph node positivity (prior to resection) have poor sensitivity and specificity. The ability to determine lymph node status, based on preoperative biopsies, would greatly assist in planning treatment in colorectal cancer. This is particularly relevant in polyp-detected cancers. This study aims to harness the potential of public gene expression repositories, to develop gene expression profiles that could accurately determine nodal status in colorectal cancer. Methods: Public gene expression repositories were screened for experiments comparing metastatic and non-metastatic colorectal cancer. A customized graphic user interface was developed to extract genes dysregulated across the majority of identified studies (i.e., consensus profiles or “CP”). The utility of CP was tested by determining if classifiers could be derived that determined nodal positivity or negativity. CP-derived classifiers were tested on separate Affymetrix and Illumina–based experiments and collated outputs compiled in summary-receiver operator curve characteristic format. The association between classification and oncologic outcome was determined using an additional, independent data set. Results: Four consensus profiles were generated from which classifiers were derived that accurately determined node positive and negative status (pooled AUC were 0.79 ± 0.04 and 0.8 ± 0.03 for nodal positivity and negativity respectively). Overall AUC ranged from 0.73 to 0.86 demonstrating high accuracy across consensus profile type, classification technique and array platform used. As CP enabled classification of nodal status, survival outcomes could be compared for those predicted node negative or positive. Patterns of disease-free and overall survival were identical to those observed for standard histopathologic nodal status. Genes contained within consensus profiles were strongly linked to the metastatic process and included FYN, WNT5A, COL8A1 and BMP. Conclusions: Microarray expression data available in public gene expression repositories can be harnessed to generate consensus profiles. The latter are a source of classifiers that have prognostic and predictive properties.

Morbidity and mortality after colorectal cancer surgery in patients with cirrhosis: A critical review of the literature.

608 Background: Cirrhotic patients with localized colorectal cancer are potential candidates for tumor resection. The aim of this review was to evaluate the morbi-mortality after colorectal surgery. Methods: Comprehensive search was conducted using PUBMED, EMBASE, and the COCHRANE Library. Prospective and retrospective studies were selected. The study population included cirrhotic patients who underwent colorectal resection for non-metastatic colorectal cancer and patients with benign and other malignant disease. The postoperative morbi-mortality and independent risk factors were analysed. Results: Eight studies were identified. Among these, four studies compared the risk of colorectal surgery in patients with and without liver cirrhosis. The number of patients varied from 41 to 6,120. The severity of cirrhosis in most of the studies was classified with the Child-Pugh score. Class B and C were observed in 20% to 60% of the patients. Sepsis represented the main postoperative complication and occurred in 48% to 77% of patients. Mortality varied according to the Child-Pugh score, ranging from 11% to 41%, and was significantly higher for patients with cirrhosis in Child-Pugh Class C. Urgent surgical procedure had a negative impact on prognosis. The average length of hospital stay ranged from 9 to 18 days. Cirrhosis was associated with a 2-3 time and a 4-10 time increased risk of postoperative mortality in the absence and presence of portal hypertension, respectively compared with non-cirrhotic patients. The independent risk factors for postoperative morbidity and mortality were encephalopathy, ascites, low haemoglobin, prolonged prothrombin time, elevated bilirubin, hypoalbuminemia, postoperative infection, total colectomy, elective or non-elective surgery, the presence of co-morbidities and MELD score ≥ 15. Conclusions: Colorectal cancer surgery is associated with an increased risk of postoperative morbidity and mortality in cirrhosis patients. Studies evaluating exclusively the operative risk for colorectal cancer surgery in this patient’s population are rare. Prospective controlled trials to optimize the perioperative management of those patients are needed.

A randomized, placebo-controlled, double-blind phase II trial of peri-operative cimetidine in early colorectal cancer.

509 Background: A Cochrane meta-analysis of randomised trials using histamine-type 2 receptor antagonists with surgery for colorectal cancer (CRC) demonstrated a hazard ratio of 0.53 for mortality if patients used cimetidine. The benefit is likely to be specific to patients whose tumours express the antigens that allow circulating cells to bind to endothelial selectin (E-selectin), the expression of which is induced by inflammatory cytokines perioperatively and inhibited by cimetidine. This trial sought to evaluate several key issues critical to informing the conduct of a phase 3 trial. Methods: Patients with non-metastatic CRC planned for curative-intent surgery were randomised to receive cimetidine 800mg BID or placebo orally for 5 weeks, starting 2-7 days preoperatively. A subset of patients had serial blood sampling for inflammatory cytokines. In addition to DFS and OS, endpoints assessed include treatment compliance and toxicity, recruitment issues, post-operative stay and complications, and tumour characteristics including expression of sialyl Lewis antigens and COX-2. Results: 123 patients (36% female) have been recruited in 4 centres over 3.5 years; another 4 are required to complete the planned 120 treated patients. The primary tumour was rectal in 45% and pathological postoperative tumour stage was 0-I, II, III, and IV in 29%, 33%, 35%, and 2% respectively. About 50% of CRC patients were eligible and fewer than half of those were recruited. Patient compliance was excellent with 89% of patients taking their medication orally in the first 2 days postoperatively. Inflammatory cytokines were commonly elevated postoperatively for up to 2 weeks but normalised by 4 weeks. Immunostaining for tumour antigens is in progress and will be presented. DFS and OS data are immature. Conclusions: Oral administration of cimetidine for 5 weeks is well-tolerated and feasible over the perioperative period, and covers the duration of elevated inflammatory cytokines. Correlative immunostaining studies will be presented. Clinical trial information: 12609000769280.