Colon Cancer Outcomes Research Articles

Identification of a Genome Instability-Associated LncRNA Signature for Prognosis Prediction in Colon Cancer.

Long non-coding RNAs (lncRNAs) were reported to have the potential in maintaining genome instability, but the identification of lncRNAs related to genome instability and their prognostic value have not been largely explored in colon cancer. In this study, we obtained 155 genome instability-associated lncRNAs based on somatic mutation profiles in colon cancer from The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis revealed the possible roles of genes co-expressed with those lncRNAs involved in some cancer, genome instability and immune related biological processes. Combined with overall survival data, a seven-lncRNA signature was established for prognosis prediction. According to the risk score calculated by this signature, high-risk patients characterized by high somatic mutation count, high microsatellite instability, significantly poorer clinical outcomes and specific tumor immune infiltration status compared with low-risk patients. The lncRNA signature was validated to be an independent prognostic indicator with good predictive performance in TCGA cohort. Furthermore, the prognostic value of the ZNF503-AS1 in lncRNA signature was confirmed in another independent dataset from Gene Expression Omnibus database. In summary, the genome instability-associated lncRNA signature in this study could be a promising tool for effectively predicting survival outcomes in colon cancer.

Cost-effectiveness of breast, lung, colon, prostate and cervical cancer outcomes in Brazil: a worldwide comparison.

IntroductionCancer is the second leading cause of death in the world, and it is expected to be the main cause by the year 2030. Current trends of higher incidence and the introduction of new treatments lead to the challenge of treating more people with increasing costs per capita. In Brazil, current and future challenges are even more significant because of the limited resources destined for healthcare.MethodsWe propose a methodology to compare cost-effectiveness performance with a regression of cancer lethality against the resources available for different nations, using the gross domestic product and the mortality-to-incidence ratio. Our objective is to evaluate and compare outcomes observed in Brazil.ResultsAccording to our methodology, Brazil is performing well in breast and prostate cancer (observed lethality 9% and 15% lower than expected, respectively). It performs close to expected in colon (0.8% higher) and cervix (2% higher). However, lung cancer had a higher lethality than expected (6.5% higher). We also found that breast, prostate and cervical cancers are the primary sites more related to income. Lung cancer had the weakest relationship with resources.ConclusionBrazil has different cost-effectiveness results in the management of cancer depending on the primary site. Also, national income has a significant and heterogeneous effect on the lethality of different tumour types. This economic analysis is important for low- to middle-income countries seeking to evaluate cancer outcomes in limited-resource settings.

ID: 3521919 IMPACT OF GROSS TUMOR MORPHOLOGY ON THE CLINICAL OUTCOMES OF NON-METASTATIC COLON CANCER : MULTICENTER RETROSPECTIVE COHORT STUDY

Background/Aims: There has been no data regarding the association between gross morphology and clinical outcomes of colon cancers. We aimed to investigate the relationship between endoscopic features and outcomes of non-metastatic colon cancer.

GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling.

Effective treatment regimens for triple-negative breast cancer (TNBC) are relatively scarce due to a lack of specific therapeutic targets. Epidermal growth factor receptor (EGFR) signaling is highly active in TNBC and is associated with poor prognosis. Most EGFR antagonists, which significantly improve outcome in lung and colon cancer, have shown limited clinical effects in breast cancer. However, limiting EGFR expression in TNBC is a potential strategy for improving the clinical efficacy of EGFR antagonists. Here, we found that the gamma-aminobutyric acid type A receptor π subunit (GABRP), as a membrane protein enriched in TNBC stem cells, interacted with EGFR and significantly sustained its expression, resulting in stemness maintenance and chemotherapy resistance. Silencing GABRP induced down-regulation of EGFR signaling, which hindered cell stemness and enhanced sensitivity to chemotherapies, including paclitaxel, doxorubicin, and cisplatin. We also identified that retigabine, an FDA-approved drug for adjunctive treatment of seizures, increased the sensitivity of EGFR to gefitinib in gefitinib-resistant cells. Our findings show that GABRP can sustain the stemness of TNBC via modulating EGFR expression, suggesting that GABRP may be a potential therapeutic target that can address EGFR inhibitor resistance in TNBC.

Landscape of homologous recombination-related (HRR) genes mutations in colon cancer.

e15525 Background: Homologous recombination deficiency (HRD) might serve as a biomarker of immunotherapy and chemotherapy response. In addtion, HRD is associated with sensitivity to PARP inhibitor (PARPi) therapy. The HRD phenotype has been defined as the presence of a non-silent somatic mutation in homologous recombination-related (HRR) genes. Here, we focused on mutational landscape of HRR genes and the relationship between HRR-related genes and clinical outcomes in colon cancer. Methods: We prospectively sequenced 784 Chinese patients with colon cancer using next-generation sequencing techniques with 808 cancer-related genes. 290 patients with somatic mutation from the TCGA project were included. The 15 HRR genes were selected on clinical evidence of sensitivity to PARP inhibitors and immunotherapy. TCGA datasets were performed to identify the correlations between HRR gene mutations and clinical outcomes. Results: In the Chinese cohort, 11.5% (90/784) patients exhibited deleterious somatic mutation in HRR genes, including ATM (3.3%), BRCA2 (2.4%), CDK12 (2.4%), BRCA1 (1.0%), BRIP1 (1.0%), CHEK2 (0.5%), BARD1 (0.4%), RAD54L (0.4%), PALB2 (0.3%), and RAD51B (0.3%). In TCGA cohort, 28.6% (83/290) patients had at least one deleterious somatic mutation in HRR genes, including ATM (14.8%), BRCA2 (9.0%), CDK12 (7.9%), BRIP1 (3.8%), BRCA1 (3.4%), FANCL (3.1%), CHEK2 (2.4%), PALB2 (2.1%), PPP2R2A (2.1%), RAD54L (2.1%), CHEK1 (1.7%), BARD1 (1.4%), RAD51C (1.4%), RAD51B (1.0%), and RAD51D (0.3%). Overall, the mutational frequency of HRR genes in the Chinese cohort was lower than that in the TCGA cohort (p < 0.001). In the TCGA cohort, colon patients with HRR-mut had significantly higher tumor mutational burden and incidence of microsatellite instability high and enhanced immune activity than patients with HRR-wt. Furthermore, In the MSK-IMPACT cohort treated by immune checkpoint inhibitor, patients with HRR-mut had significantly better OS (p = 0.009) and increased immune activities, such as infiltration of cytotoxic cells (p < 0.05) and exhausted CD8+ T cells (p < 0.01), and increased the IFN-γ scores (p < 0.05) than patients with HRR-wt. Conclusions: Our data suggest that detection of somatic mutations in HRR genes might contribute to identify patients who might benefit from immune checkpoint blockade therapy and PARP inhibitors. In addition, the molecular features of HRR provide new opportunities to predict the tumor response to multiple treatments. Exploring other biomarkers of HRD to predict the response to PARPi and immunotherapeutic in colon cancer is necessary.

Association of rurality and race with surgical treatment and outcomes for nonmetastatic colon cancer.

e18536 Background: Rural cancer patients face limited access to care due to greater travel distance and lack of specialty cancer care. Little is known about the intersection of rurality with well-documented racial disparities in colon cancer treatment and outcomes. Methods: We used fee-for-service Medicare claims to study patients age 65+ diagnosed with incident colon cancer without evidence of metastases who underwent cancer-directed surgery between 04/01/2016 and 09/30/2018. The primary exposure was rurality of patient’s residence categorized as metropolitan (metro), micropolitan, and small town/rural. Outcomes were non-elective surgery (emergency department visit or transfer within 2 days of surgery), receipt of minimally invasive surgery (laparoscopic or robotic), 90-day surgical complications, and 90-day mortality. Logistic regression adjusted for patient demographics, cancer side (right vs left), comorbidities, and Area Deprivation Index. We assessed effect modification by race/ethnicity. Results: Of 57,710 patients with incident non-metastatic colon cancer, 37,691 (65%) underwent surgery. In this surgical cohort, small town/rural and micropolitan residents were more likely to be older, white, and Medicare-Medicaid dual-eligible than metro residents. After risk adjustment, patients in small town/rural areas had higher odds of non-elective surgery (OR=1.24, 95% CI:1.13-1.36) and lower odds of minimally invasive surgery (OR=0.75, 95% CI:0.71-0.80) than patients living in metro areas. Similar results were seen for micropolitan areas. The association between rurality and 90-day outcomes differed by race/ethnicity (p-interaction=0.001 for surgical complications and mortality, see Table). Hispanics and other races had higher odds of 90-day surgical complications in non-metro versus metro areas but there was no notable difference for white patients. Likewise, compared to metro areas, racial/ethnic minorities had higher odds of 90-day mortality in small town/rural areas but white patients had lower odds. Conclusions: Small town/rural-residing Medicare beneficiaries undergoing surgery for non-metastatic colon cancer were less likely to receive optimal surgical management and worse outcomes, especially among non-white patients. The compounded effect of sociodemographic factors should be further studied to develop targeted policies and improve care for rural cancer patients.[Table: see text]

A Single Institution Propensity Score Weighted Analysis of Time to Chemotherapy After Minimally Invasive Versus Open Colorectal Surgery

Oncologic outcomes for colon cancer are optimal when chemotherapy is started within 6 to 8weeks after surgery. The study objective was to investigate the impact of operative modality and urgency on the time interval from surgery to adjuvant chemotherapy. This is a retrospective institutional tumor registry cohort study of open and laparoscopic/robotic colorectal resections for stage II-IV cancer between April 2010 and January 2018. Primary outcome was time from surgery to chemotherapy. Predictor variables were adjusted for imbalances by propensity score weighting. A total of 220 patients met inclusion criteria: 171 elective (108 laparoscopic/robotic and 63 open) and 49 urgent colectomies. After propensity score weighting, there was no significant difference in time to chemotherapy between elective minimally invasive and open surgical approaches (48days vs. 58days, P = .187). Only 68.9% of minimally invasive and 50.8% of open colectomy patients started chemotherapy within 8weeks of surgery. There was a significant difference (P = .037) among surgical sites with rectal resections having the longest (55days), and right colectomies having the shortest (46days), time to chemotherapy. Patients who had urgent operations had significantly longer hospital length of stay (P < .001) and higher post-discharge emergency department visit rates (P < .001) than the elective operation group. However, there was no significant difference in time to chemotherapy. Neither operative modality nor operative urgency resulted in a significant difference in postoperative time to initiating chemotherapy. Future efforts should be focused on identifying postoperative recovery criteria and optimum multidisciplinary communication methods that allow recovered patients to start chemotherapy sooner.

Race, Income, and Survival in Stage III Colon Cancer: CALGB 89803 (Alliance).

BackgroundDisparities in colon cancer outcomes have been reported across race and socioeconomic status, which may reflect, in part, access to care. We sought to assess the influences of race and median household income (MHI) on outcomes among colon cancer patients with similar access to care.MethodsWe conducted a prospective, observational study of 1206 stage III colon cancer patients enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial. Race was self-reported by 1116 White and 90 Black patients at study enrollment; MHI was determined by matching 973 patients’ home zip codes with publicly available US Census 2000 data. Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary, and lifestyle factors. All statistical tests were 2-sided.ResultsOver a median follow-up of 7.7 years, the adjusted hazard ratios for Blacks (compared with Whites) were 0.94 (95% confidence interval [CI] = 0.66 to 1.35, P = .75) for disease-free survival, 0.91 (95% CI = 0.62 to 1.35, P = .65) for recurrence-free survival, and 1.07 (95% CI = 0.73 to 1.57, P = .73) for overall survival. Relative to patients in the highest MHI quartile, the adjusted hazard ratios for patients in the lowest quartile were 0.90 (95% CI = 0.67 to 1.19, Ptrend = .18) for disease-free survival, 0.89 (95% CI = 0.66 to 1.22, Ptrend = .14) for recurrence-free survival, and 0.87 (95% CI = 0.63 to 1.19, Ptrend = .23) for overall survival.ConclusionsIn this study of patients with similar health-care access, no statistically significant differences in outcomes were found by race or MHI. The substantial gaps in outcomes previously observed by race and MHI may not be rooted in differences in tumor biology but rather in access to quality care.

Hyperthermic Intraperitoneal Chemotherapy Fails to Improve Colon Cancer Outcomes

Patients with colorectal cancer and peritoneal disease amenable to cytoreductive surgery are often treated with hyperthermic intraperitoneal

Stage III colon cancer: is neoadjuvant chemotherapy ready for prime time?—A narrative review of neoadjuvant chemotherapy for colon cancer

: The current standard of care for stage III colon cancer has been adjuvant chemotherapy since this was first shown to be beneficial three decades ago. Despite the improvement in outcomes after introduction of oxaliplatin a decade ago, relapse rates are still significant with associated high morbidity and mortality related to metastatic colon cancer worldwide. Discovery of novel agents for use in colon cancer has been slow and disappointing. Repurposing currently available drugs with known activity in colon cancer into a neoadjuvant chemotherapy regimen has the potential to improve outcomes in colon cancer even while we await development of new drugs. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been encouraging, demonstrating lower pathologic stage amongst treated patients, and higher rates of R0 resection. However, only early data is available and long term survival outcomes are eagerly awaited. Challenges include optimal staging and patient selection for neoadjuvant therapy, with current methods of radiologic staging lacking specificity to exclude low risk patients (who might not require chemotherapy) from trials. Novel approaches, a notable example being the use of immunotherapy for mismatch repair (MMR) deficient tumours, hold promise of higher response rates without increasing toxicity. Neoadjuvant chemotherapy for this disease still requires further data to be available before it is ready for widespread use, however shows great promise. This review article will discuss the available data regarding rationale and evidence for neoadjuvant chemotherapy for colon cancer.

Alcohol Consumption, HDL-Cholesterol and Incidence of Colon and Rectal Cancer: A Prospective Cohort Study Including 250,010 Participants.

AimsAlcohol consumption has been linked to colorectal cancer (CRC) and also to the high-density lipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aim of this study was to investigate the association between self-reported alcohol consumption, HDL-C and incidence of CRC, separately for the two sites.MethodsAltogether, 250,010 participants in Norwegian surveys have been followed-up for an average of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up, 3023 and 1439 colon and rectal cancers were registered.ResultsFor men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98–1.12) for colon and 1.08 (1.02–1.15) for rectal cancer. The corresponding figures for women were 1.03 (0.97–1.10) and 1.05 (1.00–1.10). There was a positive association between alcohol consumption and HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62–0.89) per 1 mmol/l) and positively associated with rectal cancer, although not statistically significant (1.15 (0.92–1.44). A robust regression that assigned weights to each observation and exclusion of weights ≤ 0.1 increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. The associations with rectal cancer remained unchanged.ConclusionOur results support a positive association between alcohol consumption and colon and rectal cancer, most pronounced for rectal cancer. Considering the positive relation between alcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in men remains unsettled.

Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities.

BackgroundDisparities in colon cancer (CC) outcomes may be due to a more aggressive phenotype in African American patients in the setting of a decreased tumor immunity, though the precise mechanism for this result has not been well elucidated. To explore the molecular factors underlying CC disparities, we compared the immunogenomic signatures of CC from African American and European American patients.MethodsWe identified all CC patients from the publicly available Cancer Genome Atlas for whom race and survival data are available. Immunophenotype signatures were established for African American and European American patients. Comparisons were made regarding survival and a multivariable linear regression model was created to determine the association of immune cellular components with race. Differential gene expression was also assessed.ResultsOf the 254 patients identified, 58 (23%) were African American and 196 (77%) were European American. African American patients had a decreased progression free survival (p = 0.04). Tumors from African American patients displayed a reduced fraction of macrophages and CD8+ T cells and an increased fraction of B cells compared with tumors from European Americans. Differences persisted when controlling for sex, age, and disease stage. Immunostimulatory and immunoinhibitory gene profiles including major histocompatibility complex expression differed by race.ConclusionsDifferences in the tumor immune microenvironment of African American as compared to European American CC specimens may play a role in the survival differences between the groups. These differences may provide targeted therapeutic opportunities.

A National Cancer Database (NCDB) analysis of the impact of nonmetastatic colon cancer sidedness on survival.

139 Background: Differences in embryological origin and tumor biology distinguish right-sided colon cancer (RCC) from left-sided colon cancer (LCC). Previous studies characterizing the prognostic impact of colon cancer laterality on clinical outcomes in non-metastatic colon cancer have been conflicting, thus closer examination is needed. Methods: Using the NCDB, patients with stage I-III colon cancer between 2004-2014 were stratified according to tumor location; RCC vs. LCC. Patient (pt) and tumor characteristics were compared in univariate analysis, survival (OS) was estimated by Kaplan-Meier (KM) curves and Cox proportional hazards modeling. Binomial logistic regression analysis was utilized to identify variables associated with colon cancer laterality. Results: Of the 342,735 pts who met inclusion criteria, 210,343 (61.4%) were diagnosed with RCC, and 132,392 (38.6%) with LCC. Pts with RCC were older (mean 71.6 vs. 66.4 years, p&lt; 0.001) and predominantly female (65% vs. 35%, p&lt; 0.001) compared to those with LCC. A trend towards poorer OS was seen in pts with RCC (mean 91.0 mos [95% CI: 90.2-91.8]) compared to LCC (112.2 mos [95% CI: 110.9-113.6]) in unadjusted analysis. On Cox multivariable adjusted analyses there was a significant but minimal impact on OS and laterality (hazard ratio or HR [LCC as ref] 0.978, 95% CI 0.967-0.989 p&lt; 0.0001). Multiple unadjusted KM survival analyses showed RCC with T4 disease, high-grade, LVI/PNI, positive margins, N0-N2 disease, tumor deposits, and receipt of adjuvant chemotherapy had poorer OS than those features in LCC (all p &lt; 0.0001). Binomial logistic regression showed RCCs were significantly more likely to be higher grade (odds ratio or OR 2.024) and MSI-H (OR 2.010) with trends (nonsignificant) towards more likely having N1-2 positive disease, LVI, less receipt of adjuvant chemotherapy, and fewer tumor deposits. Conclusions: The impact of sidedness on prognosis in stage I-III colon cancer is complex. In this large, population-based study, RCC tends to be associated with more adverse prognostic features than LCC. More investigation into the biologic differences between RCC and LCC is warranted and how they impact phenotype and survival.

Metastasis to lymph nodes around the vascular tie worsens long-term oncological outcomes following complete mesocolic excision and conventional colectomy for right-sided colon cancer.

Oncologic outcomes after complete mesocolic excision (CME) in colon cancer are under investigation. The aim of our study was to compare CME and conventional colectomy (CC) in terms of pathological and oncological outcomes for right colon cancer and to evaluate the impact of lymph node metastasis around the vascular tie on survival. Consecutive patients with right colon cancer who had CME or CC between January 2011 and August 2018 at two specialized centers in Turkey were included. Statistical analyses were performed with respect to demographic characteristics, operative and pathologic outcomes, harvested and metastatic lymph nodes around the vascular tie (LNVT), recurrences, and survival. There were 91 patients in the CME group (58 males, mean age 64 ± 16years) and 192 patients in the CC group (96 males, mean age 66 ± 14years). The mean number of harvested lymph nodes (CME: 42 ± 15 vs CC: 34 ± 13, p = 0.01) and LNVT were higher in the CME group (CME: 3.2 ± 2.2 vs CC: 2.4 ± 1.6, p = 0.001). LNVT metastases were 7.7% and 8.3% in the CME and CC groups, respectively (p = 0.85). Three-year overall and disease-free survival rates were 96.4% and 90.9% in the CME group and 90.4% and 87.6% in the CC group in stage I-III patients (p > 0.05). In stage III patients, the 3-year overall survival (92.5% vs 63.5%, p = 0.03) and disease-free survival (85.6% vs 52.1%, p = 0.008) were significantly better in LNVT-negative patients than in LNVT-positive patients. LNVT metastasis seems to be the key factor associated with poor disease-free and overall survival in right colon cancer regardless of the radicality of surgery.

Perioperative and long-term outcomes of robot-assisted versus laparoscopy-assisted hemicolectomy for left-sided colon cancers: a retrospective study

The objective of this study is to evaluate the perioperative and long-term outcomes of robot-assisted hemicolectomy (RAH) versus laparoscopy-assisted hemicolectomy (LAH) for left-sided colon cancers. Patients who underwent RAH and LAH from January 2012 to December 2018 were reviewed retrospectively. Patient characteristics and perioperative outcomes were compared between the two groups. Follow-up consultations were conducted to evaluate the long-term outcomes of these procedures. A total of 460 patients were included (RAH, n = 205; LAH, n = 255). There was no difference in patient characteristics between the two groups. Compared with the LAH group, the RAH group showed longer operative time (150.23 ± 43.77 min vs. 125.85 ± 38.67 min, p < 0.001) and higher surgery cost (6.33 ± 1.50 vs. 2.88 ± 0.72 thousand $, p < 0.001) and total hospital cost (14.97 ± 3.05 vs. 9.05 ± 2.31 thousand $, p < 0.001). No significant differences in tumor pathology, TNM staging, and perioperative outcomes were observed. There were no obvious differences in the 3-year and 5-year overall survival (OS) or 3-year and 5-year disease-free survival. Cox multivariate analyses showed that age, body mass index, and intravascular cancer embolus were independent risk factors for OS. Moreover, the robotic approach was not an independent risk factor for prognosis of left-sided colon cancers. RAH is an appropriate operation method for left-sided colon cancer, with perioperative and long-term outcomes comparable to those of laparoscopy. Meanwhile, RHA has longer operative time and higher cost.

Partnering to Reduce Colon Cancer Health Disparities Among the American Indian Population in Michigan

American Indian and Alaska Native people experience higher rates of several cancers, including lung, colorectal, liver, stomach, and kidney cancers, compared to non-Hispanic White people in the United States. Cancer disparities are also prominent among the American Indian population and vary by region. Disproportionately high rates of colon cancer were identified among three tribal communities in Michigan by linking each tribe’s enrollment roster to the state cancer registry. In response, in 2015 the Inter-Tribal Council of Michigan received funding from the Office of Minority Health within the U.S. Department of Health and Human Services to work with the three tribes to develop and implement the Tribal Colon Cancer Collaborative Project. The project used a community-based participatory research approach and a learning collaborative model to implement a multipronged initiative intended to improve colon cancer screening rates and outcomes among the three tribal communities. Local tribal coordinators were trained in the use of evidence-based interventions, including patient navigation and quality improvement processes, and implemented activities within their respective tribal health settings. Preliminary findings indicated increased colon cancer screening rates and improved rates of early stage cancer diagnoses. This paper describes the processes involved in implementing the project in collaboration with local tribal coordinators and the details of their journey toward improved colon cancer health outcomes.

Mining the potential prognostic value of synaptosomal-associated protein 25 (SNAP25) in colon cancer based on stromal-immune score.

BackgroundColon cancer is one of the deadliest tumors worldwide. Stromal cells and immune cells play important roles in cancer biology and microenvironment across different types of cancer. This study aimed to identify the prognostic value of stromal/immune cell-associated genes for colon cancer in The Cancer Genome Atlas (TCGA) database using bioinformatic technology.MethodsThe gene expression data and corresponding clinical information of colon cancer were downloaded from TCGA database. Stromal and immune scores were estimated based on the ESTIMATE algorithm. Sanger software was used to identify the differentially expressed genes (DEGs) and prognostic DEGs based on stromal and immune scores. External validation of prognostic biomarkers was conducted in Gene Expression Omnibus (GEO) database. Gene ontology (GO) analysis, pathway enrichment analysis, and gene set enrichment analysis (GSEA) were used for functional analysis. STRING and Cytoscape were used to assess the protein-protein interaction (PPI) network and screen hub genes. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of hub genes in clinical tissues. Synaptosomal-associated protein 25 (SNAP25) was selected for analyzing its correlations with tumor-immune system in the TISIDB database.ResultsWorse overall survivals of colon cancer patients were found in high stromal score group (2963 vs. 1930 days, log-rank test P = 0.038) and high immune score group (2894 vs. 2230 days, log-rank test P = 0.076). 563 up-regulated and 9 down-regulated genes were identified as stromal-immune score-related DEGs. 70 up-regulated DEGs associated with poor outcomes were identified by COX proportional hazard regression model, and 15 hub genes were selected later. Then, we verified aquaporin 4 (AQP4) and SNAP25 as prognostic biomarkers in GEO database. qRT-PCR results revealed that AQP4 and SNAP25 were significantly elevated in colon cancer tissues compared with adjacent normal tissues (P = 0.003, 0.001). GSEA and TISIDB suggested that SNAP25 involved in cancer-related signaling pathway, immunity and metabolism progresses.ConclusionSNAP25 is a microenvironment-related and immune-related gene that can predict poor outcomes in colon cancer.

S0323 Precancerous Polyp and Colorectal Cancer Detection Rates and Safety of Surveillance Colonoscopy in Individuals Aged 75 Years and Above

INTRODUCTION: The risk of development of colorectal cancer (CRC) increases with age and history of colonic adenomas. Currently, there is limited data and lack of consensus about the age to discontinue surveillance colonoscopy in patients aged 75 and above who have had polyps in the past. Most guidelines recommend this decision to be considered individually. We aim to determine the precancerous polyp detection rate during surveillance colonoscopies and safety for individuals above age 75. METHODS: We conducted a retrospective chart review to identify patients who underwent a colonoscopy between the years of 2012 to 2019 and were over age 75. We collected data on patient characteristics, colonoscopy findings and histology of polyps. Exclusion criteria were patients with a history of CRC, polyposis syndromes, or Inflammatory Bowel Disease were excluded. Inclusion criteria included all colonoscopies being performed due to a history of colon polyps. Statistical analyses were conducted in SPSS version 26 to compute means and frequencies of patient characteristics and colonoscopy outcomes. RESULTS: A total of 591 colonoscopies were analyzed and 173 met the inclusion criteria. Median age was 78. A majority of the patients were female (55.5%) and Caucasian (92.5%). Good bowel preparation and high cecal intubation rates were consistent in all groups (Table 1). The majority of patients took aspirin (56.1%), had an ASA level 2 or less (71.7%) while a significant proportion had metabolic syndrome (43.3%), obesity (34.1%), alcohol abuse history (35.3%) and were ex-smokers (38.7%). Precancerous polyps were found in 15/173 (8.7%) colonoscopies. Most of the precancerous polyps were small, located in the proximal colon, and tubular or tubulovillous adenomas on histology (Table 2). The proportion of distal precancerous polyps increased with age. CRC was detected in the distal colon in one patient (0.57 %). No patients developed complications during or after their colonoscopy. CONCLUSION: In contrast to prior studies in the elderly which show a higher preponderance of polyps and/or cancer in the proximal colon, our limited data shows a higher rate of distal colon polyps and one distal CRC in the subgroup who are over age 85 (8% prevalence). There were no complications observed and the majority of the patients were healthy (ASA 1 or 2). Larger studies should be performed to further validate our findings while decision regarding surveillance colonoscopy should continue to be individualized.Table 1.: Demographics, colon cancer risk factors and quality features of surveillance colonoscopyTable 2.: Polyp and Colon cancer outcomes of surveillance colonoscopy

Neutrophil-to-lymphocyte ratio is a prognostic factor for colon cancer: a propensity score analysis

BackgroundA large number of patients suffer recurrence after curative resection, and mortality from colon cancer remains high. The role of systemic inflammatory response, as reflected by neutrophil-to-lymphocyte ratio (NLR), in cancer recurrence and death has been increasingly recognized. This study aimed to analyze long-term oncologic outcomes of Stage II-III colon cancer to examine the prognostic value of NLR using a propensity score analysis.MethodsA total of 375 patients with colon cancer underwent radical surgery between 2000 and 2014 at Tokyo Medical University Hospital. Long-term oncologic outcomes of these patients were evaluated according to NLR values. A cut-off NLR of 3.0 was used based on receiver operating characteristic curve analysis. Primary outcomes were overall survival (OS) and relapse-free survival (RFS). An analysis of outcomes according to tumor sidedness was also performed.ResultsPatients with lower NLR values (“lower NLR group”) were more likely to have lymph node metastasis compared to those with higher NLR values (“higher NLR group”) before case matching. After case matching, clinical outcomes were similar between the two groups. There were no significant differences in 5-year OS and 5-year RFS rates between the two groups before case matching based on propensity scores. After case matching, 5-year OS rates were 94.5% in the lower NLR group (n = 135) and 87.0% in the higher NLR group (n = 135), showing a significant difference (p = 0.042). Five-year RFS rates were 87.8% in the lower NLR group and 77.9% in the higher NLR group, also showing a significant difference (p = 0.032). Among patients with left-sided colon cancer in the matched cohort, 5-year OS and 5-year RFS rates were 95.2 and 87.3% in the lower NLR group (n = 88), respectively, and 86.4 and 79.2% in the higher NLR group (n = 71), respectively, showing significant differences (p = 0.014 and p = 0.047, respectively).ConclusionsThe NLR is an important prognostic factor for advanced colon cancer, especially for left-sided colon cancer.

Interobserver Agreement Among Pathologists in the Differentiation of Sessile Serrated From Hyperplastic Polyps

Colorectal cancer (CRC) is the third most common cancer in the United States, with approximately 135,430 new cases and 50,260 deaths every year. 1 Jemal A. et al. J Natl Cancer Inst. 2017; 109: djx030 Crossref Scopus (777) Google Scholar ,2 Siegel R.L. et al. CA Cancer J Clin. 2017; 67: 177-193 Crossref PubMed Scopus (2659) Google Scholar It has been widely recognized now that approximately 20%–30% of CRCs arise from serrated polyps through a serrated/methylated pathway that includes BRAF mutation and DNA methylation that is distinct from the traditional adenoma-carcinoma sequence. 3 Noffsinger A.E. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol. 2009; 4: 343-364 Crossref PubMed Scopus (178) Google Scholar , 4 Ogino S. et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2009; 58: 90-96 Crossref PubMed Scopus (613) Google Scholar , 5 Kambara T. et al. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut. 2004; 53: 1137-1144 Crossref PubMed Scopus (594) Google Scholar Sessile serrated polyps are flat/sessile and have similar color to the surrounding mucosa, making it difficult to differentiate between the normal colonic mucosa and the polyp itself. Serrated lesions are classified pathologically per the World Health Organization (WHO) criteria 6 Bosman F.T. et al. WHO classification of tumours of the digestive system. World Health Organization, 2010 Google Scholar into (1) hyperplastic polyp (HP), (2) sessile serrated adenoma (SSA)/sessile serrated polyp (SSP) with or without cytologic dysplasia, and (3) traditional serrated adenoma (TSA). Differentiating sessile serrated adenomas from hyperplastic polyps is difficult but clinically important because it guides surveillance intervals.