bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hsa-miR-196a2 Rs 11614913 C>T polymorphism and CRC susceptibility: A case-control study.
Authors: Chen Li-zhu , Chen Yu , Tang Wei-feng , Chen Lin , Lin Jin , Guo Zeng-qing , Huang Yufang , Xia Xuefeng 
Published: May 2020

e16066 Background: The incidence and mortality rate of Colorectal cancer (CRC) is high worldwide. Many genetic studies have suggested that single nucleotide polymorphisms (SNPS) in genes encoding small molecule RNAs were associated with CRC risk, but the results were different in different studies. In our study, we investigated the general demographic characteristics and the relationship of hsa-mir-196a2 rs11614913 C > T polymorphism and CRC susceptibility in Chinese CRC. Methods: Our study included 1,003 CRC patients and 1,303 controls. Restriction fragment length polymorphism (RFLP-PCR) method was used for genotyping and SAS version 9.4 software for statistical analysis. Results: The incidence of smoking status,alcohol use and BMI in the CRC group (25.82%,17.35%,66.80%) were much higher than that in the control subjects (20.34%,10.44%,52.80%) respectively(P < 0.05). After adjusting age and other factors, hsa-mir-196a2 rs11614913 C > T genotypes were not statistically correlated with CRC risk and tumor location.But the TT genotype in the hsa-mir-196a2 rs11614913 C > T polymorphism reduced the risk of CRC in women (OR = 0.64, 95 CI: 0.42-0.97, P = 0.036). Conclusions: Smoking status,alcohol use and BMI may be main risk factors for CRC development in our study population.The polymorphism of hsa-mir-196a2 rs11614913 C > T gene may affect the risk of CRC in women, which requires further investigation in a larger cohort in the future.
Rural and urban disparities based on zip code of residence: Analyses of 834 and 2,159 patients in NCCTG N9741 and CALGB 80405 (Alliance) trials respectively.
Authors: Malla Midhun , Huebner Lucas J. , Piawah Sorbarikor , Lenz Heinz-Josef , Blanke Charles David , Meyerhardt Jeffrey A. , O'Reilly Eileen Mary , Shi Qian , Venook Alan P. , Goldberg Richard M. 
Published: May 2020

e16076 Background: Median overall survival (mOS) of patients (pt) with metastatic colorectal cancer (mCRC) has improved steadily over the past two decades. However, epidemiological data suggest that cancer outcomes for rural compared to urban dwelling pts are worse. In this study, we retrospectively compared progression free survival (PFS) and OS among mCRC pts residing in urban versus rural areas enrolled in N9741 (1997-2004) and CALGB 80405 (2005-2012) clinical trials. Methods: Zip code data from the Centers for Disease Control (CDC) were used to classify pts into rural or urban dwellers. Chi-square and Kruskal Wallis analyses were used to compare the groups. Survival outcomes were evaluated using Kaplan-Meier estimates, compared by stratified log rank and cox proportional hazards models. Results: In N9741 and 80405 respectively, 217 (35%) and 521 (21%) pts resided in rural areas. Median age of mCRC pts at diagnosis was 60.5 yrs. (rural) compared to 58.6 yrs. (urban) in 80405 (P < 0.01) and 59.6 yrs. to 60.2 yrs. in N9741 (P = 0.4). In 80405, pts in rural areas were less likely to be female (35% vs 43%, P < 0.01) black (6.6% vs 15.1%, P < 0.01), unmarried (51% vs 62%, P < 0.01), and to have private insurance (PI) (45% vs 50%, P = 0.03) when compared to pts in urban areas. In N9741, gender (P = 0.8) and PI (P = 0.3) distribution was similar; pts in rural areas were less likely to be black (1.4% vs 9.1%, P < 0.01). Rural vs urban pt PFS was no different in either trial. MOS was worse in pts in rural areas when compared to urban dwellers in 80405 (Table). OS outcomes stratified based on the use of cetuximab based regimen in 80405 showed worse outcomes for pts in rural compared to urban dwellers (21.9 vs 26.3 mo. HR: 1.22 (1.03-1.44), P = 0.02). Conclusions: MCRC pts from rural areas had a significantly worse mOS when compared to pts in urban areas in 80405. Furthermore, mOS with cetuximab based regimens was 4.4 months shorter in rural pts. The observed rural vs urban dweller mOS disparities in 80405 pts justifies additional research searching for causal factors and the necessity to identify actionable approaches in order to improve pt outcomes in rural areas. Support: U10CA180821, U10CA180882, U10CA180888, UG1CA180830; Pfizer, Sanofi, BMS, Genentech, https://acknowledgments.alliancefound.org . ClinicalTrials.gov Identifier: NCT00003594, NCT00265850. [Table: see text]
Correlation of LINE-1 hypomethylation with size and dysplasia in colorectal tubular adenomas, and risk for synchronous and metachronous CRC.
Authors: Jiang Alice , Sutherland Stephanie , Buckingham Lela , Melson Joshua 
Published: May 2020

e16083 Background: Conventional adenomas (tubular or tubulovillous adenoma; TA) are frequently detected in patients undergoing average risk screening colonoscopy. Risk stratification of adenomas is currently limited to histologic features and size. Molecular features of TA could help further determine risk for development of CRC. Here, we report whether size of TA, high grade dysplasia, and synchronous or metachronous CRC associate with LINE-1 methylation. Methods: LINE-1 methylation was assessed by pyrosequencing of bisulfite-converted DNA. We compared LINE-1 methylation in TA among varying sizes, in the presence of high or low grade dysplasia, and between patients with synchronous and metachronous colorectal cancer. Results: LINE-1 methlyation was found to progressively decrease in TA of increasing size and with high grade dysplasia. TA < 5mm in size (n = 45) had higher LINE-1 methylation levels compared to TA 5-9mm in size (n = 42), and > = 10mm (n = 32) (72.31 ± 6.11 vs 67.50 ± 7.00 vs 66.75 ± 11.89, p = 0.013). TA with high grade dysplasia (n = 26) had lower LINE-1 methylation levels compared to low grade dysplasia (n = 135) (59.86±7.93 vs 67.16±9.20, p < 0.001). Tumor tissue (n = 36) had the lowest levels of LINE-1 methylation at 50.36±8.40. There were lower levels of LINE-1 methylation in TA of patients with synchronous CRC compared to those without (53.07+4.5 vs 59.95+5.4 vs, p < 0.001). LINE-1 methylation was lower in normal tissue from cancer patients compared to that from patients without any neoplasia (50.36 ± 8.40 vs 71.50 ±6.47, p < 0.001). LINE-1 methylation levels were higher in patients with initial low risk TA who developed metachronous high risk TA (n = 31) compared to those who did not (n = 35) (75.78±2.45 vs 64.84±4.58, p = 0.001). LINE-1 methylation levels were not different in patients with initial TA who developed metachronous CRC (n = 2) compared to those who did not (n = 89) (70.00±5.65 vs 66.85±8.20, p = 0.69). Conclusions: High-grade dysplasia and increasing size of conventional TA were associated with greater LINE-1 hypomethylation. This is supportive of a hypothesis that greater LINE-1 hypomethylation of tubular adenomas indicates advancement along the CRC tumorigenesis pathway. Greater LINE-1 hypomethylation in TA was also seen in patients with synchronous CRC compared to those without, though no difference was found in those who developed metachronous CRC. Higher LINE-1 methylation was seen in patients with initial low risk TA, who developed metachronous high risk TA compared to those who did not.
Outcomes of rectal cancer patients treated using Polish II neoadjuvant short course radiation therapy and chemotherapy approach in comprehensive cancer center.
Authors: Haff Stephen , Kazmi Syed Mohammad Ali , Sanford Nina Niu , Aguilera Todd Anthony , Beg Muhammad Shaalan , Farkas Linda , Anandam-Matthews Joselin , Salgado Pogacnik Javier , Cheedella Naga , Karri Sirisha , Kainthla Radhika , Jones Amy Little , Verma Udit , Sanjeevaiah Aravind , Folkert Michael Ryan 
Published: May 2020

e16088 Background: Neoadjuvant short-course (SC) radiation (RT) followed by fluoropyrimidine based chemotherapy prior to surgery (Polish II approach) is a less utilized treatment in the United States for rectal cancer. Based on data suggesting equivalent or improved outcomes at lower cost compared to the long course neoadjuvant chemoradiation, our team started utilizing this approach for rectal cancer management at Simmons Comprehensive Cancer Center. We aim to document our experience with Polish II approach at NCI-designated comprehensive cancer center program. Methods: A retrospective review of stage I-IV rectal cancer patients, seen at an academic center or the Dallas County safety net hospital and treated at Simmons Comprehensive Cancer Center from Nov 2017 to Dec 2019. Patients were treated with neoadjuvant SC-RT followed by 3 cycles of FOLFOX prior to surgery and followed by adjuvant FOLFOX. Descriptive data for demographic, radiation, chemotherapy and surgery, hospitalizations, 30 day post-surgery admission, time to relapse, and laboratory parameters was collected. Results: Thirty-nine patients met the inclusion criteria (average age 58 years; 74% men/26% women). Forty-six percent of patients were Hispanic, 28.2% White, 15.4% African American and 7.7% Asian. The majority of patients had stage IIIB (46.2%), followed by IIIC (17.9%), IIA (12.8%), IIIA (7.7%), while rest were stage I, IVA or unknown (5.1%). All patients received 5 x 5 SC-RT, 100% completed 3 cycles of planned neoadjuvant FOLFOX (12.8% received 4-8 cycles) and 36/39 (92%) of patients underwent planned surgery. Median duration from SC-RT to chemotherapy was 12 days, and from chemotherapy to surgery was 37 days. Hospitalization occurred in 3 patients (7.7%) during neoadjuvant therapy, and in 8 patients (20.5%) within 30 days post-surgery. Complete pathological response was seen in 6 patients (16.6%) and near-complete pathological response in 3 patients (8.3%). Relapse occurred in 10.3% patients at time of data acquisition. Grade 3 and 4 neutropenia, anemia, and thrombocytopenia in neoadjuvant phase was observed in 8.6%, 25.7%, and 2.8% patients, respectively. Conclusions: In rectal cancer patients treated at a comprehensive cancer center, neoadjuvant Polish-II approach was feasible and well tolerated. Pathological response rates were comparable to historical data. SC-RT based neo-adjuvant therapy approach should be favored due to lower pelvic radiation dose, tolerance and convenience to patients.
Multigene mutation signatures in colorectal cancer patients: Predict for the diagnosis, pathological classification, staging and prognosis.
Authors: Zhuang Yan , Wang Hailong , Jiang Da , Li Ying , Tian Caijuan , Xu Zanmei , Su Meina , Wang Xiaowei , Zhang Jiangyan , Hu Yuanjing , Liu Pengfei 
Published: May 2020

e16113 Background: Like most cancers, early diagnosis of colorectal cancer (CRC) contributes to a good prognosis. Recently, some studies indicated that mutation gene signatures have good performances in predicting the treatment and prognosis in CRC patients. However, incomplete understanding of the genotype is not conducive to proper treatment. The objective was to give further genetic insights into CRC and provide more comprehensive references for clinical practice. Methods: In the training group, the whole genome sequencing (WGS), clinical, and demographic data of 531 patients were downloaded from The Cancer Genome Atlas (TCGA). The validation group contained 53 patients, which were collected in Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) from April 2014 to November 2018. The fresh tissues collected within 24 hours after operation were used to extract genomic DNA, and then sequenced with targeted next-generation sequencing (NGS) technology to examine somatic mutations and analyze relevant gene concerning clinical indicators. The correlation between gene variation distribution and various indexes such as cancer species, stage, total survival period, sex, age and race were evaluated. Results: A total of 44 mutant genes with mutation frequencies above 5% were found in both TCGA cases and validated cases. Mutations of TP53, APC, KRAS, BRAF and ATM covered 97.55% of TCGA population and 83.02% validation patients, which were proved to be associated with the development of CRC and could be used as a diagnostic signature. Importantly, mutations of TP53, PIK3CA, FAT4, FMN2 and TRRAP had a remarkable difference between early (I/II) and advanced (III/IV) stage patients (P < 0.0001). Besides, we also confirmed that PIK3CA, LRP1B, FAT4 and ROS1 were a mutated gene signature for the prognosis, LRP1B portended to a higher of recurrence and shorter progression-free survival (PFS); mutation of FAT4 portended to a lower of recurrence and longer PFS, which could predict the recurrence and survival of CRC patients. Conclusions: We have indicated gene mutation signatures related to the diagnosis, pathological classification, staging and prognosis in CRC, which provides further insights into the study of CRC genotype. It is helpful to further improve the personalized diagnosis and treatment.
Prognostic value of De Ritis ratio (aspartate transaminase/alanine transaminase) in patients with non-metastatic colorectal carcinoma [izmir oncology group(IZOG) study].
Authors: Oflazoglu Utku , Insan Temmuz Gurdal , Kucukzeybek Yuksel , Varol Umut , Salman Tarik , Yildiz Yasar , Saray Seray , Butun Osman , Taskaynatan Halil , Bolat Kucukzeybek Betul , Alacacioglu Ahmet 
Published: May 2020

e16114 Background: We aimed to assess the prognostic effect of preoperative De Ritis (aspartate aminotransaminase/Alanine aminotransaminase) ratio and pathological variables to find out whether it is an independent prognostic factor in patients with non-metastatic CRC. Methods: We retrospectively evaluated the patients who underwent curative surgery for non-metastatic CRC between 2006 and 2017. The potential prognostic value of De Ritis ratio was assessed by using a ROC curve analysis. The effect of the De Ritis ratio was analyzed by the Kaplan–Meier method and Cox regression hazard models for patients’ disease-free survival (DFS) and overall survival (OS). Results: We had 921 CRC patients in total. The univariate analysis demonstrated that low De-Ritis ratio and several well-established prognostic factors, including well-differentiated tumor,negative lymph node involvement, lymphatic invasion, perineural invasion and surgical margin, left tumor localization and early-stage tumor were good prognostic factors in terms of DFS and OS. On the multivariate analysis, De-Ritis ratio, lymph node involvement, perineural invasion status, surgical margin statusand tumor localization were independent prognostic factors for DFS [ De-Ritis ratio HR 0.468, 95% CI 0.358-0.613,p < 0.001]. We also found that De-Ritis ratio, degree of differentiation, lymphatic invasion status, perineural invasion statusand stage were independent prognostic factors for OS on multivariate analysis [ De-Ritis ratio HR 0.354, 95% CI 0.407-0.702, p < 0.001]. Conclusions: Our study first established a connection between the preoperative De-Ritis ratio and patients undergoing curative resection for non-metastatic colorectal cancer, suggesting that De-Ritis ratio was a simple, inexpensive, and easily measurable marker as a prognostic factor and may help to identify high-risk patients for treatment decisions.
Prognostic role of macrophage infiltration and monocyte-to-lymphocyte ratio in stage III colon cancer: The MIRROR study.
Authors: Basile Debora , Polano Maurizio , Buriolla Silvia , Gallois Claire , Cortiula Francesco , Corvaja Carla , de Scordilli Marco , Michelotti Anna , Parnofiello Annamaria , Gerratana Lorenzo , Ongaro Elena , Andreuzzi Eva , Toffoli Giuseppe , Buonadonna Angela , Mongiat Maurizio , Zaanan Aziz , Aprile Giuseppe , Canzonieri Vincenzo , Taieb Julien , Puglisi Fabio 
Published: May 2020

e16118 Background: Changes in peripheral blood cells composition may reflect immune microenvironment and its role in cancer growth. High monocyte-to-lymphocyte ratio (MLR) could be a marker of tumor’s recruitment of suppressive cells, showing a prognostic role. This study aimed to assess the prognostic impact of macrophage infiltration and MLR in stage III colon cancer (CC) patients (pts). Methods: This multicentric study retrospectively analyzed a consecutive cohort of 423 CC pts treated between 2008-2019 at the Cancer Centre of Aviano (Italy) (n = 300) and at the European Georges Pompidou Hospital of Paris (France) (n = 123). The association of MLR with disease-free survival (DFS) and overall survival (OS) was evaluated with Cox regression analyses. Random Forrest was implemented on python using h2oai. Performance was assessed in terms of accuracy (ACC) and Matthews Coefficient (MCC). Analyses was adjusted on classical prognostic factors of stage III CC such as pT, pN, grade, location, ECOG PS. Results: Overall, 77% had pT1-3, 30% pN2 and 73% G1-2 tumors. Interestingly, 25% had a lymphatic and vascular invasion, 42/230 (18%) had MSI status, 69/152(45%) and 19/114 (13%) were KRAS and BRAF mutant. 56% had CEA > 5. Pts were treated with fluoropyrimidine and oxaliplatin as adjuvant therapy. Notably, 130 cases were analyzed according to lymphocytic and macrophage infiltration (CD163, CD68, CD3, CD8). Of them, 78% had a CD163/CD8 ratio ≤3 and 74% a CD8/CD3 ratio ≤1.5. At median follow-up of 57 months, median DFS and OS were not reached, 31% of pts relapsed and 23% dead. By multivariate analysis, including statistically significant prognostic variables, CD163/CD8 ratio (HR 1.15, p = 0.039, 95%C.I. 1.1-1.32) and MLR > 0.45 (HR 2.98, p = 0.008, 95%C.I. 1.33-6.67) were associated with worse DFS. By multivariate analysis for OS, including statistically significant confounding variables, MLR > 0.45 (HR4.32, P = 0.012, 95%C.I. 1.37-9) and BRAF mutation predicted worse OS. According random survival forest for OS, CD68/CD3 were the first variable of importance (0.06), followed by MLR (0.009) and CD8 (0.007). Interestingly, high MLR followed by CEA, MSI, KRAS were the features linked with organotropism on liver (ACC 0.6 ±0.3), while high MLR, KRAS, pN, pT were mainly linked with lung colonization (ACC 0.6 ±0.2). Conclusions: High pre-treatment levels of MLR and CD163/CD8 ratio in stage III CC are independently associated with worse prognosis. The present study paves the way to a prospective validation of these promising cost-effective biomarkers.
Metastatic lymph node ratio as better prognostic tool than TNM system in colorectal cancer.
Authors: Macedo Filipa , Sequeira Hugo , Ladeira Katia , Bonito Nuno , Viana Charlene , Martins Sandra 
Published: May 2020

e16128 Background: Colorectal cancer (CRC) is the third leading cause of cancer death in the world. Lymph node metastasis is an important prognostic factor; however, the minimum number of lymph nodes that should be evaluated for adequately categorizing lymph node status is still a controversial theme. The TNM staging system has limitations in defining the pN category. The lymph node ratio (LNR) may be a better prognostic indicator. Objectives: Evaluate the impact on the prognosis of patients operated for CRC, comparing the LNR with the pN category of TNM system. Methods: We studied 1065 patients treated at a General Surgery Department from 01/01/2000 to 08/31/2012. The LNR was separated into 5 categories based on three previously calculated cut-off values: LNR0 (0), LNR1 (0.01-0.17), LNR2 (0.18- 0.41), LNR3 (0.42-0.69) and LNR4 (≥0.70). Results: The results of the univariate analysis indicated significant differences in survival according to age (p < 0.001), tumor size (p < 0.001), serosal invasion (p < 0.001), histological type (p = 0.002), differentiation (p < 0.001), pT (p < 0.001), pN (p < 0.001), LNR (p < 0.001), M (p = 0.001), TNM stage (p < 0.001), venous invasion (p < 0.001). Multivariate analysis confirmed the LRN, pN, age, venous invasion and pT as independent prognostic factors. The survival analysis showed significant differences between the categories of pN (p < .001) and LNR (p < .001). Spearman correlation analysis showed a significant correlation between the total number of dissected lymph nodes and the number of metastatic lymph nodes (rs = 0.167, p < 0.001). The total number of dissected lymph nodes is not significantly correlated with LNR (rs = -0.019, p = 0.550). Conclusions: In this study LNR seems to demonstrate a superior prognostic value when compared to the pN categories, in part due to its greater independence regarding the extent of lymphadenectomy.
Organ index of immunological and anti-tumor effect of intratumor injection of penicillin sodium combined with chemotherapy drug for tumor-bearing mice.
Authors: Fu Qiang , Han Yan , Li Bian , Zhang Jian , Chen Dong , Zhao Ming , Zheng Guoqin , Yu Baofa ,   Shandong Baofa Cancer Therapeutics, Inc.
Published: May 2020

e16134 Background: To observe the antitumor mechanism of penicillin combined with chemotherapy drugs in tumor-bearing mice. Methods: The H22 experimental tumors were randomly divided into groups when the longest diameter of the tumor reached about 4 to 7 mm. First and the second administration was performed every 7 days. Perform a skin test and observe the local response. There were 22 mice in each group, male and female. The No. 1 to No. 3 of each group of male and female are used for pharmacodynamic experiments and executed by cervical dislocation on the 13th day. The tumor tissue is removed, weighed, and the tumor growth inhibition rate is calculated. Thymus and spleen, calculate the thymus and spleen coefficients. The male and female Nos. 4 to 8 of each group was used for survival experiments. The death time of the mice was observed and recorded. And 9 to 11 mice from the male and female mice in each dose group of penicillin were taken for skin test, and the skin test response was recorded; the 4th day after the second administration (the 12th day of the experiment) the 9th to 11th of each group No. is used for the tumor formation time experiment of the contralateral tumor. The tumor formation time of the mice is observed and recorded. Results: (1) Comparison with body weight. Sustained-release chemotherapeutic agents of penicillin sustained-release medicines by hydrogen peroxide can cause less damage to mice. (2) Compared with tumor volume and tumor inhibition rate, the compound group (I-Ⅵ) could significantly inhibit tumor growth in mice after intratumoral injection, but penicillin and DNP had no obvious tumor inhibition after intratumoral injection. (3) The comparison of thymus coefficients shows that the adjuvant can obviously prevent the damage to the thymus caused by the drug and has a certain protective effect on the thymus which is very important organ for immune systems. Comparison of survival time, the survival rate and average survival time of the compound Ⅱ group were higher than those of other compound groups. Conclusions: Based on the efficacy and survival results, this intratumoral injection with penicillin could increase organ index for spleen and thymus and indicated it could increase immunological response to against whole body cancer cell.