bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of chemotherapy in improving survival in stage IV colon cancer patients without surgery: An NCDB analysis.
Authors: Chintalacheruvu Lakshmi Manogna , Buddam Avanija , Diab Osama , Silberstein Peter T. , Walters Ryan W 
Published: September 2018

e15058 Background: Approximately 20% of patients with colorectal cancer have metastases at the time of presentation. Use of systemic chemotherapy for stage IV colon cancer has greatly increased over past several years with newer advancements. With advancements in chemotherapy annual rate of Primary tumor resection dropped from 74.5 percent in 1988 to 57.4 percent in 2010 with improved survival rates. Methods: A total of 39,428 patients with stage IV colon cancer were analyzed from the national cancer data base (NCDB). Differences in demographic and clinical co-variates were compared using Fisher’s exact test, where as survival differences were estimated by the Kaplan-Meier method and associated log-rank test; p < 0.05 indicated statistical significance. Results: The log-rank tests indicated statistically significant difference in survival (p < 0.001), such that patients receiving chemotherapy survived significantly longer (median survival = 12.0 months, 95% CI = 11.8 to 12.2 months) compared to patients not receiving chemotherapy (median survival = 1.5 months, 95% CI = 1.5 to 1.5 months). Patients receiving chemotherapy were younger (63.2 +/- 13.2 vs 73.8 +/- 13.0 ) with lesser co morbidity when compared to people who did not receive chemotherapy. Conclusions: Patients receiving chemotherapy are considerably younger, with less co-morbidity, and they survive significantly longer. This study signifies the survival advantage with chemotherapy in Stage IV colon cancer patients who did not get any type of surgery. Further studies need to be establish to define the role of chemotherapy comparing to surgery in stage 4 colon cancer patients.
Positive effect on survival of epidural analgesia in patients undergoing cytoreductive surgery for peritoneal metastasis.
Authors: Eveno Clarisse , Gayat Etienne , Caballero Marie-Josee , Schiavone Roberto , Andre Thierry , Pocard Marc 
Published: September 2018

e15064 Background: Potential benefits of regional analgesia in reduction of cancer recurrence have been reported for colon and ovarian cancer. The aim of this study was to evaluate the influence of regional analgesia with patient controlled epidural analgesia (PCEA) on disease-free survival (DFS) and overall survival (OS) in patients with peritoneal metastasis (PM) of various origins operated to achieve cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: From 2006 to 2015, 734 patients were operate on curative purpose to undergone CRS and HIPEC for PM. Three hundred patients for which details on PCEA were available were included in the present study. Aiming to obtain two well-balanced cohorts for available variables influencing early outcome and survival, the PCEA group was matched 1:1 with the non PCEA group by using a propensity score-based method. Results: Matching criteria included demographic characteristics, ASA score, origin of PM, presence of liver metastasis, Peritoneal Carcinomatosis Index (PCI) and complete resection. The median duration of follow-up was 18 months. In the matched cohort (PCEA: 68, non-PCEA: 68), early outcomes were comparable between the two group in terms of blood lost (200 vs 200 ml), transfusion (15 vs 18%), length of surgery (440 vs 450 min) and of hospitalization (12 vs 13 days) and major morbidity (25 vs 22%). After PS-matching, the PCEA group had better OS comparing non-PCEA (Hazard ratio and 95% confidence interval at 0.41 [0.21 – 0.86]). Improvement of DFS rate in PCEA group was observed only in the original sample but not after PS-matching (HR 95%CI: 0.70 [0.45 – 1.07]). Conclusions: In our study, regional analgesia is associated with improved overall survival and transient effect on disease-free survival in patients with peritoneal metastasis of various origins.
Efficacy and safety of Qu Xie capsule in metastatic colorectal cancer: A double-blind, randomized, placebo-controlled trial.
Authors: Zhang Tong , Yang Yufei 
Published: September 2018

e15069 Background:Qu Xie capsule was discovered by Li Zhongzi, a traditional Chinese Medicine doctor in the Ming Dynasty. Doctor Yang Yufei improved Qu Xie capsule and used it clinically for more than 10 years. In a previous study, we found that Qu Xie capsule reduces the risk of stage II–III colorectal cancer postoperative recurrence and metastasis and prolongs the survival of patients with metastatic colorectal cancer (mCRC). The present clinical trial was designed to verify the efficacy and safety of Qu Xie capsule in patients with mCRC. Methods: The present study was a randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into two groups at a 1:1 ratio. The treatment group received conventional therapy combined with Qu Xie capsule. The control group was treated with conventional therapy combined with placebo. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Results: A total of 121 patients were enrolled and 60 patients were eligible; 54 patients were analyzed. The median OS was 23 months in the treatment group [95% confidence interval (CI) 15–not calculated] vs. 14 months in the control group (95% CI 11–22) (Kaplan–Meier, Log-rank p = 0.060). The OS of the treatment group tended to be longer than that of the control group, although the difference was not significant. This may have been related to the small sample size. In the subgroups of patients < 65 years old, left-sided colon, and ≥second-line therapy, the treatment group showed a significant survival benefit compared with the control group ( p = 0.006, 0.038, 0.013). There were no significant differences between the two groups in PFS. Safety analysis showed no severe hematological toxicity or liver and renal function injury in the treatment group. In the treatment group, one patient had 'abdominal pain' once, which may have been related to the Qu Xie capsule. No other related adverse events were reported. Conclusions:Qu Xie capsule showed good safety and efficacy, and can prolong the OS of patients with mCRC. Clinical trial information: ChiCTR-IOR-16009733.
Laparoscopic radical left hemicolectomy: Use of a bursa omentalis approach to ease splenic flexure mobilization.
Authors: Wang Wei , Wang Wei , Xiong Wenjun , Wan Jin 
Published: September 2018

e15071 Background: Laparoscopic splenic flexure mobilization was technically difficult for left colon cancer. This study was aimed to compare the safety and feasibility of laparoscopic radical left hemicolectomy using a bursa omentalis approach (BOA) versus medial-to-lateral approach (MtLA). Methods: BOA was entering the bursa omentalis prior to separating left Toldt’s fascia. We retrospectively analyzed data of 32 cases undergoing laparoscopic radical left hemicolectomy using BOA, matching with using MtLA from January 2013 and October 2016. The matching factors consisted of gender, age, ASA score, BMI, and TNM stage. Data of intraoperative and postoperative characteristics were reviewed. Splenic flexure mobilization time was defined as laparoscopic operation time minus left Toldt’s fascia separating time. Results: There was no significant difference in average time of ambulation, time to first flatus, hospital stay between two groups. The operative time was also similar between two groups (134.2±27.6 min vs 139.4±23.5 min. P = 0.42), but there are significantly shorter splenic flexure mobilization time in BOA group (25.9±12.3 min vs 35.5±22.5 min. P = 0.03). No entry to posterior pancreatic space was recorded in BOA group and 9.4% (3/32) were wrongly entering to posterior pancreatic space when separating left Toldt’s fascia in MtLA group. However, there was no significant difference in intra- or postoperative complication between groups. Conclusions: Our initial results suggest BOA for laparoscopic radical left hemicoletomy may be safe and feasible approach especially for unexperienced surgeons. The main advantages of present approach contain easy to identify pancreas and avoiding wrongly entering posterior pancreatic space when expanding the left Told’s fascia.
Clinical utility of Oncotype DX in early stage colon cancer.
Authors: Dawod Mohammed Adam Ibrahim , Sui Jane Sze Yin , Kelly Deirdre , McSorley Lynda M. , Brady Claire , Bambury Richard , O'Reilly Seamus , Andrews Emmet J , McCourt Morgan , O'Riordain Michael , Murray Kevin J. , Waldron Brian , Bennett Michael William , Feeley Ken , Power Derek Gerard 
Published: September 2018

e15076 Background: With the advent of colon cancer screening, patients with early stage colon cancer will be more common in our clinics. The evidence supporting the absolute benefit of chemotherapy in resected Stage II and (to a lesser extent) Stage IIIA disease is poor. Not all patients benefit from chemotherapy and toxicity is a problem. There is a need for validated biomarkers to assess individual patient recurrence risk and discriminate absolute treatment benefit. Several studies have validated the role of the OncotypeDX testing in Stage II/IIIA disease. Our objective is to characterize whether this test impacted oncologists’ decisions in treating patients with Stage II/IIIA in the adjuvant setting. Methods: :The Onco typeDX assay is a multi-gene reverse-transcriptase-polymerase-chain-reaction test that analyses the expression of 12 genes involved in key biologic pathways in colon cancer. Stage II and Stage IIIA colon cancers were studied in affiliated hospitals of our region in southwest Ireland. All data collected is prospective and each colon cancer was assigned a recurrence risk score. Oncologists were blinded to this score and the decision to prescribe adjuvant chemotherapy was recorded. After un-blinding the score, a second decision was recorded and comparisons made. Results: :From August 2015 to September 2016, 70 patients have been recruited with M: F of 2:1. Median age at diagnosis was 65 years. Most patients (80%) had stage II disease, 11 of whom had mismatch repair loss on IHC. OncotypeDX testing has been carried out and reported for 59 patients (85%), MMR intact. Recurrence scores: < 30 in 46 patients (77.9%), 30-40 in 10 patients, and > 40 in 3 patients. The treatment plan was altered in 16 patients (27%), of whom 12 patients (20%) received none or less intense chemotherapy. Conclusions: We have shown that the decision to prescribe adjuvant chemotherapy was changed in 27% of patients. This test has helped to define patients with low scores, where chemotherapy-related toxicity is a concern especially in older patients. Absolute benefit of adjuvant chemotherapy versus the risk of toxicity should be discussed. . Hospital managers may be interested in cost savings due to a reduction in chemotherapy use.
Measuring the effects of radiotherapy on DNA methylation in colorectal cancer.
Authors: Maher Jedi , Young Graeme P , Pedersen Susanne Kartin , Symonds Erin L. 
Published: September 2018

e15089 Background: BCAT1 and IKZF1are methylated with high frequency in colorectal cancer (CRC). This study aimed to investigate the level of methylation in these two genes in tissue samples from CRC patients who had undergone radiotherapy. Methods: Tumor and adjacent non-tumor tissue was collected from 50 CRC patients, including 14 subjected to radiotherapy prior to surgical resection. DNA was extracted, bisulfite converted and the levels of methylated BCAT1 and IKZF1 DNA were expressed as the percentage of 5ng tissue DNA (normalized to ACTB levels). Results: In the 36 CRC patients who did not receive radiotherapy prior to resection, tumor tissues had high levels of methylated BCAT1 and IKZF1 compared with adjacent non-tumor tissues (p < 0.001, Table). The CRC tissues from the 14 patients who received radiotherapy pre-surgery had significantly lower levels of methylation compared to the levels in tumors from non-treated patients (p<0.01, Table). Radiotherapy did not appear to affect the methylated BCAT1/IKZF1DNA levels in adjacent non-cancer tissues (p > 0.05, Table). In this limited dataset, a correlation was observed with %methylation and response to radiotherapy measured based on tumor size relative to original size, with the lowest methylation in the tumors associated with the greatest downsizing. Conclusions: The high levels of methylated BCAT1 and IKZF1 in CRC tissue and the low levels in the surrounding non-cancer tissue suggest that the markers are tumor specific with no obvious field effect. In contrast, in the samples obtained from patients treated with radiotherapy prior to resection, the methylation levels in CRC tissues were similar to the levels measured in the adjacent non-tumor tissues. Further studies are necessary to determine the reason for this and whether it has implications for monitoring response to therapy based on blood levels of methylated BCAT1 and IKZF1. [Table: see text]
FBI-1 expression in relation to clinicopathological variables in rectal cancers with a Swedish clinical trial of preoperative radiotherapy.
Authors: Wang Chao-Jie , Zhou Jian-Wei , Zhou Yun , Sun Xiao-Feng 
Published: September 2018

e15102 Background:FBI-1 is a recently characterized proto-oncoprotein of the POZ domain Krüppel-like (POK) family of transcription factors. Although several studies provide the evidence that FBI-1 is an important gene regulator in CRC, no analysis of any correlation between FBI-1 expression and preoperative radiotherapy (RT) has been studied in rectal cancers. Methods: This study included the patients with rectal cancer that participated in a Swedish clinical trial of preoperative RT between 1987 and 1990. Patients were divided into preoperative RT (62) and non-RT (77) groups. Applying immunohistochemstry, we detected FBI-1 expression in 118 normal mucosa, 139 primary rectal cancers, and 45 lymph node metastases, and analyzed its relationship with clinicopathological features and RT response. Results: FBI-1 was detected both in the cytoplasm and nucleus, and the cytoplasmic staining was up-regulated compared with normal mucosa both in non-RT and RT groups (74.0% vs. 17.7%, p < 0.001; 69.4% vs. 41.1%, p = 0.002), however, the nuclear staining was down-regulated compared with normal mucosa both in non-RT and RT groups (22.1% vs. 75.8%, p < 0.001; 35.5% vs. 83.9% p < 0.001). Both cytoplasmic and nuclear staining were no difference between the non-RT and RT groups (74.0% vs. 69.4%, p = 0.542; 22.1% vs. 35.5%, p = 0.080, respectively). So we combined the non-RT and RT group together for further analysis. Nuclear staining of FBI-1 was positively with TNM stage and distance recurrence, it showed higher expression in III+ IV stage than that in I+II stage (41.0% vs. 17.9%, p = 0.003). The patients with distance recurrence showed higher FBI-1 expression than that with no distance recurrence (39.7% vs. 19.8%, p = 0.010). In stage I, II and III patients, higher nuclear FBI-1 in primary cancer showed worse disease free survival (HR: 1.934; 95%CI: 1.055-3.579, p = 0.033) and overall survival (HR: 2.174; 95%CI: 1.102-4.290; p = 0.025) independent of gender, age, growth pattern, differentiation and RT. Conclusions: Higher nuclear FBI-1 is related with later TNM stage, distance recurrence, and worse prognosis, it can be used as a potential diagnostic and prognostic biomarker in rectal cancer.
Tumor associated macrophages to predict the efficacy of bevacizumab plus chemotherapy in patients with advanced colorectal cancer.
Authors: Akbulut Hakan , Dost Gunay Fatma Sena , Kirmizi Bilge Ayca , Koksoy Elif Berna , Ensari Arzu , Icli Fikri 
Published: September 2018

e15103 Background: The tumor-associated macrophage (TAM) is one of the major components of tumor microenvironment. Neuroendocrine differentiation (NED) of the tumor has been linked to poor prognosis. We aimed to investigate the role of TAM infiltration and NED in tumor tissue on the efficacy of bevacizumab plus chemotherapy in patients with advanced colorectal cancer. Methods: A total of 123 consecutive patients with advanced colorectal cancer treated with bevacizumab plus either irinotecan or oxaliplatin-based combination chemotherapy were included in the study. Along with clinicopathological parameters including age, tumor location (right versus left colon), pretreatment CEA level, KRAS mutation status, tumor grade, histologic subtype (mucinous vs non-mucinous), the presence of NED and the level of TAM infiltration were studied as covariates for survival analysis. The patients with at least 2% or more staining with either synaptophysin or chromogranin A were regarded as NED positive. The +2 or less staining with anti-CD68 was regarded as low for TAM infiltration and +3 or +4 staining as high. The overall (OS) and progression-free survival (PFS) times were calculated from the start of bevacizumab. Results: Thirty-five percent of the patients were given bevacizumab in the first line setting, the others mainly at the second line. The chemo backbone was FOLFIRI in 75% of the patients. The median OS was 15,1 and PFS 7,1 months. The ratio of NED negative and TAM infiltration low patients were 73,9% and 13,8 %, respectively. The univariate analysis yielded only the NED and higher TAM infiltration as the significant factors for PFS. However, only NED was significant for PFS in the multivariate analysis (HR:0.542). The left-sided tumors and the low levels of TAM infiltration were the favorable factors for OS in the univariate analysis. However, the TAM level was the only independent factor predicting the OS (26,7±8,8 vs 14,1±1,7 months, respectively; HR: 0,301). Conclusions: Our results suggest that the TAM infiltration in the tumor tissue could be used as a predictive marker of efficacy of bevacizumab plus combination chemotherapy in patients with advanced colorectal cancer.
Division of elderly patients in colorectal cancer: Korean national health insurance big data analysis.
Authors: Baek Sun Kyung , Lee Ji Sung , Lee Sang-Cheol , Bae Sang-Byung , Kim Jong Gwang , Kim Tae Won 
Published: September 2018

e15104 Background: This nationwide study was conducted to demonstrate the difference of the treatment and the survival of elderly patients with colorectal cancer (CRC) by the analysis of big data using the Korean National Health insurance service (NHIS). Methods: We analyzed the NHIS database of CRC patients admitted hospitals which received its quality assessment between 2011 and 2014. According to age, we divided patients into three groups, non-elderly patients ( < 65 years old), borderline elderly patients (65-74 years old) and elderly patients (≥ 75 years old). Results: We included 70,701 CRC patients. Median follow-up duration was 3.2 years (range 0.003-5.5 years). Male patients were 60% and median age was 65 years old (range 18-102 years). Comparing with non-elderly patients, elderly patients more received emergency operation (p < 0.001) and less received adjuvant therapy in stage I-III or palliative chemotherapy in stage IV (p < 0.001). Survival probability at 3 year of borderline elderly patients and elderly patients showed worse survival rate than non-elderly patients [HR 1.55, 95% confidence interval (CI) 1.46 - 1.64, HR 3.19, 95% confidence interval (CI) 3.03 -3.37, respectively]. Conclusions: These results show the treatment and the poor survival of elderly patients with CRC according to age in Korea. More study to reveal the biology of them and to improve outcome is warranted. Our study was the first to describe these data for CRC at a nationwide level.
Prognostic impact of cytomegalovirus (CMV) detection in colorectal cancer (CRC).
Authors: Lee Michael Sangmin , Selitsky Sara R. , Parker Joel S. 
Published: September 2018

e15120 Background: CMV is a widespread herpesvirus that lies latent in the majority of immunocompetent hosts but may reactivate and infect colon epithelium. Prior studies have identified CMV proteins in CRC tumors, where CMV superinfection may play an oncomodulatory role. CMV constitutively activates virally encoded chemokine receptors that may act as oncogenes via promotion of angiogenesis, proliferation, and migration. However, the clinical significance of CMV superinfection in CRC has not been clearly demonstrated. Methods: We obtained clinical and tumor characteristics from 355 CRC patients in The Cancer Genome Atlas (TCGA). TCGA RNA-seq was aligned to curated viral genomes from GenBank after first filtering out the reads that mapped to the human genome. Reads that mapped to CMV were quantified. Consensus Molecular Subtypes (CMS) by gene expression were obtained from www.synapse.org. Results: Among 355 CRC patients, 60 (16.9%) had CMV detected by RNA-seq. CMV+ was significantly associated with older median age (69.5 vs. 64 years, p = 0.016) and rectal rather than colon primary (odds ratio 3.76, 95% CI 1.87-7.57). CMV status was not significantly associated with stage, sex, race, microsatellite stability, BRAF/ KRAS/ NRAS mutation, or CMS subtype. On Cox univariate analysis, CMV+ was associated with inferior survival (HR 1.91, 95% CI 1.10-3.34), as were age (HR 1.03, 95% CI 1.01-1.05), stage (HR 2.00, 95% CI 1.54-2.59), and CMS4 subtype (HR 2.12, 95% CI 1.29-3.48). CMV+ remained significantly associated with inferior survival on multivariate Cox analysis when adjusting for age, stage, and CMS4 subtype. Conclusions: CMV+ as detected on RNA-seq is significantly associated with older age at diagnosis and rectal primary tumor and independently confers inferior prognosis. These findings warrant further investigation of the potential oncomodulatory role and prognostic value of CMV reactivation in CRC.
Quantitative MR imaging biomarkers of tumor heterogeneity predict prognosis in metastatic colorectal lesions.
Authors: Daye Dania , Kamran Sophia C. , Tabari Azadeh , Michalski Mark , Clark Jeffrey W. , Ryan David P. , Allen Jill N. , Murphy Janet E. , Hong Theodore S. , Gee Michael S. 
Published: September 2018

e15121 Background: Intra-tumor heterogeneity is an independent determinant of patient survival outcomes in several tumor subtypes. Spatial variations in tumor enhancement on MRI is a macroscopic imaging marker of tumor heterogeneity. The goal of this study is to evaluate the potential role of MRI-based enhancement heterogeneity measures as predictors of survival in patients with metastatic colorectal cancer. Methods: We retrospectively analyzed T1-weighted contrast-enhanced MRI images of metastatic hepatic lesions in 41 patients (mean age 57.2 ±14.2 years) who were diagnosed with stage IV colorectal cancer between 2007 and 2013. Tumor Kras mutation status and patient survival data for up to 95 months was available for all patients. The largest metastatic hepatic lesion was identified by a radiologist and manually segmented. 14 Haralick texture features were extracted from each lesion. Cox proportional hazards regression analysis was used to assess the association between the enhancement heterogeneity measures and patient survival, with adjustment for Kras mutation status as a potential confounder. Backward stepwise feature selection was performed using p > 0.1 (Wald test) to select for statistically significant features. Results:Mean survival time was 39±3.9 months for the study population (51±4.1 months for Kras-wildtype and 37±5.1 for Kras-mutants). 68% of the patients had left-sided colon cancer; 21% had concurrent pulmonary metastases and 0.5% had concurrent brain metastasis. 61%, 27% and 12% of patients were on Flofox, Folfiri or other chemotherapeutic regimen, respectively. Texture matrix homogeneity (HR > 10; p = 0.016), inverse difference moment (HR < 0.1; p = 0.020), entropy (HR < 0.1; p = 0.033) and standard deviation (HR > 10; p = 0.006) exhibited significant independent association with patient survival. With the exception of entropy, these features maintained significant contribution to survival prediction independent of Kras mutation status. Conclusions: MRI-based quantitativeintra-metastasis heterogeneity measures are associated with patient survival and may add information beyond genetic mutation status to optimize prognosis prediction in metastatic colon cancer.