bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of post-operative chemotherapy and prognostic factors for colorectal cancer liver: Only metastasis (CRLM) after R0 or R1 resection.
Authors: Sym Sun Jin , Kim Koen Kook , Kim Young Saing , Park Inkeun , Lee Won-Suk , Baek Jeong-Heum , Park Yeon Ho , Ahn Hee Kyung , Cho Eun Kyung , Shin Dongbok 
Published: September 2018

e15047 Background:Complete removal of all known tumor is the most important indicator that correlated with survival of CRLM. However, the role of post-operative chemotherapy for resected CRLM has not yet been clarified. We evaluate the role of post-operative chemotherapy in setting for curatively resected CRLM. Methods:We reviewed all 164 patients (pts) underwent resection of CRLM in our institute between Nov 2002 and Apr 2016, and selected 109 pts underwent R0 or R1 resection of primary and CRLM. Pts with R2, extra-hepatic, and non-regional lymph nodes metastasis were excluded. Kaplan-Meier and log-rank test was used for survival analysis. Results:The median age was 62.9 (29-88) years; male (70%). Primary tumor locations were right (24.8%), left (52.3%), and rectum (22.9%). The median number and total sum of maximum diameter of CRLM were 2 (1-13) and 4.2 (0.6-19.7) cm, respectively. Eight-one pts (74%) underwent R0 resection of both primary tumor and CRLM and 84 pts (77%) received post-operative chemotherapy (66 pts with cytotoxic chemotherapy only, 18 with cytotoxic chemotherapy with biologics). With a median follow-up of 35.7 months, median overall survival was 57.0 months, and disease free survival (DFS) was 13.7 months. Univariate analysis revealed that node-stage of primary tumor ( p= 0.024), preoperative CEA (≤ 5 v > 5 ng/ml)( p= 0.002), total sum of maximum diameter (≤ 5 v > 5 cm)( p= 0.013), and complete resection of tumor (R0 v R1)( p< 0.001) were significantly associated longer DFS. Post-operative chemotherapy did not show difference of DFS (median 7.5 months with no treatment, 14.2 months with cytotoxic chemotherapy, and 14.8 months with biologics, p= 0.739). In multivariate analysis, complete resection of tumor (Hazard Ratio (HR); 0.381, 95% confidence interval (CI); 0.215-0.646, p= 0.001) and preoperative CEA level (HR; 0.453, 95% CI; 1.015-3.621; p= 0.045) was independent factor for longer DFS. Conclusions: The post-operative chemotherapy for CRLM after R0 or R1 resection shows no difference in survival. Complete resection with negative surgical margin is the most important indicator for longer survival.
Stage IV colorectal cancer: An NCDB analysis of the surgical treatment of peritoneal carcinomatosis versus liver metastases.
Authors: Naffouje Samer A , Salti George I. 
Published: September 2018

e15067 Background: Traditionally, peritoneal carcinomatosis (PC) secondary to colorectal cancer (CRC) was perceived as a terminal disease, for which the only palliation was offered. With the emergence of new surgical approaches such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), surgical intervention in select patients with ‘curative’ intent was made possible. In this study, we compared the outcomes of the surgical intervention on stage IV CRC patients with isolated liver metastases (LM) to those with PC only. Methods: The National Cancer Database (NCDB) for CRC was analyzed excluding patients with PMP. Patients with isolated LM or with PC were identified, then divided into 2 treatment groups per the current treatment of each scenario: LM patients treated with surgery±chemotherapy (LM group), and PC patients treated with surgery+chemo±HIPEC (PC group). Results: 21,829 patients were identified; 18,932 fell in the LM group, and 2,897 in the PC group. Mean age in the LM and PC groups was 62.94±13.54 vs. 59.59±13.73. No significant difference was noted in the 30-day readmission rates (6.0% vs. 6.6%; p = 0.103). LM group had higher rates of 30- and 90-day mortality (4.3% vs. 0.3% and 8.6% vs. 1.8%, respectively; p < 0.0001), but a slightly shorter hospitalization (7.70±8.64 vs. 7.92±7.07; p = 0.024) Median overall survival was not different between the groups (27.3 vs. 25.36 months; p = 0.214). Conclusions: Surgery with systemic and IP chemotherapy can be a viable treatment option in stage IV CRC patients with PC with comparable short-term and survival outcomes to the widely accepted liver resection in patients with isolated LM.
Demographic, clinicopathologic and survival differences among left sided versus right sided metastatic colorectal adenocarcinoma.
Authors: Giri Smith , Mehta Kathan , Shrestha Shreesh , Sharma Santosh , Bhatt Vijaya Raj 
Published: September 2018

e15068 Background: Clinical outcomes may differ between left versus right sided (CA) independent of stage. We utilized a large database to identify real world differences in characteristics and overall survival (OS) of left versus right sided CA. Methods:We used the National Cancer Database (NCDB) to identify 36,271 patients with metastatic (stage IV) CA diagnosed between the years 2010 to 2012. Right-sided CA was defined as CA of the cecum, ascending colon or hepatic flexure, and left-sided CA was defined as CA of splenic flexure, descending colon, sigmoid colon and rectum. We compared demographic and pathologic features (tumor size, grade, lymphovascular invasion, metastatic site) as well as OS of CA based on laterality. Results:36% of metastatic CAs were right sided. Left versus right sided CAs were more likely to be diagnosed in older patients (median age 68 vs. 62 yr; p<0.01), females (52% vs. 43%; p<0.01), and African Americans (17% vs. 13%; p <0.01). Left-sided CAs were more likely to be >5 cm (58% vs. 54%, p<0.01), grade 3 or 4 (35% vs. 22%; p<0.01), have lymphovascular invasion (62% vs. 50%; p <0.01) and liver metastasis (72% vs 67%; p<0.01) and less likely to have lung (20% vs. 27%;p <0.01) or bone metastasis (5% vs. 6%; p value <0.01). The median OS was lower in right versus left-sided CAs(12 vs. 20 months; p <0.01) Conclusions:Our study suggests important differences in metastatic CAs based on laterality. Patients with right-sided CAs are more likely to be older, females and African Americans, present with larger tumor, lymphovascular invasion and differ in sites of metastases. Future studies should assess any difference in molecular characteristics and tumor biology based on laterality. [Table: see text]
Microsatellite instability as a prognostic factor in stadium II colon cancer patients. A meta-analysis of published literature.
Authors: Novotny Jan , Gkekas Ioannis , Pecen Ladislav , Strigard Karin , Palmquist Richard , Morgan Gilberto , Gunnarson Ulf 
Published: September 2018

e15075 Background: The prognostic role of microsatellite instability (MSI) in stage II colon cancer patients remains controversial despite it has been investigated in a number of studies. Hazard ratios differ considerably among these studies. We performed a meta-analysis to define the significance of MSI in this group of patients. Methods: Studies indexed in PubMed presenting separate data on MSI status and survival outcomes for stage II colon cancer patients have been analyzed using fixed-effect meta-analysis of hazard ratio according to the method of Peto. Results: Analysis was performed on 19 studies including 5998 patients. 47.2% patients received postoperative chemotherapy, 52.8% were males and 47.2% females. Eight studies included also rectal cancer patients. MSI was detected in 20.8 % of the patients. Hazard ration (HR) for overall survival (OS): MSI vs MSS for the entire population: 0.73 (95% confidence interval (CI): 0.33-1.65); HR for disease free survival (DFS): 0.60 (95% CI: 0.27-1.32). No statistical significant difference was found when comparing studies analyzing MSI with genotyping (MG) and immunohistochemistry (IHC) (MG vs IHC: HR OS 0.45, 95% CI 0.10-2.05 vs. 0.95, 95% CI 0.57–1.58; HR DFS 0.51, 95% CI: 0.14-1.85 vs. 0.67, 95% CI 0.26-1.70). However, numerically MSI determination with genotyping shows remarkably lower hazard ratios (further from HR equal to one) for both OS and DFS. Separate analysis of studies investigating colon cancer patients only showed HR OS 0.72 (95% CI: 0.31-1.71); HR DFS 0.60 (95% CI: 0.27-1.31). Conclusions: This is the first meta-analysis that evaluates the prognostic role of MSI in the well defined population of colon cancer patients with stage II disease. No significant relation was found between MSI status and various survival outcomes. Routine determination of MSI status to guide postoperative management of stage II colon cancer patients cannot be recommended based on the presently included studies. This study was supported from the unrestricted grant of Cancerforskningsfonden i Norrland/Lions Cancerforskningsfond LP 14-2065 and Akademisk Miljö NLL-576531.
The prognostic value of serum IL-6 and YKL-40 in colorectal cancer patients before liver resection.
Authors: Holsey Gramkow Mathias , Peltonen Reetta , Dehlendorff Christian , Osterlund Pia J. , Johansen Julia S. , Isoniemi Helena 
Published: September 2018

e15078 Background: IL-6 and YKL-40, markers of inflammation and cancer growth, are high in serum in patients with colorectal cancer (CRC) and associated with shorter overall survival (OS). We hypothesized that preoperative serum IL-6, YKL-40 and CEA are associated with disease free survival (DFS) and OS in patients with metastatic (mCRC) treated with liver resection. Methods: 457 patients (male/female: 267 (58%)/190 (42%), median age 65 [IQR: 58-71]) diagnosed with mCRC who underwent liver resection were included between March 1998 and February 2013. Preoperative serum samples were collected and stored at -80°C until analysis. Serum IL-6 (R&D Systems, UK) and YKL-40 (Quidel, USA) were determined by ELISA. For DFS and OS we estimated crude and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) with Cox regression for each biomarker separately. The biomarkers were included as log2-transformed continuous variables and adjustment included mutual adjustment between the biomarkers in addition to adjusting for sex and age. Results: The median (IQR) preoperative biomarker levels were: IL-6 (3.5 pg/ml, 2.1-6.1), YKL-40 (75 ng/ml, 48-127) and CEA (5.2 kU/L, 2.6-18.8). Univariate analysis showed that high serum IL-6 and YKL-40 were associated with shorter DFS (IL-6: HR = 1.18, 1.06-1.31, p < 0.01; YKL-40: HR = 1.19, 1.08-1.32, p < 0.01). Serum CEA was not (p = 0.80). Multivariate analysis (all biomarkers) showed that high IL-6 was associated with shorter DFS (HR = 1.15, 1.02-1.29, p = 0.02), whereas YKL-40 (p = 0.08) and CEA (p = 0.51) were not. Univariate analysis showed that high preoperative serum IL-6 and YKL-40 were associated with shorter OS (IL-6: HR = 1.16, 1.03-1.29, p = 0.01; YKL-40: HR = 1.27, 1.14-1.42, p < 0.01). Serum CEA was not associated with OS (p = 0.16). Multivariate analysis (all biomarkers) showed that high YKL-40 was associated with shorter OS (HR = 1.19, 1.05-1.34, p = 0.01), whereas IL-6 (p = 0.25) and CEA (p = 0.26) were not. Patients with elevated serum levels of all 3 biomarkers had the shortest OS (HR = 2.12; 1.29-3.50, p < 0.01). Conclusions: Serum IL-6 and YKL-40 determined before liver resection may be valuable prognostic biomarkers in patients with metastatic CRC.
Inflammatory biomarkers as independent predictive and prognostic markers in metastatic colon cancer patients over several treatment lines.
Authors: Riedl Jakob M. , Posch Florian , Bezan Angelika , Moik Florian , Smolle Maria Anna , Szkandera Joanna , Pichler Martin , Stoger Herbert , Stotz Michael , Gerger Armin 
Published: September 2018

e15084 Background: The aim of this study is to quantify the value of the inflammatory biomarkers neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP) level and the advanced lung cancer inflammation index (ALI) as predictive and prognostic markers for treatment and survival outcomes over the first three chemotherapy lines in metastatic colorectal cancer (mCRC) patients. Methods: 258 patients with mCRC undergoing palliative chemo(immuno-)therapy were included in this retrospective study. Primary endpoints were 6-month progression free survival (PFS) and overall response rate (ORR) during 1st-line, 2nd-line, and 3rd-line treatment, and 6-month OS during best supportive care. Results: In multivariable analysis adjusting for polychemotherapy, 1 standard deviation (SD) increase in NLR was associated with a 8.5% absolute lower ORR in first line (95%CI: 11-7, p < 0.0001), 3% lower ORR in second line (4-2, p < 0.0001), and 3% lower ORR in third line (8-2, p = 0.24), respectively. The other inflammatory markers were not significantly associated with ORR. Regarding PFS, a higher NLR was consistently associated with higher risk of progression or death across all treatment lines, with rising hazard ratios (HR) over treatment lines (HR 1.30, p = 0.021 first line); (HR 1.37, p < 0.0001 second line); (HR 1.44 , p = 0.042 third line). The PLR was associated with 6 month PFS over all lines. (HR 1.43 (95%CI 1.09 – 1.88, p = 0.009 first line); (HR1.67 (95%CI 1.34 – 2.09, p < 0.0001 second line) and (HR 1.43 (95%CI 1.04 – 1.98, p = 0.029 in third line)) For CRP, the prognostic association was significant in the first two chemotherapy lines and in case of BSC. (HR 1.49 (95%CI 1.23 – 1.80, p < 0.0001 first line); (HR1.25 (95%CI 1.06 – 1.47, p = 0.007 second line); (HR 1.09 (95%CI 0.81 – 1.48, p = 0.552 third line and HR 1.43 (1.15 – 1-79, p = 0.002 in BSC)). More detailed results concerning the other biomarkers will be presented at the meeting. Conclusions: Our data demonstrate that inflammatory biomarkers are important and independent indicators of response to antineoplastic chemotherapy, relevant not only in first, but also in later treatment lines.
Effect of molecular mechanisms mediating bevacizumab (BEV) and vanucizumab (VAN) on gastrointestinal perforation: Use of artificial neural networks for integrated data analysis.
Authors: Wagg Jonathan , Krieter Oliver , Ooi Chia-Huey , Croset Samuel , Leddin Mathias , Valls Raquel , Mas Jose Manuel , Boetsch Christophe 
Published: September 2018

e15108 Background: VAN is a novel bispecific mAb targeting VEGF & ANG-2. A randomized phase 2 study (McCAVE) investigating VAN & BEV, each combined with chemotherapy (mFOLFOX-6), in 1L metastatic colorectal cancer patients was completed. Reported gastrointestinal perforation (GIP) events (including GI fistula & abdominal abscess) in both arms (approx. 10%) exceeded those expected with BEV+CTx. The present work focused on identifying the explicit molecular pathways mediating VAN/BEV associated GIP. Methods: Clinical data from McCave (safety outcomes & gene expression profiling) was integrated with data from other clinical/preclinical VAN/BEV studies. Machine learning was applied to the dataset to computationally infer GIP mechanisms. The methodology was constrained by relevant biological & clinical knowledge. Literature reviews & database queries mapped 194 unique proteins to 8 biological processes previously hypothesized to play a role in GIP. Identified proteins guided construction of a GIP protein interaction network which was transformed into an artificial neural network and was fitted to the dataset to predict molecular pathways/biological processes most likely linking VEGF-A and/or ANG-2 inhibition to GIP. Results: VAN/BEV were predicted to enhance GIP risk via 4 out of 8 previously suggested biological effects: (i) reduced GI mucosal integrity; (ii) impaired wound healing; (iii) inhibition of angiogenesis (iv) increased thromboembolic risk. The specific proteins & associated interactions predicted to mediate these 4 effects were identified as solely VEGF-A inhibition driven. These effects may drive increased susceptibility to GIP triggered by secondary insults, e.g. preclinical ulcer & intramural lesion. Candidate GIP biomarkers for monitoring these effects were identified, e.g., aPTT, citrulline & I-FABP. Conclusions: The molecular pathways mediating GIP in VAN/BEV treated patients are likely driven by VEGF inhibition with no contribution from ANG-2 inhibition. It is proposed, that in addition to VAN/BEV, one or more secondary insults to the GI tract wall are required to drive perforation.
Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their diagnostic and prognostic value.
Authors: Kottorou Anastasia E , Antonacopoulou Anna G , Dimtrakopoulos Fotinos-Ioannis D. , Kalofonou Melpomeni , Diamantopoulou Georgia , Theodorakopoulos Theodoros , Oikonomou Chrysa , Katsakoulis Evangelos , Dimopoulos Nikos , Stephanou Georgia , Makatsoris Thomas , Stavropoulos Michalis , Thomopoulos Konstantinos , Kalofonos Haralabos 
Published: September 2018

e15130 Background: Expression of Transcribed Ultra Conserved Regions (T-UCRs) is often deregulated in cancer. We investigated the role of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal adenocarcinomas and their prognostic and diagnostic value. Methods: Expression and methylation levels of the T-UCRs were assessed in neoplastic and paired non-malignant fresh frozen (FF) tissue specimens from 64 colorectal cancer (CRC) patients, as well as in 6 FF adenoma tissue specimens. In addition, T-UCR methylation levels were assessed in FFPE tumor tissues from 80 CRC patients and in plasma from 161 patients (50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis). Results: Expression levels of all three T-UCRs were lower in neoplastic, compared to non-malignant tissues, although at a statistically significant level only for Uc160 ( p< 0.001). Also, methylation levels of Uc160, Uc283 and Uc346 were higher in tumors compared to non-malignant tissues ( p< 0.001, p= 0.001 and p= 0.004 respectively). Tissue methylation levels of Uc160 were associated with TTP ( p= 0.017). The combination of Uc283 and Uc346 methylation levels was related to OS, however without reaching statistical significance ( p= 0.066). Methylation status of Uc160 and Uc346 in plasma differed significantly among the four patient groups with CRC patients exhibiting the higher levels. Moreover, a strong correlation was found between Uc160 plasma methylation levels and adenoma or adenocarcinoma size and lymph node infiltration ( p< 0.001 and p= 0.024 respectively). When methylation status was used to predict if a subject has CRC, sensitivity and specificity were 35% and 89% respectively, while the values changed to 45% and 74.3% respectively when we combined the sum of the three T-UCR plasma methylation levels. For adenomas, the combination of Uc160 and Uc346 plasma methylation displayed 30.2% (sensitivity) and 80.7% (specificity). Conclusions: T-UCR expression and methylation is deregulated in CRC while their methylation has prognostic value and appears a promising non-invasive screening test for CRC and adenomas, provided that the sensitivity of the assay is improved.
Validation of the NCI colorectal cancer risk assessment tool in the CSP 380 veterans cohort.
Authors: Musselwhite Laura W. , Redding Thomas S. , Sims Kellie J. , O'Leary Meghan , Hauser Elizabeth R. , Hyslop Terry , Lieberman David A. , Provenzale Dawn T. 
Published: September 2018

e15135 Background: Refining screening to colorectal cancer (CRC) risk may promote screening effectiveness. We applied the National Cancer Institute (NCI) CRC Risk Assessment Tool to estimate 5- and 10-year CRC risk in an average-risk Veterans cohort undergoing screening colonoscopy with follow-up. Methods: This was a prospective evaluation of predicted to actual risk of CRC using the NCI CRC Risk Assessment Tool in male Veterans undergoing screening colonoscopy with a median follow-up of 10 years.Family, medical, dietary and physical activity histories were collected at enrollment and used to calculate absolute 5- and 10-year CRC risk, and to compare tertiles of expected to observed CRC risk. Sensitivity analyses were performed. Results: For 2,934 male Veterans with complete data (average age 62.4 years, 15% minorities), 1.3% (N=30) and 1.7% (N=50) were diagnosed with CRC within 5 and 10 years of survey completion. The area under the curve for predicting CRC was 0.69 (95% CI; 0.61-0.78) at 5 years and 0.67 (95% CI, 0.59-0.75) at 10 years. We calculated the sensitivity (0.60, 95% CI; 0.45-0.73), specificity (0.67, 95% CI; 0.65-0.69) positive predictive value (0.031, 95% CI; 0.02-0.04) and negative predictive value (0.99, 95% CI; 0.98-0.99). Conclusions: The NCI CRC Risk Assessment Tool was well-calibrated at 5 years and overestimated CRC risk at 10 years, had modest discriminatory function, and a high NPV in a cohort of ethnically diverse male Veterans. This tool reliably excludes 10-year CRC in low-scoring individuals and may inform patient-provider decision making when the benefit of screening is uncertain. [Table: see text]
Clinical and neurophysiologic prospective study with time-event and long-term analysis of the chronic neurotoxicity associated with oxaliplatin in patients with colorectal cancer (CRC).
Authors: Cassinello Javier , Serrano Carolina , Alvarez De Mon Melchor 
Published: September 2018

e15150 Background: The sensitive, symmetric, chronic neurotoxicity is a frequent dose-dependent and dose-limiting secondary effect of oxaliplatin (COXALIN). Time-event and long-term studies about COXALIN and its progression after the end of treatment ( coasting) are lacking. Methods: A prospective, translational, clinical and neurophysiologic study was performed in patients (p) with CRC treated with oxaliplatin. We analyzed COXALIN during and after treatment (at the time of initial, maximum coasting, improvement and maximum improvement). We followed p every 3 months the first year and every 6 months thereafter. The NCI-CTC V3.0 sensitive and modified TNSc (without motor and autonomic skills) clinical scales and Quantitave Sensitive Test and ENG were used. Results: 41 chemo naive p with CRC were included, 22 men, median age 60 y (IA:55-73).Oxaliplatin was administrated as adjuvant treatment in 36p. FOLFOX combination was used in 40p. The median cumulative doses was 825,25 mg/m2 (IA: 697-963). The median follow-up was 21,5m (11-27). 38 p developed COXALIN at median 5,5 m (IA: 4,4-6,6) and maximum coasting at median 8,5 m (IA: 7,6-9,5); in multivariant analysis, cumulative dose at 3 months (p = 0,039; OR 2,5; p = 0,027; HR 0,5) was predictive factor and female gender (p = 0,017; OR 0,11) was protective factor. Fine fiber neuropathy was detected in 47,4% p. All p improved at median 8,7m (IA: 7,1-10,2) since COXALIN, reaching the maximum improvement at 13,4 m (IA:16,0-20,4); on multivariate analysis, the COXALIN intensity was the predictive factor (p = 0,03; HR 0,42). 76,6%p showed residual COXALIN (73,9% p subclinical/mild, 17,4% p moderated and 8,7% p severe). A high correlation was found between clinical scales and neurophysiologic studies along the study (p < 0,0001). Sensitive NCI-CTC scale was more sensible than modified TNSc to evaluate COXALIN intensity in our study. Conclusions: We confirm coasting in COXALIN which prolongs 6 months after treatment. About 80% p showed residual COXALIN in the long-term but it was subclinical or mild in most cases. Sensitive NCI-CTC 3.0 scale is a simple and reliable method for the follow-up of COXALIN.