bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergency department presentation with colorectal cancer.
Authors: Zerhouni Yasmin A. , Melnitchouk Nelya , Schneider Eric , Singh Aparajita 
Published: September 2018

e15094 Background: Despite screening protocols shown to reduce mortality, colorectal cancer (CRC) remains the 2nd leading cause of cancer death in the US. CRC patients who have emergent surgery have worse outcomes than those treated electively. We examined presentation and index hospital outcomes for emergency department (ED) patients with a primary diagnosis of CRC. Methods: The 2013 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was queried and all patients with a primary ICD-9-CM diagnosis of CRC were identified. Descriptive analyses were weighted to the level of the US population. Results: Among 134,869,015 ED visits, approximately 44,717 patients received a primary diagnosis of CRC. Patients with CRC were older (68 vs. 40 years, p < 0.001) and more likely to be male (50.4% vs. 44.3%, p < 0.001) than those presenting for other reasons. Among CRC patients, 88.6% were older than 50 years with males younger than females (66 vs. 70y, p < 0.001) and 90.4% were insured. 88.6% were admitted of whom 44% underwent oncologic resection. Females were more likely to undergo resection (47% vs.42%, p = < 0.001) and to be older at time of surgery (71 vs. 68, p = < 0.001). Average length of stay was 12.5 days for surgical vs. 6.6 days for non-surgical patients (p < 0.001). After admission, 68.0% of those admitted vs. 64.7% of patients who had surgery were discharged home. 6.9% of admitted CRC patients and 4.7% of surgical patients died in-hospital. Average total charges were $124,846 for patients undergoing resection vs. $53,542 for inpatients who did not undergo surgery (p < 0.001). Conclusions: Most patients presenting to the ED for CRC are admitted and many require surgical intervention. Because nearly 90% were 50 or older and insured, further research is warranted to determine if increased screening among eligible patients might reduce the numbers of ED presentations and emergent surgical procedures for CRC.
Factors affecting survival in laparoscopic vs. open surgery among stage III colon cancer patients.
Authors: Zhang Yang , Walters Ryan W , Silberstein Peter T. 
Published: September 2018

e15095 Background: The role of laparoscopic surgery (LS) in the cure of advanced non-metastatic colon cancer is controversial. The study aims to define long-term survival of LS and open surgery (OS) of stage III colon cancer as well as to examine factors that influence the choice in surgical approaches. Methods: We abstracted 22,821 patients from the National Cancer Database who were diagnosed with stage III colon cancer from 2010 to 2012 who had undergone surgery of their primary site by either LS or OS; we only included patients who had also received adjuvant chemotherapy. The probability of undergoing a LS or OS was estimated using multivariable marginal logistic regression model, whereas the between-procedure survival difference was estimated with the Kaplan-Meier method with associated log-rank test and a multivariable marginal Cox regression model. Results: Holding the patient- and facility-level characteristics constant, significantly greater odds of receiving LS was associated with private insurance, patients living in areas with higher socio-economic status, patients receiving care at academic facilities, and patients living in the northeast United States. Kaplan-Meier results indicated that patients undergoing LS had significantly longer survival compared to patients undergoing OS (χ21 = 111.6, p < .001). Table 1 shows three-year survival estimates. After adjusting for the patient- and facility-level covariates, patients who underwent LS had 26.7% lower risk of death compared to those undergoing OS (95% CI: 21.7% to 31.4%, p < .001). In general, lower adjusted risk of death was observed in patients who were younger, female, as well as patients with fewer comorbid conditions and those with private insurance (all p< .05). Conclusions: In this largest, most recent analysis of surgical treatment of stage III colon cancer, our data suggest that long-term survival after LS is superior to conventional OS. Identification of associated demographic factors may prove useful for future allocation of treatment resources. [Table: see text]
Long-term followup of bi-shRNAfurin and GMCSF augmented autologous tumor cell immunotherapy treated colorectal cancer patients in phase I and IIa studies.
Authors: Barve Minal A. , Melnyk Anton M. , Manning Luisa , Wallraven Gladice , Birkhofer Martin , Nemunaitis John J. 
Published: September 2018

e15100 Background: Vigil is an immuno-stimulatory autologous tumor cell therapy, which uses patient tumor cells transfected with a plasmid encoding genes to upregulate GM-CSF and down regulate TGFβ 1&2. It is administered monthly by intra-dermal injection. In Phase I and IIa trials patients with over 19 different tumor types were safely treated. Rapid and durable systemic immune activation was demonstrated using an IFNγ ELISPOT assay. Methods: Data are summarized for a group of 9 patients with advanced colorectal cancer followed for up to 3.5 years. Results: Six women and 3 men with Stage III or IV colorectal cancer were treated between March, 2010 and September, 2013. Six patients received Vigil as a monotherapy and 3 in combination with FOLFOX chemotherapy. Results: Demographics and treatment details are displayed below. Two patients with Stage III disease received combination therapy after complete surgical resection, and remain disease free over 3 years from surgery. The patients received 9 and 12 Vigil injections with a brisk and durable ELISPOT reactions. Conclusions: Preliminary results suggest that Vigil can be combined safely with FOLOX chemotherapy and still elicit a systemic immune response. Long term disease free survival has been observed in several patients justifying further exploration of this combination. More detailed molecular characterization and neoantigen identification of patient tumor will be undertaken in future studies. A combination with immune checkpoint inhibitors may also be explored. [Table: see text]
Serum chitinase activity to predict survival and metastasis of colorectal cancer.
Authors: Song Zhangfa 
Published: September 2018

e15105 Background: In this study we evaluated the role of the chitinase activity (one of the biomarkers) in predicting the liver metastases of colorectal cancer in blood. Methods: The level of chitinase activity were examined in 400 colorectal cancer patients, including 53 synchronous liver metastases in peripheral blood 0.347 colorectal cancer patients peripheral blood was measured before resection of the cancer. The clinical parameters were collected, and the patient were prospectively followed up. Results: The chitinase activity was significantly over-expressed in synchronous liver metastases than colorectal cancer who has no metastases. During the follow up in 347 colorectal cancer patient, higher expression of chitinase activity, higher risk of liver metastases, bothunivariate cox analysis (HR6.0) and multivariate Cox analysis (HR 5.3) show chitinase has high value of predictive the liver metastases after resection of the primary colorectal cancer. Kaplan-Meier analysis shows the chitinase activity has significant correlation to survival in colorectal cancer patients. Moreover, the in vitro study shows the chitinase play important role in cell migration. The metastasis ratio between two groups in non-synchronic colorectal metastasis patients. Conclusions: This study provide experimental evidence that chitinase activity has the potential biomarker for predictive the liver metastases in colorectal cancer. [Table: see text]
Pharmacokinetics of cetuximab and tumor uptake of 89Zr-cetuximab as potential predictive biomarkers for benefit of cetuximab in patients with advanced colorectal cancer.
Authors: Van Helden Erik Jacobus , Menke Catharina Wilhelmina , Boon Eline , van Es Suzanne , Huisman Marc C. , Dongen G.a.M.S. van , Vugts Danielle J. , De Groot Derk Jan , Van Herpen Carla M.L.- , De Vries Elisabeth , Hoekstra Otto S. , Verheul Henk M.W. 
Published: September 2018

e15117 Background: One third of patients with RAS wild-type metastatic colorectal cancer (mCRC) do not benefit from anti-EGFR inhibitors. Thus, predictive biomarkers to identify patients with primary resistant mCRC are urgently needed. Methods: Patients with chemotherapy refractory mCRC received 500 mg/m2 cetuximab 2-weekly (NCT02117466 and NCT01691391). Patients underwent a 89Zr-cetuximab PET/CT 6 days post-injection after a therapeutic dose of cetuximab. In case of lack of tumor targeting on 89Zr-cetuximab PET, the cetuximab dose was escalated. Pharmacokinetic (PK) analyses included 89Zr-cetuximab plasma levels, EGFR saturation in skin, soluble EGFR (sEGFR), and tumor uptake and biodistribution on 89Zr-cetuximab PET. We defined treatment benefit as response or stable disease (according to RECIST v1.1) at 2 months. Results: Of the 44 patients, median age was 64 years, 25% had a right-sided primary tumor, 5 patients had a BRAF mutated (mt) tumor and 62% had treatment benefit. Cetuximab treatment dose was escalated to maximally 1250 mg/m2 in 8 patients. Visual and semiquantitative data of 89Zr-cetuximab uptake in the tumor, biodistribution and plasma activity 6 days post-injection were not correlated with treatment benefit. Although EGFR saturation in skin after 2 cycles cetuximab had a wide range (21 – 98%), saturation did not correlate with treatment benefit. On-treatment levels of sEGFR were higher than baseline (median 4.1 vs 2.0 ng/ml; p < 0.001), but levels and change of sEGFR did not correlate with PK or treatment efficacy. PFS and OS correlated with right-sided mCRC (p < 0.001 and p = 0.002 respectively) and the presence of a BRAF mt (p < 0.001 and p = 0.004 respectively). In a multivariate Cox-regression only BRAF mt remained correlated with PFS and OS (p = 0.003 and p = 0.027). Conclusions: Interpatient variances in PK and tumor uptake of 89Zr-cetuximab as performed in this setting do not predict treatment benefit of cetuximab in patients with mCRC. In contrast, BRAF status correlated with treatment benefit and warrants further research to confirm the predictive value. Clinical trial information: NCT02117466 and NCT01691391.
Evaluation of a fully automated extended RAS-BRAF test on prospectively collected plasma samples from patients with metastatic colorectal cancer.
Authors: Jacobs Bart , Claes Bart , Bachet Jean-Baptiste , Bouche Olivier , Sablon Erwin , Maertens Geert G. , Laurent-Puig Pierre 
Published: September 2018

e15127 Background: Extended analysis of RAS genes in metastatic colorectal cancer (mCRC) is not available in many settings and the need for an easy plasma test is high. Methods: Pre-treatment plasma samples from 198 mCRC patients enrolled in the prospective multicenter RASANC study (NCT02502656) were retrospectively assessed for the presence of ctDNA mutations in KRAS, NRAS and BRAF by the fully automated Idylla platform.Proper informed consent and statistical analysis were included. The study is ongoing. We used Idylla platform which allows analysis of 21 KRAS, 18 NRAS and 4 BRAF ctDNA mutations from mCRC using 2 ml of plasma. The tests were performed using prototype versions of the Idylla ctKRAS and ctNRAS-BRAF-EGFR S492R Mutation Assays (RUO), which contain all reagents for integrated sample preparation and multiplex real time PCR detection. The tests each require 1 ml of plasma, less than 1 minute hands-on time, and have a turnaround time of less than 130 minutes.As a comparator test, NGS analysis with a sensitivity of 0.2% was performed on extracted plasma ctDNA according to Pécuchet et al. (2016). Results: The Idylla ctDNA assays identified 84 KRAS mutated (42.4%), 6 NRAS mutated (3%) and 13 BRAF mutated (6.6%) cases. The Idylla assays detected 62 KRAS codon 12 (31%), 16 codon 13 (6.5%), 3 codon 61 (1.5%), and 8 codon 146 (4%), and 1 NRAS codon 13 (0.5%) and 5 (2.5%) codon 61 mutated samples. All BRAF mutations detected were V600E. Overall agreement between Idylla and NGS for KRAS, NRAS, and BRAF was 96%, 100%, and 99.5% respectively. Overall RASconcordance with the NGS reference method was 96.5% with a positive agreement of 98% and a negative agreement of 95% (Table 1). Discordancy analysis by means of ddPCR on plasma and/or tissue will be presented. Conclusions: Plasma-based analysis of 41 extended RAS and BRAF mutations in ctDNA on the Idylla platform enables rapid and reliable genotyping in patients with advanced colorectal cancers. Clinical trial information: NCT02502656. [Table: see text]
Different small leucine-rich proteoglycans expression pattern by tumor location in colorectal cancer.
Authors: Solis Hernandez Maria Del Pilar , Fernandez-Vega Ivan , García-Suárez Olivia , Perez Lopez Natalia , Quirós Luis M , García Beatriz 
Published: September 2018

e15138 Background: Colorectal cancer (CRC) is a heterogeneous disease defined by anatomic, functional and molecular differences depending on the primary tumor location (PTL). Several molecular phenotypes have been associated with aggressive behavior, and some of these markers are related with proteoglycans, which in turn show alterations in CRC. Small leucine-rich proteoglycans (SLRPs) are a family of molecules encoded by18 genes that may appear coupled to different glycosaminoglycan chains ––including chondroitin/dermatan or keratan sulphate–– or not, depending on the specific species. They are ubiquitously expressed in extracellular matrices, and it’s been described their role in organ size and shape regulation during embryonic development. This study aims to investigate the expression patterns of SLRPs in CRC depending on the PTL. Methods: A transcriptomic approach was carried out by using qPCR to analyze SLRP core protein transcriptions in 32 tumor specimens and their respective healthy tissue: 12 right-sided & 20 left-sided. When significant differences were detected, immunohistochemical techniques were used to enhance the test. Results: While right-sided (R) CRC displayed significant alterations in 2 genes (biglycan BGN overexpression p = 0.015, osteoglycin OGN underexpression p = 0.048), left-sided (L) showed differences in 5 genes (BGN overexpression p = 0.0019 and underexpression of OGN p = 0.0016, prolargin PRELP p = 0.0049, chondroadherin CHAD p = 0.0180 and podocan PODN p = 0.0061). In L tumors CHAD was the most affected gen underexpressed by 16 times, while in R it was present in only 50% of healthy tissue. Transcripts for opticin and nyctalopin were not detected in most patients regardless of PTL. Lumican, decorin, keratocan, asporin, ECM2, fibromodulin, tsukushi, osteoadherin, osteomodulin, epiphycan and PODN-like 1 were detected with no significant differences compared to healthy tissue. Conclusions: Normal mucosa of the large bowel expresses most SLRP. BGN and OGN seem to be dysregulated in both L and R CRC, but CHAD, PRELP and PODN appear to show differences only in L CRC. These alterations could be related to the interaction with different ligands and modulation of homeostasis.
Prevalence and mortality of colorectal cancer with iron deficiency anemia in the South.
Authors: Perimbeti Stuthi , Hou Kevin Ye , Lee William May , Correa Erika , Degen Kathleen , Hanson Shaun Bryan , Marconcini Luiz Antonio Liarte , Niphadkar Seema , Ward Kristine Marie , Jain Maneesh Rajiv , Nandi Neilanjan , Styler Michael 
Published: September 2018

e15141 Background: The Centers for Disease Control and Prevention has published data on incidence rates of colorectal cancer (CRC) referenced from the U.S. Cancer Statistics Working Group. Using data on admissions from the National Inpatient Sample (NIS) from 1999-2014. Iron deficiency anemia (IDA) is a commonly encountered comorbidity of CRC, particularly in late stage disease and is associated with higher rates of complications. Methods: Adult admissions with a primary diagnosis of CRC and secondary diagnosis of IDA were extracted from the NIS database using ICD-9 codes from 1999-2014 (N = 5,130, weighted N = 25,594). The sample was weighted to approximate the full inpatient population of the U.S. to analyze differences in regional distribution (Northeast, Midwest, South, and West) we assumed a normal distribution of 25% per region and then performed a chi squared analysis. Results: There were more cases of CRC with IDA in the South (38.32%) compared to the Midwest (22.76%), West (20.45%) and Northeast (18.46%) (p = 0.001). In addition, there were higher rates of mortality from CRC with IDA in the South (29.32%) compared to the Midwest (22.87%), West (21.43%) and Northeast (16.37%) (p < 0.0001). Conclusions: Our data demonstrates a correspondence between the prevalence of IDA associated CRC with a greater prevalence and increased risk of mortality in the South relative to other regions in the U.S.Regional differences in prevalence also corresponded to regional differences in mortality. Future research should investigate the factors that explain these regional disparities.
A retrospective analysis on the impact of preoperative neutrophil to lymphocyte ratio in stage II colon cancer.
Authors: Jaiswal Deepna Deepak , Mantha Suparna , Seija Luis , Munoz Yolanda , Wong Lucas 
Published: September 2018

e15146 Background: Inflammation has a critical role in tumor genesis and progression of cancer. The neutrophil to lymphocyte ratio (NLR) is an indication of balance between the immune systems pro and defense mechanism against cancer. Elevated NLR is of interest in many cancers, including colon cancer. Although surgery is the mainstay of treatment for early stage colon cancer, adjuvant chemotherapy for stage II colon cancer has remained debatable. We proposed to study the impact of the NLR in patients with stage II colon cancer and to identify high risk patients who would benefit from adjuvant chemotherapy. Methods: Three hundred and eighty patients diagnosed with Stage II colon cancer at our institution were included in this retrospective study. Kaplan-Meir curves and multivariate Cox-regression analyses were calculated for overall survival. Results: Univariate analysis showed NLR was not statistically significant as predictor of mortality (p-value = 0.0857). However, after adjusting for recurrence, chemotherapy, age, white blood cell count, the NLR was predictive for survival, with a hazard ratio of 1.05 and 95% confidence interval of (1.006 - 1.1). Recurrence and age were also significant predictors of survival (p-values of < 0.0001 for both), and HR of 3.1 (2.0 – 4.6) and 1.4 (1.2 – 1.5), respectively. Conclusions: The neutrophil to lymphocyte ratio might be an independent prognostic marker for overall survival in stage II colon cancer patients. Given the retrospective nature of our study, further studies are indicated to confirm our findings.
Pilot trial of KD018 with neo-adjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.
Authors: Kann Benjamin H , Johung Kimberly , Cheng Yung-Chi , Lam Wing , Liu Shwu-Huey , Decker Roy H. , Higgins Susan A. 
Published: September 2018

e15162 Background: Neo-adjuvant chemo-radiation (CRT) is commonly used for rectal cancer, though is associated with gastrointestinal (GI) toxicity. KD018 is a state-of-the-art adaptation of Huang-Qin-Tang, a traditional Chinese medicine used to treat GI ailments. KD018 is a standardized pharmaceutical product subjected to quality-control measures including chemical fingerprinting by liquid chromatography and mass spectroscopy, individual target bioassays, and genomic bioresponse profiling to ensure product consistency. Clinical studies showed the safety of KD018 when given with chemotherapy to reduce GI toxicity. Preclinical study showed that KD018 decreased GI toxicity of abdominal RT without compromising tumor control. Here, we present preliminary results of the first clinical trial to use KD018 in patients receiving RT (neo-adjuvant CRT for rectal cancer). Methods: We conducted a pilot phase I trial of KD018 in patients with biopsy proven rectal adenocarcinoma, clinical stage T3-T4, N0-N2, who received neo-adjuvant CRT. Patients received 3D-conformal pelvic RT to 45 Gy in 1.8 Gy fractions, followed by a 5.4 Gy tumor boost with capecitabine 825mg BID on days 1-5 of RT (weekly) and KD018 800mg PO BID on days 1-4 of RT (weekly). Accrual goal was 24 patients. Primary endpoint was grade 3-4 GI toxicity by CTCAE v4.0 assessed weekly during RT, and until at least 30 days after RT. Secondary endpoint was pathologic response. Results: Of 19 patients enrolled, 16 began treatment, and 14 completed the protocol. Of these, there were no treatment related grade 3-4 GI toxicities (Table 1). Of 11 patients who completed surgery thus far, all had pathologic partial responses. Conclusions: This is the first clinical study of KD018 with concomitant RT and demonstrates the safety and favorable toxicity profile of this regimen compared to historical controls. These preliminary results warrant further study of the efficacy of KD018 as an adjuvant to pelvic CRT or RT to reduce GI toxicity. See table. Clinical trial information: NCT02178644. [Table: see text]
Genomic profiling of young adults with colorectal cancer: A single-institution experience.
Authors: Koenig Kristin Lynn , Wu Christina Sing-Ying , Chen Wei , Frankel Wendy L , Jones Daniel , Zhao Weiqiang , Mikhail Sameh , Roychowdhury Sameek , Hays John L. , Noonan Anne M. , Goldberg Richard M. , Bekaii-Saab Tanios S. , Ciombor Kristen Keon 
Published: September 2018

e15168 Background: 2-8% of all colorectal cancer (CRC) cases are in younger adults (YAs), patients (pts) less than age 50. However, current understanding of CRC in YAs is inadequate, especially that of sporadic onset. We conducted a study to describe the landscape of genomic alterations in YA CRC pts presenting to a large academic practice. Methods: Adult pts with CRC presenting to The Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing (NGS) through a customized 22-gene Ion AmpliSeq Mutation Panel as part of clinical care. Commonly mutated areas of select genes (including AKT1, ALK, BRAF, EGFR, ERBB2/4, FBXW7, FGFR1/2/3, KRAS/NRAS, MET, NOTCH1, PIK3CA, PTEN, TP53) were sequenced from tumor sections. Institutional review board approval was obtained to retrospectively analyze this NGS testing between 1/2013-3/2016. Results: 258 CRC pts underwent genomic profiling. 57 pts (22.1%) were YAs at diagnosis (range 22-49 years); 20 pts (7.8%) were 40 years old or younger. 31 YA pts (54.4%) had metastatic disease. Of the YAs with CRC, 18 pts (31.6%) were diagnosed with R-sided colon, 16 pts (28.1%) with L-sided colon, and 22 pts (38.6%) with rectal cancer. 110 genomic alterations were found in YA pts, with a mean of 1.9 mutations per tumor (range 0-6); 35 (31.8%) of these in 32 (56.1%) YA pts were actionable. Of these 110 alterations, 41.8% were in TP53, 28.2% in KRAS/NRAS, 10.0% in PIK3CA, 3.6% in BRAF, 3.6% in FBXW7, and 2.73% in PTEN. 6 YA pts (10.5%) had microsatellite instability (MSI-H). Only 1 pt had concomitant MSI-H and a BRAF mutation; 4 pts with BRAF mutations were microsatellite stable. Comparing our YA pts to a separate cohort of pts age > 50 who had testing done, no significant difference was seen in mutation incidence in KRAS/NRAS (p = 1.0), TP53 (p = 0.3), PIK3CA (p = 0.128), or BRAF (p = 1.0). Conclusions: Genomic profiling through a targeted NGS panel is feasible as part of routine clinical practice. There is disagreement in the literature on genetic mutations in YA compared to older age CRC pts. Knowledge of the genomic landscape in YAs with CRC will lead to improved understanding of the underlying biology of CRC in YAs as it differs from CRC in older pts, and could impact future care of this cohort.