bluuebunny/crossref_metadata_2025_split huggingface dataset:
The strategy of zero-mortality due to postoperative VTE in patients with colorectal cancer.
Authors: Iwahashi Shoko , Nishi Masaaki , Tetsuya Ikemoto , Yoshikawa Kozo , Higashijima Jun , Miyatani Tomohiko , Tokunaga Takuya , Takasu Chie , Kashihara Hideya , Shimada Mitsuo 
Published: January 2019

511 Background: The best method of venous thromboembolism (VTE) prevention after surgery for colorectal cancer remains unclear. It is reported that about 20-40% of high-risk patients were diagnosed as DVT and 2-4% was diagnosed as PE and its mortality rate is 0.5-1.0%. The aim of this study is to evaluate the incidence of postoperative VTE patients with colorectal adenocarcinoma and to evaluate the efficacy of VTE preventive strategy. Methods: A total of 264 patients who had undergone curative surgical resection for colorectal cancer at Tokushima University Hospital were included in this study (n = 264 colon: rectum = 1:0.57). All patients were measured D-dimer preoperatively. When D-dimer was ≥ 1.1, lower extremities ultrasonography (US) was performed. All patients were treated with Heparin (10,000U/24h) continuously intravenous injection from the day of surgery, and administered Enoxaparin (2,000U/24h) subcutaneous injection after 24h of the operation. Results: In all 264 patients, 74 (28%) were D-dimer ≥ 1.1 and 16 (6%) diagnosed VTE in US (proximal:distal type n = 6:1). 239 (91%) were treated with postoperative anticoagulant therapy. 2 developed perioperative VTE (symptomatic: asymptomatic = 1:1) and after discharge 12 developed postoperative VTE and mortality rate of VTE was 0%. Univariate analysis indicated that obesity (BMI ≥ 25), hyperlipidemia and preoperative PE were risk factors for deep venous thrombosis (DVT) (p < 0.0001, 0.014, 0.0135, respectively) and multivariate analysis revealed that obesity was an independent risk factor for postoperative DVT (p < 0.0001). Conclusions: Obesity (BMI ≥ 25) was independent risk factor for postoperative VTE. Our preventive protocol including screening using D-dimer and lower extremities US and treatment with Enoxaparin is considered as effective for prevention of postoperative VTE.
DNA damage response pathway mutations contribute to a high proportion of hereditary colorectal cancer in patients from the Republic of Macedonia.
Authors: Staninova Marija , Matevska Geshkovska Nadica , Angelovska Biljana , Nenad Mitrevski , Panovski Milco , Dimovski Aleksandar J 
Published: January 2019

512 Background: Hereditary factors are assumed to play а role in 35-45% of all colorectal cancers with 5%-10% associated with high penetrant disease-causing mutations in genes correlating to hereditary polyposis (HP) or hereditary nonpolyposis syndromes (HNPCC). Although inherited germline mismatch repair and APC gene mutations contribute significantly to CRC, still a genetic diagnosis cannot be obtained in > 50% of familial cases. Methods: We performed a targeted NGS sequencing of 103 probands with clinically diagnosed HP (39) or HNPCC (64) using a multigene panel on two different platforms (Illumina Cancer Panel and Ion Torrent custom panel) covering coding and exon/intron sequences of 100 genes implicated in hereditary cancers. Results: Overall, the molecular defect was identified in 60 (58%) index patients. As expected, a large percentage (82%) of these patients exhibited the presence of clearly pathogenic mutations in well-known genes associated with hCRC (APC, MUTYH, BMPR1A, NTHL1 in HP, MLH1, MSH2, PMS6, MSH6 in HNPCC). Surprisingly, all except one (FLCN c.1285dupC, detected in a family with classical FAP), of the remaining mutations were located in genes involved in the DNA damage response pathway, of which 3 in CHEK2 (c.1031delT; c.1229delC; c.599T>G), 2 in BRIP1 (c.2392C>T) and 1 in each of BLM (c.1642C>T), BRCA2 (c.4446_4451dupAACAGA), FANCM (c.2953delG), FH (c.1431_1433dupAAA) and ERCC2 (c.1403C>T). Clinically, six of these cases exhibited the HNPCC type X phenotype (mutations in BRCA2, BRIP1, FANCM and CHEK2) while the other four were classified as oligopolyposis (mutations in BLM, FH and CHEK2). Conclusions: Our data indicate a significant association of DNA damage response pathway deficiencies and carcinogenesis in patients with hCRC syndromes exhibiting either the HNPCC type X or oligopolyposis phenotype. No genetic defect was detected within the analyzed gene panel in 44 (42%) families, indicating the need of extended exome/whole genome analyses in a substantial portion of patients with this disease.
Are quantitative measures of visceral adiposity obtained after neoadjuvant chemoradiation associated with postoperative morbidity in patients with locally advanced rectal cancer?
Authors: Hendrick Leah E. , Lippuner Veronica , Speaks Tyler , Scharr Travis S , Fleming Andrew M , Guerrero Whitney M , Glazer Evan Scott , Dyer Andrew W , Shibata David 
Published: January 2019

514 Background: Body mass index (BMI) is an inconsistent predictor of surgical morbidity in cancer patients. Increased visceral obesity measured before neoadjuvant chemoradiation (NCR) has been associated with post-operative morbidity in rectal cancer (RC). We sought to evaluate whether visceral obesity/BMI measured immediately after NCR correlates with postoperative complications in a heterogenous, largely underserved cohort of RC patients. Methods: 116 patients (64% white, 34% black, 2% other) underwent proctectomy for stage II/III RC after NCR. Automated CT segmentation software was used to determine body fat distribution at the L4/L5 level. Patients were classified as obese by BMI (≥ 30 kg/m2) and post-NCR CT measures of adiposity including visceral fat area (VFA; > 100cm2), visceral to subcutaneous fat area ratio (V/S; > 0.4), and perinephric fat thickness (PNF; > median) were obtained. Complications were classified (Clavien-Dindo) into low (1-2) or high (3-4) grade. Associations between measures of adiposity, short-term surgical outcomes and clinicopathologic factors were evaluated with one-way ANOVA, Chi-square, and Fischer’s exact test as appropriate for overall, white, and non-white cohorts. Results: Obese patients by adiposity measures (but not BMI) were more likely to be male by V/S (91.4% vs. 54.3%, p ≤ 0.001) and PNF (62.9% vs. 26.1%, p ≤ 0.001), Caucasian by VFA (mean 135.2 cm2vs. 93.8 cm2, p = 0.002), and have preexisting metabolic comorbidities by VFA and PNF ( p < 0.01). V/S was associated with the presence of key metabolic comorbidities in both white and non-white groups ( p < 0.05). Obesity by V/S but not BMI was associated with development of postoperative complications in the non-white group (65.5% vs. 30.8%, p = 0.049), but not in the overall or white cohorts. Conclusions: V/S as measured after NCR is associated with presence of key metabolic comorbidities in the entire cohort but with postoperative complications only in non-white patients. Given these observations, further evaluation of the impact of socioeconomic factors and change in adiposity between pre- and post-NCR time periods is warranted.
Microsatellite instability detection from plasma of colorectal cancer patients.
Authors: Sun Jing , Cai Zhenghao , He Songbing , Liu Chengliu , Zheng Minhua , Zhu Xinguo , Zhou Jian , Yao Yizhou , Han-Zhang Han , Liu Hao 
Published: January 2019

515 Background: MSI, detected in 15% of colorectal cancer (CRC) patients, is a hypermutable phenotype caused by deficiency in DNA mismatch repair system. Currently, MSI detection is limited to tissue samples. Detection of MSI from blood samples has been explored but confounded by low sensitivity due to the trace amount of ctDNA present. In this study, we developed a NGS read-count based algorithm-bMSISEA (blood MSI signature enriched analysis) to detect MSI from blood samples. Methods: Matched tumor and adjacent normal tissues were obtained from 50 MSI-H CRC patients to establish a microsatellite pattern for MSI-H tumors. White blood cells (WBCs) from 100 CRC patients were used to establish a microsatellite pattern for MSS. Plasma samples were obtained from 75 CRC patients with known MSI status assessed by IHC (38 MSI-H and 37 MSS) to validate the algorithm. Results: To establish features for MSI-H and MSS tumors, 51 microsatellite loci covered by ColonCore panel with mononucleotide repeats longer than 10bp were scanned using paired tumor and adjacent normal tissues and 8 loci with significant differential read length distribution were identified. MSI signature enrichment analysis was performed using WBCs to establish a microsatellite signature for MSS tumors. For each locus, the numbers of total reads supporting either MSI-H (denoted as K in the equation) or MSS (N-K, where N refers to the total number of reads supporting either MSI-H or MSS at a specific locus) were counted. The MSI signature enrichment analysis was performed using hypergeometric test. The log-transformed p values were used to calculate z scores. The final microsatellite status was reflected by MS score, which was the sum of z scores of all loci. A MS score of 15 was derived to differentiate MSS and MSI-H tumors. Both simulation data and data generated using clinical samples revealed more than 98% sensitivity and 100% specificity with ctDNA percentage greater than 1%. This method is still reliable if the ctDNA percentage drops to 0.4%, yielding sensitivity of 93.3% and specificity of 100%. Conclusions: We developed a sensitive algorithm which can reliably detect MSI status with ctDNA fraction greater than 0.4% with sensitivity of 93.3% and specificity of 100%.
Association between primary tumor site, perioperative CEA ratio, and overall survival in patients with colorectal cancer.
Authors: Odeny Thomas A , Farha Nicole , Vazquez Wilfred , Batool Amna , Saeed Anwaar , Paluri Ravi Kumar , Kasi Anup 
Published: January 2019

518 Background: There are differences in the incidence, clinical presentation, molecular pathogenesis and outcome of colorectal cancer (CRC) based on the tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio is a prognostic factor for CRC patients. We aimed to determine the association between tumor location, perioperative CEA ratio, and 5-year survival among patients with CRC. Methods: We analyzed 111 patients who underwent resection for CRC at KUMC. After excluding patients without pre- or post-operative CEA data, 62 patients for whom we could calculate a CEA ratio (post-op/pre-op CEA) were classified as either high ( ≥ 0.5) or low ( < 0.5) ratio. The primary outcomes were: 1) overall survival (OS) stratified by tumor location; 2) OS stratified by CEA ratio; and 3) whether there was effect modification by tumor location, of the association between perioperative CEA ratio and OS, after adjusting for tumor stage and smoking status. Kaplan-Meier method was used to estimate survival rates, and Cox proportional hazards models for multivariate analysis. Results: The median age was 61 years, 54% male, 31% smokers, 74% left-sided tumors, median pre-operative CEA was 3.3, and 60% had CEA ratio ≥ 0.5. The OS rates were 89.1% and 81.3% in patients with left-sided versus right-sided tumors respectively (p-value = 0.4). The OS rates were 83.8% and 92.0% in patients with high versus low CEA ratios respectively (p-value = 0.3). There was effect modification by tumor location on association between CEA ratio and OS, after adjusting for smoking status and tumor stage (p-value < 0.001). However, in the stratified analysis, the n was too small to permit inferential analysis. In multivariate analysis, both tumor location (HR 0.4; p = 0.3) and perioperative CEA ratio (HR 2.7; p = 0.3) were not significantly associated with OS after adjusting for smoking status and tumor stage. Conclusions: There was no difference in OS between left versus right-sided tumors. The association between perioperative CEA ratio and OS was significantly modified by tumor location. However, to attribute this modification to left versus right warrants validation in a larger cohort as our sample size was limited.
Clinical and functional analysis of SOX9 in colorectal cancer.
Authors: Lizarraga Erik , Ruiz Garcia Erika , Lopez-Camarillo Cesar , Meneses Abelardo , Astudillo Horacio , Fernandez Figueroa Edith Araceli , Lino-Silva Leonardo , Avendaño-Félix Mariana Melisa , Parra-Niebla Maryelv , Bermúdez-Cortés Mercedes , Ramos-Payán Rosalío , Silva-Benítez Erik , Romero-Quintana José Geovanni , Aguilar-Medina Elsa Maribel 
Published: January 2019

519 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. CRC develops within the intestinal epithelium, which is constantly self-renewing, developmental genes could promote the initiation and progression of cancer. SOX9 transcription factor is expressed especially in intestinal stem cells and in Paneth cells, thus alterations in expression could greatly promote neoplasia. However, the clinical significance and functional role of SOX9 in CRC remains unclear. The aim of this study is to investigate the association of SOX9 expression with relapse in CRC patients and initiate functional studies by evaluating the effects of silencing SOX9 in stem cells properties such as colonospheres formation in HCT116 CRC cells. Methods: 97 FFPE biopsies from CRC patients in stage I (N = 34) and stage II (N = 63) were analyzed. Immunoreactivity of SOX9 was classified as low and high expression groups based on the percentage of positive nucleus and tissue staining intensity. SOX9 silencing was achieved using a specific siRNA and Lipofectamine-RNAiMax and confirmed by qPCR 24 h postransfection. 40,000 HCT116 and HCT116-siSOX9 cells were seeded under adherent and ultra-low attachment conditions for tumorigenesis assays. After 72 h colonospheres were seeded and quantified. ROC analysis was used to assess the clinical correlation of SOX9 with relapse. Experimental data were expressed as means and differences tested by t-Student. Results: Data showed that 12.3% of patients relapsed. Interestingly, all of them showed lower SOX9 expression (p ≤ 0.05), regardless of their relapse free survival. In functional analysis, SOX9-deficient HCT116 cells formed smaller and less-compacted spheroid when compared to non-transfected HCT116 (p ≤ 0.05). Nonetheless, cell proliferation and migration under adherent condition were similar between the groups. Conclusions: This study did not find association between SOX9 expression and relapse. So far, in vitro assays results suggest that silencing of SOX9 inhibits colonospheres formation in HCT116 cells. Further investigation will be performed in order to evaluate the functional importance of SOX9 in chemotherapy response.
Prediction of peritoneal recurrences of gastric cancer by qPCR analysis of peritoneal lavage fluids.
Authors: Nakanishi Koki , Kanda Mitsuro , Umeda Shinichi , Tanaka Chie , Kobayashi Daisuke , Hayashi Masamichi , Yamada Suguru , Nakayama Goro , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: January 2019

52 Background: Peritoneal lavage cytology has been regarded as the only reliable method detect free cancer cells in the abdominal cavity. However, there certainly are patients who experience peritoneal recurrences despite negative cytology. Methods: Using qRT-PCR analysis, mRNA levels of 9 candidate molecular markers were quantified in peritoneal lavage fluids of from 187 patients with gastric cancer and 30 benign disease controls. ROC curve analysis was conducted to compare accuracies of the candidate markers. The cut-off points were set at the highest values of the benign disease controls. We evaluated predictive values of molecular markers in peritoneal lavage fluids for peritoneal recurrence. Results: From the result of ROC curve analysis, synaptotagmin XIII ( SYT13) and carcinoembryonic antigen ( CEA) mRNA levels were identified as predictive markers for peritoneal recurrences (The AUC value, 0.771, 0.775, respectively). 162 patients who had no concomitant peritoneal metastasis and were negative for lavage cytology (P0CY0), 13 patients (8.2%) had peritoneal recurrences. Those with either positive SYT13 or CEA mRNA level in peritoneal lavage fluids had significantly shorter peritoneal recurrence-free survival times compared to those with negative (3-years peritoneal recurrence-free survival rates, 69.5% vs 95.6%; P = 0.0069 and 79.3% vs. 93.4%; P = 0.0211, respectively). By combination of SYT13 and CEA, patients with both markers-positive had the greatest prevalence of peritoneal recurrences. Moreover, the peritoneal recurrence free survival curves of the both markers-positive group approached to that of the positive for lavage cytology group. Univariate analysis revealed that both SYT13-positive and CEA-positive were prognostic factors for peritoneal recurrence (hazard ratio: 4.21 and 3.53, respectively). In the multivariable analysis, SYT13-positive was found to be statistically significant independent prognostic factors (hazard ratio: 3.84, 95% confidence interval 1.24-13.2, P = 0.0202). Conclusions: SYT13 and CEA levels in peritoneal lavage fluids accurately predict peritoneal recurrences in patients with P0CY0.
Validation of the NCI Colorectal Cancer Risk Assessment Tool for baseline advanced neoplasia in a veterans cohort.
Authors: Musselwhite Laura W. , Redding Thomas S. , Hauser Elizabeth R. , Lieberman David A. , Provenzale Dawn T. 
Published: January 2019

521 Background: Tailoring screening strategy to colorectal cancer (CRC) risk may improve efficiency for all stakeholders. We applied the National Cancer Institute (NCI) CRC Risk Assessment Tool, which calculates 5-10-year, and 20-year absolute risk of colorectal cancer to determine whether it could be used to predict baseline risk of colorectal cancer precursors in a Veterans cohort undergoing first screening colonoscopy. Methods: This was a prospective evaluation of whether the NCI CRC Risk Assessment Tool which offers an absolute risk over time, could be used to estimate baseline cancerous precursors (advanced neoplasia) in Veterans undergoing first screening colonoscopy. Family, medical, dietary and physical activity histories were collected at the time of screening colonoscopy and used to calculate absolute 5, 10, and 20-year CRC risk, and to compare estimated CRC risk to observed AN. Sensitivity analyses were performed. Results: Of 3,121 Veterans undergoing screening colonoscopy, 94% had complete data available to calculate risk (N = 2,934, median age 63 years, 100% men, and 15% minorities). 11% (N = 313) were diagnosed with AN on baseline screening colonoscopy. The area under the curve for predicting AN was 0.60 (95% CI; 0.57-0.63, p < 0.0001) at 5 years, 0.60 (95% CI, 0.57-0.63, p < 0.0001) at 10 years and 0.58 (95% CI, 0.54-0.61, p < 0.0001) at 20 years. At 5 years, we calculated the sensitivity (0.18, 95% CI; 0.14-0.22), specificity (0.91, 95% CI; 0.90-0.92) positive predictive value (0.19, 95% CI; 0.15-0.24) and negative predictive value (0.90, 95% CI; 0.89-0.91) considering the top 10th percentile of risk tool scores as a positive result. Conclusions: The NCI CRC Risk Assessment Tool had modest discriminatory function for predicting AN risk at 5, 10 and 20 years. The Tool’s specificity and negative predictive value were quite good, highlighting its usefulness in risk prediction. This tool may beused to inform the benefit-risk assessment of screening colonoscopy for patients with competing comorbidities.
Characteristics and survival among early onset and standard onset colorectal cancer by race.
Authors: Acuna Villaorduna Ana , Goel Sanjay 
Published: January 2019

522 Background: The incidence of early-onset colorectal cancer (EO) is increasing. Guidelines recommend to start screening colonoscopy at 45 yo in Non-Hispanic Black (NHB). We compare the clinical features and outcomes between EO and standard-onset (SO) colorectal cancer (CRC) among racial groups. Methods: Patients with CRC adenocarcinoma; available race/ethnicity and stage were identified using the SEER registry. Clinical features and 5 year-overall survival (OS) is described by racial and age groups. Results: 190 670 patients were identified. EO rates were higher for minorities than NHW. Median age at diagnosis in EO was 44 and was similar among racial groups; while it was 71 in SO, being lower among minorities compared to NHW (67 vs. 72 years, p < 0.01). Left-sided tumors accounted for 77.4% of tumors in EO while it was 60.8% in SO for minorities versus NHW. The most common CRC location for EO was the rectum and sigmoid colon for SO. EO was most commonly diagnosed as stage III. Surgery and radiation rates were higher for EO for all stages. OS was higher in all stages of EO compared to SO. Conclusions: EO frequency is higher in all minority groups and most commonly located in the rectum. Despite higher stage and grade, OS is higher for EO which might be due to higher treatment rates. Early screening should be extended to all minority groups. [Table: see text]
Prevalence of KRAS, NRAS, and BRAF gene mutations in metastatic colorectal cancer patients: A systematic literature review and meta-analysis.
Authors: Lowe Kimberly , Bylsma Lauren C , Levin-Sparenberg Elizabeth D , Sangaré Laura , Fryzek Jon , Alexander Dominik D 
Published: January 2019

523 Background: A systematic literature review and meta-analysis was conducted to summarize the prevalence of KRAS, NRAS, and BRAF mutations in mCRC patients. These mutations have substantial implications for treatment decisions among mCRC patients. Methods: Multiple databases were searched to identify observational studies and clinical trials (standard of care arms only) that reported mutation status among mCRC patients. Random effects meta-analysis models were used to estimate summary prevalence estimates for each of the mutations. Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity in mutation prevalence. Results: The meta-analyses included 275 studies comprising over 77,000 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males ( KRAS: 42.2% vs. 37.3%, p = 0.011; BRAF: 11.0% vs. 7.9%, p = 0.018), and significant variation by study location was observed for both KRAS (p = 0.025) and BRAF (p = 0.002) mutation prevalence. Conclusions: The prevalence of KRAS, BRAF, or NRAS mutations in mCRC patients varies significantly by gender and study location. compared to patients with wild-type tumors. The results of these analyses are informative for clinicians, patients, and researchers.