bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence of pathogenic variants in individuals with colorectal cancer ≤ age 35.
Authors: Marshall Megan L. , Roberts Maegan , Susswein Lisa R. , McGill Anna K. , Xu Zhixiong , Klein Rachel T. , Hruska Kathleen S. 
Published: January 2019

576 Background: Young age at onset is a hallmark feature of an inherited predisposition to cancer. Recent evidence suggests that the incidence of pathogenic/likely pathogenic variants (PV) in cancer predisposition genes among individuals diagnosed with colorectal cancer (CRC) ≤ age 35 is high, but few studies have examined the frequency identified by multi-gene hereditary cancer panel testing. We report on PV yield and clinical presentation of individuals diagnosed with CRC ≤ 35 years (y). Methods: We retrospectively reviewed test requisition forms and provided pathology reports for 4,727 individuals with CRC who underwent panel testing of, at a minimum, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, and MUTYH. Two-tailed Fisher’s exact tests were used to determine statistically significant differences between groups. Results: Of the 691 individuals diagnosed with CRC ≤35y, 137 PV were identified in 126 individuals (126/691, 18.2%), including 72 with Lynch syndrome, 16 with familial adenomatous polyposis (FAP), five with MUTYH-associated polyposis, four with constitutional mismatch repair deficiency, one with juvenile polyposis syndrome, and one with Peutz-Jeghers syndrome. Thirty-eight additional PVs were identified in other non-CRC genes. Microsatellite instability (MSI) and immunohistochemistry (IHC) results were reported for 277 individuals and were reportedly abnormal in 63. The yield of PV in individuals with abnormal tumor studies was 52.4% (33/63); PV in genes other than the Lynch syndrome-associated genes were identified, commonly in the MSI-H group. While statistical significance was not observed, the positive rate was higher for individuals with non-rectal cancers (colon cancer: 104/534, 19.5%; rectal cancer: 22/157, 14.0%, p = 0.13). Conclusions: In our cohort, 18.2% of individuals diagnosed with CRC ≤35y were found to harbor a PV. Yield increased in those with abnormal MSI/IHC as well as non-rectal tumor location. Hereditary predispositions in patients diagnosed with very early-onset CRC are not limited to Lynch syndrome and FAP. Therefore, individuals with very early-onset CRC may benefit from multi-gene panel testing rather than syndromic-based testing.
Differential utilization of preventive care among colon cancer survivors compared to non-cancer patients.
Authors: Lau Sally C , Lee-Ying Richard M. , Sam Davis , Cheung Winson Y. 
Published: January 2019

577 Background: With advances in diagnosis and treatment, many cancer patients survive more than 5 years. The care of these cancer survivors (CS) represent an area of unmet need. We aim to characterize the patterns of preventive care in colon CS compared to non-cancer controls (NCC) and identify areas of deficiencies within the context of a universal health care system. Methods: Adult patients with non-metastatic colon cancer treated at the BC Cancer Agency between 2000-2012 were included. An age and gender matched cohort constructed from the provincial database served as NCC. Areas of preventive care examined include vaccinations, cancer, osteoporosis and cardiovascular diseases (CVD) screening. Multivariate regressions were done to test for associations between CS and preventive care. Results: In total, 9381 colon CS and 47187 NCC, matched at a ratio of 1:5, were analyzed. Among CS, median age of diagnosis was 68, 58% were male and 47% had stage 3 disease. The median overall survivals were 12/10/8 years for stages 1/2/3 disease respectively. 61% of these survivors died from colon cancer, 12% from other cancers and 25% from non-cancer causes. Deaths from colon cancer are more common within 5 years of diagnosis, particularly stage 3 disease. CS were more likely to receive any preventive care. In CS compared to NCC, 90% vs 85%, 47% vs 39% and 53% vs 46% of eligible patients had CVD screening, cancer screening and other preventive care respectively. This remained significant in multivariate analyses (Table). Patients who were female, had higher income and resided in urban areas were more likely to receive screening. Among CS, patients > 65 years (OR1.2, p = 0.04 95%CI 1.0-1.4), females (OR 1.5, p < 0.01 95%CI 1.3-1.8) and stages 1 or 2 disease (OR 1.3, p < 0.01 95%CI 1.1-1.5) had higher uptake of screening. Conclusions: Many colon cancer patients are long term survivors. CS are more likely to receive screening than NCC but uptake is suboptimal in certain areas. Targeted education towards certain sub-groups such as males, ≤65 years, low income and rural area patients may improve long term health outcomes. [Table: see text]
Prevalence of advanced colorectal neoplasia according to risk categories at screening colonoscopy in a tertiary referral center.
Authors: Negrete Carballo Eduardo , Huitzil Melendez Fidel David 
Published: January 2019

578 Background: Colorectal cancer (CRC) is the third most common cancer in the world. There is strong evidence that screening for colorectal cancer improves survival in conutries with high incidence. Although Mexico is considered a country with a low incidence of CRC, 4694 potentially preventable deaths occur every year. There is no established CRC screening program in our country, risk stratification of the target populations to be screened may bring potential advantages, making the strategy more cost-effective. The Asia-Pacific Colorectal Screening (APCS) score, is a validated risk-stratification tool that helps identify individuals at risk for advanced colorectal neoplasm amongst the asymptomatic population. Methods: We performed a retrospective, cross-sectional analysis of database records from 1172 patients who underwent screening colonoscopy betwen january 2013 and november 2014. Results: The prevalence of advanced colorectal neoplasia was 2.9%. Applying the APCS stratification, 91 subjects (7.8%) were in the average risk tier, 849 subjects (72.4%) in the moderate risk tier and 232 (19.8%) subjects in the high risk tier. The prevalence of advanced neoplasia in the average risk, moderate risk and high risk groups was 0%, 2.6% and 5.1%, respectively. The subjects in the high risk tier had 2.21-fold (p = 0.021) increased prevalence of advanced neoplasia than those in the average-moderate tier. Conclusions: The APCS score is a simple risk stratification index for colorectal advanced neoplasm that uses elementary clinical information on age, gender, family history and smoking to stratify the risk of colorectal advanced neoplasm in asymptomatic subjects for priority of colorectal screening.
The prognostic value of systemic inflammation in patients undergoing surgery for rectal cancer: Comparison of composite ratios and cumulative scores.
Authors: Dolan Ross , McSorley Stephen Thomas , Park James Hugh , Roxburgh Campbell SD , Horgan Paul G. , McMillan Donald C 
Published: January 2019

579 Background: Colorectal cancer is the second commonest cause of cancer death in Europe and North America with rectal cancer making up a third of this disease burden. Markers of the systemic inflammatory response (SIR) have been shown to be prognostic in cancer. These include ratio of different white blood cells/acute phase proteins such as NLR (neutrophil/lymphocytes), PLR (platelets/lymphocytes), LMR (lymphocytes/monocytes) and CAR (CRP/albumin) and cumulative prognostic scores such as NPS (Neutrophil Platelet Score)/mGPS (modified Glasgow Prognostic Score). The aim of the present study was to compare the prognostic value of SIR markers in patients undergoing surgery for rectal cancer. Methods: A prospectively maintained database of all patients undergoing elective curative rectal resection in our institution was examined. The SIR was measured by the ratios and scores NLR, PLR, LMR, CAR, NPS and mGPS using standard thresholds NLR (>5), PLR (>150), LMR (<2.4), CAR (>0.24), NPS (0, 1, 2) and mGPS (0, 1, 2). Statistical analysis was carried out in SPSS using ROC curve and Cox regression analysis for both cancer specific survival (CSS) and overall survival (OS). Results: Of the 393 patients included in the study, 237 (60%) were male, 91 (25.6%) had neoadjuvant therapy, 341 (87%) had open surgery, 285 (72.5%) had T3/4 disease and 155 (39.4%) and node positive disease. On ROC curve analysis, validated ratios and scores such as NLR (AUC: 0.534 95%CI 0.469-0.600), PLR (AUC: 0.526 95%CI 0.444-0.607), LMR (AUC: 0.574 95%CI 0.472-0.676), CAR (AUC: 0.551 95%CI 0.487-0.615), NPS (AUC: 0.578 95%CI 0.513-0.643) and mGPS (AUC: 0.571 95%CI 0.513-0.629) showed considerable similarities. On multivariate categorical analysis with TNM stage there was a significant relationship between CSS and NPS (HR: 2.09 95%CI 1.14-3.82, p=0.017), CAR > 0.22 (HR: 1.64 95%CI 1.09-2.47, p=0.018) and mGPS (HR: 3.06 95%CI 1.71-5.47, p < 0.001). Conclusions: The SIR as measured by a number of scores/ratios had prognostic value in patients with rectal cancer. Only the NPS and mGPS had prognostic value independent of TNM stage. These scores may be useful in stratifying treatment in patients with rectal cancer.
Correlation of VEGF with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.
Authors: Gonda Kenji , Shibata Masahiko , Ujiie Daisuke , Ashizawa Mai , Okayama Hirokazu , Fujita Shoutarou , Sakamoto Wataru , Nakajima Takahiro , Endo Hisahito , Saito Motonobu , Saze Zenichiro , Monma Tomoyuki , Ohki Shinji , Kono Koji , Takenoshita Seiichi 
Published: January 2019

582 Background: Although a causal relationship for inflammation and immunity of cancer is more widely accepted today, the precise cell mechanisms mediating this relationship have not been elucidated. Vascular endothelial growth factor (VEGF), previously known as vascular permeability factor. 45 kDa protein, belongs to a family of platelet-derived growth factors. VEGF, inflammation-related protein, could contribute to the accumulation of immunosuppressive cells (MDSC, Treg, TAM, and Tie-2-expressingmonocytes) in tumor-bearing hosts through direct or indirect mechanisms. Methods: We tested the serum levels of VEGF by ELISA in 106 patients including 43 with gastric and 63 with colorectal cancer, and they were increased in advanced stages of gastric and colorectal cancer. Production of IL-17, pro-inflammatory cytokine, with a stimulation of PHA was measured by ELISA and MDSC (myeloid-derived suppressor cells), one of major immunosuppressing cells, was measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and SI (stimulation index) of blastogenic response of lymphocytes were used as markers of cell-mediated immune response. Results: The concentrations of VEGF were positively correlated with levels of MDSC, production of IL-17, NLR and CRP, and were inversely correlated with IL-12 production, SI and nutritional markers including prealbumin and retinol binding protein. The patients were both divided into two groups with a serum level of VEGF (330 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer were both significantly worse in patients with high levels of VEGF than in those with low VEGF although the differences were not significant in patients with stagesⅠand II. Conclusions: The results of the present study suggested that VEGF may have an impact on advancement and progression involving inflammation and serve as useful markers of the immune suppression involving MDSC, malnutrition and poor prognosis in patients with gastric and colorectal cancer.
Identifying the barriers to cancer care at safety-net hospitals: A novel comparison of a safety-net hospital to a neighboring quaternary referral academic institution in the same health care system.
Authors: Zaidi Mohammad , Rappaport Jesse , Ethun Cecilia Grace , Gillespie Theresa Wicklin , Hawk Natalyn Nicole , Chawla Saurabh , Cardona Kenneth , Maithel Shishir , Russell Maria C. 
Published: January 2019

59 Background: The three-delays model for vulnerable and minority populations to receive care include delays in seeking, reaching, and receiving care. The dominant delay for vulnerable patients with gastric adenocarcinoma (GAC) is not known. Our aim was to define those patients with GAC who reached care at our regional safety-net hospital compared to academic centers from the National Cancer Database (NCDB). We also aimed to compare survival outcomes of patients who received curative-intent resection at our safety-net hospital to those in a nearby quaternary referral hospital. Methods: Grady-Memorial-Hospital (GMH), a safety-net hospital and Emory-University-Hospital (EUH), a quaternary referral hospital, are within the same healthcare-system. Clinicopathologic data of patients at presentation from NCDB-participating academic centers were compared with GMH from 2004-2014. Patients undergoing curative-intent resection of GAC at GMH were compared to those at EUH during a similar time period. Primary outcome for the latter was overall survival (OS). Results: At presentation, compared to NCDB-participating academic centers (n = 69,662), GMH patients (n = 154) were more likely to be black (85.1 vs 17.2%; p < 0.001), uninsured (30.5 vs 4.7%; p < 0.001), have stage IV disease (43.5 vs 30.1%; p = 0.017), and receive no treatment (40.3 vs 18.4%; p < 0.001). When only comparing those who underwent curative-intent resection at GMH (n = 23) to EUH (n = 137), median OS was similar between both groups (GMH: median not reached; EUH: 59.8mos; p = 0.785). Conclusions: Patients with gastric cancer who reached care at our safety-net hospital are more likely to be uninsured, have stage IV disease, and receive no treatment compared to academic centers. When they receive curative-intent resection, however, overall survival is similar. Efforts must be made to identify and overcome the barriers in seeking and reaching care for this vulnerable patient population, as it appears that outcomes are acceptable in those who receive care.
Characterization of genomic alterations and biomarker expression patterns of gastrointestinal cancers using a multiplatform molecular profiling tool.
Authors: Suero-Abreu Giselle Alexandra , Gonzalez Velez Miguel , McKenna Marshall , Duma Narjust , Krishnasamy Shalini R , Proverbs-Singh Tracy Ann , Gutierrez Martin 
Published: January 2019

594 Background: Given the heterogeneity of gastrointestinal cancers (GICs), molecular profiling is becoming part of the standard of care for many solid tumors. The aim of this study was to evaluate the molecular profile of patients (pts) with GICs using a multiplatform profiling tool and to assess how the pattern of detected molecular alterations could guide clinical decision-making in these tumors. Methods: We retrospectively analyzed samples of 85 pts with GICs via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) in order to evaluate clinically relevant genomic alterations (CRGAs) and clinically relevant biomarker expression (CRBs) in GICs. Results: A total of 85 pts with GICs were analyzed. 45 (53 %) were males and 40 (47%) were females. Tumors were colorectal 43 (51%), pancreatic 11 (13%) esophageal 11 (13%) gastric 8 (9%), hepatobiliary 8 (11%), anal canal 3 (4%), and small intestine 1 (1%). 80 cases (94%) had adequate sample for profiling. CRGAs were identified in 71 cases (89%) with a median of 3 CRGAs in the cohort. The most commonly detected CRGAs were TP53 45 (56%), APC 35 (44%), KRAS 32 (40%), ATM 14 (18%) and PTEN 5 (6%). The median number of CRBs was 9 and high expression levels were seen of mismatch repair biomarkers (MLH1, MSH2, MSH6, PMS2) in 45 (56%), TOPO1 in 44 (55%), PTEN in 27 (34%), TOP2A in 20 (25%), ERCC1 in 19 (24%), and both TS and TUBB3 in 17 (21%). Based on actionable CRGAs and CRBs, 94% of pts matched at least one FDA approved treatment with proven clinical benefit, with a median of 4 available therapies per pt. In addition, there was a median of 189 chemotherapy and 64 targeted therapy clinical trial opportunities available for these pts given the molecular blueprint of their GICs. Conclusions: Multiplatform molecular profiling identified a high frequency of actionable CRGAs and CRBs in GIC pts. This approach has the potential to aid in clinical decision-making by providing a stratification of beneficial therapeutic alternatives individualized to the molecular framework of tumor. Larger prospective studies are warranted to further investigate the impact of profiling guided treatment decisions on patient outcomes.
Polyp burden in Lynch syndrome patients ascertained via multigene panel testing.
Authors: Roberts Maegan , Marshall Megan L. , Webb Erica M , McGill Anna K. , Susswein Lisa R. , Xu Zhixiong , Klein Rachel T. , Hruska Kathleen S. 
Published: January 2019

596 Background: Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is a hereditary colorectal cancer syndrome thought to present with few or no polyps. It has been suggested that the majority of LS patients with colon polyps will develop 1-9 cumulative adenomatous polyps in their lifetime, while approximately 10% will develop ≥10. Our aim was to describe polyp burden in a cohort of LS patients who were ascertained via multi-gene cancer panel testing. Methods: We retrospectively reviewed the personal history for all individuals with a pathogenic or likely pathogenic variant (collectively, PV) in MLH1, MSH2 (including 3’ EPCAM deletions), MSH6, or PMS2. Individuals with more than one PV in a LS-associated or other gene were excluded. All polyp data was obtained from provided test requisition forms and/or pathology reports. Results: A total of 131 individuals reported to have colon polyps were molecularly confirmed as having LS. Of these individuals, 55% (72/131) reported a history of colorectal cancer. Overall, polyp burden was reported as follows: 83% (109/131) with 1-10 polyps, 13% (17/131) with 10-19 polyps, and 4% (5/131) with 20-50 polyps. Of the 5 individuals reporting 20-50 polyps, the average was 31.2 polyps (range 21-50). Adenomatous pathology was reported for one or more polyps in 69% (91/131) of individuals. When limited to those with adenomatous polyps, 85% (77/91) reported 1-10 polyps, 11% (10/91) reported 10-19 polyps, and 4% (4/91) reported 20-50 polyps. When breaking down by presence and absence of colorectal cancer, 18% (13/72) and 15% (9/59), respectively, reported a polyp burden ≥10. Overall, 17% (22/131) of all LS patients reported ≥10 polyps. Conclusions: Similar to previously published data, the majority of LS patients with colon polyps report a polyp burden of < 10. However, our data suggest that the proportion of LS patients with a polyp burden of ≥10 may be higher than previously reported (17% vs. 10%) stressing the importance of including the LS-associated genes for these patients. While LS has historically been referred to as a “non-polyposis” syndrome, a subset of patients actually present with an attenuated polyposis-like phenotype.
Prospective randomized controlled trial comparing efficacy of 1-L Peg-Asc with prucalopride and 2-L Peg-Asc for the bowel preparation.
Authors: Choi Seong Ji , Jeen Yoon Tae , Kim Eun Sun , Kim Woojung , Min Geeho , Lee Jae Min , Kim Seung Han , Yoo In Kyung , Choi Hyuk Soon , Keum Bora , Lee Hong Sik , Chun Hoon Jai , Kim Chang Duck 
Published: January 2019

597 Background: Though numerous researches enabled decrease of the bowel preparation solution volume, it is still a major complaint of patients preparing colonoscopy. There have been studied that additional administration of laxatives could lessen the amount of aqueous formula with prokinetic effect. Prucalopride is a serotonin (5-HT4) receptor agonist which stimulate colonic mass movements and provide main propulsive force for defecation. The aim of this study is to compare 2-L PEG-Asc and 1-L PEG-Asc plus prucalopride for quality of bowel cleansing while preparing for colonoscopy and patient compliance. Methods: Two hundred patients were prospectively enrolled. Patients referred for colonoscopy were divided into group A (the split-dose 2-L PEG-Asc) and group B (1-L PEG-Asc + prucalopride) randomly. During colonoscopy, each patient’s bowel preparation quality was evaluated with The Boston Bowel Preparation Scale (BBPS) and Aronchick Preparation Scale (APS). The tolerability and satisfaction of patients was determined based on a questionnaire-based survey. Results: One hundred patients received either 2-L PEG-Asc or 1-L PEG-Asc with prucalopride. Regarding colon cleansing outcome (BPPS and APS), the 1-L PEG-Asc with prucalopride group showed similar, but non-inferior results compared to the 2-L PEG-Asc group on both BBPS (7.65±1.27 vs 7.52±1.40, p = 0.586) and APS scales (93.3% vs 95%, p = 0.717). Tolerability was similar for both 1-L PEG-Asc with prucalopride and 2-L PEG-Asc. Conclusions: 1-L PEG-Asc plus prucalopride preparation showed comparable result to traditional 2-L PEG-Asc preparation. 1-L PEG-Asc plus prucalopride preparation method could be an alternative method for bowel preparation which can relieve patient’s discomfort. Clinical trial information: KCT0002409.
Germline pharmacogenomics of DPYD*9A (c.85T>C) variant in patients with gastrointestinal malignancies treated with fluoropyrimidines.
Authors: Khushman Moh'd M. , Patel Girijesh K. , Hosein Peter Joel , Laurini Javier , Cameron Daniel , Clarkson David Roland , Butler Thomas Wayne , Norden Carole , Baliem Wilma , Jones Vanessa , Bhadkamkar Sanjyot , Nelson Cindy , Lee Frances , Singh Ajay , Taylor William R. 
Published: January 2019

598 Background: The correlation between DPYD*9A (c.85T > C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency clinical phenotype is controversial. Reference laboratories either did not perform DPYD*9A genotyping or have stopped DPYD*9A genotyping and limited genotyping to high-risk variants (DPYD*2A, DPYD*13 and DPYD*9B) only. This study explored DPYD*9A genotype and clinical phenotype correlation in patients with gastrointestinal (GI) malignancies treated with fluoropyrimidines. Methods: Between 2011 and 2017, 67 patients with GI malignancies were genotyped for DPYD variants. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Fisher’s exact test was used for statistical analysis. Results: DPYD variants were identified in 17 out of 67 (25%) patients. One patient was homozygous for DPYD*9A variant and one patient was double heterozygous for DPYD*9A and DPYD*9B variants. 13/17 (76%) patients had DPYD*9A variant, 3/17 (18%) patients had DPYD*2A variant and 2/17 (12%) patient had DPYD*9B variant. Only patients genotyped prior to 2015 were genotyped for DPYD*9A variant (N = 28). Of those, 13/28 patients (46%) had DPYD*9A variant. Grade 3-4 diarrhea was associated with DPYD*9A variant in patients treated with full dose fluoropyrimidines (P = 0.0055). Conclusions: In our cohort, DPYD*9A variant was the most common diagnosed variant. The correlation between DPYD*9A genotype and DPD deficiency clinical phenotype was noticeable in patients who received full dose fluoropyrimidines as they all experienced grade 3-4 toxicities (diarrhea).