bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment rectal tumors quantitative dynamic contrast-enhanced MRI characterization and predictability of outcome: Pilot study.
Authors: Shabana Wael , Saif Sameh , Cron Greg , Thornhill Rebecca , Koudrina Natalia , Koudrina Anna , Jonker Derek J. 
Published: February 2017

416 Background: Treatment of rectal cancer is currently a one-size-fits-all approach. Unfortunately, some rectal tumors do not respond well to treatment and/or give rise to latent metastases. Therefore, a need exists for biomarkers which can better characterize tumor aggressiveness and help guide treatment decisions. We investigated the feasibility and performance of dynamic contrast-enhanced (DCE) MRI (performed pre-treatment) as a potential biomarker to predict rectal cancer response to treatment. Methods: 47 patients with rectal masses underwent DCE-MRI at 3T pre-treatment. DCE-MRI was performed with 3D FLASH (TR/TE/flip 6ms/1.6 ms/25 deg). Gadolinium concentration-versus-time in tissue was estimated with the aid of a variable-flip-angle T1 mapping procedure performed pre-DCE. The arterial input function was estimated by measuring phase-versus-time in major arteries. Tracer kinetic modeling was used to obtain maps of the quantitative perfusion parameters Ktrans and Kep. Treatment outcome was categorized as successful (regression) or unsuccessful (progression, stable, or recurrence). We also dichotomized latent metastases as absent or present. The pathology outcome of the lesions was categorized as cancerous or non-cancerous. A support vector machine classifier was constructed from the perfusion parameters, and the accuracy of each classifier was determined by 10-fold cross validation. Results: Clinical characteristics were 31 successful outcomes, 8 unsuccessful; 25 with latent metastases absent, 5 with latent metastases present; 40 cancerous, 7 non-cancerous. The accuracies of quantitative DCE-MRI parameters for predicting treatment outcome, latent metastases, and pathology outcome were 78%, 83%, and 84%, respectively. Conclusions: Pre-treatment DCE-MRI appears to be a useful predictor of rectal tumor malignancy, treatment outcome, and latent metastases. Perfusion parameters have very promising potential to predict rectal cancer outcome and may serve as an added tool for rectal cancer treatment planning.
Effect of genetic counseling on detection of Lynch syndrome (LS) in colorectal cancer (CRC) patients (pts).
Authors: Haraldsdottir Sigurdis , Hampel Heather , Frankel Wendy , Wu Christina Sing-Ying , Pan Xueliang Jeff , Bekaii-Saab Tanios S. , Goldberg Richard M. 
Published: February 2017

419 Background: LS, characterized by germline mutations in MLH1, MSH2, MSH6, or PMS2, leads to defective DNA mismatch repair (dMMR) and causes 2%-3% of CRC cases. Ohio State University (OSU) began immunohistochemistry (IHC) screening on all CRC cases in 2006. In 2006 results were reported in pathology reports without further follow-up. From 2007 to 2010 genetic clinic (GC) counselors contacted pts and recommended further testing. Since 2011, GC counselors met pts at a follow-up appointment. This retrospective study aims to assess if type of follow-up after abnormal IHC, affects rate of conclusive testing. Methods: All CRC pts diagnosed at OSU from 03/06-06/12 had MMR testing per IHC. All pts’ charts were reviewed. Conclusive testing, following the initial MMR IHC, includes either MLH1-hypermethylation testing and/or gene sequencing to identify LS from non-LS pts. Chi-square test was used for categorical parameters and t-test for continuous variables to compare differences between pts with conclusive test vs those without. Results: One-hundred and twenty two tumors of 777 (15.7%) tested had dMMR by IHC. The GC follow-up of abnormal results significantly affected the rate of conclusive testing. The rate of conclusive testing went from 14.3% in 2006 to 38.4% in 2007-2010 and after 2011, 90.5% of the pts had conclusive testing done. Among 51 pts undergoing full testing, 13 pts were diagnosed with LS, 29 pts had MLH1-hypermethylated tumors, and 9 pts were not found to have any mutations on gene sequencing. Conclusions: Conclusive testing rates after abnormal universal screening with IHC improved significantly with GC involvement and was most effective when GC counselors met with the pts during their appointment. [Table: see text]
Development of a metabolite profile for colorectal cancer detection.
Authors: Gu Haiwei , Dai Jin , Carnevale Neto Fausto , Djukovic Danijel , Zhu Jiangjiang , Raftery Daniel 
Published: February 2017

422 Background: While carcinogenesis of colorectal cancer (CRC) is a complex process involving genetic abnormalities, metabolomics, which aims to establish metabolic responses of living systems to external or internal perturbations, has great potential to develop a metabolite profile specific to CRC for both early detection and treatment monitoring purposes. In this pilot study, we examined the colon cancer-induced alterations of amino acids and their distribution in the three domains of free amino acids (FAAs), free amino acids and soluble peptide amino acids (FAASPAAs), and proteome amino acids (PAAs). Methods: 56 serum samples were collected from 28 colon cancer patients and 28 healthy controls. FAAs were extracted after protein precipitation. FAASPAAs and PAAs were obtained using traditional acid hydrolysis. We utilized LC-MS/MS to make the amino acid measurements, and performed penalized logistic regression analysis on the amino acid signals in the three domains, both individually and in combination. Results: There were 10, 9, and 14 amino acids with low P-values (<0.05) in FAAs, FAASPAAs, and PAAs, respectively, when comparing the two groups. The penalized logistic regression model based on amino acids from the three domains had a sensitivity of 65% when the specificity was 95%. An area under the receiver operator curve (AUROC) of 0.91 was achieved for the combined statistical model. Significant amino acids in statistical modeling included aspartic acid, glutamic acid, glutamine/lysine, and histidine from FAAs, lysine from FAASPAAs, and arginine, serine, and tyrosine from PAAs. Conclusions: To the best of our knowledge, this is the first study to perform a combined analysis of amino acids in the three domains and derive a multivariate statistical model for detecting colon cancer. It was discovered that amino acid concentrations in all three domains are changed significantly in colon cancer and their relative distributions are also altered. The combined analysis helped improve the statistical model for detecting colon cancer. Since this study aims to investigate amino acids that directly connect the metabolome and proteome, it potentially brings new insights to the diagnosis of and mechanism involved in colon cancer development.
A case series of Lynch syndrome-associated breast cancer.
Authors: Zbuk Kevin M. , Goldberg Mira , Bell Kathleen , Semotiuk Kara , Gallinger Steven , Aronson Melyssa 
Published: February 2017

432 Background: Studies suggest breast cancer (BC) might be a feature of Lynch syndrome (LS). Further characterization of this risk is required before recommending increased surveillance for BC in LS families. This study describes the prevalence and characteristics of BC amongst LS families in a large familial cancer registry. Methods: The pedigrees of 325 families carrying an MMR gene mutation (149 MSH2 46%, 113 MLH1 35%, 38 MSH6 12%, 19 PMS2 5%, and 6 EPCAM 2%) within the Familial Gastrointestinal Cancer Registry (FGICR) were screened for a diagnosis of BC. The analysis was limited to known or obligate carriers of a MMR gene mutation. The diagnosis and age of diagnosis of BC was confirmed utilizing clinic records and pathology reports where available. Descriptive and Chi-squared statistics were utilized. Results: 39 female mutation carriers from 33 unrelated families with a diagnosis of BC were identified. The average age of BC diagnosis was 53y. The vast majority of families (25/33, 76%) carried MSH2 mutations. Of the 8 remaining families there were 6 (18%) MLH1 carriers, 1 (2.5%) MSH6 carrier, and 1 PMS2 carrier. The mutation distribution amongst the LS patients with BC was statistically different from those without BC (p = 0.008), reflecting the predominance of MSH2 mutations amongst patients with BC. Twenty-nine of 33 LS families with BC met Amsterdam Criteria (88%), compared with 142 of 292 LS families without BC in a known carrier (48%) (p = 0.03). LS associated BCs tended to be high grade (10 of 19 were grade 3), and 50% were ER/PR/Her2 negative. Additional manifestations in patients with BC included 9 women with colorectal cancer, 4 with multiple (2-4) colorectal cancers, 20 with endometrial cancer, 7 with cutaneous manifestations of LS, and 5 with genitourinary cancers. The mean number of additional LS related manifestations for these patients with BC was 1.5 (range 0-8) per patient. Conclusions: Within the registry utilized in this study, LS associated BC is strongly associated with MSH2 mutation status. Most patients with LS associated BC harbored multiple manifestations of LS, and their families almost always met Amsterdam criteria. LS associated BC was frequently high grade and often hormone receptor negative, suggesting an aggressive histology.
Distribution and histopathology of colorectal polyps in the Asian population in the United States.
Authors: Patel Samarth , Bansal Raghav , Gandhi Divyangkumar , Sidhu Loveleen , Walfish Aron , Rajnish Ishita 
Published: February 2017

436 Background: Limited data exists for colorectal polyps in Asian population in U.S. Advanced polyps are considered as a high risk for CRC and require close surveillance. The aim of the study was to evaluate and compare the characteristics of polyps based on patient demographics, anatomic distribution, size, and histopathology in the Asian population living in one of the most heavily populated and diverse communities in U.S. Methods: We conducted a retrospective, single center chart review study of all asymptomatic Asian patients who underwent screening colonoscopy at a New York City hospital from Jan 2006 to Dec 2010. The patients without polyps were excluded from the study. Based on histopathology and size, polyps were divided into 2 groups: advanced and non-advanced. Results: Of the total 1,300 patients, 311 were found to have colon polyps. Mean age of the study population was 60.8 years (range 50-82). There were 173 males and 138 females, with male to female ratio 1.3:1. In gender analysis, 61% of the advanced polyps were found in males, however, the difference was not statistically significant (p = 0.255). 41% of patients had right sided polyps, 49% had left sided polyps, and 10% had bilateral polyps. Analysis showed significant increase in the proportion of patients with advanced polyps on left side (65%, p < 0.05). Large size (≥ 1 cm) of the polyp correlated with advanced nature of the polyp (p < 0.0001). On pathology review of the patients with polyps, 191 had non-advanced tubular adenoma, 38 had advanced tubular adenoma, 33 had hyperplastic polyp, 35 had villous/tubulovillous, and 13 had high grade dysplasia/colorectal cancer. Only 43 out of 86 patients (49%) with advanced polyps had follow-up colonoscopy. Conclusions: Polyps located on the left side were independently associated with advanced nature of polyp. Our results also revealed that large size polyps (≥ 1 cm) were strongly associated with being advanced in nature.Vigilant approach of the left side and large lesions should be exercised during screening colonoscopy in Asian Americans. Failure of the patients to follow up could be secondary to poor access to health care, language barrier, or health care beliefs. Efforts should be made to ensure adequate follow-up for surveillance colonoscopy.
Interaction between visfatin and resistin and the risk of colorectal adenoma.
Authors: Maejima Aiko , Yamada Yasuhide , Yamaji Taiki , Honma Yoshitaka , Okita Natsuko T. , Takashima Atsuo , Iwasa Satoru , Kato Ken , Hamaguchi Tetsuya , Shimada Yasuhiro , Tsugane Shoichiro 
Published: February 2017

438 Background: Colorectal adenoma is a well-established precursor lesion of colorectal cancer, so the prevention of adenoma may also contribute to the prevention of cancer. Adipocyte secretes hormones, namely adipocytokines, some of which are likely to be associated with malignancies such as colorectal, breast, and prostate gland cancer. Among several adipocytokines, resistin and visfatin have been suggested to be associated with the progression of colon cancer, and they could therefore be good biomarkers for colorectal adenoma and cancer. Methods: Prior to any procedures, healthy volunteers provided their venous blood, from which we obtained the plasma to measure concentrations of adiponectin, visfatin, and resistin. We underwent total colonoscopy, and identified 776 adenoma cases (522 males, 254 females), 734 controls (478 males, 256 females) were selected from those without adenoma. An unconditional logistic regression model was used to estimate odds ratios for colorectal adenoma after adjustment for potential confounders, including body mass index (BMI). Results: We found no positive association between the presence of colorectal adenoma and the levels of either visfatin (P trend: male 0.24, female 0.87), or resistin (P trend: male 0.85, female 0.71). After adjusting for potential confounders, we still saw no association. On the other hand, adiponectin levels showed a correlation with both BMI (P: male <0.0001, female 0.0007) and the volume of fat. Furthermore, adiponectin levels indicated no positive correlation with visfatin (P: male 0.656, female 0.1445) or resistin (P: male 0.2116, female 0.1352). Conclusions: In this study, no association was observed between visfatin/resistin levels and colorectal adenoma, and they showed no positive correlation with BMI or the volume of intra-abdominal fat. However, other confounders may account for these results, so we plan to conduct further differential analyses.
Early detection to neoadjuvant chemotherapy response in locally advanced rectal cancer using 18F-FDG PET.
Authors: Hasegawa Junichi , Nishimura Junichi , Ogawa Yoji , Kim Ho Min , Hitora Toshiki , Murakami Masahiro , Hirota Masaki , Yoshikawa Masato , Ikenaga Masakazu , Shimizu Junzo , Mikata Shoki , Miwa Hideaki 
Published: February 2017

440 Background: Early detection of treatment response of neoadjuvant chemotherapy (CTx) for locally advanced rectal cancer may spare patients the toxicity of ineffective CTx. We evaluated prospectively tumor response with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the early course of preoperative CTx. Methods: A total of 15 patients with locally advanced rectal cancer (T3 or T4 and N0-N2) received neoadjuvant CTx (XELOX or XELOX+bevacizumab). Patients underwent 18F-FDG PET before CTx, at the end of first cycle of CTx (12-38 days: median 15days), and before surgical resection. Scans were interpreted using SUVmax parameter. Magnetic resonance imaging (MRI) was undergone before CTx, at the end of 2 cycles of CTx (25-54 days: median 38 days), and before resection. The tumor longest diameter was measured by MRI T2-weighted images. After resection, SUVmax and diameter were compared with the Tumor Regression Grade (TRG). Results: Of 15 patients, TRG1 was in 1 patient, TRG2 was in 5 patients, and TRG3 was in 9 patients. We divided into 2 groups, non-responder (NR) group was TRG1 and TRG2, and responder (R) group was TRG3. There was no significant difference as for clinicopathological parameters before CTx including tumor diameter and SUVmax. The tumor size before surgery was significantly smaller in R group than NR group (22.2 mm vs. 35.0 mm; p = 0.017). SUVmax in R group was significantly lower at the end of first cycle of CTx (4.9 vs. 9.3; p = 0.023), and before surgical resection (3.2 vs. 10.3; p = 0.007) than that in NR group. Conclusions: In this study, 18F-FDG PET at the end of first neoadjuvant CTx successfully predict pathological response of locally advanced rectal cancer.
Prolonged bevacizumab exposure accompanied by EGFR activation in colorectal cancer (CRC) models to provide a rational for combinations of bevacizumab and erlotinib in the GERCOR DREAM phase III trial.
Authors: Larsen Annette K. , de Gramont Aimery , André Thierry , Tournigand Christophe , Savina Ariel , Batistella Aude , Poindessous Virginie , Mésange Paul 
Published: February 2017

449 Background: Combinations of EGFR and VEGF(R)-targeted agents have consistently shown at least additive activity in preclinical CRC models when the targeted agents were administered alone (Larsen et al., Pharmacol Therap. 131:80, 2011; Poindessous et al., Clin Cancer Res. 17:6522, 2011) paving the way for the GERCOR DREAM-OPTIMOX3 phase III trial in metastatic CRC. Although use of EGFR-directed mAbs are counter-indicated in CRC patients with mutant KRAS, the situation is less clear for EGFR-targeted TKIs like erlotinib. Methods: Three human CRC xenograft models expressing wt KRAS/BRAF, mutant KRAS or mutant BRAF were established in nude mice. Animals were treated with bevacizumab and erlotinib, alone or in combination, and the influence on tumor growth, viability and the presence of phosphorylated ErbB/HER family members was determined. Treatment-related toxicity was estimated by weight loss. Results: Combinations of bevacizumab and erlotinib were significantly more active than either agent alone for all three xenograft models although the advantage of combining the two agents was particularly striking for the KRAS/BRAF wt xenograft model. Unexpectedly, erlotinib alone showed strong antitumor activity in the BRAF mutant HT-29 xenograft model. The bevacizumab plus erlotinib combination was less toxic, as determined by weight loss, compared to erlotinib alone. Interestingly, IHC analysis showed that bevacizumab activates EGFR in all three xenograft models. Conclusions: We here report that bevacizumab and erlotinib combinations are significantly more active than either agent alone in CRC models with different KRAS and BRAF status. We further demonstrate that bevacizumab activates EGFR signaling similar to what has been described for irinotecan and ionizing radiation. Taken together, our findings suggest that mutant KRAS and BRAF have lesser influence on the sensitivity to EGFR-targeted TKIs than is the case for the EGFR directed mAbs and provide a mechanistic basis for the increased activity of the bevacizumab and erlotinib combination.
Integrin genetic variants and risk of thromboembolic events in patients with colorectal cancer.
Authors: Prager Gerald , Schuler Alexandra , Ay Cihan , Pausz Clemens , Lenz Heinz-Josef , Pabinger Ingrid , Zielinski Christoph 
Published: February 2017

462 Background: Patients with colorectal cancer are at increased risk of venous thromboembolism (VTE). Integrin beta-3 are involved in tumor biology as well as platelet aggregation, thus, we tested as a primary endpoint whether a comprehensive panel of germline single nucleotide polymorphisms (SNPs) in the integrin beta-3 gene could predict the risk of VTE in colorectal cancer patients. Methods: The study population comprises patients recruited into the Vienna Cancer and Thrombosis Study (CATS) (Ay, C et al; JCO 2011 vol. 29 no. 15), an ongoing prospective observational cohort study initiated in October 2003 at the Medical University of Vienna. In 114 out of 139 patients diagnosed with colon cancer DNA was assessable for integrin beta-3 germline SNPs rs3809865, rs5918, rs4642 characterization. Whole blood samples were analyzed using PCR-RFLP or direct DNA-sequencing. VTE events were statistical analyzed using one-way Anova testing. Results: The patient’s demographics and tumor characteristics were balanced between groups. VTE occurred in 14 patients (12.28%). In colorectal cancer patients with an rs3809865 A/A allele profile a statistical significant (p=0.0015) increased risk of VTE events was observed as 12 (25%) of 48 patients experienced VTE. Only 2 of 52 patients (3.85%) harboring an A/T allele VTE was diagnosed. None (0%) of the T/T subgroup had any VTE. Other SNPs revealed no predictive value for VTE. In multivariable analysis including age, sex, chemotherapy, and anti-VEGF therapy rs3809865 A/A allele profile remained a statistical significant risk factor for VTE. Conclusions: This study identifies germline polymorphisms in integrin genes as independent prognostic markers for VTE in colorectal cancer. These data may help to select subgroups of patients who may benefit from an enforced prophylaxis of venous thromboembolism (VTE).
Changes in expression levels of excision repair cross-complementing group 1 (ERCC1) and dihydropyrimidine dehydrogenase (DPD) after first-line oxaliplatin-based chemotherapy for metastatic colorectal cancer: Results of a multicenter study.
Authors: Baba Hideo , Baba Yoshifumi , Uemoto Shinji , Oki Eiji , Ikeda Yasuharu , Yamamoto Masakazu , Matsuda Hiroyuki , Shimada Mitsuo , Kokudo Norihiro 
Published: February 2017

463 Background: Our previous single-center study showed that expression levels of ERCC1 (a nucleotide excision repair pathway gene) and DPD (a pyrimidine catabolic pathway gene) in liver metastases from colorectal cancers (CRCs) were significantly higher in patients given oxaliplatin as first-line chemotherapy than those not given oxaliplatin. We conducted this multicenter study to validate our findings and better define a basic rationale for second-line therapy for metastatic CRC resistant to first-line therapy. Methods: Irinotecan-naive patients with mCRC (n = 190) were enrolled at 17 sites in Japan. Resected liver metastases were available for 91 patients who had received FOLFOX (or FOLFOX plus bevacizumab; FOLFOX group) and 99 who had not received oxaliplatin-based chemotherapy (non-oxaliplatin group). We measured mRNA expression levels of ERCC1 and DPD by real-time RT-PCR. Protein expression levels of ERCC1 and DPD were evaluated immunohistochemically. The methylation level of the long interspersed nucleotide element-1 (LINE-1; a surrogate m arker of global DNA methylation) was determined by pyrosequencing. Results: The median age at liver resection was 64 years (range, 32–89). Baseline features (e.g., sex, histology) were similar in the groups. Expression levels of DPD at the mRNA and protein levels were significantly higher in the FOLFOX group than in the non-oxaliplatin group (p < 0.05). The mRNA expression level of ERCC1 was slightly, but not significantly higher in the FOLFOX group than in the non-oxaliplatin group (p = 0.053). Interestingly, ERCC1 expression levels correlated with DPD expression levels (r = 0.38, p< 0.0001). LINE-1 methylation levels were similar in the groups. Conclusions: This multicenter study confirmed increased expression levels of DPD after first-line oxaliplatin-based chemotherapy, which may affect chemosensitivity to subsequent therapy. ERCC1 expression and epigenetic control by mechanisms such as aberrant promoter methylation of specific genes warrant further investigation.