bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for colorectal cancer in France: Third edition of the EDIFICE survey.
Authors: Viguier Jérôme , Morere Jean F. , Pivot Xavier B. , Coscas Yvan , Blay Jean-Yves , Roussel Claire , Eisinger Francois 
Published: February 2017

411 Background: In France, after a pilot population-based screening program (2002-2003), a national organized program targeting 17 million persons was progressively implemented starting in 2005 and generalized after 2009. The EDIFICE 3 survey was conducted in 2011, after EDIFICE 1 (2005) and EDIFICE 2 (2008), to provide a better understanding of the participation of the French population in the colorectal cancer screening program and to assess the evolution between the three periods. Methods: This third nationwide observational study, EDIFICE 3, was conducted through phone interviews among a representative sample of 1603 subjects aged between 40 and 75years, using the quota method. This analysis focused on the target population of the national screening program (50-74 years old). Results: In 2011, 59% of subjects between 50 and 74 years (N=946) declared having performed a screening test for colorectal cancer (including fecal test or colonoscopy) versus 38% in 2008 (p<0.05) and 25% in 2005 (p<0.05). Colorectal cancer screening increased significantly in all age groups, especially between 65 and 69 years, and for both sexes. Among the screened population, the recommended interval between two tests was respected in 51% of cases in EDIFICE 3. 62% of unscreened individuals plan to undergo a screening test in the near future. The main factors increasing the probability of screening were: being encouraged by one’s family, the existence of a case colorectal cancer in the family circle, higher frequency of medical consultation, better knowledge of the screening process and being reassured by the screening. The main reasons for not undergoing the screening were: not feeling concerned, fear of exams or results, no recommendation by the GP and carelessness. Conclusions: The European guideline objective rate of participation for colorectal cancer screening (65%) is not yet reached. This goal could be achieved by motivating the unscreened population already planning to perform a test. The trend for increasing testing will probably be confirmed in the future if the reasons for non-attendance in an organized program are addressed.
Breast cancer in Irish families with Lynch syndrome.
Authors: Jordan E. J. , Farrell M. P. , Clarke R. M. , Kell M. R. , McCaffrey J. A. , Connolly E. M. , Boyle T. , Kennedy M. J. , Morrison P. J. , Gallagher D. J. 
Published: February 2017

413 Background: Breast cancer is not a recognised malignant manifestation of Lynch Syndrome which includes colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland, and a genotype phenotype correlation was investigated. One kindred was omitted due to the presence of a biallelic MMR and BRCA1 mutation. The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in 16 pedigrees was as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Six MSH2 mutations and 1 MSH6 mutation were identified in the 7 Lynch syndrome kindreds. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. Final results of immunohistochemistry for mismatch repair protein expression on breast cancer samples are pending and will be reported at the meeting. One breast cancer has been tested to date and demonstrated loss of MSH2 protein expression in an individual carrying an MSH2 mutation. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.
Association of interval appendectomy with risk of neoplasm.
Authors: Furman Matthew Jason , Cahan Mitchell , Cohen Philip , Whalen Giles Francis , Lambert Laura A. 
Published: February 2017

430 Background: The role of interval appendectomy after conservative management of perforated appendicitis remains controversial. Determining the etiology of perforated appendicitis is one reason to perform interval appendectomies. This study hypothesizes that there is an increased rate of neoplasm in patients undergoing interval appendectomy. Methods: This is a retrospective review of all patients over 18 years of age who underwent appendectomy for presumed appendicitis from January, 2006 to December, 2010 at a single, tertiary care institution. Demographic data, pathologic diagnosis, clinico-pathologic characteristics, interval resection rate, and complication data were collected and analyzed. Results: During the study period, 376 patients underwent appendectomy. The mean age was 41 years (range 18 to 94). Interval appendectomy was performed in 18 patients (5.0%) (age 28 to 74). Neoplasms were identified in 14 patients (3.7 %); 6 were found in patients who had undergone interval appendectomy (33%). Nine were mucinous tumors (69.2%), 5 of which were associated with interval appendectomies. Neoplasms were identified in 8.3% of patients between 35 and 55 years old. Conclusions: Mucinous neoplasms of the appendix were found in 33% of patients undergoing interval appendectomy. Interval appendectomies should be considered in all patients 35 years and older due to increased risk of appendiceal neoplasm. [Table: see text]
Timing of testing for K-ras mutational status in metastatic colorectal cancer (mCRC).
Authors: Corral Mitra , Sotak Michelle , Chastek Benjamin , Penrod John R. , Cairns Jessica , Williams David A. 
Published: February 2017

441 Background: The objective of this study was to examine physician perspectives on K-ras testing in mCRC at two time points: diagnosis of mCRC and after treatment failure. Methods: Interviews were conducted with 16 oncologists experienced in treating mCRC to obtain information on treatment patterns. Based upon the interview data, a two-round Delphi panel web survey was then used to obtain consensus on specific percentages of patients in a separate sample of 25 oncologists. Both samples were asked to respond to two scenarios: at metastatic diagnosis and after treatment failure. Results: The majority of interviewed physicians reported that they primarily test at diagnosis of mCRC versus later in treatment. Both the interviewed physicians and Delphi respondents said most patients have a tissue sample available at metastatic diagnosis for K-ras testing (Delphi median 90%, mean 81.2% at diagnosis, 78.8% after treatment failure). For patients without tissue, it was stated that a tissue sample would be obtainable in most patients (Delphi median 90%, mean 87.8% at diagnosis, 85.8% after treatment failure). Of patients with K-ras wild-type mCRC, the Delphi panel estimated that 75-80% would receive an EGFR inhibitor (mean 75.5% at diagnosis, 81.5% after treatment failure, median 80%) while only 0-5% of patients with K-ras mutated mCRC would receive an EGFR inhibitor (mean 4.6% at diagnosis, 5.3% at EGFR decision, median 0%). For a scenario where K-ras information is unknown, the Delphi panel estimated that a small percentage of patients may receive EGFR inhibitors (at diagnosis: mean 12.2%, median 5%; after treatment failure: mean 14.1%, median 0%) although it was noted this is uncommon and many insurers will not cover EGFR inhibitors without K-ras status. Conclusions: Current guidelines for mCRC recommend that K-ras testing be conducted as part of the diagnostic workup. In this study, two samples of oncologists reported that the majority of patients they treat are tested for K-ras mutations at metastatic diagnosis rather than later in therapy. Both samples reported minimal use of EGFR inhibitors in patients with K-ras mutated mCRC or patients with unknown K-ras status, consistent with clinical guidelines and many insurance policies.
Colorectal cancers in United Arab Emirates nationals: The Sheik Khalifa Medical Center's experience.
Authors: Dehni Nidal , Al Hassani Ali , Nimeri Abdulrahman 
Published: February 2017

442 Background: Previous reports suggested that colorectal cancers (CRC) appear at younger age in the United Arabs Emirates (UAE). However, these reports included nationals and expatriates in their analysis with heterogeneous population leading to biased analysis. our objective was to determine age and stage of disease in newly diagnosed UEA nationals with CRC treated at one major referral hospital in Abu Dhabi (SKMC) Methods: Charts of all patients diagnosed and/ or treated for CRC at SKMC between January 2000 and May 2011 were reviewed. Ultimately, only UEA nationals with diagnosis of adenocarcinoma of the colon and rectum were retained for further analysis. Results: Two hundreds six patients were diagnosed at SKMC as having colon or rectal carcinomas. Ninety two were expatriates and in 10 out of 113 nationals, the final diagnosis was squamous or adenosquamous carcinoma leaving 103 patients forming the population of this study. Median age was 57(10-100 years), with 59 men. The patient’s condition necessitated emergency operation in 38 and 15 either refused or were unfit for treatment mainly because of very advanced disease or severe co morbidity. The tumor location was: sigmoid: 46%, rectum: 33:, right colon :17% and 4% for descending and transverse colon. The stage of the disease was I; 4 pts, II: 16 pts, III 25 pts, IV in 49 pts and undetermined in 7. Resection was curative for 46 pts, palliative in 45, unknown in 10 and 2 refused surgery. Fifty one patients had their treatment essentially at SKMC and the others were treated both at SKMC and abroad. Average follow-up was 2 years and at last FU 39 were confirmed deceased, 29 were alive and the outcome in the remaining was unknown. Conclusions: UAE nationals with CRC presenting to our facility have relatively young age but presented with stage IV disease in half of the cases. Screening program for this population is warranted. Because a substantial number of patients had had their treatment abroad, rigorous follow-up and cancer outcome assessment was unreliable.
Phase II study of EZN-2208 (PEG-SN38) with or without cetuximab in patients with metastatic colorectal cancer (CRC).
Authors: Goldberg Richard M. , Garrett Chris R. , Berkowitz Noah C. , Bekaii-Saab Tanios S. , Ryan Theresa , Fisher George A. , Clive Sally , Kavan Petr , Shmueli Einat , Buchbinder Aby 
Published: February 2017

448 Background: EZN-2208 is a water-soluble, parenterally-delivered PEGylated conjugate of SN38 that increases solubility, exposure, and apparent half-life of SN-38. Methods: Patients with metastatic or locally recurrent CRC previously treated with fluoropyrimidines, oxaliplatin and irinotecan, and no more than 2 distinct progressions, were screened for K-Ras mutation and stratified accordingly. Patients with K-Ras tumor mutation (Mut) were treated with EZN-2208 (9mg/m2 SN-38 equivalents) over 1-h IV on days 1, 8, 15 in 4-wk cycles (Arm A). Patients with K-Ras wild type (WT) tumors were randomized (2:1) to EZN-2208 (as above) and cetuximab (250mg/m2 weekly following 400mg/m2 on D1) (Arm B) or to irinotecan (125mg/m2) over 90min IV days 1, 8 in 3 week cycles and cetuximab (as above) (Arm C). The primary objectives of the study were to determine the overall response rates (ORR) and progression free survival (PFS) (Arm A) and compare PFS (Arms B and C). A comparison of safety and toxicity of EZN-2208 and irinotecan was planned as well. Results: Demographic and efficacy parameters are summarized in the table . Common adverse events (Arms A%, B%, C%), observed in > 25% of patients in at least one arm of the study, were diarrhea (45%, 64%, 55%), fatigue (56%, 56%, 39%), nausea (43%, 59%, 47%), vomiting (31%, 46%, 39%), constipation (27%, 26%, 37%), abdominal pain (25%, 28%, 32%), anemia (33%, 21%, 21%), dermatitis acneiform (0%, 28%, 26%), hypokalemia (17%, 28%, 26%), and alopecia (12%, 28%, 3%). Conclusions: EZN-2208 in combination with cetuximab is active in patients in the 3rd line setting of CRC and comparable to irinotecan in combination with cetuximab. EZN-2208 monotherapy did not result in responses in patients with CRC following progression on irinotecan. EZN-2208 has an acceptable safety and tolerability profile as monotherapy, and in combination with cetuximab. [Table: see text]
Circadian robustness as an independent predictor of prolonged progression-free survival (PFS) and overall survival (OS) in 436 patients with metastatic colorectal cancer (mCRC).
Authors: Levi Francis , Parganiha Arti , Karaboué Abdoulaye , Innominato Pasquale F. , Giacchetti Sylvie , Garufi Carlo , Dispersyn Garance , Focan C. N. J. , Iacobelli Stefano , Bjarnason Georg A , Moreau Thierry , Dugue Pierre Antoine , Waterhouse Jim ,   ARTBC International Chronotherapy Group
Published: February 2017

464 Background: The rest-activity rhythm is a biomarker of the circadian timing system (CTS), whose disruption accelerates cancer progression in experimental models. Prior studies in cancer pts identified a reliable measure of CTS function in cancer pts based on non invasive wrist actigraphy monitoring. Methods: The prognostic value of I<O, the ratio between activity counts in-bed vs out-of-bed, was explored for PFS and OS in mCRC. The rest-activity rhythm was recorded for >48 h in 436 mCRC pts from 3 international cohorts. Data were stratified per cohort, and analyzed with Kruskall-Wallis ANOVA, log rank tests, and multivariate Cox analyses. Results: Median age was 59.2 y. Pts were mainly men (62.6%); had good performance status (PS = 0, 58.2%; 1, 33%); > 2 metastatic sites (51.6%); metastases in liver (79%) or lung (38.8%); were chemotherapy-naïve (54.6%). After baseline actigraphy recording, pts received a median of 8 courses of oxaliplatin- or irinotecan-based chemotherapy, including chronomodulated schedules (chrono; 81.4%). Despite a strong correlation with PS (p< 0.0001), I<O independently influenced both PFS and OS. Thus, both median PFS and OS nearly doubled in the pts with I<O above 97.5% (upper two quartiles) as compared to those with I<O below 93.2% (lowest quartile). Median PFS ranged from 4.8 to 10.6 months (log rank, p<0.001) and median OS from 10.1 to 20.6 months (p<0.001). In multivariate analyses, I<O ranked as the second best independent predictor of PFS, after metastases surgery, with a hazard ratio (HR) of 0.967 [95% C.L., 0.95-0.98] (p<0.001). I<O ranked as first independent predictor of OS, with a HR of 0.95 [0.94-0.97] (p<0.001). Forrest plots revealed consistent HR of I<O for PFS and OS in each cohort. Conclusions: The circadian biomarker indicator I<O is a robust, consistent and independent quantitative predictor of both PFS and OS in mCRC pts. Rest-activity rhythm monitoring deserves further testing for helping accurate determination of mCRC prognosis. The biological significance of I<O implies that specific treatments of circadian disruption could enhance survival in cancer pts.
Is there a clinical benefit in testing for UGT1A1*28 prior to irinotecan therapy?
Authors: Kularatne Bihani Yoshana , Marinaki Anthony , Karavasilis Vasilis , Spicer James F. , Ross Paul J. , Pectasides Dimitrios G. , Makatsoris Thomas , Pentheroudakis George E. , Fountzilas George 
Published: February 2017

478 Background: Irinotecan is used in the treatment of colorectal cancer, with severe neutropenia and diarrhoea being the main dose limiting toxicities. UGT1A1 variants have been shown to predict irinotecan associated toxicity. Despite an FDA warning in 2005, few centres have undertaken UGT1A1 testing prior to the commencement of therapy. The reason for this has been the lack of consistent data supporting its use as a marker of either neutropenia or diarrhoea. Where significance has been shown, sample sizes have been small and confidence intervals wide. Methods: We retrospectively correlated the presence of UGT1A1*28 polymorphism with severe neutropenia or diarrhoea in Greek patients receiving irinotecan-based chemotherapy for metastatic colorectal cancer. Severe (grade 3 or 4) neutropenia or diarrhoea (Common Terminology Criteria version 4) for cycles 1-4 were recorded for all patients using electronic case notes. Patients were genotyped for UGT1A1*28 polymorphism. Results: Of the 362 patients evaluated, 205 (56.6%) received irinotecan (180-255 mg/m2, 3 weekly) in combination with capecitabine and 155 (42.8%) received irinotecan (160-200 mg/m2, 2 weekly) in combination with 5-FU. Forty four (12%) patients experienced severe diarrhoea and 19 (5%) severe neutropenia. Clinical response data was unavailable in 162 (45%) patients. A favourable radiological response (stable disease, partial or complete response) was seen in 170/200 (85%) patients. A homozygous UGT1A1*28 genotype was detected in 38/362 patients. Of these, three (8%) experienced grade 3 or 4 diarrhoea during cycles 1-4 and three (8%) experienced severe neutropenia. There was no statistically significant correlation between genotype and toxicity in this patient group. Conclusions: Our study of a Caucasian group of Greek patients, the largest study to date, failed to show any correlation with UGT1A1*28 polymorphism and the occurrence of grade 3 or 4 neutropenia or diarrhoea. The results of this study suggest that testing for the UGT1A1*28 mutation prior to the start of irinotecan therapy may not be clinically useful.
Discovering pathways in the tumor microenvironment important for recurrence-free survival in patients with colorectal liver metastasis.
Authors: Rhodes Terence Duane , Morse Michael , Lyerly H. Kim , Nevins Joseph R. , Clary Bryan M. , Hsu Shiaowen David 
Published: February 2017

480 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Curative treatment for CRC liver metastasis can be achieved by surgical resection, but 5 year survival ranges between 20-40%. Current treatment strategies to prevent recurrences after resection of CRC liver metastases have focused on the use of chemotherapy cytotoxic to malignant epithelial cells of the tumor. However, stromal components within the tumor microenvironment have recently been implicated as contributors to the aggressiveness of the malignancy. We hypothesized that genomic based signatures associated with tumor stroma would be prognostic for recurrence after CRC hepatic metastasectomy. Methods: Thirteen independent CRC liver metastatic samples were subjected to laser-capture microdissection to isolate the tumor epithelium and tumor-associated stroma separately. Microarray analysis using class neighbors and gene set enrichment analysis (GSEA) was applied to the stromal mRNA to identify differentially expressed genes and pathways between samples from patients with early recurrence (<1yr) after resection (Group R) and those who remain disease free (>2yrs) (Group NoR). Results: Class neighbor analysis revealed a greater number of genes associated with immunity and cell to cell adhesion in Group R compared to Group NoR (p<0.05). Using GSEA, gene sets associated with T-cell immunity, Wnt pathway, and homeostasis were enriched in stroma Group R when compared to stroma Group NoR (p<0.05). Conclusions: These findings suggest several pathways are prognostic for recurrence of CRC liver metastasis. Development of stroma-directed therapy combined with tumor-directed therapy in preclinical models could hold the promise of major advances in the treatment of colorectal cancer liver metastasis in order to improve the clinical outcomes of these patients.
Cytologic and molecular characterizations of CTC detected in patients with metastatic colorectal carcinomas.
Authors: Coget Julien , Blanchard France , Lamy Aude , Toure Emmanuel , Di Fiore Frédéric , iwanicki-Caron Isabelle , Michel Pierre , Michot Francis , Sabourin Jean-Christophe 
Published: February 2017

485 Background: Circulating tumor cells (CTC) appear to be associated with poor prognosis in patients with metastatic colorectal cancer (mCRC). ScreenCell technology, which is based on the separation of CTCs from other circulating cells by blood filtration, could allow clinical use of this new biomarker. The aim of our study was to demonstrate the feasibility of CTC filtration in a clinical situation and to compare CTC cytological/molecular characterizations. Methods: Sampling of venous blood was performed in 39 patients with mCRC before starting chemotherapy regimen. For cytology, blood were filtered using ScreenCell Cyto devices. After staining with hematoxylin, each filter was analyzed by a cytopathologist. Cells visualized on the filter were considered as tumoral if they met the following morphological criteria: nuclear diameter >7micron, anisocytosis, membrane irregularities, presence of large nucleolus. For molecular biology, blood were filtered using ScreenCell MB columns: DNA was then extracted for KRAS genotyping. Prior to the clinical study, HCT116 cells were used in order to establish biological procedures. Results: 3 samples were not analysed due to blood coagulation. The presence of CTC was identified in 23/36 patients with mCRC (64%). KRAS mutation was present in 40% of tumor patients. In those patients, no mutation was observed on CTC specimens even when using whole gene amplification and PNA selective PCR, whereas KRAS mutation was detected in 10 HCT116 cells diluted in 3ml of normal blood using this same procedure. Conclusions: ScreenCell Technology allows cytological studies which appear to be fast and efficient for the detection of CTC in mCRC patients. Detection of CTC molecular abnormalities is a major challenge: implementation of molecular tests such as KRAS genotyping, allowing tumor characterization directly from minimally invasive blood sampling, could have tremendous clinical applications. Our first in vitro results highlight the fact that detection of somatic molecular alterations is feasible, from just a few tumoral cells diluted in blood, which encourages further developments using other molecular approaches.