bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori infection and the risk of colorectal cancer: A meta-analysis of epidemiologic evidence.
Authors: Njei Basile M. , Ditah Ivo C. , Appiah Juliet , Jinjuvadia Raxitkumar , Birk John W. 
Published: February 2017

408 Background: The association between Helicobacter pylori infection (HPI) and gastric cancer is well known, but it is unclear whether HPI is also a risk factor for colorectal cancer. Several epidemiological studies on the latter association have yielded conflicting results. The aim of this study is to summarize available evidence on the association between HPI and CRC, evaluating its magnitude and direction in a meta-analysis. Methods: Two reviewers independently conducted a systemic search on Medline, OvidSP and PubMed databases from January 1980 to July 2011 for studies on the association between HPI and CRC. The reference lists of eligible studies were next reviewed for additional studies on the subject. Firstly, a combined analysis including all studies was done. Next, subgroup analysis by study design and country of study (USA Vs Europe Vs Asia) were also performed. All analyses were done using the random effects model. Publication bias was assessed using the Begg’s and Egger’s tests and visual inspection of funnel plot. All analyses were performed using STATA 11. Results: Sixteen studies (14 retrospective and 2 prospective) including 12,892 participants were included in the analysis. Overall, HP was associated with a 49% significantly higher risk of CRC (OR 1.49, 95% CI: 1.22-1.82; P < 0.001). By study design, the association persisted only among the retrospective studies with a pooled OR of 1.43 (95% CI: 1.31-1.56, P = 0.004). The subgroup analysis by study region showed significant associations in Europe (OR 1.35, 95% CI 1.09-1.66) and Asia (RR 1.43, 95% CI 1.29-1.58). Though there was a 17% higher risk noted among studies done in the USA, this was not statistically significant. There was no evidence of publication bias in all the analyses. Conclusions: Current evidence on the association between H. pylori infection and CRC remains inconclusive. The absence of any association among the prospective studies (with less risk of bias) suggests that the association seen among the retrospective studies could be due to residual confounding. Better quality data is required before a conclusive statement on the association between HPI and CRC can be made.
Detection of hereditary nonpolyposis colorectal cancer (HNPCC) in non-Caucasian patients.
Authors: Russell Maria C. , Rodriguez-Bigas Miguel A. , Chang George J. , Skibber John Michael , Feig Barry W. , You Y. Nancy 
Published: February 2017

417 Background: HNPCC is the most common hereditary colorectal cancer (CRC) syndrome. Its characterization has been limited to Caucasians in Europe or North America, and non-Caucasians in their countries of descent. Little is known about HNPCC in ethnically diverse patients in the U.S. Methods: Patients whose self-reported ethnicity was not Caucasian and who were the probands in their families to undergo germline testing (GT) for DNA mismatch repair (MMR) genes between 1998 and 2011 were identified. Tumor microsatellite (MSI) testing was informative if immunohistochemistry (IHC) showed MMR protein loss of expression, and/or if PCR-based MSI testing showed >30% markers shifted. Tumor studies guided further GT. Results: Fifty-eight unrelated probands (female, 53.4%) included 19 (32.8%) who were Hispanic, 18 (31.0%) African-American, 18 (31.0%) Asian, and 3 (5.2%) Arabic/Other. Amsterdam I, II and revised Bethesda criteria were satisfied in 9 (15.5%), 14 (24.1%) and 43 (74.1%) respectively. They were affected by 106 malignancies, most commonly: CRC (73.9%), endometrial (10.9%), small bowel (5.4%) and skin (sebaceous neoplasm, 3.3%). The CRCs arose from proximal colon (51.5%), distal colon (25%), rectum (16.2%) or multifocal/other (7.4%), at a median age of 46 (IQR: 38-55). PCR-MSI results were concordant with abnormal IHC, although less for MSH6 and PMS2. In GT, pathogenic mutations were detected in only a minority of patients ( Table ). Conclusions: Ethnically diverse patients with informative tumor MSI results exhibited low rates of detectable pathogenic mutations. Caution should be exercised when GT is utilized to detect HNPCC in the absence of tumor studies as patients to be managed as HNPCC may be missed. [Table: see text]
The effect of insurance status on the stage of colorectal cancer at diagnosis.
Authors: Greenbaum Arieh , Singhal Vinay , Cosgrove John Morgan , Farkas Daniel T 
Published: February 2017

420 Background: There is currently a lot of focus on the number of uninsured patients in the country. Part of the recent healthcare debate revolved around the lack of preventative medicine and screening in such patients. The assumption is that patients without insurance present to hospitals with later stages of disease. The purpose of this study was to evaluate patients with colorectal cancer, and to see if their insurance status was related to the stage of their cancer at diagnosis. Methods: All patients in our tumor registry with a diagnosis of colorectal cancer between 2000 and 2010 were initially included. Those who did not have their complete care in our hospital, or those for whom insurance information was not available, were excluded. Patients were categorized into insured and uninsured patients. Cancer staging at the time of diagnosis was done according to the American Joint Committee on Cancer guidelines, and patients with stage 3 or 4 disease were classified as having advanced cancer. Results: There were 489 patients in the tumor registry for these ten years, of which 435 had their care in our hospital and were fully staged. Insurance information was available for 383 patients (88%). There were 360 patients (94.0%) in the insured group and 23 patients (6.0%) in the uninsured. In the insured group there were 128 patients (33.4%) with advanced cancer, while in the uninsured group there were 15 patients (65.2%). This difference was highly significant (Chi-square, p=0.007). Conclusions: Patients without insurance present with more advanced stages of colorectal cancer. In our series, uninsured patients were almost twice as likely to present with stage 3 or 4 disease. Efforts at helping more patients gain access to healthcare insurance could perhaps lead to fewer people presenting with advanced stages of cancer.
Validation of a plasma-based miRNA PCR test for early detection of colorectal cancer.
Authors: Nielsen Søren Jensby , Willenbrock Hanni , Fog Jacob , Stenvang Jan , Blondal Thorarinn , Orntoft Torben , Brünner Nils , Andersen Claus Lindbjerg , Nielsen Hans J. , Baker Adam 
Published: February 2017

424 Background: Colorectal cancer (CRC) is a major cause of mortality in the western world. Early detection of CRC improves survival and screening for CRC has been clinically proven to lower CRC-related mortality in the screening population. However, although population screening programs have been implemented in a number of countries, screening rates among the 50-75 year olds are unsatisfactory. There is therefore a clear unmet need for a quick, sensitive, specific, and minimally invasive screening assay to select at risk individuals for definitive diagnosis by colonoscopy. Methods: In order to detect microRNA (miRNA) biomarkers for CRC in blood plasma, we developed an LNA-enhanced miRNA RT-qPCR platform with high sensitivity and linearity for optimal quantitation of miRNAs from limited plasma samples. A clinical reference- lab compatible workflow that allows for the entire procedure from sample preparation through data acquisition and QC to test result to be completed within one working day was established. A reference melting curve database has been implemented to ensure the integrity of each data point, and appropriate controls monitor plate-to-plate and day-to-day variation. State-of-the-art normalization protocols have been evaluated to ensure optimal normalization of datasets prior to data analysis. Results: We previously determined a miRNA signature in a multi hospital discovery cohort that is differentially expressed between healthy individuals and stage II CRC patients. Here we report on the validation of this miRNA signature in an independent set of plasma samples from CRC patients and healthy volunteers. We have counter-screened the miRNA signature in a set of patients with other prevalent diseases, including hypertension, diabetes, diverticulitis, and others. Conclusions: A plasma miRNA signature for early detection of CRC from patient plasma was developed and validated in an independent clinical sample set. The signature was specific with respect to other diseases prevalent in the screening population. A second large-scale validation project is on-going. We conclude that plasma miRNA biomarkers can constitute an effective minimally invasive approach to population-wide CRC screening.
Determina KRAS: A consolidated project.
Authors: Garcia-Foncillas Jesus 
Published: February 2017

428 Background: The identification of KRAS mutation status as a predictive biomarker for the activity of anti-EGFR in mCRC patients, was the start of the personalize medicine. ASCO recognized it as a major advance in 2008 and it also gave a clinical opinion so every candidate for anti-EGFR therapy should be tested for KRAS mutations. NCCN guidelines recommends to do it at the first diagnose of metastatic disease. KRAS status testing was no widely available in Spain by 2008. The project Determina KRAS was developed in order to provide access to this test throughout the country to any mCRC patient. Methods: Five well known Spanish centres were trained and provided with equipment so they could analyze KRAS status in a five working day period. First centre was initiated in July 2008, being the last one in October 2008. A validated KRAS mutation kit (DxS Ltd, Manchester, UK) which identifies 7 different somatic mutations located in codons 12 and 13 using allele-specific real-time polymerase chain reaction was used. Results: 15.330 samples from mCRC patients have been analyzed since July 2008. 53,7% samples showed wild type KRAS status. G12D mutation was the most frequent mutation observed in general (35,1% of all mutation). G13D mutation was the most frequent of the codon 13 mutation, with a 20,2% of the global mutations. Conclusions: KRAS status testing allows to patients with mCRC receive a personalized medicine. KRAS status testing is essencial for treatment decision-making in mCRC and access to it must be guaranteed for any patient. The determination of biomarkers to choose the most effective treatment for each patient will be the future of oncology. These futures assessments must be available for all patients through national Networks, as the Determina KRAS project has made with KRAS testing.
Randomized clinical trial of preoperative chemoradiotherapy by S-1 versus UFT to rectal cancer for personalized therapy.
Authors: Miyatani Tomohiko , Utsunomiya Toru , Kurita Nobuhiro , Iwata Takashi , Sato Hirohiko , Nishioka Masanori , Morimoto Shinya , Yoshikawa Kozo , Higashijima Jun , Kashihara Hideya , Mikami Chie , Shimada Mitsuo 
Published: February 2017

432 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Our purpose of this study was to determine the effects and adverse events of CRT (S-1 or UFT) and to predict the response to CRT in rectal cancer by using both miRNA and DNA expression patterns. Methods: Rectal cancer patients (n=60) who underwent preoperative CRT were randomly divided into two groups (40Gy radiotherapy combined with S-1: 31 patients or UFT: 29 patients). The effects and adverse events of CRT were compared between S-1 group and UFT group. Additionally, RNA and DNA isolated from biopsy specimens of rectal cancer before preoperative CRT were hybridized to miRNA and DNA microarrays. Response to CRT was determined by histopathologic examination of surgically resected specimens. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60%(S-1) and 52%(UFT) (p=0.52). Adverse events of CRT did not differ significantly between the 2 groups, and there was no adverse event of grade 3 or 4. As candidate predictive genes, 184 genes (S-1 group) and 193 genes (UFT group) were identified by DNA microarray, while 6 miRNA (S-1 group) and 16 miRNA (UFT group) were isolated by miRNA microarray as candidate predictive miRNA. Conclusions: Preoperative CRT using S-1 or UFT to rectal cancer is effective and the adverse events were acceptable. Expression profiling of both gene and miRNA may predict the effects of preoperative CRT, implicating the possible personalized therapy for patients with rectal cancer.
CT imaging interval after complete cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) for well-differentiated adenocarcinoma of the appendix (WDAA).
Authors: Beaty Karen A. , Hill Joshua S. , Rafeeq Safia , Overman Michael J. , Sagebiel Tara L. , Matamoros Aurelio , Royal Richard E. , Mansfield Paul F. , Fournier Keith F. 
Published: February 2017

434 Background: WDAA with peritoneal dissemination (PD) is a rare disease with a prognosis related to the ability to perform adequate cytoreductive surgery (CRS) with cytoreductive scores of 0 or 1 (CC0 or CC1) followed by HIPEC. Diagnostic imaging is an important aspect of post-operative surveillance. Often, surveillance imaging follows metastatic colon cancer guidelines with frequent CT scans performed during the first 5 years after resection (every 3 months for 2 years, then every 6 months). Minimal evidence-based data exists to direct recommendations regarding optimal imaging intervals in patients with WDAA. Methods: All patients with a pathologic diagnosis of WDAA with PD who were evaluated at a single institution between August 1993 and January 2010 were retrospectively reviewed to identify patients who underwent a CC0 CRS and HIPEC. Parameters evaluated included demographics, time to recurrence and time to intervention after recurrence. Disease free survival was calculated using the Kaplan-Meier method. Results: 688 patients were evaluated during the study period. 67 patients (9.7%) had WDAA and underwent CC0 CRS/HIPEC. The mean age at diagnosis was 54.8 years. Twenty-two (32%) were male. Mean follow-up was 50.4 months. Disease free survival of the entire cohort at 10 yrs was 72 %. Eleven patients (16 %) experienced a recurrence. Median time to recurrence was 18.2 months. After recurrence, mean time to intervention was 6 months. In those patients that recurred, only 3 patients underwent intervention within 24 months of the index CRS/HIPEC (4% of overall cohort). Recurrence after 36 months occurred in only one patient (1.5% of cohort). Conclusions: Patients with WDAA/PD who undergo CC0 CRS/HIPEC have an overall very favorable prognosis and low risk of recurrence. Surveillance imaging, as often done for colorectal cancer, every 3-4 months is inappropriate. For this group of patients, follow-up CT scans every 6 months for 2 years, and then annually is recommended.
Neutrophil to lymphocyte ratios and pathologic response to neoadjuvant therapy in esophageal cancer.
Authors: Bronson Nathan W. , Luna Renato , Bloker Lisa M. , Douthit Miriam A. , Diggs Brian S. , Dolan James P. , Hunter John G. 
Published: February 2017

44 Background: Esophageal cancer (EC) is increasing in incidence dramatically, and is associated with suboptimal outcomes despite the widespread adoption of neoadjuvant multimodality therapy (NAT) as a de-facto standard-of-care for clinically resectable disease. Between one-quarter and one-third of patients (pts) are found to have no evidence of tumor (pCR) at the time of surgical resection, a prognostic indicator of superior survival benefit. However, we currently lack a method to prospectively identify pts who will respond to (NAT). Identifying complete responders could reduce the number of patients requiring esophagectomy. The specific aim of this study was to determine if the pre-operative neutrophil to lymphocyte ratio (NLR), which has been reported as a prognosticator of mortality, is prognostic of pCR to NAT. Methods: A prospectively collected database was queried for all pts that have undergone esophagectomy for EC, including both squamous cell carcinoma and adenocarcinoma. Records were evaluated for preoperative complete blood count (CBC) with differential from which a NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. A NLR greater than 5 was considered elevated. Pts were classified as pCR if they had no residual tumor on final pathology, partial responders (PR) if they demonstrated down staging after neoadjuvant therapy, or non-responders (NR) if they did not show any improvement in their stage on final pathology. Results: Of 114 pts who underwent both NAT and esophagectomy for EC, 41 had a pre-operative CBC with differential from which a NLR could be calculated. There were 19 NR, 14 PR and 8 CR. These groups were demographically similar. The average NLR was 5.92 for NR, 6.56 for PR, and 4.89 among CR, with no statistically significant difference between groups. Overall survival at 5 years was 33%. By multivariate analysis NLR>5 did not correlate with pathologic response (p=0.78), and NLR >5 did not correlate with survival (p=0.33). Conclusions: Elevated neutrophil to lymphocyte ratios are not predictive of pathologic response to NAT in esophageal cancer.
Evaluation of the prognostic value of guanylyl cyclase C (GCC) lymph node (LN) classification in patients with stage II colon cancer: A pooled analysis.
Authors: Sargent Daniel J. , Shi Qian , Resnick Murray B. , Lyle Stephen , Meyers Michael O. , Goldar-Najafi Atoussa , Clancy Thomas E. , Gill Sharlene , Haince Jean-Francois , Fradet Yves 
Published: February 2017

443 Background: Identification of a sensitive and specific prognostic marker would aid in the management of patients (pts) with standard histopathology node negative colon cancer (CC). We conducted a pooled individual pt data analysis to confirm the prognostic value of GCC for disease recurrence in untreated stage II CC. Methods: GCC mRNA was quantified by RT-qPCR using formalin-fixed LN from 310 stage II pts diagnosed from 1991-2006 enrolled in two studies (Sargent 2011 [study1] and Haince 2009 [study2]). Patients were classified by GCC LN ratio (LNR) (high risk: LNR ≥ 0.1; low risk: LNR < 0.1), with LNR defined as number of GCC positive LN divided by number of informative LNs. Clinical outcomes included time to recurrence (TTR), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Stratified log-rank tests and multivariate Cox models assessed the association between clinical outcomes and GCC LN status. Results: The 5-year recurrence rate in study 1 (n=241) was 15.8%, 24.9% in study 2 (n=69). GCC LNR high risk pts had significantly higher risk of TTR, OS, DSS and DFS, which remained after adjusting for age, T stage, grade, number of LNs examined, and presence of lymphovascular invasion ( Table ). In a secondary analysis of low risk stage II pts (T3, ≥12 LNs examined, and negative surgical margins, n=241), a strong relationship between GCC LNR and each endpoint remained (TTR HR=4.34, 95% CI=2.07 – 9.13, p<0.001). Conclusions: Pts with GCC LNR high risk status have significantly poorer outcomes compared to pts with low risk status, particularly among those traditionally considered to be low risk. [Table: see text]
Predictive and prognostic markers of recurrence after resection of primary or metastatic colorectal cancer.
Authors: VanDeusen Jeffrey Bryan , Uronis Joshua , Morse Michael , Gatza Michael L. , Datto Michael B. , Mantyh Christopher , Lyerly H. Kim , Nevins Joseph R. , Clary Bryan M. , Hsu Shiaowen David 
Published: February 2017

447 Background: Current biomarkers for colorectal cancer sub-classify tumors based on single mutations, such as KRAS; however, studies of single mutations belie the molecular complexity of colorectal cancer in which an average of 14 key genes per tumor is dysregulated. We hypothesize that colorectal cancer may be molecularly sub-classified based on an oncogenic pathway prediction model in which tumors are grouped based on patterns of oncogenic pathway dysregulation/expression. Methods: Affymetrix microarray data from 850 patients with primary colorectal cancer from publically available datasets were combined using Bayesian factor regression modeling normalization. The activity of 19 separate oncogenic pathways was predicted among tumors to generate patterns of pathway activity for each sample. Mixture modeling was applied to these samples to identify subgroups of tumors with unique patterns of pathway dysregulation. Validation of subclasses was performed on a dataset of 133 primary and metastatic colorectal cancer samples of patients undergoing curative surgical resection at our institution. Tumors were subgrouped according to our previous model and recurrence free survival was calculated. In vivo validation was performed by treating NOD/SCID mice bearing patient derived tumors with everolimus with changes in tumor size calculated between day 0 and day 21. Results: Mixture modeling resulted in 6 individual subgroups of colorectal cancer based on pathway dysregulation. Kaplan Meier curves revealed that patients in subclass 4 had the poorest prognosis while patients in subclass 6 had the best prognosis (p=0.05). Further, tumors in subclass 4 were generally enriched for high mTOR pathway activation and patient derived explants from subclass 4 with high predicted mTOR activity were found to be sensitive to the MTOR pathway inhibitor everolimus. Conclusions: Prediction of oncogenic signaling pathway activity is a powerful tool that may be used to molecularly sub-classify colorectal cancer into biologically relevant subgroups. These subgroups have prognostic and predictive implications for recurrence following surgical resection and responsiveness to targeted therapy.