bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori and the Prevention of Gastric Cancer
Authors: Sullivan Terrence , Ashbury Fredrick D , Fallone Carlo A , Naja Farah , Schabas Richard , Hébert Philip C , Hunt Richard , Jones Nicola 
Published: March 2016

BACKGROUND: Helicobacter pylori is an important cause of stomach cancer that infects a substantial proportion of the Canadian adult population. H pylori can be detected by noninvasive tests and effectively eradicated by medical treatment. Screening for and treatment of H pylori may represent a significant opportunity for preventive oncology.METHODS: Cancer Care Ontario organized a workshop held in Toronto, Ontario, on October 24 and 25, 2002, to: review the current state of knowledge regarding H pylori treatment and cancer prevention; determine if there is currently sufficient evidence to consider the promotion of H pylori treatment for the purpose of cancer prevention; identify critical areas for research; and advise Cancer Care Ontario on H pylori and cancer prevention.RESULTS: Workshop participants developed a number of recommendations for research into the relationship between H pylori and stomach cancer, including determining the prevalence of infection in different regions of Canada, the pathogenetic sequence of carcinogenesis from H pylori infection, and the implementation of a prospective observational study.INTERPRETATION: Although the rate of H pylori infection is declining in Canada and the treatment of H pylori is generally accepted to be safe, the evidence to date may not warrant the implementation of population screening for H pylori infection to prevent gastric carcinoma in average-risk populations. Rather, a demonstration project is needed to estimate prevalence, evaluate the merits of screening, measure patient compliance and physician participation, develop education materials, establish a registry for monitoring and evaluation, and develop a quality assurance framework.
Endoscopic Perforation Rates at a Canadian University Teaching Hospital
Authors: Misra Tarun , Lalor Eoin , Fedorak Richard N 
Published: March 2016

BACKGROUND: Despite advances in training, operative techniques and endoscopic technology, upper and lower endoscopic procedures continue to have potential for intestinal perforation. Perforation rates provided to patients at the time of consent have frequently been derived from historical cohorts and survey datasets.OBJECTIVE: This study examined the perforation rates of upper and lower endoscopic procedures at a major Canadian tertiary care centre.METHODS: Inpatient and outpatient gastroscopies and colonoscopies performed during a three year period were evaluated. Endoscopies with perforations occurring within 14 days of procedure were retrospectively isolated using the International Classification of Diseases ‐‐ 9th Revision code descriptions, then retrieved and hand searched to confirm a procedure‐related perforation. Data were extracted to identify risk factors and patient outcomes.RESULTS: A total of 21,217 endoscopies (13,792 gastroscopies and 7425 colonoscopies) were reviewed. Of these, 359 were identified, isolated and hand searched for confirmation of a perforation event. Eighteen were found to have an endoscopy‐associated perforation. Ten perforations occurred with colonoscopy (0.13%) (incidence, 1.3/1000 procedures), resulting in one death (0.013%) (incidence, 0.13/1000 procedures). Eight perforations occurred with gastroscopy (0.06%) (incidence, 0.6/1000 procedures), resulting in zero mortality. Of colonoscopy procedures the rate of perforation with diagnostic colonoscopy was 0.13% (incidence, 1.3/1000 procedures) and with therapeutic colonoscopy was 0.14% (incidence, 1.4/1000 procedures). Of gastroscopy procedures the rate with therapeutic gastroscopy was 0.15% (incidence, 1.5/1000 procedures). No perforations occurred with diagnostic gastroscopy.CONCLUSION: Gastroscopy and colonoscopy procedures, especially those with therapeutic maneuvers, continue to carry morbidity and mortality risks associated with perforation.
A Canadian Clinical Practice Algorithm for the Management of Patients with Non-Variceal Upper Gastrointestinal Bleeding
Authors: Barkun Alan , Fallone Carlo A , Chiba Naoki , Fishman Marty , Flook Nigel , Martin Janet , Rostom Alaa , Taylor Anthony ,   for the Nonvariceal Upper GI Bleeding Consensus Conference Group
Published: March 2016

AIM:To use current evidence-based recommendations to provide a user-friendly clinical algorithm for the management of upper gastrointestinal bleeding, adapted to the Canadian environment.METHODS:A multidisciplinary consensus group of 25 participants representing 11 national societies used a seven-step approach to develop recommendations according to accepted standards. Sources of data included narrative and systematic reviews as well as published and new meta-analyses. A small writing subgroup subsequently created the algorithm.RESULTS:Recommendations emphasize appropriate initial resuscitation of the patient and a multidisciplinary approach to clinical risk stratification that determines the need for early endoscopy. Early endoscopy allows safe and prompt discharge of selected patients classified as low risk. Endoscopic hemostasis is reserved for patients with high-risk endoscopic lesions. Although monotherapy with injection or thermal coagulation is effective, the combination is superior to either treatment alone. High-dose intravenous proton-pump inhibition is recommended in patients who have undergone successful endoscopic therapy. Routine second-look endoscopy is not recommended. Patients with upper gastrointestinal bleeding secondary to ulcer disease should be tested and treated forHelicobacter pyloriinfection.CONCLUSIONS:This algorithm should facilitate appropriate risk stratification, use of endoscopic therapy and the appropriate utilization of proton-pump inhibition to optimize the care of patients with upper gastrointestinal bleeding. The algorithm should be customized to the resources of individual medical centres. Its application should be studied with appropriate outcomes recorded and validation performed.
Predicting Residual Rectal Adenocarcinoma in the Surgical Specimen after Preoperative Brachytherapy with Endoscopic Ultrasound
Authors: Romagnuolo Joseph , Parent Josée , Vuong Té , Bélanger Mélanie , Michel René P , Belliveau Paul J , Trudel Judith L 
Published: March 2016

BACKGROUND AND STUDY AIMS:A novel brachytherapy (BT) protocol evaluated at McGill University has shown promise in terms of downstaging and achieving high tumour sterilization rates in rectal cancer. Endoscopic ultrasound (EUS) has emerged as the imaging modality of choice for local staging of rectal cancer. However, external beam radiotherapy appears to decrease the accuracy of EUS from 85% to 40%. The aim of the present study was to prospectively evaluate the accuracy of EUS in assessing the response of rectal cancer to BT.PATIENTS AND METHODS:Thirty-three patients with locally advanced (stage T2 or T3) operable rectal carcinomas were included in an experimental protocol involving a novel conformal technique, using three-dimensional planning, to administer high-dose rate preoperative BT. The 18 patients who were able to have a post-BT EUS exam arranged within two weeks before surgery (eg, four to eight weeks post-BT) were included in this study. Tumour (T)- and lymph node (N)-staging on radial EUS, as well as interpretation of the residual tumour, were assessed prospectively. Pathologists were blinded to the post-BT EUS results.RESULTS:The mean age was 70 years (SD ±11; range, 52 to 93 years) and 78% of the patients were male. Pre-BT EUS indicated that 16 patients (89%) were stage T3, and two were stage T2. Five patients (28%) had positive nodes (N1) by ultrasound. With BT, the mean maximal wall thickness on EUS decreased from 14 mm to 9.4 mm (PÃ0.001). At the time of surgery, seven of the 18 patients (39%) had no detectable tumour in the resected specimen; one had carcinoma in situ, one was stage T1, one was stage T2, and eight were stage T3. Eleven patients (61%) underwent an abdominoperineal resection, including four of the 11 (36%) with no ultimate evidence of residual carcinoma. Eight patients (44%) were node-positive. The sensitivity, specificity, and positive and negative predictive values of post-BT EUS in predicting residual tumour were 82%, 29%, 64% and 50%, respectively. The post-BT EUS accurately predicted the T-stage in eight (44%) patients; most errors were due to overstaging.CONCLUSIONS:Rectal cancer T-staging by EUS post-BT is inaccurate, and although it appears sensitive in predicting the presence or absence of residual tumor in rectal adenocarcinoma after preoperative BT, the low predictive values in this setting limit its utility at this time.
Clinical Presentation and Prevalence of Spontaneous Bacterial Peritonitis in Patients with Cryptogenic Cirrhosis and Features of Metabolic Syndrome
Authors: Sorrentino P , Tarantino G , Conca P , Perrella A , Perrella O 
Published: March 2016

BACKGROUND:Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis. The prevalence and clinical relevance that spontaneous bacterial peritonitis may have in complicating ascites due to NASH-related cirrhosis have yet to be defined.METHODS:Among 611 cases of cirrhosis-associated ascites, 45 patients with cryptogenic cirrhosis were retrospectively identified. Of these, 36 patients and a control group of subjects with viral-associated ascites were followed up and compared in a case control study. Information on the onset of ascites, with or without spontaneous bacterial peritonitis, history of risk factors for multimetabolic syndrome, and serological and ascitic laboratory data were compared between groups.RESULTS:Spontaneous bacterial peritonitis occurred significantly more often in patients with cryptogenic cirrhosis than in equally symptomatic viral controls. The prevalence of obesity, diabetes and spontaneous bacterial peritonitis was significantly higher in patients with cryptogenic cirrhosis. Although liver function was similar in both groups, cryptogenic cirrhosis patients had lower aminotransferase levels. Multivariate analysis identified diabetes, juvenile obesity and spontaneous bacterial peritonitis as independent factors associated with ascites due to cryptogenic cirrhosis.CONCLUSIONS:Features suggestive of NASH are more frequently observed in patients with ascites and cryptogenic cirrhosis than in age- and sex-matched ascitic patients with well-defined viral etiology. Ascites may be a presenting symptom of NASH-related cirrhosis, and affected patients have a twofold greater risk of spontaneous bacterial peritonitis.
Serum Beta2-Microglobulin Levels in Hepatitis B e Antigen-Negative Chronic Hepatitits B Patients under Long-Term Lamivudine Monotherapy: Relationship with Virological Breakthrough
Authors: Elefsiniotis Ioannis S , Scarmeas Nikolaos , Glynou Irene , Pantazis Konstantinos D , Kada Helen , Mavrogiannis Christos 
Published: March 2016

OBJECTIVES:To evaluate the predictive value of serum beta2-microglobulin (&#946;2m) levels for virological breakthrough in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy.METHODS:Serum &#946;2m levels were calculated at baseline and every three months during lamivudine monotherapy in 25 patients with chronic hepatitis B, using microparticle enzyme immunoassay technology to investigate their association with biochemical, virological and histological outcome data. Cox proportional hazard models were used to investigate the association between serum &#946;2m levels and virological breakthrough.RESULTS:Seven of 25 (28%), nine of 25 (36%) and 14 of 25 (56%) chronic hepatitis B patients exhibited virological breakthrough at months 12, 24 and 36 of treatment, respectively. All chronic hepatitis B patients who did not show virological breakthrough in the follow-up period exhibited &#946;2m elevation in month 3 of treatment. The duration (in months) of serum &#946;2m elevation was significantly higher in the responders group than the nonresponders group (7.3±2.6 versus 3.8±3.4, P=0.02). In contrast to patients whose serum &#946;2m levels were increased at three months, patients whose &#946;2m levels were decreased had a 4.6 times higher risk of experiencing virological breakthrough (hazards ratio 4.6, 95% CI 1.22 to 17.36). When age, pretreatment serum alanine aminotransferase and hepatitis B virus DNA levels, and grade of liver disease were simultaneously included in the same Cox model, decreased &#946;2m status was still associated with increased risk of virological breakthrough (hazards ratio 12.2, 95% CI 1.28 to 116.8).CONCLUSIONS:In hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy, serum &#946;2m levels at three months of treatment, compared with baseline levels, are good predictors of risk for virological breakthrough.
Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer—Combined Analysis of the PORTEC Cohorts
Authors: Stelloo Ellen , Nout Remi A. , Osse Elisabeth M. , Jürgenliemk-Schulz Ina J. , Jobsen Jan J. , Lutgens Ludy C. , van der Steen-Banasik Elzbieta M. , Nijman Hans W. , Putter Hein , Bosse Tjalling , Creutzberg Carien L. , Smit Vincent T.H.B.M. 
Published: March 2016

Abstract
Purpose: Recommendations for adjuvant treatment for women with early-stage endometrial carcinoma are based on clinicopathologic features. Comprehensive genomic characterization defined four subgroups: p53-mutant, microsatellite instability (MSI), POLE-mutant, and no specific molecular profile (NSMP). We aimed to confirm the prognostic capacity of these subgroups in large randomized trial populations, investigate potential other prognostic classifiers, and integrate these into an integrated molecular risk assessment guiding adjuvant therapy.
Experimental Design: Analysis of MSI, hotspot mutations in 14 genes including POLE, protein expression of p53, ARID1a, β-catenin, L1CAM, PTEN, ER, and PR was undertaken on 947 available early-stage endometrioid endometrial carcinomas from the PORTEC-1 and -2 trials, mostly high-intermediate risk (n = 614). Prognostic value was determined using univariable and multivariable Cox proportional hazard models. AUCs of different risk stratification models were compared.
Results: Molecular analyses were feasible in &gt;96% of the patients and confirmed the four molecular subgroups: p53-mutant (9%), MSI (26%), POLE-mutant (6%), and NSMP (59%). Integration of prognostic molecular alterations with established clinicopathologic factors resulted in a stronger model with improved risk prognostication. Approximately 15% of high-intermediate risk patients had unfavorable features (substantial lymphovascular space invasion, p53-mutant, and/or &gt;10% L1CAM), 50% favorable features (POLE-mutant, NSMP being microsatellite stable, and CTNNB1 wild-type), and 35% intermediate features (MSI or CTNNB1-mutant).
Conclusions: Integrating clinicopathologic and molecular factors improves the risk assessment of patients with early-stage endometrial carcinoma. Assessment of this integrated risk profile is feasible in daily practice, and holds promise to reduce both overtreatment and undertreatment. Clin Cancer Res; 22(16); 4215–24. ©2016 AACR.
A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu–Expressing Tumor in HLA-A2 Transgenic Mice
Authors: Tran Thi , Diniz Mariana O. , Dransart Estelle , Gey Alain , Merillon Nathalie , Lone Yu Chun , Godefroy Sylvie , Sibley Craig , Ferreira Luis CS , Medioni Jacques , Oudard Stephane , Johannes Ludger , Tartour Eric 
Published: March 2016

Abstract
Purpose: E75, a peptide derived from the Her2/neu protein, is the most clinically advanced vaccine approach against breast cancer. In this study, we aimed to optimize the E75 vaccine using a delivery vector targeting dendritic cells, the B-subunit of Shiga toxin (STxB), and to assess the role of various parameters (Her2/neu expression, combination with trastuzumab) in the efficacy of this cancer vaccine in a relevant preclinical model.
Experimental Design: We compared the differential ability of the free E75 peptide or the STxB-E75 vaccine to elicit CD8+ T cells, and the impact of the vaccine on murine HLA-A2 tumors expressing low or high levels of Her2/neu.
Results: STxB-E75 synergized with granulocyte macrophage colony-stimulating factors and CpG and proved to be more efficient than the free E75 peptide in the induction of multifunctional and high-avidity E75-specific anti-CD8+ T cells resulting in a potent tumor protection in HLA-A2 transgenic mice. High expression of HER2/neu inhibited the expression of HLA-class I molecules, leading to a poor recognition of human or murine tumors by E75-specific cytotoxic CD8+ T cells. In line with these results, STxB-E75 preferentially inhibited the growth of HLA-A2 tumors expressing low levels of Her2/neu. Coadministration of anti-Her2/neu mAb potentiated this effect.
Conclusions: STxB-E75 vaccine is a potent candidate to be tested in patients with low Her2/neu–expressing tumors. It could also be indicated in patients expressing high levels of Her2/neu and low intratumoral T-cell infiltration to boost the recruitment of T cells—a key parameter in the efficacy of anti-Her2/neu mAb therapy. Clin Cancer Res; 22(16); 4133–44. ©2016 AACR.
Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques
Authors: Dewi Fitriya N. , Wood Charles E. , Willson Cynthia J. , Register Thomas C. , Lees Cynthia J. , Howard Timothy D. , Huang Zhiqing , Murphy Susan K. , Tooze Janet A. , Chou Jeff W. , Miller Lance D. , Cline J. Mark 
Published: March 2016

Abstract
Endogenous estrogens influence mammary gland development during puberty and breast cancer risk during adulthood. Early-life exposure to dietary or environmental estrogens may alter estrogen-mediated processes. Soy foods contain phytoestrogenic isoflavones (IF), which have mixed estrogen agonist/antagonist properties. Here, we evaluated mammary gland responses over time in pubertal female cynomolgus macaques fed diets containing either casein/lactalbumin (n = 12) or soy protein containing a human-equivalent dose of 120 mg IF/day (n = 17) for approximately 4.5 years spanning menarche. We assessed estrogen receptor (ER) expression and activity, promoter methylation of ERs and their downstream targets, and markers of estrogen metabolism. Expression of ERα and classical ERα response genes (TFF1, PGR, and GREB1) decreased with maturity, independent of diet. A significant inverse correlation was observed between TFF1 mRNA and methylation of CpG sites within the TFF1 promoter. Soy effects included lower ERβ expression before menarche and lower mRNA for ERα and GREB1 after menarche. Expression of GATA-3, an epithelial differentiation marker that regulates ERα-mediated transcription, was elevated before menarche and decreased after menarche in soy-fed animals. Soy did not significantly alter expression of other ER activity markers, estrogen-metabolizing enzymes, or promoter methylation for ERs or ER-regulated genes. Our results demonstrate greater ER expression and activity during the pubertal transition, supporting the idea that this life stage is a critical window for phenotypic modulation by estrogenic compounds. Pubertal soy exposure decreases mammary ERα expression after menarche and exerts subtle effects on receptor activity and mammary gland differentiation. Cancer Prev Res; 9(5); 385–95. ©2016 AACR.
Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice
Authors: Mercer Kelly E. , Pulliam Casey , Hennings Leah , Lai Keith , Cleves Mario , Jones Ellen , Drake Richard R. , Ronis Martin 
Published: March 2016

Abstract
In this study, diethylnitrosamine-treated male mice were assigned to three groups: (i) a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, (ii) the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/SPI), (iii) and a chow group. EtOH feeding continued for 16 weeks. As expected, EtOH increased the incidence and multiplicity of basophilic lesions and adenomas compared with the chow group, P &lt; 0.05. Soy protein replacement of casein in the EtOH diet significantly reduced adenoma progression when compared with the EtOH and EtOH/SPI group (P &lt; 0.05). Tumor reduction in the EtOH/SPI group corresponded to reduced liver injury associated with decreased hepatic Tnfα and Cd14 antigen (Cd14) expression and decreased nuclear accumulation of NF-κB1 protein compared with the EtOH group (P &lt; 0.05). Detection of sphingolipids using high-resolution matrix-assisted laser desorption/ionization–Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging mass spectrometry revealed increased accumulation of long acyl chain ceramide species, and sphingosine-1-phosphate (S1P) in the EtOH group that were significantly reduced in the EtOH/SPI group. Chronic EtOH feeding also increased mRNA expression of β-catenin transcriptional targets, including cyclin D1 (Ccnd1), matrix metallopeptidase 7 (Mmp7), and glutamine synthetase (Glns), which were reduced in the EtOH/SPI group (P &lt; 0.05). We conclude that soy prevents tumorigenesis by reducing proinflammatory and oxidative environment resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of β-catenin signaling. These mechanisms may involve changes in sphingolipid signaling. Cancer Prev Res; 9(6); 466–75. ©2016 AACR.
Evolution of Mitral Valve Prolapse
Authors: Delling Francesca N. , Rong Jian , Larson Martin G. , Lehman Birgitta , Fuller Deborah , Osypiuk Ewa , Stantchev Plamen , Hackman Brianne , Manning Warren J. , Benjamin Emelia J. , Levine Robert A. , Vasan Ramachandran S. 
Published: March 2016

Background—
Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking.

Methods and Results—

We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57±11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all
P
<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height ≥5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all
P
<0.05).

Conclusions—
NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression.