Endoscopic screening for esophageal squamous cell carcinoma

Esophageal cancer (EC) is the eighth common cancer and the sixth most common cause of death from cancer worldwide. Esophageal squamous cell carcinoma (ESCC) remains the most common type of EC in the developing world and an important health problem in high-risk areas. Most of ESCC cases present in late stages, resulting in delayed diagnosis and poor prognosis. Prevention is the most effective strategy to control ESCC. Primary and secondary preventive methods may be considered for ESCC. In primary prevention, we try to avoid known risk factors. The aim of the secondary preventive method (ESCC screening programs) is to detect and eliminate premalignant precursor lesion of ESCC, preventing its progression into advanced stages. Similar to all population-based screening programs, any screening for early detection of ESCC must be cost-effective; otherwise, screening may not be indicated in that population. Endoscopy with iodine staining has been accepted as a population-level ESCC screening program in some high-risk areas including parts of China. This method may be too expensive and invasive in other high-risk communities. Nonendoscopic methods may be more applicable in these populations for population-based screenings. The limitations (questionable validity and costs) of new endoscopic imaging modalities, including narrow-band imaging (NBI), made them inappropriate to be used in population-level ESCC screening programs. Low-cost, less-invasive endoscopic imaging methods with acceptable diagnostic performance may make screening of ESCC in high-risk areas cost-effective

Risk factors for esophageal squamous cell carcinoma

Aims: The etiology of esophageal squamous cell carcinoma (ESCC) in the high risk areas is largely unknown and a few environmental risk factors which have been identified do not explain its oddly high incidence in esophageal cancer belt. The aims of this thesis were to investigate the association of opium/tobacco consumption, serologic gastric atrophy, gastric mucosa-associated microbiota and contact with farm animals with the risk of ESCC. Methods: The population of Golestan Province in northeastern Iran has very high rates of ESCC. From 2003 to 2007, we administered a validated structured questionnaire to 300 incident ESCC cases and 571 controls. Controls were matched to cases for neighborhood of residence, age (± 2 years), and sex. We measured serum pepsinogen I and II among 293 incident cases and 524 matched controls. Conditional logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for potential confounders. Furthermore we obtained a frozen gastric tissue biopsy from subjects with ESCC, esophageal squamous dysplasia, mid esophagus esophagitis, and age/sex-matched endoscopy clinic controls with healthy esophagus. To characterize bacterial lineage present in gastric mucosa, we performed a multiplex sequencing with GS-FLX Titanium targeting 16S rRNA. Results: Risk of ESCC was increased in those who used opium only (OR = 2.12, 95% CI: 1.21 - 3.74), and in those who used both tobacco and opium (2.35, 95% CI: 1.50 - 3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Gastric atrophy (defined by a validated criterion, pepsinogen I <55 μg/dl) was associated with a two-fold increased risk (OR = 2.01, 95% CI: 1.18 - 3.45) of ESCC in the absence of non-atrophic pangastritis (defined as pepsinogen II < 11.8 μg/dl). Sequencing of 16S rRNA in gastric biopsy samples resulted 2075 operational taxonomic units (OTUs). Conditional logistic regression model based on principal coordinate analysis (PCoA) showed a marginal variation in pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) between subjects with esophageal cancer or dysplasia and controls. No such difference between subjects with mid-esophagitis and controls was observed. Among four groups of farm animals (equines, ruminants, domestic canine and poultry) contact with ruminants was associated with an 8-fold increase in risk of ESCC. This association stayed stable when duration and level of contact were considered. Conclusions: Though opium and tobacco consumption are associated with the risk of ESCC in the study area, they do not explain the extreme high incidence in northern Iran. Changes in gastric environment might be linked to ESCC risk as fundal atrophy may increase the risk for ESCC and pattern of gastric microbiota differs in patients with esophageal squamous dysplasia (and ESCC) from subjects with normal esophagus. The observed relationship between lifelong contact with ruminants and ESCC needs further investigation

An Analysis of Remedial Reading Preparation for Beginning Information Systems Students at Eastern Shore Community College

The hypotheses under investigation during the course of this study were as follows: 1. Students who complete the developmental reading course (ENG 04, Reading Improvement) at ESCC earn grades in the introductory computer course (IST 114, Fundamentals of Computer Information Systems) comparable to those students who did not need remediation. 2. The developmental reading course prepares the remedial reading students to comprehend the technical material required to complete the introductory computer course at a level comparable to those students who did not need remediation

Non-coding RNAs in saliva: emerging biomarkers for molecular diagnostics.

Saliva is a complex body fluid that comprises secretions from the major and minor salivary glands, which are extensively supplied by blood. Therefore, molecules such as proteins, DNA, RNA, etc., present in plasma could be also present in saliva. Many studies have reported that saliva body fluid can be useful for discriminating several oral diseases, but also systemic diseases including cancer. Most of these studies revealed messenger RNA (mRNA) and proteomic biomarker signatures rather than specific non-coding RNA (ncRNA) profiles. NcRNAs are emerging as new regulators of diverse biological functions, playing an important role in oncogenesis and tumor progression. Indeed, the small size of these molecules makes them very stable in different body fluids and not as susceptible as mRNAs to degradation by ribonucleases (RNases). Therefore, the development of a non-invasive salivary test, based on ncRNAs profiles, could have a significant applicability to clinical practice, not only by reducing the cost of the health system, but also by benefitting the patient. Here, we summarize the current status and clinical implications of the ncRNAs present in human saliva as a source of biological information

Predictive value of clinical and 18F-FDG-PET/CT derived imaging parameters in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

Aim of this study was to validate the prognostic impact of clinical parameters and baseline 18F-FDG-PET/CT derived textural features to predict histopathologic response and survival in patients with esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiation (nCRT) and surgery. Between 2005 and 2014, 38 ESCC were treated with nCRT and surgery. For all patients, the 18F-FDG-PET-derived parameters metabolic tumor volume (MTV), SUVmax, contrast and busyness were calculated for the primary tumor using a SUV-threshold of 3. The parameter uniformity was calculated using contrast-enhanced computed tomography. Based on histopathological response to nCRT, patients were classified as good responders (< 10% residual tumor) (R) or non-responders (≥ 10% residual tumor) (NR). Regression analyses were used to analyse the association of clinical parameters and imaging parameters with treatment response and overall survival (OS). Good response to nCRT was seen in 27 patients (71.1%) and non-response was seen in 11 patients (28.9%). Grading was the only parameter predicting response to nCRT (Odds Ratio (OR) = 0.188, 95% CI: 0.040-0.883; p = 0.034). No association with histopathologic treatment response was seen for any of the evaluated imaging parameters including SUVmax, MTV, busyness, contrast and uniformity. Using multivariate Cox-regression analysis, the heterogeneity parameters busyness (Hazard Ratio (HR) = 1.424, 95% CI: 1.044-1.943; p = 0.026) and contrast (HR = 6.678, 95% CI: 1.969-22.643; p = 0.002) were independently associated with OS, while no independent association with OS was seen for SUVmax and MTV. In patients with ESCC undergoing nCRT and surgery, baseline 18F-FDG-PET/CT derived parameters could not predict histopathologic response to nCRT. However, the PET/CT derived features busyness and contrast were independently associated with OS and should be further investigated

THE EFFECTS OF COMMUNITIES OF PRACTICE ON THE SUCCESS OF AN EXPERT RECOMMENDING SERVICE

This article presents an explorative study of the impact of Communities of Practice (CoPs) on the success of a certain category of Knowledge Management Systems, hereafter called Expert Recommender Information Systems. They regroup Information Systems that identify and display individuals who have been qualified by the system as experts, and who are in a position to help users solve problems involving a business process breakdown. Rather than focusing on the Expert Recommending Information System itself, the author concentrates on the service it delivers, the Expert Recommending Service (ERS). Using multiple case study research, five different organizations were investigated, essentially in order to identify how CoPs influence the success of their ERS.IS success; Communities of Practice; Expert Recommending Services; Experts

Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis

<p>Abstract</p> <p>Background</p> <p>Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA) is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC). Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1) to study HA-synthase (HAS) expression and regulation in human ESCC, and (2) to translate the <it>in vitro </it>results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan.</p> <p>Methods</p> <p>mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU), an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3), the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT). HA content, cellular composition and proliferation (Ki67) were determined histologically.</p> <p>Results</p> <p>mRNA of HAS isoform 3 (HAS3) was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF) receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression <it>in vitro</it>. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by ESCC is accountable for major changes in tumour environment <it>in vivo</it>.</p> <p>Conclusions</p> <p>Systemic inhibition of HA-synthesis and knockdown of tumour cell HAS3 cause decreased ESCC progression accompanied by tumour stroma remodelling and may therefore be used in novel approaches to ESCC therapy.</p

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies