Hereditary Diffuse Gastric Cancer: Updated Clinical Practice Guidelines

Hereditary Diffuse Gastric Cancer (HDGC) is an autosomal dominant cancer syndrome that is characterised by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, although pathogenic variants in CTNNA1 occur in a minority of HDGC families. Here, the International Gastric Cancer Linkage Consortium (IGCLC) has updated practice guidelines for HDGC, recognising the emerging evidence of variability in gastric cancer risk between HDGC families, the growing capability of endoscopic and histological surveillance in HDGC and greater experience managing long-term sequelae post total gastrectomy in young patients. To redress the balance between the accessibility, cost and acceptance of genetic testing and greater identification of pathogenic variant carriers, the HDGC genetic testing criteria have been relaxed, mainly through less restrictive age limits. Prophylactic total gastrectomy remains the recommended option for gastric cancer risk management in pathogenic CDH1 variant carriers. However, there is increasing confidence from the IGCLC that endoscopic surveillance in expert centres can be safely offered to patients who wish to postpone surgery or to those whose risk is not well defined

Research advances in esophageal diseases: bench to bedside.

Over the last year, significant steps have been made toward understanding the pathogenesis of esophageal diseases and translating this knowledge to clinical practice. Gastroesophageal reflux disease (GERD) is the most common outpatient diagnosis in gastroenterology and has a high prevalence in the general population. As many as 40% of patients with GERD have incomplete response to medical therapy, and the pathophysiological mechanisms underlying lack of response are now better understood. Novel medical and minimally invasive interventions are available to optimize management of GERD. Esophageal cancer, regardless of the histological subtype, has among the worst survival statistics among all malignancies. Taking advantage of technological advances in genome sequencing, the mutational spectra in esophageal cancer are now emerging, offering novel avenues for targeted therapies. Early diagnosis is another strand for improving survival. While genome-wide association studies are providing insights into genetic susceptibility, novel approaches to early detection of cancer are being devised through the use of biomarkers applied to esophageal samples and as part of imaging technologies. Dysmotility and eosinophilic esophagitis are the differential diagnoses in patients with dysphagia. New pathophysiological classifications have improved the management of motility disorders. Meanwhile, exciting progress has been made in the endoscopic management of these conditions. Eosinophilic esophagitis is still a relatively new entity, and the pathogenesis remains poorly understood. However, it is now clear that an allergic reaction to food plays an important role, and dietary interventions as well as biologic agents to block the inflammatory cascade are novel, promising fields of clinical research

Barrett's esophagus and cancer risk: how research advances can impact clinical practice.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), whose incidence has increased sharply in the last 4 decades. The annual conversion rate of BE to cancer is significant, but small. The identification of patients at a higher risk of cancer therefore poses a clinical conundrum. Currently, endoscopic surveillance is recommended in BE patients, with the aim of diagnosing either dysplasia or cancer at early stages, both of which are curable with minimally invasive endoscopic techniques. There is a large variation in clinical practice for endoscopic surveillance, and dysplasia as a marker of increased risk is affected by sampling error and high interobserver variability. Screening programs have not yet been formally accepted, mainly due to the economic burden that would be generated by upper gastrointestinal endoscopy. Screening programs have not yet been formally accepted, mainly due to the economic burden that would be generated by widespread indication to upper gastrointestinal endoscopy. In fact, it is currently difficult to formulate an accurate algorithm to confidently target the population at risk, based on the known clinical risk factors for BE and EAC. This review will focus on the clinical and molecular factors that are involved in the development of BE and its conversion to cancer and on how increased knowledge in these areas can improve the clinical management of the disease

Emerging Optical Methods for Endoscopic Barrett’s Surveillance

Barrett’s oesophagus is an acquired metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma, prompting the use of surveillance regimes to detect early malignancy for endoscopic therapy with curative intent. The currently accepted surveillance regime uses white light endoscopy together with random biopsies, but suffers poor sensitivity and discards information from numerous light-tissue interactions that could be exploited to probe structural, functional and molecular changes in the tissue. Advanced optical methods are now emerging that are exquisitely sensitive to these changes and hold significant potential to improve surveillance of Barrett’s oesophagus if they can be applied endoscopically. The next decade will see some of these exciting new methods applied to Barrett’s surveillance in new device architectures for the first time, potentially leading to a longawaited improvement of the standard of care

Quantitative imaging of the complexity in liquid bubbles' evolution reveals the dynamics of film retraction

The dynamics and stability of thin liquid films have fascinated scientists over many decades. Thin film flows are central to numerous areas of engineering, geophysics, and biophysics and occur over a wide range of length, velocity, and liquid properties scales. In spite of many significant developments in this area, we still lack appropriate quantitative experimental tools with the spatial and temporal resolution necessary for a comprehensive study of film evolution. We propose tackling this problem with a holographic technique that combines quantitative phase imaging with a custom setup designed to form and manipulate bubbles. The results, gathered on a model aqueous polymeric solution, provide an unparalleled insight into bubble dynamics through the combination of full-field thickness estimation, three-dimensional imaging, and fast acquisition time. The unprecedented level of detail offered by the proposed methodology will promote a deeper understanding of the underlying physics of thin film dynamics

Revised British Society of Gastroenterology recommendation on the diagnosis and management of Barrett's oesophagus with low-grade dysplasia.

The most recent guidelines for the management of Barrett's oesophagus published in 2014 recommended endoscopic surveillance for patient with histological evidence of low-grade dysplasia (LGD) on random biopsies.1 In the last 2 years, new evidence on the natural history of LGD in Barrett's oesophagus and on the safety and efficacy of endoscopic treatment in this subgroup of patients has been published

Quantitative imaging of the complexity in liquid bubbles’ evolution reveals the dynamics of film retraction

Thin liquid films: Seeing bubbles in a better light A procedure for imaging the complex fluid dynamics in bubbles could greatly assist efforts to understand and exploit thin liquid films in applications ranging through medicine, industrial chemistry and engineering. Thin liquid films are ubiquitous in nature, found in such varied systems as soap bubbles, biological membranes, detergents, oils, insulation, foods and geological magma. Researchers in Italy led by Biagio Mandracchia at the Institute of Applied Science and Intelligent Systems in Naples, devised a novel holographic phase imaging technique to watch bubbles as they form, develop, burst and retract. The researchers built customized apparatus to create and manipulate the bubbles. The unprecedented level of detail being revealed offers deeper understanding of the physics underlying thin film behavior. Insights into the complex fluid dynamics within bubbles could advance thin film technology for many applications

Pilot randomized crossover study comparing the efficacy of transnasal disposable endosheath with standard endoscopy to detect Barrett's esophagus.

BACKGROUND AND STUDY AIMS: The transnasal endosheath endoscope is a new disposable technology with potential applicability to the primary care setting. The aim of this study was to evaluate the efficacy of transnasal endosheath endoscopy (TEE) for the detection of Barrett's esophagus, by comparing the diagnostic accuracy of TEE with that of standard endoscopy. PATIENTS AND METHODS: This was a prospective, randomized, crossover study performed in a single tertiary referral center. Consecutive patients undergoing surveillance for Barrett's esophagus or referred for diagnostic assessment were recruited. All patients were randomized to undergo TEE followed by standard endoscopy or the reverse. Endoscopy experiences and patient preferences were evaluated using a questionnaire. Endoscopic and histologic diagnosis of Barrett's esophagus, and optical image quality of both endoscopic procedures, were compared. RESULTS: A total of 21 of 25 patients completed the study. TEE had sensitivity and specificity of 100 % for an endoscopic diagnosis of Barrett's esophagus, and of 66.7 % and 100 %, respectively, for the histologic diagnosis of Barrett's esophagus. The mean optical quality of standard endoscopy was significantly better than that of TEE (7.11 ± 0.42 vs. 4.06 ± 0.27; P < 0.0001). However, following endoscopy, patients reported a significantly better experience with TEE compared with standard endoscopy (7.05 ± 0.49 vs. 4.35 ± 0.53; P = 0.0006), with 60 % preferring TEE and 25 % preferring sedated standard endoscopy. CONCLUSIONS: In this study, TEE had equal accuracy for an endoscopic diagnosis of Barrett's esophagus compared with standard endoscopy, at the expense of reduced image quality and a lower yield of intestinal metaplasia on biopsy. TEE was better tolerated and preferred by patients. Hence, TEE needs further evaluation in primary care as an initial diagnostic tool.This study was supported by funding from Cambridge Experimental Cancer Medicine Centre, NIHR Cambridge Biomedical Research Centre, and a core grant for RCF from the Medical Research Council. M.K.S. was supported by the BUPA Foundation.This is the author accepted manuscript. The final version is available from Thieme Publishing Group via http://dx.doi.org/10.1055/s-0034-139331

Effect of the αs1-casein genotype and its interaction with diet degradability on milk production, milk quality, metabolic and endocrinal response of Girgentana goats

We studied interaction between diet degradability and genotype at CSN1S1 locus in lactating goats.•We evaluated productive, metabolic and hormonal response of goats at different αs1-casein genotype.•Little effect of diet degradability and interaction with genotype on production and quality.•Higher milk yield, casein percentage and lower urea in goats with strong alleles at CSN1S1 locus.•Higher tyroid hormones in goats with strong alleles

Translating Material Science into Bone Regenerative Medicine Applications: State-of-The Art Methods and Protocols

In the last 20 years, bone regenerative research has experienced exponential growth thanks to the discovery of new nanomaterials and improved manufacturing technologies that have emerged in the biomedical field. This revolution demands standardization of methods employed for biomaterials characterization in order to achieve comparable, interoperable, and reproducible results. The exploited methods for characterization span from biophysics and biochemical techniques, including microscopy and spectroscopy, functional assays for biological properties, and molecular profiling. This review aims to provide scholars with a rapid handbook collecting multidisciplinary methods for bone substitute R&amp;D and validation, getting sources from an up-to-date and comprehensive examination of the scientific landscape