Development and validation of a risk prediction model to diagnose Barrett's oesophagus (MARK-BE): a case-control machine learning approach

Background: Screening for Barrett’s Oesophagus (BE) relies on endoscopy which is invasive and has a low yield. This study aimed to develop and externally validate a simple symptom and risk-factor questionnaire to screen for patients with BE. Methods: Questionnaires from 1299 patients in the BEST2 case-controlled study were analysed: 880 had BE including 40 with invasive oesophageal adenocarcinoma (OAC) and 419 were controls. This was randomly split into a training cohort of 776 patients and an internal validation cohort of 523 patients. External validation included 398 patients from the BOOST case-controlled study: 198 with BE (23 with OAC) and 200 controls. Identification of independently important diagnostic features was undertaken using machine learning techniques information gain (IG) and correlation based feature selection (CFS). Multiple classification tools were assessed to create a multi-variable risk prediction model. Internal validation was followed by external validation in the independent dataset.This research/study/project was funded by the Charles Wolfson Trust and Guts UK and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. This work was also supported by the CRUK Experimental Cancer Medicine Centre at UCL and the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) at UCL; [203145Z/16/Z]. BEST2 was funded by Cancer Research UK (12088 and 16893)

Latinas in Congress: Lack of Party Support and Disproportionate Underrepresentation

Latinx are the fastest-growing demographic group in the United States, and as such many researchers have looked into Latinas as political candidates and as voters, establishing that Latinas in particular run stronger candidacies than their male counterparts (Bejarano, 2014; Holman & Schneider, 2018; Ocampo & Ray, 2019). Despite this, Latinas hold fewer than 25 percent of seats than Latinos in all levels of government, with their success concentrated under the Democratic Party (Bialik, 2019; Vital Statistics, 2019). In order to determine whether a partisan-gap is present in recruiting and supporting Latina candidates, I looked at four Congressional House primary election cycles from 2012 to 2018 in the Latinx dense states of Arizona, California, Florida, and Texas to see where Latinas were running, where they were successful, and under what party label. My results indicate that there is a significant difference in Latina success by political party, as significantly more Democratic Latinas ran and won their House primaries compared to Republican Latinas, even in red-leaning states and districts during favorable years for Republicans. Additionally, more Republican House primary Latina candidates ran in opposing Party districts and uncontested races compared to Democratic Latina candidates, suggesting that Republican Latinas do not benefit equally from running in strong partisan districts or competitive races. Latina candidates of both parties also seem to be competing against each other in the same districts, suggesting some are friendlier to Latina candidates than others. Latinas offer unique contributions to policy discussions, and in today’s politically hostile anti-woman and anti-Latinx environment, it is more important than ever that Latinas are represented in political office

Signatures of Mutational Processes and Associated Risk Factors in Esophageal Squamous Cell Carcinoma: A Geographically Independent Stratification Strategy?

Cancer Research UKThis is the accepted manuscript. The final version is available at http://www.sciencedirect.com/science/article/pii/S001650851600370X

Barrett's oesophagus and oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) has increased dramatically in Western countries, including the UK, over the past 30 years. It usually presents de novo, but is often preceded by Barrett's oesophagus (BO), a premalignant condition whereby the normal squamous epithelium is replaced by columnar lined epithelium with intestinal metaplasia. The main risk factors for BO include male sex, obesity and chronic gastro-oesophageal reflux of acid and bile. The estimated annual risk of BO progression is 0.3%, increasing substantially, up to 30%, when dysplasia is present. Endoscopic surveillance is recommended to detect neoplastic changes at an early stage and considerable evidence supports endoscopic treatment for confirmed low- and high-grade dysplasia, and intramucosal adenocarcinoma. Most OACs are diagnosed at a more advanced stage requiring CT-PET assessment and multi-modal treatment. Surgical treatment is performed in specialist centres, increasingly combined with cytotoxic chemotherapy and radiotherapy, involving close liaison between members of the multidisciplinary team. Molecular targeted therapies, such as HER2 and VEGFR-inhibitors, are beginning to penetrate clinical practice, but high molecular heterogeneity has impeded progress. In view of the overall dismal survival (<20%) for advanced OAC, there is renewed interest in screening techniques for early detection and intervention of dysplastic BO

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

MUC16 Mutations and Prognosis in Gastric Cancer: A Little Goes a Long Way.

Gastric cancer is a global health problem; although incidence rates are declining, it remains the third most common cause of cancer death worldwide. Patients with advanced disease have limited treatment options, and most will live for less than 2 years. Therefore, exploration of gastric cancer disease biology is warranted to identify new targets for treatment. Recent comprehensive molecular analyses have identified distinct subgroups of gastric cancer that may have therapeutic relevance. With the exception of microsatellite-unstable tumors, however, the potential for genomically guided therapy has not been realized

Nurturing quality science learning and teaching: the impact of a reading group

Teachers are key to the delivery of quality science education experiences in Australian classrooms. In achieving this, there is a need for teachers to be better supported in thinking reflexively and critically about their practice. The Centre for [de-identified] at [de-identified] University took action to address this need by forming a reading group to encourage interested teachers of science from primary and secondary schools to meet regularly to discuss relevant journal articles and implications for their practice. This paper explores how forming a community of practice around a reading group impacted on participants’ approaches to science learning and teaching

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

Body Mass Index, Smoking, and Alcohol and Risks of Barrett’s Esophagus and Esophageal Adenocarcinoma: A UK Prospective Cohort Study

BACKGROUND: The timing of the risk factors cigarette smoking, alcohol and obesity in the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) is unclear. AIMS: To investigate these exposures in the aetiology of BE and EAC in the same population. METHODS: The cohort included 24,068 men and women, aged 39–79 years, recruited between 1993 and 1997 into the prospective EPIC-Norfolk Study who provided information on anthropometry, smoking and alcohol intake. The cohort was monitored until December 2008 and incident cases identified. RESULTS: One hundred and four participants were diagnosed with BE and 66 with EAC. A body mass index (BMI) above 23 kg/m(2) was associated with a greater risk of BE [BMI ≥23 vs. 18.5 to <23, hazard ratio (HR) 3.73, 95 % CI 1.37–10.16], and within a normal BMI, the risk was greater in the higher category (HR 3.76, 95 % CI 1.30–10.85, BMI 23–25 vs. 18.5 to >23 kg/m(2)). Neither smoking nor alcohol intake were associated with risk for BE. For EAC, all BMI categories were associated with risk, although statistically significant for only the highest (BMI >35 vs. BMI 18.5 to <23, HR 4.95, 95 % CI 1.11–22.17). The risk was greater in the higher category of a normal BMI (HR 2.73, 95 % CI 0.93–8.00, p = 0.07, BMI 23–25 vs. 18.5 to >23 kg/m(2)). There was an inverse association with ≥7 units alcohol/week (HR 0.51, 95 % CI 0.29–0.88) and with wine (HR 0.49, 95 % CI 0.23–1.04, p = 0.06, drinkers vs. non-drinkers). CONCLUSIONS: Obesity may be involved early in carcinogenesis and the association with EAC and wine should be explored. The data have implications for aetiological investigations and prevention strategies

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