Search

In this first of three papers, we seek to understand how the new "integrated care" global policy directive, pursuing greater alignment for health and social care systems, will be translated into preparation for practice concerning interprofessional education (IPE) from pre-to-post registration level and for continuing professional development. We ask questions about the implications for leaders and practitioners in the field of IPE and collaborative practice (CP). In seeking to understand this new global policy directive, we explore the plethora of definitions, concepts and perspectives, continuously evolving and at times counterproductive as they try to synthesize complexity, to describe how health and social care systems and practitioners work together. We trace research on how integrated care is understood drawing upon transnational current understandings of integrated working in North America, Europe and the UK. We ask questions of the ambitions of integrated care aligned to forging closer working relationships between health and social care practitioners to tackle modern complex healthcare challenges. In reading the literature we have sought to identify the themes which emerge to direct the field of IPE and CP so that the workforce is prepared to deliver care, as policy makers intended, within locally designed new innovative care systems. We conclude that it remains unclear as to whether these new policy aspirations will achieve the connectivity required, for a supported workforce, committed to working together to deliver care envisaged to help people experiencing complex long-term conditions, disadvantage and health inequalities. In our second paper, we review the developmental pathway for IPE, taking a closer look at preparation for integrated care pathways and collaborative practice, seeking evidence to guide us. Finally, in our third paper, we turn our attention to the implications for the workforce composition, dynamics, and relationships, exploring heightened progressive ever-changing roles and responsibilities, focusing on social work.

In the first of three articles we shared our understanding of integrated care and traced the evolution of interprofessional learning from organic to strategic and systemic, prepared to play its part in the implementation of integrated care. In this third article, joined by Lee-Ann Fenge, we focus on the role of the social worker in integrating care and clarifying their roles in collaboration with other professions. We distinguish between social work as a profession and social care as a field of practice, which includes many professions as well as other occupations. We share the literature on where social work plays a role in integrated care and ask questions about the lack of interprofessional education involving social workers and without whom integrated care cannot succeed.

In the first of three articles, we scanned global and national sources to help understand the concept and scope of integrated care. New policy directives seek closer working relationships between health and social care systems and practitioners to tackle modern challenges relating to the ageing population, poverty, disadvantage, and mental health. We identified that the practitioner workforce has not been fully considered or prepared for large shifts in working practices, often bringing new practitioners' roles to address local needs in newly managed interprofessional working systems for integrated care. In this second article, we consider the major themes identified by our review of integrated care policy to explore their implications for interprofessional learning, drawing on developmental pathways for interprofessional education from organic to strategic and systemic responses, to ask in what ways we will need to prepare our learners for these new ways of delivering integrated care.

Interprofessional education (IPE) interventions aiming to promote collaborative competence and improve the delivery of health and social care processes and outcomes continue to evolve. This paper reports on a protocol for an update review that we will conduct to identify and describe how the IPE evidence base has evolved in the last 7 years. We will identify literature through a systematic search of the following electronic databases: Medline, Embase, CINAHL, Education Source, ERIC, and BEI. We will consider all IPE interventions delivered to health professions students and accredited professionals. Peer-reviewed empirical research studies published in any language from June 2014 onwards will be eligible for inclusion. The outcomes of interest are changes in the reaction, attitudes/perceptions, knowledge/skills acquisition, behaviors, organizational practice, and/or benefits to patients. We will perform each task of screening, critical appraisal, data abstraction, and synthesis using at least two members of the review team. The review will enable an update and comprehensive understanding of the IPE evidence base to inform future IPE developments, delivery and evaluation across education and clinical settings.

Objectives: Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy., Design: A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes., Setting: Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted., Participants: We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined., Results: Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments., Conclusion: We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials., Competing Interests: Competing interests: KR received educational grants from Erbe and Medtronic. RH received research infrastructure support from Medtronic, Cook Endoscopy and Pentax Europe. LBL received research infrastructure support from Medtronic. All other authors disclosed no financial relationships relevant to this article., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability., Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression., Results: Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1)., Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach., Impact: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis., (©2022 American Association for Cancer Research.)

Pancreatic cancer claims over 460,000 victims per year. The carbohydrate antigen (CA) 19-9 test is the blood test used for pancreatic cancer's detection; however, its levels can be raised in symptomatic patients with other non-malignant diseases, or with other tumors in the surrounding area. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has demonstrated exceptional potential in cancer diagnostics, and its clinical implementation could represent a significant step towards early detection. This proof-of-concept study, investigating the use of ATR-FTIR spectroscopy on dried blood serum, focused on the discrimination of both cancer versus healthy control samples, and cancer versus symptomatic non-malignant control samples, as a novel liquid biopsy approach for pancreatic cancer diagnosis. Machine learning algorithms were applied, achieving results of up to 92% sensitivity and 88% specificity when discriminating between cancers ( n = 100) and healthy controls ( n = 100). An area under the curve (AUC) of 0.95 was obtained through receiver operating characteristic (ROC) analysis. Balanced sensitivity and specificity over 75%, with an AUC of 0.83, were achieved with cancers ( n = 35) versus symptomatic controls ( n = 35). Herein, we present these results as demonstration that our liquid biopsy approach could become a simple, minimally invasive, and reliable diagnostic test for pancreatic cancer detection.

Background: A promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data., Methods: The BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett's oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared., Results: NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data., Conclusion: NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT., Trial Registration: ISRCTN54190466 (BOSS) 1 Oct 2009., (© 2021. The Author(s).)

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Many problems in mechanobiology urgently require characterization of the micromechanical properties of cells and tissues. Brillouin light scattering has been proposed as an emerging optical elastography technique to meet this need. However, the information contained in the Brillouin spectrum is still a matter of debate because of fundamental problems in understanding the role of water in biomechanics and in relating the Brillouin data to low-frequency macroscopic mechanical parameters. Here, we investigate this question using gelatin as a model system in which the macroscopic physical properties can be manipulated to mimic all the relevant biological states of matter, ranging from the liquid to the gel and the glassy phase. We demonstrate that Brillouin spectroscopy is able to reveal both the elastic and viscous properties of biopolymers that are central to the structure and function of biological tissues., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Background: Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy)., Objectives: We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b))., Search Methods: We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012., Selection Criteria: Types of studies: RCTs comparing endotherapies with surgery in the treatment of high-grade dysplasia or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately., Types of Participants: patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus. Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent., Data Collection and Analysis: Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9., Main Results: We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies., Authors' Conclusions: This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The aims of this study were to compare neoplasia detection rates for nontargeted biopsies (Seattle protocol) versus acetic acid-targeted biopsies (Portsmouth protocol) during Barrett's surveillance and to explore feasibility, patient/clinician experience, acceptance, and barriers/enablers to study participation and implementation of the acetic acid technique., Methods: This was a mixed-methods feasibility study including a pilot multicenter, randomized, crossover trial with qualitative interviews. Patients under Barrett's surveillance with no history of neoplasia were included. Patients underwent two endoscopies, one with each protocol, 8 weeks apart. Outcomes included recruitment and retention rates, neoplasia yield, and number of biopsies., Results: 200 patients were recruited from 6 centers, and 174 (87.0 %) underwent both procedures. Neoplasia prevalence was 4.7 % (9/192). High grade dysplasia and cancer were detected with both protocols. Five low grade dysplasias were detected (two with acetic acid, four with nontargeted biopsies; one lesion was detected with both techniques). A total of 2139 biopsies were taken in the nontargeted arm and 226 in the acetic acid arm. Both patients and clinicians found the acetic acid technique acceptable. Based on these data, a noninferiority, tandem, crossover trial would require an estimated 2828 patients., Conclusions: We demonstrated the feasibility of performing a crossover endoscopy trial in Barrett's surveillance. Low neoplasia yield makes this design necessary and qualitative results demonstrated patient and clinician acceptance. The reduced numbers of biopsies suggest that the acetic acid technique could result in cost savings, providing the lack of missed pathology can be proven in a fully powered definitive trial., Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aims: Endoscopic resection (ER) is safe and effective for Barrett's esophagus (BE) containing high-grade dysplasia (HGD) or mucosal adenocarcinoma (T1A). The risk of metachronous neoplasia is reduced by ablation of residual BE by using radiofrequency ablation (RFA) or argon plasma coagulation (APC). These have not been compared directly. We aimed to recruit up to 100 patients with BE and HGD or T1A confirmed by ER over 1 year in 6 centers in a randomized pilot study., Methods: Randomization was 1:1 to RFA or APC (4 treatments allowed at 2-month intervals). Recruitment, retention, dysplasia clearance, clearance of benign BE, adverse events, healthcare costs, and quality of life by using EQ-5D, EORTC QLQ-C30, or OES18 were assessed up to the end of the trial at 12 months., Results: Of 171 patients screened, 76 were randomized to RFA (n = 36) or APC (n = 40). The mean age was 69.7 years, and 82% were male. BE was <5 cm (n = 27), 5 to 10 cm (n = 45), and >10 cm (n = 4). Sixty-five patients completed the trial. At 12 months, dysplasia clearance was RFA 79.4% and APC 83.8% (odds ratio [OR] 0.7; 95% confidence interval [CI], 0.2-2.6); BE clearance was RFA 55.8%, and APC 48.3% (OR 1.4; 95% CI, 0.5-3.6). A total of 6.1% (RFA) and 13.3% (APC) had buried BE glands. Adverse events (including stricture rate after starting RFA 3/36 [8.3%] and APC 3/37 [8.1%]) and quality of life scores were similar, but RFA cost $27491 more per case than APC., Conclusion: This pilot study suggests similar efficacy and safety but a cost difference favoring APC. A fully powered non-inferiority trial is appropriate to confirm these findings. (Clinical trial registration number: NCT01733719.)., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus., Methods: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77., Findings: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events., Interpretation: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus., Funding: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cancer is responsible for an extraordinary burden of disease, affecting 90.5 million people worldwide in 2015. Outcomes for these patients are improved when the disease is diagnosed at an early, or even precancerous, stage. Raman spectroscopy is demonstrating results that show its ability to detect the molecular changes that are diagnostic of precancerous and cancerous tissue. This review highlights the new advances occurring in this domain. Areas covered: PubMed searches were undertaken to identify new research in the utilisation of Raman spectroscopy in cancer diagnostics. The areas in which Raman spectroscopy is showing promise are covered, including improving the accuracy of identifying precancerous changes, using the technology in real time, in vivo modalities, the search for a biomarker to aid potential screening and predicting the response of the cancer to the treatment regimen. Expert commentary: Many of the examples in this review are focused on Barrett's oesophagus and oesophageal adenocarcinoma as this is my area of expertise and perfectly exemplifies where Raman spectroscopy could be utilised in clinical practise. The authors discuss the areas where they believe current knowledge is lacking and how Raman spectroscopy could answer the dilemmas that are still faced in the management of cancer.

Interprofessional education (IPE) emphasizes collaborative practice that aims at promoting the working relationships between two or more healthcare professions. However, there is paucity of literature about the effectiveness of IPE program in the healthcare. This systematic review and meta-analysis aims to objectively determine the effectiveness of IPE in that field in terms of the improvement of students' knowledge, skills and attitudes. The databases of OVID, ISI Knowledge of Science, and Medline (PubMed) were searched for the full-text English language articles published during 2000-2016 using the MeSH terms "interprofessional education" AND "healthcare professionals" AND "multi-professional" AND "impact" AND "effectiveness" OR "collaborative practice" OR "medical students" in Endnote X7. A systematic search finally selected 12 articles for detailed review and meta-analysis. The effect summary value of 1.37 with confidence interval of 0.92-1.82 identifies statistically significant effectiveness of intervention by IPE program in healthcare. The Z test value of 5.99, significant at 5% level of significance, also shows a significant impact of IPE intervention as calculated by the random-effects model. This meta-analysis shows a positive impact and effectiveness of educational intervention by IPE program in various disciplines of healthcare. However, analysis of further clinical trials may be helpful in identifying the effect of IPE program on the students' clinical competence., (Copyright © 2018. Published by Elsevier Taiwan.)

Background: Development of a nonendoscopic test for Barrett's esophagus would revolutionize population screening and surveillance for patients with Barrett's esophagus. Swallowed cell collection devices have recently been developed to obtain cytology brushings from the esophagus: automated detection of neoplasia in such samples would enable large-scale screening and surveillance., Methods: Fourier transform infrared (FTIR) spectroscopy was used to develop an automated tool for detection of Barrett's esophagus and Barrett's neoplasia in esophageal cell samples. Cytology brushings were collected at endoscopy, cytospun onto slides and FTIR images were measured. An automated cell recognition program was developed to identify individual cells on the slide., Results: Cytology review and contemporaneous histology was used to inform a training dataset containing 141 cells from 17 patients. A classification model was constructed by principal component analysis fed linear discriminant analysis, then tested by leave-one-sample-out cross validation. With application of this training model to whole slide samples, a threshold voting system was used to classify samples according to their constituent cells. Across the entire dataset of 115 FTIR maps from 66 patients, whole samples were classified with sensitivity and specificity respectively as follows: normal squamous cells 79.0% and 81.1%, nondysplastic Barrett's esophagus cells 31.3% and 100%, and neoplastic Barrett's esophagus cells 83.3% and 62.7%., Conclusions: Analysis of esophageal cell samples can be performed with FTIR spectroscopy with reasonable sensitivity for Barrett's neoplasia, but with poor specificity with the current technique.

Background and Study Aims: Barrett's esophagus is a potentially pre-cancerous condition, affecting 375,000 people in the UK. Patients receive a 2-yearly endoscopy to detect cancerous changes, as early detection and treatment results in better outcomes. Current treatment requires random mapping biopsies along the length of Barrett's, in addition to biopsy of visible abnormalities. As only 13 % of pre-cancerous changes appear as visible nodules or abnormalities, areas of dysplasia are often missed. Acetic acid chromoendoscopy (AAC) has been shown to improve detection of pre-cancerous and cancerous tissue in observational studies, but no randomized controlled trials (RCTs) have been performed to date., Patients and Methods: A "tandem" endoscopy cross-over design. Participants will be randomized to endoscopy using mapping biopsies or AAC, in which dilute acetic acid is sprayed onto the surface of the esophagus, highlighting tissue through an whitening reaction and enhancing visibility of areas with cellular changes for biopsy. After 4 to 10 weeks, participants will undergo a repeat endoscopy, using the second method. Rates of recruitment and retention will be assessed, in addition to the estimated dysplasia detection rate, effectiveness of the endoscopist training program, and rates of adverse events (AEs). Qualitative interviews will explore participant and endoscopist acceptability of study design and delivery, and the acceptability of switching endoscopic techniques for Barrett's surveillance., Results: Endoscopists' ability to diagnose dysplasia in Barrett's esophagus can be improved. AAC may offer a simple, universally applicable, easily-acquired technique to improve detection, affording patients earlier diagnosis and treatment, reducing endoscopy time and pathology costs. The ABBA study will determine whether a crossover "tandem" endoscopy design is feasible and acceptable to patients and clinicians and gather outcome data to power a definitive trial.

To improve outcomes for patients with cancer, in terms of both survival and a reduction in the morbidity and mortality that results from surgical resection and treatment, there are two main areas that require improvement. Accurate early diagnosis of the cancer, at a stage where curative and, ideally, minimally invasive treatment is achievable, is desired as well as identification of tumor margins, lymphatic and distant disease, enabling complete, but not unnecessarily extensive, resection. Optical imaging is making progress in achieving these aims. This review discusses the principles of optical imaging, focusing on fluorescence and spectroscopy, and the current research that is underway in GI tract carcinomas.

Objective: Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA., Design: We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk., Results: We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 ( MGST1 ); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10 -5 ) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1 . Three such variants were associated with similar elevations in OA risk., Conclusions: This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Interprofessional collaborative practice is widely documented as a strategy to improve quality of healthcare. To develop collaborative practitioners, educators need interprofessional curricula with proper cognitive demand and methods of delivery and assessment. The University of the Western Cape in South Africa incorporated an Interprofessional Core Courses Curriculum for all undergraduate students enrolled in the health sciences faculty. The objective of this study was to analyse the curriculum content to determine its cognitive rigor. Cognitive rigor can be measured by the quantitative content analysis method using the Depth of Knowledge (DOK) framework. This approach tests whether the rigor of instructional activities and assessments is aligned with learning outcomes. The curriculum content evaluated in this study found that assessment activities were less demanding than instructional activities and infrequently aligned with learning outcomes. This approach may be useful to other educators seeking to evaluate and plan interprofessional curriculum.

Background and study aims  Acetic acid chromoendoscopy (AAC) enhances the ability to correctly identify Barrett's neoplasia, and is increasingly used by both expert and nonexpert endoscopists. Despite its increasing use, there is no validated training strategy to achieve competence. The aims of our study were to develop a validated training tool in AAC-assisted lesion recognition, to assess endoscopists' baseline knowledge of AAC-assisted lesion recognition, and to evaluate the efficacy and impact of this training tool. Methods  A validated assessment of 40 images and 20 videos was developed. A total of 13 endoscopists with experience of Barrett's endoscopy but no formal training in AAC were recruited to the study. Participants underwent: baseline assessment 1, online training, assessment 2, interactive seminar, assessment 3. Results  Baseline assessment demonstrated a sensitivity of 83 % and a negative predictive value (NPV) of 83 %. The online training intervention significantly improved sensitivity to 95 % and NPV to 94 % ( P  < 0.01). Further improvement was seen after a 1-day interactive seminar including live cases, with sensitivity increasing to 98 % and NPV to 97 %. Conclusions  The data demonstrate the need for training in AAC-assisted lesion recognition as baseline performance, even by Barrett's experts, was poor. The online training and testing tool for AAC for Barrett's neoplasia was successfully developed and validated. The training intervention improved performance of endoscopists to meet ASGE PIVI standards. The training tool increases the endoscopist's degree of confidence in the use of AAC. The training tool also leads to shift in attitudes of endoscopists from Seattle protocol towards AAC-guided biopsy protocol for Barrett's surveillance., (© Georg Thieme Verlag KG Stuttgart · New York.)

Whilst interest in interprofessional learning (IPL) in practice contexts has grown in recent years, the complexities involved have led many universities to rely on IPL in the classroom, online, and/or simulated contexts. Curtin University's Faculty of Health Sciences has successfully implemented a multi-award winning, large-scale Interprofessional Practice Programme. This programme, which began with five small pilots in 2009, provides team-based interprofessional practice placements for over 550 students from nine professions per annum. Drawing on both the literature and Curtin University's experience, this Interprofessional Education and Practice Guide aims to assist university and practice-based educators to "weigh the case" for introducing team-based interprofessional placements. The key lessons learned at Curtin University are identified to offer guidance to others towards establishing a similar programme for students during their prequalifying courses in health, social care, and related fields.

Background: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma., Methods: We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10 -8 ). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms., Findings: Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10 -10 ), MSRA (rs17749155; p=5·2 × 10 -10 ), LINC00208 and BLK (rs10108511; p=2·1 × 10 -9 ), KHDRBS2 (rs62423175; p=3·0 × 10 -9 ), TPPP and CEP72 (rs9918259; p=3·2 × 10 -9 ), TMOD1 (rs7852462; p=1·5 × 10 -8 ), SATB2 (rs139606545; p=2·0 × 10 -8 ), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10 -8 ). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10 -8 ) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10 -6 ) belonged to muscle cell differentiation and to mesenchyme development and differentiation., Interpretation: Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies., Funding: US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Across the globe, a "fit for purpose" health professional workforce is needed to meet health needs and challenges while capitalizing on existing resources and strengths of communities. However, the socio-economic impact of educating and deploying a fit for purpose health workforce can be challenging to evaluate. In this paper, we provide a brief overview of six promising strategies and interventions that provide context-relevant health professional education within the health system. The strategies focused on in the paper are:1. Distributed community-engaged learning: Education occurs in or near underserved communities using a variety of educational modalities including distance learning. Communities served provide input into and actively participate in the education process.2. Curriculum aligned with health needs: The health and social needs of targeted communities guide education, research and service programmes.3. Fit for purpose workers: Education and career tracks are designed to meet the needs of the communities served. This includes cadres such as community health workers, accelerated medically trained clinicians and extended generalists.4. Gender and social empowerment: Ensuring a diverse workforce that includes women having equal opportunity in education and are supported in their delivery of health services.5. Interprofessional training: Teaching the knowledge, skills and attitudes for working in effective teams across professions.6. South-south and north-south partnerships: Sharing of best practices and resources within and between countries.In sum, the sharing of resources, the development of a diverse and interprofessional workforce, the advancement of primary care and a strong community focus all contribute to a world where transformational education improves community health and maximizes the social and economic return on investment.

Background: Interprofessional education (IPE) aims to bring together different professionals to learn with, from, and about one another in order to collaborate more effectively in the delivery of safe, high-quality care for patients/clients. Given its potential for improving collaboration and care delivery, there have been repeated calls for the wider-scale implementation of IPE across education and clinical settings. Increasingly, a range of IPE initiatives are being implemented and evaluated which are adding to the growth of evidence for this form of education., Aim: The overall aim of this review is to update a previous BEME review published in 2007. In doing so, this update sought to synthesize the evolving nature of the IPE evidence., Methods: Medline, CINAHL, BEI, and ASSIA were searched from May 2005 to June 2014. Also, journal hand searches were undertaken. All potential abstracts and papers were screened by pairs of reviewers to determine inclusion. All included papers were assessed for methodological quality and those deemed as "high quality" were included. The presage-process-product (3P) model and a modified Kirkpatrick model were employed to analyze and synthesize the included studies., Results: Twenty-five new IPE studies were included in this update. These studies were added to the 21 studies from the previous review to form a complete data set of 46 high-quality IPE studies. In relation to the 3P model, overall the updated review found that most of the presage and process factors identified from the previous review were further supported in the newer studies. In regard to the products (outcomes) reported, the results from this review continue to show far more positive than neutral or mixed outcomes reported in the included studies. Based on the modified Kirkpatrick model, the included studies suggest that learners respond well to IPE, their attitudes and perceptions of one another improve, and they report increases in collaborative knowledge and skills. There is more limited, but growing, evidence related to changes in behavior, organizational practice, and benefits to patients/clients., Conclusions: This updated review found that key context (presage) and process factors reported in the previous review continue to have resonance on the delivery of IPE. In addition, the newer studies have provided further evidence for the effects on IPE related to a number of different outcomes. Based on these conclusions, a series of key implications for the development of IPE are offered.

Barrett's oesophagus is a condition characterized by a change in the lining of the oesophagus that markedly increases the risk of adenocarcinoma. We demonstrate the first site-matched application of Brillouin microscopy, Raman microscopy and FTIR micro-spectroscopic imaging to ex-vivo epithelial tissue - Barrett's oesophagus. The mechanical and chemical characters of the epithelium were assessed in histological sections from a patient subjected to endoscopic oesophageal biopsy. Previous studies have shown that both these properties change within the oesophageal wall, owing to the presence of distinct cellular and extracellular constituents which are putatively affected by oesophageal cancer. Brillouin microscopy enables maps of elasticity of the epithelium to be obtained, whilst Raman and FTIR imaging provide 'chemical images' without the need for labelling or staining. This site-matched approach provides a valuable platform for investigating the structure, biomechanics and composition of complex heterogeneous systems. A combined Brillouin-Raman device has potential for in-vivo diagnosis of pathology. First application of site-matched micro Brillouin, Raman and FTIR spectroscopic imaging to epithelial tissue in Barrett's oesophagus., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Emergency laparotomy (EL) is a procedure that puts a strain on healthcare resources and is associated with a significant morbidity and mortality. Despite these implications little improvement in the outcome of patients undergoing this procedure has been made in the UK over the last few decades. A delay in transferring patients to theatre has been shown to negatively affect outcome of EL. A prospective case-control study was carried out to evaluate which preoperative factors may contribute towards a delay in theatre transfer., Methods: The time between decision to operate and anaesthetic start time was recorded for all patients undergoing EL between April and September 2013 at Gloucestershire Royal Infirmary. Patient selection criteria were based on the National Emergency Laparotomy Audit guidelines. Patients were divided into two groups depending on whether the transfer to theatre was delayed or not. Binary logistic regression analysis was performed on perioperative factors to determine independent predictors of delay., Results: A total of 84 EL were included for analyses with 31 classified as delayed. In the delayed group time for theatre transfer was increased at 6.9 vs. 2.3 h (p < 0.005) respectively. Unavailability of emergency theatres due to other cases taking priority was the most frequent cause for delay (n = 24). On binary logistic regression analysis, indication for laparotomy (OR 4.96, CI 1.4-17.6, p < 0.05), patient age (OR 1.04, CI 1.00-1.07, p < 0.04) and presence of a consultant surgeon (OR 0.16, CI 0.03-0.79, p < 0.03) were found to be independent predictors of delay in EL., Conclusion: In this study, factors that were associated with a delay in commencing EL were operative indication and patient age whereas the presence of a consultant surgeon made a delay less likely. These findings may highlight points of interest for researchers analysing and auditing the provision of EL in the UK., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Objectives: The absolute annual risk of patients with Barrett's oesophagus (BO) developing oesophageal adenocarcinoma (OAC) is ≤ 0.5%. Screening BO patients for malignant progression using endoscopic surveillance is widely practised. To assess the efficacy and cost-effectiveness of this, we developed a protocol for a randomized controlled trial of surveillance versus 'at need' endoscopy., Methods: In a multicentre trial, 3400 BO patients randomized to either 2-yearly endoscopic surveillance or 'at need' endoscopy will be followed up for 10 years. Urgent endoscopy will be offered to all patients who develop symptoms of dysphagia, unexplained weight loss > 7lb (3.2 kg), iron deficiency anaemia, recurrent vomiting, or worsening upper gastrointestinal symptoms. Participants must have endoscopically and histologically confirmed BO, with circumferential BO ≥ 1 cm or maximal tongue/island length ≥ 2 cm. Candidates with existing oesophageal high-grade dysplasia or cancer, or previous upper gastrointestinal cancer will be excluded. Primary outcome will be overall survival. Secondary outcomes will be cost effectiveness (cost per life year saved and quality adjusted life years); cancer-specific survival; time to OAC diagnosis and stage at diagnosis; morbidity and mortality related to any interventions; and frequency of endoscopy., Conclusions: This randomized trial will provide data to evaluate the efficacy and cost-effectiveness of screening BO patients for OAC., (© The Author(s) 2015.)

Objectives: Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD)., Methods: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations., Results: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients., Conclusions: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

We report results from a study utilizing infrared spectral cytopathology (SCP) to detect abnormalities in exfoliated esophageal cells. SCP has been developed over the past decade as an ancillary tool to classical cytopathology. In SCP, the biochemical composition of individual cells is probed by collecting infrared absorption spectra from each individual, unstained cell, and correlating the observed spectral patterns, and the variations therein, against classical diagnostic methods to obtain an objective, machine-based classification of cells. In the past, SCP has been applied to the analysis and classification of cells exfoliated from the cervix and the oral cavity. In these studies, it was established that SCP can distinguish normal and abnormal cell types. Furthermore, SCP can differentiate between truly normal cells, and cells with normal morphology from the vicinity of abnormalities. Thus, SCP may be a valuable tool for the screening of early stages of dysplasia and pre-cancer.

Background: The uptake of minimally invasive oesophagectomy (MIO) in the UK has increased dramatically in recent years. Post-oesophagectomy diaphragmatic hernias (PODHs) are rare, but may be influenced by the type of approach to resection. The aim of this study was to compare the incidence of symptomatic PODH following open and MIO in a UK specialist centre., Methods: Consecutive patients undergoing oesophagectomy for malignant disease between 1996 and 2012 were included. A standardised, radical approach to the abdominal phase was employed, irrespective of the type of procedure undertaken. Patient demographics, details of surgery and post-operative complications were collected from patient records and a prospective database., Results: A total of 273 oesophagectomies were performed (205 open; 68 MIO). There were 62 hybrid MIOs (laparoscopic abdomen and thoracotomy) and six total MIOs. Seven patients required conversion and were analysed as part of the open cohort. Nine patients (13.2 %) developed a PODH in the MIO cohort compared with two patients (1.0 %) in the open cohort, (p < 0.001). Five patients developed hernias in the early post-operative period (days 2-10): all following MIO. Both PODHs in the open cohort occurred following transhiatal oesophagectomy. All PODHs were symptomatic and required surgical repair. CT thorax confirmed the diagnosis in 10 patients. Seven hernias were repaired laparoscopically, including two cases in the early post-operative period. PODHs were repaired using the following techniques: suture (n = 6), mesh reinforcement (n = 4) and omentopexy to the anterior abdominal wall without hiatal closure (n = 1). There were two recurrences (18 %)., Conclusions: The incidence of symptomatic PODH may be higher following MIO compared to open surgery. The reasons for this are unclear and may not be completely explained by the reduction in adhesion formation. Strategies such as fixation of the conduit to the diaphragm and omentopexy to the abdominal wall may reduce the incidence of herniation.

Background & Aims: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations., Methods: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls., Results: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9))., Conclusions: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Barrett's oesophagus shows appearances described as 'intestinal metaplasia', in structures called 'crypts' but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands., Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry., Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell., Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Endoscopic resection (ER) is emerging as a curative technique in patients with high-grade dysplasia (HGD), intramucosal cancer (IMC), and early submucosal cancer (T1sm1) within Barrett's oesophagus., Methods: This consecutive case series of 72 patients with HGD or IMC reports outcomes of ER, with or without mucosal ablation, in a single institution after a median of 38 months follow-up between 2004 and 2011. The primary outcome was disease progression to submucosal invasion. Secondary outcomes included disease regression, the effect of ER on staging compared to biopsy and procedure-related complications., Results: 72 patients (mean age 73.0 - range 52.0-93.0) were treated by ER ± ablative therapy with curative intent for HGD (88% patients) or IMC (12%). 38% had one or more severe systemic co-morbidities. A median of 4 (1-11) procedures were undertaken per patient. In addition to ER, 43% of patients were treated with argon plasma coagulation, 17% with radiofrequency ablation, and 11% with photodynamic therapy. 8 (13%) patients with HGD at baseline and 0 (0%) with IMC progressed to invasive carcinoma. The median time to progression was 26.3 and 12.6 months respectively. 51% patients experienced disease regression. Disease staging was upgraded by ER in 27% of patients., Discussion: This case series reports on a minimally invasive technique in an elderly population with multiple co-morbidities, demonstrating disease regression with long-term follow-up., Conclusion: ER ± ablation is an effective and potentially curative option for patients with HGD or IMC. The benefit of endoscopic resection for disease staging was clearly demonstrated., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

The management of Barrett's oesophagus and associated neoplasia has evolved considerably in recent years. Modern endoscopic strategies including endoscopic resection and mucosal ablation can eradicate dysplastic Barrett's and prevent progression to invasive oesophageal cancer. However, several aspects of Barrett's management remain controversial including the stage in the disease process at which to intervene, and the choice of endoscopic or surgical therapy. A review of articles pertaining to the management of Barrett's oesophagus with or without associated neoplasia, was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Embase and Cochrane databases were searched to identify literature relevant to eight pre-defined areas of clinical controversy. The following search terms were used: Barrett's oesophagus; dysplasia; intramucosal carcinoma; endotherapy; endoscopic resection; ablation; oesophagectomy. A significant body of evidence exists to support early endoscopic therapy for high-grade dysplasia (HGD). Although not supported by randomised controlled trial evidence, endoscopic therapy is now favoured ahead of oesophagectomy for most patients with HGD. Focal intramucosal (T1a) carcinomas can be managed effectively using endoscopic and surgical therapy, however surgery should be considered the first line therapy where there is submucosal invasion (T1b). Treatment of low grade dysplasia is not supported at present due to widespread over-reporting of the disease. The role of surveillance endoscopy in non-dysplastic Barrett's remains controversial.

The application of semi-supervised methodology to improve the classification performance of a Raman spectroscopic probe for the diagnosis of oesophageal cancer is described. It is well known that gold standard histopathology diagnosis can be highly subjective, particularly for diseases which have several stages, such as cancer. A 'consensus' pathology decision can be obtained to ensure a robust gold standard by obtaining a diagnosis from several experts and samples are then only included in standard classification models if they have been assigned the same pathology by all experts. This can result in a significant number of samples that are excluded from the analysis as no consensus was reached. In this work semi-supervised methodology was used to extend Principal Component Analysis followed by Linear Discriminant Analysis (PCA-LDA) to incorporate samples without consensus pathology when discriminating between benign and oesophageal cancer specimens measured using a Raman endoscopic probe ex vivo. We demonstrate that a fully semi-supervised approach improved sensitivity and specificity from 73% and 78% (PCA-LDA) to 78% and 84% (semi-supervised) for discriminating between intestinal metaplasia and dysplasia and from 44% and 66% (PCA-LDA) to 63% and 72% (semi-supervised) when discriminating between intestinal metaplasia and low grade dysplasia.

The incidence of oesophageal adenocarcinoma has increased by 500% over the past 30 years [1]. Improved understanding of the mechanisms of neoplastic progression provides an opportunity to reverse this trend. A thorough review of emerging strategies aiming to prevent the formation of oesophageal malignancy is presented. These include dietary modification, chemoprevention, early endoscopic identification and treatment of premalignant disease, and the potential for a non-endoscopic screening test. Oesophageal adenocarcinoma has become a major public health problem in the West and it is essential that clinicians are fully informed of risk reduction strategies so that they can be actively promoted in the community., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Background: Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus., Objective: To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma., Design: A total of 798 one-second spectra were measured from 673 ex vivo esophageal tissue samples, collected from patients with Barrett's esophagus by using a novel endoscopic Raman probe. Spectra were correlated with consensus histopathology. Multivariate analysis was used to evaluate the classification accuracy of ERS ex vivo., Setting: Probe measurements were conducted in the laboratory. Tissue specimens were collected from the operating theatre and endoscopy unit., Patients: Tissue from 62 patients was included in the study., Interventions: Endoscopic biopsy/resection or esophagectomy was performed where indicated clinically., Main Outcome Measurement: Diagnostic performance of ERS for detection of HGD and esophageal adenocarcinoma., Results: ERS demonstrated a sensitivity of 86% and a specificity of 88% for detecting HGD and adenocarcinoma. The ability to grade dysplasia and differentiate intestinal metaplasia from nonintestinal metaplasia columnar-lined esophagus was also demonstrated. Diagnostic classification was based on objective measurement of the biochemical profile of different tissue types. The potential for combination ERS and narrow-band imaging was also demonstrated., Limitations: Measurements were taken from ex vivo tissue., Conclusion: ERS enables rapid, accurate, objective diagnosis of superficial esophageal disease (metaplasia, dysplasia, intramucosal cancer) in clinically applicable time scales., (Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.)

Designing the learning environment for the health care professionals of tomorrow is less than complete unless and until it includes interprofessional education (IPE). Progress depends on establishing a shared understanding of IPE between architects and teachers as the dialogue between them during the forum confirmed. My brief presentation provided no more than the catalyst. This paper goes further. It locates IPE within a coherent, consistent and pervasive rationale distilled over time from its roots in different countries and fields of practice, including the formulation of objectives, the adaptation of a repertoire of learning methods, the adoption of a definition and values and the framing of principle and competency-based outcomes, before alerting readers to some of the many complexities during the planning process.

Light interacts with tissue in a number of ways including, elastic and inelastic scattering, reflection and absorption, leading to fluorescence and phosphorescence. These interactions can be used to measure abnormal changes in tissue. Initial optical biopsy systems have potential to be used as an adjunct to current investigative techniques to improve the targeting of blind biopsy. Future prospects with molecular-specific techniques may enable objective optical detection providing a real-time, highly sensitive and specific measurement of the histological state of the tissue. Raman spectroscopy has the potential to identify markers associated with malignant change and could be used as diagnostic tool for the early detection of precancerous and cancerous lesions in vivo. The clinical requirements for an objective, non-invasive, real-time probe for the accurate and repeatable measurement of pathological state of the tissue are overwhelming. This paper discusses some of the recent advances in the field., (Copyright © 2013 Elsevier B.V. All rights reserved.)