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We aimed to develop a computer aided characterization system that can support the diagnosis of dysplasia in Barrett's esophagus (BE) on magnification endoscopy.Videos were collected in high-definition magnification white light and virtual chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic/ non-dysplastic BE (NDBE) from 4 centres. We trained a neural network with a Resnet101 architecture to classify frames as dysplastic or non-dysplastic. The network was tested on three different scenarios: high-quality still images, all available video frames and a selected sequence within each video.57 different patients each with videos of magnification areas of BE (34 dysplasia, 23 NDBE) were included. Performance was evaluated using a leave-one-patient-out cross-validation methodology. 60,174 (39,347 dysplasia, 20,827 NDBE) magnification video frames were used to train the network. The testing set included 49,726 iscan-3/optical enhancement magnification frames. On 350 high-quality still images the network achieved a sensitivity of 94%, specificity of 86% and Area under the ROC (AUROC) of 96%. On all 49,726 available video frames the network achieved a sensitivity of 92%, specificity of 82% and AUROC of 95%. On a selected sequence of frames per case (total of 11,471 frames) we used an exponentially weighted moving average of classifications on consecutive frames to characterize dysplasia. The network achieved a sensitivity of 92%, specificity of 84% and AUROC of 96% The mean assessment speed per frame was 0.0135 seconds (SD, + 0.006) CONCLUSION: Our network can characterize BE dysplasia with high accuracy and speed on high-quality magnification images and sequence of video frames moving it towards real time automated diagnosis.

Study DesignRetrospective cohort studyObjectivesTo investigate the effect of perioperative gabapentin administration on postoperative pain and opioid use in elderly patients after elective posterior lumbar fusion.MethodsThis was a single-center study of patients over the age of 65 who underwent elective posterior lumbar fusion. The cohort was stratified into two groups based on perioperative gabapentin administration defined as use both in the immediate preoperative period and postoperatively during hospitalization. Mean daily visual analogue scale (VAS) pain scores and mean daily morphine equivalent dosage (MED) during the postoperative hospital stay were compared between these groups using traditional regression and inverse probability weighting.ResultsThere were 350 patients who received gabapentin perioperatively and 78 patients who did not receive gabapentin. Multivariate regression did not demonstrate a difference in daily MED (ß=-6.6 mg, p=0.816) or daily pain scores (ß=0.04, p=0.257) averaged over the first seven postoperative days. Sub-analysis stratifying by each individual postoperative day also did not demonstrate a difference in MED or pain scores.ConclusionThis study did not find perioperative gabapentin administration to be beneficial in reducing postoperative VAS pain scores or opioid use in the acute postoperative period for elderly patients undergoing posterior lumbar fusion. These findings are consistent with recent literature suggesting gabapentin is of minimal benefit in postoperative multimodal analgesia regimens.Level of Evidence3

Background ContextPostoperative delirium is a clinically significant acute disorder of consciousness especially prevalent in older adult patients, of which more than 100,000 per year undergo spinal fusion surgery. There are no proven preventative therapies, and delirium is associated with increased postoperative complications, functional decline, morbidity, and mortality.PurposeTo identify perioperative risk factors for postoperative delirium (POD) after lumbar spinal fusion procedures in patients aged 65 or older.Study DesignRetrospective ReviewPatient Sample702 patients who underwent lumbar spinal fusion surgery from 11/13/2017 to 1/30/2021.Outcome MeasuresThe primary outcome was the presence of postoperative delirium assessed by the Delirium Observation Screening Scale (DOSS) and Confusion Assessment Method for the ICU (CAM-ICU).MethodsDemographic, surgical, and perioperative data were obtained from the electronic medical records. The primary outcome was presence of postoperative delirium. Univariate and multivariate analyses were performed. A binomial logistic regression model was designed using a custom written MATLAB script.ResultsOf the 702 patients included in the study, 173 (24.6%) developed POD. Our analysis revealed that older age (p < 0.001), lower preoperative hemoglobin (p < 0.001), and higher ASA grade (p < 0.001), were significant preoperative risk factors for developing POD. The only significant intraoperative risk factor was a higher number of spinal levels that were instrumented (p < 0.001). Higher pain scores on postoperative day 1 (p < 0.001), and lower postoperative hemoglobin (p < 0.001) were associated with increased POD; as were ICU admission (p < 0.001) and increased length of ICU stay (p < 0.001). Patients who developed POD had a longer hospital stay (p < 0.001) with lower rates of discharge to home as opposed to an inpatient facility (p < 0.001).ConclusionsRisk factors for older adults undergoing lumbar spinal fusion surgery include advanced age, lower preoperative and postoperative hemoglobin, higher ASA grade, greater extent of surgery, and higher postoperative pain scores. Patients with delirium had a higher incidence of postoperative ICU admission, increased length of stay, decreased likelihood of discharge to home and increased mortality, all consistent with prior studies. Further studies will determine whether adequate management of anemia and pain lead to a reduction in the incidence of postoperative delirium in these patients.

Critical details remain unresolved about the organization of the human auditory cortical hierarchy and its relationship to higher order brain networks. We investigated this organization using diffusion map embedding (DME) applied to resting state intracranial electroencephalography (iEEG) obtained in neurosurgical patients. DME was applied to functional connectivity measured between regions of interest (ROIs). ROIs exhibited a hierarchical organization, symmetric between the two hemispheres and robust to the choice of iEEG frequency band, connectivity metric, and imaging modality. Tight clusters of canonical auditory and prefrontal ROIs were maximally segregated in embedding space. Clusters consistent with ventral and dorsal auditory processing streams were paralleled by a cluster suggestive of a third stream linking auditory and limbic structures. Portions of anterior temporal cortex were characterized as global hubs. This approach lays the foundation for identifying network changes during active speech and language processing and elucidating mechanisms underlying disorders of auditory processing.

A clear understanding of the potential complications or adverse events (AEs) of diagnostic endoscopy is an essential component of being an endoscopist. Creating a culture of safety and prevention of AEs should be part of routine endoscopy practice. Appropriate patient selection for procedures, informed consent, periprocedure risk assessments and a team approach, all contribute to reducing AEs. Early recognition, prompt management and transparent communication with patients are essential for the holistic and optimal management of AEs. In this review, we discuss the complications of diagnostic upper gastrointestinal endoscopy, including their recognition, treatment and prevention.

A 6-year-old boy with autistic spectrum disorder was diagnosed with tuberculosis infection following contact tracing of his mother who had isoniazid-resistant pulmonary tuberculosis. He progressed to develop mediastinal lymphadenopathy causing a persistent cough. He was too small to undergo endobronchial ultrasound-guided biopsy. As an alternative, he underwent esophageal endoscopic ultrasound-guided biopsy, leading to confirmation of the diagnosis. We believe this approach to diagnostic biopsy is underrecognized in pediatric practice, and highlight its utility with this case and a brief literature review.

The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase.External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance.A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed.1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS.In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.

Substance use disorders (SUDs) are heterogenous and complex, making the development of translationally predictive rodent and non-human primate models to uncover their neurobehavioral underpinnings difficult. Neuroscience-focused outcomes have become highly prevalent, and with this, the notion that SUDs are disorders of the brain embraced as a dominant theoretical orientation to understand SUD etiology and treatment. These efforts, however, have led to few efficacious pharmacotherapies, and in some cases (as with cocaine or methamphetamine), no pharmacotherapies have translated from preclinical models for clinical use. In this review and theoretical commentary, we first describe the development of animal models of SUDs from a historical perspective. We then define and discuss three logical fallacies including 1) circular explanation, 2) affirming the consequent, and 3) reification that can apply to developed models. We then provide three case examples in which conceptual or logical issues exist in common methods (i.e., behavioral economic demand, escalation, and reinstatement). Alternative strategies to refocus behavioral models are suggested for the field in an attempt to better bridge the translational divide between animal models and the clinical condition of SUDs.

BACKGROUND AND AIMS: Seattle protocol biopsies for Barrett's Esophagus (BE) surveillance are labour intensive with low compliance. Dysplasia detection rates vary, leading to missed lesions. This can potentially be offset with computer aided detection. We have developed convolutional neural networks (CNNs) to identify areas of dysplasia and where to target biopsy. METHODS: 119 Videos were collected in high-definition white light and optical chromoendoscopy with i-scan (Pentax Hoya, Japan) imaging in patients with dysplastic and non-dysplastic BE (NDBE). We trained an indirectly supervised CNN to classify images as dysplastic/non-dysplastic using whole video annotations to minimise selection bias and maximise accuracy. The CNN was trained using 148,936 video frames (31 dysplastic patients, 31 NDBE, two normal esophagus), validated on 25,161 images from 11 patient videos and tested on 264 iscan-1 images from 28 dysplastic and 16 NDBE patients which included expert delineations. To localise targeted biopsies/delineations, a second directly supervised CNN was generated based on expert delineations of 94 dysplastic images from 30 patients. This was tested on 86 i-scan one images from 28 dysplastic patients. FINDINGS: The indirectly supervised CNN achieved a per image sensitivity in the test set of 91%, specificity 79%, area under receiver operator curve of 93% to detect dysplasia. Per-lesion sensitivity was 100%. Mean assessment speed was 48 frames per second (fps). 97% of targeted biopsy predictions matched expert and histological assessment at 56 fps. The artificial intelligence system performed better than six endoscopists. INTERPRETATION: Our CNNs classify and localise dysplastic Barrett's Esophagus potentially supporting endoscopists during surveillance. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:10 issue:6 pages:528-537 ispartof: location:England status: published

Simple Summary Gastric adenocarcinoma has remained a highly lethal disease. Awareness and recognition of preneoplastic conditions (including gastric atrophy and intestinal metaplasia) using high-resolution white-light endoscopy as well as chromoendoscopy is therefore essential. Helicobacter pylori, a class I carcinogen, remains the main contributor to the development of sporadic distal gastric neoplasia. Management of early gastric neoplasia with endoscopic resections should be in line with standard indications. A multidisciplinary approach to any case of an early gastric neoplasia is imperative. Hereditary forms of gastric cancer require a tailored approach and individua-lized surveillance. Abstract The mortality rates of gastric carcinoma remain high, despite the progress in research and development in disease mechanisms and treatment. Therefore, recognition of gastric precancerous lesions and early neoplasia is crucial. Two subtypes of sporadic gastric cancer have been recognized: cardia subtype and non-cardia (distal) subtype, the latter being more frequent and largely associated with infection of Helicobacter pylori, a class I carcinogen. Helicobacter pylori initiates the widely accepted Correa cascade, describing a stepwise progression through precursor lesions from chronic inflammation to gastric atrophy, gastric intestinal metaplasia and neoplasia. Our knowledge on He-licobacter pylori is still limited, and multiple questions in the context of its contribution to the pathogenesis of gastric neoplasia are yet to be answered. Awareness and recognition of gastric atrophy and intestinal metaplasia on high-definition white-light endoscopy, image-enhanced endoscopy and magnification endoscopy, in combination with histology from the biopsies taken accurately according to the protocol, are crucial to guiding the management. Standard indications for endoscopic resections (endoscopic mucosal resection and endoscopic submucosal dissection) of gastric dysplasia and intestinal type of gastric carcinoma have been recommended by multiple societies. Endoscopic evaluation and surveillance should be offered to individuals with an inherited predisposition to gastric carcinoma.

BACKGROUND: Gastric antral vascular ectasia (GAVE) is a rare cause of gastrointestinal bleeding, often causing iron deficiency anaemia. Previous studies have looked at the management of this with argon plasma coagulation, laser therapy and endoscopic band ligation. METHODS: This was a single-centre prospective study to evaluate the efficacy and safety of radiofrequency ablation (RFA) in patients with GAVE with persistent anaemia refractory to at least one session of first-line endoscopic therapy. Patients were treated with a through-the-scope (TTS) radiofrequency catheter at two endoscopic sessions six weeks apart. The primary outcome was change in haemoglobin at six months posttreatment. The secondary outcomes were reduction in blood or iron requirements, endoscopic surface area regression and complications. RESULTS: Twenty patients were treated. The mean change in haemoglobin at six months was +12.6 g/l (95% confidence interval 11.7–24.3 g/l), paired t test p

Background and objectivesThe UK bowel cancer screening programme (BCSP) has been established for the early detection of colorectal cancer offering colonoscopy to patients screened positive by faecal occult blood tests. In this multisite, prospective, randomised controlled trial, we aimed to compare the performance of Standard Definition Olympus Lucera (SD-OL) with Scope Guide and the High Definition Pentax HiLine (HD-PHL).Patients and methodsSubjects undergoing a colonoscopy as part of the UK National BCSP at four UK sites were randomised to an endoscopy list run using either SD-OL or HD-PHL. Primary endpoints were polyp and adenoma detection rate (PDR and ADR, respectively) as well as polyp size, morphology and histology characteristics.Results262 subjects (168 males, mean age 66.3±4.3 years) were colonoscoped (133 patients with HD-PHL while 129 with SD-OL). PDR and ADR were comparable within the two optical systems. The HD-PHL group resulted in a PDR 55.6% and ADR 43.6%; the SD-OL group had PDR 56.6% and ADR 45.7%. HD-PHL was significantly superior to SD-OL in detection of flat adenomas (18.6% vs 5.2%, pConclusionPDR and ADR were not significantly different between devices. The high-resolution colonoscopy system HD-PHL may improve polyp detection as compared with standard resolution technology in detecting flat adenomas. This advantage may have clinically significant implications for missed lesion rates and post-colonoscopy interval colorectal cancer rates.

Summary Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding UK National Institute for Health Research Health Technology Assessment Programme.

Background and study aims Cryoablation with the Cryoballoon device is a novel ablative therapy that uses cycles of freezing and thawing to induce cell death. This single-center prospective study evaluated the feasibility of the focal cryoablation device for the treatment of areas of refractory esophageal neoplasia in patients who had undergone first line endoscopic eradication therapy (EET). Complete remission of dysplasia (CR-D) and complete remission of intestinal metaplasia (CR-IM) at first follow-up endoscopy, durability of disease reversal, rates of stenosis and adverse events were studied. Patients and methods Eighteen cases were treated. At baseline, nine patients had low-grade dysplasia (LGD), six had high-grade dysplasia (HGD) and three had intramucosal carcinoma (IMC). Median length of dysplastic Barrett’s esophagus (BE) treated was 3 cm. The median number of ablations per patient was 11. Each selected area of visible dysplasia received 10 seconds of ablation. One session of cryoablation was performed per patient. Biopsies were performed at around 3 months post-ablation. Results CR-D was achieved in 78 % and CR-IM in 39 % of patients. There were no device malfunction or adverse events. Stenosis was noted in 11 % of cases. At a median follow up of 19-months, CR-D was maintained in 72 % of patients and CR-IM in 33 %. Conclusions Cryoablation appears to be a viable rescue strategy in patients with refractory neoplasia. It is well tolerated and successful in obtaining CR-D and CR-IM in patients with treatment-refractory BE. Further trials of dosimetry, efficacy and safety in treatment-naïve patients are underway.

Gastric adenocarcinoma develops after stepwise progression from normal mucosa through to adenocarcinoma most commonly after being triggered by Helicobacter pylori (H. pylori) infection. As disease is often diagnosed late, the prognosis for gastric adenocarcinoma is poor. Identifying pre-malignant mucosal lesions such as atrophic gastritis, intestinal metaplasia and dysplasia is one strategy adopted by clinicians to reduce cancer related mortality. Surveillance of high-risk individuals and endoscopic resection of dysplastic lesions is recommended by international and UK guidelines. The early detection and endoscopic management reduce the need for invasive surgery. The advancement of image enhanced endoscopy technology, endoscopic training, risk stratification and histological assessment has proven pivotal to the management of pre-malignant lesions. In this review we outline the development of a high-risk stomach, endoscopic assessment and review practical guidelines on identifying pre-malignant gastric mucosa.

IntroductionPatients with chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are at risk of developing gastric adenocarcinoma. Their diagnosis and management currently rely on histopathological guidance after random endoscopic biopsy sampling (Sydney biopsy strategy). This approach has significant flaws such as under-diagnosis, poor reproducibility and poor correlation between endoscopy and histology. This prospective, international multicentre study aims to establish whether endoscopy-led risk stratification accurately and reproducibly predicts CAG and IM extent and disease stage.Methods and analysisPatients with CAG and/or IM on standard white light endoscopy (WLE) will be prospectively identified and invited to undergo a second endoscopy performed by an expert endoscopist using enhanced endoscopic imaging techniques with virtual chromoendoscopy. Extent of CAG/IM will be endoscopically staged with enhanced imaging and compared with standard WLE. Histopathological risk stratification through targeted biopsies will be compared with endoscopic disease staging and to random biopsy staging on WLE as a reference. At least 234 patients are required to show a 10 % difference in sensitivity and accuracy between enhanced imaging endoscopy-led staging and the current biopsy-led staging protocol of gastric atrophy with a power (beta) of 80 % and a 0.05 probability of a type I error (alpha).Ethics and disseminationThe study was approved by the respective Institutional Review Boards (Netherlands: MEC-2018-078; UK: 19/LO/0089). The findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNTR7661; Pre-results.

IntroductionEndoscopic therapy for the management of patients with Barrett’s oesophagus (BE) neoplasia has significantly developed in the past decade; however, significant variation in clinical practice exists. The aim of this project was to develop expert physician-lead quality indicators (QIs) for Barrett’s endoscopic therapy.MethodsThe RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgement of experts to develop quality indicators for Barrett’s endotherapy in four subgroups: pre-endoscopy, intraprocedure (resection and ablation) and postendoscopy. International experts, including gastroenterologists, surgeons, BE pathologist, clinical nurse specialist and patient representative, participated in a three-round process to develop 15 QIs that fulfilled the RAND/UCLA definition of appropriateness.Results17 experts participated in round 1 and 20 in round 2. Of the 24 proposed QIs in round 1, 20 were ranked as appropriate (put through to round 2) and 4 as uncertain (discarded). At the end of round 2, a final list of 15 QIs were scored as appropriate.ConclusionsThis UK national consensus project has successfully developed QIs for patients undergoing Barrett’s endotherapy. These QIs can be used by service providers to ensure that all patients with BE neoplasia receive uniform and high-quality care.

Objective: Assess microRNA (miRNA) expression in healthy and diseased gingival tissue of human subjects and identify potential miRNA-target gene interactions and biological pathways relevant to periodontal pathogenesis. Methods: Gingival biopsies were obtained from subjects meeting the criteria for “healthy” or “diseased” according to the current AAP guidelines. Total RNA (including miRNA) was isolated using miRNeasy kit (Qiagen). Global human miRNA expression was quantified using microRNA microarray (LC Sciences μParaflo® technology platform). Potential gene targets and biological pathways of differentially expressed miRNAs were predicted using bioinformatics analysis. Results: Our results show significantly different expression levels of miRNAs when comparing inflamed and healthy gingival biopsies. Among differentially expressed miRNAs, 35 were upregulated and 29 were downregulated in diseased tissue. Using pathway analysis, these miRNAs were predicted to influence the following pathways: ECM-receptor interaction, cell adhesion molecules (CAMs), MAPK signaling pathway, and cAMP signaling pathway. Genes associated with these pathways were scanned for potential miRNA binding sites. We identified IKBKB as a target gene, an endogenous inhibitor of NF-kappa-B and MAPK signaling, which possesses multiple binding sites for candidate miRNAs including hsa-miR-195-5p. Conclusion: Our findings reveal human miRNA expression profiles are significantly different in healthy and diseased gingival tissues. Post-transcriptional regulation of gene expression by miRNAs can modulate inflammatory biological pathways, suggesting their integral role in periodontal pathogenesis.

AIM To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy. METHODS Patients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed. Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management. Study outcomes include the presence of lymph-node metastases, disease-specific mortality and overall survival. RESULTS A total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk). Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR). All LNM occurred in patients with high-risk lesions and this represented 21% of the total high-risk lesions. Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (P = 0.636) and disease-specific survival time was also comparable between the two treatment strategies (P = 0.376). CONCLUSION T1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good out-comes. In selected patients, endoscopic therapy may be appropriate for high-risk lesions.

A 27-year-old, previously healthy woman with no history of migraine presented to the emergency department with sudden-onset left hemiparesis. Her only stroke risk factor was oral contraceptive use for the past several months. She awoke in normal health but soon developed left-sided weakness. On arrival to the emergency department, she had a blood pressure of 126/73 and a heart rate of 88. National Institutes of Health Stroke Scale was 5 for a left facial droop, hemiparesis, and dysarthria. Her computed tomography head was normal. She received intravenous tPA (tissue-type plasminogen activator) at her local hospital and was transferred to a comprehensive stroke center. On arrival, she had improved to a National Institutes of Health Stroke Scale of 2 for left facial droop and left arm drift. Magnetic resonance imaging of the brain revealed diffusion restriction within the right insula, putamen, and caudate (Figure [A] and [B]). Magnetic resonance angiography of the head and neck showed no intracranial or extracranial stenosis (Figure [C] and [D]). Fat-saturated imaging was considered but not done because she had widely patent arteries and no symptoms suggestive of dissection, such as headache or neck pain. She underwent an extensive workup, including transesophageal echocardiogram with bubble study, cardiac monitoring for paroxysmal atrial fibrillation, hemoglobin A1c, lipid panel, lupus anticoagulant, anticardiolipin antibodies, antinuclear antibodies, antithrombin-3, β-2 glycoprotein, homocysteine, protein C and S, and genetic testing for prothrombin gene mutation and Factor V Leiden. All testing was negative for a potential cause of stroke. She was diagnosed with cryptogenic stroke and discharged on aspirin and statin. Her oral contraceptive pills (OCPs) were stopped. Figure. Magnetic resonance imaging shows a right-sided infarction on diffusion-weighted imaging ( A ). Intracranial ( B ) and extracranial vessels were widely patent ( C and D ). This case illustrates a common scenario where the only potential risk factor for …

We thank Drs Shahidi and Bourke1 for their kind interest in our British Society of Gastroenterology guidelines.2 They present a valid argument that endoscopic mucosal resection (EMR) rather than endoscopic submucosal dissection (ESD) should be the first-line therapy for all gastric neoplasia, irrespective of lesion size, location or histopathology, citing supportive evidence from the Japan Gastroenterological Endoscopy Society (JGES)3 and the European Society of Gastrointestinal Endoscopy (ESGE),4 and three systematic reviews.5–7 We accept the compelling, although low-quality evidence from the systematic reviews demonstrating that en bloc resection, R0 resection and recurrence rates favoured ESD overall. Although the JGES guidelines state that ESD is better than EMR, they provide the caveat that there have been no randomised controlled trials examining the therapeutic results between EMR and ESD in …

BACKGROUND Esophageal dysmotility may predispose to Barrett's esophagus (BE). We hypothesized that high-resolution manometry (HRM) performed with additional physiologic challenge would better delineate dysmotility in BE. METHODS Included patients had typical reflux symptoms and underwent endoscopy, HRM with single water swallows and adjunctive testing with solids and rapid drink challenge (RDC) before ambulatory pH-impedance monitoring. BE and endoscopy-negative reflux disease (ENRD) subjects were compared against functional heartburn patient-controls (FHC). Primary outcome was incidence of HRM contractile abnormalities with standard and adjunctive swallows. Secondary outcomes included clearance measures and symptom association on pH-impedance. KEY RESULTS Seventy-eight patients (BE 25, ENRD 27, FHC 26) were included. Water swallow contractility was reduced in both BE (median DCI 87 mm Hg/cm/s) and ENRD (442 mm Hg/cm/s) compared to FHC (602 mm Hg/cm/s; P

Background The RASCAL (R efractory A ngina S pinal C ord stimulation and usuAL care) pilot study seeks to assess the feasibility of a definitive trial to assess if addition of spinal cord stimulation (SCS) to usual care is clinically superior and more cost-effective than usual care alone in patients with refractory angina. Methods/design This is an external pilot, patient-randomized controlled trial. The study will take place at three centers in the United Kingdom - South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital), Dudley Group of Hospitals NHS Foundation Trust, and Basildon and Thurrock University Hospitals NHS Foundation Trust. The subjects will be 45 adults with refractory angina, that is, limiting angina despite optimal anti-angina therapy, Canadian Cardiovascular Society Functional Classification Class III and IV, angiographically documented coronary artery disease not suitable for revascularization, satisfactory multidisciplinary assessment and demonstrable ischemia on functional testing. The study will be stratified by center, age and Canadian Cardiovascular Society Functional Classification. Interventions will involve spinal cord stimulation plus usual care (‘SCS group’) or usual care alone (‘UC group’). Usual care received by both groups will include consideration of an education session with a pain consultant, trial of a transcutaneous electrical neurostimulation, serial thoracic sympathectomy and oral/systemic analgesics. Expected outcomes will be recruitment and retention rates; reasons for agreeing/declining participation; variability in primary and secondary outcomes (to inform power calculations for a definitive trial); and completion rates of outcome measures. Trial patient-related outcomes include disease-specific and generic health-related quality of life, angina exercise capacity, intake of angina medications, frequency of angina attacks, complications and adverse events, and satisfaction. Discussion The RASCAL pilot trial seeks to determine the feasibility and design of a definitive randomized controlled trial comparing the addition of spinal cord stimulation to usual care versus usual care alone for patients with refractory angina. Fifteen patients have been recruited since recruitment opened in October 2011. The trial was originally scheduled to end in April 2013 but due to slow recruitment may have to be extended to late 2013. Trial registration ISRCTN65254102

Introduction Endoscopic resection (ER) followed by Radiofrequency ablation (RFA) is the first line treatment for neoplastic Barrett’s oesophagus (BE). Metachronous neoplasia after focal eradication of disease is ~20%. We examine data from the UK registry of 28 centres to establish if residual metaplastic BE carries a risk of disease recurrence. Methods Visible lesions were removed by EMR. Patients then underwent RFA 3 monthly. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Dysplasia recurrence was compared in patients who had complete reversal of BE and neoplasia (CR-IM) to those in whom dysplasia alone was eradicated (CR-D only). Residual BE was confirmed with visible columnar epithelium proximal to the OGJ with biopsies showing IM. Results 517 patients achieved CR-IM & 96 patients achieved CR-D only after 12 months treatment . Sex & ER rates were not significantly different between groups. The CR-D only group were older (mean age 70 vs 67, p Conclusion Endotherapy should aim to clear neoplasia and underlying metaplastic BE to improve long term outcome. Patients with CR-D but not CR-IM at the end of treatment have an increased risk of neoplasia recurrence. This may have implications for post treatment surveillance intervals. Disclosure of Interest None Declared

Endoscopic imaging is in part responsible for the recent drop in deaths from gastrointestinal cancers and also for detecting pre-cancerous and non-cancerous conditions and allowing them to be treated effectively, although techniques are far from perfect. Endoscopic imaging has evolved considerably from fiber optic systems 50 years ago to high resolution and high definition systems used at present. Moreover, image enhancement using filters and processors has led to the technique of ‘electronic chromoendoscopy’ to visualize mucosal blood vessels and surface pit patterns clearly. Magnification by optical zoom or confocal laser microscopy has enabled real time diagnosis and ‘virtual histology’. These techniques have contributed to the early detection, assessment and treatment of various gastrointestinal pathologies. The focus of future research is directed towards molecular targeted imaging.

Tree hollows provide shelters for a large number of forest-dependent vertebrate species worldwide. In Madagascar, where high historical and ongoing rates of deforestation and forest degradation are responsible for a major environmental crisis, reduced availability of tree hollows may lead to declines in hollow-dwelling species such as sportive lemurs, one of the most species-rich groups of lemurs. The identification of native tree species used by hollow-dwelling lemurs may facilitate targeted management interventions to maintain or improve habitat quality for these lemurs. During an extensive survey of sportive lemurs in northern Madagascar, we identified one tree species, Strychnos madagascariensis (Loganiaceae) , the spineless monkey orange tree, as a principal sleeping site of two species of northern sportive lemurs, Lepilemur ankaranensis and L. milanoii (Lepilemuridae). This tree species represented 32.5% (n=150) of the 458 sleeping sites recorded. This result suggests that S. madagascariensis may be valuable for the conservation of hollow-dwelling lemurs. Resume De nombreux vertebres forestiers a travers le monde trouvent refuge dans des cavites et des trous d’arbres. A Madagascar, les taux de deforestation historiques et actuels sont responsables d’une crise environnementale majeure. Dans ce contexte, une disponibilite reduite d’arbres pourvus de cavites pourrait entrainer le declin des especes dependant de ces abris comme par exemple les lepilemurs, un des groupes de lemuriens les plus riches en especes. L’identification des especes d’arbres indigenes creuses de trous et utilises par les lemuriens pourrait faciliter la mise en place d’actions de conservation ayant pour but de maintenir ou ameliorer l’habitat de ces lemuriens. Au cours d’une etude realisee dans le Nord de Madagascar, nous avons observe que Strychnos madagascariensis (Loganiaceae) etait frequemment utilise comme site dortoir par les deux especes de lepilemurs presentes, Lepilemur ankaranensis and L. milanoii (Lepilemuridae). Cette espece d’arbre concernait 32,5% (n = 150) des 458 sites dortoirs enregistres. Ce resultat suggere que S. madagascariensis pourrait etre important pour la conservation des lemuriens dependant de sites dortoirs.

Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. This is regarded as being due to accelerated coronary atherosclerosis. We describe a 62-year-old man with seropositive erosive RA and extraarticular manifestations but no history of cardiovascular disease. Noninvasive assessment of myocardial blood flow by adenosine stressed thallium scanning showed reversible ischemia and diffusely poor myocardial perfusion. Repeat assessment after intensive immunosuppression for rheumatoid vasculitis revealed resolution of the ischemic changes and generally increased myocardial perfusion. Coronary angiography revealed no significant atheroma, suggesting that myocardial microvascular disease was responsible for the ischemia. This may be an important determinant of cardiovascular outcome in RA, and this case indicated that it can be reversed with immunosuppression.

Introduction The incidences of Barrett9s oesophagus (BE) and associated oesophageal adenocarcinoma are increasing rapidly in the UK. Radiofrequency ablation (RFA) with a circumferential balloon based device (CA) and endoscope-mounted focal ablation device (FA) are promising modalities for treating dysplasia arising in BE. Aim To determine the safety and efficacy of RFA for treating dysplastic BE in a UK patient cohort. Study Design Multicentre UK registry (seven teaching and private hospitals; treatment period from April 2007 to November 2009). Patients with histological evidence of dysplasia or intramucosal cancer (IMC) arising in BE confirmed by two specialist GI pathologists were included in the study. A prior endoscopic mucosal resection (EMR) was permitted, provided that residual dysplasia remained in the BE region for ablation. RFA was performed every 3 months with follow-up biopsy upon achieving either complete endoscopic eradication of BE or after four consecutive ablations. The primary endpoint was complete response for high-grade dysplasia (CR-HGD), dysplasia (CR-D) and intestinal metaplasia (CR-IM), defined as no biopsy showing each respective finding. Results A total of 106 patients (79% male, median age 69 years, interquartile range (IQR) 50–83 years) have been treated so far. Accrual rates now exceed 15 patients per quarter. 83 had HGD, 22 IMC, 1 LGD. Median length of BE was 6 cm (IQR 1–15 cm). 54% had prior EMR, 25% had previous photodynamic therapy (PDT) or argon plasma coagulation (APC). 42 patients have completed treatment with at least 1 follow-up biopsy session (median follow-up 4 months, IQR 2–24). Median number of treatments is 1 CA (IQR 0–3) and 1 FA (IQR 0–3). CR-HGD was achieved in 90% of patients, CR-D in 79% and CR-IM in 33%. There were eight new strictures, three mucosal injuries during RFA (1.5%) and one perforation (patient previously treated with PDT) (0.5%). Conclusion Reversal of IM is currently poor, but many of these patients have had multiple previous ablative therapies and may represent a particularly difficult group to treat. Despite this, radiofrequency ablation safely achieved a CR- HGD in 90% of patients treated within a UK multicentre registry. These data are similar to other registries.