Real-time artificial intelligence for detection of upper gastrointestinal cancer by endoscopy: a multicentre, case-control, diagnostic study.

Abstract: Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made remarkable progress in medical imaging […]

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Impedance and Histologic Characteristics of the Sub-laryngeal Esophagus Distinguish Eosinophilic Esophagitis From Other Esophageal Disorders.

Abstract: The region of the esophagus 15-17 cm below the incisors, called the sub-upper esophageal sphincter (sub-UES), has not been characterized in adults with eosinophilic esophagitis (EoE) but appears different […]

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Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial.

Abstract: Chemotherapy for patients with advanced oesophageal squamous cell carcinoma offers poor long-term survival prospects. We report the final analysis from our study of the immune checkpoint PD-1 inhibitor nivolumab […]

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Magnetic Sphincter Augmentation Superior to Proton Pump Inhibitors for Regurgitation in a 1-year Randomized Trial.

Abstract: Regurgitative gastroesophageal reflux disease (GERD) refractive to medical treatment is common and caused by mechanical failure of the anti-reflux barrier. We compared the effects of magnetic sphincter augmentation (MSA) […]

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Small Bowel Healing Detected by Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis Factor.

Abstract: It is important to objectively assess Crohn`s disease (CD) activity in patients treated with antibodies against tumor necrosis factor (anti-TNF). Detection of healing by endoscopy (endoscopic healing) associates with […]

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How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery).

Abstract: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the […]

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British Society of Gastroenterology guidelines for oesophageal manometry and oesophageal reflux monitoring.

These guidelines on oesophageal manometry and gastro-oesophageal reflux monitoring supersede those produced in 2006. Since 2006 there have been significant technological advances, in particular, the development of high resolution manometry (HRM) and oesophageal impedance monitoring. The guidelines were developed by a guideline development group of patients and representatives of all the relevant professional groups using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. A systematic literature search was performed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool was used to evaluate the quality of evidence and decide on the strength of the recommendations made. Key strong recommendations are made regarding the benefit of: (i) HRM over standard manometry in the investigation of dysphagia and, in particular, in characterising achalasia, (ii) adjunctive testing with larger volumes of water or solids during HRM, (iii) oesophageal manometry prior to antireflux surgery, (iv) pH/impedance monitoring in patients with reflux symptoms not responding to high dose proton pump inhibitors and (v) pH monitoring in all patients with reflux symptoms responsive to proton pump inhibitors in whom surgery is planned, but combined pH/impedance monitoring in those not responsive to proton pump inhibitors in whom surgery is planned. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG.

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Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy.

There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment.We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old, 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers.After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35, 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102, 31.4%) (P=.018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13, 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27, 33.3%) (P=.286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

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Endoscopy in the coagulopathic patient.

The presence of coagulopathy in patients profoundly affects the performance of gastrointestinal endoscopy. However, the coagulopathy in chronic liver disease (CLD) and therapeutic anticoagulation to lower thromboembolic risk are different. In this review, we briefly discuss the hemostatic alterations in CLD leading to coagulopathy and the periprocedure management of antithrombotic medications in patients needing emergency or elective gastrointestinal endoscopy.Prothrombin time (PT) and international normalized ratio (INR) are unreliable measures of bleeding risk and hemostasis in CLD. Therefore, expert opinion advises no preprocedure fresh frozen plasma (FFP) infusion to correct the INR. There has been a proliferation of and increasing use of antithrombotic medications for therapeutic anticoagulation. Their management depends on the gastrointestinal endoscopy procedure bleeding risk, the acuity of the procedure, and the underlying thromboembolic risk of the patient.Cirrhotic coagulopathy features a rebalancing of procoagulant and anticoagulant factors. PT and INR do not accurately measure this rebalanced hemostasis. Thus, expert opinion does not recommend FFP infusion to correct the PT or INR before performing gastrointestinal endoscopy. Management of therapeutic anticoagulation in endoscopy depends on the acuity of the indication, the procedure bleeding risk, and the thromboembolic risk of stopping anticoagulation. At present, there are only expert opinion recommendations concerning periendoscopy coagulopathy management in CLD and in therapeutic anticoagulation. More controlled clinical studies will clarify bleeding risks when performing gastrointestinal procedures in these patients and better direct patient care. Until then, clinical management of antithrombotic medications are based an individual patient’s medical conditions and available options for treatment.

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Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation.

Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children ?0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn’s disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals.Retrospectively registered; clinicaltrials.gov ID NCT03588013 .

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Phenotypes of Gastroesophageal Reflux Disease: Where Rome, Lyon, and Montreal Meet.

Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice. From a conventional pathophysiological perspective GERD is conceptualized as incompetence of the antireflux barrier at the esophagogastric junction; the more severe that incompetence, the worse the disease. However, it is increasingly clear that many presentations of GERD represent distinct phenotypes with unique predisposing cofactors and pathophysiology outside of this paradigm. Three major consensus initiatives have grappled with this dilemma (the Montreal Consensus, The Rome Foundation, and the Lyon Consensus), each from a different perspective. Montreal struggled to define the disease, Rome sought to characterize its “functional” attributes, while Lyon examined its physiological attributes. Our objective in this review is to merge the three, developing the concept that what has come to be known as GERD is actually a family of syndromes with a complex matrix of contributing pathophysiology. A corollary to this is that the concept of one size fits all to therapeutics does not apply and that while escalating treatment with proton pump inhibitors (PPIs) may be pertinent to healing esophagitis, its applicability beyond that is highly questionable. Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, visceral and central hypersensitivity on symptom severity has greatly over-simplified the problem. That over-simplification has led to excessive use of PPIs for everything captured under the GERD umbrella and revealed a broad spectrum of syndromes less amenable to PPI therapy in any dose. It is with this in mind that we delineate this precision medicine concept of GERD.

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Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial.

Pre-clinical and clinical evidence suggests that simultaneous blockade of VEGF receptor-2 (VEGFR-2) and PD-1 or PD-L1 enhances antigen-specific T-cell migration, antitumour activity, and has favourable toxicity. In this study, we aimed to assess the safety and preliminary antitumour activity of ramucirumab (an IgG1 VEGFR-2 antagonist) combined with pembrolizumab (an IgG4 PD-1 antagonist) in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma, non-small-cell lung cancer, or urothelial carcinoma.We did a multicohort, non-randomised, open-label, phase 1a/b trial at 16 academic medical centres, hospitals, and clinics in the USA, France, Germany, Spain, and the UK. We enrolled adult patients aged 18 years or older with histologically confirmed gastric or gastro-oesophageal junction adenocarcinoma (cohorts A and B), non-small-cell lung cancer (cohort C), or urothelial carcinoma (cohort D), whose disease had progressed on one or two lines of previous therapy (for those with gastric or gastro-oesophageal junction adenocarcinoma) or one to three lines of previous therapy (for those with non-small-cell lung cancer and urothelial carcinoma) that included platinum (for all tumour types) or fluoropyrimidine or both (for gastric or gastro-oesophageal junction adenocarcinoma). Eligibility criteria included presence of measurable disease and an Eastern Cooperative Oncology Group performance status of 0-1. Patients with previously untreated gastric or gastro-oesophageal junction adenocarcinoma and non-small-cell lung cancer were also enrolled (in two additional separate cohorts); the results for these cohorts will be reported separately. The first 21-day treatment cycle was a dose-limiting toxicity observation period (phase 1a; safety run-in), followed by a phase 1b cohort expansion stage. Pembrolizumab 200 mg was administered intravenously on day 1, and intravenous ramucirumab was administered at 8 mg/kg on days 1 and 8 for cohort A or at 10 mg/kg on day 1 for cohorts B, C, and D, every 3 weeks, until disease progression or other discontinuation criteria were met. The primary endpoint was the safety and tolerability of ramucirumab in combination with pembrolizumab assessed by the incidence of adverse events in both phase 1a and 1b and as dose-limiting toxicities during phase 1a. The safety and activity analysis set included all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02443324, and is no longer enrolling patients.Between July 30, 2015 and June 24, 2016, we enrolled and treated 92 patients (41 with gastric or gastro-oesophageal junction adenocarcinoma, 27 with non-small-cell lung cancer, and 24 with urothelial carcinoma). Median follow-up was 32·8 months (IQR 28·1-33·6). During the first cycle of treatment (phase 1a safety run-in; n=11), one patient with gastro-oesophageal junction adenocarcinoma who received the 8 mg/kg dose of ramucirumab had grade 3 abdominal pain, colitis, hepatitis, interstitial lung disease, and jaundice, and grade 4 cholestasis, and died on treatment on day 40; the death was deemed related to progressive disease. No additional dose-limiting toxicities occurred and the decision was made to maintain the full planned doses of ramucirumab and pembrolizumab in phase 1b (n=81). Treatment-related adverse events occurred in 75 (82%) of 92 patients, the most common of which was fatigue (in 33 patients [36%]), predominantly of grade 1 or 2 severity. 22 patients (24%) had one or more treatment-related adverse events of grade 3 or worse, most commonly hypertension (six patients; 7%) and colitis (five patients; 5%). Serious adverse events occurred in 53 (58%) of 92 patients, and were deemed related to treatment in 22 (24%) patients. The most common treatment-related serious adverse events were abdominal pain in patients with gastric or gastro-oesophageal junction adenocarcinoma (in three [7%] of 41 patients); asthenia and myocardial infarction in patients with non-small-cell lung cancer (two [7%] of 27 patients), and colitis in patients with urothelial carcinoma (two [8%] of 24 patients). Six (7%) of 92 patients discontinued treatment because of treatment-related adverse events, and one death (from pulmonary sepsis in a patient with gastric or gastro-oesophageal junction adenocarcinoma) was deemed related to treatment. The number of patients achieving an objective response was three (7%; 95% CI 1·5-19·9) of 41 in the gastric or gastro-oesophageal junction adenocarcinoma cohort, eight (30%; 13·8-50·2) of 27 in the non-small-cell lung cancer cohort, and three (13%, 2·7-32·4) in the urothelial carcinoma cohort.Ramucirumab in combination with pembrolizumab showed a manageable safety profile with favourable antitumour activity in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma, non-small-cell lung cancer, and urothelial carcinoma. Our results contribute to the growing evidence that supports dual inhibition of the VEGF-VEGFR2 and PD-1-PD-L1 pathways. This combination could be further explored with or without chemotherapy, especially for patients with tumours for which single-agent checkpoint inhibitors have shown no additional benefit over chemotherapy.Eli Lilly and Company, and Merck and Co.

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Practical guide to the management of chronic pancreatitis.

Chronic pancreatitis (CP) is an irreversible fibroinflammatory disorder of the pancreas. It presents with relapsing, remitting upper abdominal pain accompanied by features of malabsorption due to pancreatic exocrine insufficiency and endocrine deficiency with the development of diabetes mellitus. The associated increased hospitalisation and high economic burden are related to CP often presenting at advanced stage with irreversible consequences. Diagnosing CP at an early stage is still challenging and therefore CP is believed to be under-reported. Our understanding of this disease has evolved over the last few years with attempts to redesign the definition of CP. Better recognition of the risk factors and conditions associated with CP can lead to an earlier diagnosis and coupled with a multidisciplinary approach to treatment, ultimately reduce complications. This article reviews the epidemiology, risk factors, diagnosis and management of CP.

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Premature dissolution of the Agile patency device: implications for capsule endoscopy.

The main risk of capsule endoscopy is retention of the capsule behind a stricture. Passage of an intact Agile patency device (Medtronic, Dublin, Ireland) through the small bowel is widely used to ensure luminal patency, although capsule retention has occurred in patients who have had a reassuring patency study. The device is designed to remain intact for at least 30?hours postingestion, such that loss of signal from the radiofrequency identification tag contained within, or absence of the device on radiological imaging, implies unimpeded intestinal transit.To identify the rate of premature dissolution (<30 hours postingestion) of the Agile patency device.Outcomes of all consecutive patients having an Agile patency device were analysed.Premature dissolution of the patency device occurred in 5 of 307 patients, an incidence of 1.3%. This was recognised by the detection of a persistent radiofrequency signal after radiological imaging had failed to identify the patency device, prompting a careful search for the radiofrequency tag on the CT scout film. The tag was difficult to detect because of an oblique lie making it appear smaller than its 13×3?mm size and confusion with intra-abdominal or other metallic fragments.In the absence of radiological evidence of an intact Agile patency device, premature dissolution should be suspected in patients registering a persistent radiofrequency signal and confirmed by identifying the radiofrequency identification tag. Failure to do so might result in false reassurance that capsule endoscopy could be performed without risk of retention.

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