Endoscopic eradication therapy (EET) for Barrett’s esophagus (BE)-related neoplasia is safe and effective in the short term, however there are limited data on long-term outcomes. We aim to provide further evidence on the long-term efficacy of EET in patients with BE-related high-grade dysplasia (HGD) or low-risk T1 esophageal adenocarcinoma (EAC). This prospective cohort study enrolled patients with early BE-related neoplasia at a single tertiary referral center between January 2005 and December 2022. We included patients who had a baseline histological diagnosis of HGD, T1a or superficial T1b EAC (invasion into the submucosa less than 500 µ) and received endoscopic therapy with either primary radiofrequency ablation or endoscopic resection (ER). Our primary outcome assessed disease-specific mortality (DSM), which is defined as death following progression to advanced adenocarcinoma not amenable to curative treatment. Secondary outcomes evaluate overall survival, endoscopic recurrence, progression to esophagectomy and major post-procedure complications. We included 330 patients (HGD n = 135; T1a EAC n = 170; T1b EAC n = 25), of which 283 patients were treated with primary endoscopic resection (ER) whereas 47 patients were treated with RFA alone. Median follow up was 55.35 months (IQR 36.5–86.5). DSM was 2.2

ABSTRACT Introduction Specialist guidelines recommend endoscopic surveillance for Barrett's esophagus to reduce mortality related to esophageal adenocarcinoma, but the setting for optimal Barrett's esophagus monitoring is unclear. We assessed progression rate and disease‐specific mortality in a large cohort of patients followed up at a single Barrett's esophagus expert center. Methods For this prospective longitudinal single center cohort study, we recruited patients with a previous diagnosis of Barrett's esophagus between 2004 and 2022. Endoscopists were trained in Barrett's esophagus surveillance standards and image‐enhanced techniques, and biopsies were reviewed by expert pathologists. Exclusion criteria were a single surveillance endoscopy, high‐grade dysplasia, or esophageal adenocarcinoma at or within 12 months from index endoscopy and patients with < 12 months follow‐up. The primary outcome was the neoplastic progression rate of Barrett's esophagus with intestinal metaplasia to high‐grade dysplasia/esophageal adenocarcinoma. Secondary outcomes included cancer stage and disease‐specific mortality, risk factors for progression and progression rate in patients with Barrett's esophagus with only gastric metaplasia or irregular z‐line and intestinal metaplasia (IZL‐IM). Results A total of 1932 patients were recruited, of which 969 were included in the primary analysis with a median follow‐up of 5.8 years. Of these, 109 developed high‐grade dysplasia or esophageal adenocarcinoma with a progression rate of 1.63%/year. Overall, 48 patients received an esophageal adenocarcinoma diagnosis, of which 89,5% (43/48) had stage 1%, and 0.3% patients (3/969) had disease‐specific mortality. Multivariate analysis showed that age, alcohol consumption, esophagitis, Barrett's esophagus length, hiatus hernia length, low‐grade dysplasia and neutrophil/lymphocyte ratio were risk factors for progression. The rate of progression in patients with Barrett's esophagus—gastric metaplasia or IZL‐IM was 0.06%/year. Conclusions Endoscopic surveillance in an expert Barrett's esophagus center leads to a high neoplastic progression rate, and a low rate of disease‐specific mortality. Further research to correlate disease‐specific mortality and cancer stage with dysplasia detection rate is warranted to develop diagnostic quality indicators specific for Barrett's esophagus.

Abstract Background High-grade dysplasia (HGD) and intramucosal (T1a) esophageal adenocarcinoma (EAC) are indication for endoscopic eradication therapy (EET) with endoscopic resection (ER) and/or radiofrequency ablation (RFA). The goal of the endoscopic therapy is to prevent progression to advanced EAC and cure the underlying Barrett’s esophagus (BE) when present. Previous studies have showed high rate of success of EET in short term, however little is known about long term results of EET. We aimed to evaluate long-term outcome of EET with particular reference to disease specific mortality and progression to major surgery. Methods We conducted a single center retrospective study including patients who underwent EET for HGD and T1a EAC January 2005-December 2022. We excluded patients with gastric disease and evidence of T1b EAC at baseline ER. Primary outcomes assessed disease specific mortality (DSM) of esophageal cancer in this longitudinal cohort, which is defined as death within 12 months of progression to advanced cancer. Secondary outcomes evaluate endoscopic recurrence, progression to esophagectomy, post-procedure complications and 5-year overall survival. Results 299 patients were included in this study. 252 were treated with a combination of ER and RFA, whereas 47 only received primary RFA. Median number of EET sessions in both patient groups is 4(p=0.48). Patients with HGD were more likely to be detected on surveillance compared to those with T1a EAC (p=0.004). We demonstrate a DSM rate of 2.7%(n=8), with a 5-year overall survival of 74.6%(n=223). 5.7%(n=17) of patients sustained severe post-procedure complications (Clavien-Dindo>3). Endoscopic recurrence occurred in 18.7%(n=56) and 6.7%(n=20) developed disease progression that required surgical intervention. Baseline T1a was associated with higher rates of esophagectomy compared to HGD (p=0.0135). Conclusion EET is a safe and effective treatment for patients with early-stage esophageal neoplasia. In comparison to esophago-gastric surgery, EET offers excellent results with a significantly lower morbidity and mortality risk. However, it is resource intensive as patients often require multiple treatments with long-term, routine surveillance. Patients also require strict compliance to maximize therapeutic outcomes and prevent recurrence or progression. Further studies are required to improve risk-stratification in this cohort and determine the optimal surveillance strategy post EET.

Acid-related disorders, including gastro esophageal reflux disease (GERD), duodenal ulcers, and gastric ulcers, are managed by H receptor antagonists and proton pump inhibitors (PPIs). PPIs represent first choice for 2 + + treating acid-peptic ulcers inhibits the gastricH / K -ATPase through covalent binding to cysteine residues of the proton pump. Achlorhydria and acute renal failure are the most common drawbacks. A reversible acid pump antagonist (APAs), currently in clinical trial removes these problems. The APAs are the conceivable future drugs for the treatment of acid-peptic disorders.

Introduction Radiofrequency ablation (RFA) is the treatment of choice for dysplastic Barrett's oesophagus (BO), however recurrence occurs in up to 25% of cases, usually at the gastro-oesophageal junction (GOJ). We have shown that a multi-gene methylation panel (ZNF345, TFPI2 and ZNF569) can differentiate BO from normal GOJ epithelium. This study aims to determine whether this methylation panel can predict risk of relapse post-RFA. Methods This is a prospective cohort study on patients who achieved endoscopic remission post-RFA. Patients were eligible if they had 1) no endoscopic evidence of BO or islands ≥5mm, 2) no suspicious dysplastic lesion at GOJ, and 3) no histological evidence of oesophageal intestinal metaplasia (IM) at first post-RFA follow-up (GOJ IM allowed). Patients received endoscopy at baseline, 6 and 12 months. Methylation score (Meth-score) was assessed by Methylight assay on random or targeted GOJ biopsies. The primary outcome was the correlation of Meth-score and histological outcome. The secondary outcome was the correlation of total baseline methylation level and dysplastic recurrence at follow-up. Results We included 56 patients with a total of 90 endoscopies at various timepoints of follow-up. Mean age, circumferential and maximum length of BO pre-RFA was 68.6 years (standard deviation, SD 7.5), 2.2cm (SD 3.0) and 4.4cm (SD 3.0), respectively. Seven (13%), 28 (50%) and 21 (38%) patients had pre-RFA low-grade dysplasia (LGD), high-grade dysplasia (HGD) and intramucosal carcinoma (IMC), respectively. Meth-score comparing patients with gastric metaplasia (GOJ-GM, n=60) and intestinal metaplasia (GOJ-IM, n=25) was 1.2% vs 36.9%, p<0.001, and between GOJ-GM and dysplasia (n=5) was 1.2% vs 43.4%, p<0.001. When assessing baseline Meth-score stratified by highest histology at any time during follow-up, patients with non-dysplastic recurrence (n=50) had a lower total baseline methylation compared to dysplastic recurrence (n=6), with Meth-score of 8.5% vs 39.0%, p=0.03. Conclusion A multi-gene methylation panel can discriminate patients with GM, IM and dysplasia on GOJ biopsies. Patients with stable histological remission (no IM or dysplasia at follow-up) had low baseline methylation levels. This biomarker panel can risk-stratify patients so that stricter surveillance is offered only to those with higher total methylation levels who are more likely to develop recurrence.

Background Endoscopic surveillance of Barrett’s esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). Methods We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. Results Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0–19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00–1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04–1.40; P = 0.01). Conclusions In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection.

Abstract Background Upper GI surgery, and particularly upper GI cancer surgery can result in quality of life limiting symptoms months and years later. While some of these symptoms may be unavoidable, there are a number of conditions which can be treated with the intention of improving quality of life. We developed and assessed the impact of a CNS and dietitian-led protocol for the investigation and management of late effects after upper GI cancer surgery at Addenbrooke’s Hospital, Cambridge. Methods A multi-disciplinary team including nurses, dietitians, pharmacists and with medical input from surgery, gastroenterology and clinical biochemistry produced a pragmatic guideline for the investigation and management of gastrointestinal, nutritional and endocrinological late effects. The protocol was instituted then retrospectively assessed for impact. The patients were divided in two groups, according to the beginning of their investigations: before or after the introduction of the protocol. Key measures were: proportion of patients being investigated for late effects, the time from presentation of symptoms to diagnosis and which late effects patients were diagnosed. Results In the analysis we included a total of 63 patients, 43 from the pre-protocol group and 20 from the post-protocol group. Patients investigated more than once have been interpreted individually making 51 cases pre-protocol and 22 post-protocol. In the pre-protocol group, 78.43% of patients were investigated for late effects. Among them 55% were diagnosed SIBO, 22.9% PEI. In the post-protocol group, 36.36% of patients were investigated for late effects. Among them 50% were diagnosed SIBO and 37.5% PEI. The average time from symptoms to diagnosis in the pre-protocol group was 10 months while in the post-protocol group 2 months. Conclusions The protocol has proved a popular adjunct to AHP-led follow-up clinics. The time from symptom onset to diagnosis has significantly improved from 10 to 2 months with the new protocol. Interestingly, the protocol appears to have reduced the number of patients investigated, however as the proportion of patients with SIBO has not changed, suggesting some patients may not be being identified. However, this may reflect the small study numbers and will likely change over time. We are keen to demonstrate our early experience with this standardised, nurse/dietitian-led approach to management of symptoms after Upper GI cancer surgery.

IntroductionEosinophilic oesophagitis (EO) has emerged as an increasingly common gastrointestinal condition over the last few decades and is characterised by dense eosinophilic infiltration of the oesophagus. The latest BSG guidelines from 2022 suggest different proton-pump inhibitors (PPIs), elimination diet and topical swallowed steroids as alternative treatment options for the management of EO. Treatment response varies depending on treatment used and there is no clear indication as to which of the available modalities should be employed as first-line. In this study, we evaluated the efficacy of PPIs as first-line treatment in EO based on clinical and histological improvement.MethodsA retrospective analysis of 110 EO patients on PPI monotherapy as first line treatment between January 2015 and September 2022 was performed at a tertiary hospital. Data collected included age, sex, ethnicity, past history and family history of atopy, presenting symptom triggering initial diagnosis, baseline endoscopic findings, clinical, endoscopic and histological response to treatment, and where applicable second- or third-line treatments.ResultsOur patient cohort had a mean age of 42 years and a male:female ratio of 2.1:1. The majority of patients presented with either dysphagia (n=83, 75.5%) or food impaction (n=22, 20.0%). Out of 110 patients, 15 had no follow-up data and were thus excluded, leaving 95 patients for the clinical response analysis. of these, 93 (97.9%) displayed some clinical response to PPIs. Complete, near-complete and partial clinical response was observed in 50 (52.6%), 21 (22.1%) and 22 (23.2%) patients, respectively. Only 2 (2.1%) patients showed no clinical response and had to be switched to alternative treatments. Data on post-therapy gastroscopy and biopsies were available for 57 patients. of these, 41 (72.0%) showed histological response, either complete (n=24, 42.1%) or partial (n=17, 29.8%). No response was seen in 16 (28.1%) cases.ConclusionIn our experience, first-line PPI monotherapy achieved histological response in 72% and clinical response in 98% of EO patients. Complete/Near-complete response was achieved in 42% cases based on histology and 75% cases based on clinical resolution of symptoms. These numbers suggest that PPIs have much higher efficacy that previously reported as first-line agents for EO, and make a case for their use as the initial therapy in this context. Further prospective studies are needed to evaluate this.

BACKGROUND & AIMS: Dysplasia in Barrett's esophagus often is invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence imaging (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers vs HRWLE with Seattle protocol biopsies. METHODS: Barrett's esophagus patients with no dysplastic lesions were block-randomized to standard endoscopy (HRWLE with the Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6 to 12 weeks. The primary end point was the histologic diagnosis from all study biopsies (trial histology). A sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from the first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. The primary outcome was diagnostic accuracy for dysplasia by real-time pCLE vs HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P = .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P <.001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; P=.16), with an area under the receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. The addition of molecular biomarkers could improve diagnostic accuracy.

INTRODUCTION: A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. METHODS: Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at −20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. RESULTS: Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 μg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16–30 years; 67% for >30 years; P = 0.016). DISCUSSION: The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the “European Registry on Helicobacter pylori management.” METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.

Introduction Dysplasia in Barrett’s oesophagus (BO) is often invisible at white light endoscopy (WLE) and Seattle protocol is labour intensive. There is lack of randomised evidence that advanced imaging improves dysplasia detection. Probe-based confocal endomicroscopy (pCLE) is accurate for high-grade dysplasia (HGD) and intramucosal cancer (IMC) associated to visible lesions, but due to the narrow field requires combination with a red-flag technique for long-segment inconspicuous BO. We aimed to assess the diagnostic accuracy of optical biopsy by pCLE targeted by autofluorescence imaging (AFI) for any grade of dysplasia in patients without visible lesions. Methods In this prospective multi-centre randomised cross-over trial BO patients were randomised to WLE with Seattle protocol (standard arm) https://mail.addenbrookes.nhs.uk/owa/auth/logon.aspx?replaceCurrent=1&url=https%3a%2f%2fmail.addenbrookes.nhs.uk%2fowa%2 for AFI-directed pCLE (experimental arm), and crossed over to the other arm after 6–12 weeks. The experimental arm consisted of (i)WLE inspection (ii)AFI to flag endoscopic areas (iii)pCLE on AFI areas and (iv)targeted biopsies. The 6 endoscopists were blinded to referral histology. Patients with unequivocal neoplastic lesions on WLE were excluded. Two GI pathologists confirmed histological diagnoses. The primary outcome was real-time diagnosis of dysplasia by pCLE. Two histological endpoints were analysed: (a) trial histology from all study biopsies; (b) overall histology, which included (a) + biopsies within the 12 months of enrolment. Secondary outcomes included procedural time. Results 133 patients completed both arms. 27.8% of patients received a diagnosis of dysplasia (LGD; n=19, HGD/IMC; n=18). In primary analysis (trial histology), pCLE had a sensitivity and specificity for dysplasia of 73.0% and 68.8%, respectively and 72.2% and 61.7% for HGD/IMC. Seattle protocol had a sensitivity of 73.0% for dysplasia and 83.3% for HGD/IMC, with no significant difference between arms. In secondary analysis (overall histology), pCLE had a similar sensitivity to Seattle protocol for dysplasia (61.8% vs. 49.1%; p=0.09) and HGD/IMC (70.0% vs 50.0%; p=0.11). The procedural time in the experimental arm was longer than standard arm (Mean mins 22.3 vs. 16.4; p<0.05), with evidence of learning curve (Q4 vs Q1 27.0 vs 19.0; p<0.05). Conclusions In combination with AFI, pCLE detects inconspicuous dysplasia in approximately three quarters of cases. pCLE has equal diagnostic accuracy for dysplasia compared to Seattle protocol dispensing extensive sampling but at expense of longer procedural time.