The endoscopic management of oesophageal strictures.

An oesophageal stricture refers to a narrowing of the oesophageal lumen, which may be benign or malignant. The cardinal feature is dysphagia, and this may result from intrinsic oesophageal disease or extrinsic compression. Oesophageal strictures can be further classified as simple or complex depending on stricture length, location, diameter, and underlying aetiology. Many endoscopic options are now available for treating oesophageal strictures including dilatation, injectional therapy, stenting, stricturotomy, and ablation. Self-expanding metal stents have revolutionised the palliation of malignant dysphagia, but oesophageal dilatation with balloon or bougienage remains first-line therapy for most benign strictures. The increase in endoscopic and surgical interventions on the oesophagus has seen more benign refractory oesophageal strictures that are difficult to treat, and often require advanced endoscopic techniques. In this review, we provide a practical overview on the evidence-based management of both benign and malignant oesophageal strictures, including a practical algorithm for managing benign refractory strictures.

Risk of metastasis among patients diagnosed with high-risk T1 esophageal adenocarcinoma who underwent endoscopic follow-up.

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8-25] and 10.9% (95% CI, 3.6-30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6-26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5-71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed.

Peroral endoscopic myotomy for the management of symptomatic cricopharyngeal bar (C-POEM): a case series and video demonstration.

Background: A cricopharyngeal bar refers to a radiological description of a prominent cricopharyngeal muscle. While these may be incidental, they can lead to significant oropharyngeal dysphagia due to incoordination of the upper esophageal sphincter and true luminal narrowing. Various treatments have been used for the management of cricopharyngeal bar, including botulinum toxin injection, dilation, and surgical myotomy. Cricopharyngeal peroral endoscopic myotomy (C-POEM) is a novel procedure that uses the principles of "third-space" endoscopy to treat symptomatic cricopharyngeal bar. Methods: We report a retrospective case series of 5 patients referred with oropharyngeal dysphagia to 2 UK tertiary referral centers between 2022 and 2023 who subsequently underwent C-POEM. Technical success was defined as completion of all steps of the C-POEM procedure and clinical success as a reduction in the pre-treatment Dakkak and Bennett score to ≤1, or 0 if the pre-treatment score was 1. Results: C-POEM was associated with a technical success of 100% and clinical success of 100% over a median follow up of 2 months (interquartile range 1-8). There was 1 adverse event due to a small mucosal defect and associated leak on barium swallow, which was the result of difficult access during mucosal closure. This was managed conservatively with antibiotics. A step-by-step video demonstration of the procedure is provided. Conclusion: C-POEM offers an alternative upfront therapy for symptomatic cricopharyngeal bar, but should be undertaken by endoscopists with significant experience in third-space endoscopy in view of the difficulty of working within the hypopharynx.

Success rates of fixation techniques on prevention of esophageal stent migration: a systematic review and meta-analysis.

BACKGROUND: Esophageal stenting is an important intervention for managing malignant and benign dysphagia, with stent migration representing a common drawback. This systematic review with meta-analysis aimed to assess the benefit of stent fixation over nonfixation. METHODS: A systematic search was performed in MEDLINE, Cochrane, Scopus, and ClinicalTrials.gov databases until January 2023 for comparative studies evaluating the migration rates of esophageal stents with versus without (control) fixation. The primary outcome was migration rate. Secondary outcomes included adverse event rate. A subgroup analysis stratified the results based on different fixation techniques: suturing, over-the-scope (OTS) clipping, and through-the-scope (TTS) clipping. Meta-analysis was based on a random effects model and the results were reported as odds ratios (ORs) with 95 %CIs. RESULTS: 10 studies (1014 patients) were included. The rate of stent migration was significantly lower after fixation (OR 0.20, 95 %CI 0.11-0.37; I2  = 59 %, P = 0.01). The adverse event rate was similar between fixation and control groups (OR 0.65, 95 %CI 0.28-1.52; I2  = 55 %, P = 0.06). In the subgroup analysis, all fixation techniques remained superior to nonfixation of stents (suturing OR 0.23, 95 %CI 0.10-0.53; OTS clips OR 0.31, 95 %CI 0.17-0.58; TTS clips OR 0.10, 95 %CI 0.03-0.38); however, only the OTS and TTS clip groups achieved nonsignificant heterogeneity (I2  = 0 %, P = 0.67 and P = 0.73, respectively). No difference between techniques was recorded for migration rates. CONCLUSION: Esophageal stent fixation was associated with significantly lower migration rates compared with nonfixation of stents, regardless of fixation technique and stenting indication.

Endoscopic Management of Dysplastic Barrett's Oesophagus and Early Oesophageal Adenocarcinoma.

Barrett's oesophagus is a pathological condition whereby the normal oesophageal squamous mucosa is replaced by specialised, intestinal-type metaplasia, which is strongly linked to chronic gastro-oesophageal reflux. A correct endoscopic and histological diagnosis is pivotal in the management of Barrett's oesophagus to identify patients who are at high risk of progression to neoplasia. The presence and grade of dysplasia and the characteristics of visible lesions within the mucosa of Barrett's oesophagus are both important to guide the most appropriate endoscopic therapy. In this review, we provide an overview on the management of Barrett's oesophagus, with a particular focus on recent advances in the diagnosis and recommendations for endoscopic therapy to reduce the risk of developing oesophageal adenocarcinoma.

Metabolic and Bariatric Endoscopy: A Mini-Review.

We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty.

Minimally invasive endoscopic therapies for gastro-oesophageal reflux disease.

The prevalence of the gastro-oesophageal reflux disease (GORD) in the western world is increasing. Uncontrolled GORD can lead to harmful long-term sequela such as oesophagitis, stricture formation, Barrett's oesophagus and oesophageal adenocarcinoma. Moreover, GORD has been shown to negatively impact quality of life. The current treatment paradigm for GORD consists of lifestyle modification, pharmacological control of gastric acid secretion or antireflux surgery. In recent years, several minimally invasive antireflux endoscopic therapies (ARET) have been developed which may play a role in bridging the unmet therapeutic gap between the medical and surgical treatment options. To ensure optimal patient outcomes following ARET, considered patient selection is crucial, which requires a mechanistic understanding of individual ARET options. Here, we will discuss the differences between ARETs along with an overview of the current evidence base. We also outline future research priorities that will help refine the future role of ARET.

Effect of gastro-esophageal reflux symptoms on the risk of Barrett's esophagus: A systematic review and meta-analysis.

BACKGROUND AND AIM: Gastro-esophageal reflux (GER) is the main predisposing factor for Barrett's esophagus (BE). A more precise estimate of the association of GER symptoms with the risk of BE would be important to prioritize endoscopic screening. We conducted a systematic review and meta-analysis to examine this issue. METHODS: MEDLINE, EMBASE, and EMBASE Classic were searched to identify cross-sectional studies that reported the prevalence of BE based on presence of GER symptoms. The prevalence of BE was compared according to presence or absence of GER symptoms using an odds ratio (OR), with a 95% confidence interval (CI). Specificity and sensitivity of GER symptoms for predicting BE was calculated. RESULTS: Of 10,463 citations evaluated, 19 studies reported the prevalence of BE in 43,017 subjects. The pooled OR among individuals with weekly GER symptoms compared with those without was 1.67 (95% CI 1.30-2.15) for endoscopically suspected BE, and 2.42 (95% CI 1.59-3.68) for histologically confirmed BE. No significant association was found between weekly GER symptoms and the presence of short segment BE (OR 1.30; 95% CI 0.86-1.97), whereas a strong association was present with long segment BE, with an OR of 6.30 (95% CI 2.26-17.61). CONCLUSIONS: Gastro-esophageal reflux symptoms are associated with an increased odds of BE, with a further increase when weekly symptoms are present. Overall, GER symptoms showed low sensitivity and specificity for predicting BE; however, a strong association was found between weekly GER symptoms and long segment BE, but not short segment BE, suggesting that it may be worth considering screening individuals with weekly GER symptoms to rule out long segment BE.

Applications of Artificial Intelligence for the Diagnosis of Gastrointestinal Diseases.

The development of convolutional neural networks has achieved impressive advances of machine learning in recent years, leading to an increasing use of artificial intelligence (AI) in the field of gastrointestinal (GI) diseases. AI networks have been trained to differentiate benign from malignant lesions, analyze endoscopic and radiological GI images, and assess histological diagnoses, obtaining excellent results and high overall diagnostic accuracy. Nevertheless, there data are lacking on side effects of AI in the gastroenterology field, and high-quality studies comparing the performance of AI networks to health care professionals are still limited. Thus, large, controlled trials in real-time clinical settings are warranted to assess the role of AI in daily clinical practice. This narrative review gives an overview of some of the most relevant potential applications of AI for gastrointestinal diseases, highlighting advantages and main limitations and providing considerations for future development.

The natural history of low-grade dysplasia in Barrett's esophagus and risk factors for progression.

BACKGROUND AND AIM: Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma. The optimal management of low-grade dysplasia arising in Barrett's esophagus remains controversial. We performed a retrospective study from a tertiary referral center for Barrett's esophagus neoplasia, to estimate time to progression to high-grade dysplasia/esophageal adenocarcinoma in patients with confirmed low-grade dysplasia compared with those with downstaged low-grade dysplasia from index presentation and referral. We analyzed risk factors for progression. METHODS: We analyzed consecutive patients with low-grade dysplasia in Barrett's esophagus referred to a single tertiary center (July 2006-October 2018). Biopsies were reviewed by at least two expert pathologists. RESULTS: One hundred and forty-seven patients referred with suspected low-grade dysplasia were included. Forty-two of 133 (32%) of all external referrals had confirmed low-grade dysplasia after expert histopathology review. Multivariable analysis showed nodularity at index endoscopy (P < 0.05), location of dysplasia (P = 0.05), and endoscopic therapy after referral (P = 0.09) were associated with progression risk. At 5 years, 59% of patients with confirmed low-grade dysplasia had not progressed versus 74% of patients in the cohort downstaged to non-dysplastic Barrett's esophagus. CONCLUSION: Our data show variability in the diagnosis of low-grade dysplasia. The cumulative incidence of progression and time to progression varied across subgroups. Confirmed low-grade dysplasia had a shorter progression time compared with the downstaged group. Nodularity at index endoscopy and multifocal low-grade dysplasia were significant risk factors for progression. It is important to differentiate these high-risk subgroups so that decisions on surveillance/endotherapy can be personalized.

Bariatric and Metabolic Endoscopy: A New Paradigm.

The prevalence of obesity, type 2 diabetes mellitus, and metabolic syndromes is increasing globally. Minimally invasive metabobariatric (MB) endoscopic therapies are adjunct treatments that can potentially bridge the gap between surgical interventions and medical therapy. A growing number of MB techniques are becoming available, allowing for more personalized and patient-targeted treatment options for specific disease states. MB techniques are less invasive than surgery and can precisely target different parts of the gastrointestinal tract that may be responsible for the pathophysiology of obesity and metabolic syndromes such as type 2 diabetes mellitus. These alternatives should be selected on an individualized patient basis to balance the expected clinical outcomes and desired anatomical targets with the level of invasiveness and degree of acceptable risk. Each MB intervention presents great flexibility allowing for a tailored intervention and different levels of patient engagement. Patient awareness and motivation are essential to avoid therapy withdrawal and failure. Differences between MB procedures in terms of weight loss and metabolic benefit will be discussed in this review, along with the insights on clinical decision-making processes to evaluate the potential of further evolution and growth of bariatric and metabolic endoscopy.

Side effects of long-term use of proton pump inhibitors: practical considerations.

Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs due to the increasing incidence of acid­related disorders, but a large number of prescriptions are issued with inappropriate indications. Despite PPIs being effective and well tolerated, there have been growing concerns about potential adverse effects associated with long­term use of these drugs. Indeed, pharmacovigilance agencies have issued broad-based product warnings on the association between treatment with PPIs and long­term complications, including increased risk of fractures and impaired magnesium absorption. On the contrary, despite plausible underlying biological mechanisms, the available clinical evidence for most side effects is weak or contradictory, and the benefits of PPI treatment seem to outweigh the potential adverse effects. This review aims to discuss the most important and established side effects of long-term use of PPIs and provide practical considerations for their clinical management.

Systematic review with meta-analysis: risk factors for Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms.

BACKGROUND: Gastro-oesophageal reflux is considered the main risk factor for Barrett's oesophagus. The role of other potential risk factors for the development of Barrett's oesophagus in patients with gastro-oesophageal reflux symptoms is controversial. AIMS: To perform a systematic review and meta-analysis examining risk factors in development of Barrett's oesophagus. METHODS: Medline, Embase and Embase Classic were searched (until December 2020) to identify cross-sectional studies reporting prevalence of Barrett's oesophagus based on presence of one or more proposed risk factors in individuals with gastro-oesophageal reflux symptoms. Prevalence of Barrett's oesophagus was compared according to presence or absence of each risk factor in individuals with gastro-oesophageal reflux symptoms. RESULTS: Of 7164 citations evaluated, 13 studies reported prevalence of Barrett's oesophagus in 11 856 subjects. Pooled prevalence of histologically confirmed Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms in all studies was 7.0% (95% CI 4.8% to 9.6%). Prevalence was higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Other features including non-steroidal anti-inflammatory drugs and/or aspirin use (OR 1.19; 95% CI 1.00 to 1.42), smoking (OR 1.14; 95% CI 0.96 to 1.35) or obesity (OR 1.10; 95% CI 0.92 to 1.33) were not significantly associated with Barrett's oesophagus. CONCLUSIONS: The prevalence of Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms was higher in those who drank alcohol, although this association was modest. The strongest association found was between hiatal hernia and Barrett's oesophagus. Other potential risk factors assessed in this study did not appear to be associated with presence of Barrett's oesophagus among individuals with gastro-oesophageal symptoms.

New Devices for Endoscopic Treatments in Gastroenterology: A Narrative Review.

Endoscopy is in a period of continuous innovations in terms of image quality, endoscopes, post-processing software and lastly, application of Artificial Intelligence. Therapeutic boundaries have expanded, widening the grey zone between endoscopy and surgery, and increasing endoscopic approaches in clinical scenarios where, until a few years ago, surgery was the only option. New scopes and accessories have made it easier to access critical areas such as the biliary tree and the small bowel intestine. In the field of hepato-pancreato-biliary endoscopy (HPB), it is now possible to directly access the biliary ducts or cystic lesions though dedicated stents and scopes, rather than having to rely only on fluoroscopy and ultrasound, increasing the diagnostic and therapeutic options by applying a three-dimensional approach. This narrative review will give an overview of some of the most relevant emerging fields in luminal and HPB endoscopy, highlighting advantages and main limitations of the techniques, and providing considerations for future development.

Gastric cancer prevention strategies: A global perspective.

Gastric cancer (GC) is the fifth most common cancer worldwide, and mortality rates are still high. Primary preventive strategies, aimed to reduce risk factors and promote protective ones, will lead to a decrease in GC incidence. Helicobacter pylori infection is a well-established carcinogen for GC, and its eradication is recommended as the best strategy for the primary prevention. However, the role of other factors such as lifestyle, diet, and drug use is still under debate in GC carcinogenesis. Unfortunately, most patients with GC are diagnosed at late stages when treatment is often ineffective. Neoplastic transformation of the gastric mucosa is a multistep process, and appropriate diagnosis and management of preneoplastic conditions can reduce GC-related mortality. Several screening strategies in relation to GC incidence have been proposed in order to detect neoplastic lesions at early stages. The efficacy of screening strategies in reducing GC mortality needs to be confirmed. This review provides an overview of current international guidelines and recent literature on primary and secondary prevention strategies for GC.

Decellularized Human Gut as a Natural 3D Platform for Research in Intestinal Fibrosis.

BACKGROUND: The current methodologies for the identification of therapeutic targets for inflammatory bowel disease (IBD) are limited to conventional 2-dimensional (2D) cell cultures and animal models. The use of 3D decellularized human intestinal scaffolds obtained from surgically resected intestine and engineered with human intestinal cells may provide a major advancement in the development of innovative intestinal disease models. The aim of the present study was to design and validate a decellularization protocol for the production of acellular 3D extracellular matrix (ECM) scaffolds from the human duodenum. METHODS: Scaffolds were characterized by verifying the preservation of the ECM protein composition and 3D architecture of the native intestine and were employed for tissue engineering with primary human intestinal myofibroblasts for up to 14 days. RESULTS: Engrafted cells showed the ability to grow and remodel the surrounding ECM. mRNA expression of key genes involved in ECM turnover was significantly different when comparing primary human intestinal myofibroblasts cultured in 3D scaffolds with those cultured in standard 2D cultures on plastic dishes. Moreover, incubation with key profibrogenic growth factors such as TGFß1 and PDGF-BB resulted in markedly different effects in standard 2D vs 3D cultures, further emphasizing the importance of using 3D cell cultures. CONCLUSIONS: These results confirm the feasibility of 3D culture of human intestinal myofibroblasts in intestinal ECM scaffolds as an innovative platform for disease modeling, biomarker discovery, and drug testing in intestinal fibrosis.