Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study.

BACKGROUND: Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications. AIM: To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications DESIGN: We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs. RESULTS: 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett's without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett's with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide. CONCLUSION: Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.

Minimal access surgery of corrosive and thermal strictures of the foregut.

Background and Aim: : Conventional surgery for caustic/thermal strictures (CS/TS) entails considerable trauma, which may be mitigated by minimal access surgery (MAS). Experience with its use in CS/TS is both heterogeneous and limited, hence, warrants a comprehensive review. Methods: : Medical literature/indexing databases were systematically searched for pertinent articles published in English, from 1990 to 2021, and analysed. Results: : Fifty relevant articles, pertaining to over 200 patients, were found. They showed that MAS is feasible in CS/TS management. It reduces the access damage in chest and abdomen whilst facilitating resection or bypass of the affected gut segment through different combination of operations, sequence of steps, conduits and routes. The procedures range from completely minimal access to hybrid ones, with reduced complications and faster recovery. Hybrid procedures prove as expeditious as open ones. Conclusions: : MAS proves efficacious in restoring alimentary continuity in corrosive/thermal strictures of the foregut.

Eosinophilic oesophagitis: recent advances and practical management.

Eosinophilic oesophagitis (EoE) is a disease identified just over 30 years ago. The main symptom is dysphagia. EoE is initially inflammatory and progresses to fibrosis. There are differences in clinical presentation between young children and adults. Diagnosis is by endoscopy and six biopsies at varying positions of the oesophageal lining. Blood tests are of no diagnostic value as the condition is mediated by IgG4 local mucosal pathology. Endoscopic signs are distinct from those of gastro-oesophageal reflux. Histological signs of EoE are >15 eosinophils/high-power field on a background of hyperplastic mucosa. Options of therapy include diet restriction, proton pump inhibitors therapy and topical steroids but there is a dearth of randomised control trials to define the optimum approach. The only licenced therapy for EoE is budesonide orodispersible tablet, a specific formulation for oesophageal topical steroid therapy. EoE is the most common cause of spontaneous perforation in the oesophagus. Stricture formation occurs in up to 10% and may require therapeutic dilatation.

Post-transplant lymphoproliferative disorder as a cause of oesophageal ulceration and stricture: case report and literature review.

Post-transplant lymphoproliferative disorder (PTLD) of the oesophagus is a rare complication of solid organ transplant that requires a high index of suspicion to diagnose. A literature review conducted on Ovid Medline database retrieved 24 articles, among which five previous cases of oesophageal PTLD were identified. Development of oesophageal strictures related to PTLD has not been reported in the literature. We report a case of oesophageal PTLD following lung transplant, presenting with extensive, circumferential ulceration in the oesophagus. PTLD was successfully treated with chemotherapy but subsequently, this patient developed a severe oesophageal stricture at the site of her PTLD. She presented with an episode of food bolus impaction requiring endoscopic retrieval. In the following years, our patient required multiple endoscopic dilatations of this PTLD-related oesophageal stricture.

Factors affecting the outcome of endoscopic dilatation in refractory post-corrosive oesophageal stricture in Egyptian children: a single-centre study.

BACKGROUND: An important complication of corrosive ingestion is oesophageal stricture. Improvements in endoscopes and accessories have supported an increase in the number of patients who are conservatively treated with endoscopic dilations. In this study, we aimed to detect factors affecting the outcome of endoscopic dilatation for refractory post-corrosive oesophageal stricture. METHODS: This study was carried out in the Paediatric Endoscopy Unit in the Children's Hospital and included 100 children older than 2 years of age of both sexes who had an established diagnosis of post-corrosive oesophageal stricture on repeated endoscopic dilatation sessions. The duration of the condition was more than 6 months, and dilatation failed to achieve a diameter of 14 mm during the first five sessions at 2-week intervals (refractory), excluding other causes of oesophageal stricture. RESULTS: Males represented 63% of patients. The mean age of enrolled children was 5.9 ± 2.6 years; 90% of patients ingested an alkaline corrosive substance (potash). The total number of dilatation sessions ranged from 16 to 100, with a mean number of sessions ranging from 37.2 ± 14.9. Fifty-four patients (54%) were well controlled by regular endoscopic dilatation with good clinical and endoscopic outcomes, and no more dilatations were needed. CONCLUSION: Endoscopic dilation is an effective method for managing refractory post-corrosive oesophageal strictures that require a long follow-up period. There are a lot of factors affecting the outcome.

Management of benign oesophageal strictures.

Benign oesophageal strictures are an important gastrointestinal condition that can cause substantial morbidity. There are many different aetiologies and each case needs careful evaluation and individualised treatment. Management usually involves targeting therapy to the underlying cause, but oesophageal dilatation is an important part of the algorithm. The recent British Society of Gastroenterology guidelines provide advice on the use of dilatation for benign strictures and cover patient preparation, the dilatation procedure and disease-specific considerations. This article provides a summary of the key messages from the guidelines and applies them to routine clinical practice. It also includes practical advice on the clinical assessment, investigation and management of benign oesophageal strictures and gives an approach to the management of refractory strictures. Areas where evidence is sparse and further research is needed are highlighted.

Histopathological changes in the oesophageal mucosa in Egyptian children with corrosive strictures: A single-centre vast experience.

BACKGROUND: The caustic ingestion continues to be a major problem worldwide especially in developing countries. The long-term complications include stricture and increased life time risk of oesophageal carcinoma. Patients suffered from corrosive induced oesophageal strictures have more than a 1000-fold risk of developing carcinoma of the oesophagus. AIM: To determine the possibility of oesophageal mucosal dysplasia after prolonged dilatation in post corrosive stricture. METHODS: This observational study was conducted at the Paediatric Endoscopy Unit in Cairo University Children's Hospital. It included children of both sexes older than 2 years of age who had an established diagnosis of post-corrosive oesophageal stricture and repeated endoscopic dilatation sessions for more than 6 mo. All patients were biopsied at the stricture site after 6 mo of endoscopic dilatation. A histopathological examination of an oesophageal mucosal biopsy was performed for the detection of chronic oesophagitis, inflammatory cellular infiltration and dysplasia. RESULTS: The mean age of the enrolled children was 5.9 ± 2.6 years; 90% of the patients had ingested an alkaline corrosive substance (potash). The total number of endoscopic dilatation sessions were ranging from 16 to 100 with mean number of sessions was 37.2 ± 14.9. Histopathological examination of the specimens showed that 85% of patients had evidence of chronic oesophagitis (group A) in the form of basal cell hyperplasia, hyperkeratosis and subepithelial fibrosis. Thirteen percent of the patients had evidence of reactive atypia (group B) in the form of severe neutrophilic intraepithelial inflammatory cellular infiltration, and 2 patients (2%) had mild squamous dysplasia (group C); we rebiopsied these two patients 6 mo after the initial pathological assessment, guided by chromoendoscopy by Lugol's iodine. CONCLUSION: The histopathology of oesophageal mucosal biopsies in post-corrosive patients demonstrates evidence of chronic oesophagitis, intraepithelial inflammatory cellular infiltration and dysplasia. Dysplasia is one of the complications of post-corrosive oesophageal stricture.

Risk factors for refractory anastomotic strictures after oesophageal atresia repair: a multicentre study.

OBJECTIVE: To determine the incidence of refractory anastomotic strictures after oesophageal atresia (OA) repair and to identify risk factors associated with refractory strictures. METHODS: Retrospective national multicentre study in patients with OA born between 1999 and 2013. Exclusion criteria were isolated fistula, inability to obtain oesophageal continuity, death prior to discharge and follow-up <6 months. A refractory oesophageal stricture was defined as an anastomotic stricture requiring ≥5 dilations at maximally 4-week intervals. Risk factors for development of refractory anastomotic strictures after OA repair were identified with multivariable logistic regression analysis. RESULTS: We included 454 children (61% male, 7% isolated OA (Gross type A)). End-to-end anastomosis was performed in 436 (96%) children. Anastomotic leakage occurred in 13%. Fifty-eight per cent of children with an end-to-end anastomosis developed an anastomotic stricture, requiring a median of 3 (range 1-34) dilations. Refractory strictures were found in 32/436 (7%) children and required a median of 10 (range 5-34) dilations. Isolated OA (OR 5.7; p=0.012), anastomotic leakage (OR 5.0; p=0.001) and the need for oesophageal dilation ≤28 days after anastomosis (OR 15.9; p<0.001) were risk factors for development of a refractory stricture. CONCLUSIONS: The incidence of refractory strictures of the end-to-end anastomosis in children treated for OA was 7%. Risk factors were isolated OA, anastomotic leakage and the need for oesophageal dilation less than 1 month after OA repair.

Oesophageal stents for the treatment of radiation and anastomotic oesophageal strictures.

Benign oesophageal strictures can arise in the treatment of oesophageal cancer as a result of radiation therapy, or at anastomotic sites, post-oesophagectomy. Data on the benefit of stenting of these types of stricture is limited. We analyzed the effects of oesophageal stents on such benign esophageal strictures. In this retrospective study, data was obtained from consecutive patients, 18 years and above from January 2000 to May 2016. Inclusion criteria comprised of oesophageal stenting in post-radiation strictures and anastomotic strictures, without any malignant residual disease. 17 patients had 22 stents inserted. 11 of these were female. 17 stents were self-expanding metallic stents (SEMS) and five were biodegradable (BDS). 12 strictures occurred post-radiation, while five were anastomotic strictures. Technical and clinical success rates were 100% and 86.4% respectively. Overall longterm clinical success was 45.5% (47% for BDS, 40% for SEMS). Minor, short-term complications, including pain and/or vomiting, were observed in 54.6% (n=12). The overall mean dysphagia score pre- and post-stenting was 2.95 and 1.36 (p=0.0001). Comparison of the dysphagia free survival for anastomotic and post-radiation strictures was statistically similar (p=0.22), as was the dysphagia free survival comparison between BDS and SEMS (p=0.055). BDS and SEMS are a safe and effective treatment modality for oesophageal strictures arising post-radiation or at the site of anastomoses. Retrospective study design and a low number of patients remain limiting factors of the study.

UK guidelines on oesophageal dilatation in clinical practice.

These are updated guidelines which supersede the original version published in 2004. 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. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.

Recurrent Complete Pharyngo-Oesophageal Stricture Treated by Multidisciplinary Anterograde-Retrograde Endoscopic Dilation.

Complete pharyngo-oesophageal stricture (PES) after radiotherapy for head and neck cancer is a relatively rare and difficult complication to manage. Historically this condition has been treated surgically, but endoscopic approaches are now available. We present a 61-year-old man with an epidermoid carcinoma of the supraglottic stage and a micro-invasive epidermoid carcinoma of the oropharynx treated surgically and subsequently by adjuvant radiotherapy. Eight months after the end of the radiotherapy, a complete PES was diagnosed and treated with a combined anterograde-retrograde endoscopic dilation (CARD). The procedure was performed using a transoral anterograde progression with a rigid pharyngoscope and a retrograde progression with an extra-slim nasal endoscope using the percutaneous gastrostomy already in place. Using both transillumination and direct visualisation from both sides of the complete stenosis patency was restored between the neopharynx and the oesophagus. Despite the use of an endoprosthesis, the complete PES recurred and the technique had to be performed a second time. Illustrating the complexity of the case different types of endoprosthesis and several dilations had to be performed for our patient to achieve and maintain a normal oral intake. This case report illustrates that even in complicated recurrent radiation-induced complete PES a CARD can be performed safely and successfully using different types of endoprosthesis.

Oesophageal stenting for benign and malignant strictures: a systematic approach.

Oesophageal stenting is now standard treatment for managing both benign and malignant stenosis of the oesophagus. There is a wide choice in oesophageal stents currently available on the market, with variations in the stent material, size and design. Most oesophageal stents are made from metal alloy compounds for use in malignant strictures, although there are stents made of durable polymers, and now of biodegradable (BD) material, for use in both benign and malignant strictures. With the development of self-expanding plastic stents, self-expanding metal stents and BD stents, stent placement for oesophageal pathologies can be safe and cost-effective. Oesophageal stenting has several challenges for a therapeutic endoscopist which is determined by the location of stricture or tumour, the anatomy of the stenosis and the nature of stent selected. Strictures that have narrow or tortuous lumens can be particularly difficult to stent as the luminal diameter must allow access of at least a 0.035 inch guide wire. This review covers the indications and outcomes of different stents in clinical situations to help rational decision-making.

Update on basic and clinical aspects of eosinophilic oesophagitis.

The identification of a distinct syndrome, designated eosinophilic oesophagitis (EoE), with its own clinical and histopathological characteristics, was first described in the early 1990s. Meanwhile intense research has uncovered many molecular, immunological and clinical aspects of this chronic-inflammatory disorder. This article focuses exclusively on basic and clinical insights of EoE gathered during the last few years. Regarding aetiopathogenesis it has become clear that EoE is a food-triggered disease with milk and wheat as the dominant culprit food categories. However, it is still debated whether a disturbed mucosal integrity allowing allergens to cross the mucosal barrier, or changes in wheat and milk manufacturing might induce these inflammatory responses. Furthermore, basic science and clinical studies have accordingly confirmed that a chronic eosinophilic inflammation leads to a remodelling of the oesophagus with micro- and macro-morphological alterations, ending in a strictured oesophagus with impaired function. Fortunately, long-term therapeutic trials, using either topical corticosteroids or dietary allergen avoidance, have demonstrated that this sequela can be prevented or even reversed. This finding is of clinical relevance as it supports the initiation of a consistent anti-inflammatory therapy. Nevertheless, EoE is still an enigmatic disease and the long list of unanswered questions will certainly stimulate further research.

Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium.

OBJECTIVE: As a major cellular defence mechanism, the Nrf2/Keap1 pathway regulates expression of genes involved in detoxification and stress response. Here we hypothesise that Nrf2 is involved in oesophageal barrier function and plays a protective role against gastro-oesophageal reflux disease (GERD). DESIGN: Human oesophageal biopsy samples, mouse surgical models and Nrf2(-/-) mice were used to assess the role of the Nrf2/Keap1 pathway in oesophageal barrier function. Trans-epithelial electrical resistance (TEER) was measured with mini-Ussing chambers. HE staining and transmission electron microscopy were used to examine tissue morphology, while gene microarray, immunohistochemistry, western blotting and chromatin immunoprecipitation (ChIP) analysis were used to assess gene expression. RESULTS: Nrf2 was expressed in normal oesophageal epithelium and activated in GERD of both humans and mice. Nrf2 deficiency and gastro-oesophageal reflux in mice, alone or in combination, reduced TEER and increased intercellular space in oesophageal epithelium. Nrf2 target genes and gene sets associated with oxidoreductase activity, mitochondrial biogenesis and energy production were downregulated in the oesophageal epithelium of Nrf2(-/-) mice. Consistent with the antioxidative function of Nrf2, a DNA oxidative damage marker (8OHdG) dramatically increased in oesophageal epithelial cells of Nrf2(-/-) mice compared with those of wild-type mice. Interestingly, ATP biogenesis, Cox IV (a mitochondrial protein) and Claudin 4 (Cldn4) expression were downregulated in the oesophageal epithelium of Nrf2(-/-) mice, suggesting that energy-dependent tight junction integrity was subject to Nrf2 regulation. ChIP analysis confirmed the binding of Nrf2 to Cldn4 promoter. CONCLUSIONS: Nrf2 deficiency impairs oesophageal barrier function through disrupting energy-dependent tight junction.

A candidal oesophageal stricture responsive to fluconazole therapy.

We report a case of candidal oesophageal stricture in an 81 year-old man with a 2 year history of gradual onset dysphagia and odynophagia to solids. Although rare, most cases have reported treatment success with oesophageal balloon dilation. We report the first case of candidal oesophageal stricture resolution with a prolonged course of anti-fungal therapy.