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.

Performance and safety of percutaneous cholangioscopy: a systematic review and meta-analysis.

Background: Percutaneous cholangioscopy (PerC) offers an alternative for patients with an inaccessible biliary tree. This systematic review and meta-analysis aimed to evaluate the performance of this technique. Methods: A search in Medline, Cochrane and ClinicalTrials.gov databases was performed for studies assessing PerC up to October 2022. The primary outcome was diagnostic success, defined as successful stone identification or stricture workup. Secondary outcomes included therapeutic success (stone extraction, stenting) and complication rate. A subgroup analysis compared previous-generation and modern cholangioscopes. We performed meta-analyses using a random-effects model and the results were reported as percentages with 95% confidence interval (CI). Results: Fourteen studies (682 patients) were eligible for analysis. The rate of diagnostic success was 98.7% (95%CI 97.6-99.8%; I2=31.19%) and therapeutic success was 88.6% (95%CI 82.8-94.3%; I2=74.92%). Adverse events were recorded in 17.1% (95%CI 10.7-23.5%; I2=77.56%), of which 15.9% (95%CI 9.8-21.9%; I2=75.98%) were minor and 0.6% (95%CI 0.1-1.2%; I2=0%) major. The Spyglass system showed null heterogeneity for all outcomes; compared with older-generation endoscopes it offered comparable diagnostic success, but yielded significantly superior therapeutic success (96.1%, 95%CI 90-100%; I2=0% vs. 86.4%, 95%CI 79.2-93.6%; I2=81.41%; P=0.02]. Conclusion: PerC, especially using currently available cholangioscopes, is associated with high diagnostic and therapeutic success.

Epidemiology and Socioeconomic Impact of Pancreatic Cancer: An Analysis of the Global Burden of Disease Study 1990-2019.

INTRODUCTION: The aim of this study is to estimate the global burden of pancreatic cancer from 1990 to 2019. METHODS: We reconstructed the Global Burden of Diseases (GBD) study results for pancreatic cancer across 204 countries and territories. Our study generated estimates for key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and cost. Linear regression analysis of the natural logarithm of age-standardized outcomes was used to calculate annual percent change. RESULTS: In 2019, there were a total of 530,296 incident and 442,101 prevalent cases of pancreatic cancer, resulting in 531,107 deaths and 11.5 million DALYs lost. The age-standardized incidence and prevalence of pancreatic cancer has increased from 5.22 (95% CI 4.97-5.40) to 6.57 (CI 6.00-7.09) per 100,000 people per year, and 4.1 (95% CI 3.95-4.26) to 5.4 (CI 4.96-5.87), respectively. This equated to 10 million (95% CI 9.5 to 10.4 million) incident cases of pancreatic cancer. The number of DALYs lost as a result of pancreatic cancer was 225 million years (95% CI 216-234 million years). Mortality from pancreatic cancer increased over the study period from 3.7 (95% CI 3.54-3.83) to 6.9 (95% CI 6.36-7.32). Incidence, prevalence, DALYs, and mortality were higher in countries with a higher socio-demographic index. CONCLUSIONS: Pancreatic cancer is rising around the world and is associated with a high economic burden. Programs aimed at reducing modifiable risk factors are needed.

Endoscopic Management of Difficult Biliary Stones: An Evergreen Issue.

Choledocholithiasis is one of the most common indications for endoscopic retrograde cholangiopancreatography (ERCP) in daily practice. Although the majority of stones are small and can be easily removed in a single endoscopy session, approximately 10-15% of patients have complex biliary stones, requiring additional procedures for an optimum clinical outcome. A plethora of endoscopic methods is available for the removal of difficult biliary stones, including papillary large balloon dilation, mechanical lithotripsy, and electrohydraulic and laser lithotripsy. In-depth knowledge of these techniques and the emerging literature on them is required to yield the most optimal therapeutic effects. This narrative review aims to describe the definition of difficult bile duct stones based on certain characteristics and streamline their endoscopic retrieval using various modalities to achieve higher clearance rates.

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.

Cannulation rates and technical performance evaluation of commericially available single-use duodenoscopes for endoscopic retrograde cholangiopancreatography: A systematic review and meta-analysis.

BACKGROUND: Single use duodenoscopes were developed to reduce the risk of infection transmission from contaminated reusable duodenoscopes. To this end, we examined various biliary interventions using single use duodenoscopes in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Medline, Embase, Scopus, and Cochrane databases were searched from inception through Aug 2022 to identify studies reporting on the performance of single use duodenoscopes for ERCP. RESULTS: Seven articles were included in the final analysis that included 642 patients (318 males). The Exalt Model D duodenoscope was used in most cases (88.8%) followed by the aScope Duodeno (11.2%) for ERCP. Most ERCPs had a complexity grade of 2 (n = 303) and 3 (n = 198). The pooled cumulative rate of successful cannulation was 95% (95% Confidence Interval (CI): 93-96%, I2=0%, P = 0.46). Sphincterotomy was successfully performed in all cases. The pooled cumulative rate of PEP was 2% (95% CI: 0.4-3.4%, I2=0%, P = 0.80). The pooled cumulative rate of total adverse events was 7% (95% CI: 4-10%, I2=47%, P = 0.08). CONCLUSIONS: The results of this systematic review and meta-analysis show that single use duodenoscopes are associated with high cannulation rates, technical performance, and safety profile.

Nonalcoholic fatty liver disease test: an external validation cohort.

PURPOSE: Non-invasive diagnosis of nonalcoholic fatty liver disease (NAFLD) and its advanced phenotypes (e.g., nonalcoholic steatohepatitis; NASH) is a hot research topic. The aim of this report was the validation of a novel non-invasive index of NAFLD, the "NAFLD test," recently introduced for the diagnosis of NAFLD (vs. non-NAFLD controls). METHODS: This was a post-hoc analysis of a previous study. The NAFLD test was calculated in NAFLD patients and non-NAFLD controls; the performance of the test was compared with that of other non-invasive indices of NAFLD (fatty liver index [FLI] and hepatic steatosis index [HSI]), and other indices of NASH (index of NASH [ION] and cytokeratin-18/homeostasis model assessment-insulin resistance/aspartate transaminase index [CHAI]). RESULTS: The NAFLD test was higher in NAFLD patients than in controls (1.89 ± 0.14 vs. 1.30 ± 0.06, respectively; p < 0.001). In NAFLD patients, the NAFLD test was higher in NASH patients than in those with simple nonalcoholic fatty liver (NAFL) (2.21 ± 0.24 vs. 1.57 ± 0.08, respectively; p = 0.007). The area under the receiver operating characteristic curve (AUC) of the NAFLD test was 0.84 (95% CI: 0.74-0.94; p < 0.001) for differentiation between NAFLD and non-NAFLD controls and its performance was similar to that for FLI and HSI. For differentiation between NASH and NAFL patients, the AUC of the NAFLD test was 0.88 (95% CI: 0.62-0.96; p = 0.007) and its performance was superior to that for ION and CHAI. CONCLUSIONS: The NAFLD test was validated in this external cohort for the non-invasive diagnosis of NAFLD patients vs. non-NAFLD individuals. It was also shown to differentiate between NASH and NAFL patients with acceptable accuracy.

Models and scores to predict adequacy of bowel preparation before colonoscopy.

Adequate bowel preparation is of paramount importance for the effectiveness of preventive colonoscopy as it allows visualization of the mucosal surface and adenomas detection, the pre-malignant lesions leading to colon cancer. Still, a considerable portion of patients fail to achieve adequate bowel cleansing, with predictors of inadequate bowel preparation being at the focal point of several studies, so far. Incorporation of these factors within predictive models has been implemented in an effort to promptly identify patients at risk for inadequate bowel preparation and thus, timely adopt practices that have the potential to improve bowel cleansing. Ultimately, this could lead to improved procedural outcomes not only in terms of neoplastic detection rate but also interval repeat procedures, expenses, patient convenience and adverse events risk. Aim of this manuscript is to present an up to date overview of all predictive scores/models addressing bowel cleansing adequacy in everyday clinical practice.

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.

Potential impact of trained innate immunity on the pathophysiology of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) occurs in a low-grade inflammatory milieu dependent on highly complex networks that span well-beyond the hepatic tissue injury. Dysfunctional systemic metabolism that characterizes the disease, is further induced in response to environmental cues that modify energy and metabolic cellular demands, thereby altering the availability of specific substrates that profoundly regulate, through epigenetic mechanisms, the phenotypic heterogeneity of immune cells and influence hematopoietic stem cell differentiation fate. This immuno-metabolic signaling drives the initiation of downstream effector pathways and results in the decompensation of hepatic homeostasis that precedes pro-fibrotic events. Recent evidence suggests that innate immune cells reside in different tissues in a memory effector state, a phenomenon termed trained immunity, that may be activated by subsequent exogenous (e.g., microbial, dietary) or endogenous (e.g., metabolic, apoptotic) stmuli. This process leads to long-term modifications in the epigenetic landscape that ultimately precondition the cells towards enhanced transcription of inflammatory mediators that accelerates MAFLD development and/or progression. In this mini review we aimed to present current evidence on the potential impact of trained immunity on the pathophysiology of MAFLD, shedding light on the complex immunobiology of the disease and providing novel potential therapeutic strategies to restrain the burden of the disease.

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.

Performance of endoscopic submucosal dissection for undifferentiated early gastric cancer: a multicenter retrospective cohort.

Background and study aims Undifferentiated early gastric cancer (UD-EGC) represents an extended indication for endoscopic submucosal dissection (ESD) based on the existing guidelines. This study evaluated the prevalence of UD-EGC recurrence after ESD, and potentially implicated risk factors. Patients and methods Data from 17 centers were collected retrospectively including demographics, endoscopic and pathological findings, and follow-up data from UD-EGC cases treated by ESD. Patients with incomplete resection or advanced disease were excluded. Descriptive statistics quantified variables and calculated the incidence of recurrence. Chi-square test was applied to assess any link between independent variables and relapse; significantly associated variables were inserted to a multivariable regression model. Results Seventy-one patients were eligible, with 2:1 female to male ratio and age of 65.8 ± 11.8 years. Mean lesion size was 33.5 ± 18.8 mm and the most frequent histological subtype was signet ring-cells UGC (2:1). Patients were followed-up every 5.6 ± 3.7 months with a mean surveillance period of 29.3 ± 15.3 months until data collection. Four patients (5.6%) developed local recurrence 8.8 ± 6.5 months post-ESD, with no lymph node or distal metastases been reported. Lesion size was not associated with recurrence ( P = 0.32), in contrast to lymphovascular and perineural invasion which were independently associated with local recurrence ( P = 0.006 and P < 0.001, respectively). Conclusions ESD could be considered as the initial step to manage UD-EGC, providing at least an "entire-lesion" biopsy to guide therapeutic strategy. When histology confirms absence of lymphovascular and perineural invasion, this modality could be therapeutic, providing low recurrence rates.

Effect of add-on devices with projections on screening colonoscopy: a systematic review and meta-analysis.

Background: Add-on devices with projections, e.g., Endocuff, Endocuff Vision, EndoRings, and Wingcap, placed on the distal tip of the colonoscope promise to improve the detection of precancerous lesions. We performed a meta-analysis to evaluate the performance of these devices exclusively among individuals undergoing colonoscopy for screening purpose. Methods: A computerized literature search was performed across MEDLINE and Cochrane Library databases for randomized controlled trials that compared standard colonoscopy (SC) to procedures using add-on devices. The primary outcome was adenoma detection rate (ADR), while secondary outcomes included polyp detection rate (PDR), advanced ADR (AADR), and sessile serrated lesion detection rate (SSLDR). The effect size on study outcomes was calculated using a random-effects model and presented as the risk ratio (RR) and 95% confidence interval (CI). Results: Seven studies enrolling a total of 5785 patients were included. The use of add-on-devices with projections was associated with a higher ADR compared to SC: 45.9% vs. 41.1%; RR 1.18, 95%CI 1.02-1.37; P=0.03; I2=79%. Although PDR was higher in screening colonoscopies assisted by add-on devices as compared to SC, the difference failed to reach significance: 55.1% vs. 50.8%; RR 1.10, 95%CI 0.96-1.26; P=0.17; I2=75%. No difference was found between procedures assisted by add-on devices with projections and SC colonoscopies in terms of AADR (18.5% vs. 17.6%; RR 1.00, 95%CI 0.79-1.27; P=0.98; I2=56%) or SSLDR (6.8% vs. 5.8%; RR 1.17, 95%CI 0.95-1.44; P=0.15; I2=0%). Conclusion: Colonoscopy assisted by add-on devices with projections achieves a better ADR compared to SC among individuals undergoing screening for bowel cancer.

PERcutaneous transhepatic CHOLangioscopy using a new single-operator short cholangioscope (PERCHOL): European feasibility study.

OBJECTIVES: A new short device for percutaneous endoscopic cholangioscopy was recently developed. However, feasibility and safety has not yet been evaluated. The aim of this study was to assess clinical success, technical success, and adverse events (AEs). METHODS: This observational multicenter retrospective study included all patients who underwent percutaneous cholangioscopy using a short cholangioscope between 2020 and 2022. The clinical success, defined as the complete duct clearance or obtaining at least one cholangioscopy-guided biopsy, was assessed. The histopathological accuracy, technical success, and the AE rate were also evaluated. RESULTS: Fifty-one patients (60 ± 15 years, 45.1% male) were included. The majority of patients had altered anatomy (n = 40, 78.4%), and biliary stones (n = 34, 66.7%) was the commonest indication. The technique was predominantly wire-guided (n = 44, 86.3%) through a percutaneous sheath (n = 36, 70.6%) following a median interval of 8.5 days from percutaneous drainage. Cholangioscopy-guided electrohydraulic lithotripsy was performed in 29 cases (56.9%), combined with a retrieval basket in eight cases (27.6%). The clinical success was 96.6%, requiring a median of one session (range 1-3). Seventeen patients (33.3%) underwent cholangioscopy-guided biopsies. There were four (7.8%) cholangioscopy-related AEs (cholangitis and peritonitis). Overall, the technical success and AE rates were 100% and 19.6%, respectively, in a median follow-up of 7 months. CONCLUSION: Percutaneous endoscopic cholangioscopy with a new short device is effective and safe, requiring a low number of sessions to achieve duct clearance or accurate histopathological diagnosis.