Introduction

Proximal oesophageal strictures are less common than distal oesophageal strictures, but can share an aetiology such as eosinophilic or peptic. However, often proximal oesophageal strictures have an unclear aetiology. This results in symptomatic treatment with dilatation, without treatment of the underlying causative factor to prevent further stricture formation. We hypothesised that most proximal oesophageal strictures without a clear aetiology may be secondary to Candida oesophagitis.

Aims & Methods

The aim was to determine the cause of proximal oesophageal strictures of unclear aetiology, and examine the outcomes of medical and endoscopic treatment. Retrospective analysis was performed to identify all cases of proximal oesophageal stricture (≤30cm from incisors) without clear aetiology at Guy’s and St. Thomas’ Trust from 2007 to 2024. Procedures were extracted from the electronic endoscopy database using the keyword ‘dilat’. Patients with Barrett’s oesophagus, Schatzki ring, eosinophilic oesophagitis, anastomotic stricture, radiofrequency ablation, peptic stricture, oesophagectomy, chemo/radiotherapy, Crohn’s disease, achalasia or caustic ingestion were excluded. Oesophageal histopathology taken at any point was assessed for candidiasis. Data collected included demographics, clinical presentation, endoscopic findings, histopathology results, medical and endoscopic treatment and outcomes.

Results

Between 2007 and 2024, 19 patients were identified with a proximal oesophageal stricture without an alternative aetiology. All patients had Candida oesophagitis at either at presentation with the stricture or predating it. The mean age at presentation was 57 years (range 40-80, 95% CI ±5.7) and 78.9% of patients were male. Eight patients (42.1%) were immunocompetent and not prescribed immunosuppressant drugs e.g. corticosteroids.
All strictures were between 15 and 30cm from the incisors (median 24cm). Only two strictures were passable with a standard endoscope, and thus were not dilated. Histopathology of the strictures confirmed no eosinophilia. The most common finding on histopathology was lymphocytic inflammation. On average, each patient had 2 balloon dilatations performed (range 0-12). Following treatment with antifungals and dilatation, 53.3% of patients had resolution of the stricture, 31.3% had ongoing Candida plus a stricture, 13.3% had a stricture without Candida present. Patients with failure of anti-fungal therapy to treat Candida had an increased number of dilatations required.

Conclusion

In conclusion, this case series of 19 patients shows that proximal oesophageal strictures due to Candida are more common than previously thought. At our centre, all patients with a proximal stricture of unknown cause had oesophageal candidiasis. Where a clear alternative cause has not been identified, Candida should be considered, even in patients who are immunocompetent. Anti-fungal therapy is essential to remove the underlying causative factor, and approximately half of patients will have resolution of their stricture following dilatation once Candida has been treated. Patients who did not have resolution of Candida with antifungals were more likely to require a higher number of dilatations.

Introduction

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive and effective treatment for obesity. However, concerns remain regarding gastric mucosal folding and the resulting reduced visibility of the gastric lining. To address these limitations, we developed a novel peroral endoscopic myo-neurotomy (POEM-N) technique (1), adapted from peroral endoscopic myotomy (POEM), as a weight-loss procedure. Although promising, the original POEM-N was time-consuming. This study aims to evaluate the safety and efficacy of a revised POEM-N (R-POEM-N) technique using a submucosal approach as a less invasive bariatric option in a porcine model.

Aims & Methods

Twelve pigs were assigned to either the R-POEM-N group (n = 8) or a sham endoscopic control group (n = 4). Myo-neurotomy was performed at four gastric sites in the R-POEM-N group: two on the greater curvature of the gastric body and two in the antrum. All pigs were fed a hypercaloric diet (twice the standard weight-based intake) and monitored for eight weeks post-procedure. The primary outcome was the proportional change in body weight at 8 weeks, calculated as the ratio of weight change to baseline weight. Secondary outcomes included food intake, changes in serum glucolipid levels, and assessments of safety and procedural duration.

Results

R-POEM-N was successfully completed in all pigs without major adverse events. The mean procedure time was 171.3 ± 3.0 minutes. At 8 weeks, the proportional change in body weight was significantly lower in the R-POEM-N group compared to controls (P = 0.017). Food intake was also significantly reduced in the R-POEM-N group (P < 0.05). No significant differences were observed in serum glucolipid levels between groups.

Conclusion

R-POEM-N effectively limited weight gain in a porcine model and demonstrated a favorable safety profile. These findings suggest that R-POEM-N may serve as a promising, minimally invasive bariatric intervention.

References

(1) Hamada K, Yamasaki Y, Takaki A, et al. Gastric peroral endoscopic myo-neurotomy as less-invasive bariatric surgery in porcine models: an experimental study. iGIE. 2024; 3: 358–65 doi: 10.1016/j.igie.2024.06.002.

Introduction

Recent insights in polyp molecular biology have suggested that hyperplastic polyps (HP) are closely related to sessile serrated lesions (SSL). Their hallmark serrated crypts closely resemble those found in SSL. Furthermore, similar to SSL, specific subtypes of HP can harbor BRAFV600E-mutations. These findings, amongst others, have raised the hypothesis that some HP may have an intrinsic malignant potential through the serrated neoplasia pathway. However, in everyday clinical practice, no routine HP subdifferentiation is performed. Therefore, we aimed to develop a deep learning algorithm to classify molecular subclasses of HP, namely microvesicular hyperplastic polyps (MVHP) and goblet cell-rich hyperplastic polyps (GCHP), based on their endoscopic features.

Aims & Methods

In this single-center trial 238 hyperplastic polyps from 159 patients were retrospectively selected. All polyps had high quality endoscopic video in white light endoscopy and virtual chromoendoscopy (i-scan) using Pentax EC38-i20c and EC34-i10 endoscopes. All histological slides were reviewed by an expert pathologist, updating diagnoses to MVHP, GCHP or mixed HP. We selected the polyps without mixed constitution for development of a deep learning algorithm. These polyps were randomly split into 70% for training, 10% for validation and 20% for testing. Sequences of still images of the polyps were manually annotated and subsequently used to train a deep learning algorithm, with dataset imbalance addressed by randomly oversampling the MVHP.

Results

The 238 HPs were reclassified as 152 GCHP, 59 MVHP and 27 mixed HPs after expert histological review. We subsequently trained a convolutional neural network on the 211 HPs without mixed constitution. This resulted in a model with an AUC of 0.817, corresponding to a sensitivity of 80.0% for predicting MVHP and 78.4% for predicting GCHP. However, due to the low prevalence of MVHP (28%) the positive predictive value for MVHP is only 33.3%, whilst the positive predictive value for GCHP is 96.7%.

Conclusion

We successfully developed a deep learning algorithm capable of differentiating between molecular subclasses of hyperplastic polyps (MVHP vs GCHP) based on their endoscopic features. This model demonstrated a robust AUC of 81.7% with a sensitivity of 80.0% and 78.4% for predicting MVHP and GCHP respectively. However, the low prevalence of MVHP (28%) limited its positive predictive value (33.3%) for predicting MVHP. Despite these challenges, this pilot study serves as a proof of concept that artificial intelligence is capable of predicting hyperplastic polyp subclasses based on endoscopic appearance. Furthermore, it highlights the potential of artificial intelligence to enhance the diagnostic precision, which could contribute to more tailored surveillance and management strategies in the future.

Disclosure

The authors declare no conflicts of interest.

Introduction

Chronic viral hepatitis is among the principal public health problems and a leading cause of morbidity and mortality. The advent of direct-acting antiviral agents (DAAs) impressively changed the management of chronic Hepatitis C virus (HCV) infection. In parallel, WHO's global hepatitis strategy aims to reduce new hepatitis infections by 90% and deaths by 65% from 2016 to 2030 and to identify undiagnosed individuals with chronic hepatitis infection before clinical progression. Currently, a free screening for HCV infection is offered in Italy to subjects born between 1969 and 1989 and also to subjects under the care of addiction services (SerD) and those in detention. In line with national screening plans, the Tuscany Region activated free screening among these subjects.

Aims & Methods

This study aimed to define the prevalence of chronic HCV infection in patients over 55, specifically those not included in free HCV screening programs, aligning with global, regional, and national plans for HCV elimination. Additionally, the study provides a linkage to the care of those infected, evaluates the hepatitis B virus (HBV) prevalence in a subgroup of patients, and describes the clinical features of this study population. Patients born before 1969 hospitalized to the Internal Medicine and Gastroenterology Divisions at Santa Maria alle Scotte Hospital in Siena prospectively underwent screening for HCV antibodies. The gastroenterology cohort was evaluated for HBV infection. All enrolled patients were assessed for comorbidities, treatment and transaminase levels (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]).

Results

A total of 207 subjects, of whom 169 resided in Siena, were divided into three cohorts based on the department where they were admitted and underwent HCV screening. Patients present a high prevalence of comorbidities (88.4%), among them common were cardiovascular diseases (68.1%), cancer (35.3%), liver and hepatobiliary diseases (28%), and diabetes (22.2%). In the entire study population, 15.5% of patients received immunomodulating drugs. Overall, 63 patients (30.4%) showed the presence of elevated transaminase levels, 8 patients (3.9%) were anti-HCV positive, and 2 were HCV RNA positive (0.9%). Of 96 patients in the gastroenterology cohort, 9 (9.4%) had HBV infection, of whom 8.4% had HBsAg-negative infection.

Conclusion

An active HCV infection prevalence of 0.9% was found in hospitalized patients (> 55 years old). A substantial proportion of people in the gastroenterology cohort residing in South-Eastern Tuscany carried occult HBV infection (8.4%). The increase in transaminase levels can be linked to the combined presence of liver and hepatobiliary diseases and the administration of immunomodulatory drugs. This study confirms that an opportunistic screening can contribute to identifying the submerged people affected by viral hepatitis.

References

1. World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. Accessed June 2016. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf
2. Ministero della Salute. DECRETO 14 Maggio 2021. Esecuzione dello Screening Nazionale per L’eliminazione del Virus dell’HCV. (21A04075) (GU Serie Generale n.162 del 08-07-2021). https://www.gazzettaufficiale.it/eli/id/2021/07/08/21A04075/sg (accessed on 8 July 2021).
3. REGIONE TOSCANA. Avvio di un Programma di Screening Gratuito per Prevenire, Eliminare ed Eradicare il Virus Dell’epatite C, in Attuazione Dell’art. 25-Sexies del D.L.n. 162/2019. http://www301.regione.toscana.it/bancadati/atti/Contenuto.xml?id=5355950&nomeFile=Delibera_n.1538_del_27-12-2022 (accessed on 31 December 2022)

Disclosure

Prof. Brillanti reports grants and personal fees from Gilead Sciences.

Introduction

Endoscopic depth diagnosis is essential for the treatment decision of Barrett's esophageal adenocarcinoma (BEA). However, it is sometimes difficult to diagnose due to the anatomy of the esophagogastric junction, such as the difficulty of luminal distension. For inconclusive cT1a or cT1b lesions, we introduced staging ESD, allowing for histologic diagnosis for depth invasion. However, the clinical feasibility and significance of staging ESD remain unclear.

Aims & Methods

In this study, we evaluated the performance of endoscopic depth diagnosis of cT1 BEA and the appropriate treatment strategy.
This study included cT1N0M0 BEA treated with ESD or surgery from January 2015 to June 2024. The cases with poorly differentiated component on target biopsy were excluded. Endoscopic depth diagnosis was based on macroscopic appearance (such as the following findings suggestive of cT1b: polypoid, mixed macroscopic type, thickness, hardness, severe redness, and ulceration). EUS was added at the discretion of the endoscopist. We made the treatment decision based on our multidisciplinary conference, and the final diagnosis was classified as conclusive cT1a or cT1b, and inconclusive cT1a or cT1b. We performed ESD for conclusive cT1a, and surgery for conclusive cT1b. And we performed staging ESD for inconclusive cT1a or cT1b. Curative resection was defined as pT1a with R0 resection, and without lymphovascular invasion or poorly differentiated component.

Results

This study included 54 lesions in 52 patients. The median age was 66 years (43-92). There were 42 male patients. Siewert type [type I/type II] were 12 and 42, respectively. Background Barrett’s esophagus [SSBE/LSBE] were 36 and 16, respectively. The median size was 20mm (5-50). Major macroscopic appearances [0-I/0-IIa/0-IIb/0-IIc] were 11, 19, 1, and 23, respectively. Histology on targeted biopsy [tub1/tub2] were 41, 13, respectively. 39 lesions were diagnosed by white light endoscopy alone, and 15 lesions were comprehensively diagnosed by additional EUS. 41 lesions were diagnosed as cT1a and 13 lesions were diagnosed as cT1b. ESD and surgery were performed for 47 and 7 lesions, respectively. Pathologic depths [T1a/T1b/T2] were 42, 11, and 1, respectively. The sensitivity, specificity, and positive predictive value of endoscopic diagnosis of T1b were 25.0%, 76.2%, and 23.1%, respectively. 10 of 54 (18.5%) T1a lesions were overdiagnosed. Staging ESD was performed for 20 lesions, and all of them achieved en bloc resection without adverse events. R0 resection was achieved in 13 of 14 (92.9%) cT1a and 5 of 6 (83.3%) cT1b, respectively. Curative resection was achieved in 8 of 14 (57.1%) cT1a and 4 of 6 (60.0%) cT1b, respectively. 3 of 54 (5.6%) T1a were diagnosed as conclusive cT1b, and underwent surgery, leading to overtreatment.

Conclusion

The diagnostic performance of endoscopic depth diagnosis is insufficient, leading to overdiagnosis. Staging ESD for inconclusive cT1 BEA is technically feasible and can be an option to avoid overtreatment.

Introduction

Increased intestinal permeability, mediated by zonulin, has been implicated in the pathogenesis of insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). Small intestinal bacterial overgrowth (SIBO) may further contribute to metabolic dysfunction through endotoxin-induced inflammation.

Aims & Methods

The aim was to determine zonulin concentrations in patients with dyslipidemia and NAFLD and analyze their relationships with metabolic parameters and the prevalence of small intestinal bacterial overgrowth (SIBO). A total of 342 patients with dyslipidemia were enrolled; NAFLD was confirmed in 152 of them based on ultrasound and steatometry. Fecal zonulin levels were measured using ELISA; SIBO was assessed by hydrogen breath test. Lipid profiles, high-sensitivity C-reactive protein (hsCRP), and HDL-C levels were also analyzed.

Results

Zonulin levels in patients with NAFLD (115±2.76 ng/g) exceeded the normal range (≤107 ng/g), compared to 87±0.28 ng/g in the dyslipidemia group without NAFLD (p<0.05). SIBO was present in 45% of dyslipidemic patients and 53.2% of those with NAFLD. A positive correlation was found between zonulin and hsCRP (r=0.65) and triglycerides (r=0.58), and a negative correlation between SIBO and HDL-C (r=–0.78) in the dyslipidemia group.

Conclusion

Elevated zonulin and increased intestinal permeability are associated with higher cardiometabolic risk in patients with NAFLD and dyslipidemia. Both zonulin and SIBO may serve as potential therapeutic targets for preventing progression of NAFLD and related metabolic disturbances.

Introduction

Gilbert's Syndrome (GS) is a benign polymorphism of the UGT1A1 gene, leading to decreased enzyme activity in the liver and mildly increased levels of unconjugated bilirubin in blood (= hyperbilirubinemia), that is affecting 5-12% of the worldwide population. A mild hyperbilirubinemia (HBIL) is associated with reduced chronic inflammation, a lower risk for metabolic and cardiovascular disorders, and lower levels of reactive oxygen species (ROS). Despite these associations, HBIL effects on the intestine, as the primary site of bilirubin excretion, and its interactions with the gut microbiota remain unclear. We propose that chronic HBIL redirects bilirubin excretion through the intestinal epithelium that affects microbe-host interactions in the colon.

Aims & Methods

Germ-free (GF) and specific-pathogen-free (SPF) C57BL/6N wildtype (WT) mice with induced HBIL and transgenic mice with the human UGT1A1*28 polymorphism (TG) were investigated, the latter one mimicking chronic HBIL. WT mice with induced HBIL received intraperitoneal bilirubin injections for 12-14 days. Bilirubin levels, in the intestine, gut content and serum were analyzed using the fluorescent protein UnaG, which specifically binds to unconjugated bilirubin, and microbiota composition was analyzed by 16S rRNA gene sequencing. To characterize HBIL-associated antioxidative function, colonic adenoma cell lines (Ptk-6, HCT116, HT-29-MTX-E12) and small intestinal organoids were incubated with different levels of bilirubin and the generation of ROS and oxidative stress markers measured.

Results

In general, mice of the induced HBIL groups exhibited higher bilirubin levels in the colonic mucosa, indicating "intestinal HBIL" with increased concentrations of mucosal bilirubin being detected in SPF HBIL > GF HBIL mice (SPF HBIL = 12.34 nM/mg, GF HBIL = 9.9 nM/mg; SPF control = 0.5951 nM/mg; GF control = 8.21 nM/mg), as well as a lower hepatic Ugt1a1 expression. Intracellular uptake of bilirubin was confirmed when different human and murine colonic epithelial cell lines were treated with bilirubin in vitro. Intestinal HBIL led to altered gut microbiota compositions, characterized by decreased abundances of operational taxonomic units (OTUs) associated with Gram-negative taxa (e.g., Prevotellaceae) and increased levels of OTUs associated with Gram-positive taxa (e.g., Lachnospiraceae) under intestinal HBIL conditions. Gut microbiota changes were more pronounced in TG (=chronic HBIL) compared to induced HBIL mice. In vitro experiments showed decreased detection of ROS and markers of cellular oxidative stress in a HCT116 reporter cell line dependent on bilirubin presence (Nfk-⁠β, Nrf2 and Hif1α). Small intestinal organoids from TG mice showed an altered proliferation pattern in comparison to WT organoids.

Conclusion

The results suggest an altered bilirubin excretion through the intestinal epithelium under mild HBIL that alters gut microbiota composition. These effects were more pronounced under chronic HBIL conditions, suggesting a sustained effect of GS-like HBIL on the gut microbiota.