Optimal Assessment, Treatment, and Monitoring of Adults with Eosinophilic Esophagitis: Strategies to Improve Outcomes.

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammation-mediated disease characterized by an eosinophil-predominant inflammation of the esophagus and symptoms of esophageal dysfunction. Relevant treatment outcomes in the setting of EoE include the improvement of histology, symptoms, and endoscopy findings, quality of life (QoL), and the psychological burden of the disease. Established validated tools for the assessment of EoE include questionnaires on dysphagia and QoL (ie, DSQ, EEsAI, and EoE-IQ). More recently, esophageal symptom-specific anxiety and hypervigilance, assessed using the esophageal hypervigilance and anxiety scale (EHAS), have emerged as contributors to disease burden, confirming the importance of psychological aspects in EoE patients. The EoE endoscopic reference score (EREFS) is the only validated endoscopy score in EoE and can quantify mucosal disease burden. However, esophageal panometry using the functional lumen imaging probe (FLIP) and high-resolution manometry (HRM) have shown potential to optimize the assessment of fibrostenotic features of EoE, providing novel insights into the pathophysiology of symptoms. There is a growing number of licenced and off-label therapeutic options in EoE, with various randomized controlled trials demonstrating the efficacy of proton pump inhibitors, topical steroids, food elimination diets, biological drugs, and esophageal dilatation. However, standardized optimal management strategies of EoE are currently lacking. In this review, we provide an overview of established and novel assessment tools in EoE including patient reported outcomes, FLIP panometry, HRM, endoscopy, and histology outcome measures to improve the outcomes of EoE patients. In addition, we summarize available therapeutic options for EoE based on the most recent evidence.

Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. METHODS: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. RESULTS: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.

Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome.

BACKGROUND AND AIMS: The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and included epithelial barrier dysfunction, a key element at the interface between the gut lumen and the deeper intestinal layers. Beneath the epithelial barrier there is the vascular one representing the last barrier to avoid luminal antigen dissemination The aims of this study were to correlate morpho-functional aspects of epithelial and vascular barriers with symptom perception in IBS. METHODS: Seventy-eight healthy subjects (controls) and 223 IBS patients were enrolled in the study and phenotyped according to validated questionnaires. Sugar test was used to evaluate in vivo permeability. Immunohistochemistry, western blot and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing the mucosal expression of plasmalemma vesicle-associated protein-1 and vascular endothelial cadherin (VEC). Caco-2 or HUVEC monolayers were incubated with soluble mediators released by mucosal biopsies to highlight the mechanisms involved in permeability alteration. Correlation analyses have been performed among experimental and clinical data. RESULTS: Intestinal epithelial barrier was compromised in IBS patients throughout the gastrointestinal tract. IBS soluble mediators increased Caco-2 permeability via a downregulation of tight junction gene expression. Blood vessel density and vascular permeability were increased in the IBS colonic mucosa. IBS mucosal mediators increased permeability in HUVEC monolayers through the activation of protease-activated receptor (PAR)-2 and histone deacetylase (HDAC)11, resulting in VEC downregulation. Permeability changes correlated with intestinal and behavioral symptoms and health-related quality of life of IBS patients. CONCLUSION: Epithelial and vascular barriers are compromised in IBS patients and contribute to clinical manifestations.

The Revised Reflux Symptom Index (R-RSI): development, internal and external validation study.

INTRODUCTION: This study proposes a revised version of the Reflux Symptom Index (R-RSI), a seventeen-item questionnaire that was revised to increase the suspicion of laryngo-pharyngeal reflux disease (LPRD). METHODS: Internal validation involved 213 participants, comprising160 subjects without a previous LPRD diagnosis and 53 subjects with a self-reported previous diagnosis of LPRD with or without gastro-esophageal reflux disease (GERD). Test-retest reliability and internal consistency were calculated. For the external validation, 56 patients (independent from the previous cohort) were enrolled to explore the R-RSI Screening Properties and determine a cut-off using 24-h MII-pH as the gold standard. RESULTS: R-RSI test-retest reliability was high, both for the total score (ICC: 0.970) and for each item (ranging from 0.876 to 0.980). Cronbach's alpha was 0.910, indicating excellent internal consistency of the questionnaire. Participants with a previous self-reported diagnosis scored significantly higher (mean 24.94 ± 7.4; median 26, IQR 20-29) than those without a previous diagnosis (mean 4.66 ± 5.3; median 4, IQR 1-6) (p-value < 0.0001). Participants with both previous LPRD and GERD diagnoses had higher scores (27.20 ± 7.8) compared to those with only LPRD (21.77 ± 5.5) (p-value=0.003). Using 24-h MII-pH diagnosis as a gold standard, the optimal R-RSI cut-off point was determined to be 18, with a sensitivity of 84.5% and a specificity of 81.8%, positive predictive value of 95% and negative predictive value of 60%. CONCLUSIONS: Our results suggest that the R-RSI may be useful to suspect LPRD, with or without GERD. The R-RSI is a self-administered patient-reported outcome questionnaire that demonstrates excellent reliability and high screening properties. Employing a cut-off of ≥18 the R-RSI can assist in diagnosing and monitoring LPRD.

Distinguishing features of autoimmune gastritis depending on previous H. pylori infection or positivity to anti-parietal cell antibodies: results from the Autoimmune gastRitis Italian netwOrk Study grOup (ARIOSO).

OBJECTIVES: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at eight Italian tertiary referral centers. We retrieved clinical data from all histologically proven AIG patients. Differences between H. pylori-exposed vs H. pylori-naïve, and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated to gNEN was fitted. RESULTS: 1598 patients with AIG (median age 58 years, IQR 46-68; F:M ratio 2.7:1) were included. H. pylori-naïve patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; p=0.012), type 1 diabetes mellitus (4.9% vs 2.3%; p=0.025), and pernicious anemia (30.9% vs 21.1%; p=0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; p<0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; p<0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% CI 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with an 16.44 (95% CI 9.94-27.20 p<0.001) hazard ratio of gNEN. CONCLUSIONS: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori. In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection.

Esophageal motor disorders across ages: A retrospective multicentric analysis.

BACKGROUND: Age-related changes in the gastrointestinal system are common and may be influenced by physiological aging processes. To date, a comprehensive analysis of esophageal motor disorders in patients belonging to various age groups has not been adequately reported. METHODS: We conducted a retrospective assessment of high-resolution manometry (HRM) studies in a multicenter setting. HRM parameters were evaluated according to the Chicago Classification version 4.0. Epidemiological, demographic, clinical data, and main manometric parameters, were collected at the time of the examination. Age groups were categorized as early adulthood (<35 years), early middle-age (35-49 years), late middle-age (50-64 years), and late adulthood (≥65 years). RESULTS: Overall, 1341 patients (632, 47.0% male) were included with a median age of 55 years. Late adulthood patients reported more frequently dysphagia (35.2%) than early adulthood patients (24.0%, p = 0.035), early middle-age patients (21.0%, p < 0.0001), and late middle-aged patients (22.7%, p < 0.0001). Esophagogastric junction outflow obstruction was more prevalent in late adulthood (16.7%) than in early adulthood (6.1%, p = 0.003), and in early middle-age (8.1%, p = 0.001). Patients with normal esophageal motility were significantly younger (52.0 years) than patients with hypercontractile esophagus (61.5 years), type III achalasia (59.6 years), esophagogastric junction outflow obstruction (59.4 years), absent contractility (57.2 years), and distal esophageal spasm (57.0 years), in multivariate model (p < 0.0001). CONCLUSION: The rate of esophageal motor disorders is higher in older patients, in particular esophagogastric junction outflow obstruction and hypercontractile esophagus. Future prospective studies are necessary to confirm our results and to find tailored strategies to improve clinical outcomes.

Nutrient Composition of Four Dietary Patterns in Italy: Results from an Online Survey (the INVITA Study).

Though Italy is a native land of Mediterranean diet, its adherence in the Italian population is low, witnessed by the high rates of overweight in its inhabitants. Vegetarian dietary patterns (i.e., lacto-ovo-vegetarian and vegan) are increasing in western countries, and also in Italy, where 9.5% of the population self-declared as vegetarian in 2023. Though the vegetarian diet has been associated with beneficial health effects, speculation on its alleged nutrient inadequacy exists. For this reason, we assessed the nutrient composition of the diet of 470 participants enrolled in an online survey (the INVITA study), who completed a weighted food questionnaire on three different days. Participants were divided into four dietary groups obtained according to their self-declared dietary intakes: 116 Meat Eaters (MEs), 49 Fish Eaters (FEs), 116 Lacto-Ovo-Vegetarians (LOVs), and 189 VegaNs (VNs). The mean intake of most of the main nutrients was similar among all groups and within the normal range expected for the Italian population, supporting the adequacy of diets within our Italian sample, especially the LOV and VN diet. Since the Mediterranean diet is a plant-based diet, some of its components still persist in the current Italian diet, representing a staple also for people adopting a vegetarian diet.

Immune landscape of the enteric nervous system differentiates Parkinson's disease patients from controls: The PADUA-CESNE cohort.

BACKGROUND: Gastrointestinal dysfunction has emerged as a prominent early feature of Parkinson's Disease, shedding new light on the pivotal role of the enteric nervous system in its pathophysiology. However, the role of immune-cell clusters and inflammatory and glial markers in the gut pathogenetic process needs further elucidation. OBJECTIVES: We aimed to study duodenum tissue samples to characterize PD's enteric nervous system pathology further. Twenty patients with advanced PD, six with early PD, and 18 matched controls were included in the PADUA-CESNE cohort. METHODS: Duodenal biopsies from 26 patients with early to advanced stage PD and 18 age-matched HCs were evaluated for the presence of surface markers (CD3+, CD4+, CD8+, CD20+, CD68+, HLA-DR), presence of misfolded alpha-synuclein and enteric glial alteration (GFAP). Correlation of immulogic pattern and clinical characteristic were analyzed. RESULTS: The findings validate that in patients with Parkinson's Disease, the activation and reactive gliosis are linked to the neurodegeneration triggered by the presence of misfolded alpha-synuclein in the enteric nervous system. This process intensifies from the initial to the advanced stages of the disease. The clusters of T- and B-lymphocytes in the enteric system, along with the overall expression of HLA-DR in antigen-presenting cells, exceeded those in the control group. Conversely, no differences in terms of macrophage populations were found. CONCLUSIONS: These findings broaden our understanding of the mechanisms underlying the enteric nervous system's involvement in PD and point to the gastrointestinal system as a potential therapeutic target, especially in the early stages of the disease. Moreover, our results propose a role of T- and B-lymphocytes in maintaining inflammation and ultimately influencing alpha-synuclein misfolding and aggregation.

Impact of inflammatory bowel disease on women's reproductive life: a questionnaire-based study.

Background: Inflammatory bowel diseases (IBDs) have a peak incidence between the second and fourth decades of life and can affect women's reproductive life. Objectives: Our study aimed to assess the impact of IBD on the reproductive life of female patients with this condition. Design: Cross-sectional study. Methods: Women with IBD followed at our IBD Unit and a group of healthy controls were enrolled. Data on reproductive life were collected using a dedicated questionnaire. Results: The study included 457 women, of whom 228 had IBD, and 229 age-matched healthy controls. No differences were found in the use of contraceptives, infertility, and endometriosis. The risk of spontaneous and voluntary abortions was significantly higher in IBD patients than in healthy controls [odds ratio (OR) 2 and 3.62, respectively]. The risk of obstetrical complications in the IBD population was more than six times higher in patients who experienced disease reactivations during pregnancy than in those with persistent remission [OR 6.9, 95% confidence interval (CI) 1.51-31.28]. Finally, we found that the chances of breastfeeding were 66% lower in patients with IBD than in controls (OR 0.44, 95% CI 0.22-0.91). Conclusion: Our study underlines the negative impact of IBD on women's reproductive life, supporting the need for proactive preconception counseling.

Reproductive life in IBD women Summarise the established knowledge on this subject Most women with Inflammatory Bowel Diseases are affected during their reproductive years.Women with IBD have fear, uncertainty, and poor knowledge of how the disease can impact their reproductive life. What are the significant and/or new findings of this study?Higher prevalence of abortions in women with IBD.Confirmed adverse pregnancy outcomes in the case of IBD activity.A lower chance of breastfeeding in women with IBD.Pro-active counselling is needed, which start from the moment of conception choice, with correct management of the pathology.

Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications.

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.

Eosinophilic esophagitis in adults and adolescents: epidemiology, diagnostic challenges, and management strategies for a type 2 inflammatory disease.

Background: Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs. Objectives: To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities. Design: An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings. Data sources and methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps. Results: The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise. Conclusion: Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.

Understanding and improving care for eosinophilic esophagitis: bridging gaps in diagnosis and treatment Eosinophilic esophagitis (EoE) is a chronic inflammatory condition affecting the esophagus. We reviewed studies on how common EoE is and how it's managed. In Italy, about 41 out of 100,000 people may have it. Diagnosis can be tricky due to vague symptoms, and current treatments vary in effectiveness. We found a need for better ways to diagnose and treat EoE, including exploring new therapies. A promising development is a biologic called Dupilumab. Future research should also consider the costs and social aspects of caring for people with EoE.

Diagnostic delay in achalasia.

BACKGROUND: Achalasia is a rare disorder characterized by impaired esophageal motility and symptoms like dysphagia, regurgitation, chest pain, and weight loss. A timely diagnosis is crucial to adequately manage this condition. AIMS: This study aimed to assess the diagnostic delay from symptom onset to a definite diagnosis of achalasia, and to identify associated factors. METHODS: This retrospective, single-center study included patients diagnosed with achalasia between January 2013 and September 2023. Demographic data, symptoms, manometric, endoscopic, and radiological findings were collected. We also considered socio-economic deprivation. Early diagnosis was defined as occurring within 12 months of symptom onset, while late diagnosis was defined as occurring more than 12 months. RESULTS: We included 278 patients (142 males, median age 58 years). Dysphagia was the most common symptom (96 %), followed by regurgitation (70.1 %). The median diagnostic delay was 24 months (IQR 12-72, range 0-720), with 213 patients (76.6 %) experiencing late diagnosis. Early diagnosis was more common in patients with weight loss (63.1% vs. 42.0 %, p = 0.003). Lower material deprivation correlated with shorter diagnostic delay (24 months, IQR 10-60 vs. 60 months, IQR 18-300, p = 0.001). CONCLUSIONS: Achalasia diagnosis is often delayed. Weight loss along with socio-economic factors, influence the timeliness of diagnosis. Improving awareness of disease and relevance of initial symptoms may facilitate earlier diagnosis and treatment.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Immune-Mediated Inflammatory Diseases Awareness and Management among Physicians Treating Patients with Inflammatory Bowel Disease: An IG-IBD Survey.

(1) Background: Inflammatory bowel disease (IBD) is frequently associated to other immune-mediated inflammatory diseases (IMIDs). This study aims at assessing physicians' awareness of the issue and the current status of IMID management. (2) Methods: A web-based survey was distributed to all 567 physicians affiliated to IG-IBD. (3) Results: A total of 249 (43.9%) physicians completed the survey. Over 90% of the responding physicians were gastroenterology specialists, primarily working in public hospitals. About 51.0% of the physicians had access to an integrated outpatient clinic, where gastroenterologists collaborated with rheumatologists and 28.5% with dermatologists. However, for 36.5% of physicians, integrated ambulatory care was not feasible. Designated appointment slots for rheumatologists and dermatologists were accessible to 72.2% and 58.2% of physicians, respectively, while 20.1% had no access to designated slots. About 5.2% of physicians report investigating signs or symptoms of IMIDs only during the initial patient assessment. However, 87.9% inquired about the presence of concomitant IMIDs at the initial assessment and actively investigated any signs or symptoms during subsequent clinical examination. (4) Conclusions: While Italian physicians recognize the importance of IMIDs associated with IBD, organizational challenges impede the attainment of optimal multidisciplinary collaboration. Efforts should be directed toward enhancing practical frameworks to improve the overall management of these complex conditions.

Gastric Carcinoma in Autoimmune Gastritis: A Histopathologic and Molecular Study.

Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathologic and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from 4 Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, mismatch repair (MMR) proteins, and p53 and EBV-encoded RNA (EBER) in situ hybridization were performed. Histologic and immunohistochemical features were jointly reviewed by 5 expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%) and they were located in the corpus/fundus (58%) and associated with operative link for gastritis assessment stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia, and enterochromaffin-like-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine-non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 combined positive score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) microsatellite instability (MSI) cases and 7 (37%) tumor mutational burden (TMB) high. The most frequently altered genes were TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [2 amplified and 5 mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with longstanding misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB high.

The Role of High-Resolution Manometry Prior to and Following Antireflux Surgery: The Padova Consensus.

BACKGROUND: In the last two decades the development of high-resolution manometry (HRM) has changed and revolutionized the diagnostic assessment of patients complain foregut symptoms. The role of HRM before and after antireflux procedure remains unclear, especially in surgical practice, where a clear understanding of esophageal physiology and hiatus anatomy is essential for optimal outcome of antireflux surgery (ARS). Surgeons and gastroenterologists (GIs) agree that assessing patients following antireflux procedures can be challenging. Although endoscopy and barium-swallow can reveal anatomic abnormalities, physiologic information on HRM allowing insight into the cause of eventually recurrent symptoms could be key to clinical decision making. METHOD: A multi-disciplinary international working group (14 surgeons and 15 GIs) collaborated to develop consensus on the role of HRM pre- and post- ARS, and to develop a postoperative classification to interpret HRM findings. The method utilized was detailed literature review to develop statements, and the RAND/University of California, Los Angeles Appropriateness Methodology (RAM) to assess agreement with the statements. Only statements with an approval rate >80% or a final ranking with a median score of 7 were accepted in the consensus. The working groups evaluated the role of HRM prior to ARS and the role of HRM following ARS. CONCLUSION: This international initiative developed by surgeons and GIs together, summarizes the state of our knowledge of the use of HRM pre- and post-ARS. The Padova Classification was developed to facilitate the interpretation of HRM studies of patients underwent ARS.

Patient journey in gastroesophageal reflux disease: real-world perspectives from Italian gastroenterologists, primary care physicians, and ENT specialists.

Background: Gastroesophageal reflux disease (GERD) is a challenging condition that involves different physicians, such as general practitioners (GPs), gastroenterologists, and ears, nose and throat (ENT) specialists. A common approach consists of proton-pump inhibitors (PPIs) administration. Adjunctive pharmacological treatment may have a role in the management of non-responders to PPIs. Objectives: We aimed to survey GPs and different medical specialists to investigate the medical approaches to patients reporting GERD symptoms. In addition, we examined the use of adjunctive pharmacological treatments in patients with GERD symptoms who do not respond to PPIs. Design: Retrospective observational study. Methods: A survey was conducted among a large sample of gastroenterologists, GPs, and ENT specialists. Symptoms were divided into typical and extraesophageal, and their severity and impact on quality of life were explored with the GERD Impact Scale and with Reflux Symptom Index (RSI). All therapies administered usually for GERD were investigated. Results: A total of 6211 patients were analyzed in this survey. Patients with typical symptoms were 53.5%, while those with extraesophageal symptoms were 46.5%. The latter were more frequently reported by ENT patients (53.6%, p < 0.0001). The GSI was higher in patients followed by gastroenterologists (9 points) and GPs (9 points) than ENT specialists (8 points), but the RSI was higher in the ENT group (14.3 ± 6.93) than in GPs and gastroenterologist groups (10.36 ± 6.36 and 10.81 ± 7.30, p < 0.0001). Chest pain had the highest negative impact on quality of life (p < 0.0001). Of the 3025 patients who used PPIs, non-responders showed a lower GSI when treated with a combination of adjunctive pharmacological treatments and bioadhesive compounds, than with single-component drugs. Conclusion: Patients with GERD referred to a gastroenterologist had more severe disease and poorer quality of life. The combination of adjunctive pharmacological treatments and bioadhesive compounds seems to be effective in the management of PPI refractory patients.

Gastroesophageal reflux disease management: real-world perspectives from Italian gastroenterologists, primary care physicians and ENT specialists Gastroesophageal reflux disease (GERD) is a prevalent and chronic condition that affects millions of individuals worldwide, causing significant discomfort and impacting their overall quality of life. In the comprehensive management of GERD, a collaborative approach involving different physicians is essential to address the various aspects of this complex condition. Given the wide range of diagnostic and therapeutic possibilities in clinical practice, we aimed to investigate how GERD is managed in clinical practice by general practitioners and different medical specialists, including gastroenterologists and ears, nose, and throat (ENT) specialists. A total of 6,211 observations were carried out from a survey. The severity and impact of GERD on quality-of-life was higher in patients followed by gastroenterologists and general practitioners than ENT specialists. Non-cardiac chest pain had the highest negative impact on quality-of-life. Of the 3,025 patients who used PPIs, non-responders showed an improved quality of life when treated with a combination of adjunctive pharmacological treatments and bio adhesive compounds.

Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.