Clinical Outcome of Patients with Gastric, Duodenal, or Rectal Neuroendocrine Tumors after Incomplete Endoscopic Resection.

Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study's main endpoints. Statistical analysis was performed using MedCalc® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22-116.99], HR: 12.54 [95% CI: 1.28-122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients' clinical outcomes.

Advancements in Barrett's esophagus detection: The role of artificial intelligence and its implications.

Artificial intelligence (AI) is making significant strides in revolutionizing the detection of Barrett's esophagus (BE), a precursor to esophageal adenocarcinoma. In the research article by Tsai et al, researchers utilized endoscopic images to train an AI model, challenging the traditional distinction between endoscopic and histological BE. This approach yielded remarkable results, with the AI system achieving an accuracy of 94.37%, sensitivity of 94.29%, and specificity of 94.44%. The study's extensive dataset enhances the AI model's practicality, offering valuable support to endoscopists by minimizing unnecessary biopsies. However, questions about the applicability to different endoscopic systems remain. The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Endoscopic Resection for Duodenal Neuroendocrine Neoplasms between 10 and 20 mm-A Systematic Review and Meta-Analysis.

Background. The optimal management of duodenal neuroendocrine neoplasms (dNENs) sized 10-20 mm remains controversial and although endoscopic resection is increasingly performed instead of surgery, the therapeutic approach in this setting is not fully standardized. We performed a systematic review of the literature and a meta-analysis to clarify the outcomes of endoscopic resection for 10-20 mm dNENs in terms of efficacy (i.e., recurrence rate) and safety. Methods. A computerized literature search was performed using relevant keywords to identify pertinent articles published until January 2023. Results. Seven retrospective studies were included in this systematic review. The overall recurrence rate was 14.6% (95%CI 5.4-27.4) in 65 patients analyzed, without significant heterogeneity. When considering studies specifically focused on endoscopic mucosal resection, the recurrence rate was 20.5% (95%CI 10.7-32.4), without significant heterogeneity. The ability to obtain the free margin after endoscopic resection ranged between 36% and 100%. No complications were observed in the four studies reporting this information. Conclusions. Endoscopic resection could be the first treatment option in patients with dNENs sized 10-20 mm and without evidence of metastatic disease. Further studies are needed to draw more solid conclusions, particularly in terms of superiority among the available endoscopic techniques.

Autoimmune pancreatitis: Cornerstones and future perspectives.

Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.

Ultrasound muscle assessment for sarcopenia detection in inflammatory bowel disease: A prospective study.

BACKGROUND: Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in this population. METHODS: 153 consecutive patients were included, 100 in the training cohort and 53 in the study cohort. Three superficial muscles (rectus femoris = RF, rectus abdominis = RA, and biceps brachii = BB) were selected for the detection of sarcopenia using muscle ultrasound (US). The training cohort consisted of consecutive patients with or without IBD and was used to evaluate the feasibility and inter- and intra-observer variability of the US measurement. The study cohort consisted of only IBD patients and served to test US diagnostic accuracy. In the latter, muscle US, bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were used to measure muscle parameters. RESULTS: Sarcopenia prevalence in IBD patients was 50%. Muscle US showed excellent inter-rater and intra-rater reliability (ICC >0.95) and a good diagnostic accuracy in detecting sarcopenia compared to BIA with area under the receiver operating characteristic curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined as the sum of the RA, BB, and RF thickness divided by the square of the patient's height, resulting in an AUROC of 81%. Muscle thresholds for sarcopenia were detected, with RA and USMI values correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Additionally, the agreement between the US and MRI measurements of RA was excellent (ICC 0.96). CONCLUSIONS: The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. This research has significant implications for disease management in IBD patients and underscores the need for further investigations to validate these findings in larger cohorts.

Endoscopic management of gastric, duodenal and rectal NETs: Position paper from the Italian Association for Neuroendocrine Tumors (Itanet), Italian Society of Gastroenterology (SIGE), Italian Society of Digestive Endoscopy (SIED).

The present paper reflects the position of the Italian Association for Neuroendocrine Tumors (Itanet), the Italian Society of Gastroenterology (SIGE), and the Italian Society of Digestive Endoscopy (SIED) regarding the management of patients affected by gastric, duodenal, and rectal neuroendocrine neoplasms (NENs) amenable to endoscopic treatment. The key questions discussed in this paper are summarized in Table 1. Data were extracted from the MEDLINE database through searches; expert opinions and recommendations are provided in accordance with the available scientific evidence and the authors' expertise. Recommendations are presented alongside a level of evidence and grade of recommendation based on the GRADE system. This paper specifically focuses on subgroups of NENs considered suitable for endoscopic management according to current international guidelines: i. well-differentiated gastric neuroendocrine tumors (gNET) type 1 < 2 cm and selected cases of type 3; ii. well-differentiated duodenal, non-functioning, non-ampullary NET with size < 2 cm; and well-differentiated rectal NET with size < 2 cm.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

Eosinophilic esophagitis: does age matter?

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with increasing prevalence worldwide. It is a multifactorial disease caused by a combination of immunologic, genetic, and environmental factors. The clinical presentation of EoE varies largely, especially between different age groups. While diagnostic criteria and therapeutic goals are similar in children and adults, there are differences in treatment, with a more cautious approach in children to avoid growth disturbances. In addition, close monitoring and follow-up are essential in children to ensure uninterrupted growth. AREAS COVERED: A search in PubMed/MEDLINE, EMBASE, and SCOPUS databases was conducted to identify relevant studies published between January 2010 and January 2023 to give an overview of the state-of-the-art of EoE epidemiology, diagnosis, and treatment while focusing on similarities and differences between the adult and the pediatric population. EXPERT OPINION: The current state of research indicates that while significant progress has been made in understanding and treating EoE, further research and advances are needed to optimize diagnostic strategies, tailored treatment approaches, monitoring, and follow-up, and improve long-term outcomes for patients. With further innovation, the management of EoE can become more precise and tailored, leading to better patient outcomes and improved quality of life.

Small Bowel Imaging in Celiac Disease: Is there a role for Small Bowel Ultrasound?

PURPOSE OF REVIEW: The incidence of celiac disease (CD) has increased over the last decades in part due to better disease awareness. Small bowel ultrasound (sb US) enables dynamic assessment of the bowel; although this topic has been addressed, the use of sb US in the diagnosis and in the follow-up of CD patients is limited to a few specialized tertiary referral centers. Herein, we aimed at summarizing the available literature on this topic to better define the potential clinical implications of sb US in CD, also through a comparison with other available diagnostic techniques. RECENT FINDINGS: According to available data, sb US can be of help in confirming or excluding CD in patients with clinical suspicion; specifically, the finding of increased gall bladder volume, free abdominal fluid and enlargement of mesenteric lymph nodes reliably and accurately predicts the diagnosis of CD, whereas the absence of bowel dilatation and increased peristalsis may exclude the diagnosis. However, the place of intestinal US in the diagnostic algorithm of CD is likely to vary depending on the probability of the disease in a given population. There are only a few studies on the role of sb US in complicated CD, even if recent reports suggest a possible clinical role. There is a lack of data on follow-up of CD patients, particularly with the aim of detecting a poor diet adherence. According to current data sb US parameters have been shown to be of value in confirming and excluding the diagnosis of CD. Prospective studies with large sample size are warranted to determine whether to include sb US in the available guidelines for CD diagnosis and monitoring.

Mechanistic Insights into Eosinophilic Esophagitis: Therapies Targeting Pathophysiological Mechanisms.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by eosinophilic infiltration of the esophagus. It arises from a complex interplay of genetic predisposition (susceptibility loci), environmental triggers (allergens and dietary antigens), and a dysregulated immune response, mainly mediated by type 2 T helper cell (Th2)-released cytokines, such as interleukin (IL)-4, IL-5, and IL-13. These cytokines control eosinophil recruitment and activation as well as tissue remodeling, contributing to the characteristic features of EoE. The pathogenesis of EoE includes epithelial barrier dysfunction, mast cell activation, eosinophil degranulation, and fibrosis. Epithelial barrier dysfunction allows allergen penetration and promotes immune cell infiltration, thereby perpetuating the inflammatory response. Mast cells release proinflammatory mediators and promote eosinophil recruitment and the release of cytotoxic proteins and cytokines, causing tissue damage and remodeling. Prolonged inflammation can lead to fibrosis, resulting in long-term complications such as strictures and dysmotility. Current treatment options for EoE are limited and mainly focus on dietary changes, proton-pump inhibitors, and topical corticosteroids. Novel therapies targeting key inflammatory pathways, such as monoclonal antibodies against IL-4, IL-5, and IL-13, are emerging in clinical trials. A deeper understanding of the complex pathogenetic mechanisms behind EoE will contribute to the development of more effective and personalized therapeutic strategies.

Therapeutic Challenges for Gastric Neuroendocrine Neoplasms: Take It or Leave It?

Background and Objectives: Gastric neuroendocrine neoplasms (gNENs) represent rare but increasingly recognized tumors. They are distinguished into three main clinical types (type-1, type-2, and type-3) according to gastrin level and at histological evaluation in well-differentiated G1, G2, or G3 lesions, as well as poorly-differentiated lesions. Small type-1 and type-2 neoplasms with low proliferation indices demonstrated excellent survival without progression during an extended follow-up period, and for these reasons, active endoscopic observation or endoscopic resection are feasible options. On the other hand, surgery is the treatment of choice for more aggressive type-3, G3, or infiltrating neoplasms. The present study aims to comprehensively review and compare the available therapeutic strategies for gNENs. Materials and Methods: A computerized literature search was performed using relevant keywords to identify all of the pertinent articles with particular attention to gNEN endoscopic treatment. Results: In recent years, different endoscopic resective techniques (such as endoscopic mucosal dissection, modified endoscopic mucosal resection, and endoscopic full-thickness resection) have been developed, showing a high rate of complete resection for advanced and more aggressive lesions. Conclusions: Overall, gNENs represent a heterogeneous group of lesions with varying behavior which require personalized management. The non-operative approach for small type-1 gNENs seems to be feasible and should be promoted. A step-up approach with minimally invasive endoscopic therapies might be proposed, particularly for type-1 gNEN. On the other hand, it is important to recognize the negative prognostic factors in order to identify those rare cases requiring more aggressive approaches. A possible therapeutic algorithm for localized gNEN management is provided.

Get Fit: Muscle Health for Crohn's Disease Surgical Outcome Optimization.

Muscular health, encompassing sarcopenia and myosteatosis, has a pivotal role in optimizing surgical outcomes in patients with Crohn's disease. A comprehensive approach is advocated for improving patient well-being after surgery.

Incidence and prevalence of gastric neuroendocrine tumors in patients with chronic atrophic autoimmune gastritis.

BACKGROUND: The incidence of type I gastric neuroendocrine neoplasms (gNENs) has increased significantly over the past 50 years. Although autoimmune gastritis (AIG) increases the likelihood of developing gNENs, the exact incidence and prevalence of this association remain unclear. AIM: To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG. METHODS: Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022. Circulating levels of CgA and gastrin were assessed at enrollment. Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions, enterochromaffin-like (ECL) cell hyperplasia, and the development of gNEN. RESULTS: We included 176 patients [142 women (80.7%), median age 64 years, interquartile range (IQR) 53-71 years] diagnosed with AIG between January 1990 and June 2022. At enrollment. One hundred and sixteen patients (65.9%) had ECL hyperplasia, of whom, 29.5% had simple/linear, 30.7% had micronodular, and 5.7% had macronodular type. The median follow-up time was 5 (3-7.5) years. After 1032 person-years, 33 patients developed a total of 50 type I gNENs, with an incidence rate of 0.057 person-years, corresponding to an annual cumulative incidence of 5.7%. Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not. Conversely, gastrin levels were significantly higher in AIG patients who developed gNENs [median 992 pg/mL IQR = 449-1500 vs 688 pg/mL IQR = 423-1200, P = 0.03]. Calculated gastrin sensitivity and specificity were 90.9% and 1.4%, respectively, with an overall diagnostic accuracy of 30% and a calculated area under the gastrin receiver operating characteristic curve (AUROC or AUC) of 0.53. CONCLUSION: Type I gNENs are a significant complication in AIG. Gastrin's low diagnostic accuracy prevents it from serving as a marker for early diagnosis. Effective strategies for early detection and treatment are needed.

Prevalence of Disease-Related Malnutrition and Micronutrients Deficit in Patients with Inflammatory Bowel Disease: A Multicentric Cross-Sectional Study by the GSMII (Inflammatory Bowel Disease Study Group).

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients might experience disease-related malnutrition (DRM), but prevalence and risk factors are not well defined. The primary aim of the study was to define the prevalence of DRM and micronutrient deficiency in IBD patients; the secondary aim was to assess variables related to DRM. MATERIALS AND METHODS: A multicenter, cross-sectional study was performed including consecutive adult IBD patients during a period of 2 weeks. Nutritional status was assessed with the body mass index (BMI) and the Malnutrition Universal Screening Tool. DRM was defined according to European Society for Clinical Nutrition and Metabolism guidelines. RESULTS: Among the 295 enrolled patients, the prevalence of DRM was 23%, with no statistical difference between Crohn's disease and ulcerative colitis. Compared with well-nourished patients, patients with DRM showed higher rate of hospitalization in the previous month, were more often receiving systemic steroids, and had lower hemoglobin, albumin, and prealbumin levels and higher median C-reactive protein levels. At univariate logistic regression, current hospitalization, hospitalization in the previous month, low serum albumin, low BMI, high C-reactive protein, high Crohn's Disease Activity Index, and female sex were variables related to DRM. At the multivariate logistic regression, low BMI, current hospitalization and hospitalization in the previous month were significantly associated with DRM. In 23% of IBD patients, a deficiency of at least 1 micronutrient was observed, with no difference between ulcerative colitis and Crohn's disease. CONCLUSIONS: DRM and microelements malnutrition are frequent conditions in the IBD population. DRM seems to be associated with disease activity and hospitalization.

Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis: Insights into mechanisms, pathophysiology, and treatment options.

BACKGROUND: Autoimmune gastritis (AIG) is a progressive, chronic, immune-mediated inflammatory disease characterized by the destruction of gastric parietal cells leading to hypo/anacidity and loss of intrinsic factor. Gastrointestinal symptoms such as dyspepsia and early satiety are very common, being second in terms of frequency only to anemia, which is the most typical feature of AIG. AIM: To address both well-established and more innovative information and knowledge about this challenging disorder. METHODS: An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published in the last 10 years. RESULTS: A total of 125 records were reviewed and 80 were defined as fulfilling the criteria. CONCLUSION: AIG can cause a range of clinical manifestations, including dyspepsia. The pathophysiology of dyspepsia in AIG is complex and involves changes in acid secretion, gastric motility, hormone signaling, and gut microbiota, among other factors. Managing dyspeptic symptoms of AIG is challenging and there are no specific therapies targeting dyspepsia in AIG. While proton pump inhibitors are commonly used to treat dyspepsia and gastroesophageal reflux disease, they may not be appropriate for AIG. Prokinetic agents, antidepressant drugs, and non-pharmacological treatments may be of help, even if not adequately evidence-based supported. A multidisciplinary approach for the management of dyspepsia in AIG is recommended, and further research is needed to develop and validate more effective therapies for dyspepsia.