Gastrointest. Disord., Volume 6, Issue 2 (June 2024) – 9 articles

Non-IgE immune-mediated gastrointestinal disorders constitute a heterogeneous group of enigmatic conditions that are on the rise. This category encompasses entities like food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). These are immune-mediated reactions to certain foods without the involvement of allergen-specific IgE in their pathogenesis. Eosinophilic esophagitis (EoE) is also included in this group, acknowledged for its mixed IgE and non-IgE-mediated characteristics. The diagnostic landscape is fraught with challenges, given the poorly understood nature of these disorders and their propensity to manifest with varying and overlapping clinical presentations, typically emerging in infancy with common potential triggers such as cow’s milk and soy. Presently, confirmatory testing for most of these conditions is limited and invasive, emphasizing the pivotal role of a thorough history and physical examination in reaching a diagnosis. Notably, there are limited guidelines for diagnosis and management for most of these disorders. This article elucidates the key distinctions among these disorders, provides an overview of existing diagnostic and therapeutic approaches, and addresses existing knowledge and research gaps. The considerable impact on the quality of life of non-IgE immune-mediated allergic disorders of the gastrointestinal tract, which can result in debilitating complications such as nutritional deficiencies, mental health disorders, and eating disorders, underscores the urgency for comprehensive exploration and management strategies. Full article

Background/Aims: The purpose of this study was to determine the factors affecting positive diagnostic yields in patients with obscure gastrointestinal bleeding (OGIB) according to the guideline of small bowel capsule endoscopy (SBCE). Method: Patients with a complaint of melena or hematochezia who were admitted were consecutively enrolled. In patients with gastrointestinal bleeding, examination was performed according to the guideline. When OGIB was suspected, SBCE was performed. Patients were categorized into two subgroups based on the SBCE results: a positive group (n = 78) and a negative group (n = 67). Results: The rate of the positive diagnostic yield of SBCE was 53.8% (78/145). In patients over 60 years, the diagnostic yield was 61.5%, which was higher than in patients younger than 60 years (40.7%). In the multivariate analysis, there was a significant difference in the positive diagnostic yield in the patients aged over 60 years (p < 0.01). Factors related to the procedure and clinical characteristics also showed significant differences in the positive predictive rates according to the degree of bowel preparation, small bowel transit time, and transfusion requirements. Conclusions: SBCE could be recommended as a diagnostic tool for OGIB, especially in those with old ages (>60 years) and those who need transfusion, because of its relatively high diagnostic yields in these populations. Proper bowel preparation and a prolonged small bowel transit time may have clinical significance in relation to the positive diagnostic yield of SBCE in patients with OGIB. Full article

Purpose: Food insecurity and colorectal cancer (CRC) are widely prevalent problems in the U.S. However, the long-term effects of food insecurity among people living with CRC are not well explored (e.g., risk of mortality). Methods: Data from the U.S. National Health and Nutrition Examination Survey (years 1999–2010) were linked with mortality data from the National Death Index up to 31 December 2019. Results: A total of 30,752 adults comprised the analytic sample; 222 were living with CRC and more than a tenth were food-insecure (11.6%). In our adjusted analysis, individuals who were food insecure and had CRC were 4.13 times more likely to die of any cause and 9.57 times more likely to die of cardiovascular diseases (compared to those without CRC and food insecurity). Conclusions: Colorectal cancer is among the top cancers diagnosed in American adults and more than a tenth of adult Americans with CRC live with food insecurity. Given the higher risk of mortality with co-occurring CRC and food insecurity, collaborative healthcare models can help address food insecurity and other social needs of people with CRC, and surveillance measures for food insecurity should be widely implemented across health systems. Full article

Inflammatory bowel disease (IBD) represents a heterogenous and complex group of idiopathic chronic inflammatory conditions affecting the gastrointestinal tract and other extraintestinal systems with rising global incidences. The interplay of genetic predisposition and environmental factors contributes to its pathogenesis. Among the key cytokines implicated in IBD molecular alterations, IL-33 stands out for its multifaceted roles in both pathogenesis and repair mechanisms. IL-33, known for its action in initiating immune responses, is closely associated with Th2 immunity and is considered a potent inflammatory factor with dual functions, acting both as a pro-inflammatory cytokine and a transcriptional regulator. Primarily expressed by non-hematopoietic cells in the gastrointestinal tract, IL-33 interacts with its receptor, ST2, to modulate immune responses. In IBD, dysregulated IL-33 expression exacerbates mucosal inflammation, compromising barrier integrity and promoting tissue damage and fibrosis. Additionally, IL-33 plays a complex role in IBD-related colorectal cancer (CRC), affecting tumor progression and angiogenesis. This review summarizes the multifaceted roles of IL-33 in gastrointestinal health and disease, emphasizing its significance in the pathogenesis of IBD and CRC. Moreover, we thought it of interest to provide new insights into potential therapeutic avenues targeting IL-33 signaling for the management of these debilitating conditions. Full article

A severe condition of sepsis can be a complication of necrotizing enterocolitis (NEC), which can occur in premature infants and becomes a medical challenge in the neonatal intensive care unit (NICU). It is a multifactorial intestinal disease (can affect both the small and large intestine) that can lead to ischemia of the intestinal tissues that evolves into acute organ necrosis. One of these factors is that different types of nutrition can influence the onset or the progression of the disease. Cow-milk-based infant formulas have been shown to cause it in premature infants more frequently than human milk. Recently, nutrition has been shown to be beneficial after surgery. Several issues still under study, such as the pathogenesis and the insufficient and often difficult therapeutic approach, as well as the lack of a common and effective prevention strategy, make this disease an enigma in daily clinical practice. Recent studies outlined the emerging role of the host immune system and resident gut microbiota, showing their close connection in NEC pathophysiology. In its initial stages, broad-spectrum antibiotics, bowel rest, and breastfeeding are currently used, as well as probiotics to help the development of the intestinal microbiota and its eubiosis. This paper aims to present the current knowledge and potential fields of research in NEC pathophysiology and therapeutic assessment. Full article

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs. Full article

Introduction: Hepatectomy (HP) is, along with liver transplantation, the only potentially curative treatment for Hepatocellular Carcinoma (HCC). The high prevalence of Metabolic Syndrome (MS) may be causing a shift in the HCC spectrum. Hepatic Pedicle Clamping (HPC), used to reduce perioperative bleeding during HP, has been theorized to increase the risk of recurrence. Cytokeratin 19 (CK19) and glypican-3 (GLP-3) have been identified as markers of worse prognosis in HCC. Materials and Methods: A clinical and pathological review of 59 patients undergoing HP for HCC between 2005 and 2013 was performed. Chronic liver disease was observed in 53 patients (89.8%), with cirrhosis in 54.2% [most frequent etiologies: ethylism (47.5%), HCV (25.4%) and HBV (11.9%)]. MS was in 36% of patients. In addition, 95% of patients had Child–Pugh class A and 5% class B, and there was a median MELD of 8 (6–18). A single nodule was observed in 46 patients (78%) with an average size of 5.4 cm. Microscopic vascular invasion (MiVI) was in 49% of patients and macroscopic (MaVI) in 17. HPC was in 43 patients (74.1%). Statistical analysis was performed with SPSS™ 21.0. Survival tests (Kaplan–Meier, log-rank and Cox regression). Statistical significance was with p < 0.05. Results: Major morbidity in 22% of patients. Mortality in 5.1%. Median overall survival (OS) of 71 months and median disease-free survival (DFS) of 37. In a multivariate analysis: MaVI (p = 0.001), MiVI (p = 0.005) and HCV infection (p = 0.002) were associated with worse OS; MS was associated with better OS (p = 0.001); MaVI (p = 0.000), MiVI (p = 0.035) and HPC (p = 0.012) were associated with worse DFS. CK19+/GLP-3− (p = 0.007) and CK19−/GLP-3+ (p = 0.029) patients were associated with worse DFS and CK19−/GLP-3− (p = 0.031) with better DFS. Discussion/Conclusions: HPC was an independent factor of worse DFS. The ischemia-reperfusion injury (IRI) produced by HPC could promote a more angiogenic and angioinvasive phenotype of tumor cells, resulting in higher recurrence. HCV etiology was associated with worse OS. MS was associated with better OS, highlighting the importance of a hepatectomy in these cases. The combined detection of CK19 and GLP-3 was an independent prognostic factor in HCC patients allowing for the identification of more aggressive tumors. Full article

Traditional cancer treatments have not significantly improved the survival rates for individuals with colorectal cancer. As a result, there is a dire need to explore novel treatment modalities that can target cancer-specific niches, transform cold colorectal tumors into hot ones, and disrupt the tumor niche. Therapeutic focused ultrasound, recognized for its capacity to induce thermal and mechanical impacts on tissue, can potentially eliminate cancer cells and elicit the body’s anticancer reaction by disrupting the tumor microenvironment. This article provides an overview of recent developments in employing therapeutic focused ultrasound (TFUS) to enhance the body’s natural defenses against colorectal cancers. It also discusses studies examining the utility of TFUS in treating colorectal cancer patients and recent research indicating its potential to stimulate the body’s anticancer response in various in vitro and in vivo colorectal cancer models. Furthermore, it explores the therapeutic effects of TFUS on the immune system in colorectal cancers. This article also highlights the safety and effectiveness of TFUS in managing colorectal cancer, providing relief from pain, and potentially improving survival rates. Given the indications that TFUS may bolster the body’s immune response and augment the impacts of TFUS therapy in clinical and preclinical colorectal cancer models, it has the potential to emerge as a pivotal tool in clinical settings. Full article

The enteric nervous system (ENS), consisting of neurons and glial cells, is situated along the gastrointestinal (GI) tract’s wall and plays a crucial role in coordinating digestive processes. Recent research suggests that the optimal functioning of the GI system relies on intricate connections between the ENS, the intestinal epithelium, the immune system, the intestinal microbiome, and the central nervous system (CNS). Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory disorders, such as Crohn’s disease (CD) and ulcerative colitis (UC), characterized by recurring inflammation and damage to the GI tract. This review explores emerging research in the dynamic field of IBD and sheds light on the potential role of ENS alterations in both the etiology and management of IBD. Specifically, we delve into IBD-induced enteric glial cell (EGC) activation and its implications for persistent enteric gliosis, elucidating how this activation disrupts GI function through alterations in the gut–brain axis (GBA). Additionally, we examine IBD-associated ENS alterations, focusing on EGC senescence and the acquisition of the senescence-associated secretory phenotype (SASP). We highlight the pivotal role of these changes in persistent GI inflammation and the recurrence of IBD. Finally, we discuss potential therapeutic interventions involving senotherapeutic agents, providing insights into potential avenues for managing IBD by targeting ENS-related mechanisms. This approach might represent a potential alternative to managing IBD and advance treatment of this multifaceted disease. Full article