Search Results (86)

Background: Intentional occlusion of the internal iliac artery (IIA) during endovascular repair of aorto-iliac aneurysms may predispose patients to pelvic ischemic complications such as gluteal claudication, erectile dysfunction, and bowel ischemia. Iliac branch devices (IBDs) have been developed to preserve hypogastric perfusion. E-Liac (Artivion/Jotec) is one of the latest modular IBDs yet reports on mid-term performance are limited to small single-center cohorts with short follow-up. The CAMpania PugliA bRanch IliaC (CAMPARI) study is a multicenter investigation of E-Liac outcomes. Methods: A retrospective observational cohort study was conducted across five Italian vascular centers. All consecutive patients undergoing E-Liac implantation for aorto-iliac or isolated iliac aneurysms between January 2015 and December 2024 were identified from prospectively maintained registries. Inclusion criteria comprised elective or urgent endovascular repair of aorto-iliac aneurysms in which an adequate distal sealing zone was not available without covering the IIA and suitability for the E-Liac device according to its instructions for use (IFU). Patients with a life expectancy < 1 year or hostile anatomy incompatible with the IFU were excluded. The primary end point was freedom from branch instability (occlusion/stenosis, kinking, or detachment of the bridging stent). Secondary end points included freedom from any endoleak, freedom from device-related reintervention, freedom from gluteal claudication, aneurysm-related and all-cause mortality, acute renal failure, and sac regression > 5 mm. Results: A total of 69 consecutive patients (68 male, 1 female, median age 72.0 years) received 74 E-Liac devices, including 5 bilateral implantations. The mean infrarenal aortic diameter was 45 mm and the mean CIA diameter 34 mm; 14 patients (20.0%) had a concomitant IIA aneurysm (>20 mm). Concomitant fenestrated or branched aortic repair was performed in 23% of procedures. Two patients received a standalone IBD without implantation of a proximal aortic endograft. Technical success was achieved in 71/74 cases (96.0%); three failures occurred due to inability to catheterize the IIA. Distal landing was in the main IIA trunk in 58 cases and in the posterior branch in 13 cases. Over a median follow-up of 18 (6; 36) months, there were four branch instability events (5.4%): three occlusions and one bridging stent detachment. Seven patients (9.5%) developed endoleaks (one type Ib, two type II, two type IIIa, and two type IIIc). Five patients (6.8%) required reintervention, and five (6.8%) reported gluteal claudication. There were seven all-cause deaths (10%), none within 30 days or related to aneurysm rupture; causes included COVID-19 pneumonia, acute coronary syndrome, melanoma, gastric cancer, and stroke. No acute renal or respiratory failure occurred. Kaplan–Meier analysis showed 92% (95% CI 77–100) freedom from branch instability in the main-trunk group and 89% (60–100) in the posterior-branch group (log-rank p = 0.69). Freedom from any endoleak at 48 months was 87% (95% CI 75–95), and freedom from reintervention was 93% (95% CI 83–98). Conclusions: In this multicenter cohort, the E-Liac branched endograft demonstrated high technical success and favorable early–mid-term outcomes. Preservation of hypogastric perfusion using E-Liac was associated with low rates of branch instability, endoleak, and reintervention, with no 30-day mortality or aneurysm-related deaths. These findings support the safety and efficacy of E-Liac for aorto-iliac aneurysm management, although larger prospective studies with longer follow-up are needed. Full article

Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD), two major intestinal pathologies. Therefore, the mechanisms involved in butyrate transport across colonic epithelial cell membranes (uptake transporters: monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1); efflux transporters: breast cancer resistance protein (BCRP) and MCT1/monocarboxylate transporter 4 (MCT4)), which are determinant for its intracellular levels, are of primary importance for its beneficial effects at the colonic level. The available data suggest that all these butyrate transporters can be modulated by redox and inflammatory status, but the evidence is scarce and rather inconsistent. Nevertheless, a role of nuclear factor erythroid 2-related factor 2 (Nrf2) and of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mediating the effect of oxidative stress and inflammation, respectively, on MCT1 and SMCT1 is suggested. So, more investigation on this subject is needed, given the fact that increased oxidative stress levels and inflammatory status are present in a series of intestinal conditions and pathologies, including CRC and IBD, which could help to establish these transporters as potential cellular targets in these diseases. Full article

Intestinal health is essential for maintaining systemic physiological balance through nutrient absorption, immune regulation, and host–microbiota interactions. Atractylodes macrocephala (Baizhu), a traditional medicinal plant long used for gastrointestinal dysfunction, has attracted growing interest because its polysaccharides (AMPs) show promises in intestinal disorders. In this review, we summarize preclinical studies on AMPs identified through searches of PubMed, Web of Science, ScienceDirect, Google Scholar and the China National Knowledge Infrastructure (CNKI), focusing on their extraction, purification, structural features and gut-related activities. Experimental evidence suggests that AMPs are metabolized by gut microbiota into short-chain fatty acids and other bioactive metabolites that regulate mucosal immunity, enhance epithelial barrier function and modulate host metabolic pathways. AMPs have been shown to promote the growth of beneficial taxa, restore dysbiotic communities, up-regulate tight junction proteins, suppress intestinal inflammation and modulate gut–brain axis signaling involved in intestinal motility and visceral sensitivity. These actions underlie their protective effects reported in models of irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colorectal cancer, chemotherapy-induced mucosal injury, and metabolic-associated systemic inflammation. Overall, current data support AMPs as microbiota-modulating, immunomodulatory, epithelial-protective and neuro-regulatory agents with potential as functional food-derived interventions for intestinal health. In this review, we also highlight key limitations and priorities for future research on structure–function relationships and clinical translation. Full article

The gastrointestinal (GI) tract is a complex organ system affected by multiple disorders with diverse etiologies ranging from infections to immune dysfunction disorders and cancers. Various GI disorders, such as Helicobacter pylori infection, inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome (IBS), and colon cancer, are common and cause significant morbidity, mortality, and healthcare costs. These disorders present with overlapping signs and symptoms, warranting the need for accurate laboratory diagnostic tests for appropriate treatment implementation and treatment monitoring. The gold standard confirmatory diagnostic test for most GI disorders is endoscopy and biopsy for histological analysis. Biomarkers in blood and stool are also routinely used either as first-line screening tests or for treatment monitoring in many GI disorders. This review summarizes common GI disorders along with related currently used clinical laboratory tests in screening, diagnosis, and monitoring of these diseases, outlining the methodology, utilization, advantages, and limitations of these tests. We also highlight the effectiveness of each test as well as the professional recommendations and clinical guidelines for their use where available. Finally, we shed some light on potential future tests and biomarkers that aid in diagnosing GI disorders and how these biomarkers can be used in conjunction to complement the current tests. Some of the potential future biomarkers discussed include the differential expression of gut microbiota and their respective metabolites, as well as cytokines, as potential tests that can be used to diagnose diseases, distinguish between disease subtypes, predict disease severity and occurrence, and optimize treatment decisions. Comprehending the effectiveness of various methodologies for laboratory diagnosis of GI disorders is crucial for health care personnel, including clinical laboratory professionals and clinicians, regarding testing options, test utilization, and interpretations of results. Insights into future tests in GI diseases in the context of microbiomes, metabolites, and immune mediators based on advanced technology are also important in their appropriate clinical utilization. Full article

Sessile serrated lesions (SSLs) are well-known precursors of colorectal cancer in the general population, but their role in inflammatory bowel disease (IBD) is less clear. This narrative review summarizes what is known about the prevalence, molecular features, endoscopic detection, malignant potential, and management of SSLs in patients with IBD, highlighting where evidence supports action nowadays and where prospective studies are urgently needed. IBD-associated colorectal cancer has long been considered a consequence of the inflammation–dysplasia–carcinoma sequence, distinct from the conventional adenoma–carcinoma pathway. Increasing evidence, however, suggests that the serrated pathway, typically characterized by SSLs and traditional serrated adenomas (TSAs), may also contribute to IBD-related oncogenesis. This review synthesizes histopathological, molecular, endoscopic, and clinical data on SSLs in patients with IBD, with contextual reference to TSAs, sessile serrated lesions with dysplasia, and serrated epithelial change only when relevant to their interpretation or risk stratification. SSLs are now more frequently identified in IBD surveillance, especially in ulcerative colitis and the proximal colon, although prevalence estimates remain heterogeneous due to evolving definitions and significant interobserver variability. Molecular studies indicate that IBD-associated serrated lesions often harbor BRAF mutations but display a lower CpG island methylator phenotype than their sporadic counterparts, suggesting an inflammation-modified biology. While most hyperplastic polyps and non-dysplastic SSLs appear to pose limited neoplastic risk, dysplastic serrated lesions carry a markedly higher likelihood of synchronous or metachronous advanced neoplasia. Advances in high-definition endoscopy and chromoendoscopy improve the detection of these subtle, mucus-capped, flat lesions, while endoscopic resection is nowadays feasible in expert hands. Future priorities should include prospective multicenter cohorts integrating molecular profiling to refine surveillance strategies. Full article

Natural bioactive chemicals sourced from marine species have attracted growing interest due to their immunomodulatory, antioxidant, and gut microbiota-regulating characteristics. These chemicals, especially peptides, offer therapeutic approaches for addressing inflammation, immunological dysfunction, and intestinal barrier disturbance, which are frequently observed in conditions such as inflammatory bowel disease (IBD). This review centers on current discoveries about marine-derived peptides from octopus, sea conch, and scallop. These substances have demonstrated a considerable ability to restore intestinal integrity, regulate immune cell function, reduce pro-inflammatory cytokines, and rebalance dysbiotic gut microbiota. We consider several in vivo scenarios, encompassing dextran sulphate sodium (DDS)-induced colitis and cyclophosphamide-induced immunosuppression. These compounds raise the expression of tight junction proteins (including ZO-1 and occludin), boost the production of mucin, and encourage the growth of good bacteria such as Lactobacillus and Lachnospiraceae. Their effects are mechanistically associated with the inhibition of critical inflammatory pathways (e.g., Nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR-4)) and the modulation of both innate and adaptive immune responses. These versatile bioactives can serve as dietary supplements or complementary therapies for gastrointestinal and cancer-related issues. This review emphasizes the therapeutic potential of marine peptides, concentrating on gut–immune–microbiota interactions, as well as exploring future avenues for clinical translation and drug development Full article

Background/Objectives: Because of the chronic course of the disease, clinicians managing IBD frequently encounter patients with a prior or newly diagnosed cancer. This can be related to the specific background cancer risk in that subject, aging, familial/genetic factors, or ongoing chronic inflammation. However, a potential influence of some therapeutic agents should also be considered. This setting, in the absence of controlled trials and few open series reports available, raises issues such as correct screening, prevention, and surveillance, but also eventual modification or adaptation of the medical management. Methods and Results: Few consensus guidelines and studies are available on the management of IBD patients with a history of cancer, and therefore, we aim to review the recommendations of the current guidelines and the evidence reported in the most recent real-world cohorts. Conclusions: This review will offer (a) an understanding of the background of cancer risk in IBD patients; (b) analysis and discussion of the risk of cancer related to IBD therapy; and, finally, (c) some clues for the management of IBD in patients with a previous or current history of cancer. Full article

Quinoa (Chenopodium quinoa Willd.) is an ancient Andean crop renowned for its exceptional nutritional profile and diverse bioactive compounds, including polysaccharides, polyphenols, saponins, and essential fatty acids. As global incidence of colonic diseases such as inflammatory bowel disease (IBD), colorectal cancer (CRC), and celiac disease continues to rise, the therapeutic potential of quinoa has garnered increasing scientific attention. This review systematically examines the role of quinoa, with focus on quinoa polysaccharides (QPs), in maintaining and improving colonic health. It summarizes the molecular structure, functional properties, and gut microbiota-modulating effects of QPs, alongside emerging findings on their anti-inflammatory, antioxidant, immunomodulatory, and anticancer activities. Furthermore, the review explores quinoa’s auxiliary effects in mitigating CRC progression and chemotherapy resistance, alleviating intestinal inflammation, and supporting gastrointestinal integrity in celiac patients. By integrating evidence from multi-omics technologies, cell and animal models, and limited clinical studies with mechanistic insights, this review provides a focused synthesis of quinoa bioactive compounds in relation to colonic health. It highlights how precision nutrition and multi-omics approaches could guide future applications of quinoa as a novel functional food-based intervention for colonic diseases. Full article

Inflammatory bowel disease (IBD) is an autoimmune condition with an increasing incidence worldwide, which manifests in two pathological forms: Crohn’s disease (CD) or ulcerative colitis (UC). Both cause chronic inflammation of the digestive tract, although they can present different locations and with different symptoms. To date, the pathogenesis of IBD remains unclear. One of the major complications of these diseases is colorectal cancer. Several studies have reported a correlation between chronic intestinal inflammation and an increased risk of malignancy. Persistent inflammation damages the intestinal mucosa and epithelial wall, altering gut permeability and the local microenvironment. Moreover, the heightened activity of the immune system leads to an increased production of reactive oxygen and nitrogen species (ROS and RNS), increasing the risk of DNA mutation and cell transformation. In addition, some current therapies used to treat IBD and induce remission may contribute to carcinogenesis or impair immune surveillance due to their immunosuppressive activity. The management of cancer risk for IBD patients remains a challenge, and existing screening methods are often invasive (endoscopies, biopsies), resulting in low patient compliance. To address this unmet clinical need, researchers have started using proteomics to identify novel biomarkers that could predict cancer risk in IBD patients in a non-invasive manner. This review aims to examine the current state of knowledge regarding the correlation between IBD and cancer, with a special focus on the biomarkers discovered through proteomic approaches, and their potential application in routine clinical screening. In our view, proteomics represents a powerful and rapidly evolving strategy for biomarker discovery, with the potential to complement or even replace invasive procedures. Its future clinical impact will rely on translating current research advances into robust and accessible diagnostic tools. Full article

Background/Objectives: Chronic inflammation and Western-style diets elevate colorectal cancer (CRC) risk, particularly in individuals with colitis, a feature of inflammatory bowel disease (IBD). Diets rich in polyphenol-containing functional foods, such as cocoa, may reduce gut inflammation and modulate the gut microbiome. This study investigated the impact of cocoa polyphenol (CP) supplementation on inflammation and microbiome composition in mice with colitis, fed either a healthy or Western diet, before, during, and after the onset of disease. We hypothesized that CPs would attenuate inflammation and promote distinct shifts in the microbiome, especially in the context of a Western diet. Methods: A 2 × 2 factorial design tested the effects of the basal diet (AIN93G vs. total Western diet [TWD]) and CP supplementation (2.6% w/w CocoaVia™ Cardio Health Powder). Inflammation was induced using the AOM/DSS model of colitis. Results: CP supplementation did not reduce the severity of colitis, as measured by disease activity index or histopathology. CPs did not alter gene expression in healthy tissue or suppress the colitis-associated pro-inflammatory transcriptional profile in either of the two diet groups. However, fecal microbiome composition shifted significantly with CPs before colitis induction, with persistent effects on several rare taxa during colitis and recovery. Conclusions: CP supplementation did not mitigate inflammation or mucosal injury at the tissue level, nor did it affect the expression of immune-related genes. While CPs altered microbiome composition, most notably in healthy mice before colitis, these shifts did not correspond to changes in inflammatory signaling. Basal diet remained the primary determinant of inflammation, mucosal damage, and colitis severity in this model. Full article

Background: Ulcerative colitis (UC) is a chronic inflammatory condition associated with the colon and rectum, often predisposing individuals to inflammatory bowel disease-related colorectal cancer (IBD-CRC). Current therapeutic options for UC, including corticosteroids and immunosuppressive drugs, pose significant side effects. Punica granatum peel powder (PPPG), a traditional herbal remedy in Ayurveda medicine for colitis, exhibits promising therapeutic effects with a favorable safety profile. Objectives: This study aims to explore the therapeutic potential and mechanism of action of a modified PPPG formulation in UC treatment. Methods: Using NCM460 cells and an acetic acid-induced UC murine model, the efficacy of modified PPPG was evaluated. Results: Therapy with modified PPPG significantly improved UC-associated symptoms, such as improvements in body weight, colon length, and disease activity index, as validated by histological examination. Transcriptomic sequencing identified downregulation of the IL-6/STAT3 signaling pathway and reduced inflammatory markers like p-NF-κB, IL-1β, and NLRP3 on PPPG therapy. Conclusions: These findings suggest that modified PPPG holds promise as a novel therapeutic strategy for UC intervention, targeting key inflammatory pathways implicated in UC pathogenesis and potentially mitigating the risk of IBD-CRC. Full article

Introduction: The introduction of biologic therapies and small molecule drugs has revolutionized the management of inflammatory bowel disease (IBD), providing targeted control of inflammation. However, concerns remain regarding their long-term safety profiles, particularly in relation to cancer risk. Chronic inflammation and immunosuppressive therapies contribute to malignancy risk, including skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This review examines the evidence on skin cancer risks associated with these therapies, focusing on specific drug classes and their mechanisms. Results: Tumor necrosis factor (TNF) inhibitors have shown conflicting evidence regarding melanoma risk, with some studies reporting a modest increase and others finding no significant association. Anti-integrin agents, such as vedolizumab, and interleukin (IL)-12/23 inhibitors, including ustekinumab, have demonstrated favorable safety profiles with minimal skin cancer risks. Selective IL-23 inhibitors and sphingosine-1-phosphate (S1P) receptor modulators have limited long-term data, but early findings indicate a low incidence of skin malignancies. Janus kinase (JAK) inhibitors do not show an increased risk of skin cancers in IBD. Conclusions: Current evidence suggests that skin cancer risk in IBD patients treated with biologics and small molecule drugs varies by drug class. TNF inhibitors and JAK inhibitors are associated with higher risks, while other therapies show lower malignancy risks. Regular skin cancer screening and protective measures remain critical, particularly for patients with additional risk factors. Further long-term studies are essential to refine safety profiles and inform clinical practice in this evolving therapeutic landscape. Full article

Bile acids and their corresponding intestinal epithelial receptors, the farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5), play crucial roles in the physiological and pathological processes of intestinal epithelial cells. These acids and receptors are involved in the regulation of intestinal absorption, signal transduction, cellular proliferation and repair, cellular senescence, energy metabolism, and the modulation of gut microbiota. A comprehensive literature search was conducted using PubMed, employing keywords such as bile acid, bile acid receptor, FXR (nr1h4), TGR5 (gpbar1), intestinal epithelial cells, proliferation, differentiation, senescence, energy metabolism, gut microbiota, inflammatory bowel disease (IBD), colorectal cancer (CRC), and irritable bowel syndrome (IBS), with a focus on publications available in English. This review examines the diverse effects of bile acid signaling and bile receptor pathways on the proliferation, differentiation, senescence, and energy metabolism of intestinal epithelial cells. Additionally, it explores the interactions between bile acids, their receptors, and the microbiota, as well as the implications of these interactions for host health, particularly in relation to prevalent intestinal diseases. Finally, the review highlights the importance of developing highly specific ligands for FXR and TGR5 receptors in the context of metabolic and intestinal disorders. Full article

The glutathione shunt is one of the most important contributors to the cellular redox state, with implications across cancer, chronic diseases, diseases of ageing, and autoimmune diseases, including inflammatory bowel disease (IBD). Traditionally, the redox state is gauged by the ratio of the surrogate metabolites GSH and GSSG. However, this presents methodological challenges and offers a constrained illustration of metabolites without a systems-level understanding of redox dynamics, failing to elucidate variations across an entire biochemical network. Targeted proteomics can fill this void. Here, we describe an in-parallel metabolomic and proteomic targeted method to encompass measurements directly related to the shunt. Samples are simultaneously prepared to extract the substrate building blocks, cysteine, cystine, methionine, glutamic acid, and kynurenine; and the proteins, SLC7A11 (xCT), Glutamate Cysteine Ligase (GSH1), Glutathione Synthetase (GSH2), Glutathione Peroxidase (GPx), and Glutathione Reductase (GSHR) for targeted mass spectrometry. We demonstrate the method by targeted analysis of proteins in plasma, serum, nasal swab, and saliva and apply the multi-omic method to assess changes in the glutathione shunt in the serum of patients diagnosed with IBD. This allows for a broader narrative to establish context at which the glutathione shunt is operating. Full article

Introduction: In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. Methods: A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. Results: A total of 71 patients had colonic dysplasia. The mean age was 54 years old (SD ± 17). The majority were male (72%), white (69%), and non-Hispanic (94%). A total of 76% had ulcerative colitis (UC) and 24% had Crohn’s disease (CD). Of all dysplastic lesions, 57 (80%) patients had unifocal disease and the remainder had multifocal disease. A total of 39 (55%) patients had R-sided dysplasia, 24 (34%) had L-sided dysplasia, and 8 (11%) had both R- and L-sided dysplasia. Patients with UC were more likely to have L-sided dysplasia (92% vs. 8% in CD; p = 0.04). Pseudopolyps were more likely associated with R- and L-sided dysplasia (38% in R- and L-sided dysplasia, 10% in R-sided dysplasia, and 4% in L-sided dysplasia; p = 0.03). Conclusions: Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD. Full article