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16 pages, 2235 KiB  
Article
Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma
by Tomoyuki Iwasaki, Hidekazu Shirota, Eiji Hishinuma, Shinpei Kawaoka, Naomi Matsukawa, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, Masanobu Takahashi, Chikashi Ishioka, Seizo Koshiba and Hisato Kawakami
Int. J. Mol. Sci. 2025, 26(15), 7528; https://doi.org/10.3390/ijms26157528 - 4 Aug 2025
Abstract
Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host [...] Read more.
Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Genomics of Tumors)
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15 pages, 540 KiB  
Review
Achalasia and Gut Microbiota: Is Dysbiosis an Overlooked Factor in Postoperative Surgical Outcomes?
by Agostino Fernicola, Giuseppe Palomba, Armando Calogero, Antonella Sciarra, Annachiara Cavaliere, Felice Crocetto, Caterina Sagnelli, Antonio Alvigi, Raffaele Basile, Domenica Pignatelli, Andrea Paolillo, Federico Maria D’Alessio, Giacomo Benassai, Gennaro Quarto and Michele Santangelo
Surgeries 2025, 6(3), 63; https://doi.org/10.3390/surgeries6030063 - 28 Jul 2025
Viewed by 298
Abstract
Background: Esophageal achalasia is a rare motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and food stasis. Surgical interventions, including Heller myotomy with fundoplication or peroral endoscopic myotomy (POEM), effectively alleviate symptoms but induce significant anatomical and functional alterations. In [...] Read more.
Background: Esophageal achalasia is a rare motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and food stasis. Surgical interventions, including Heller myotomy with fundoplication or peroral endoscopic myotomy (POEM), effectively alleviate symptoms but induce significant anatomical and functional alterations. In various gastrointestinal surgeries, microbiota have been implicated in modulating clinical outcomes; however, their role in achalasia surgery remains unexplored. Methods: We performed a narrative literature search of various databases to identify studies exploring potential interactions between the gastroesophageal microbiota, achalasia pathophysiology, and surgical treatment, proposing clinical implications and future research avenues. Results: Chronic esophageal stasis in achalasia promotes local dysbiosis by facilitating aberrant bacterial colonization. Surgical restoration of esophageal motility and gastroesophageal transit induces substantial shifts in the microbial ecosystem. Analogous microbiota alterations following procedures such as fundoplication, gastrectomy, and bariatric surgery underscore the significant impact of mechanical modifications on microbial composition. Comprehensive microbiota profiling in patients with achalasia may enable the identification of dysbiotic phenotypes predisposed to complications, thereby providing personalized therapeutic interventions including probiotics, prebiotics, dietary modulation, or targeted antibiotic therapy. These insights hold promise for clinical benefits, including the mitigation of inflammation and infection, monitoring of surgical efficacy through microbial biomarkers, and optimization of postoperative nutritional strategies to reestablish microbial homeostasis, ultimately enhancing patient outcomes beyond conventional treatment paradigms. Conclusions: The gastroesophageal microbiota is a compelling mediator of surgical outcomes in achalasia. Future investigations integrating microbiological and inflammatory profiling are warranted to elucidate the functional role of the gastroesophageal microbiota and assess its potential as a biomarker and therapeutic target. Full article
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9 pages, 1860 KiB  
Case Report
Eosinophilic Esophagitis in a 3-Year-Old Girl with Spinal Muscular Atrophy Type 1: The First Reported Case
by Aleksandra Marzec, Elżbieta Jarocka-Cyrta and Marta Ruskań-Bakun
Pediatr. Rep. 2025, 17(4), 80; https://doi.org/10.3390/pediatric17040080 - 28 Jul 2025
Viewed by 210
Abstract
Background: Spinal muscular atrophy type 1 (SMA1) is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy, including the muscles of the oral cavity and esophagus. Eosinophilic esophagitis (EoE), a chronic, allergic disease, presents with eosinophilic infiltration of the esophagus, leading [...] Read more.
Background: Spinal muscular atrophy type 1 (SMA1) is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy, including the muscles of the oral cavity and esophagus. Eosinophilic esophagitis (EoE), a chronic, allergic disease, presents with eosinophilic infiltration of the esophagus, leading to esophageal dysmotility. Feeding difficulties may occur in both conditions. So far, the coexistence of EoE and SMA1 has not been described; we present the first such case. Case presentation: The patient was a girl with SMA1 diagnosed shortly after birth, treated with nusinersen and onasemnogene abeparvovec, and fed a standard industrial diet through a gastrostomy. In her second year of life, she developed increasing symptoms: distress during feeding, regurgitation, vomiting, and weight loss. She was treated with proton pump inhibitors without clinical improvement. Gastroscopy was performed, revealing superficial epithelial damage with bleeding in the proximal esophagus. Histopathology showed chronic inflammation with up to 150 eosinophils per high-power field, microabscesses, spongiosis, and basal layer hypertrophy. The girl was diagnosed with EoE. Her diet was switched from a standard industrial formula to an amino acid-based formula, which led to marked clinical improvement, the resolution of symptoms, and appropriate weight gain. Conclusions: This case report highlights the challenges of diagnosing EoE in SMA1 patients and emphasizes the need for multidisciplinary approaches and further investigation of allergic manifestations in SMA1 patients. Full article
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12 pages, 1565 KiB  
Case Report
Severe Rectal Syphilis in the Setting of Profound HIV Immunosuppression: A Case Report Highlighting ERG/CD38 Immunophenotyping and a Review of the Literature
by Diana Marcela Carmona Valencia, Juan Diego López, Shirley Vanessa Correa Forero, Diana Marcela Bonilla Bonilla, Jorge Karim Assis and Yamil Liscano
Infect. Dis. Rep. 2025, 17(4), 85; https://doi.org/10.3390/idr17040085 - 16 Jul 2025
Viewed by 357
Abstract
Background and Aim: Syphilis, caused by Treponema pallidum, classically presents with genital or anal chancres; rectal involvement is rare and frequently misdiagnosed as inflammatory bowel disease or malignancy. We describe an unusually severe case of syphilitic proctitis in the setting of advanced [...] Read more.
Background and Aim: Syphilis, caused by Treponema pallidum, classically presents with genital or anal chancres; rectal involvement is rare and frequently misdiagnosed as inflammatory bowel disease or malignancy. We describe an unusually severe case of syphilitic proctitis in the setting of advanced HIV-related immunosuppression (CD4 39 cells/µL), in which targeted immunophenotyping (ERG and CD38) was a valuable adjunctive tool in the differential diagnosis. Case Presentation: A 46-year-old man with a recent history of erosive gastritis and esophageal candidiasis presented after six months of unintentional 20 kg weight loss, profound fatigue, intermittent fevers, profuse diarrhea, and two episodes of hematemesis. Workup revealed a new diagnosis of HIV infection (CD4: 39 cells/µL; viral load: 87,837 copies/mL). Contrast-enhanced CT demonstrated uniform, concentric rectal wall thickening (“target sign”). Colonoscopic biopsy showed exuberant granulation tissue and dense plasma cell infiltrates. Immunohistochemistry revealed a dense infiltrate of CD38-positive plasma cells and ERG-positive endothelial proliferation. These findings, in the context of positive serology, were highly supportive of a spirochetal etiology and helped differentiate it from potential mimics. Serology was positive for latent late syphilis (VDRL 1:64). The patient received three weekly doses of intramuscular benzathine penicillin; lumbar puncture excluded neurosyphilis. Discussion: This is among the first reported cases of syphilitic proctitis in a patient with CD4 < 50 cells/µL, where advanced immunophenotyping differentiated syphilitic inflammation from neoplastic or inflammatory mimics. Profound immunosuppression accelerates disease progression and yields atypical clinical features. Conclusion: In HIV-infected patients with chronic rectal symptoms, especially those with CD4 < 50 cells/µL, syphilitic proctitis must be considered. Integration of radiologic assessment, histopathology with ERG/CD38 staining, and serologic testing permits prompt diagnosis. Early benzathine penicillin therapy and rigorous clinical and serologic follow-up are essential to prevent complications, including neurosyphilis. Full article
(This article belongs to the Section Bacterial Diseases)
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43 pages, 4357 KiB  
Systematic Review
Vitamin D’s Impact on Cancer Incidence and Mortality: A Systematic Review
by Sunil J. Wimalawansa
Nutrients 2025, 17(14), 2333; https://doi.org/10.3390/nu17142333 - 16 Jul 2025
Viewed by 1534
Abstract
Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This [...] Read more.
Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. Results: Beyond genomic actions via calcitriol [1,25(OH)2D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin’s and non-Hodgkin’s lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40–80 ng/mL) significantly lowers cancer risks and mortality. Conclusions: While many observational studies support vitamin D’s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D3 doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality. Full article
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17 pages, 4202 KiB  
Article
The Dichloromethane Fraction of Sanguisorba tenuifolia Inhibits Inflammation in Cells Through Modulation of the p38/ERK/MAPK and NF-κB Signaling Pathway
by Yue Wang, Yiming Lu, Fuao Niu, Siqi Fa, Li Nan and Hyeon Hwa Nam
Int. J. Mol. Sci. 2025, 26(14), 6732; https://doi.org/10.3390/ijms26146732 - 14 Jul 2025
Viewed by 213
Abstract
Sanguisorba tenuifolia is a wild plant of the genus Sanguisorba officinalis. This study aimed to investigate the regulatory effect of the dichloromethane fraction of Sanguisorba tenuifolia on LPS-induced inflammatory responses in RAW264.7 cells, thereby providing a new scientific basis for the medicinal [...] Read more.
Sanguisorba tenuifolia is a wild plant of the genus Sanguisorba officinalis. This study aimed to investigate the regulatory effect of the dichloromethane fraction of Sanguisorba tenuifolia on LPS-induced inflammatory responses in RAW264.7 cells, thereby providing a new scientific basis for the medicinal development of Sanguisorba tenuifolia. Initially, we used 75% ethanol to crudely extract the roots of Sanguisorba tenuifolia, followed by fractional extraction using dichloromethane (CH2Cl2), ethyl acetate (EtOAc), butanol (BuOH), and distilled water (DW) as solvents. By measuring the inhibitory effects of each fractionated extract on NO production, we determined that the SCE (Dichloromethane fraction of Sanguisorba tenuifolia) exhibited the most potent anti-inflammatory activity, leading to its progression to the next experimental stage. Subsequently, we evaluated the effects of SCE on cell viability and LPS-induced inflammatory cytokine secretion in RAW264.7 cells. A rat model of reflux esophagitis was also used to validate the in vivo anti-inflammatory effects of SCE. Additionally, we utilized UPLC/MS-MS to identify and analyze the active components of SCE. The results indicated that SCE could effectively inhibit LPS-induced cellular inflammation by modulating the p38/ERK/MAPK and NF-κB signaling pathways, and also reduced the damage of the esophageal mucosa in rats with reflux esophagitis. UPLC/MS-MS analysis of SCE identified 423 compounds, including 12 active ingredients such as triterpenoids, phenols, and steroids. This discovery not only provides scientific support for the potential of Sanguisorba tenuifolia as an anti-inflammatory agent but also lays the groundwork for the development of new therapeutics for the treatment of inflammatory diseases. Full article
(This article belongs to the Section Molecular Pharmacology)
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17 pages, 283 KiB  
Review
Food-Specific IgG Antibodies: Decoding Their Dual Role in Immune Tolerance and Food Intolerance
by Jenny Valentina Garmendia, Juan Bautista De Sanctis and Alexis Hipólito García
Immuno 2025, 5(3), 25; https://doi.org/10.3390/immuno5030025 - 27 Jun 2025
Viewed by 1252
Abstract
IgG antibodies, particularly those of the IgG4 subclass, have generated significant debate regarding their role in immune tolerance versus food intolerance. This article comprehensively reviews the literature on the subject, exploring evidence from healthy individuals and patient populations with varied clinical conditions. On [...] Read more.
IgG antibodies, particularly those of the IgG4 subclass, have generated significant debate regarding their role in immune tolerance versus food intolerance. This article comprehensively reviews the literature on the subject, exploring evidence from healthy individuals and patient populations with varied clinical conditions. On one hand, IgG—especially IgG4—is frequently detected in individuals without adverse food reactions and may represent a normal adaptive immune response to constant dietary antigen exposure, contributing to the development of regulatory T-cell–mediated tolerance. On the other hand, several studies have linked elevated food-specific IgG levels with conditions characterized by increased intestinal permeability and inflammation, including eosinophilic esophagitis, irritable bowel syndrome, inflammatory bowel disease, and autoimmune disorders. The review discusses multiple investigations where IgG-guided elimination diets have yielded symptomatic improvements, suggesting a potential benefit for targeted dietary interventions. However, these findings are tempered by the observation that IgG antibodies are commonly present in asymptomatic individuals, thereby questioning their specificity as markers of adverse food reactions. Current diagnostic guidelines from leading allergy and immunology organizations discourage routine IgG testing for food allergies and intolerances, highlighting that these antibodies might instead indicate exposure or underlying inflammation rather than an actual pathogenic mechanism. There is a need for well-controlled, large-scale studies to clearly define the clinical relevance of food-specific IgG responses. Until more substantial evidence is provided, clinicians are advised to interpret the IgG results cautiously and to consider them within the broader context of each patient’s clinical presentation before recommending restrictive dietary changes. Full article
28 pages, 707 KiB  
Review
Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications
by Valentina Schiavoni, Tiziana Di Crescenzo, Valentina Membrino, Sonila Alia, Sonia Fantone, Eleonora Salvolini and Arianna Vignini
Pharmaceuticals 2025, 18(7), 966; https://doi.org/10.3390/ph18070966 - 27 Jun 2025
Viewed by 648
Abstract
Bardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, [...] Read more.
Bardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, controlling the expression of genes involved in antioxidant defense, detoxification, and mitochondrial function. By inducing Nrf2 and promoting the transcription of downstream antioxidant response element (ARE)-driven genes, bardoxolone methyl enhances cellular resilience to oxidative stress and inflammation. This mechanism is central not only to its cytoprotective effects but also to its emerging role in oncology. A number of studies investigated the effects of bardoxolone methyl in several malignancies including breast cancer, lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, oral and esophageal squamous cell carcinoma, ovarian cancer and glioblastoma. Studies in the literature indicate that bardoxolone methyl exhibits anticancer activity through several mechanisms, including the suppression of cell proliferation, induction of cell cycle arrest and apoptosis, inhibition of epithelial–mesenchymal transition (EMT), and impairment of cancer cell stemness. Additionally, bardoxolone methyl modulates mitochondrial function, reduces glycolytic and oxidative phosphorylation capacities, and induces reactive oxygen species (ROS)-mediated stress responses. In this review, we summarize the available literature regarding the studies which investigated the effects of bardoxolone methyl as anticancer agent. Full article
(This article belongs to the Section Pharmacology)
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9 pages, 4551 KiB  
Article
Pediatric Heterotopic Gastric Mucosa of the Cervical Esophagus (Inlet Patch): Case Series with Clinical, Endoscopic, and Histopathological Correlation
by Javier Arredondo Montero, Samuel Sáez Álvarez, Andrea Herreras Martínez, Ana Fernández-García and Cristina Iglesias Blázquez
Children 2025, 12(6), 752; https://doi.org/10.3390/children12060752 - 10 Jun 2025
Viewed by 500
Abstract
Introduction: Inlet patch (IP) is a congenital anomaly characterized by gastric heterotopia in the cervical esophagus. While extensively described in adults, it remains poorl characterized in pediatric populations. Material and Methods: This retrospective, single-center study included all pediatric patients (0–14 years) diagnosed with [...] Read more.
Introduction: Inlet patch (IP) is a congenital anomaly characterized by gastric heterotopia in the cervical esophagus. While extensively described in adults, it remains poorl characterized in pediatric populations. Material and Methods: This retrospective, single-center study included all pediatric patients (0–14 years) diagnosed with IP between 2018 and 2025. Sociodemographic and clinical data were collected. A blinded pathologist assessed the presence and severity of inflammation within the IP. Results: Nine patients (median age, 12 years; range, 6–14 years) were included, with 78% beingmale. Cervical esophageal symptoms were identified in 67%, primarily dysphagia and gastroesophageal reflux disease-related complaints, although concomitant conditions such as eosinophilic esophagitis were frequently present. Three patients had symptoms potentially attributable to IP (33%). Endoscopic examination revealed characteristic well-demarcated salmon-red plaques in all patients, with multiple lesions observed in three cases. Histology confirmed gastric heterotopia with varying degrees of chronic inflammation in all cases. A potential association was observed between the severity of gastritis in the stomach, the severity of inflammation in the IP, and the presence of H. pylori, with 75% of patients with moderate-to-severe IP inflammation also exhibiting gastric H. pylori-associated gastritis. All patients except one received proton pump inhibitors, and symptoms improved in all cases. Conclusions: A thorough and targeted examination of the cervical esophagus significantly increased IP detection at our center, with most cases (89%) being diagnosed in the last 12 months. While mostly asymptomatic and incidental, IP can be symptomatic. In this case, series, we found a possible association between the severity of inflammation in the IP, the severity of gastritis, and the presence of H. pylori. Further studies are needed to define the clinical significance of pediatric IP and optimal management. Full article
(This article belongs to the Special Issue Advances in Pediatric Gastroenterology)
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19 pages, 552 KiB  
Review
Current and Emerging Therapies for Eosinophilic Esophagitis (EoE): A Comprehensive Review
by Brooke G. Musburger, Maria Gonzalez Echeandia, Elias L. Suskind, David L. Suskind, Hengqi Betty Zheng and Dominique Mark
Pharmaceutics 2025, 17(6), 753; https://doi.org/10.3390/pharmaceutics17060753 - 7 Jun 2025
Viewed by 1514
Abstract
Eosinophilic Esophagitis (EoE) is a chronic, immune-mediated disorder that is characterized by symptoms of esophageal dysfunction and the presence of increased eosinophils in the esophageal mucosa. It is becoming increasingly prevalent among children and adults and its pathogenesis arises from the complex interaction [...] Read more.
Eosinophilic Esophagitis (EoE) is a chronic, immune-mediated disorder that is characterized by symptoms of esophageal dysfunction and the presence of increased eosinophils in the esophageal mucosa. It is becoming increasingly prevalent among children and adults and its pathogenesis arises from the complex interaction of genetic predisposition and environmental triggers, both which contribute to esophageal inflammation. Current societal guidelines recommend the use of proton pump inhibitors, topical steroids, and dietary interventions such as elimination diets as first-line treatments, however, the recent approval of Dupliumab has provided an additional therapeutic avenue. There are a number of investigational biologic agents targeting other immune pathways which are making their way through the pipeline of pharmacologic options in treating this chronic disorder. Full article
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12 pages, 295 KiB  
Review
The Influence of Metabolic Syndrome on the Development of Gastrointestinal Malignant Tumors—A Review
by Vesna Brzački, Andrija Rančić, Snežana Tešić Rajković, Ivan Nagorni, Marko Stamenković, Elena Stanković, Nikola Milutinović and Aleksandar Vukadinović
Medicina 2025, 61(6), 1025; https://doi.org/10.3390/medicina61061025 - 31 May 2025
Viewed by 747
Abstract
Background and Objectives: Metabolic syndrome (MetS) is characterized by a cluster of metabolic abnormalities, including abdominal obesity, hyperglycemia, insulin resistance, dyslipidemia, and hypertension. Growing evidence suggests that these components may contribute to the development of gastrointestinal (GI) malignancies. This review aims to [...] Read more.
Background and Objectives: Metabolic syndrome (MetS) is characterized by a cluster of metabolic abnormalities, including abdominal obesity, hyperglycemia, insulin resistance, dyslipidemia, and hypertension. Growing evidence suggests that these components may contribute to the development of gastrointestinal (GI) malignancies. This review aims to explore the association between MetS and GI cancers, including esophageal, gastric, pancreatic, and colorectal cancers. Materials and Methods: A narrative literature review was conducted using PubMed, incorporating 22 sources published between 1991 and 2024. Search terms included “gastrointestinal malignant tumors”, “metabolic syndrome”, “diabetes mellitus”, and “obesity”. Priority was given to large-scale studies from Europe, America, and Asia. Case reports, commentaries, and conference abstracts were excluded. Results: By analyzing the available literature data, this study determined that hyperinsulinemia (IGF-1 pathway), hyperglycemia, and obesity (>102 cm in men and >88 cm in women) are highly associated with the development of esophageal cancer (primarily with Barret’s long and short segment as precancerosis), gastric cancer (through reactive oxygen species), and both pancreatic (1.5–2.4 higher risk) and colorectal cancer (30% higher risk). Patients with a high BMI (>40 kg/m2) show a 20%- or 1.18-times greater risk of developing colorectal cancer and a 1.72-times higher risk of developing pancreatic cancer. There is not enough evidence on the specific influence of hypertriglyceridemia, low HDL cholesterol, and high blood pressure on the development of gastrointestinal malignancy. However, those three conditions have shown a low to moderate association (from 6% to 12%) with the development of colorectal cancer. Conclusions: Metabolic syndrome (MetS) is increasingly being recognized as a significant risk factor for the development and progression of gastrointestinal cancers. Key components such as obesity, hyperglycemia, insulin resistance, and type 2 diabetes mellitus appear to contribute to carcinogenesis through mechanisms involving chronic inflammation, oxidative stress, and immune dysregulation. Further research is needed to clarify the biological pathways linking MetS to gastrointestinal malignancies and to inform effective prevention strategies. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
14 pages, 604 KiB  
Review
Targeting Gastrointestinal Cancers with Carvacrol: Mechanistic Insights and Therapeutic Potential
by Nitika Patwa, Gagandeep Singh, Vikas Sharma, Priyanka Chaudhary, Bunty Sharma, Shafiul Haque, Vikas Yadav, Shakti Ranjan Satapathy and Hardeep Singh Tuli
Biomolecules 2025, 15(6), 777; https://doi.org/10.3390/biom15060777 - 27 May 2025
Viewed by 1064
Abstract
Gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, liver, and colorectal malignancies, represent a major global health burden due to their high incidence, aggressive nature, and limited treatment outcomes. This review explores the therapeutic potential of carvacrol, a naturally occurring monoterpenoid phenol predominantly found [...] Read more.
Gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, liver, and colorectal malignancies, represent a major global health burden due to their high incidence, aggressive nature, and limited treatment outcomes. This review explores the therapeutic potential of carvacrol, a naturally occurring monoterpenoid phenol predominantly found in oregano and other aromatic plants. Carvacrol has demonstrated strong anticancer properties by modulating multiple molecular pathways governing apoptosis, inflammation, angiogenesis, and metastasis. Preclinical studies have revealed its ability to selectively target cancer cells while sparing healthy tissue. Advances in nanotechnology have further enhanced its pharmacological profile by improving solubility, stability, and tumor-targeted delivery. Additionally, carvacrol shows synergistic effects when used in combination with conventional chemotherapeutics. While the evidence is promising, clinical studies are needed to validate its translational potential. This review aims to consolidate current findings and encourage further investigation into carvacrol’s application as an adjunct or alternative therapeutic agent in GI cancer management. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment (3rd Edition))
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21 pages, 5680 KiB  
Review
Endoscopic Dilation for Fibrostenotic Complications in Eosinophilic Esophagitis—A Narrative Review
by Marco Michelon, Edoardo Vincenzo Savarino, Michele Montori, Maria Eva Argenziano, Pieter Jan Poortmans, Pierfrancesco Visaggi, Roberto Penagini, David J. Tate, Marina Coletta and Andrea Sorge
Allergies 2025, 5(2), 17; https://doi.org/10.3390/allergies5020017 - 26 May 2025
Viewed by 1410
Abstract
Esophageal fibrotic remodeling is a major complication of chronic inflammation in eosinophilic esophagitis (EoE) and represents one of the main determinants of symptoms in adult patients with EoE, with a remarkable impact on patients’ quality of life and the healthcare system. Esophageal fibrotic [...] Read more.
Esophageal fibrotic remodeling is a major complication of chronic inflammation in eosinophilic esophagitis (EoE) and represents one of the main determinants of symptoms in adult patients with EoE, with a remarkable impact on patients’ quality of life and the healthcare system. Esophageal fibrotic remodeling is diagnosed through upper gastrointestinal endoscopy, radiological studies, and a functional luminal imaging probe. However, diagnostic underestimation of esophageal strictures and suboptimal adherence to EoE guidelines still represent limitations of current clinical practice. Combined with medical therapy and/or elimination diets, endoscopic dilation remains the cornerstone treatment for esophageal strictures and rings, offering a safe and effective option for managing obstructive symptoms. Different modalities are available for esophageal endoscopic dilation of EoE, including mechanical and balloon dilators. Mechanical dilators provide tactile feedback during the procedure and exert longitudinal and radial forces. In contrast, balloon dilators apply a purely radial force and enable direct visualization of the esophageal mucosa during the procedure. Both mechanical and balloon dilators are safe and effective, with no single modality demonstrating clear superiority. Consequently, the choice of dilation technique is guided by stricture characteristics, the expertise of the endoscopist, and considerations related to the financial and environmental sustainability of the devices. This review aims to summarize the most relevant evidence on the endoscopic evaluation and dilation of fibrostenotic complications in EoE, also providing practical guidance for clinicians to optimize the endoscopic management of these patients. Full article
(This article belongs to the Section Diagnosis and Therapeutics)
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16 pages, 803 KiB  
Review
The Role of Microbiota in Upper Gastrointestinal Cancers
by Giovanni Marasco, Luigi Colecchia, Daniele Salvi, Angelo Bruni, Cecilia Capelli, Elton Dajti, Maria Raffaella Barbaro, Cesare Cremon, Vincenzo Stanghellini and Giovanni Barbara
Cancers 2025, 17(10), 1719; https://doi.org/10.3390/cancers17101719 - 21 May 2025
Viewed by 868
Abstract
The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota [...] Read more.
The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota vary, with standardization being essential for reliable results. Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) are associated with an enrichment of Gram-negative bacteria, promoting inflammation and cancer progression. Esophageal squamous cell carcinoma (ESCC) also shows distinct microbial patterns, with reduced diversity and increased harmful bacteria like Porphyromonas gingivalis and Fusobacterium nucleatum. In gastric cancer (GC), Helicobacter pylori (HP) and non-HP gastric microbiota play significant roles, with diverse microbial communities contributing to cancer development through nitrate reduction, immune modulation, and inflammation. Emerging evidence highlights the role of non-HP bacteria in promoting carcinogenesis, with specific taxa like Fusobacterium nucleatum and Lactobacillus influencing tumor growth and immune evasion. Further research is needed to elucidate the complex interactions between gut microbiota and upper GI cancers, paving the way for novel diagnostic and therapeutic approaches. Understanding these microbial dynamics offers potential for microbiota-based interventions, improving the early detection, prognosis, and treatment of upper GI cancers. This comprehensive review summarizes the available evidence on the role of microbiota in upper GI oncology and the need for continued exploration in this field. Full article
(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)
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15 pages, 1141 KiB  
Case Report
Clinical Heterogeneity of Early-Onset Autoimmune Gastritis: From the Evidence to a Pediatric Tailored Algorithm
by Ivan Taietti, Martina Votto, Riccardo Castagnoli, Mirko Bertozzi, Maria De Filippo, Antonio Di Sabatino, Ombretta Luinetti, Alessandro Raffaele, Alessandro Vanoli, Marco Vincenzo Lenti, Gian Luigi Marseglia and Amelia Licari
Diseases 2025, 13(5), 133; https://doi.org/10.3390/diseases13050133 - 25 Apr 2025
Viewed by 1449
Abstract
Autoimmune gastritis (AIG) is an uncommon and often underestimated condition in children, characterized by chronic stomach inflammation leading to the destruction of oxyntic glands with subsequent atrophic and metaplastic changes. This condition is associated with hypo-/achlorhydria, impairing iron and vitamin B12 absorption. The [...] Read more.
Autoimmune gastritis (AIG) is an uncommon and often underestimated condition in children, characterized by chronic stomach inflammation leading to the destruction of oxyntic glands with subsequent atrophic and metaplastic changes. This condition is associated with hypo-/achlorhydria, impairing iron and vitamin B12 absorption. The pathogenesis involves the activation of helper type 1 CD4+/CD25-T-cells against parietal cells. Clinical manifestations in children are not specific and include abdominal pain, bloating, nausea, vomiting, and iron deficiency anemia (IDA). The disease is also linked to an increased risk of pernicious anemia, intestinal-type gastric cancer, and type I neuroendocrine tumors. AIG is often diagnosed through the presence of autoantibodies in the serum, such as parietal cell (APCA) and intrinsic factor (IF) antibodies. However, therapeutic recommendations for pediatric AIG are currently lacking. We aim to present two clinical cases of pediatric-onset AIG, highlighting the heterogeneous clinical manifestations and the challenges in diagnosis with the support of an updated literature review. A 9-year-old girl presented with refractory IDA, initial hypogammaglobulinemia, and a 12-year-old boy was initially diagnosed with eosinophilic esophagitis. Both cases underline the importance of considering AIG in children with chronic gastrointestinal symptoms and gastric atrophy. Diagnostic workup, including endoscopy and serological tests, is crucial for accurate identification. A better understanding of this condition is imperative for timely intervention and regular monitoring, given the potential long-term complications, including the risk of malignancy. These cases contribute to expanding the clinical spectrum of pediatric AIG and highlight the necessity for comprehensive evaluation and management in affected children. Full article
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