Search Results (2,120)

(1) Background: Transesophageal echocardiography (TEE) is the gold standard for diagnosing patent foramen ovale (PFO) in cryptogenic ischemic stroke. However, false-positive diagnoses remain clinically relevant, exposing patients to unnecessary invasive procedures. (2) Methods: We retrospectively analyzed 346 patients with cryptogenic ischemic stroke who underwent TEE for PFO from 2012–2021. PFO was confirmed in 326 patients (94.2%), whereas 20 patients (5.8%, 95% CI 3.6–8.9%) were adjudicated as false positives during subsequent cardiac catheterization (intracardiac echocardiography, angiography, and inability to cross the interatrial septum). Univariable and multivariable logistic regression identified predictors of diagnostic accuracy. (3) Results: False-positive cases were associated with less frequent use of the mid-esophageal bicaval view (50% vs. 87%, p < 0.001) and absence of early bubble transit. Multivariable analysis confirmed the mid-esophageal bicaval view as an independent predictor of accurate diagnosis (OR 5.23, 95% CI 2.11–12.9, p < 0.001). (4) Conclusion: False-positive PFO diagnoses occur in ~6% of patients referred for closure. Three quality criteria—mid-esophageal aortic valve short axis, bicaval view, and bubble test with x-plane analysis—may improve diagnostic reliability. These hypothesis-generating findings require prospective validation and alignment with ASE/ESC guidelines to reduce unnecessary invasive procedures. Full article

Background: Esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) follow divergent incidence trajectories in the United States. Rising use of electronic nicotine delivery systems (ENDS) and evolving demographic risk profiles may be reshaping these trends. We aimed to characterize national incidence patterns of EAC and ESCC from 2000 through 2022—stratified by age, sex, and race/ethnicity—and to place these in the context of changing behavioral exposures. Methods: We performed a retrospective cohort study using Surveillance, Epidemiology, and End Results SEER 21 registry data (covering 48% of the U.S. population). We included first-primary, histologically confirmed EAC (ICD-O-3 codes 8140–8576) and ESCC (8050–8084) in individuals aged ≥ 15 years diagnosed between 2000 and 2022. Age-adjusted incidence rates (per 100,000 person-years; 2000 U.S. standard) and annual percent changes (APCs) were estimated via Joinpoint regression models. Results: A total of 90,290 EAC and 47,916 ESCC cases were identified. EAC incidence increased from 2.3 to 2.8 per 100,000 (APC +0.90%; 95% CI, 0.45–1.35), with the largest relative rises in ages 15–39 years (APC +1.50%) and among women (APC +2.65%). Non-Hispanic Black and American Indian/Alaska Native populations experienced the most pronounced EAC increases. Overall ESCC incidence declined (APC −0.78%; 95% CI, −1.10 to −0.46), though Asian/Pacific Islander (+3.59%) and American Indian/Alaska Native (+1.58%) groups saw rising rates. Conclusions: EAC incidence continues to climb—especially in younger adults, women, and select racial/ethnic minorities—while ESCC declines are uneven. These histology-specific patterns highlight the urgency of tailored prevention, targeted early-detection efforts, and mechanistic studies on emerging exposures such as vaping. Full article

Background/Objectives: Age-related changes in the gastric mucosa remain incompletely understood. We aimed to assess and compare clinical, endoscopic and histologic changes in the gastric mucosa associated with aging, and to explore whether gastric aging is associated with a distinct histological pattern. Methods: Single-center observational study. Younger (18–45 years) and older (≥70 years) adults undergoing elective upper endoscopy were included and underwent gastric biopsies. The clinical, endoscopic and histologic features were analyzed and compared. Results: A total of 100 patients were included (45 men/55 women), 50 with 18–45 years and 50 with ≥70 years. Dyspepsia, gastro-esophageal reflux disease and peptic ulcer disease were the most common indications for upper endoscopy. Gastric lesions (erythema, erosions, ulceration and polyps) were more common in older patients (80% vs. 50%, p = 0.003), as well as histologic changes such as chronic gastritis (56% vs. 38%, p = 0.004), chronic atrophic gastritis (CAG; 28% vs. 4%, p < 0.001) and intestinal metaplasia (28% vs. 4%, p < 0.001). These findings persisted after adjusting for Helicobacter pylori (H. pylori) status and proton pump inhibitor intake on the multivariate analysis. Prevalence of H. pylori was similar between both groups (28% vs. 32%, p = 0.189). Conclusions: Aging is associated with clinical, endoscopic and histologic changes in the gastric mucosa including CAG and metaplasia, independent of the presence of H. pylori. These findings may result from several aging-related pathophysiological processes and decades of cumulative gastric injury and support the hypothesis of an aging stomach phenotype, underscoring the need for an age-adjusted interpretation of gastric biopsies. Full article

Cytoskeleton-associated protein 4 (CKAP4) has emerged as a critical player in gastrointestinal (GI) cancer progression, diagnosis, and therapy. This comprehensive review synthesizes current knowledge on CKAP4′s multifaceted roles across GI malignancies, providing novel insights into its mechanisms of action and clinical potential. Its interaction with DKK1 and subsequent activation of the PI3K/AKT pathway underscores its role in promoting tumor growth. This review also highlights novel insights into CKAP4′s mechanisms of action beyond the well-established DKK1-CKAP4 axis, including its interaction with integrin β1 and involvement in angiogenesis through the FMNL2/EGFL6/CKAP4/ERK pathway. CKAP4′s impact on tumor microenvironment and immune evasion is elucidated, offering a new perspective on its contribution to cancer progression. In addition, CKAP4 arises as a promising serum biomarker for early detection and prognosis across multiple GI cancers, emphasizing its potential superiority over traditional markers. The therapeutic potential of targeting CKAP4 is extensively explored, including novel approaches like anti-CKAP4 antibodies and aptamers, and their synergistic effects with existing treatments. By integrating findings from esophageal, gastric, pancreatic, and colorectal cancers, this review provides a unique, comprehensive overview of CKAP4 in GI oncology, underscoring CKAP4′s potential to revolutionize GI cancer diagnosis and treatment and paving the way for future translational research. Full article

Background: Anastomotic leakage (AL) is a major complication after esophago-gastric surgery, with incidence rates of 11–21% and mortality up to 14%. Early intervention is essential to reduce morbidity. Endoscopic treatments have advanced, with self-expandable metal stents (SEMSs) as the traditional standard (success ~90%), but they carry risks like migration, stenosis, and need for drainage. Endoscopic vacuum therapy (EVT), applying negative pressure to drain secretions and promote healing, has shown success rates of 66–100%. Limited comparative data exists from small retrospective studies. This study compares SEMS and EVT for safety and efficacy in AL management. Methods: A retrospective case–control study from a prospective database at our institution was performed (March 2012–2025). We included patients with AL post-esophageal/gastric surgery treated endoscopically (SEMS or EVT). We excluded patients treated with conservative or surgical management. Demographics, comorbidities, oncology, surgery type, leak details, treatments, and outcomes were collected. Primary outcome was complete healing of the leak, while secondary outcomes were time to success, number of procedures needed, hospital stay, complications, mortality. Results: From 592 resections, we extracted 68 AL (11.5%), 45 of which met the inclusion criteria (22 SEMS, 23 EVT). Groups were similar demographically, but SEMS had more respiratory issues (43% vs. 8.7%, p = 0.018). SEMS were used more after esophagectomy (86.4% vs. 56.5%, p = 0.004); EVT was performed mostly after gastrectomy (34.7% vs. 9.1%, p = 0.009). Success rate was 86.4% for SEMS vs. 95.6% for EVT (p = 1.000). Complications were significantly lower in EVT (8.3% vs. 50%, p = 0.001; SEMS: 36.4% migrations, 18.2% stenoses). Leak onset time, modality of diagnosis, and leak size were comparable among the groups. Need for jejunostomy was higher in EVT (43.5% vs. 9.1%, p = 0.015), while chest drains in SEMS (63.7% vs. 13.1%, p < 0.001). Hospital stays (33–38 days, p = 0.864) and mortality (22.7% vs. 8.7%, p = 0.225) were similar. No differences were observed in terms of long-term mortality (log-rank p = 0.815). Conclusions: SEMS and EVT are both effective for AL after esophago-gastric surgery. EVT offers fewer complications and shorter treatment, so it is favored especially for esophago-jejunal leaks. Full article

A nine-year-old, 10.5 kg, female-spayed Poodle-mix dog presented with a five-day history of vomiting and regurgitation. Thoracic radiographs revealed an area with increased opacity within the esophageal lumen. A ductal esophageal lesion with intraluminal extension and mild left axillary lymphadenopathy were detected on computed tomography. Esophagoscopy revealed a large vascular, obstructive mass with a smooth surface, in the mid part of the esophagus. Endoscopic biopsies were collected, and histopathologic findings were consistent with an inflammatory polyp. Surgical excision of the mass via sternotomy was performed and the mass was sent for histopathologic evaluation. Histopathological examination of the mass revealed an esophageal plasmacytoma with perivascular amyloid deposition, which was confirmed by immunohistochemical staining. There was no evidence of regrowth until 18 months after surgical removal, when evidence of regrowth was identified. The dog had only one episode of vomiting and regurgitation which was resolved after symptomatic treatment. Full article

Coumarin derivatives, whether natural or synthetic, have attracted considerable interest from medicinal chemists due to their versatile biological properties. Their appealing pharmacological activities—such as anticancer, anti-inflammatory, neuroprotective, anticoagulant, and antioxidant effects—combined with the ease of their synthesis and the ability to introduce chemical modifications at multiple positions have made them a widely explored class of compounds. In the scientific literature, there are many examples. On the other hand, dithiocarbamates, originally employed as pesticides and fungicides in agriculture, have recently emerged as potential therapeutic agents for the treatment of serious diseases such as cancer and microbial infections. Moreover, dithiocarbamates bearing diverse organic functionalities have demonstrated significant antifungal properties against resistant phytopathogenic fungi, presenting a promising approach to combat the growing global issue of fungal resistance. Dithiocarbamates linked to coumarin derivatives have been shown to exhibit cytotoxic activity against various human cancer cell lines, including MGC-803 (gastric), MCF-7 (breast), PC-3 (prostate), EC-109 (esophageal), H460 (non-small cell lung), HCCLM-7 (hepatocellular carcinoma), HeLa (cervical carcinoma), MDA-MB-435S (mammary adenocarcinoma), SW480 (colon carcinoma), and Hep-2 (laryngeal carcinoma). Numerous studies have revealed that the inclusion of a dithiocarbamate moiety can provide central nervous system (CNS) activity, particularly through inhibitory potency and selectivity toward acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and MAO-B). Recently, it has been reported that coumarin–dithiocarbamate derivatives exhibit α-glucosidase inhibitory effects and also possess promising antimicrobial activity. This study presents an overview of recent progress in the chemistry of coumarin–dithiocarbamate derivatives, with a focus on their biological activity. Previous review papers focused on coumarin derivatives as multitarget compounds for neurodegenerative diseases and described various types of compounds, with dithiocarbamate derivatives representing only a small part of them. Our work deals exclusively with coumarin dithiocarbamates and their biological activity. Full article

The gastrointestinal (GI) tract is seriously affected by systemic sclerosis (SSc), due to fibrosis and persistent inflammation. Patients with GI involvement frequently exhibit poor nutritional status, which affects disease burden and quality of life. The aim of the present review was to discuss all nutritional issues in SSc and serve as a primer for the nutritional assessment of patients with scleroderma. Patients with SSc suffer from GI impairments that affect the oral cavity, esophagus, stomach, and small and large intestines. Symptomatology includes microstomia, xerostomia, dysphagia, reflux, esophageal dysmotility, small intestinal bacterial overgrowth (SIBO), and fecal incontinence, among others, which may contribute to inadequate food intake. As a result, patients often suffer from malnutrition, sarcopenia, and frailty, while presenting with micronutrient deficiencies that impact disease outcomes and worsen their condition. This aggravated nutritional status is related to greater disease severity, organ involvement, reduced physical function, and increased length of hospitalization and mortality. GI involvement is well-documented within the SSc population, yet routine nutritional assessments are lacking in the hospital setting. Currently, there is a lack of specific recommendations from scientific societies regarding the nutritional care of patients with SSc. Given the high risk of nutritional impairments in this population, systematic assessments should be undertaken, and novel tools tailored to their unique needs should be developed and implemented. Full article

Background: Immune checkpoint inhibitors (ICIs) such as pembrolizumab (Pem) have demonstrated clinical benefits in esophageal cancer. Cisplatin, 5-fluorouracil, and Pem combination (CF plus Pem) has emerged as a promising first-line regimen. However, dose reduction of cytotoxic agents is necessary in real-world practice in patients with advanced age and/or renal dysfunction. This study aimed to evaluate the real-world effectiveness and safety of CF plus Pem therapy and assess survival outcomes based on the initial dose intensity. Methods: We retrospectively analyzed patients with unresectable or recurrent esophageal cancer who received CF plus Pem between February 2022 and February 2025. Clinical data, including patient characteristics, treatment details, tumor response, adverse events, and survival outcomes, were collected and analyzed. Results: We included 54 patients (median age, 72.5 years; 74.1% male). The initial CF dose was reduced in 55.6% of the patients. The overall response and disease control rates were 55.6% and 81.5%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 18.6 and 6.5 months, respectively, with no significant differences observed among groups based on dose reduction, age, or change in treatment interval. Grade ≥ 3 adverse events occurred in 16.7% of patients, with fewer events and higher treatment continuity in the dose-reduction group. Conclusions: Thus, CF plus Pem therapy is effective and tolerable in real-world settings. Initial dose reduction does not compromise survival and supports individualized dosing strategies for esophageal cancer treatment. Full article

Background: Achalasia is a rare primary esophageal motility disorder characterized by impaired lower esophageal sphincter relaxation and progressive loss of peristalsis. Although its pathogenesis remains incompletely understood, autoimmune mechanisms have been repeatedly proposed. Thyroid disorders, particularly autoimmune thyroiditis and Graves’ disease, have been reported as frequent comorbidities, suggesting a shared autoimmune background. Methods: We conducted a narrative review of PubMed, Scopus, and Web of Science from January 2005 to August 2025. Eligible studies included observational cohorts, case–control analyses, and case reports describing thyroid disease in achalasia. Mechanistic and immunological studies relevant to thyroid autoimmunity were also considered. Data were synthesized narratively and summarized in tables and figures. Results: Despite heterogeneity, evidence consistently indicates an increased prevalence of thyroid disease in achalasia. Early reports described dysfunction in up to one quarter of cases, while Romero-Hernández et al. demonstrated a threefold higher risk of autoimmune thyroid disease. Multicenter data confirmed thyroid autoimmunity in about one fifth of patients. Although thyroid disease did not alter short-term procedural outcomes, unrecognized dysfunction may complicate postoperative evaluation. Immunological findings, including human leukocyte antigen (HLA) susceptibility and lymphocytic infiltration of myenteric plexus, further support a shared autoimmune predisposition. Conclusions: Thyroid disorders, particularly autoimmune hypothyroidism, are more common in achalasia than in the general population. Although the evidence remains limited, the consistent signal suggests a non-random association. Early recognition may improve patient management, while prospective multicenter studies are needed to clarify causality and to determine whether achalasia should be considered part of a broader autoimmune spectrum. Full article

Background/Objectives: Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. This review investigates the biological functions, expression patterns, and clinical relevance of omentin across gastrointestinal malignancies. Methods: A comprehensive review of the literature was conducted using PubMed, Scopus, and Web of Science up to August 2025 to evaluate the role of omentin in gastrointestinal cancers. Both preclinical and clinical studies evaluating omentin, its analogues and omentin-enhancing agents in gastric, colorectal, hepatic, pancreatic, and esophageal cancers were included. Results: Omentin exhibits anti-proliferative, anti-inflammatory, and anti-angiogenic effects within the tumor microenvironment in several GI malignancies. However, evidence also indicates a dual role. High intratumoral omentin expression correlates with improved prognosis in colorectal, gastric, and hepatic cancers; in contrast, elevated circulating levels–particularly in colorectal and pancreatic cancers–have been paradoxically associated with increased cancer risk and poor outcomes. Mechanistically, omentin modulates PI3K/Akt, NF-κB, AMPK, and oxidative stress pathways, and interacts with TMEM207. However, most available studies are small-scale and heterogeneous, with methodological inconsistencies and limited multi-omics integration, leaving major knowledge gaps. Conclusions: This review highlights omentin’s distinct systemic and local roles across GI cancers, underscoring its translational implications. Omentin emerges as a promising but context-dependent biomarker and therapeutic target, with future research needed to address heterogeneity, standardize assays, and validate its clinical utility in large-scale prospective studies. Full article

Background/Objectives: Sugemalimab demonstrated clinical efficacy in the GEMSTONE-303 trial, but its cost-effectiveness remains unclear. This study aims to evaluate the cost-effectiveness of sugemalimab in combination with chemotherapy (CAPOX) as a first-line treatment for patients with advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, compared to chemotherapy alone, from the perspective of Taiwan’s healthcare payer. Methods: A partitioned survival model was developed to simulate outcomes over a 40-year time horizon, and model parameters were derived from GEMSTONE-303 and the wider literature. Health benefits were measured in quality-adjusted life-years (QALYs), and only direct medical costs were included, with both discounted at an annual rate of 3%. The willingness-to-pay threshold was set at three times the 2024 GDP per capita. Deterministic and probabilistic sensitivity analyses were conducted alongside scenario analyses. Results: Compared to capecitabine and oxaliplatin (CAPOX) alone, adding sugemalimab yielded an incremental gain of 0.39 QALYs at an additional cost of USD 47,020, resulting in an incremental net monetary benefit of −USD 7478. Conclusions: Sugemalimab plus CAPOX is not cost-effective for advanced or metastatic G/GEJ adenocarcinoma from the Taiwan payer’s perspective. Achieving cost-effectiveness would require a 20–30% price reduction for sugemalimab (to USD 1204–USD 1376 per 600 mg), assuming first-line therapy is administered for the median treatment duration observed in the GEMSTONE-303 trial. If reimbursement continued until disease progression, a reduction of approximately 68% would be required (USD 550 per 600 mg). Full article

Background/Objectives: The combination of anti-programmed death-1 (PD-1) inhibitors and chemotherapy is the standard first-line treatment for unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, real-world data remain limited, particularly regarding prognostic biomarkers. Methods: This multi-institutional retrospective study analyzed patients with metastatic or unresectable ESCC who received first-line pembrolizumab or nivolumab plus fluoropyrimidine and platinum-based chemotherapy. Treatment regimens mirrored those in KEYNOTE-590 and CheckMate 648. Efficacy, safety, and prognostic factors were assessed. Prognostic factors were identified using multivariable Cox regression, and a point-based risk scoring system was developed. Results: Among 87 patients, the objective response rate was 48.3%, and the disease control rate was 77.0%. Median progression-free survival (PFS) was 5.6 months (95% CI, 4.5–8.7), and the median overall survival (OS) was 13.1 months (95% CI, 10.6–not reached). Grade 3–4 treatment-related adverse events occurred in 51.7% of patients. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, elevated C-reactive protein, and lower programmed death-ligand 1 (PD-L1) combined positive score (CPS) were independently associated with worse PFS and OS. A prognostic risk score ranging from 0 to 5 based on these factors stratified patients into four prognostic groups with distinct survival outcomes. Median PFS ranged from not reached in the low-risk group to 2.1 months in the high-risk group. Stratifying PD-L1 CPS into three levels (<10, 10–49, ≥50) revealed a graded association between CPS and treatment outcomes, supporting the need for more nuanced PD-L1 evaluation beyond binary classification. Conclusions: First-line anti-PD-1 therapy combined with chemotherapy demonstrated favorable real-world outcomes in ESCC. The proposed prognostic scoring system may help personalize treatment strategies. Full article

Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacterium that colonizes the human stomach and is linked to various gastroduodenal diseases. The severity of different clinical outcomes may be determined by the combination of virulence genes. The aim of this study was to assess the combinations of the cytotoxin-associated gene A (cagA), the vacuolating cytotoxin A gene (vacA), the outer inflammatory protein A gene (oipA), and the blood group antigen-binding adhesin gene (babA2) genotypes in H. pylori and their associations with the clinical outcomes of infection in patients from Central Brazil. This cross-sectional study included 106 patients who underwent endoscopy or gastrectomy. The presence and genotypes of H. pylori were confirmed using Polymerase Chain Reaction (PCR). Gastropathies were classified according to established severity criteria. Multivariate logistic regression and Venn diagrams were used to evaluate gene combinations. In this study, the infection prevalence was 65.1%. The cagA/vacA/oipA/babA2 combination showed a protective effect against erosive esophagitis (p = 0.002), erosive duodenitis (p = 0.003), and general duodenitis (p < 0.001). No significant association was observed between this gene combination and severe gastric diseases, although a trend toward protection against gastric atrophy was noted (p = 0.049). These findings suggest that the coexistence of cagA/vacA/oipA/babA2 may play a protective role against inflammatory lesions. Further studies should explore the functional role of these gene combinations, also considering the immunogenetic profile of the host. Full article

The research interest in the oral microbiome’s role in esophageal cancer is growing, yet a comprehensive synthesis of available evidence is still lacking. This study aimed to explore the effects of oral microbiome on the development of esophageal cancer through a systematic review of existing literature retrieved from the Embase, PubMed, and Web of Science databases. Eighteen studies published between 2015 and 2024 were obtained, involving 1191 cases and 1403 controls, mostly using oral saliva samples and 16S rRNA gene sequencing. Findings on alpha-diversity were inconsistent, while most studies reported significant beta-diversity differences between cases and controls. Notably, several investigations on esophageal squamous cell carcinoma showed higher levels of Prevotella, Porphyromonas, and Fusobacterium, while two studies on esophageal adenocarcinoma reported elevated levels of Actinomyces species. A fixed-effect meta-analysis of two studies showed that individuals with specific oral microbial signatures had significantly higher odds of developing esophageal squamous cell carcinoma (OR = 9.50; 95% CI: 5.89–15.29). Quality assessments highlighted methodological strengths but noted variability in group comparability and local applicability. These results reveal the potential of oral microbiome shift as an early detection biomarker and for developing personalized strategies in treating esophageal cancer, meriting further clinical investigation. Full article