Search Results (359)

Background and Clinical significance: Cowden syndrome is an autosomal dominant disorder caused by germline loss-of-function mutations in the PTEN tumor suppressor gene. It is characterized by multiple hamartomas and an increased lifetime risk of malignancies affecting the breast, thyroid, endometrium, and gastrointestinal (GI) tract. Pediatric presentations may include macrocephaly, scrotal tongue, and intellectual disability. Gastrointestinal involvement is frequent, with juvenile-like hamartomatous polyps occurring in at least half of patients and distributed throughout the GI tract, posing a risk for malignant transformation. Early diagnosis and surveillance are crucial for improving patient outcomes. Case Presentation: We report a case of a 10-year-old Caucasian female with Cowden syndrome, with a history of a malignant germ cell tumor of the ovary consisting of a yolk sac tumor and low-grade immature teratoma diagnosed at age six, and thyroidectomy at age nine. The patient has mild intellectual disability. Routine radiological surveillance revealed a right colon intraluminal mass, prompting referral for pediatric gastroenterology evaluation. Endoscopy identified multiple polyps throughout the colon, stomach, and small intestine. Polypectomy of larger lesions was performed, and histopathology confirmed juvenile-like hamartomatous polyps without dysplasia or malignancy. This case highlights the necessity of comprehensive gastrointestinal evaluation in pediatric Cowden syndrome patients. Endoscopic surveillance is essential for early detection and management of polyps. Conclusions: Given the multisystem involvement and elevated cancer risk associated with PTEN mutations, a multidisciplinary approach that includes genetic counseling, dermatologic evaluation, and ongoing oncologic monitoring is recommended. Increased awareness of gastrointestinal manifestations enables timely intervention and may reduce morbidity and mortality in this high-risk population. Full article

Background/Objectives: Incidence of malnutrition varies greatly among gastrointestinal (GI) cancer patients and has a major impact on prognosis. We performed a meta-analysis to identify risk factors for malnutrition risk, malnutrition diagnosis, and cachexia in patients with GI cancer. Methods: A systematic search was performed on 31 October 2025 on the PubMed (Medline), Embase, and Cochrane Library databases. Eligible studies reported on risk factors for malnutrition risk, malnutrition diagnosis, malnutrition-related complication risk and cachexia in adult patients with GI cancer. Articles on neuroendocrine tumours, primary cancer outside the GI tract, and the paediatric population were excluded. The random-effects model yielded the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the investigated risk factors. Results: A total of 37,624 records were identified. Data from 262,525 patients from 578 articles were included in the analysis. Older age (≥65) was associated with higher odds for malnutrition risk across all GI cancers. In gastric cancer, males had a lower odds for malnutrition risk (OR 0.84; 95% CI 0.75–0.95); however, the sex difference across other cancer types was heterogeneous, and mostly not significant. Tumour location influenced the odds for malnutrition-related complication risk in pancreatic ductal adenocarcinoma (head vs. body/tail—OR 1.48; 95% CI 0.98–2.23) and colorectal cancer (colon vs. rectal—OR 1.39; 95% CI 1.07–1.81; right-sided vs. left-sided—OR 1.54; 95% CI 1.34–1.77). Increased C-reactive protein alone indicated higher odds for malnutrition risk at baseline. Conclusions: Inflammatory biomarkers and tumour characteristics may indicate malnutrition risk in GI cancer at baseline. There is a great need for standardised and harmonised approaches in nutritional status assessment in GI cancer. Full article

Cryotherapy involves flash freezing of tissue and removing unwanted tissue. Mechanism of injury is causing cell membrane rupture by rapid multiple freeze–thaw cycles, while reserving tissue architecture and the collagen matrix. This promotes favorable wound healing. In recent years, it has gained increasing attention as a treatment option for upper gastrointestinal diseases (Barrett’s Esophagus and early cancer). Currently, two FDA-approved delivery methods are available in the GI tract: Cryoballoon and spray cryotherapy, which will be discussed. In this review, we also propose to examine the expanding role of cryotherapy in gastrointestinal practice, drawing from both clinical studies and illustrative vignettes. In addition, we will highlight its established role in eradicating Barrett’s with low and high-grade dysplasia and compare its outcomes and safety profile with radiofrequency ablation (RFA). We will also discuss the application and safety of spray cryotherapy in the palliation of malignant esophageal strictures when compared with Esophageal stent placement. Cryotherapy may have immunological potential, and it may shrink both primary and metastatic diseases. Ongoing research in this field of Cryo-immunology will be highlighted. Beyond esophageal neoplasia, cryotherapy is increasingly utilized in other upper gastrointestinal precancerous conditions. Through this synthesis, our goal is to provide a timely and comprehensive overview of advancements in cryotherapy and its potential to reshape novel therapeutic approaches in upper gastrointestinal cancers. Finally, we highlight the evolution of a novel platform using nitrous oxide delivered by a handheld device, a contact balloon, and a small replaceable cartridge. This approach may make delivery of cryogen application favorable and a first-line approach in the management of Barrett’s esophagus and early cancer. In addition, Cryoballoon therapy for dysphagia palliation for malignant esophageal strictures may become a preferred approach as more data evolves. Full article

Human missions into deep space will expose astronauts to the unique and complex radiation environment of galactic cosmic radiation (GCR), a mixed field of high-energy protons and heavy ions predicted to substantially increase long-term cancer risk. To support effective risk stratification, early detection, and mitigation strategies, there is a need to identify biomarkers indicative of GCR-induced cancer risk. Here, we applied a Tandem Mass Tag (TMT)-based quantitative proteomics approach to identify potential biomarkers associated with GCR-induced gastrointestinal (GI) and mammary tumorigenesis using the female Apc^Min/+ mouse, a well-established model of human colorectal and breast cancer. Eight- to ten-week-old Apc^Min/+ mice were exposed to 75 cGy of simulated GCR and serum and tissue samples were collected 100–110 days post-exposure for molecular and histopathological analyses. Tumor incidence was scored by blinded observers, and serum proteomes exhibiting a fold change > 1.2 or <0.83 with p < 0.05 were considered significantly altered. Bioinformatics analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and unsupervised clustering, were employed to delineate GCR-responsive molecular networks. Validation of differentially expressed proteins (DEPs) was performed using immunoblotting, ELISA, and enzyme activity assays. GCR exposure resulted in a significant increase in both GI and mammary tumor burden relative to controls. Proteomic profiling revealed 194 upregulated and 461 downregulated proteins, distinguishing GCR-exposed from control serum proteomes. Functional enrichment analyses highlighted alterations in metabolic processes, PI3K-AKT, HIF-1, and PPAR signaling pathways, alongside the suppression of antioxidant defense mechanisms. Notably, mice exposed to GCR exhibited elevated serum levels of TGF-β1 and MMP9, accompanied by reduced levels and enzymatic activities of key antioxidant defenses. Cross-referencing 36 GCR-induced serum SASP factors with the Human Protein Atlas revealed 11 SASP proteins associated with human breast and colorectal cancers. Together, these findings show that GCR exposure triggers a pro-tumorigenic serum proteomic signature that may serve as a biomarker for assessing cancer risk in astronauts during deep-space missions. Full article

Gastrointestinal (GI) cancers represent a heterogeneous group of malignant neoplasms arising from the digestive tract, including gastric, colorectal, hepatic, pancreatic, and biliary cancers. These tumors represent a major public health challenge due to their aggressive nature and poor prognosis. Although significant progress has been made in diagnostic imaging, endoscopy, and multimodal therapies, early detection remains difficult. Conventional serum biomarkers often lack sufficient sensitivity and specificity for reliable diagnosis, prompting a growing interest in identifying novel, minimally invasive biomarkers. In this context, liquid biopsy is emerging as a revolutionary tool in oncology. Among its components, extracellular vesicles (EVs) have gained increasing attention because they carry a wide range of molecular cargoes that reflect the biological state of their tumor of origin. In particular, EV-associated microRNAs (miRNAs) hold great promise as biomarkers for early cancer detection, real-time monitoring of disease progression, and assessment of therapeutic response. This review discusses the diagnostic and prognostic potential of EVs as novel biomarkers in GI cancers, emphasizing EV-contained miRNAs as a key resource for the development of personalized and precision medicine strategies. Full article

Background: Acute gastrointestinal (GI) toxicity is a frequent adverse effect of pelvic radiotherapy (RT) in prostate cancer and predicts chronic complications. Identifying predictive factors, especially modifiable ones, is essential to guide supportive interventions. Methods: This prospective observational non-randomized cohort included 32 patients with prostate cancer treated with pelvic RT. Patient-reported GI symptoms were measured using the EORTC QLQ-PRT20 module, and clinician-reported toxicity was graded with CTCAE v5.0. Associations between GI outcomes and clinical, demographic, and lifestyle variables—including the systemic immune-inflammation index (SII) and the Diet Quality Index (DQI)—were examined using uni- and multivariable models. Results: Ninety-one percent of patients reported worsening GI symptoms during RT (median QLQ-PRT20 score increased from 4.2 to 26.8, p < 0.0001). In our final model, higher SII values were independently associated with greater symptom worsening (p = 0.001), whereas obesity (p = 0.03) and higher diet quality (p = 0.015) were protective. No significant interactions were found between SII and BMI or DQI, although diet quality partially attenuated the association between SII and symptom progression. Clinician-reported grade ≥ 2 GI toxicity occurred in 41% of patients and was significantly less frequent in obese individuals (adjusted OR = 0.04, 95% CI 0.0009–0.57, p = 0.02), with higher SII tending to increase risk and higher DQI showing a protective trend. Conclusions: In this exploratory analysis, systemic inflammation was associated with increased GI symptom burden, whereas obesity appeared to mitigate both patient- and clinician-reported outcomes. Higher dietary quality was similarly protective for patient-reported symptoms and showed a non-significant protective trend for clinician-reported toxicity. These findings highlight the interplay between metabolic and inflammatory status in shaping RT-related GI outcomes and support integrating nutritional and inflammatory profiling to guide personalized preventive strategies. Full article

Malnutrition in patients with gastrointestinal (GI) cancers can be the result of functional and/or anatomical changes in the alimentary tract, secondary to malignancy or oncologic therapies. Understanding the underlying mechanisms of malnutrition in these patients is imperative in providing appropriate interventions that can not only improve quality of life for these individuals, but also improve their tolerance of oncologic treatment and progression towards remission or cure. In this narrative review, we address common nutritional deficiencies associated with GI malignancies, including pancreatic, biliary, and hepatic cancers. Furthermore, we address common issues related to these deficiencies and causes of nutrition barriers as they relate to organ malfunction or surgical alterations of anatomy. Recommendations for counseling, dietary modifications, nutritional supplements, and pharmacologic interventions are provided based on individual barriers and the vital role of multidisciplinary care is highlighted. Additionally, we highlight novel techniques, such as the role of psychosocial care, prehabilitation, digital health, and machine learning, which can improve nutritional outcomes, provide patient-directed care, and improve risk stratification for this complex and multifaceted issue that faces patients diagnosed with GI cancers. Full article

Introduction: Although patients with upper gastrointestinal (GI) cancer have an increased risk of developing small intestinal bacterial overgrowth (SIBO) due to disease- and treatment-related factors, SIBO remains underdiagnosed in oncology. Aim and Methods: This prospective study evaluated the prevalence of SIBO and its impact on symptom-related quality of life (QoL) in patients with current or prior upper GI cancer. Between April 2021 and May 2022, patients reporting SIBO-related symptoms like bloating and/or diarrhea completed a standardized symptom questionnaire. QoL impact was scored from 0 (none) to 3 (severe). Patients with scores > 1 and no recent antibiotic use underwent upper endoscopy with duodenal aspirate. SIBO was defined as >10³ CFU/mL. Results: Ninety patients were enrolled (51% female; median age of 65 years): 35% had pancreatic, 34% gastric, 17% biliary, and 14% esophageal cancer. Sixty reported SIBO-related symptoms: 35% reported bloating, 11% diarrhea, and 54% both. Of these, 36 underwent endoscopy; 53% were diagnosed with SIBO. Among SIBO-positive patients, 95% reported bloating and 58% reported diarrhea. Prior abdominal surgery was recorded in 63% of SIBO cases. Conclusions: SIBO was identified in more than half of symptomatic upper GI cancer patients, with a strong association with bloating and previous abdominal surgery. These findings emphasize the importance of clinical awareness and appropriate diagnostic evaluation for SIBO in this high-risk group to improve symptom control and quality of life. Full article

Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up was 48 months. The 3- and 5-year biochemical relapse-free survival rates were 80% and 69%. The RT schedule consisted of a median total dose of 67.5 Gy with a median number of 25 fractions and a median fraction dose of 2.7 Gy to the prostate bed (PB) and 60% of patients simultaneously received whole pelvis irradiation (WP; fraction dose: 1.8 Gy, median total dose of 46.8 Gy). Results: The rate of acute toxicity was 54% for gastrointestinal (GI) and 36% for genitourinary (GU). No grade 3 acute toxicity was observed. Late toxicity was as follows: G1, G2, and G3 GI events in 25.5%, 3.6%, and 1.8% of the cases, respectively; G1, G2, and G3 GU events in 37.1%, 11.1%, and 7.4%, respectively. The toxicity-free survival (TFS) curves showed a different trend for acute and late toxicity. TFS was significantly associated with RT volume, except for acute GI toxicity. Specifically, the concomitant irradiation of PB and WP appeared to be a significant risk factor for late GI and GU toxicity (p = 0.029 and p = 0.012, respectively). Conclusions: At the 48-month median timepoint considered by our study, postoperative hypofractionated RT achieved promising results in terms of clinical outcomes with acceptable toxicity. Only the irradiated volume seems to be an important predictor for toxicity. Full article

Background/Objective: The global burden of gastrointestinal (GI) cancers is rising sharply among the elderly, with a projected doubling of incidence and mortality by 2050. Given the heterogeneity of aging and the limitations of traditional performance scales such as ECOG or KPS, integrating geriatric assessment (GA) into oncology has become essential for tailoring safe and effective treatment strategies in this population. This paper provides a practical framework for implementing geriatric assessment and management (GAM) in GI oncology, particularly in resource-limited settings, and highlights validated screening instruments suitable for clinical integration. Methods: A systematic search was performed across PubMed, Scopus, and Web of Science databases for publications between January 2019 and August 2025 using combinations of the keywords geriatric assessment, gastrointestinal cancer, frailty screening, elderly, oncology, and comprehensive geriatric assessment. International and regional clinical practice guidelines from ASCO, ESMO, and SIOG were reviewed in detail. Articles were included when they addressed validated screening tools, oncology focused strategies, or clinical outcomes associated with GA-based interventions. Studies focusing exclusively on non-oncologic geriatric populations were excluded. Relevant data were extracted regarding study design, population, tool validation, predictive performance, and feasibility. Results: GA improves prediction of treatment-related toxicity, supports individualized treatment planning, and enhances quality of life and functional outcomes. Two-step screening approaches, initial frailty screening followed by comprehensive geriatric assessment for those with positive results, were found most effective. Practical GA models and telehealth-based applications were identified as feasible even in low- and middle-income contexts. Conclusions: Integrating GA into GI oncology fosters patient-centered, evidence-based care that optimizes treatment tolerance, reduces complications, and aligns therapeutic goals with patient values. Institutional commitment, interdisciplinary collaboration, and targeted training are pivotal for establishing GA as a standard of care across diverse healthcare settings. Full article

Mucosal melanoma (MM) is a rare, aggressive cancer whose incidence has increased continuously over the years. This subtype of melanoma arises from melanocytes on hairless surfaces, typically in the respiratory tract, gastrointestinal (GI) tract, and urogenital tract. The most common sites of occurrence include the head and neck, the anorectal region, and the vulvovaginal region, while the rare sites of MM are the urinary tract and the upper and lower GI tract, including the esophagus, duodenum and the gallbladder. MM arises in melanocytes of the ectodermal mucosa that originate from neural crest cells and migrate through embryonic mesenchyme to their destination. Although melanocytes are located mainly in the epidermis and dermis, their presence in various extracutaneous sites, such as the eyes, mucosal tissue, and leptomeninges, is known. Although both cutaneous melanoma (CM) and MM differ in their epidemiology, genetic profile, and clinical presentation, their treatment options are similar. In contrast to the higher treatment response of CM, MM is characterized by a lower response rate to available treatment options, resulting in a poorer survival rate. In this review, we provide an overview of the biology of MM and the mechanisms regulating its development, progression and treatment resistance. Full article

Introduction: Robotic-assisted surgery offers technological advantages such as three-dimensional visualization and improved dexterity, yet its clinical adoption in gastrointestinal (GI) malignancies is supported by evidence of varying quality, consisting mainly of retrospective studies. This review provides a structured summary of the current evidence for robotic surgery in pancreatic, gastric, liver, and colorectal cancers. Methods: A comprehensive literature review was conducted to assess and summarize the perioperative, long-term, and oncological outcomes of robotic-assisted surgery compared to laparoscopic and open approaches for the aforementioned GI malignancies. Results: The application of the robotic platform is most advanced in colorectal surgery. High-quality evidence for rectal cancer demonstrates improved quality of mesorectal specimens, better preservation of urinary and sexual function, and lower local recurrence rates. Across all reviewed GI malignancies, robotic surgery consistently shows advantages in lower conversion-to-open rates, reduced intraoperative blood loss, and shorter hospital stays, though it is associated with longer operative times and higher costs. The evidence for pancreatic and liver surgery is less mature due to the complexity of these procedures. Data for gastric surgery suggests improved lymph node retrieval and, in one long-term study, better disease-free survival. Conclusions: The highest-quality evidence supports the robotic approach for rectal cancer, showing clear functional and oncological benefits. While several perioperative advantages are consistently reported across all GI sites, robust data demonstrating superior long-term survival are still limited for most procedures. 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

Transient Receptor Potential Vanilloid (TRPV) channels represent one of the seven subfamilies of TRP receptors and are widely expressed throughout the human body where they play pivotal roles in various physiological processes. In the gastrointestinal (GI) system, TRPV channels regulate critical functions such as nutrient absorption, motility, and secretions. Beyond maintaining cellular homeostasis, these channels are involved in pain and inflammation, contributing to diverse pathologies. Their central role in the pathophysiology of different digestive system disorders has made TRPV channels a significant focus of research. Moreover, the involvement of TRPV channels in numerous GI cancers has further heightened research interest in the role of these channels. Accordingly, this review elucidates the structural components and intricate signaling pathways of TRPV channels, focusing on the unique characteristics of each family member (TRPV1–6) in GI physiology. Furthermore, we explore the therapeutic potential of targeting these channels to modulate their physiological and pathological roles, highlighting their promise in treating GI disorders. Additionally, we address the challenges associated with their therapeutic application, considering their interactions in different systems, inherent biochemical characteristics, and the alterations required for effective design. Full article

ADAM10 is a transmembrane metalloprotease that regulates diverse signalling functions via the shedding of membrane protein ectodomains, and is implicated in tumour development, including glioblastoma multiforme (GBM) and gastrointestinal (GI) cancers, where high ADAM10 expression is associated with poor prognosis. We assessed the role of ADAM10 by gene knockout (KO) in U251 GBM cells, and its effects on protein shedding and protein expression on cell proliferation and on the growth of tumour xenografts in mice. The growth of tumours was severely delayed, relative to modest effects on proliferation in vitro, suggesting roles particularly in the context of the tumour microenvironment (TME). Proteomics analysis of KO cell-conditioned medium showed decreased levels of known ADAM10 targets such as Notch and Eph receptors and ligands, as well as other proteins involved in cell–cell adhesion, migration, signalling, metabolism, differentiation, and development, including angiogenesis. KO cell and tumour lysate analysis also showed modulation of proteins associated with metabolic and catalytic activity, cell–matrix organisation and differentiation. Similar effects were also observed in the SW620 colon cancer model, indicating broader significance. Furthermore, expression of the associated protein sets also correlated with ADAM10 expression in human GBM and colon cancer specimens (TCGA datasets), indicating clinical relevance. Collagens and proteins associated with matrix deposition and fibril organisation were notably reduced in ADAM10 KO GBM tumours, and histology confirmed decreased collagen fibrils and blood vessels. Unexpectedly, increased chondrocyte differentiation was evident in ADAM10 KO U251 tumours, suggesting a role for ADAM10 in maintaining an undifferentiated phenotype in vivo. Together, our data indicate the importance of ADAM10 in diverse signalling mechanisms in tumours and the TME that promote tumour development. Full article