Search Results (586)

Background: Comprehensive genomic profiling (CGP) is a tool used in precision oncology to identify genomic alterations and match them with targeted therapies across several tumor types. However, real-world data on its clinical utility and impact remains limited. The FRONTAL study (Foundation Medicine Real wOrld evideNce in porTugAL) is a multicenter academic initiative that established a national registry of Portuguese patients with solid tumors who underwent CGP with FoundationOne CDx, Liquid CDx or FoundationOne Heme assays. Methods: Eligible patients had advanced solid tumors not suitable for curative treatment at the time of recruitment. Prior CGP testing was permitted if taken within 12 months before study initiation. Genomic profiling data were extracted from FoundationOne Medicine reports, and clinical information was extracted from medical records. Actionable alterations were defined as those associated with approved treatments or with clinical evidence of benefit in other cancers, per NCCN guidelines. Variant interpretation was also reviewed according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. The primary outcome was disease control at 16 weeks, defined by the absence of progression. Results: The study included 205 patients between 2020 and 2025 across 10 sites, with colorectal (40, 19.5%), sarcomas (28, 13.7%), and other gastrointestinal tumors (22, 10.7%) being the most common pathologies. Actionable alterations were identified in 104 cases (50.7%). Genomic findings guided therapy decisions in 50 patients (24.4%), of whom 30 achieved disease control at 16 weeks (14.6%). Conclusions: The FRONTAL study highlighted the clinical relevance of CGP in advanced solid tumors. Over half of the patients had actionable alterations, a quarter had therapy changes based on CGP results, and improved disease outcome was observed in approximately 15% of the cohort. Full article

Background and Objectives: Posthepatectomy liver failure (PHLF) remains a major cause of morbidity and mortality for patients undergoing major liver resections. Recent research highlights the expanding role of machine learning (ML), a crucial subfield of artificial intelligence (AI), in optimizing risk stratification. The aim of the current study was to review, elaborate on and critically analyze the available literature regarding the use of ML-driven risk prediction models for posthepatectomy liver failure. Materials and Methods: A systematic search was conducted in the PubMed/MEDLINE, Scopus and Web of Science databases. Fifteen studies that trained and validated ML models for prediction of PHLF were further included and analyzed. Results: The available literature supports the value of ML-derived models for PHLF prediction. Perioperative clinical, laboratory and imaging features have been combined in a variety of different algorithms to provided interpretable and accurate models for identifying patients at risk of PHLF. The ML-based algorithms have consistently demonstrated high area under the curve and sensitivity values, surpassing traditionally used risk scores in predictive performance. Limitations include the small sample sizes, heterogeneity in populations included, lack of external validation and a reported poor ability to distinguish between true positive and false positive cases in several studies. Conclusions: Despite the constraints, ML-driven tools, in combination with traditional scoring systems and clinical insight, may enable early and accurate PHLF risk detection, personalized surgical planning and optimization of postoperative outcomes in liver surgery. Full article

Introduction: The proportion of elderly patients with IBD is steadily increasing due to the aging population and improved survival. Patients in this age group present specificities in diagnosis and treatment, particularly regarding the use of biological agents, where immunosenescence, multimorbidity, and polypharmacy affect the precise assessment of benefit and risk. Aim: This systematic review, which was conducted in accordance with the PRISMA 2020 statement, aims to synthesize available data on the epidemiology, clinical characteristics, and therapeutic management of IBD in the elderly, with emphasis on the most recent data and practical guidelines for the use of biological therapies. Methods: A systematic search of PubMed, Scopus, and Embase was conducted. A total of 40 studies were included, comprising 5 randomized controlled trials, 15 prospective cohort studies, and 20 retrospective observational studies. Eligible studies included randomized controlled trials, observational cohort studies, and population-based analyses. Given substantial clinical and methodological heterogeneity, findings were synthesized narratively. Data on demographics, disease phenotype, comorbidities, and treatment outcomes were extracted and analyzed. In addition, a narrative synthesis of major randomized trials of biologic therapies, recent guidelines, and data from prospective studies and patient registries was performed with a focus on safety and real-world outcomes in the elderly. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) and the Cochrane Risk of Bias tool. Results: The majority of included studies (85%) were found to have a low to moderate risk of bias, providing a reliable basis for the synthesis. Data show an increasing incidence of IBD in the elderly, often with a milder clinical course and a higher ratio of UC to CD. Multimorbidity and polypharmacy are significant challenges that increase the risk of adverse events. Although classic therapies remain effective, in many cases, a lower threshold is required to initiate advanced therapies, such as biologic agents. Anti-tumor necrosis factor (anti-TNF) agents, as well as biologics with alternative mechanisms of action such as vedolizumab (α4β7 integrin antagonist) and ustekinumab (interleukin-12/23 inhibitor), represent key therapeutic options in elderly patients with IBD. These biologic factors have efficacy comparable to that in younger patients and are considered attractive options due to reduced systemic immunosuppression and favorable safety profiles. JAK inhibitors are a practical option but are associated with an increased thromboembolic risk and require careful patient selection. Older age is associated with higher absolute rates of serious infections, hospitalizations, and, in some series, mortality. Individualized decision-making, including frailty assessment, vaccination coverage, infection control, and dose adjustments based on renal and hepatic function, is essential for optimal care. Conclusions: IBD in the elderly is a distinct clinical entity with unique challenges in diagnosis and management. A multidisciplinary approach and individualized treatment strategies are essential to ensure the balance between disease control and minimizing the risks associated with comorbidity and polypharmacy. Further research, including specifically designed clinical trials, is needed to optimize treatment and outcomes in this unique patient group. Full article

Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients. Full article

Introduction/Object: Gastrointestinal cancers are among the most common types of neoplasms and are often associated with malnutrition, which affects physical performance, treatment tolerance and prognosis. This paper aims to synthesize, through a systematic search, the evidence on the impact of nutritional interventions on nutritional status in patients with digestive cancers prone to malnutrition. Methods: A systematic search was performed in PubMed, MDPI, Web of Science and ScienceDirect, for articles published between 2009 and 2025. Overall, 14,503 records were identified, and after screening of titles, abstracts and full-text evaluation, 80 studies (cross-sectional and cohort) were included. Data extraction was performed by a single researcher, using pre-established criteria and a standardized table, and the assessment of study quality was performed qualitatively, taking into account study design, sample size, nutritional assessment methods and clarity of reporting of results. Results: Evidence suggests that individualized and early applied nutritional interventions contribute to maintaining weight and protein status, improve tolerance to oncological treatments and may positively influence patient survival. Conclusions: Nutritional therapy plays a crucial role in preventing complications and supporting the body during oncological treatment, optimizing patients’ quality of life. This review provides a clear synthesis of the current evidence and recognizes methodological limitations related to the qualitative assessment of the included studies. Full article

Background: Radiotherapy is a common treatment for gynecological malignancies, often accompanied by significant side effects that impact patient nutritional status. The ketogenic diet has been proposed as a complementary nutritional strategy to enhance treatment efficacy, manage side effects, and preserve body composition. However, its safety and feasibility in the oncological setting remain under-investigated. Methods: The KOMPARC study is a prospective, randomized controlled trial evaluating the adherence, safety, and clinical tolerability of a ketogenic diet versus a standard Mediterranean diet in patients with cervical and endometrial cancer undergoing radiotherapy. Before the start of the treatment, patients were randomized to either the ketogenic diet or the standard diet groups. Anthropometric measures, Hand Grip Test, and body composition parameters from bioimpedance analysis were taken before the start of treatment and at the end. Adherence, adverse events, and patient-reported outcomes were monitored throughout the treatment period. Results: A total of 33 patients were enrolled. Adherence rates were comparable between the KD and standard diet groups (46.1% vs. 25.0% interruption rate, p = 0.21). No significant differences were observed in the incidence of gastrointestinal toxicities (p = 0.56), diarrhea (p = 0.81), nausea (p = 0.94), or weight loss (p = 0.24). Both groups experienced significant weight reduction during therapy without differential loss of body cell mass or other body composition parameters. Quality of life assessments indicated varied symptom profiles, with the KD group reporting increased appetite loss and worry about weight. Conclusions: Preliminary findings suggest that the ketogenic diet is a safe and feasible nutritional intervention during radiotherapy for pelvic tumors. These results support further investigation into ketogenic dietary strategies as adjuncts in oncologic care. Full article

Background: The introduction of tyrosine kinase inhibitors has revolutionised the treatment of gastrointestinal stromal tumours (GISTs), yet the role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal GISTosis remains controversial. Methods: A retrospective analysis was conducted on patients with peritoneal GISTosis who underwent CRS plus HIPEC in an 18-year period. We analysed the clinicopathological characteristics and evaluated the perioperative and long-term outcomes based on the extent of disease (peritoneal cancer index, PCI), the resection (completeness of cytoreduction score) and the IM-administration. The survival factors were also analysed and the Kaplan–Meier estimator to model and estimate overall (OS) and progression-free survival (PFS). The median follow-up period was 72 months (range, 12–146). Results: A total of 25 patients (M:F = 15:10) with a median age of 57 years (range, 32–69) underwent CRS with HIPEC for peritoneal GIST metastases, detected either synchronously (n = 11) or metachronously (n = 14). The media PCI score was 9 (range, 4–20) and complete cytoreduction was achieved in 80%. Grade III complications were observed in two patients, whereas there was no postoperative mortality. Neoadjuvant imatinib-mesylate (IM) therapy was administered in 60% of patients who detected with metachronous metastases (n = 8/14), whereas adjuvant IM therapy was administered in 19 of 25 patients. Median OS was 62 months (95% CI = 22.8–101.2). Median OS and DFS for patients with PCI scores ≤ 10 were significantly longer compared to those with PCI scores > 10 (p = 0.009 and p = 0.024, respectively). Patients with CC scores of 0–1 had a significantly longer OS compared to those with CC scores of 2 (p = 0.005) and 3 (p = 0.002) and longer PFS compared to those with CC scores of 3 (p = 0.005). The need for imatinib did not significantly impact OS (p = 0.240) or PFS (p = 0.243). Conclusions: CRS combined with HIPEC shows promising results in peritoneal GISTosis, especially in patients with lower PCI and CC scores. Until larger studies validate its safety and efficacy, it should be primarily performed in expert hands in specialised peritoneal surface oncology centres. Full article

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

Metformin, a 60-year-old biguanide and cornerstone of type 2 diabetes therapy, continues to challenge and inspire modern pharmaceutical science. Despite its chemical simplicity, metformin displays highly complex pharmacokinetic and pharmacodynamic behavior driven by transporter dependence, luminal activity, and formulation-sensitive exposure. Originally regarded as limited by low permeability and incomplete absorption, metformin has emerged as a paradigm for gut-targeted therapy, controlled- and delayed-release systems, and personalized pharmaceutics. Growing evidence has repositioned the intestine, rather than systemic plasma exposure, as a major site of action, highlighting the central role of organic cation transporters and multidrug efflux systems in determining efficacy, variability, and gastrointestinal tolerability. Beyond metabolic control, insights into transporter regulation, pharmacogenetics, microbiome interactions, and manufacturing quality have expanded metformin’s relevance as a model compound for contemporary drug development. Advances in formulation design, quality-by-design manufacturing, and regulatory control have further reinforced its clinical robustness, while repurposing efforts in oncology, immunometabolism, and regenerative medicine underscore its translational potential. This review integrates mechanistic pharmacology, formulation science, and clinical translation to position metformin not merely as an antidiabetic agent, but as a didactic model illustrating the evolution of pharmaceutics from molecule-centered design to system-oriented, precision-driven therapy. Full article

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. While imatinib revolutionized first-line therapy, resistance and specific mutation profiles necessitate subsequent generations of tyrosine kinase inhibitors (TKIs). Sunitinib, regorafenib, and avapritinib represent second-line, third-line, and mutation-specific therapies, respectively, offering improved precision and disease control. This review summarizes clinical trial evidence, real-world data, and translational studies evaluating the efficacy, safety, and mechanistic basis of second- and third-generation TKIs in GIST. Emphasis is placed on therapeutic sequencing, resistance mechanisms, and molecularly guided treatment selection. Sunitinib, a multitargeted TKI inhibiting KIT, PDGFR, and VEGFR, provides effective disease control in imatinib-resistant or intolerant patients. Regorafenib, a broad-spectrum multikinase inhibitor, improves progression-free survival in refractory GIST and targets additional angiogenic and oncogenic pathways. Avapritinib, a next-generation TKI, selectively inhibits PDGFRA D842V and KIT exon 17 mutations, addressing a previously untreatable, mutation-driven subgroup. Integration of these agents into treatment algorithms exemplifies a shift toward personalized therapy, with outcomes guided by mutation profiling and biomarker-driven decisions. Second- and third-generation TKIs have transformed the management of advanced GIST, extending survival and offering mutation-specific precision therapy. Ongoing research into resistance mechanisms, combination strategies, and novel inhibitors promises further optimization of patient-centered care. Full article

Background and Objectives: Surgical stress during robotic-assisted radical prostatectomy (RARP) elicits a measurable systemic inflammatory response despite the minimally invasive approach. Intravenous lidocaine has been increasingly investigated for its potential anti-inflammatory, analgesic, and immunomodulatory benefits, but evidence in robotic urologic oncology remains limited. This study aimed to evaluate whether intraoperative lidocaine infusion attenuates postoperative inflammation, improves analgesic outcomes, and accelerates early recovery following RARP. Materials and Methods: This prospective non-randomized observational study included 80 patients undergoing elective RARP, divided into a Lidocaine Group (n = 40) receiving an intraoperative bolus and continuous infusion, and a Control Group (n = 40) receiving standard anesthesia without lidocaine. Serum IL-6, TNF-α, CRP, and fibrinogen were measured at baseline, end of surgery, and 24 h postoperatively. Postoperative pain scores, opioid consumption, gastrointestinal recovery, ambulation, and length of stay were recorded. Statistical analyses included repeated-measures ANOVA, correlation testing, and between-group comparisons. Results: Baseline characteristics were similar between groups. At 24 h postoperatively, lidocaine administration was associated with a significantly attenuated inflammatory response, with lower levels of IL-6 (45.7 ± 10.8 vs. 68.9 ± 12.6 pg/mL, p < 0.01) and TNF-α (20.5 ± 5.1 vs. 27.2 ± 6.4 pg/mL, p < 0.01) compared with controls. Patients receiving lidocaine reported lower postoperative pain scores and required significantly less opioid analgesia, with a total 24 h consumption of 8.9 ± 3.4 vs. 14.8 ± 5.2 mg morphine milligram equivalents (p < 0.001). Lidocaine was also associated with faster recovery, including earlier oral intake and a shorter length of hospital stay (2.9 ± 0.7 vs. 3.6 ± 0.9 days, p = 0.003). No lidocaine-related adverse events were observed. Conclusions: In this prospective observational study, intraoperative intravenous lidocaine was associated with attenuated early postoperative inflammation, improved analgesic outcomes, and enhanced early recovery following RARP. These findings support the potential role of intravenous lidocaine as a safe adjunct in multimodal perioperative management; however, given the non-randomized observational design, causal inferences should be interpreted with caution. Further randomized controlled trials are warranted to confirm causality and to validate long-term clinical and mechanistic effects. Potential residual confounding inherent to the observational design should be considered when interpreting these findings. 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

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

Fecal microbiota transplantation (FMT) is a therapeutic strategy designed to modify and enrich the recipient’s gut microbiota by administering processed donor stool, with the goal of treating dysbiosis and related conditions. In 2013, the United States Food and Drug Administration (FDA) approved FMT for recurrent Clostridioides difficile infection (rCDI). Since then, its use has been proposed and investigated in several other disorders characterized by gut microbiota imbalance and altered host–microbiota interactions, including inflammatory bowel disease (IBD), immune checkpoint inhibitor-induced colitis (ICI-iC), and gastrointestinal graft-versus-host disease (GI-GVHD). This review aims to highlight the commonalities among these conditions, the pathophysiological mechanisms that support the rationale for FMT, and emerging evidence from clinical studies. Although available studies are heterogeneous, FMT is a rapidly evolving field of research with promising potential to treat IBD and improve outcomes following oncological immunotherapy and allogenic stem cell transplantation. With further validation, FMT could become an important approach in managing immune-mediated gastrointestinal diseases. Full article