Search Results (536)

Background: There is a lack of population-based and real-world data on sex and age differences in gastric cancer care. The aim of this study was to close this data gap and to analyze the sex and age differences in the clinicopathological characteristics of gastric adenocarcinoma. Methods: The analysis focused on patients diagnosed with gastric adenocarcinomas (ICD-10: C16.0–C16.9) documented in the cancer registry of the Federal State of Brandenburg from 2000 to 2020. The patient variables include sex, age at time of tumor diagnosis and the ECOG performance status. The tumor variables included location, grading, clinical TNM classification, clinical UICC stage and synchronous distant metastasis. Results: Of n = 8582 patients, 38% (n = 3263) were women. Compared with males, females had fewer adenocarcinomas located in the cardia (24.1% vs. 12.5%, p < 0.001), more signet ring cell carcinomas (13.2% vs. 22.8%, p < 0.001), more high-grade tumors (55.4% vs. 63.1%, p < 0.001) and a higher tumor cUICC stage (cUICC IV: 44.9% vs. 48.4%, p = 0.001). There was an interaction between sex and age modulating the differences between males and females. Conclusions: We were able to demonstrate several relevant prognostic differences in gastric cancer between men and women in terms of tumor location, stage, and metastases in a large patient cohort. Full article

Helicobacter pylori is a gastric pathogen that induces chronic gastritis, which may progress to neutrophilic activity, glandular atrophy, intestinal metaplasia, and gastric carcinoma. The aim of this study was to evaluate H. pylori-induced tissue damage. A total of 602 gastric biopsy samples were collected, categorized, and analyzed using hematoxylin and eosin and Giemsa staining, followed by molecular confirmation through PCR targeting the species-specific 16S rRNA gene. H. pylori density and histopathological features were evaluated and graded according to the updated Sydney classification system. H. pylori was detected in 55% (n = 334) of cases, and the antrum (50.83%, p < 0.00001) was the predominant site. A slightly higher prevalence was observed in females, accounting for 56.9% compared to males at 43.1%, which was attributed to sociocultural exposure differences. Individuals aged 11–40 years accounted for 58.3% (n = 195), highlighting early-age acquisition of infection. H. pylori infection was significantly linked to moderate-to-severe inflammation (63.2%, p < 0.00001) and neutrophilic activity (53.3%, p < 0.00001). Intestinal metaplasia and atrophy were infrequent, present in 0.6% (95% CI, 0.02, p = 0.149) and 0.9% (95% CI, 0.05, p = 0.430) of individuals. H. pylori infection causes chronic inflammation and neutrophilic infiltration of the stomach mucosa. Early identification and histopathological examination are essential in assessing H. pylori-related gastric pathology. Full article

Background/Objectives: To elucidate the differential transcriptional and intercellular signaling features of tumor components across various cancers, we conducted a comparative analysis using single-cell RNA sequencing (scRNA-seq). This technology enables detailed characterization of tumor ecosystems and may explain variations in tumor behavior among distinct cancer types. Methods: We analyzed publicly available scRNA-seq datasets (GEO) from seven cancer types—pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), thyroid cancer (TC), gastric cancer (GC), and colorectal cancer (CRC)—to define their unique molecular characteristics and intercellular interactions. Results: PDAC displayed a distinct tumor microenvironment (TME) dominated by myeloid cells (~42%), including abundant CXCR1/CXCR2-expressing tumor-associated neutrophils (TANs) that preferentially interacted with immune rather than cancer cells. The competitive receptor ACKR1 was minimally expressed on endothelial cells, consistent with PDAC hypo-vascularity. In HCC, tumor cells lacked EPCAM and expressed complement and stem cell markers; cancer-associated fibroblasts (CAFs) were scarce, and stellate cells expressed the pericyte marker RGS5. CAFs were abundant in ESCC and BC, with IGF1/2 expression, while in GC, these markers were uniquely found in plasma cells. Since BC and GC subtypes exhibit distinct TME patterns, it is necessary to perform subtype-specific analyses for these cancers. TC showed high expression of tumor-suppressor genes, including HOPX, in tumor cells. Differential interactions and the presence of “dominant signaling cell populations “ with dominant outgoing signals may underlie the heterogeneity in tumor aggressiveness across these cancers. Conclusions: Comparative scRNA-seq analysis of multiple cancers reveals distinct tumor phenotypes and cell–cell communication patterns, offering insights into the molecular architecture of human solid tumors. Full article

Chemerin, encoded by the RARRES2 gene, is an adipokine with potent immunometabolic functions mediated through CMKLR1, GPR1, and CCRL2. Its regulation is tissue- and context-dependent, conferring dual protective and pathogenic roles. In the upper GI tract, chemerin facilitates immune tolerance in Barrett’s adenocarcinoma and promotes invasion in esophageal and gastric cancers. In pancreatic disease, it acts as a biomarker of acute and chronic injury, while modulating β-cell function and carcinogenesis. In the liver, chemerin contributes to NAFLD/NASH pathogenesis with both anti-inflammatory and pro-steatotic actions, predicts prognosis in cirrhosis, and demonstrates tumor-suppressive potential in hepatocellular carcinoma. In IBD, chemerin exacerbates colitis via impaired macrophage polarization, yet protects epithelial antimicrobial defense, underscoring its context-specific biology. Collectively, these findings position chemerin as a versatile regulator bridging metabolic dysfunction, inflammation, and gastrointestinal malignancy, and as a potential candidate for biomarker development and therapeutic intervention. Full article

Objective: Early-signet-ring cell carcinoma has a low malignancy and good prognosis, while advanced signet-ring cell carcinoma has high malignancy and high mortality. So, we need to understand the risk factors of early-signet-ring cell carcinoma, analyze the relationship between early gastric signet-ring cell carcinoma and non-Signet-ring cell carcinoma, and between pure signet-ring cell carcinoma and mixed signet-ring cell carcinoma, in order to provide the basis for the early diagnosis and treatment of signet-ring cell carcinoma. Methods: In this study, a retrospective analysis of 424 cases of early gastric cancer that underwent endoscopic submucosal dissection and surgical treatment between March 2019 and March 2023 in Shanghai Oriental Hospital was carried out. Among the cases, the two groups, namely, the signet-ring cell carcinoma and non-signet-ring cell carcinoma group, and the pure signet-ring cell carcinoma and mixed signet-ring cell carcinoma group, were compared and analyzed. With the help of logistic regression analysis, gender, age, smoking history, alcohol consumption history, tumor site, pathological characteristics, disease progression, tumor size, infiltration depth, and H. pylori infection were investigated between the two groups. Result: The results of the univariate regression analyses in the signet-ring cell carcinoma and non-signet-ring cell carcinoma groups showed that being female (p = 0.001), age < 60 years (p = 0.001), with cancer foci in the middle part of the stomach (p = 0.001), and with a mixed type of cancer foci (p = 0.007) were the risk factors for signet-ring cell carcinoma. In the multifactorial regression analysis, age < 60 years (OR = 1.037, CL = 1.008–1.067, p = 0.012), cancer foci in the middle part of the stomach (OR = 2.094, CL = 1.488–2.948, p = 0.001), mixed-type patients (OR = 0.702, CL = 0.519–0.951, p = 0.022), and women (OR = 0.421, CL = 0.254–0.698, p = 0.001) were the risk factors for signet-ring cell cancer. These are independent risk factors for signet-ring cell carcinoids. Univariate regression analysis on the pure and mixed signet-ring cell carcinoma groups showed that Helicobacter pylori infection (p = 0.001), Kimura–Takemoto classification O1–O3 (p = 0.013), flat and concave types (p = 0.004), and age < 60 years (p = 0.013) were risk factors affecting the development of pure signet-ring cell carcinoma. In the multifactorial regression analysis, age (OR = 0.233, CL = 0.059–0.930, p = 0.039) was the main independent risk factor for pure signet-ring cell carcinoma. Conclusions: Age < 60 years, cancer foci located in the middle of the stomach, mixed type, and female are associated with the development of early gastric signet-ring cell carcinoma; age < 60 years is related to the development of pure signet-ring cell carcinoma, so we need to pay attention to these clinical and pathological factors to prevent the growth of ring cell carcinoma. Full article

C1q/TNF-related protein 6 (CTRP6) is emerging as a critical regulator of cancer biology with direct implications for clinical outcomes. Across a wide spectrum of malignancies, CTRP6 plays a central role in coordinating key oncogenic processes and linking metabolic, inflammatory, and signaling pathways that drive tumor progression. While CTRP6 generally promotes oncogenic behavior in cancers such as hepatocellular carcinoma, lung cancer, and clear cell renal cell carcinoma, conflicting findings have been reported in gastric cancer and oral or head and neck squamous cell carcinoma, where its tumor-promoting versus tumor-suppressive roles remain unresolved. CTRP6 has been shown to modulate fundamental processes including angiogenesis, ferroptosis, proliferation, apoptosis, migration, invasion, and inflammation. These effects are primarily mediated through activation of the PI3K/AKT and MEK/ERK signaling pathways, which are central to tumor growth, metastasis, and therapeutic resistance. Beyond its mechanistic roles, CTRP6 demonstrates potential as a diagnostic and prognostic biomarker, with altered expression patterns linked to cancer initiation, progression, and patient survival. Inhibition of CTRP6 in preclinical models enhances ferroptotic cell death and suppresses tumor progression, highlighting its promise as a therapeutic target. By consolidating current evidence from multiple cancer models, this review provides a comprehensive overview of CTRP6’s contributions to oncogenesis and underscores its dual potential as both a biomarker and a therapeutic target. Advancing a deeper understanding of CTRP6 in specific tumor contexts will be critical for unlocking its clinical utility and may open new opportunities to improve diagnosis, optimize therapeutic strategies, and ultimately enhance patient outcomes. Full article

Cervical cancer is a major global health concern with serious implications for women’s health. It is most often caused by persistent infection with high-risk human papillomavirus (HPV) types. However, about 5–11% of cervical carcinoma cases are HPV-independent, entities with their own unique set of histopathological, molecular, and clinical features. The histopathological forms of HPV-independent cervical cancer include gastric-type adenocarcinoma, clear-cell, mesonephric, and endometrioid carcinoma. Unlike HPV-associated cervical cancers, which require E6 and E7 oncogenes for their expression, HPV-independent tumors exhibit specific mutations such as TP53, PIK3CA, KRAS, STK11, and PTEN. These mutations lead to alternative oncogenic pathways. Diagnosis of HPV-independent cervical adenocarcinoma is often delayed because of possible misclassification as endometrial adenocarcinomas, which frequently results from inadequate HPV testing. This often leads to advanced presentation stages, higher rates of lymphovascular invasion, and, in many cases, a reduced response to chemotherapy and immunotherapy—though outcomes can vary across histotypes and selected patient subgroups—due to the immune-cold tumor microenvironment. Although these morphologic and molecular characteristics describe tumors that are very difficult to manage, PI3K/mTOR and KRAS inhibitors may offer potential therapeutic options for selected patients. This review focuses on the pathogenic and molecular mechanisms, histopathological features, prognosis, and therapeutic difficulties of HPV-independent cervical cancers. Moreover, it provides a comprehension of contemporary issues in diagnostic methods and some new therapeutic approaches, suggesting the need for precision medicine in this aggressive type of cervical cancer. Further studies are necessary to enhance early detection, improve treatment results, and increase survival rates for patients with HPV-independent cervical cancer. Full article

Cadherin 17 (CDH17) is a cell adhesion glycoprotein essential for epithelial integrity. It is frequently overexpressed in various cancers, where it is associated with aggressive behaviour. While evidence indicates that CDH17 functions as an upstream regulator of Wnt/β-catenin signalling, findings are inconsistent across tumour types, limiting the assessment of CDH17 as a biomarker or therapeutic target for Wnt pathway in cancer. In this study, we systematically review and meta-analyse the relationship between CDH17 and Wnt/β-catenin signalling in human cancers and evaluate whether CDH17 modulation affects tumour behaviour through Wnt-related mechanisms. Our search of Medline, Web of Science and Scopus identified five studies examining CDH17 expression in the Wnt/β-catenin pathway in vitro and in vivo. All five studies identified CDH17 as a key driver of canonical Wnt signalling, directly influencing cancer progression in hepatocellular carcinoma (HCC), gastric cancer (GC), and colorectal cancer (CRC). Meta-analysis (MA) showed that CDH17 inhibition consistently reduced Wnt/β-catenin downstream T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcriptional activity (MD = −1.32, 95% CI: −1.64 to −0.99, p < 0.00001). Narrative synthesis found that CDH17 suppression decreased total and nuclear β-catenin, phosphorylated glycogen synthase kinase-3 beta (GSK-3β), and cyclin D1 while increasing tumour suppressors, retinoblastoma (Rb) and p53/p21. These changes were associated with reduced proliferation, colony formation, migration, invasion and cell cycle arrest. In vivo, CDH17 suppression resulted in 80–95% tumour growth suppression (Mean Difference (MD) = −96.67, 95% CI: [−144.35, −48.98], p < 0.0001), with immunohistochemistry confirming cytoplasmic β-catenin sequestration and lower cyclin D1 levels. Collectively, these findings show CDH17 as a critical upstream effector sustaining Wnt/β-catenin signalling, cancer progression, tumour proliferation, stem cell properties, and metastasis, and support CDH17 inhibition as a promising therapeutic target across multiple cancer types. Full article

Oral administration remains the most patient-friendly drug delivery route, yet its efficacy is limited by physiological barriers including gastric degradation and inefficient cellular uptake. pH-responsive nanogels have shown promise for gastrointestinal drug delivery, though their effectiveness is often constrained by poor membrane interaction. Inspired by natural membrane-anchoring mechanisms, a series of comb-like anionic polymers were designed via grafting alkylamines of different chain lengths (C₁₀, C₁₄, C₁₈) at varying densities (10–30%) onto a biodegradable poly(L-lysine isophthalamide) (PLP) backbone. These pH-responsive comb-like polymers self-assembled into nanogels for loading the hydrophobic chemotherapeutic agent camptothecin. The alkyl length and grafting density significantly influenced pH-responsive behavior, membrane disruption, and drug release profiles. The optimal formulation—the nanogel prepared with PLP grafted 30% C₁₄—achieved a high drug-loading capacity, ideal particle size and stability, and offered superior protection in acidic conditions (only 7 ± 5% release at pH 1.2 over 24 h), while enabling rapid intestinal release (78 ± 2% at pH 7.4 within 24 h). The nanogels significantly enhanced cellular uptake, cytoplasmic delivery, and cytotoxicity against colorectal carcinoma cells. This study demonstrates the key role of hydrophobic modification in designing effective oral nanocarriers, providing a promising platform for the treatment of intestinal diseases. Full article

Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers. 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

Objectives: miR-21-5p, miR-145-5p and miR-382-5p have been associated with angiogenesis, which plays a central role in tumor growth and metastasis formation. The aim of the study was to determine whether expression of these three potentially angiogenic miRNAs is related to the lymphatic spread capability of gastric adenocarcinoma and patient survival. Methods: Pathoclinical data of 123 patients who underwent elective gastric resection for adenocarcinoma between 1 August 2006 and 31 December 2013 were retrospectively retrieved. The major concerns were the total number of lymph nodes retrieved, the number of positive nodes, depth of the tumor invasion to the stomach wall, pTNM stage of the disease, Lauren histological tumor type, presence of a mucinous component in the cancer tissue, tumor location in the stomach and survival outcome. The cancer tissues of patients were examined for the expression levels of miR-21-5p, miR-145-5p and miR-382-5p. Results: Elevated hsa-miR-21-5p expression levels and downregulated hsa-miR-145-5p levels were observed in patients with a higher pT stage, lymph node metastasis and advanced pTNM stage. Additionally, hsa-miR-145-5p expression was lower in patients with cardia involvement and a Lauren intestinal-type carcinoma. hsa-miR-382-5p levels were higher in patients with non-mucinous gastric carcinoma. Both hsa-miR-145-5p and hsa-miR-21-5p were predictors of the presence of node metastasis, even when adjusted for pT status. hsa-miR-145-5p was significantly associated with improved survival. hsa-miR-145-5p was significantly associated with an increased probability of surviving 3 years, while increased hsa-miR-21 expression was significantly associated with reduced 3-year survival. All these associations were confirmed in multivariate models, which also included pT and M staging. Conclusions: The upregulation of miR-21-5p and downregulation of miR-145-5p are independent prognostic factors for lymph node metastasis and could serve as specific biomarkers of the lymphatic spread of gastric adenocarcinoma. miR-145-5p downregulation is an independent prognostic factor for overall survival. Full article

Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated between December 2018 and December 2024 were retrospectively reviewed. The study included 12 GAS, 48 SCC, and 30 UEA cases. Evaluated parameters included tumor morphology, cystic components, uterine cavity fluid, N/M staging, tumor diameter, the cervical lesion maximum standardized uptake value (SUVmax), and the tumor-to-liver maximum standardized uptake ratio (T/L SUVmax). Results: GAS predominantly exhibited diffuse infiltrative growth (11/12), in contrast to mass-like growth observed in SCC (37/48) and UEA (24/30) (both p < 0.001). Cystic components, uterine cavity fluid, and peritoneal metastasis occurred significantly more frequently in GAS (12/12, 11/12, 5/12, respectively) compared to SCC and UEA (all p < 0.001). Elevated CA19-9 levels were more common in GAS (9/12) compared with SCC (p < 0.001). Tumor diameter did not differ significantly among the groups (p > 0.05). SUVmax and T/L SUVmax values were significantly lower in GAS (7.5 ± 3.8 and 2.5 ± 1.6, respectively) than in UEA (19.1 ± 11.4 and 5.7 ± 3.4) and SCC (17.4 ± 6.7 and 5.5 ± 2.6) (all p < 0.001). Conclusion: The clinical characteristics of GAS include infiltrative tumor growth, fluid accumulation in the uterine cavity, frequent formation of microcystic or macrocystic components, peritoneal metastasis, and elevated CA19-9 levels. In this cohort, SUVmax and T/L SUVmax values in GAS were significantly lower than those observed in SCC and UEA. Full article

Background: Immune checkpoint inhibitors (ICIs) have transformed outcomes in advanced cancers; however, the value of continuing treatment after radiologic progression remains uncertain. We systematically assessed the efficacy and safety of ICI continuation beyond progression, focusing on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Methods: PubMed/MEDLINE, Embase, and the Cochrane Library were searched from inception to 31 March 2025. Eligible reports included retrospective cohorts, prospective trials, post hoc analyses, and pooled regulatory reviews that compared outcomes after ICI continuation versus discontinuation or historical controls. Quality was appraised with the Newcastle–Ottawa Scale (observational designs) and the Cochrane Risk-of-Bias tool (randomized trials). Results: Fifty studies involving 8989 patients met the inclusion criteria: 41 retrospective cohorts; 6 post hoc analyses; 2 randomized trials (1 phase III, 1 phase II); and 1 pooled FDA review. Continuing ICIs beyond progression produced ORRs of 9.3–39% in non-small cell lung cancer (n = 5102), 14–100% in melanoma (n = 669), and 8–33% in renal cell carcinoma (n = 458). Median OS ranged from 8.9 to 18.2 months in lung cancer, 12 to 29.9 months in melanoma, and up to 34.8 months in RCC. Modest but clinically meaningful benefits were reported in colorectal, head-and-neck, gastric, liver, and urothelial tumors. Conclusions: Select patients—particularly those with melanoma, lung cancer, RCC, or gastric cancer—may derive sustained benefit from ICI therapy after radiologic progression. Decisions should incorporate tumor biology, performance status, and emerging biomarkers. Prospective, biomarker-driven trials are needed to define optimal patient selection and the duration of post-progression immunotherapy. Full article

Objective: The high expression of prostate-specific membrane antigen (PSMA) associated with neovascularization in non-prostatic malignant tumors and metastatic lesions has been documented in many studies. By taking advantage of the absence of PSMA-related background activity in brain tissue, in recent years, PSMA has been used for the imaging of glial tumors, especially for postoperative follow-up. The aim of this prospective study was to investigate the diagnostic value of ⁶⁸Ga-PSMA-11 PET/CT by comparing ⁶⁸Ga-PSMA-11 PET/CT, ¹⁸F-FDG PET/CT, and MRI findings in patients with brain metastases (BM). Materials and Method: In this prospective study, 27 cases, 11 female and 16 male, with a mean age of 59.48 ± 12.21 years, were included. Patients diagnosed with BM on ¹⁸F-FDG PET/CT or CT/MRI at initial diagnosis or in the follow-up period were included in the study. PET findings of BM lesions obtained from ¹⁸F-FDG and ⁶⁸Ga-PSMA-11 PET/CT imaging, demographic characteristics, histopathological data of the primary foci, and other clinical features were evaluated together. Results: Twenty-four (89%) patients were included in the study for restaging, two (7%) patients for local recurrence assessment, and one (4%) patient for local recurrence and suspicion of additional lesions. The indications for ¹⁸F-FDG PET/CT were breast carcinoma for 37% (n:10), followed by lung carcinoma for 26% (n:7), colorectal adenocarcinoma for 14% (n:4), squamous cell larynx carcinoma for 7% (n:2), gastric signet ring cell carcinoma for 4% (n:1), pancreatic NET3 for 4% (n:1), thyroid papillary carcinoma for 4% (n:1), and malignant melanoma for 4% (n:1). In total, 26/27 included patients had PSMA-positive brain metastases but only one patient had PSMA-negative brain metastases with ⁶⁸Ga-PSMA-11 PET/CT imaging. This patient was followed with a diagnosis of primary larynx squamous carcinoma and had a mass suspected of brain metastases. Further tests and an MRI revealed that the lesion in this patient was a hemorrhagic metastasis. The smallest metastatic focus on ⁶⁸Ga-PSMA-11 PET/CT imaging was 0.22 cm, also confirmed by MRI (range: 0.22–2.81 cm). The mean ± SD SUVmax of the BM lesions was 17.9 ± 8.6 and 6.8 ± 5.2 on ¹⁸F-FDG PET/CT and ⁶⁸Ga-PSMA-11 PET/CT imaging, respectively. Metastatic foci that could not be detected by ¹⁸F-FDG PET/CT imaging were successfully detected with ⁶⁸Ga-PSMA-11 PET/CT imaging in 11 cases (42%). The distribution and number of metastatic lesions observed on cranial MRI and ⁶⁸Ga-PSMA-11 PET/CT were compatible with each other for all patients. Immunohistochemical staining was performed in the primary tumor of 10 (38%) cases, and positive IHC staining with PSMA was detected in 5 patients. In addition, positive IHC staining with PSMA was detected in all of the four surgically excised brain metastatic tumor foci. Conclusions: In this study,⁶⁸Ga-PSMA-11 PET/CT appears to be superior to ¹⁸F-FDG in detecting BM from various tumors, largely due to its high expression associated with neovascularization and the absence of PSMA expression in normal brain parenchyma. This lack of physiological uptake in healthy brain tissue provides excellent tumor-to-background contrast, further supporting the advantage of ⁶⁸Ga-PSMA-11 over ¹⁸F-FDG for BM imaging. However, larger studies are required to confirm these findings, particularly through comparisons across tumor types and histopathological subgroups, integrating PSMA immunohistochemistry (IHC) scores with ⁶⁸Ga-PSMA-11 uptake levels. Beyond its diagnostic potential, our results may also inform PSMA-targeted therapeutic strategies, offering new perspectives for the management of patients with brain metastases from diverse primary tumors. Full article