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18 pages, 593 KB  
Systematic Review
Esophageal Schwannoma—Systematic Review of Clinicopathologic Factors and Treatment
by Rashad Khazen, Raneem Bader, George Asfour, Barak Bar-Zakai, Guy Pines and Harbi Khalayleh
J. Clin. Med. 2026, 15(8), 2862; https://doi.org/10.3390/jcm15082862 (registering DOI) - 9 Apr 2026
Abstract
Background: Esophageal schwannomas are extremely rare, benign mesenchymal tumors originating from the nerve sheath tissues of autonomic nerves, accounting for less than 2% of all esophageal tumors. This systematic review aims to provide a detailed analysis of esophageal schwannomas (ESs), focusing on [...] Read more.
Background: Esophageal schwannomas are extremely rare, benign mesenchymal tumors originating from the nerve sheath tissues of autonomic nerves, accounting for less than 2% of all esophageal tumors. This systematic review aims to provide a detailed analysis of esophageal schwannomas (ESs), focusing on tumor characteristics, diagnostic methods, and treatment options. Methods: A systematic search of English literature databases, including ScienceDirect, Springer, PubMed, and Google Scholar, was conducted up to 2023. The keywords used were ‘esophageal schwannoma,’ ‘gastrointestinal schwannoma,’ ‘esophageal neurinoma,’ and ‘esophageal neurilemoma.’ Studies were reviewed for patient demographics, clinical presentation, diagnostic methods, tumor characteristics, and management options. Results: A total of 370 articles met the inclusion criteria, with 80 articles (89 cases) included in the final analysis. The mean age of patients was 51.8 years, with a female predominance (73%). Most cases were reported from East Asia (60.7%). Most (71%) patients presented with dysphagia, and 12% were asymptomatic. Preoperative diagnosis often involved CT scans (75.28%), upper endoscopy (73.03%), and EUS (49.4%). Tumors averaged 77.86 mm in size as per CT, MRI and PET-CT, with the upper esophagus being the most common location (55.55%). Surgical resection was the primary treatment, with enucleation being the most frequent procedure (58.9%). The prognosis was generally excellent, with no reported recurrences during follow-up periods. Conclusions: Esophageal schwannomas are extremely rare. Surgical resection remains the treatment of choice, with a high success rate and excellent prognosis. Further studies are needed to standardize diagnostic and treatment protocols for these rare tumors. Full article
(This article belongs to the Special Issue Recent Clinical Advances in Esophageal Surgery)
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8 pages, 814 KB  
Case Report
Atypical Skull Base Osteomyelitis of the Clivus Mimicking a Malignant Lesion: A Case Report
by Magdalena Stocker, Johanna Felber and Patricia Bäck
Diseases 2026, 14(4), 138; https://doi.org/10.3390/diseases14040138 - 9 Apr 2026
Abstract
Background/Objectives: Atypical skull base osteomyelitis (ASBO) is a rare disease, typically involving the basisphenoid and basiocciput. Diagnosis consists of clinical examination, imaging methods such as PET-CT scans and MRI, microbiological testing, and possibly native tissue samples. Long-term intravenous antibiotic therapy is the treatment [...] Read more.
Background/Objectives: Atypical skull base osteomyelitis (ASBO) is a rare disease, typically involving the basisphenoid and basiocciput. Diagnosis consists of clinical examination, imaging methods such as PET-CT scans and MRI, microbiological testing, and possibly native tissue samples. Long-term intravenous antibiotic therapy is the treatment of choice. Methods/Case Report: We present a case of ASBO of the clivus initially suspected to be a malignant lesion due to malignant melanoma in the patient’s history. Several tissue biopsies were taken, and microbiological testing of native tissue biopsies in combination with PET-CT and MRI imaging led to the diagnosis of ASBO. The patient received long-term antibiotic therapy with meropenem and drastically improved in his overall health. Discussion and Conclusions: This case highlights the challenges encountered in the diagnosis and management of ASBO, especially with relevant possible differential diagnoses. Full article
(This article belongs to the Section Infectious Disease)
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19 pages, 1991 KB  
Article
Multimodal Deep Learning for Prediction of Progression-Free Survival in Patients with Neuroendocrine Tumors Undergoing 177Lu-Based Peptide Receptor Radionuclide Therapy
by Simon Baur, Tristan Ruhwedel, Ekin Böke, Zuzanna Kobus, Gergana Lishkova, Christoph Wetz, Holger Amthauer, Christoph Roderburg, Frank Tacke, Julian M. Rogasch, Wojciech Samek, Henning Jann, Jackie Ma and Johannes Eschrich
Cancers 2026, 18(8), 1194; https://doi.org/10.3390/cancers18081194 - 8 Apr 2026
Abstract
Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine tumors (NETs), yet long-term disease control occurs only in a subset of patients. Predicting progression-free survival (PFS) could support individualized treatment planning. This study evaluates laboratory, imaging, and multimodal [...] Read more.
Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine tumors (NETs), yet long-term disease control occurs only in a subset of patients. Predicting progression-free survival (PFS) could support individualized treatment planning. This study evaluates laboratory, imaging, and multimodal deep learning models for PFS prediction in PRRT-treated patients. Methods: In this retrospective, single-center study 116 patients with metastatic NETs undergoing [177Lu]Lu-DOTATOC were included. Clinical characteristics, laboratory values, and pretherapeutic somatostatin receptor positron emission tomography/computed tomographies (SR-PET/CTs) were collected. Seven models were trained to classify low- vs. high-PFS groups, including unimodal (laboratory, SR-PET, or CT) and multimodal fusion approaches. Performance was assessed via repeated 3-fold cross-validation with area under the receiver operating characteristic curve (AUROC) and area under the precision–recall curve (AUPRC). Explainability was evaluated by feature importance analysis and gradient based saliency maps. Results: Forty-two patients (36%) displayed short PFS (≤1 year) and 74 patients displayed long PFS (>1 year). Groups were similar in most characteristics, except for higher baseline chromogranin A (p = 0.003), elevated γ-GT (p = 0.002), and fewer PRRT cycles (p < 0.001) in short-PFS patients. The Random Forest model trained only on laboratory biomarkers reached an AUROC of 0.59 ± 0.02. Unimodal three-dimensional convolutional neural networks using SR-PET or CT performed worse (AUROC 0.42 ± 0.03 and 0.54 ± 0.01, respectively). A multimodal fusion model integrating laboratory values, SR-PET, and CT—augmented with a pretrained CT branch—achieved the best results (AUROC 0.72 ± 0.01, AUPRC 0.80 ± 0.01). Explainability analyses provided insights into model predictions, with explainability patterns in the fusion model appearing physiologically plausible and predominantly tumor-focused. Conclusions: Multimodal deep learning combining SR-PET, CT, and laboratory biomarkers outperformed unimodal approaches for PFS prediction after PRRT. Upon external validation, such models may support risk-adapted follow-up strategies. Full article
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13 pages, 2172 KB  
Article
Bridging Research and Clinical Practice: Automated [68Ga]Ga-FAPi-46 Synthesis and Quality Control for Oncological PET Imaging
by Caiubi Rodrigues de Paula Santos, Luciana Malavolta, Jorge Mejia, Leonardo Lima Fuscaldi, Lilian Yuri Itaya Yamaga and Marycel Figols de Barboza
Pharmaceuticals 2026, 19(4), 594; https://doi.org/10.3390/ph19040594 - 8 Apr 2026
Abstract
Background/Objectives: Fibroblast activation protein (FAP) has emerged as a promising target for oncologic molecular imaging due to its high expression in cancer-associated fibroblasts and low presence in healthy tissues. Among available FAP ligands, [68Ga]Ga-FAPi-46 has shown rapid tumor accumulation, low background [...] Read more.
Background/Objectives: Fibroblast activation protein (FAP) has emerged as a promising target for oncologic molecular imaging due to its high expression in cancer-associated fibroblasts and low presence in healthy tissues. Among available FAP ligands, [68Ga]Ga-FAPi-46 has shown rapid tumor accumulation, low background uptake, and broad tumor applicability. This study reports the successful translation of [68Ga]Ga-FAPi-46 from preclinical development to routine clinical radiopharmacy practice, detailing automated synthesis, quality control performance, radiochemical stability, and the first clinical imaging results. Methods: Automated radiolabeling of FAPi-46 with gallium-68 was performed using a synthesis module. Quality control included radiochemical purity assessments by iTLC, SPE, and RP-HPLC (pH, appearance, endotoxin levels, and membrane integrity testing). Radiochemical stability was evaluated in saline (up to 6 h) and human serum (up to 90 min). In vitro characterization included the partition coefficient and serum protein binding determination. A clinical evaluation was conducted in a woman with newly diagnosed lung adenocarcinoma who underwent both [18F]FDG PET/CT and [68Ga]Ga-FAPi-46 PET/CT. Results: Automated synthesis of [68Ga]Ga-FAPi-46 achieved a high radiochemical yield (87.9 ± 1.3%) and radiochemical purity greater than 98%. All batches met release specifications for sterility, apyrogenicity, and physicochemical parameters. The radiotracer demonstrated high stability in saline and human serum, with radiochemical purity consistently above 95% at all evaluated time points. The compound showed a hydrophilic profile (LogP = −3.32 ± 0.14) and 40–60% serum protein binding. Clinically, [68Ga]Ga-FAPi-46 PET/CT provided superior lesion delineation compared to [18F]FDG, revealing additional mediastinal, supraclavicular, and brain metastases. Conclusions: [68Ga]Ga-FAPi-46 can be reliably synthesized using automated procedures under routine radiopharmacy conditions, meeting regulatory quality standards and demonstrating excellent stability. Its enhanced lesion detectability compared with [18F]FDG in the first patient case supports its potential value for oncological staging and clinical implementation. Full article
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15 pages, 751 KB  
Review
Positron Emission Tomography/Computed Tomography in Bladder Cancer: The Role of [18F]FDG and Non-FDG Radiotracers
by Hanna Falińska, Ewa Witkowska-Patena, Karolina Krzyżanowska and Mirosław Dziuk
Medicina 2026, 62(4), 703; https://doi.org/10.3390/medicina62040703 - 7 Apr 2026
Viewed by 154
Abstract
Background and Objectives: Bladder cancer is one of the most common malignancies of the urinary tract and poses a significant clinical challenge due to its biological heterogeneity and high rates of recurrence and progression. Urothelial carcinoma represents the predominant histological subtype, ranging [...] Read more.
Background and Objectives: Bladder cancer is one of the most common malignancies of the urinary tract and poses a significant clinical challenge due to its biological heterogeneity and high rates of recurrence and progression. Urothelial carcinoma represents the predominant histological subtype, ranging from non-muscle-invasive disease with relatively favorable outcomes to aggressive muscle-invasive and metastatic forms associated with poor prognosis. Accurate diagnosis, staging, prognostic stratification, and assessment of treatment response are therefore essential for optimal patient management. The objective of this review is to summarize and critically evaluate the current evidence on the role of positron emission tomography/computed tomography (PET/CT) in bladder cancer, with particular emphasis on [18F]FDG PET/CT and non-FDG radiotracers. Materials and Methods: A narrative review of the available literature was performed, focusing on clinical studies, review articles, and guideline documents addressing the use of PET/CT in bladder cancer. The literature search included articles published between 2000 and 2025, while earlier landmark studies were selectively included if considered historically important for understanding the development of PET/CT imaging in bladder cancer. The initial search yielded over 500 records; after screening titles and abstracts, more than 100 articles were selected for full-text evaluation. The analyzed evidence encompasses the clinical applications of [18F]FDG PET/CT and alternative radiotracers, including choline-, acetate-, methionine-, and sodium fluoride-based tracers, and fibroblast activation protein inhibitors (FAPI), across different stages of disease and clinical settings. Results: Conventional imaging modalities, such as computed tomography and magnetic resonance imaging, provide important anatomical information but remain limited in the evaluation of lymph node involvement, early metastatic disease, treatment response, and disease recurrence. Despite limitations related to physiological urinary excretion, [18F]FDG PET/CT has demonstrated clinical value in selected scenarios, particularly for staging, prognostic assessment, detection of recurrence, and response evaluation. To overcome FDG-related constraints, several non-FDG radiotracers have been investigated. Among these, FAPI PET/CT has emerged as a promising modality due to its ability to target the tumor stroma, potentially improving lesion detectability and tumor-to-background contrast. Conclusions: This review summarizes and critically evaluates current evidence on the role of PET/CT in bladder cancer, with a focus on [18F]FDG PET/CT and non-FDG radiotracers. The discussed studies highlight their applications in primary diagnosis, staging, prognostic assessment, detection of recurrence, and evaluation of treatment response, as well as their respective advantages and limitations. Furthermore, potential future directions for PET/CT imaging in clinical practice are outlined, emphasizing the need for further research to clarify the optimal use of established and emerging radiotracers. Full article
(This article belongs to the Special Issue Interventional Radiology and Imaging in Cancer Diagnosis)
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3 pages, 2282 KB  
Interesting Images
Testicular Plasmacytoma as the First Manifestation of Systemic Multiple Myeloma
by Patricia Rodriguez-Parras, Alberto Zambudio-Munuera, Miguel Herraez-Marcos, Francisco Gutierrez-Tejero and Miguel Angel Arrabal-Polo
Diagnostics 2026, 16(7), 1101; https://doi.org/10.3390/diagnostics16071101 - 6 Apr 2026
Viewed by 171
Abstract
Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells, usually confined to the bone marrow. Extramedullary disease (EMD) occurs in 7–18% of patients during the disease course and is associated with poor prognosis. Among extramedullary sites, testicular involvement is [...] Read more.
Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells, usually confined to the bone marrow. Extramedullary disease (EMD) occurs in 7–18% of patients during the disease course and is associated with poor prognosis. Among extramedullary sites, testicular involvement is extremely rare, with an incidence of less than 2%. We present a rare case of testicular plasmacytoma as the first manifestation of systemic multiple myeloma, highlighting its imaging features and clinical implications. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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11 pages, 14031 KB  
Case Report
Extracranial Metastases in Glioblastoma, IDH-Wildtype: A Case Series
by Valèria Richart, Marta García de Herreros, Juan Andrés Mora, Camilo Pineda, Iban Aldecoa, Estela Pineda, Izaskun Valduvieco, José Juan González, Laura Oleaga and Sofía González-Ortiz
Diagnostics 2026, 16(7), 1094; https://doi.org/10.3390/diagnostics16071094 - 5 Apr 2026
Viewed by 197
Abstract
Background: Extracranial metastasis (EM) from glioblastoma (GB), IDH-wildtype (WHO CNS 2021 grade 4) is rare and often under-recognized, yet it has immediate implications for staging and management. We report a case series integrating advanced neuroimaging, whole-body imaging, and pathology/biomarkers to characterize imaging–pathology [...] Read more.
Background: Extracranial metastasis (EM) from glioblastoma (GB), IDH-wildtype (WHO CNS 2021 grade 4) is rare and often under-recognized, yet it has immediate implications for staging and management. We report a case series integrating advanced neuroimaging, whole-body imaging, and pathology/biomarkers to characterize imaging–pathology correlates of EM and highlight practical clinical triggers that should prompt systemic evaluation. Case presentation: We report three patients with adult-type, IDH-wildtype GB who developed EM confirmed by cytology/histology and/or concordant multimodality imaging. Brain MRI (1.5T/3T) demonstrated aggressive primary tumors with qualitative elevation of DSC-perfusion and frequent tumor–surface contact (dural, ependymal/leptomeningeal contact). Intratumoral susceptibility signal reached grade 3 where assessed. All patients underwent surgical resection followed by temozolomide-based chemoradiation; two received fotemustine and bevacizumab, and one underwent re-irradiation. EM presented with clinical triggers including severe axial/back pain, palpable cervical masses, and/or cytopenias. Initial EM sites were bone marrow/vertebrae (n = 1) and cervical lymph nodes (n = 2); staging revealed additional osseous disease in both nodal cases and a small pulmonary nodule in one. Nodal and osseous lesions were FDG-avid on 18F-FDG PET/CT. OLIG2-positive cytology confirmed cervical nodal metastases, and bone marrow aspiration with GFAP/OLIG2 positivity confirmed medullary infiltration. All tumors shared a molecular profile of TERT-promoter mutation, ATRX wild-type, TP53 mutation, and MGMT-promoter methylation. Despite attempts at second- and third-line therapies, disease progression was rapid, and all patients succumbed within 8–16 months of diagnosis. Discussion: This series underscores that EM can occur despite MGMT-promoter methylation and supports the concept of heterogeneous metastatic phenotypes in GB. Our cases reinforce that new axial/back pain or hematologic abnormalities may signal osseous or marrow involvement, and necrotic cervical lymphadenopathy in GB patients warrants dedicated imaging and tissue confirmation with glial markers. Integrating brain MRI features (high perfusion, surface contact, susceptibility burden) with FDG-PET/CT and targeted cytology/pathology can expedite diagnosis and inform multidisciplinary care. Conclusions: EM can arise despite MGMT-promoter methylation in IDH-wildtype GBM. Imaging red flags (high perfusion, surface contact, necrotic/FDG-avid cervical nodes) and clinical cues (axial pain, cytopenias, neck masses) should prompt early systemic staging (CT/PET-CT) and targeted tissue confirmation to advance management. Full article
(This article belongs to the Special Issue Clinical Advances and Applications in Neuroradiology: 2nd Edition)
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18 pages, 736 KB  
Perspective
Do We Need a New Diagnostic Model for Lung Cancer—Are We Ready? A Narrative Review of European Rapid Diagnostic Programs and an Operational Unified FTC-LCU Model
by Joanna Maksymowicz-Jaroszuk, Lukasz Minarowski and Robert Marek Mroz
Cancers 2026, 18(7), 1167; https://doi.org/10.3390/cancers18071167 - 4 Apr 2026
Viewed by 206
Abstract
Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Survival outcomes are strongly stage-dependent. Many patients are diagnosed at advanced stages due to pre-clinical and diagnostic delays. While advances in imaging, bronchoscopic techniques, molecular diagnostics, and systemic therapies have improved [...] Read more.
Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Survival outcomes are strongly stage-dependent. Many patients are diagnosed at advanced stages due to pre-clinical and diagnostic delays. While advances in imaging, bronchoscopic techniques, molecular diagnostics, and systemic therapies have improved individualized treatment, system-level delays continue to limit their impact. Aim of the study: The aim of this narrative review is a synthesis with an implementation-oriented framework proposal. Part I synthesizes the peer-reviewed literature, Part II presents an operational framework integrating a Fast Trac Clinic (FTC) and a network of Lung Cancer Units (LCUs) including proposed turnaround-time (TAT) goals. Methods: A narrative review of the literature of selected European policy documents addressing diagnostic delays, rapid-access lung cancer pathways, and coordinated care models was conducted. Results: European models demonstrate that structured referral criteria, centralized coordination, and predefined interval targets can achieve the first specialist assessment within 7–10 days and the completion of diagnostics within 21–28 days in optimized settings. Key determinants of timeliness include: direct primary care referral, parallel diagnostic processes, prioritized pathology and molecular testing, and multidisciplinary team (MDT) assessment. We propose operational TAT targets for chest CT, PET-CT, histopathology, NGS, PFTs, and MDT decision-making. Conclusions: Reducing avoidable diagnostic and therapeutic delays in LC requires a coordinated, system-level approach. A standardized FTC-LCU pathway with explicit TAT benchmarks, multidisciplinary governance, and digital support infrastructure may improve diagnostic efficiency, increase the proportion of patients treated at earlier stages, and enhance patient experience. Prospective evaluation of implementation impact on stage distribution and survival is advised. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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16 pages, 3039 KB  
Article
A Preclinical Study of a PSMA Ligand-Based Dual-Modality Probe for Radical Prostatectomy
by Haoxi Zhou, Zhiqiang Chen, Long Yi, Baojun Wang, Shaoxi Niu, Yu Gao and Xu Zhang
Pharmaceuticals 2026, 19(4), 564; https://doi.org/10.3390/ph19040564 - 1 Apr 2026
Viewed by 309
Abstract
Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and [...] Read more.
Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [68Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [68Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [68Ga]Ga, a dual-modality radionuclide-fluorescence probe ([68Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/106 cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [68Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [68Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article
(This article belongs to the Section Medicinal Chemistry)
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17 pages, 290 KB  
Article
Dietary Patterns and Cerebral Glucose Metabolism in Older Adults: Findings from the Western Australian Memory Study
by Carolina B. Castro, Samantha L. Gardener, Farzana Jahan, Juliana Chen, Belinda M. Brown, Ruey L. Loo, Kevin Taddei, Stephanie R. Rainey-Smith, Michael Weinborn, Ana Caroline R. dos Reis, Shipra Verma, Nick Carrigan, Charles Inderjeeth, Vincent Doré, Manohar L. Garg, Ralph N. Martins and Hamid R. Sohrabi
Nutrients 2026, 18(7), 1136; https://doi.org/10.3390/nu18071136 - 1 Apr 2026
Viewed by 375
Abstract
Alzheimer’s disease (AD) is characterized by significant reductions in glucose metabolism, reflecting underlying synaptic dysfunction, correlating with cognitive decline. We aimed to explore the impact of dietary patterns on the change in glucose metabolism. Methods: This longitudinal, prospective study included 132 community-dwelling older [...] Read more.
Alzheimer’s disease (AD) is characterized by significant reductions in glucose metabolism, reflecting underlying synaptic dysfunction, correlating with cognitive decline. We aimed to explore the impact of dietary patterns on the change in glucose metabolism. Methods: This longitudinal, prospective study included 132 community-dwelling older adults without a diagnosed dementia history enrolled in the Western Australian Memory Study (WAMS). Participants completed a food frequency questionnaire at baseline and underwent [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at baseline and at up to two follow-up assessments scheduled approximately 18 months apart, over a maximum follow-up period of 43 months. Principal component analysis yielded two dietary patterns—named Western Diet and Prudent Diet. Linear mixed-effect models evaluated the association between dietary adherence and glucose metabolism, including potential confounders. Analysis was repeated stratified by sex. Results: Adherence to a Western Diet, characterized by high sugars and saturated fats, was associated with faster decline in glucose metabolism in the left fusiform gyrus (β = −0.00062; SE = 0.00025; FDR-adjusted p = 0.043), neocortex (β = −0.00063; SE = 0.00026; FDR-adjusted p = 0.047), left ventrolateral prefrontal (β = −0.00083; SE = 0.00032; FDR-adjusted p = 0.045 and inferior parietal region (β = −0.00344; SE = 0.00129; FDR-adjusted p = 0.033) in females. A Prudent Diet, characterized by a high intake of fruits, vegetables, and whole grains, showed no significant effects. Conclusions: Our study highlights the following: (a) The potential detrimental impact of a Western Diet on brain glucose metabolism, particularly for females, who are at higher risk for AD. The decline was observed in regions essential for cognitive functions, including visual processing and facial recognition, emphasizing the role of diet in brain health. (b) No significant associations were observed between adherence to a Prudent dietary pattern and changes in glucose metabolism. Full article
20 pages, 1181 KB  
Review
Surgical Perspectives on Neoadjuvant Therapy in Borderline Resectable and Locally Advanced Pancreatic Cancer
by Jingcheng Zhang, Menghang Geng, Helmut Friess, Ihsan Ekin Demir and Florian Scheufele
Cancers 2026, 18(7), 1131; https://doi.org/10.3390/cancers18071131 - 1 Apr 2026
Viewed by 333
Abstract
Background/Objectives: Neoadjuvant therapy (NAT) is now central to the management of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic ductal adenocarcinoma (PDAC). This narrative review summarizes contemporary evidence and guidelines from a surgical perspective, with emphasis on pretreatment classification, post-NAT selection for [...] Read more.
Background/Objectives: Neoadjuvant therapy (NAT) is now central to the management of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic ductal adenocarcinoma (PDAC). This narrative review summarizes contemporary evidence and guidelines from a surgical perspective, with emphasis on pretreatment classification, post-NAT selection for exploration, intraoperative vascular strategy, and postoperative management. Methods: We conducted a structured narrative review of randomized and prospective studies, high-quality observational cohorts, and major international guidelines published through 31 July 2025. Results: BRPC and LAPC remain primarily defined by vascular anatomy, but biologic and conditional factors are increasingly integrated into decision-making. NAT is the preferred initial strategy for BRPC and the standard induction approach for LAPC, with resection considered only in carefully selected responders. After NAT, contrast-enhanced CT combined with CA19-9 kinetics remains the core restaging platform, while FDG-PET, diffusion-weighted MRI, radiomics, and circulating biomarkers may serve as adjuncts in equivocal cases. Surgical exploration should be guided by physiologic recovery, the absence of metastatic progression, and multidisciplinary reassessment. Staging laparoscopy remains useful for detecting occult metastatic disease. Intraoperatively, vascular resection should be margin-driven rather than routine, with portal–mesenteric venous resection established in expert centers, whereas arterial resection remains highly selective. Periarterial divestment represents an artery-sparing alternative in selected cases. NAT does not appear to worsen short-term postoperative outcomes, but anticoagulation after venous reconstruction remains non-standardized. Conclusions: NAT has transformed BRPC/LAPC PDAC into a biology-gated, time-sequenced surgical pathway. Standardized reassessment, careful candidate selection, and the centralization of complex vascular procedures are essential to optimize outcomes. Full article
(This article belongs to the Special Issue The Progress of Pancreatectomy for Pancreatic Cancer Treatment)
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14 pages, 514 KB  
Article
Prognostic Value of the SUVmax–IPI Composite Score on Overall Survival in Metastatic Prostate Cancer
by Emine Türkmen, Atike Pınar Erdoğan, Mustafa Şahbazlar, Gözde Mütevelizade and Ferhat Ekinci
J. Clin. Med. 2026, 15(7), 2655; https://doi.org/10.3390/jcm15072655 - 31 Mar 2026
Viewed by 225
Abstract
Objective: This study aimed to evaluate the prognostic value of the SUVmax–IPI composite score, generated by integrating the maximum standardized uptake value (SUVmax) derived from metastatic 68Ga-PSMA PET/CT imaging with the inflammatory prognostic index (IPI), in predicting overall survival in patients with [...] Read more.
Objective: This study aimed to evaluate the prognostic value of the SUVmax–IPI composite score, generated by integrating the maximum standardized uptake value (SUVmax) derived from metastatic 68Ga-PSMA PET/CT imaging with the inflammatory prognostic index (IPI), in predicting overall survival in patients with metastatic prostate cancer. Materials and Methods: This retrospective, single-center cohort study included 146 patients diagnosed with metastatic prostate adenocarcinoma between 2009 and 2025. Among them, 125 patients with available PET/CT imaging were included in the SUVmax–IPI analysis. The composite score was calculated by multiplying the metastatic SUVmax value by the IPI. The optimal cut-off value was determined using receiver operating characteristic curve analysis. Overall survival was evaluated using the Kaplan–Meier method and compared using the log-rank test. Independent prognostic factors were identified using multivariable Cox proportional hazards regression analysis with a forward (stepwise) selection approach. Results: Using the predefined cut-off value (82), the median overall survival was 125 months in patients with SUVmax–IPI ≤ 82 and 19 months in those with SUVmax–IPI > 82 (log-rank p = 0.001). In the forward multivariable Cox regression model, SUVmax–IPI > 82 remained independently associated with worse overall survival after adjustment for ALP, AST, PSA nadir, and androgen deprivation modality (hazard ratio [HR]: 7.92; 95% confidence interval [CI]: 2.97–21.10; p < 0.001). Conclusions: The SUVmax–IPI composite score, integrating PSMA PET/CT-derived metabolic tumor activity with systemic inflammatory burden, is independently associated with overall survival in metastatic prostate cancer. These findings suggest that combining metabolic and inflammatory parameters may enhance prognostic stratification beyond conventional clinical and biochemical markers. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Approaches to Urologic Oncology)
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23 pages, 3201 KB  
Review
Multimodal Radiogenomic Imaging in Oropharyngeal Squamous Cell Carcinoma: Implications for Dentomaxillofacial Radiology
by Elaine Dinardi Barioni, Kaan Orhan, Ana Cristina Borges-Oliveira, Sérgio Lúcio Pereira de Castro Lopes and Andre Luiz Ferreira Costa
Med. Sci. 2026, 14(2), 174; https://doi.org/10.3390/medsci14020174 - 31 Mar 2026
Viewed by 315
Abstract
Radiogenomics examines associations between imaging phenotypes and underlying biological characteristics across cancer types. This structured narrative review focuses on oropharyngeal squamous cell carcinoma (OPSCC) and evaluates how genomic programs characteristic of HPV-positive and HPV-negative tumors have been investigated across computed tomography (CT), magnetic [...] Read more.
Radiogenomics examines associations between imaging phenotypes and underlying biological characteristics across cancer types. This structured narrative review focuses on oropharyngeal squamous cell carcinoma (OPSCC) and evaluates how genomic programs characteristic of HPV-positive and HPV-negative tumors have been investigated across computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) as variations in heterogeneity, diffusion patterns, perfusion and metabolic activity. A structured literature search was conducted in PubMed/MEDLINE, Scopus and Web of Science to identify studies on radiomics and radiogenomics in OPSCC and related head and neck cancers. After screening and eligibility assessment, 81 studies were included in the narrative synthesis. The reviewed literature indicates that imaging-derived features have been associated with HPV status, hypoxia-related signatures, extranodal extension and treatment outcomes. However, the current evidence base remains heterogeneous and is largely composed of retrospective, single-institution studies with relatively small cohorts. Methodological challenges, including variability in imaging acquisition, segmentation and feature harmonization, limit reproducibility and generalizability. Although cone-beam computed tomography (CBCT) is not used for primary OPSCC staging and no CBCT-based radiogenomic studies in OPSCC have been reported, existing radiomics research in dentomaxillofacial imaging suggests its potential as a hypothesis-generating modality for future investigation. Overall, current evidence supports the biological plausibility of radiogenomic imaging signatures in OPSCC, while emphasizing the need for larger multicenter datasets, standardized imaging protocols and prospective validation before clinical implementation. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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17 pages, 2368 KB  
Article
LANTERN-XGB: An Interpretable Multi-Modal Machine Learning for Improving Clinical Decision-Making in Lung Cancer
by Davide Dalfovo, Carolina Sassorossi, Elisa De Paolis, Annalisa Campanella, Dania Nachira, Leonardo Petracca Ciavarella, Luca Boldrini, Esther G. C. Troost, Róza Ádány, Núria Farré, Ece Öztürk, Angelo Minucci, Rocco Trisolini, Emilio Bria, Steffen Löck, Stefano Margaritora and Filippo Lococo
Int. J. Mol. Sci. 2026, 27(7), 3128; https://doi.org/10.3390/ijms27073128 - 30 Mar 2026
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Abstract
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality globally. While multi-modal artificial intelligence (AI) models offer significant predictive potential, their translation into routine clinical practice is delayed by the “black box” nature of complex algorithms and the fragmentation of [...] Read more.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality globally. While multi-modal artificial intelligence (AI) models offer significant predictive potential, their translation into routine clinical practice is delayed by the “black box” nature of complex algorithms and the fragmentation of heterogeneous data. We present LANTERN-XGB, a hierarchical machine learning workflow designed to bridge this gap by generating interpretable “digital human avatars” for precision oncology. The methodology employs a multi-stage scalable tree boosting system (XGBoost) architecture utilizing shapley additive explanations (SHAP) for rigorous hierarchical feature selection, missing value management, and patient-specific decision support. The workflow was developed and benchmarked using a retrospective cohort of 437 patients with clinical N0 NSCLC, followed by validation on a prospective dataset (n = 100) and an independent external dataset (n = 100). The pipeline integrates diverse data modalities to predict occult lymph node metastasis (OLM). LANTERN-XGB identified a robust consensus signature driven by non-linear interactions among CT textural fragmentation, PET metabolic heterogeneity, tumor density distribution, and systemic clinical modulators. Exploratory transcriptomic pathway analysis (GSVA) revealed that high-risk predictions strongly correlate with systemic molecular dysregulation, such as the enrichment of immune-inflammatory signaling and metabolic stress pathways. The model achieved robust discrimination in external validation (AUC ≈ 0.77), performing comparably to state-of-the-art nomogram benchmarks. Crucially, the LANTERN-XGB framework demonstrated superior utility in handling diagnostic ambiguity; local force plots allowed for the correct reclassification of “borderline” prediction by visualizing feature interactions that standard linear models fail to capture. LANTERN-XGB provides a validated, open-source framework that successfully balances predictive power with clinical transparency. By empowering clinicians to visualize and verify the logic behind AI predictions, this workflow offers a pragmatic path for integrating reliable multi-modal avatars into daily medical decision-making. Full article
(This article belongs to the Special Issue Omics Science and Research in Human Health and Disease)
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14 pages, 1195 KB  
Article
Pilot Study on Dynamic Long-Axial Field-of-View [18F]FDG PET/CT in Liver Transplant Recipients as a Non-Invasive Alternative to Routine Biopsies
by Martin Bloch, Susanne Dam Nielsen, Barbara Malene Fischer, Allan Rasmussen, Hans-Christian Pommergaard, Flemming Littrup Andersen, Gro Linno Willemoe, Thomas Lund Andersen and Per Karkov Cramon
Diagnostics 2026, 16(7), 1021; https://doi.org/10.3390/diagnostics16071021 - 28 Mar 2026
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Abstract
Background/Objectives: Routine liver biopsies play an important role in monitoring liver allografts but carry non-negligible risks. This pilot study assesses the feasibility of dynamic long-axial field-of-view (LAFOV) [18F]FDG PET/CT as a non-invasive alternative to biopsy. Methods: Liver transplant (LTx) [...] Read more.
Background/Objectives: Routine liver biopsies play an important role in monitoring liver allografts but carry non-negligible risks. This pilot study assesses the feasibility of dynamic long-axial field-of-view (LAFOV) [18F]FDG PET/CT as a non-invasive alternative to biopsy. Methods: Liver transplant (LTx) recipients meeting the inclusion criteria of ≥10 months post-transplantation and scheduled routine biopsy were prospectively enrolled, along with healthy controls. All participants underwent dynamic LAFOV [18F]FDG PET/CT, followed by biopsy in LTx recipients, who were stratified by inflammatory severity using the BANFF score. Hepatic kinetic parameters (K1, k2, k3, k4) and SUVmean/SUVmax were compared using Mann–Whitney U tests. Correlations were assessed using Spearman’s rank correlation. A p-value < 0.05 was considered significant. Analyses were performed in RStudio (version 2024.12.10563). Results: Sixteen LTx recipients (mean age 48.6 years; seven female, nine male) and eight healthy controls (mean age 35.4 years; six female, two male) were included. Healthy controls had mean k3 and k4 values of 0.0037 min−1 ± 0.0003 min−1 and 0.0019 min−1 ± 0.0011 min−1, respectively. LTx recipients showed significantly higher k3 and k4 values, both when including and excluding patients with biopsy-confirmed inflammation. Descriptive comparisons between LTx recipients with and without significant inflammation (n = 3) showed no clear differences. Spearman analysis showed no significant correlations between the BANFF score and kinetic parameters. The strongest degree of correlation was found between BANFF score and k3, indicating a moderate positive but non-significant association (k3: rs = 0.396, p = 0.128). Conclusions: Elevated k3 and k4 values in LTx recipients were not explained by allograft inflammation, suggesting altered FDG kinetics post-transplant. These differences may confound [18F]FDG PET interpretation. Larger studies are needed to assess the clinical applicability of dynamic LAFOV [18F]FDG PET/CT. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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