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18 pages, 2572 KB  
Case Report
Dumbbell Spinal Desmoid Tumor Mimicking a Giant Schwannoma: Case Report and Literature Review
by Hajar Nafidi, Rossella Rispoli, Stefano Pizzolitto, Corrado Iaccarino, Giacomo Pavesi and Barbara Cappelletto
J. Clin. Med. 2025, 14(21), 7596; https://doi.org/10.3390/jcm14217596 (registering DOI) - 26 Oct 2025
Abstract
Background/Objectives: Desmoid tumors (DTs) are rare benign soft tissue neoplasms characterized by local aggressiveness and high rate of recurrence. Spinal localization is only anecdotally reported in the literature. When presenting in a dumbbell-shaped configuration, they can mimic neurogenic tumors. Methods: We report a [...] Read more.
Background/Objectives: Desmoid tumors (DTs) are rare benign soft tissue neoplasms characterized by local aggressiveness and high rate of recurrence. Spinal localization is only anecdotally reported in the literature. When presenting in a dumbbell-shaped configuration, they can mimic neurogenic tumors. Methods: We report a rare case of a spinal intracanalar–intrathoracic DT, initially suspected to be a schwannoma, and review the literature. Results: A 24-year-old asymptomatic man was incidentally found to have a mediastinal mass on chest X-ray. CT and MRI revealed a left thoracic paravertebral mass (T9–T12), with intracanalar extension through the T10–T11 foramen, suggestive of a dumbbell-shaped neurogenic tumor. After embolization, the patient underwent surgery via a posterior combined intracanalar and endothoracic approach. Histology and immunohistochemistry analysis identified the tumor as a desmoid type fibromatosis (β catenin positive; S100, CD34, SMA negative). Follow-up MRI at 8, 12, and 18 months showed stable residual intrathoracic mass. Conclusions: To date, only 36 cases of spinal DTs have been reported in the literature, of which only 6 exhibited dumbbell morphology. Immunohistochemical and molecular pathological testing is essential for diagnosis. Although wide resection is preferred, anatomical limitations often necessitate marginal or subtotal surgery, which increases the risk of recurrence (24–77%). Our review showed a 29% overall recurrence rate (50% after subtotal, 29% marginal, 20% wide resection). Adjuvant radiotherapy or systemic therapies may help improve outcomes. Spinal DTs pose significant diagnostic and therapeutic challenges. In the absence of established guidelines, management should be individualized and multidisciplinary. Lifelong follow-up is essential due to the high risk of recurrence. Full article
(This article belongs to the Section Clinical Neurology)
22 pages, 11428 KB  
Article
Cold Atmospheric Plasma Selectively Targets Neuroblastoma: Mechanistic Insights and In Vivo Validation
by Ligi Milesh, Bindu Nair, Ha M. Nguyen, Taylor Aiken, J. Leon Shohet and Hau D. Le
Cancers 2025, 17(21), 3432; https://doi.org/10.3390/cancers17213432 (registering DOI) - 25 Oct 2025
Abstract
Background: Neuroblastoma (NB) presents significant challenges in pediatric oncology, particularly in high-risk cases where local recurrence occurs in ~35% of patients. Cold Atmospheric Plasma (CAP) has emerged as a promising treatment due to its selective cytotoxicity toward cancer cells while sparing normal cells. [...] Read more.
Background: Neuroblastoma (NB) presents significant challenges in pediatric oncology, particularly in high-risk cases where local recurrence occurs in ~35% of patients. Cold Atmospheric Plasma (CAP) has emerged as a promising treatment due to its selective cytotoxicity toward cancer cells while sparing normal cells. Methods: This study assessed CAP efficacy using in vitro NB cell lines (SK-N-AS and LAN-5) and in vivo xenograft murine models. In vitro, CAP was applied via a helium jet, and cellular responses were evaluated for viability, reactive oxygen species (ROS), lipid peroxidation, DNA damage, and cell cycle, while apoptosis was measured by Annexin V/PI flow cytometry. In vivo, CAP was applied to unresected tumors and residual tumors after incomplete resection. Tumor regrowth was monitored, and histological analysis was performed. Results: CAP reduced NB cell viability in a dose- and time-dependent manner by increasing intracellular ROS and lipid peroxidation. CAP-treated NB cells showed a 50% rise in oxidative DNA damage, a two-fold increase in apoptosis, and alterations in cell-cycle progression, while normal fibroblasts showed modest effects. CAP predominantly induced apoptosis, though secondary necrosis appeared with prolonged exposures, consistent with caspase-3 and PARP pathways. In xenografts, CAP reduced tumor diameter by 60% and increased caspase-3-positive cells, with minimal effects on normal tissue. Conclusions: CAP demonstrates strong therapeutic potential as a targeted, non-invasive NB treatment, particularly for residual tumors near vascular structures with consistent exposure times (60–300 s). Full article
(This article belongs to the Section Methods and Technologies Development)
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21 pages, 910 KB  
Review
Characterizing the Microenvironment of Cerebral Arteriovenous Malformations to Test Novel Treatment Modalities
by Kavin Wazhi, Fred C. Lam, Santosh Guru, Yusuke S. Hori, Deyaldeen AbuReesh, Lorelei Shoemaker, David J. Park and Steven D. Chang
Brain Sci. 2025, 15(11), 1145; https://doi.org/10.3390/brainsci15111145 (registering DOI) - 25 Oct 2025
Abstract
Brain arteriovenous malformations (bAVMs) consist of a tangled nidus of abnormal dilated vessels characterized by direct connections between arteries and veins that lack an intervening capillary bed, creating a high-to-low flow pressure system that is predisposed to spontaneous hemorrhage with significant associated neurologic [...] Read more.
Brain arteriovenous malformations (bAVMs) consist of a tangled nidus of abnormal dilated vessels characterized by direct connections between arteries and veins that lack an intervening capillary bed, creating a high-to-low flow pressure system that is predisposed to spontaneous hemorrhage with significant associated neurologic morbidity and mortality. Treatment options for bAVMs include the following: surgical resection, intravascular embolization to obliterate blood flow through the AVM, and radiosurgery. Understanding the molecular mechanisms of bAVM formation and factors that predispose it to hemorrhage can lead to novel treatments that can improve the prognosis for patients. This review summarizes emerging insights into the complex and dynamic molecular mechanisms of bAVMs. Dysregulation in key VEGF, TGF-β/BMP9/10–ENG–ALK1–SMAD4, Notch, and MAPK/ERK signaling pathways drive abnormal angiogenesis in both syndromic and sporadic forms, with KRAS/BRAF/MAPK21 mutations specifically linked to the latter. Advances in bAVM-induced animal models have corroborated many of the genetic profiles found in humans, and they continue to provide novel insights into bAVM mechanisms. Collectively, these mechanistic findings are guiding translational advances, with targeted therapies and liquid biopsy approaches emerging as avenues for precision treatment and improved patient outcomes. Full article
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12 pages, 1062 KB  
Review
Current Surgical Perspective on the Prognosis of Small-Cell Lung Cancer
by Hüseyin Fatih Sezer
Diagnostics 2025, 15(21), 2704; https://doi.org/10.3390/diagnostics15212704 (registering DOI) - 25 Oct 2025
Abstract
Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour that can metastasise early, may show resistance to systemic treatment, and has a poor prognosis. The use of tobacco products is closely related to the duration of their use, and approximately 95% of [...] Read more.
Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour that can metastasise early, may show resistance to systemic treatment, and has a poor prognosis. The use of tobacco products is closely related to the duration of their use, and approximately 95% of those diagnosed have a history of smoking. No satisfactory progress has been made in the prognosis with current treatment methods up to the present day. The treatment approach has traditionally involved long-term chemotherapy (CT) and radiotherapy (RT), and recent literature has focused on immunotherapy and genetic advancements. Surgery can only be performed in cases detected at an early stage. Although both chemotherapy and radiotherapy are indispensable options for most patients, their impact on prognosis and survival is limited. Although promising developments are expected in immunotherapy, its impact on survival is still very limited, lasting only about 2 months. In patients undergoing surgical resection as part of their treatment, overall survival (OS) ranges from 34 to 69 months. OS for 1 year is 84.8–93.8%, for 3 years is 60–71.2%, and for 5 years is 51.1–63.8%. The five-year survival rates are reported as follows: stage I 31–63.8%, stage II 25–65.5%, stage III 15–27.8%, and stage IV 0%. In this study, the prognosis and factors affecting prognosis in SCLC were investigated in light of current literature from a surgical perspective, and predictions were attempted to be made to lay the groundwork for personalised treatment approaches. Compared to non-small-cell lung cancer, the number of studies is quite limited. Most of the surgical case series were conducted in the past, retrospectively, and involved a small number of patients. Advances in immunotherapy are promising. In the early stages, resection and subsequent chemotherapy may be the main treatment. Full article
(This article belongs to the Special Issue Recent Advances in the Diagnosis and Prognosis of Lung Cancer)
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20 pages, 459 KB  
Review
Treatment Duration in Bacterial Prosthetic Joint Infections: A Narrative Review of Current Evidence
by Hajer Harrabi, Christel Mamona-Kilu, Eloïse Meyer, Emma d’Anglejan Chatillon, Nathalie Dournon, Frédérique Bouchand, Clara Duran, Véronique Perronne, Karim Jaffal and Aurélien Dinh
Antibiotics 2025, 14(11), 1066; https://doi.org/10.3390/antibiotics14111066 (registering DOI) - 25 Oct 2025
Abstract
Background/Objectives: The optimal duration of antibiotic therapy for bacterial prosthetic joint infections (PJI) remains a topic of considerable debate. Current recommendations are often based on limited evidence and expert consensus. Emerging data suggest that shorter antibiotic courses may be as effective as prolonged [...] Read more.
Background/Objectives: The optimal duration of antibiotic therapy for bacterial prosthetic joint infections (PJI) remains a topic of considerable debate. Current recommendations are often based on limited evidence and expert consensus. Emerging data suggest that shorter antibiotic courses may be as effective as prolonged treatments in select cases. Shortening the duration of therapy offers several advantages, including a reduced risk of bacterial resistance, fewer adverse events, and cost savings. However, this approach must be carefully balanced with the individual patient’s risk of treatment failure. This narrative review aims to synthesize current evidence regarding the duration of antibiotic therapy in PJIs, according to surgical strategies—DAIR (debridement, antibiotics, and implant retention), one-stage exchange, two-stage exchange, and resection without reimplantation—and to identify parameters that may guide individualized and potentially shortened regimens. Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane Library databases through January 2025, including observational studies, randomized controlled trials, and international guidelines. Reference lists of key articles were also screened. Results: Studies on DAIR suggest that longer regimens (e.g., 8–12 weeks) are necessary, especially in staphylococcal infections, as confirmed by the DATIPO trial, which showed higher failure rates with 6 weeks compared to 12 weeks. Evidence on one-stage exchange is limited but increasingly suggests that 6 weeks may be sufficient in selected patients; however, no dedicated trial has confirmed this. In two-stage exchange, small retrospective series report successful outcomes with short antibiotic therapy combined with local antibiotics, but randomized trials show trends favoring longer regimens. For patients treated with permanent resection arthroplasty, arthrodesis, or amputation, antibiotic durations are highly variable, with few robust data. Across all strategies, most studies are limited by methodological weaknesses, including small sample sizes, retrospective design, lack of microbiological stratification, and heterogeneous outcome definitions. Conclusions: Despite growing interest in shortening antibiotic durations in PJIs, high-quality evidence remains limited. Until additional randomized trials are available—particularly in one- and two-stage exchange settings—12 weeks remains the safest reference duration for most patients, especially those with retained hardware. Future studies should incorporate stratification by infection type, causative organism, and host factors to define tailored and evidence-based antibiotic strategies. Full article
(This article belongs to the Special Issue Orthopedic Infections: Epidemiology and Antimicrobial Treatment)
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10 pages, 881 KB  
Article
Examining the Concordance of Detection of Hereditary Cancer Gene Variants Between Blood, Tumour, and Normal Tissue in Patients with High-Grade Serous Ovarian Carcinoma
by L. Mui, J. Kerkhof, C. M. McLachlin, K. Panabaker, J. McGee, B. Sadikovic and E. A. Goebel
Genes 2025, 16(11), 1260; https://doi.org/10.3390/genes16111260 (registering DOI) - 25 Oct 2025
Abstract
Background/Objectives: Access to genetic counselling and BRCA1/2 germline testing is standard of care for patients with high-grade serous ovarian carcinoma (HGSOC). While tumour testing reliably detects pathogenic variants in hereditary cancer genes, it cannot distinguish somatic from germline variants. Concurrent testing of non-cancerous [...] Read more.
Background/Objectives: Access to genetic counselling and BRCA1/2 germline testing is standard of care for patients with high-grade serous ovarian carcinoma (HGSOC). While tumour testing reliably detects pathogenic variants in hereditary cancer genes, it cannot distinguish somatic from germline variants. Concurrent testing of non-cancerous (normal) tissue obtained during surgery may improve triage for germline testing and clinical genetics referral. This study evaluated the concordance of inherited variant detection among tumour, normal tissue, and blood to determine whether archived normal tissue can reliably identify germline pathogenic variants. Methods: Patients with HGSOC who had a pathogenic variant identified by targeted Next Generation Sequencing (NGS) tumour testing and underwent germline hereditary cancer gene panel (HCP) testing between April 2019 and November 2020 were included. HCP testing was performed on formalin-fixed, paraffin-embedded normal tissue from the original resection. Variant results were compared across tumour, normal tissue, and germline (blood) samples to determine concordance, false-negative, and false-positive rates. Results: Forty-one patients had confirmed tumour variants in BRCA1/2 or other HCP genes. Of these, 24 harboured a corresponding germline pathogenic variant. Archived normal tissue was available for 23 of these 24 cases, and all germline variants were detected in normal tissue, showing 100% concordance. Among the 17 patients without germline variants, all corresponding normal tissue samples were negative, also demonstrating 100% concordance. No false positives or negatives were identified. Conclusions: NGS testing of normal tissue at surgical resection reliably identifies germline pathogenic variants in patients with HGSOC. Incorporating this approach may help triage patients for clinical genetics assessment. Full article
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6 pages, 2063 KB  
Interesting Images
Perineurial Malignant Peripheral Nerve Sheath Tumor of the Cauda Equina: Diagnostic Challenge
by Tomonori Kawasaki, Tomoaki Torigoe, Takuya Watanabe, Satoshi Kanno, Masataka Hirasaki, Arisa Kokubo, Kojiro Onohara, Masanori Wako, Tetsuhiro Hagino and Jiro Ichikawa
Diagnostics 2025, 15(21), 2697; https://doi.org/10.3390/diagnostics15212697 (registering DOI) - 24 Oct 2025
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas with an extremely rare perineurial subtype. Herein, we present a case of a perineurial MPNST in the cauda equina. Clinically and radiologically, a mass extending from within the spinal canal at the L5 level [...] Read more.
Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas with an extremely rare perineurial subtype. Herein, we present a case of a perineurial MPNST in the cauda equina. Clinically and radiologically, a mass extending from within the spinal canal at the L5 level to outside the intervertebral foramen was identified, raising suspicion of a neurogenic tumor as the primary diagnosis. Computed tomography-guided biopsy suggested an intermediate- to low-grade malignancy; however, a definitive diagnosis could not be established. Two years later, worsening neurological symptoms prompted further imaging, which revealed significant tumor growth and bone invasion. Open biopsy was performed to obtain a definitive diagnosis of perineurial MPNST. MPNSTs lack distinctive imaging features and are generally diagnosed based on a combination of radiological and histopathological findings. Although MPNSTs have a poor prognosis, the perineurial subtype is considered to have a relatively favorable outcome. Given these factors, early diagnosis followed by surgical resection or radiation therapy is recommended. Full article
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14 pages, 1287 KB  
Article
Comparative Evaluation of Two Dynamic Navigation Systems vs. Freehand Approach and Different Operator Skills in Endodontic Microsurgery: A Cadaver Study
by Umberto Gibello, Elina Mekhdieva, Mario Alovisi, Luca Cortese, Andrea Cemenasco, Anna Cassisa, Caterina Chiara Bianchi, Vittorio Monasterolo, Allegra Comba, Andrea Baldi, Vittorio Fenoglio, Elio Berutti and Damiano Pasqualini
Appl. Sci. 2025, 15(21), 11405; https://doi.org/10.3390/app152111405 (registering DOI) - 24 Oct 2025
Abstract
Background/Objectives: The purpose of the study is to determine and compare the accuracy and efficiency of two dynamic navigation systems (DNS)—Navident (ClaroNav, Canada) and X-Guide (Nobel Biocare, Switzerland)—vs. a free-hand (FH) approach in performing endodontic microsurgery (EMS) on human cadavers. Methods: a total [...] Read more.
Background/Objectives: The purpose of the study is to determine and compare the accuracy and efficiency of two dynamic navigation systems (DNS)—Navident (ClaroNav, Canada) and X-Guide (Nobel Biocare, Switzerland)—vs. a free-hand (FH) approach in performing endodontic microsurgery (EMS) on human cadavers. Methods: a total of 119 roots of six cadavers were randomly divided into three groups (Navident/X-Guide/FH). The cadavers’ jaws were scanned pre-operatively with computed tomography. The DICOM data were uploaded and digitally managed with software interfaces for registration, calibration, and virtual planning of EMS. Osteotomy was performed under DNS control and using a dental operating microscope (FH control group). Post-operative scans were taken with same settings as preoperative. Accuracy was then determined by comparing pre- and post-scans of coronal and apical linear, angular deviation, angle, length, and depth of apical resection. Efficiency was determined by measuring the procedural time of osteotomy, apicectomy, retro-cavity preparation, the volume of substance, and cortical bone loss, as well as iatrogenic complications. Outcomes were also evaluated in relation to different operators’ skill levels. Descriptive statistics and inferential analyses were conducted using R software (4.2.1). Results: DNS demonstrated better efficiency in osteotomy and apicectomy, second only to FH in substance and cortical bone loss. Both DNS approaches had similar accuracy. Experts were faster and more accurate than non-experts in FH, apart from resection angle, length and depth, and retro-cavity preparation time, for which comparison was not statistically significant. The Navident and X-guide groups had similar trends in increasing efficiency and accuracy of EMS. All complications in the FH group were performed by non-experts. The X-guide group demonstrated fewer complications than the Navident group. Conclusions: Both DNS appear beneficial for EMS in terms of accuracy and efficacy in comparison with FH, also demonstrating the decreasing gap of skill expertise between experts and novice operators. Through convenient use X-guide diminishes the level of iatrogenic complications compared to Navident. Full article
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26 pages, 1535 KB  
Article
Prognostic and Predictive Significance of B7-H3 and CD155 Expression in Gastric Cancer Patients
by Ozlem Dalda, Zehra Bozdag, Sami Akbulut, Hasan Gokce, Yasin Dalda, Ayse Nur Akatli and Mustafa Huz
Diagnostics 2025, 15(21), 2695; https://doi.org/10.3390/diagnostics15212695 (registering DOI) - 24 Oct 2025
Abstract
Background/Objectives: This study aimed to characterize the expression patterns of B7 homolog 3 (B7-H3) and cluster of differentiation 155 (CD155), two immune-related transmembrane glycoproteins, in resectable gastric adenocarcinoma and to elucidate their clinicopathological, prognostic, and molecular implications. Methods: The study included [...] Read more.
Background/Objectives: This study aimed to characterize the expression patterns of B7 homolog 3 (B7-H3) and cluster of differentiation 155 (CD155), two immune-related transmembrane glycoproteins, in resectable gastric adenocarcinoma and to elucidate their clinicopathological, prognostic, and molecular implications. Methods: The study included 112 patients who underwent gastrectomy for gastric adenocarcinoma between 2020 and 2025, along with 30 samples of normal gastric tissue obtained from sleeve gastrectomy specimens. Histological subtype, grade of differentiation, TNM stage, and invasion parameters were re-evaluated. Immunohistochemical expression of B7-H3 and CD155 was quantified for membranous, stromal and membranous/cytoplasmic staining patterns. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed on 29 tumor and 25 normal samples to confirm mRNA expression levels, with fold change ≥2 considered biologically significant upregulation and ≤0.5 considered downregulation. Machine learning models were developed to predict metastasis and mortality based on clinical and immunohistochemical features. Results: 78.5% of tumors were at an advanced stage (T3–T4), and metastasis was present in 22.3% of patients. Perineural invasion (PNI) and lymphovascular invasion (LVI) were observed in 67.9% and 88.4% of cases, respectively. Increased B7-H3 and CD155 expression were significantly associated with advanced tumor stage, metastasis, and the presence of PNI and LVI (all p < 0.05). In metastatic tumors, median membranous B7-H3, stromal B7-H3, and CD155 scores were 60, 130, and 190, respectively, compared with 20, 90, and 120 in non-metastatic tumors. A significant positive correlation was found between stromal B7-H3 and CD155 expression (r = 0.384, p < 0.001), indicating parallel upregulation. Quantitative RT-PCR confirmed significant overexpression of both genes in tumor tissues relative to normal controls. B7-H3 was upregulated in 75.9% and CD155 in 58.6% of samples, with co-upregulation in 55.2%. Fold-change levels were markedly higher in metastatic versus non-metastatic cases (B7-H3: 7.69-fold vs. 3.04-fold; CD155: 7.44-fold vs. 1.79-fold). ML analysis using the XGBoost model achieved 91.1% accuracy for metastasis prediction (F1-score 0.800). Key variables included pathological T4b stage, perineural invasion, N3b status, T4a stage, and CD155 score. The mortality model yielded 86.7% accuracy (F1-score 0.864), with metastasis, differentiation status, nodal involvement, age, lymph node ratio, and perineural invasion emerging as principal predictors. Conclusions: Combined evaluation of B7-H3 and CD155, supported by immunohistochemical staining and RT-PCR quantification of B7-H3 and CD155 mRNA expression levels, provides meaningful prognostic insights and supports their potential as dual molecular biomarkers for aggressive gastric adenocarcinoma phenotypes. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 404 KB  
Article
Endoscopic Ultrasound for Nodal Staging in Patients with Resectable Cholangiocarcinoma
by David M. de Jong, Lydi M. J. W. van Driel, Sundeep Lakhtakia, Mohan Ramchandani, Sana Fathima Memon, Abhishek Tyagi, Parathasarathy Kumaraswamy, Shreeyash Modak, Anuradha Sekaran, Marco J. Bruno, Duvvur Nageshwar Reddy and Hardik Rughwani
J. Clin. Med. 2025, 14(21), 7545; https://doi.org/10.3390/jcm14217545 (registering DOI) - 24 Oct 2025
Abstract
Background: Lymph node (LN) involvement is a negative prognostic factor for patients with cholangiocarcinoma (CCA). Preoperative assessment of the LN could potentially aid therapy decision making. Endoscopic ultrasound (EUS) can be used to sample suspicious LN. The aim of this study was [...] Read more.
Background: Lymph node (LN) involvement is a negative prognostic factor for patients with cholangiocarcinoma (CCA). Preoperative assessment of the LN could potentially aid therapy decision making. Endoscopic ultrasound (EUS) can be used to sample suspicious LN. The aim of this study was to evaluate the clinical impact of EUS for suspicious LN in patients with presumed resectable CCA. Methods: In this single-center cohort study, patients with potentially resectable CCA who underwent preoperative linear EUS between 2019 and 2024 were retrospectively included. The primary aims were the percentage of malignant LN detected and the clinical impact of EUS, which was defined as the percentage of patients who were precluded from surgical exploration due to pathologically confirmed LN metastases found with EUS tissue acquisition (EUS-TA). The secondary aim was the complication rate of EUS-TA. Results: A total of 135 patients were included, of whom 12 (8.9%) had intrahepatic CCA (iCCA), 65 (48.1%) had perihilar CCA (pCCA), 13 had (9.6%) middle bile duct CCA (mCCA), and 45 (33.3%) had distal CCA (dCCA). Across 148 EUS procedures, 139 LNs were identified, and EUS-TA was performed on 63 LNs among 55 patients. LN metastases were detected by EUS-TA for iCCA, pCCA, mCCA, and dCCA, in 25%, 6.2%, 15.4%, and 4.4%, respectively. EUS and EUS-TA influenced surgical work-up for iCCA, pCCA, mCCA, and dCCA in 25%, 1.5%, 15.4%, and 0.0%, respectively. No complications associated with EUS were noted. Conclusions: Preoperative EUS for nodal staging had an important clinical impact in patients with presumed resectable iCCA and mCCA, but less for pCCA and dCCA. Further prospective studies should investigate whether systematic nodal staging with EUS could improve preoperative decision making even further. Full article
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24 pages, 1035 KB  
Systematic Review
Metabolic Imaging as Future Technology and Innovation in Brain-Tumour Surgery: A Systematic Review
by Thomas Kapapa, Ralph König, Jan Coburger, Benjamin Mayer, Kornelia Kreiser and Volker Rasche
Curr. Oncol. 2025, 32(11), 597; https://doi.org/10.3390/curroncol32110597 (registering DOI) - 24 Oct 2025
Abstract
Background: Standard imaging in neurosurgery often fails to visualize infiltrative tumor regions that extend beyond contrast enhancement. Metabolic imaging using hyperpolarized 13C-MRI may offer new intraoperative insights into tumor biology. Objective: To systematically assess the clinical and technical evidence on hyperpolarized MRI for [...] Read more.
Background: Standard imaging in neurosurgery often fails to visualize infiltrative tumor regions that extend beyond contrast enhancement. Metabolic imaging using hyperpolarized 13C-MRI may offer new intraoperative insights into tumor biology. Objective: To systematically assess the clinical and technical evidence on hyperpolarized MRI for metabolic tumour characterization in patients with malignant brain tumors. Eligibility criteria: We included original human studies reporting on hyperpolarized 13C-MRI for perioperative and diagnostic use in brain tumor patients. Reviews, animal studies, and technical-only reports were excluded. Information sources: Searches were conducted in PubMed, Embase, and Web of Science on 26 December 2024. Risk of bias: Methodological quality was assessed using the QUADAS-2 tool. Synthesis of results: A qualitative synthesis was performed, and where feasible, random-effects meta-analysis was used to calculate standardized mean differences (SMDs) and heterogeneity statistics. Results: Three studies (n = 15 patients) met inclusion criteria. The bicarbonate-to-pyruvate ratio showed a significant difference between tumor and non-tumour brain (SMD = 1.34, p = 0.002), whereas pyruvate-to-lactate ratio (kPL) values showed minimal difference (SMD = 0.06, p = 0.730). Asmall effect was observed for kPL between tumor and normal-appearing white matter (SMD = –0.33). One study provided qualitative data only. Overall heterogeneity was high (I2 = 69.4%). Limitations: Limitations include small sample sizes, heterogeneous methodologies, and limited availability of patient-level data. Interpretation: Hyperpolarized 13C-MRI shows metabolic differentiation between tumor and healthy tissue in certain parameters, especially bicarbonate metabolism. While promising, the technology requires further clinical validation before routine intraoperative application. Full article
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12 pages, 548 KB  
Article
The Prognostic Role of Para-Aortic Lymph Node Metastasis in Patients with Resected Pancreatic Adenocarcinoma
by Maximilian Brunner, Lena Kitzke, Anke Mittelstädt, Susanne Merkel, Georg F. Weber, Robert Grützmann and Christian Krautz
Cancers 2025, 17(21), 3418; https://doi.org/10.3390/cancers17213418 (registering DOI) - 24 Oct 2025
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Abstract
Background: This study aimed to evaluate the prognostic significance of para-aortic lymph node dissection (PALND) during pancreatic head resection and the impact of para-aortic lymph node metastasis (PALN+) on survival outcomes in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective analysis [...] Read more.
Background: This study aimed to evaluate the prognostic significance of para-aortic lymph node dissection (PALND) during pancreatic head resection and the impact of para-aortic lymph node metastasis (PALN+) on survival outcomes in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective analysis was conducted on 198 patients who underwent primary pancreatic head resection for PDAC at the University Hospital Erlangen between 2003 and 2022. Patients were stratified based on the presence or absence of PALND and PALN metastases, and their clinicopathological characteristics and survival outcomes were compared. Results: Of the 198 patients, 113 (57%) underwent additional PALND. PALND itself had no significant impact on overall survival (OS) or disease-free survival (DFS) compared to those without PALND. Among patients who underwent PALND, 17 (15%) had PALN metastases (PALN+). PALN+ patients exhibited significantly worse pathological features, including a higher rate of regional lymph node metastases (pN+), lymphovascular invasion (L1) and vascular invasion (V1). Survival analysis showed that PALN+ was associated with significantly poorer OS (8.7 vs. 29.3 months, p < 0.001) and DFS (3.8 vs. 17.0 months, p < 0.001). In multivariate analysis, PALN+ was confirmed as an independent prognostic factor for both OS (HR 1.9 [1.0–3.6], p = 0.035) and DFS (HR 2.2 [1.2–4.0], p = 0.006). Conclusions: While PALND does not impact survival outcomes in PDAC, it plays a crucial role in identifying PALN+ patients, who have significantly worse prognoses. PALN status should be integrated into clinical decision-making, particularly when considering intensified adjuvant therapy. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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10 pages, 1040 KB  
Case Report
Primary Intracranial Meningeal Melanocytoma with Malignant Transformation: A Case Report and Comparison of Early Versus Late Immunotherapy Interventions
by Yi-Qi Zhang, Kun-Ming Rau, Cheng-Loong Liang, Yu-Duan Tsai, He-Tai Jheng and Kuo-Wei Wang
Curr. Oncol. 2025, 32(11), 595; https://doi.org/10.3390/curroncol32110595 - 24 Oct 2025
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Abstract
Primary meningeal melanocytoma is an uncommon, pigmented neoplasm that rarely undergoes malignant transformation, and therapeutic guidelines remain undefined. We report a 43-year-old woman who initially presented with a sudden headache and a right temporal intraparenchymal mass. Subtotal resection revealed a melanocytoma (WHO grade [...] Read more.
Primary meningeal melanocytoma is an uncommon, pigmented neoplasm that rarely undergoes malignant transformation, and therapeutic guidelines remain undefined. We report a 43-year-old woman who initially presented with a sudden headache and a right temporal intraparenchymal mass. Subtotal resection revealed a melanocytoma (WHO grade I); residual tumor was treated with Gamma Knife. About 15 months later, she deteriorated rapidly due to malignant transformation with cerebral hemorrhage and spinal leptomeningeal metastasis. Pembrolizumab was initiated within four weeks of the malignant diagnosis and produced transient neurological improvement. Due to symptomatic progression, ipilimumab plus nivolumab was commenced and achieved temporary radiographic stabilization, but the patient succumbed to diffuse progression later. Including this case, only five intracranial melanocytomas with malignant transformation treated with immune checkpoint inhibitors have been reported. Our experience supports initiating immunotherapy promptly after malignant transformation and suggests that sequential dual-agent blockade may modestly extend disease control. Full article
(This article belongs to the Section Neuro-Oncology)
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16 pages, 619 KB  
Article
Indications, Trends and Outcomes in Pediatric Lung Resections: A 12-Year Study in a Tertiary Referral Center
by Gloria Mandrile, Giulia Barone, Vittorio Guerriero, Girolamo Mattioli and Michele Torre
Children 2025, 12(11), 1438; https://doi.org/10.3390/children12111438 - 23 Oct 2025
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Abstract
Background: Lung resections in children are rare but critical for congenital lung malformations (CLMs) and acquired pathologies; few studies have analyzed the full spectrum of indications. This study evaluated indications, complications, outcomes, and temporal trends in a tertiary pediatric center. Methods: [...] Read more.
Background: Lung resections in children are rare but critical for congenital lung malformations (CLMs) and acquired pathologies; few studies have analyzed the full spectrum of indications. This study evaluated indications, complications, outcomes, and temporal trends in a tertiary pediatric center. Methods: We retrospectively analyzed patients who underwent lung resection (2012–2024), focusing on indications, approaches, complications, and outcomes. Comparisons between pathologies (CLMs vs. acquired pathologies), approaches (thoracoscopy vs. thoracotomy), an temporal trends were evaluated. Results: Among 160 patients (mean age: 7.8 years), acquired lesions (68.6%) were more common than CLMs (31.4%), predominating in children under 8 years. Compared with thoracotomy, thoracoscopy (72.8% of cases, conversion rate: 22.8%) was correlated with shorter operative times (p < 0.001) and hospital stays (p = 0.001). The complication rate was 19.5%, with 71.9% of patients achieving disease-free, asymptomatic status at follow-up. Risk factors for conversion from thoracoscopy to open surgery included intraoperative adhesions (p = 0.003), underlying pathology (p = 0.013), and age < 8 years (p = 0.017). Compared with acquired lesions, CLMs were associated with fewer complications (14.3% vs. 23.1%, p = 0.041) and more favorable outcomes (89.2% vs. 64.7%; p < 0.05). Over time, the use of thoracoscopy increased (p = 0.012), with reduced operative time (p = 0.005); complication and outcome rates remained stable. Conclusions: Pediatric lung resections address diverse pathologies; outcomes are linked to the pathology, and CLMs are associated with lower complication rates in our cohort. Thoracoscopy has progressively become the preferred approach in the last decade, offering advantages particularly in postoperative recovery, though its success depends on careful, pathology-driven patient selection. Full article
(This article belongs to the Special Issue Challenges and Innovations in Pediatric General Surgery)
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16 pages, 254 KB  
Review
Advanced Neuroimaging and Emerging Systemic Therapies in Glioblastoma: Current Evidence and Future Directions
by Ilona Bar-Letkiewicz, Anna Pieczyńska, Małgorzata Dudzic, Michał Szkudlarek, Krystyna Adamska and Katarzyna Hojan
Biomedicines 2025, 13(11), 2597; https://doi.org/10.3390/biomedicines13112597 - 23 Oct 2025
Viewed by 224
Abstract
Despite technological progress, glioblastoma (GBM) continues to confer dismal prognoses. Modern neuroimaging methods are assuming an ever greater role in diagnosing and monitoring brain tumors. This review shows current neuroimaging approaches and systemic therapeutic strategies for glioblastoma, with a focus on emerging and [...] Read more.
Despite technological progress, glioblastoma (GBM) continues to confer dismal prognoses. Modern neuroimaging methods are assuming an ever greater role in diagnosing and monitoring brain tumors. This review shows current neuroimaging approaches and systemic therapeutic strategies for glioblastoma, with a focus on emerging and innovative treatments. Advances in multiparametric magnetic resonance imaging—MRI (diffusion, perfusion, and spectroscopy) and novel positron emission tomography (PET) tracers, complemented by radiomics and artificial intelligence (AI), now refine tumor delineation, differentiate progression from treatment effects, and may help predict treatment responses. Maximal safe resection followed by chemoradiotherapy with temozolomide remains the standard, with the greatest benefit seen in O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. Bevacizumab and other targeted modalities offer mainly progression-free, not overall survival, gains. Immune checkpoint inhibitors (e.g., nivolumab) have not improved survival in unselected GBM, while early multi-antigen CAR-T (chimeric antigen receptor T-cell) strategies show preliminary bioactivity without established durability. While actionable alterations (NTRK fusions and BRAF V600E) justify selective targeted therapy trials, their definitive benefit in classical GBM is unproven. Future priorities include harmonized imaging molecular integration, AI-driven prognostic modeling, novel PET tracers, and strategies to breach or transiently open the blood–brain barrier to enhance drug delivery. Convergence of these domains may convert diagnostic precision into improved patient outcomes. Full article
(This article belongs to the Special Issue Medical Imaging in Brain Tumor: Charting the Future)
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