Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems.

Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity is a crucial parameter for designing drug delivery devices. Nanofibrous membranes loaded with different percentages of Dacarbazine (the drug of choice for melanoma) and a synthetic derivative of Dacarbazine were produced and compared to membranes loaded with AuM1, a highly active Au-complex with low affinity to the matrix. AFM morphologies showed that the surface profile of nanofibers loaded with affine substances is similar to one of the unloaded systems, thanks to the nature of the matrix-filler interaction. FTIR analyses proved the efficacy of the interaction between the amidic group of the Dacarbazine and the polycaprolactone. In AuM1-loaded membranes, because of the weak matrix-filler interaction, the complex is mainly aggregated in nanometric domains on the nanofiber surface, which manifests a nanometric roughness. Consequently, the release profiles follow a Fickian behavior for the Dacarbazine-based systems, whereas a two-step with a highly prominent burst effect was observed for AuM1 systems. The performed antitumoral tests evidence the high-cytotoxic activity of the electrospun systems against melanoma cell lines, proving that the synthetic substances are more active than the commercial dacarbazine.

Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells.

Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl- or I-) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 µM, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 µM. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead.

Electrospun Membranes Designed for Burst Release of New Gold-Complexes Inducing Apoptosis of Melanoma Cells.

Two non-commercial metallic Au-based complexes were tested against one of the most aggressive malignant melanomas of the skin (MeWo cells), through cell viability and time-lapse live-cell imaging system assays. The tests with the complexes were carried out both in the form of free metallic complexes, directly in contact with the MeWo cell line culture, and embedded in fibers of Polycaprolactone (PCL) membranes produced by the electrospinning technique. Membranes functionalized with complexes were prepared to evaluate the efficiency of the membranes against the melanoma cells and therefore their feasibility in the application as an antitumoral patch for topical use. Both series of tests highlighted a very effective antitumoral activity, manifesting a very relevant cell viability inhibition after both 24 h and 48 h. In the case of the AuM1 complex at the concentration of 20 mM, melanoma cells completely died in this short period of time. A mortality of around 70% was detected from the tests performed using the membranes functionalized with AuM1 complex at a very low concentration (3 wt.%), even after 24 h of the contact period. The synthesized complexes also manifest high selectivity with respect to the MeWo cells. The peculiar structural and morphological organization of the nanofibers constituting the membranes allows for a very effective antitumoral activity in the first 3 h of treatment. Experimental points of the release profiles were perfectly fitted with theoretical curves, which easily allow interpretation of the kinetic phenomena occurring in the release of the synthesized complexes in the chosen medium.

A paraneoplastic limbic encephalitis from an anorectal small cell neuroendocrine carcinoma: a case report.

BACKGROUND: Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in cancer patients. PLE is difficult to diagnose and presents a variable response to treatment, depending on the characteristics of the tumor and neuronal autoantibodies. CASE PRESENTATION: A 64-year-old, Caucasian, non-smoker man presented with a rapidly developing cognitive impairment, personality change, spatial disorientation, and short-term memory loss associated with anorexia and cervical and inguinal lymph nodes. The 18F-FDG PET scan documented intensely hypermetabolic lymph nodes, which histologically corresponded to a metastasis from a small cell neuroendocrine carcinoma. The brain MRI revealed a high T2-weighted FLAIR signal of the hippocamps, consisted with a PLE. The presence of anti-neuronal Hu antibodies confirmed the diagnosis. The patient underwent plasmapheresis, associated to a systemic chemotherapy resulting in a partial and temporary improvement of the neurological symptoms. Four cycles of intravenous immunoglobulins were also necessary. After six cures of chemotherapy, the lymph node metastases regressed. However, a new anorectal lesion was detected and was histologically confirmed as a primary small cell neuroendocrine carcinoma, which was treated with concomitant chemoradiotherapy. At the end of this treatment, the patient showed a rapid tumor progression leading to his death. CONCLUSIONS: This case highlights the rare entity, PLE, which is difficult to diagnose and manage. In addition, this is the first published case of PLE associated with an anorectal small cell neuroendocrine carcinoma, which appeared after completion of systemic chemotherapy.

Psychological and social determinants of physical activity from diagnosis to remission among French cancer patients (PERTINENCE): protocol for a mixed-method study.

BACKGROUND: Many effective physical activity (PA) interventions have focused on individual factors or a single theoretical model, limiting our understanding of the determinants of PA practice and their interactions in the cancer trajectory. The present mixed-method study aims to capture social and psychological determinants of PA practice from diagnosis to remission among cancer patients, and to identify key levers for PA practice. METHODS/DESIGN: A nested sequential mixed-method design QUAN (QUAL+QUAL) will be used, with qualitative studies embedded in the quantitative study to broaden our understanding of the determinants of PA practice. The design is sequential, since qualitative data on medical staff will be collected before patient inclusion (Phase 1), followed by quantitative patient data collection lasting one year (Phase 2) and a final qualitative data collection one year after inclusion (Phase 3). Phase 1 will be a case study in the two hospitals involved in the study, exploring knowledge of and support for PA practice among medical staff. Through interviews and documental analyses, the PA support dynamic will be evaluated with regard to PA prescription. Phase 2 will be a one-year observational study among 693 cancer patients. Quantitative medical, social, dispositional and psychological data, PA practices and preferences, will be collected at diagnosis, and six months and one year thereafter. Phase 3 will be a retrospective study, evaluating societal and policy factors, as well as unexpected factors playing a role in PA levels and preferences among cancer patients. For this phase thirty patients will be identified six months after inclusion on the basis of their PA profiles. Quantitative data will provide the main dataset, whilst qualitative data will complete the picture, enabling determinants of PA practice and their interactions to be captured throughout the cancer trajectory. DISCUSSION: The present study aims to identify key levers and typical trajectories for PA practice among cancer patients, adapted to different times in the course of cancer and taking into account "what works", "for whom", "where" and "how". The challenge is the tailoring of PA interventions to patients at different times in their cancer trajectory, and the implication of medical staff support. TRIAL REGISTRATION: Clinical Trial NCT03919149 , 18 April 2019. Prospectively registered.

Taurolidine/Citrate Lock Therapy for Primary Prevention of Catheter-Related Infections in Cancer Patients: Results of a Prospective, Randomized, Phase IV Trial (ATAPAC).

BACKGROUND: Totally implantable venous access port (TIVAP)-related infections (RIs) remain a serious health problem in cancer patients receiving an intravenous (i.v.) therapy. PATIENTS AND METHODS: The ATAPAC study was a prospective, randomized, monocentric, phase IV trial evaluating the efficacy of taurolidine lock solution versus standard saline solution for primary TIVAP-RI prevention in nonhematological cancer patients receiving i.v. chemotherapy. The primary endpoint was the TIVAP-RI incidence rate. From December 2014 to September 2015, 163 patients were enrolled in the study (taurolidine: n = 86 vs. CONTROL: n = 77). Four patients in the control group (5%) had a Staphylococcus epidermidis TIVAP-RI, and 1 patient (1%) in the taurolidine group had a Staphylococcus aureus infection. The TIVAP-RI incidence rate was 0.4 and 0.1‰ catheter-days, respectively (p = 0.21). The infection-free TIVAP survival was not statistically significant (p = 0.09). TIVAP-RI required a total of 22 hospitalization days in the taurolidine group versus 106 days in the control arm with associated costs of EUR 4,849 and EUR 36,020, respectively. Taurolidine-related toxicity was transitory and classified as grade I. CONCLUSIONS: The ATAPAC trial did not show a significant risk-infection reduction by TauroLock™. A larger, prospective, randomized trial is needed to assess TauroLock efficacy for primary TIVAP-RI prevention in low-risk cancer patients.

A late, solitary brain metastasis of epithelial ovarian carcinoma.

BACKGROUND: Brain metastasis from epithelial ovarian cancer (EOC) is very rare with a reported incidence of less than 2%. It is usually associated with a poor prognosis that is related to several factors, the most important including: single vs multiple lesions, performance status, platinum-sensitive disease, tumor grade, extracranial disease, and multimodal approach treatment. At the time of diagnosis, an extracranial disease is found in over half of patients. The most common histology is the serous type. The median time from primary diagnosis to development of cerebral lesions is directly correlated to initial tumor grade and stage. Several therapeutic approaches can be proposed, including best supportive care +/- corticosteroids, surgery, radiotherapy and chemotherapy. A multimodal therapy approach may achieve an improved outcome and should therefore be utilized whenever applicable. CASE PRESENTATION: We present the case of a patient with a solitary brain metastasis which appeared 11 years after a locally advanced and aggressive EOC (FIGO stage III C) and which totally regressed after surgery and adjuvant chemotherapy. Clinically, she showed progressive headaches, decreased visual acuity, balance and memory disorders associated with a confusional state. Brain CT scan and MRI documented a solitary, necrotic lesion in the left central parietal region with an important cerebral surrounding edema and initial cranial herniation. No other extracranial metastases were observed at the PET scan. Laboratory tests were in the normal range and CA 125 was moderatly increased at 81 UI/ml. The patient underwent surgical removal of tumor lesion, post-surgical whole-brain radiotherapy (WBRT) and systemic chemotherapy with carboplatin alone for six cycles. At a follow-up of 13 months, she is alive, in good clinical condition and tumor progression free. CONCLUSION: The peculiarity of this case relies on the isolated brain relapse of a BRCA-1/BRCA-2 non-mutated EOC, which is uncommon and rare, and to the very long time, of 11 years, from diagnosis of primary cancer and development of brain metastasis. A multimodal, aggressive approach of this isolated brain metastasis led to a complete and prolonged tumor control.

Verification of the Self-Healing Ability of PP-co-HUPy Copolymers in Epoxy Systems.

This work concerns the verification of the self-healing ability of PP-co-HUPy copolymers dispersed in epoxy systems. PP is the acronym for the Poly-PEGMA polymer, and HUPy refers to the HEMA-UPy copolymers based on ureidopyrimidinone (UPy) moieties. In particular, this work aims to verify whether this elastomer characterized by an intrinsic self-healing ability can activate supramolecular interactions among polymer chains of an epoxy resin, as in the elastomer alone. The elastomer includes a class of polyethylene glycol monomethyl ether methacrylate-based copolymers, with different percentages of urea-N-2-amino-4-hydroxy-6-methyl pyrimidine-N'-(hexamethylene-n-carboxyethyl methacrylate) (HEMA-UPy) co-monomers. The self-healing capability of these copolymers based on possible quadruple hydrogen bond interactions between polymer chains has been verified. The formulated epoxy samples did not show self-healing efficiency. This can be attributed to the formation of phase segregation that originates during the curing process of the samples, although the PP-co-HUPy copolymers are completely soluble in the liquid epoxy matrix EP. The morphological investigation highlighted the presence of crystals of PP-co-HUPy copolymers, which are in greater quantity in the sample containing the highest weight percentage (7.8 wt%) of HUPy units. Furthermore, the crystals act as promotors for increasing the curing degree (DC) of the epoxy systems containing HUPy units. DC goes from 91.6% for EP to 96.1% and 95.4% for the samples containing weight percentages of 2.5 and 7.8 wt% of HUPy units, respectively. Dynamic mechanical analysis (DMA) shows storage modulus values for epoxy systems containing PP-co-HUPy units lower than that of the unfilled resin EP. The values of maximum in Tan δ (Tg), representing the temperature at which the glass transition occurs, are 220 for the unfilled resin EP, 228 for the sample containing 2.5 wt% of HEMA-UPy units, and 211 for the sample containing 7.8 wt% of HEMA-UPy units.

Correction: Gorrasi et al. Fabrication and Characterization of Electrospun Membranes Based on "Poly(ε-caprolactone)", "Poly(3-hydroxybutyrate)" and Their Blend for Tunable Drug Delivery of Curcumin. Polymers 2020, 12, 2239.

In the original publication [...].

Multifunctional Properties of Polyhedral Oligomeric Silsesquioxanes (POSS)-Based Epoxy Nanocomposites.

In this study, a tetrafunctional epoxy resin was loaded with 5 wt% of three different types of polyhedral oligomeric silsesquioxane (POSS) compounds, namely, DodecaPhenyl POSS (DPHPOSS), Epoxycyclohexyl POSS (ECPOSS), Glycidyl POSS (GPOSS), and 0.5 wt% of multi-walled carbon nanotubes (CNTs) in order to formulate multifunctional structural nanocomposites tailored for aeronautic and aerospace applications. This work aims to demonstrate how the skillful combination of desired properties, such as good electrical, flame-retardant, mechanical, and thermal properties, is obtainable thanks to the advantages connected with nanoscale incorporations of nanosized CNTs with POSS. The special hydrogen bonding-based intermolecular interactions between the nanofillers have proved to be strategic in imparting multifunctionality to the nanohybrids. All multifunctional formulations are characterized by a Tg centered at values close to 260 °C, fully satisfying structural requirements. Infrared spectroscopy and thermal analysis confirm the presence of a cross-linked structure characterized by a high curing degree of up to 94% and high thermal stability. Tunneling atomic force microscopy (TUNA) allows to detect the map of the electrical pathways at the nanoscale of the multifunctional samples, highlighting a good dispersion of the carbon nanotubes within the epoxy resin. The combined action of POSS with CNTs has allowed to obtain the highest values of self-healing efficiency if compared to those measured for samples containing only POSS in the absence of CNTs.

Nanometric Mechanical Behavior of Electrospun Membranes Loaded with Magnetic Nanoparticles.

This work analyzes on nanoscale spatial domains the mechanical features of electrospun membranes of Polycaprolactone (PCL) loaded with Functionalized Magnetite Nanoparticles (FMNs) produced via an electrospinning process. Thermal and structural analyses demonstrate that FMNs affect the PCL crystallinity and its melting temperature. HarmoniX-Atomic Force Microscopy (H-AFM), a modality suitable to map the elastic modulus on nanometric domains of the sample surface, evidences that the FMNs affect the local mechanical properties of the membranes. The mechanical modulus increases when the tip reveals the magnetite nanoparticles. That allows accurate mapping of the FMNs distribution along the nanofibers mat through the analysis of a mechanical parameter. Local mechanical modulus values are also affected by the crystallinity degree of PCL influenced by the filler content. The crystallinity increases for a low filler percentage (<5 wt.%), while, higher magnetite amounts tend to hinder the crystallization of the polymer, which manifests a lower crystallinity. H-AFM analysis confirms this trend, showing that the distribution of local mechanical values is a function of the filler amount and crystallinity of the fibers hosting the filler. The bulk mechanical properties of the membranes, evaluated through tensile tests, are strictly related to the nanometric features of the complex nanocomposite system.

Role of MWCNTs Loading in Designing Self-Sensing and Self-Heating Structural Elements.

This work proposes nanocomposites with carbon nanotubes characterized by self-sensing and self-heating properties. Recently, a growing interest in these two properties has been found in many industrial sectors, especially in the aerospace and automotive fields. While the self-sensing function allows diagnosing the presence of micro-damage in the material thanks to the detection of residual resistance, the self-heating function is exploited to properly tune the heating performance in terms of the heating rate and final temperature values. An electrical percolation value of around 0.5% by weight of carbon nanotubes was found by electrical characterization. The AC conductivity of the nanocomposites, in the range of 100 Hz to 1 MHz, evidences that beyond a CNTs amount of 0.5% wt/wt, they are characterized by a purely resistive behavior. The self-sensing analysis displayed a gauge factor value of 4.1. The solid thermal stability up to 300 °C makes the material suitable as a heating element at high temperatures. SEM investigations and temperature maps evidence a good dispersion of the conductive filler in the epoxy matrix and, consequently, good isotropy in heat distribution. As regards the trend of electrical resistance by varying the temperature, the electro-thermal investigation has shown the presence of both Positive Temperature Coefficient (PTC) and Negative Temperature Coefficient (NTC) behaviors with a predominance of NTC as soon as the temperature becomes closer to the glass transition temperature of the epoxy resin.

Contribution of peripheral blood mononuclear cells isolated by advanced filtration system to myogenesis of human bone marrow mesenchymal stem cells co-cultured with myoblasts.

Background: Contribution of peripheral blood mononuclear cells (PBMCs) in myogenesis is still under debate, even though blood filtration systems are commonly used in clinical practice for successfully management of critic limb ischemia. Objectives: A commercial blood filter used for autologous human PBMC transplantation procedures is characterized and used to collect PBMCs, that are then added to well-established 2D in vitro myogenic models assembled with a co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and skeletal myoblasts (hSkMs) whit the aim of investigating their potential contribution to stem cell myogenic commitment. Methods: A commercial blood filter was physically and chemically studied to understand its morphological characteristics and composition. PBMCs were concentrated using this system, further isolated by Ficoll-Paque density gradient centrifugation, and then added in an upper transwell chamber to a 2D co-culture of hBM-MSCs and hSkMs. Myogenic commitment was investigated by RT-PCR, immunofluorescence, and flow cytometry immunophenotyping. Cytokine levels were monitored by ELISA assay in culture media. Results: The blood filtration system was disassembled and appeared to be formed by twelve membranes of poly-butylene terephthalate fibers (diameters, 0.9-4.0 µm) with pore size distribution of 1-20 µm. Filter functional characterization was achieved by characterizing collected cells by flow cytometry. Subsequently, collected PBMCs fraction was added to an in-vitro model of hBM-MSC myogenic commitment. In the presence of PBMCs, stem cells significantly upregulated myogenic genes, such as Desmin and MYH2, as confirmed by qRT-PCR and expressed related proteins by immunofluorescence (IF) assay, while downregulated pro-inflammatory cytokines (IL12A at day 14) along the 21 days of culture. Novelty: Our work highlights chemical-physical properties of commercial blood filter and suggests that blood filtrated fraction of PBMC might modulate cytokine expression in response to muscle injury and promote myogenic events, supporting their clinical use in autologous transplantation.

A primary small cell neuroendocrine carcinoma (SCNC) of the oral cavity (cheek mucosa): Description of a case report.

BACKGROUND: Small cell neuroendocrine carcinoma (SCNC) of the oral cavity is a poorly differentiated, high-grade and very aggressive tumor with a poor prognosis. CASE DESCRIPTION: A 64-year-old, Caucasian, smoker man consulted for an ulcero-necrotic, exophytic, lesion of the right retromolar trigone. Haed&neck CT scan showed a right tonsillar tumor lesion. The 18F-PET scan confirmed the presence of a right, highly hypermetabolic tonsillar lesion and two homolateral, cervical lymph nodes. Histology and immunohistochemistry were consisted with the diagnosis of a primary SCNC of the oral cavity. As the tumor was locally advanced and unresectable, the patient underwent a definitive radio-chemotherapy with a cisplatin/etoposide combined regimen (4 cycles). The treatment was well tolerated and led to a complete tumor response. CONCLUSION: The particularity of this case relies on the rarity of the oral SCNC, its difficult and challenging diagnosis, and the complexity of its management that is not validated by large clinical trials, data being extrapolated from small cell lung cancer. In our case, the patient presenting a locally advanced tumor was treated by a combined radio-chemiotherapy leading to a complete tumor regression. The patient's follow up is too short to assess the real benefit of this treatment on overall survival.

Intravesical Gentamicin: An Option for Therapy and Prophylaxis against Recurrent UTIs and Resistant Bacteria in Neurogenic Bladder Patients on Intermittent Catheterization.

This is a retrospective study of our experience with Gentamicin intravesical instillation as therapy and prophylaxis in patients with lower urinary tract infections (UTIs) undergoing clean intermittent catheterization because of a neurogenic bladder. It is an alternative therapy when all other systemic treatments have failed as it is still an off-label prescription.

A fatal primary gastric melanoma treated by a double immunotherapy with ipilimumab/nivolumab: description of a case report.

Background: Primary gastric melanoma (GM) is a very uncommon tumor with a poor prognosis. Until now, only a few cases have been reported in the literature. Case Description: A 70-year-old, Caucasian, ex-smoker man, presented with asthenia, anorexia, and weight loss of 5 kg during the last 2 months. Biological test showed high levels of transaminases and a microcytic, hypochromic anemia. Whole body CT-scan documented a gastric tumor lesion with concomitant loco-regional lymph node and hepatic metastases. Histology was consisted with the diagnosis of a primary GM. A double immunotherapy with nivolumab and ipilimumab was started but, 2 weeks later, the patient presented an acute hepatic failure quickly leading to his death despite a high dose corticotherapy. Conclusions: The particularity of this case relies on the rarity of GM, its difficult diagnosis representing a clinical challenge, and the complexity of its management that is not validated by large clinical trials, data being extrapolated from the treatment protocols routinely used in cutaneous melanoma. In our case, the patient died 2 weeks after the first cycle of a nivolumab/ipilimumab combined treatment for an acute hepatic failure that could be related to a treatment toxicity or a tumor hyperprogression. The patient's survival was very short not allowing any accurate evaluation of the efficacy of this therapy.

Electromagnetically Stimuli-Responsive Nanoparticles-Based Systems for Biomedical Applications: Recent Advances and Future Perspectives.

Nanoparticles (NPs) in the biomedical field are known for many decades as carriers for drugs that are used to overcome biological barriers and reduce drug doses to be administrated. Some types of NPs can interact with external stimuli, such as electromagnetic radiations, promoting interesting effects (e.g., hyperthermia) or even modifying the interactions between electromagnetic field and the biological system (e.g., electroporation). For these reasons, at present these nanomaterial applications are intensively studied, especially for drugs that manifest relevant side effects, for which it is necessary to find alternatives in order to reduce the effective dose. In this review, the main electromagnetic-induced effects are deeply analyzed, with a particular focus on the activation of hyperthermia and electroporation phenomena, showing the enhanced biological performance resulting from an engineered/tailored design of the nanoparticle characteristics. Moreover, the possibility of integrating these nanofillers in polymeric matrices (e.g., electrospun membranes) is described and discussed in light of promising applications resulting from new transdermal drug delivery systems with controllable morphology and release kinetics controlled by a suitable stimulation of the interacting systems (nanofiller and interacting cells).

A 50-Year-Old Man with Fulminant Alpha-Fetoprotein-Producing Gastric Carcinoma and Disseminated Intravascular Coagulation.

BACKGROUND Alpha-fetoprotein-producing gastric carcinoma (AFPGC) is a rare but aggressive cancer with a poor prognosis. Disseminated intravascular coagulation (DIC) is usually associated with several tumors, including gastric cancer, but only a few cases have been reported in patients with AFPGC. This report describes a case of advanced-stage AFPGC associated with DIC in a 50-year-old White man. CASE REPORT A 50-year-old, White, non-smoker man was hospitalized for a recent left hemiparesis associated with anorexia and loss of weigh. Clinically, we had multiple, hard, irregular, subcutaneous nodules, left supraclavicular lymph nodes, and a left, complete hemiparesis. Laboratory tests showed a DIC. A whole-body CT scan documented multiple lymph node, liver, subcutaneous, bone, and muscular metastases, a right femoral venous thrombosis, a left popliteal arterial thrombosis, and splenic and renal infarcts. The patient underwent an excisional biopsy of a subcutaneous lesion. Histology and immunohistochemistry confirmed the diagnosis of a metastasis from a high-grade AFPGC. Before starting any systemic treatment, the patient presented a massive intraventricular brain hemorrhage, quickly leading to his death. CONCLUSIONS We report a case of metastatic AFPGC associated with a DIC and multiple venous and arterial thromboses resulting in a fatal intracerebral hemorrhage. AFPGC is a distinctive and very difficult to diagnose tumor showing aggressive behavior and poor prognosis.