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Background: Ziconotide is an intrathecal drug administered for the treatment of chronic pain. The current literature lacks an exhaustive benefit/risk assessment on this drug. We herein focus on Ziconotide's pharmacology and clinical applications. Methods: Literature research was conducted to identify studies on Ziconotide administration for the treatment of chronic pain, published between January 1990 and March 2023 and located via PubMed, Embase, Medline, Cinahl, and Web of Science, using the following keywords: Ziconotide, Omega conotoxin, Prialt, SNX-111, intrathecal therapy, and neuropathic pain. Only publications written in English were selected. Results: Among the 86 selected studies, we found 4 Randomized Controlled Trials (RCTs) and 3 prospective long-term studies concerning the intrathecal use of Ziconotide as a monotherapy in chronic pain. Other studies described the intrathecal infusion of Ziconotide combined with other drugs. Overall, Ziconotide has been proved to have strong efficacy for relieving chronic pain, although patients with co-morbid psychiatric disorders require a careful monitoring when treated with Ziconotide. Conclusions: Overall, the use of Ziconotide, as a monotherapy or in conjunction with other therapies for the treatment of chronic pain, was reported to be efficacious. Overall, its use in patients with chronic pain refractory to other pharmacologic agents outweighs the possible adverse consequences, thus resulting in a favorable benefit/risk assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Thalamic gliomas are rare neoplasms that represent a major surgical challenge and are characterized by poor postoperative survival. Surgical resection, although associated with improved overall survival (OS), is not always feasible. The aim of our retrospective study was to analyze the associations between possible prognostic factors such as tumor volume, histological grade, the extent of resection, performance status and OS. Surgical removal was demonstrated to be an important prognostic factor when gross total resection/subtotal resection was obtained. Furthermore, patients with a stable 3-month performance status after surgery demonstrated to have a better prognosis in terms of OS. In conclusion, in such kinds of tumors, a precise evaluation of the predictors of the 3-month postoperative Performance Status appears to be crucial in choosing between performing a biopsy or attempting the surgical removal of the tumor. Thalamic gliomas represent a heterogeneous subset of deep-seated lesions for which surgical removal is advocated, although clear prognostic factors linked to advantages in performance status or overall survival are still lacking. We reviewed our Institutional Cancer Registry, identifying patients who underwent surgery for thalamic gliomas between 2006 and 2020. Associations between possible prognostic factors such as tumor volume, grade, the extent of resection and performance status (PS), and overall survival (OS) were evaluated using univariate and multivariate survival analyses. We found 56 patients: 31 underwent surgery, and 25 underwent biopsy. Compared to biopsy, surgery resulted positively associated with an increase in the OS (hazard ratio, HR, at multivariate analysis 0.30, 95% confidence interval, CI, 0.12–0.75). Considering the extent of resection (EOR), obtaining GTR/STR appeared to offer an OS advantage in high-grade gliomas (HGG) patients submitted to surgical resection if compared to biopsy, although we did not find statistical significance at multivariate analysis (HR 0.53, 95% CI 0.17–1.59). Patients with a stable 3-month KPS after surgery demonstrated to have a better prognosis in terms of OS if compared to biopsy (multivariate HR 0.17, 95% CI, 0.05–0.59). Age and histological grades were found to be prognostic factors for this condition (p = 0.04 and p = 0.004, respectively, chi-square test). Considering the entire cohort, p53 positivity (univariate HR 2.21, 95% CI 1.01–4.82) and ATRX positivity (univariate HR 2.69, 95% CI 0.92–7.83) resulted associated with a worse prognosis in terms of OS. In this work, we demonstrated that surgery aimed at tumor resection might offer a stronger survival advantage when a stable 3-month KPS after surgery is achieved. [ABSTRACT FROM AUTHOR]

Simple Summary: Central Nervous System (CNS) hemangioblastomas (HBs) are rare and benign tumors that may be sporadic or hereditary, linked mainly to von Hippel–Lindau disease. Considering their slow-growing behavior and the possible risks related to surgical treatment, a careful, tailored approach should be adopted. This work aims to provide a systematic overview of the clinical appearance and neuroradiological characteristics of CNS HBs, along with a report of clinical–radiological data of a mono-institutional retrospective cohort, with particular emphasis on the possible role of intraoperative multimodal imaging to guide surgical strategy. Hemangioblastomas (HBs) are rare, benign tumors often related to von Hippel–Lindau disease. They represent the most frequent primary cerebellar tumors in adults. Neurosurgical procedures aim to obtain a gross-total resection of tumor nodules, avoiding intra-postoperative hemorrhage. The introduction of new intraoperative imaging techniques has considerably changed surgical strategies in neuro-oncology. We present an overview of clinical and radiological data of a mono-institutional retrospective cohort, focusing on the role of intraoperative multimodal imaging in surgical strategy. From 2015 to 2021, we identified 64 (81%) cranial (42 cerebellar, 8 supratentorial, and 14 of the brainstem) HBs and 15 (19%) spinal (4 cervical and 11 dorsal) HBs in 79 patients. Intraoperatively, indocyanine green videoangiography with FLOW800 was used in 62 cases (52 cranial and 10 spinal), intraoperative ultrasound and contrast-enhanced ultrasounds in 22 cases (18 cranial and 4 spinal HBs), and fluorescein in 10 cases (in 6 cranial and 2 spinal cases used as SF-VA). Gross total resection was achieved in 100% of the cases (53 mural nodule removal and 26 complete resections of the solid tumor). No side effects were reported following the combination of these tools. Multimodal intraoperative techniques provide valuable and reliable information to identify the tumor and its vasculature, guiding a more precise and safer resection and reducing the risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective  Primary goal in spheno-orbital meningioma (SOM) surgery still remains complete resection. Nevertheless, given their highly infiltrative nature, a growing body of literature suggests to shift toward function-sparing surgeries. We here present our experience in the management of SOMs through the endoscopic superior eyelid approach (SEA). Methods  Surgical database from our multidisciplinary work group was retrospectively reviewed to identify patients treated for SOMs in the last 10 years by our senior authors, analyzing and correlating clinical, radiological, and outcome variables among the different approaches used. Results  There were 35 patients (mean age of 57.3 ± 12.86 years), with a mean follow-up of 31.5 months (range: 6–84 months). The most common preoperative complaint was proptosis (62.9%) followed by diplopia and visual deficit. Greater and lesser sphenoid wings were the areas mainly involved by the pathology (91.4% and 88.6%, respectively), whereas orbital invasion was evidenced in one-third of cases. Patients were operated on through craniotomic (48.6%), endoscopic superior eyelid (37.1%), and combined cranioendoscopic (14.3%) approaches. Simpson grades 0 to II were accomplished in 46.2% of SEA and 76.5% of craniotomies. All patients with a preoperative visual deficit improved in the postoperative period, independently from the approach used. On patients who underwent endoscopic SEA, there was improved their short-/long-term postoperative Karnofsky Performance Status. Conclusions  Endoscopic SEA is a safe and effective alternative to transcranial approaches in very selected cases of SOMs, where the planned primary objective was to obtain a maximally safe resection, aimed at symptom relief, rather than a gross total resection at any cost. [ABSTRACT FROM AUTHOR]

Background: Olfactory function preservation is a desirable objective in anterior skull base (ASB) surgery. The "infracerebral-supraolfactory nerve" corridor is presented. Method: The technique for preserving the olfactory nerves (OlfNs) in anterior ASB meningioma removal involves the following points: deep knowledge of the ASB vascular and meningeal anatomy, precise preoperative planning, wide and sharp dissection of the OlfNs away from the frontal lobes, gravity-aided frontal lobe retraction, Gelfoam-assisted hemostasis on nervous structures, and access to the lesion through an infracerebral-supraolfactory nerve corridor. Conclusions: This technique may be a valid option for patients affected by anterior skull base meningiomas with intact preoperative olfactory function. [ABSTRACT FROM AUTHOR]

To describe a novel bilaterally pedicled pericranial flap for anterior cranial base reconstruction after removal of complex frontobasal cancers extending to the frontal region, thus precluding the use of standard reconstructive techniques. In selected oncologic cranial base surgeries, the use of the standard galea frontalis pericranial flap for reconstructive purposes may be precluded by tumor infiltration. In such cases, dura mater reconstruction and exclusion of frontal sinuses from the intracranial space can be performed using a large superficial temporal artery bilaterally pedicled pericranial flap obtained from both temporoparietal regions. Surgical technique, indication, contraindication, complications, and degree of resection are recorded to evaluate the efficacy of this surgical method. A 48-year-old man affected by a recurrence of frontobasal squamous cell carcinoma was surgically treated by combined transcranial and endoscopic endonasal resection. A large pericranial flap pedicled bilaterally on the parietal branches of the superficial temporal artery was obtained, transposed anteriorly, carefully watertight sutured to the dural defect, and used to exclude cranialized frontal sinuses as well. The reconstruction was successful, and the patient was discharged home on the tenth postoperative day without any complications and/or development of cerebrospinal fluid leak. Contrast-enhanced magnetic resonance imaging 3 months after surgery was clear from disease with consolidated surgical outcomes. This novel pericranial flap seems to be easily obtained and effective for anterior cranial base reconstruction when the use of a traditional galea frontalis flap is precluded for oncologic reasons and there are concerns for the possible development of contaminations and cerebrospinal fluid leaks. [ABSTRACT FROM AUTHOR]

Background. Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. Methods. MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients. MCs were cultured and the adherent population on fibronectin (FN-MCs), after immunocytochemistry and flow cytometry characterization, was loaded with Paclitaxel (FN-MCs-PTX). Antiproliferative and migration activity of FN-MCs-PTX was evaluated in two-dimensional (2D) and three-dimensional (3D) co-culture assays with red fluorescent U87 Malignant Glioma cells and primary GBM cells. Antiangiogenic properties of FN-MCs-PTX were tested on cultures with endothelial cells. Results. Phenotypical characterization showed a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in vitro (P < 0.01). Moreover, tumor-induced migration of MCs, although partially affected by the PTX cargo, remained statistically significant when compared with unprimed cells and this was confirmed in a 3D Matrigel model (P < 0.01) and in aTrans-well assay (P < 0.01). FN-MCs-PTX also disclosed considerable antiangiogenic properties. Discussion. Our results suggest that the fibronectin-adherent population of MCs isolated from peripheral blood can be an effective tool to inhibit GBM growth. Given the relative facility to obtain such cells and the short time needed for their culture and drug loading this approach may have potential as an adjuvant therapy for GBM. [ABSTRACT FROM AUTHOR]

References 1 Agosti E, Alexander AY, Doglietto F, Fontanella MM (2021) Letter to the Editor: "Olfactory nerve sparing technique for anterior skull base meningiomas: how I do it." This article is part of the Topical Collection on Tumor - Other We thank Dr. Agosti and co-authors for their observations [[1]] concerning our previous "how I do it" article on olfactory nerve (olfN) sparing technique during surgical management of anterior skull base (ASB) meningiomas [[2]]. [Extracted from the article]

A letter to the editor is presented in response to the article Postoperative acute cerebellar swelling after pineal surgery: pathogenesis and treatment published in a previous issue.

Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and fluorescent-aided techniques, histopathological analysis still remains the gold-standard for diagnosis, with frozen section as the most used, rapid and precise intraoperative histopathological method that permits an intraoperative differential diagnosis. Unfortunately, due to the various limitations linked to this technique, it is still unsatisfactorily for obtaining real-time intraoperative diagnosis. Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data in neurosurgery, due to its established use in other non-neurosurgical fields. Still far to be widely implemented in current neurosurgical clinical practice, this technology was initially studied in preclinical experiences confirming its utility in identifying brain tumors, microvasculature and tumor margins. Hence, ex vivo and in vivo clinical studies evaluated the possibility with this technology of identifying and classifying brain neoplasms, discerning between normal and pathologic tissue, showing very promising results. This systematic review has the main objective of presenting a state-of-the-art summary on actual clinical applications of confocal laser imaging in neurosurgical practice. [ABSTRACT FROM AUTHOR]

Surgery for anterior cranial base lesions is challenging because tumors often spread from their origin to sinuses, orbits, and middle cranial fossa, resulting in risky surgeries. 1,2 To approach such complex diseases, recently combined multiportal approaches have been proposed. 3,4 At the best of our knowledge, operative application of a combined endoscopic endonasal and transcranial surgery for complex anterior cranial base lesions has not been described. Therefore a surgical video of such an approach is presented. A 37-year-old woman affected by a huge recurrence of a tuberculum meningioma extended to right orbit presented to our department, complaining of right ocular bulb dislocation with multidirectional limitations in eye movements (Video 1). Given the complexity and localization of the lesion, a combined endoscopic endonasal–transcranial surgery was performed. Such a combined approach, although demanding in terms of the presence of both otolaryngologist and neurosurgeon during the surgery, also requires strong synergy among them and permits them to control anterior cranial base lesions from both specialists' perspectives, simultaneously. In this case, while an endonasal corridor permitted an accurate excision of ethmoidal and medial orbital wall part of the lesion, a bicoronal approach allowed the aggression of the anterior cranial base portion of the tumor, allowing good control of cranial base neurovascular structures, eventually obtaining a gross total resection, without perioperative complications. Furthermore, a combined multiportal approach allows cooperative strategies among the surgeons involved, leading to safer, quicker, and more effective resections with less brain retraction, given the wide angles of views to the lesion that a multiportal approach can offer. [ABSTRACT FROM AUTHOR]

Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this tumor. Several dyes have been tested for improving tumor visualization; however, few reports with different protocols of fluorophores use are available and the results are inconsistent. Hence, we report our experience with sodium fluorescein in MB surgery, aiming to assess the role of this technique on the extent of resection. Furthermore, we performed a literature review of this topic. Fluorescence characteristics, extent of resection, and clinical outcome were analyzed in 9 consecutively operated patients with MB. A comprehensive literature search and review for English-language articles concerning fluorescein application in MB was conducted. In our cohort, no side effect related to fluorescein occurred; all tumors presented with an intense or moderate yellow-green enhancement, and fluorescein was judged fundamental in distinguishing tumors from viable tissue in 7 of 9 cases. Gross total resection or near-total resection (i.e., a residual tumor volume <1.5 cm3) was achieved in 8 patients. The review explored the different techniques and surgical interpretations as well as surgical radicality; we did not find a homogenous protocol for fluorescein injection in the published articles. Fluorescence appeared moderate or intense in almost all cases, with a high percentage of usefulness and consensual achievement of a high rate of gross total resection. Based on these results, we can infer that fluorescein-guided surgical resection is a safe and valuable method for patients with MB. [ABSTRACT FROM AUTHOR]

It is commonly reported that maximizing surgical resection of contrast-enhancing regions in patients with glioblastoma improves overall survival. Efforts to achieve an improved rate of resection have included several tools: among those, the recent widespread of fluorophores. Sodium fluorescein is an unspecific, vascular dye which tends to accumulate in areas with an altered blood–brain barrier. In this retrospective analysis of patients prospectively enrolled in the FLUOCERTUM study, we aimed to assess the role of fluorescein-guided surgery on surgical radicality, survival, and morbidity. A retrospective review based on 93 consecutively and prospectively enrolled IDH wild-type glioblastoma patients (2016–2022) was performed; fluorescence characteristics, rate of resection, clinical outcome, and survival were analyzed. No side effect related to fluorescein occurred; all of the tumors presented a strong yellow-green enhancement and fluorescein was judged fundamental in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 77 cases out of 93 patients (82.8%). After a mean follow-up time of 17.4 months (3–78 months), the median progression-free survival was 12 months, with a PFS-6 and PFS-12 of 94.2% and 50%, respectively, whereas median overall survival was estimated to be 16 months; survival at 6, 12, and 24 months was 91.8%, 72.3%, and 30.1%, respectively. Based on these results, we can assert that the fluorescein-guided technique is a safe and valuable method for patients harboring a newly diagnosed, untreated glioblastoma. [ABSTRACT FROM AUTHOR]

Despite the increasing popularity of flow diverters (FDs) as an endovascular option for intracranial aneurysms, the treatment of complex aneurysms still represents a challenge. Combined strategies using a flow-preservation bypass could be considered in selected cases. In this study, we retrospectively reviewed our series of patients with complex intracranial aneurysms submitted to bypass. From January 2015 to May 2022, 23 patients were selected. We identified 11 cases (47.8%) of MCA, 6 cases (26.1%) of ACA and 6 cases (26.1%) of ICA aneurysms. The mean maximal diameter was 22.73 ± 12.16 mm, 8 were considered as giant, 9 were fusiform, 8 presented intraluminal thrombosis, 10 presented wall calcification, and 18 involved major branches or perforating arteries. Twenty-five bypass procedures were performed in 23 patients (two EC–IC bypasses with radial artery graft, seventeen single- or double-barrel STA–MCA bypasses and six IC–IC bypasses in anterior cerebral arteries). The long-term bypass patency rate was 94.5%, and the total aneurysm exclusion was 95.6%, with a mean follow-up of 28 months. Median KPS values at last follow-up was 90, and a favorable outcome (KPS ≥ 70 and mRS ≤ 2) was obtained in 87% of the cases. The use of bypass techniques represents, in selected cases, a valid therapeutic option in the management of complex anterior circulation aneurysms when a simpler direct approach, including the use of FD, is considered not feasible. [ABSTRACT FROM AUTHOR]

Introduction: Intradiploic pseudomeningoceles, also called intradiploic cerebrospinal fluid (CSF) fistulas, are abnormal CSF collections between the two bony tables of the calvaria resulting from postsurgical CSF leakage. To date, only six cases of intradiploic pseudomeningocele have been reported, all occurring in the occipital area. In this paper, we report the seventh case of late-onset occipital intradiploic pseudomeningocele (OIP) occurring in a young female patient who underwent surgery for the removal of a cerebellar pilocytic astrocytoma. In this regard, we also review the literature on the few recognized cases of OIP. Case Presentation: The case of an 18-year-old female patient known to our institute for an operation 12 years earlier to remove a pilocytic astrocytoma is illustrated. At admission, the patient complained only of occasional orthostatic headache. Brain imaging demonstrated a pseudomeningocele extended intradiploically from the occipital squama to the condylar and clivus regions, thinning both occipital bone tables and dilating the CSF-filled diploe. Watertight duroplasty and cranioplasty were effectively performed. Conclusion: Pediatric patients undergoing posterior cranial fossa craniotomy/craniectomy may postoperatively develop OIP. In this setting, treatment of any dural CSF fistula should be considered because of the risk of progressive extension and bone erosion. [ABSTRACT FROM AUTHOR]

Objectives  We illustrate endoscopic endonasal odontoidectomy for the Chiari-I malformation respecting craniovertebral junction (CVJ) stability. Design  Case report of a 12-year-old girl affected by the Chiari-I malformation. Magnetic resonance imaging (MRI) showed tonsillar herniation, basilar invagination, and dental retroversion, causing angulation and compression of the bulbomedullary junction. Patient underwent endoscopic third ventriculostomy (ETV) with reduction of ventricular size and resolution of gait disturbances, but she complained the Valsalva-induced headaches, hiccup, and dysesthesias in the lower limbs. Endoscopic endonasal odontoidectomy was chosen to decompress the cervicomedullary junction. Setting  The research was conducted at University Hospital "Ospedale di Circolo," Department of Neurosurgery at Varese in Italy. Participants  Patients were from neurosurgical and ENT (ear, nose, and throat) skull base team. Main Outcome Measures  A bilateral paraseptal approach was performed, using a four-hand technique. After resection of posterior edge of the nasal septum, the choana is entered and a rhinopharynx muscle–mucosal flap is dissected subperiosteal and transposed in oral cavity. The CVJ is exposed and, using neuronavigation and neuromonitoring, odontoidectomy is fulfilled until dura is reached, preserving the anterior arch of C1. Reconstruction is obtained suturing the flap previously harvested. Results  Postoperative course was unremarkable and the patient experienced improvement of symptoms. Postoperative MRI documented the appearance of tight cerebrospinal fluid (CSF) film anterior to bulbomedullary junction and in retrotonsillar spaces, opening of the bulbomedullary angle, and slight tonsils reduction. No CVJ instability was occurred with any need of posterior fixation. Conclusion  Endoscopic endonasal odontoidectomy is a feasible approach for CVJ malformation. In this case, bulbar decompression was achieved preserving CVJ stability and avoiding posterior fixation. The link to the video can be found at: https://youtu.be/VIobocHfCuc. [ABSTRACT FROM AUTHOR]

Localization of chemotherapy at the tumor site can improve therapeutic efficacy and reduce systemic toxicity. In previous studies we have shown that mesenchymal stromal cells (MSCs) isolated from bone marrow or adipose tissue can be loaded with the anti-cancer drug Paclitaxel (PTX) and kill cancer cells when localized nearby. We here investigated the capacity of human micro-fragmented adipose tissue (MFAT), used as a natural scaffold of MSCs, to deliver PTX with the idea to improve local drug concentration and to prolong the therapeutic activity. Surprisingly, we found that both fresh but also devitalized MFAT (DMFAT) (by freezing/thawing procedure) were able to deliver and release significant amount of PTX, killing several human cancer cell lines in vitro with a long lasting activity. In an orthotopic mice model of Neuroblastoma (NB) transplant, DMFAT loaded with PTX prevents or delays NB relapse when placed in the surgical area of tumor resection, without any collateral toxicity. We concluded that MFAT, but also DMFAT, may represent very innovative natural biomaterials able to localize and release anti-cancer molecules at the tumor site, helping to fight cancer in human. Unlabelled Image • Structural integrity of fat tissue after micro-fragmentation (MFAT) is maintained • MFAT devitalization, by freezing/thawing procedure, does not alter fat structure and cellular component • MFAT and DMFAT work as natural scaffold able to deliver and release Paclitaxel (PTX) • PTX released by MFAT and DMFAT have a long lasting anti-cancer activity • DMFAT loaded with PTX prevent or delay Neuroblastoma relapse in vivo. [ABSTRACT FROM AUTHOR]

Objective Idiopathic normal pressure hydrocephalus (iNPH) may present, besides the classic triad of symptoms, with extrapyramidal parkinsonianlike movement disorders. We present a randomized prospective study comparing adjustable ventriculoperitoneal (VP) shunt insertion plus dopamine oral therapy (group A) versus VP shunt alone (group B) in patients affected by iNPH associated with parkinsonism. Methods A detailed screening process included neurologic, neurosurgical, and neuropsychological evaluations, followed by a cerebrospinal fluid tap test and resistance outflow measurement. Outcome was evaluated through the Japanese NPH Grading Scale-Revised (JNPHGSR) and the motor (third) section of the Unified Parkinson's Disease Rating Scale, Motor Section (UPDRS-m). Friedman analysis of variance with a Wilcoxon post hoc test was used to evaluate the difference in JNPHGSR and UPDRS-m scores between pretreatment and follow-up (12 months) in the 2 groups, and a Kruskal-Wallis statistic and post hoc Mann-Whitney test were used to compare the change in JNPHGSR and UPDRS-m scores between the 2 groups. Results Thirty-two of 54 (59%) patients (mean age, 73.2 years) screened in 36 months met the inclusion criteria, but only 30 were enrolled (2 refused surgery) (15 in each group). Preoperative 123 I-ioflupane-cerebral single-photon emission computed tomography (DaTSCAN) revealed striatal dopaminergic deficit in 14/30 patients (46.5%). At the final 12 months follow-up, both groups improved JNPHGSR and UPRDS-m scores. The UPDRS-m score improvement was significant in both groups, but greater in group A ( P = 0.003); JNPHGSR score improvement was similar in the 2 groups. Conclusions iNPH associated with parkinsonism may be a frequent finding. In these cases, patients may benefit from VP shunt plus dopamine oral therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapeutic approaches to increase localization of chemotherapy at the tumor site, reducing systemic toxicity, are under deep investigation. In previous studies, we have shown that microfragmented adipose tissue (MFAT) may act as a natural scaffold able to deliver anti-cancer drugs. We demonstrated that MFAT and its devitalized counterpart (DMFAT) are able to absorb significant amounts of the chemotherapeutic drug Paclitaxel (PTX), with the ability to kill many different human cancer cell lines in vitro and in vivo, preventing tumor relapse when placed in the surgical area of tumor resection. We demonstrated here for the first time that DMFAT loaded with PTX was also very effective in inhibiting the in vivo growth of hepatocellular carcinoma (HCC) in an advanced stage of progression, suggesting it as a new potent and viable drug-delivery system that may be hypothetically translated to treat inoperable primary tumors in humans. Hepatocellular carcinoma (HCC) is poorly beneficiated by intravenous chemotherapy due to inadequate availability of drugs at the tumor site. We previously demonstrated that human micro-fragmented adipose tissue (MFAT) and its devitalized counterpart (DMFAT) could be effective natural scaffolds to deliver Paclitaxel (PTX) to tumors in both in vitro and in vivo tests, affecting cancer growth relapse. Here we tested the efficacy of DMFAT-PTX in a well-established HCC in nude mice. MFAT-PTX and DMFAT-PTX preparations were tested for anti-cancer activity in 2D and 3D assays using Hep-3B tumor cells. The efficacy of DMFAT-PTX was evaluated after a single-shot subcutaneous injection near a Hep-3B growing tumor by assessing tumor volumes, apoptosis rate, and drug pharmacokinetics in an in vivo model. Potent antiproliferative activity was seen in both in vitro 2D and 3D tests. Mice treated with DMFAT-PTX (10 mg/kg) produced potent Hep-3B growth inhibition with 33% complete tumor regressions. All treated animals experienced tumor ulceration at the site of DMFAT-PTX injection, which healed spontaneously. Lowering the drug concentration (5 mg/kg) prevented the formation of ulcers, maintaining statistically significant efficacy. Histology revealed a higher number of apoptotic cancer cells intratumorally, suggesting prolonged presence of PTX that was confirmed by the pharmacokinetic analysis. DMFAT may be a potent and valid new tool for local chemotherapy of HCC in an advanced stage of progression, also suggesting potential effectiveness in other human primary inoperable cancers. [ABSTRACT FROM AUTHOR]

Whereas several studies have been so far presented about the surgical outcomes in terms of mortality and perioperative complications for elderly patients submitted to neurosurgical treatments, the management of elderly moyamoya patients is unclear. This review aims to explore the available data about the clinical manifestation, characteristics, and outcome after surgery of older patients with moyamoya arteriopathy (MA). We found only two articles strictly concerning elderly patients with MA. We have also evaluated other reported adult series of moyamoya patients, including elderly cases in their analysis. Patients with MA above 50 years old may be considered a peculiar subset in which patients are often presenting with ischemic symptoms and a higher Suzuki grade. Conservative treatment may be proposed in asymptomatic or stable cases due to their fragility and possible increase of post-operative complications, while the best surgical options in symptomatic cases are still under investigation, although we believe that a minimal invasive superficial temporal artery—middle cerebral artery bypass could be considered the treatment of choice for the immediate effect on brain perfusion with a limited rate of post-operative complications. [ABSTRACT FROM AUTHOR]

Glioblastoma extensively infiltrates the brain; despite surgery and aggressive therapies, the prognosis is poor. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of glioblastoma evolution in every single patient, with the aim of tailoring therapeutic weapons. In particular, the ultimate goal of biomathematics for cancer is the identification of the most suitable theoretical models and simulation tools, both to describe the biological complexity of carcinogenesis and to predict tumor evolution. In this report, we describe the results of a critical review about different mathematical models in neuro-oncology with their clinical implications. A comprehensive literature search and review for English-language articles concerning mathematical modelling in glioblastoma has been conducted. The review explored the different proposed models, classifying them and indicating the significative advances of each one. Furthermore, we present a specific case of a glioblastoma patient in which our recently proposed innovative mechanical model has been applied. The results of the mathematical models have the potential to provide a relevant benefit for clinicians and, more importantly, they might drive progress towards improving tumor control and patient's prognosis. Further prospective comparative trials, however, are still necessary to prove the impact of mathematical neuro-oncology in clinical practice. [ABSTRACT FROM AUTHOR]