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Introduction: Craniopharyngiomas are usually slow growing, benign epithelial tumors, arising from cell remnants of Rathke's pouch with its ultimate site of origin being the embryologic stomadeum. Although considered WHO grade I tumors, they are often locally aggressive. However, malignant transformation is extremely rare. Until now, 42 cases of malignant craniopharyngioma have been reported. In this article, the interdisciplinary, i.e. neurosurgical and maxillofacial, approach to a case of secondary malignant craniopharyngioma with multiple recurrences is discussed.Case report A 73-year-old woman with a history of recurrent, extracranially expanding craniopharyngioma was referred to the department of Neurosurgery following the MRI finding of a 7th tumor recurrence, located at the level of the right lateral orbital wall. Previously, the patient had already undergone five surgical resections and three radiotherapeutic treatments elsewhere. Histopathological examination revealed an adamantinomatous craniopharyngioma with sites of malignant transformation. Tumor resection with exenteration of the right eye was performed with an immediate reconstruction using a PEEK-PSI (Patient Specific Implant) and anterolateral thigh flap. Histopathological examination confirmed the diagnosis of craniopharyngioma with malignant transformation. Conclusions: Malignant transformation in a craniopharyngioma is uncommon but has a poor prognosis. The assumed correlation between radiotherapy and malignant transformation is not yet clearly established. Therefore, radiotherapy remains a good choice to reduce recurrence of a benign cranopharyngioma. PEEK implantation seems a safe option for allogenic reconstruction in patients with large maxillofacial defects. In complex cases the benefit of a multidisciplinary approach should not be underestimated.

Background: Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm (IA) is a devastating condition with high morbidity and mortality. Individuals with a positive family history of aneurysmal subarachnoid hemorrhage (aSAH) or IA can have an increased risk for aSAH or IA themselves. Screening is currently recommended in families with ≥2 affected first-degree relatives. We sought to assess the usefulness and cost-effectiveness of IA screening in individuals with a positive first-degree family history, relative to the number of family members affected., Methods: We performed a systematic literature search using PubMed and Google Scholar and identified additional studies by reviewing reference lists. Only original studies and review papers were considered. We excluded genetic diseases associated with IA and studies with unclear data concerning the number of first-versus second-degree relatives affected., Results: This review included 37 articles. Individuals with ≥2 affected first-degree relatives had a greater prevalence of IA (average 13.1% vs. 3% in the general population). Similarly, we found a greater prevalence of IA in individuals with ≥1 affected first-degree relative (average 4.8%, up to 19% in individuals with additional risk factors). The risk of aSAH also was increased in both categories. Recent studies stressed the importance of serial screening over time and suggested that such screening can be cost-effective in persons with only one first-degree relative with IA or aSAH., Conclusions: While current guidelines do not recommend screening individuals with ≥1 first-degree relative affected, we found strong arguments in favor of this approach., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Nowadays, several techniques have been developed in order to guide neurosurgeons during intended maximal safe resection of high-grade gliomas (HGG). Fluorescence-guided microsurgery using 5-aminolevulinic acid (5-ALA) is one of these. A large amount of studies have been performed evaluating benefits in newly diagnosed HGG. However, little is known about the safety, accuracy and efficacy in recurrent HGG. The primary objective of this thesis is to examine the value of 5-ALA in patients with recurrent HGG concerning diagnostic accuracy, extent of resection (EOR), safety and survival compared to white-light resection. As a secondary objective, we compared these results with current literature concerning 5-ALA in newly diagnosed HGG., Patients and Methods: We performed a systematic review and included eighteen articles obtained from MEDLINE, EMBASE, Web of Science and TRIP database. Search terms include "glioma" and "aminolevulinic acid". Additional studies were identified through checking the reference lists. This study is in conformity with the PRISMA and BMJ guidelines., Results: 5-ALA shows similar results regarding diagnostic accuracy in recurrent HGG compared to newly diagnosed HGG, although specificity and negative predictive value seem lower. It shows complementary value in identifying tumor boundaries compared to MRI-neuronavigation. Diagnostic accuracy is not influenced by previous chemo- or radiotherapy. New neurological deficits proved to be similar and were in general mainly temporary. However, adverse events overall were more common. Therefore, indications for repeat surgery should be followed strictly. 5-ALA might increase overall survival in recurrent gliomas, but has no clear impact on progression-free survival., Conclusion: 5-ALA should be regarded as a useful and safe intraoperative tool in recurrent glioma surgery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Objective: Transcranial magnetic stimulation (TMS) is a useful technique to help localize motor function prior to neurosurgical procedures. Adequate modelling of the effect of TMS on the brain is a prerequisite to obtain reliable data., Methods: Twelve patients were included with perirolandic tumors to undergo TMS-based motor mapping. Several models were developed to analyze the mapping data, from a projection to the nearest brain surface to motor evoked potential (MEP) amplitude informed weighted average of the induced electric fields over a multilayer detailed individual head model. The probability maps were compared with direct cortical stimulation (DCS) data in all patients for the hand and in three for the foot. The gold standard was defined as the results of the DCS sampling (with on average 8 DCS-points per surgery) extrapolated over the exposed cortex (of the tailored craniotomy), and the outcome parameters were based on the similarity of the probability maps with this gold standard., Results: All models accurately gauge the location of the motor cortex, with point-cloud based mapping algorithms having an accuracy of 83-86%, with similarly high specificity. To delineate the whole area of the motor cortex representation, the model based on the weighted average of the induced electric fields calculated with a realistic head model performs best. The optimal single threshold to visualize the field based maps is 40% of the maximal value for the anisotropic model and 50% for the isotropic model, but dynamic thresholding adds information for clinical practice., Conclusions: The method with which TMS mapping data are analyzed clearly affects the predicted area of the primary motor cortex representation. Realistic electric field based modelling is feasible in clinical practice and improves delineation of the motor cortex representation compared to more simple point-cloud based methods., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Endoscopic third ventriculostomy (ETV) has been accepted as the procedure of choice for the treatment of obstructive hydrocephalus in children and adults. The role and outcome of this procedure in the elderly has not been evaluated yet., Materials and Methods: Over an 11-year interval we retrospectively analyzed data of patients, 65+ years of age, who underwent ETV in our center. Success of the procedure was assessed in terms of symptom relief and/or elimination of the need for shunting. Additionally pre- and postoperative ventricular volumes were estimated using Evan's index (Ei) and fronto-occipital horn ratio (FOR). In our analysis we compared the results of the elderly patients with those of the pediatric and adult age groups treated in our center., Results: We obtained data of 16 elderly cases (11 males, 5 females), mean age 72.8 years (66-83 years) out of the 91 patients treated with ETV in total. The success rate was 75% in this age group; mean follow-up 18.4 months (2-55 months). In 10 patients a mass lesion was the underlying cause of hydrocephalus. Mean ventricular size reduction was 18% and 13.5% (Ei and FOR) in the success group vs. 7.6% and 6.2% in the failure group. Three out of four patients who had shunting pre-EVT, became shunt independent post-operatively. The presence of flow void over the stoma was 100% correlated with success. All 7 patients with a primary or metastatic brain tumor were able to receive radiation therapy., Conclusion: Also in elderly, ETV is a safe and efficient procedure, with success rates similar to the younger population. Further research is required to set up a prognostic scoring system for this age group., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Aims: One of the major challenges of dendritic cell (DC) vaccination is the establishment of harmonized DC production protocols. Here, we report the transfer and validation of a successfully used open DC manufacturing method into a closed system, good manufacturing practice (GMP)-compatible protocol., Methods: All production steps (lysate generation, monocyte selection, DC culture and cryopreservation) were standardized and validated., Results: Tumor lysate was characterized by histology, mechanically homogenized and avitalized. This preparation yielded a median of 58 ± 21 μg protein per milligram of tumor tissue. Avitality was determined by trypan blue staining and confirmed in an adenosine triphosphate release assay. Patient monocytes were isolated by elutriation or CD14 selection, which yielded equivalent results. DCs were subsequently differentiated in Teflon bags for an optimum of 7 days in CellGro medium supplemented with interleukin (IL)-4 and granulocyte macrophage colony stimulating factor and then matured for 48 h in tumor necrosis factor-α and IL-1ß after pulsing with tumor lysate. This protocol resulted in robust and reproducible upregulation of DC maturation markers such as cluster of differentiation (CD)80, CD83, CD86, human leukocyte antigen-DR and DC-SIGN. Functionality of these DCs was shown by directed migration toward C-C motif chemokine ligand 19/21, positive T-cell stimulatory capacity and the ability to prime antigen-specific T cells from naive CD8(+) T cells. Phenotype stability, vitality and functionality of DCs after cryopreservation, thawing and washing showed no significant loss of function. Comparison of clinical data from 146 patients having received vaccinations with plate-adherence versus GMP-grade DCs showed no inferiority of the latter., Conclusions: Our robust, validated and approved protocol for DC manufacturing forms the basis for a harmonized procedure to produce cancer vaccines, which paves the way for larger multi-center clinical trials., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Aggressiveness of advanced melanomas relates in part to their marked propensity to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles, galectin (gal)-1 expressed and/or secreted by both cancer and endothelial cells stimulates proliferation and angiogenesis. This study first shows that gal-1 is more highly expressed at both mRNA and protein levels than its congeners in melanomas and particularly in advanced lesions. The roles of gal-1 were further investigated in vivo in the highly proliferating and vascularized pseudometastatic B16F10 mouse melanoma model using stable knockdown B16F10 cells and wild-type versus gal-1 knockout mice, and then in vitro in B16F10 tumoral and lung microvascular cells. Gal-1 depletion in the B16F10 tumor cells but not in the tumor-bearing mice significantly increased melanoma-bearing mice survival. Tumor-derived gal-1 thus seems to have more critical roles than the host-derived one. In fact, gal-1 displays distinct effects on the H-Ras-dependent p53/p21 pathways: in primary lung microvessel endothelial cells, gal-1 seems to be involved in the maintenance of senescent status through the induction of both p53 and p21 while it stimulates B16F10 cancer cell proliferation through a p53/p21 decrease. Altogether, these data point to gal-1 as a potential target to combat melanomas.

We have successfully treated over two hundred high-grade glioma (HGG) patients with immunotherapy consisting of vaccination with autologous dendritic cells (DCs) loaded with autologous tumour lysate. It has been documented that regulatory T cells (Treg) can counteract anti-tumour immune responses. Therefore, monitoring of Treg in these patients is essential. Up till now, Treg have been characterized based on the expression of the transcription factor Foxp3. Here, we validated IL-7 receptor alpha subunit (CD127)dim expression as a marker for human Treg within HGG patients, as a less laborious assay for routine use in tumour vaccination trials. We noted a strong positive correlation between Foxp3 expression and CD127dim expression in CD4+CD25+ and CD4+ cells. The suppressive function of CD4+CD127dim cells was assessed in an allogeneic mixed lymphocyte reaction (MLR). We conclude that CD127 staining is a fast, well-suited and reproducible Treg monitoring tool in HGG patients treated with immunotherapy., (Copyright 2009 Elsevier B.V. All rights reserved.)