Point-of-Care 3-Dimensional-Printed Polyetheretherketone Customized Implants for Cranioplastic Surgery of Large Skull Defects.

BACKGROUND AND OBJECTIVES: 3-Dimensional (3D) printing has become a common tool to aid implant molding for cranioplastic surgery of large skull defects. Until now, 3D printing of cranial implants itself has not been used, mainly because of medicolegal concerns. With a 3D printer developed for printing medical applications and with implant-grade polyetheretherketone (PEEK) filament available, we established a workflow (in compliance with medical device regulations) to 3D print cranial implants for cranioplastic surgery directly at the point of care (POC). Here, we describe the implementation of 3D printing these PEEK implants for cranioplastic surgery at our academic hospital. METHODS: A thorough design and 3D printing process, in accordance with local medical device regulations, was developed. Implants are digitally designed based upon pre- and post-craniectomy cranial computed tomography scans by trained 3D printing experts from the department of medical engineering at our institution. Implants are then produced on a medical 3D printer with implant-grade PEEK filament using the fused filament fabrication process. After postprocessing and steam sterilization, implantation for reconstruction of the skull can be performed. RESULTS: Cranioplastic surgery with a 3D-printed PEEK implant was performed at our institution in a patient with a large frontotemporoparietal skull defect after traumatic brain injury with consecutive decompressive craniectomy. No intra- or post-operative complications occurred. Postoperative cranial computed tomography scans showed perfect reconstruction of precraniectomy skull shape. The aesthetic result was promising and satisfactory to the patient. CONCLUSION: This novel 3D printing workflow enables the production of patient-specific cranial implants from PEEK, to reconstruct large skull defects directly at the POC in accordance with the European Medical Device Regulation. This marks an unprecedented technological and legal advancement, enabling the hospital infrastructure not only to deliver the cranioplastic surgery itself, but also additive manufacturing of the implant directly at the POC.

Extra- and Intracranial Diffuse Large B-Cell Lymphoma (DLBCL) Mimicking Meningioma: A Case Report and Literature Review.

Primary central nervous system lymphomas (PCNLSs) are malignant non-Hodgkin lymphomas solely affecting the central nervous system (CNS). Here, we present a rare case of extra- and intracranial manifestation without adjacent calvarial infiltration. We report a 67-year-old woman who presented with right leg paresis and hypoesthesia, facial hypoesthesia, focal epileptic seizures, and an indolent tumor on the left parietal scalp. MRI showed a left paramedian extra- and intracranial contrast-enhancing tumor with infiltration of the superior sagittal sinus, but without osseous infiltration on CT. The tumor was radiologically suspected to be a meningioma and resection was performed. Histological examination, however, revealed a diffuse large B-cell lymphoma (DLBCL). Thus, the patient received adjuvant treatment according to the MATRix protocol. We provide a detailed analysis of this rare case with a focus on preoperative radiological findings and differential diagnoses. To the best of our knowledge, this is one of only four published cases of DLBCL with extra- and intracranial manifestation without bone affection.

Coexistence of Two Distinct Tumor Types Within One Posterior Fossa Mass Lesion in an Adult Patient Verified by DNA-Methylation Analysis: A Case Report.

We report an 81-year-old patient who underwent microsurgical resection of a posterior fossa mass lesion. Intraoperative findings were suggestive of the presence of two distinctly different tumor types within the lesion, one of which was well-circumscribed and avascular, whereas the other one showed an adhesive growth pattern and extensive vascularisation. Histopathological analysis, including deoxyribonucleic acid (DNA)-methylation-based classification, substantiated the intraoperative impression and confirmed the presence of a subependymoma central nervous system (CNS) World Health Organization (WHO) grade 1 as well as the presence of a hemangioblastoma CNS WHO grade 1. To our knowledge, our patient represents only the second reported case of such a rare constellation. Even though DNA-methylation-based classification is not yet required for the classification of all CNS tumor types by the 2021 WHO classification of tumors of the CNS, it proved to be crucial to verify the final diagnosis in our patient. In the future, DNA-methylation analysis will most likely become an important asset in neuro-oncological diagnostics and further help to guide treatment strategies in complex or rare clinical cases.

Surgeon experience in glioblastoma surgery of the elderly-a multicenter, retrospective cohort study.

PURPOSE: To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. METHODS: GBM patients aged ≥ 65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). RESULTS: 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0-12.0); median EOR was 89.4%. Surgery-related morbidity affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P < .001); patients with surgery-related morbidity were less likely to receive adjuvant treatment (P = .002). In multivariable testing, adjuvant therapy (P < .001; HR = 0.064, 95%CI 0.028-0.144) remained the only significant predictor for improved OS. CONCLUSION: Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial for generating a treatment benefit for this cohort.

A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature.

Here, we report on a patient presenting with two histopathologically distinct gliomas. At the age of 42, the patient underwent initial resection of a right temporal oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade II followed by adjuvant radiochemotherapy with temozolomide. 15 months after initial diagnosis, the patient showed right hemispheric tumor progression and an additional new left frontal contrast enhancement in the subsequent imaging. A re-resection of the right-sided tumor and resection of the left frontal tumor were conducted. Neuropathological work-up showed recurrence of the right-sided oligodendroglioma with features of an anaplastic oligodendroglioma WHO Grade III, but a glioblastoma WHO grade IV for the left frontal lesion. In depth molecular profiling revealed two independent brain tumors with distinct molecular profiles of anaplastic oligodendroglioma IDH mutated 1p/19q co-deleted WHO Grade III and glioblastoma IDH wildtype WHO grade IV. This unique and rare case of a patient with two independent brain tumors revealed by in-depth molecular work-up and epigenomic profiling emphasizes the importance of integrated work-up of brain tumors including methylome profiling for advanced patient care.

The "springform" technique in cranioplasty: custom made 3D-printed templates for intraoperative modelling of polymethylmethacrylate cranial implants.

BACKGROUND: Manual moulding of cranioplasty implants after craniectomy is feasible, but does not always yield satisfying cosmetic results. In contrast, 3D printing can provide precise templates for intraoperative moulding of polymethylmethacrylate (PMMA) implants in cranioplasty. Here, we present a novel and easily implementable 3D printing workflow to produce patient-specific, sterilisable templates for PMMA implant moulding in cranioplastic neurosurgery. METHODS: 3D printable templates of patients with large skull defects before and after craniectomy were designed virtually from cranial CT scans. Both templates - a mould to reconstruct the outer skull shape and a ring representing the craniectomy defect margins - were printed on a desktop 3D printer with biocompatible photopolymer resins and sterilised after curing. Implant moulding and implantation were then performed intraoperatively using the templates. Clinical and radiological data were retrospectively analysed. RESULTS: Sixteen PMMA implants were performed on 14 consecutive patients within a time span of 10 months. The median defect size was 83.4 cm2 (range 57.8-120.1 cm2). Median age was 51 (range 21-80) years, and median operating time was 82.5 (range 52-152) min. No intraoperative complications occurred; PMMA moulding was uneventful and all implants fitted well into craniectomy defects. Excellent skull reconstruction could be confirmed in all postoperative computed tomography (CT) scans. In three (21.4%) patients with distinct risk factors for postoperative haematoma, revision surgery for epidural haematoma had to be performed. No surgery-related mortality or new and permanent neurologic deficits were recorded. CONCLUSION: Our novel 3D printing-aided moulding workflow for elective cranioplasty with patient-specific PMMA implants proved to be an easily implementable alternative to solely manual implant moulding. The "springform" principle, focusing on reconstruction of the precraniectomy skull shape and perfect closure of the craniectomy defect, was feasible and showed excellent cosmetic results. The proposed method combines the precision and cosmetic advantages of computer-aided design (CAD) implants with the cost-effectiveness of manually moulded PMMA implants.

Genotypical glioblastoma of the frontal lobe mimicking ganglioglioma: A case report and review of the literature.

This case of severe phenotype-genotype mismatch brain tumor morphologically mimicking benign ganglioglioma emphasizes the urgent need for advanced molecular profiling in brain tumor diagnosis in the era of sophisticated molecular profiling.

Rapid Microscopic Detection of Bacillus anthracis by Fluorescent Receptor Binding Proteins of Bacteriophages.

Bacillus anthracis, the etiological agent of anthrax disease, is typically diagnosed by immunological and molecular methods such as polymerase chain reaction (PCR). Alternatively, mass spectrometry techniques may aid in confirming the presence of the pathogen or its toxins. However, because of the close genetic relationship between B. anthracis and other members of the Bacillus cereus sensu lato group (such as Bacillus cereus or Bacillus thuringiensis) mis- or questionable identification occurs frequently. Also, bacteriophages such as phage gamma (which is highly specific for B. anthracis) have been in use for anthrax diagnostics for many decades. Here we employed host cell-specific receptor binding proteins (RBP) of (pro)-phages, also known as tail or head fibers, to develop a microscopy-based approach for the facile, rapid and unambiguous detection of B. anthracis cells. For this, the genes of (putative) RBP from Bacillus phages gamma, Wip1, AP50c and from lambdoid prophage 03 located on the chromosome of B. anthracis were selected. Respective phage genes were heterologously expressed in Escherichia coli and purified as fusions with fluorescent proteins. B. anthracis cells incubated with either of the reporter fusion proteins were successfully surface-labeled. Binding specificity was confirmed as RBP fusion proteins did not bind to most isolates of a panel of other B. cereus s.l. species or to more distantly related bacteria. Remarkably, RBP fusions detected encapsulated B. anthracis cells, thus RBP were able to penetrate the poly-γ-d-glutamate capsule of B. anthracis. From these results we anticipate this RBP-reporter assay may be useful for rapid confirmative identification of B. anthracis.

Diffuse midline glioma of the cervical spinal cord with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma: a case report and review of the literature.

Here, we report on a 28-year old male patient presenting with neck and shoulder pain, dysesthesia of all four limbs and hypesthesia of both hands, without motor deficits. Magnetic resonance imaging showed an intradural, intramedullary mass of the cervical spinal cord of 6.4 cm length and 1.7 cm diameter. The patient underwent surgical resection. Histological and immunohistochemical evaluation showed pleomorphic glial tumor cells, mitoses, calcifications, and atypical ganglioid cells compatible with the morphology of anaplastic ganglioglioma (WHO Grade III). Extensive molecular workup revealed H3F3A K27M, TERT C228T and PDGFRα Y849C mutations indicating poor prognosis. The H3F3A K27M mutation assigned the tumor to the molecular group of diffuse midline glioma (WHO Grade IV). Epigenome-wide methylation profiling confirmed the methylation class of diffuse midline glioma. Thus, this is a very rare case of malignant glioma with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma. This case emphasizes the importance of comprehensive morphological and molecular workup including methylome profiling for advanced patient care.