maintaining-human-glioblastoma-cellular-diversity-ex-vivo-using-three

Maintaining Human Glioblastoma Cellular Diversity <em>Ex vivo</em> using Three-Dimensional Organoid Culture

Glioblastoma (GBM) is the most commonly occurring primary malignant brain cancer with an extremely poor prognosis. Intra-tumoral cellular and molecular ...

Cleveland Clinic

Microsurgical removal is the preferred treatment for most deep-seated, intraaxial tumors in the pediatric population. The feasibility of surgery as an option has improved with advances in surgical technology and technique. Tubular retractors disperse retraction forces over a greater surface area than do conventional retractors, which can lower the risk of ischemic complications. The authors describe their experience utilizing a new tubular retractor system specifically designed for cranial applications in conjunction with frameless neuronavigation.

Use of a minimally invasive tubular retraction system for deep-seated tumors in pediatric patients.

The papillary tumor of the pineal region (PTPR) is a distinct entity that is particularly rare in the pediatric population. The authors document the youngest reported patient with this clinicopathological entity to date. A case of PTPR in a 15-month-old boy is described. Initially thought to be a tectal glioma, the tumor was later identified as a pineal region tumor after demonstrating growth on routine imaging. Diagnosis of PTPR was established by histopathological evaluation of biopsy samples, which revealed papillary, cystic, and solid tumor components. The patient's postoperative course was complicated by tumor growth despite several debulking procedures and chemotherapy, as well as persistent hydrocephalus requiring 2 endoscopic third ventriculostomies and eventual ventriculoperitoneal shunt placement. After a 15-month follow-up period, the patient has received proton-beam therapy and has a stable tumor size. The PTPR is a recently described tumor of the CNS that must be included in the differential diagnosis of pineal region masses. The biological behavior, prognosis, and appropriate treatment of PTPR have yet to be fully defined.

Papillary tumor of the pineal region in a 15-month-old boy.

Poland syndrome is characterized by hypoplastic unilateral chest wall structures. These chest wall deformities may be associated with upper extremity anomalies. The association of Poland syndrome with either intercostal liver herniation or a spinocerebral deformity has been described, but there is no report of both findings encountered simultaneously. This is the first report of a newborn child with Poland syndrome associated with an intercostal liver segment herniation and thoracic myelomeningocele with features of an Arnold-Chiari II cerebral malformation.

Poland syndrome with extracorporeal intercostal liver herniation and thoracic myelomeningocele.

Technological advances have made it possible to seamlessly integrate modern neuroimaging into the neurosurgical operative environment. This integration has introduced many new applications improving surgical treatments. One major addition to the neurosurgical armamentarium is intraoperative navigation and MRI, enabling real-time use during surgery. In the 1970s, the American College of Radiology issued safety guidelines for diagnostic MRI facilities. Until now, however, no such guidelines existed for the MRI-integrated operating room, which is a high-risk zone requiring standardized protocols to ensure the safety of both the patient and the operating room staff. The forces associated with the strong 1.5- and 3.0-T magnets used for MRI are potent and hazardous, creating distinct concerns regarding safety, infection control, and image interpretation. Authors of this paper provide an overview of the intraoperative MRI operating room, safety considerations, and a series of checklists and protocols for maintaining safety in this zero tolerance environment.

Surgical briefings, checklists, and the creation of an environment of safety in the neurosurgical intraoperative magnetic resonance imaging suite.

Intraoperative magnetic resonance imaging (IoMRI) is used to improve the extent of resection of brain tumors. Most previous studies evaluating the utility of IoMRI have focused on enhancing tumors.

Use of high-field intraoperative magnetic resonance imaging to enhance the extent of resection of enhancing and nonenhancing gliomas.

Primary central nervous system lymphoma (PCNSL) is an aggressive type of extra-nodal non-Hodgkin lymphoma. Without treatment, PCNSL is associated with significant morbidity and mortality, including rapid neurological deterioration. In contrast to other high-grade intracranial neoplasms, PCNSL is considered to have a high response rate to conventional medical therapy, especially in younger patients, and therefore warrants particular attention in terms of nonsurgical treatment.

Hyperosmolar and methotrexate therapy avoiding surgery in the acute presentation of primary central nervous system lymphoma.

We describe a pediatric patient with an atypical teratoid rhabdoid tumor (AT/RT) exclusively of the lumbar spine, with a different presentation from the two previously reported pediatric lumbar AT/RT. AT/RT are rare pediatric tumors of the central nervous system, with a dismal prognosis. Although there is sufficient literature on brain AT/RT, spinal AT/RT continues to be a rare entity, with a lumbar location even less frequently reported. A 30-month-old African American boy with multiple comorbidities presented with the inability to ambulate, encopresis and urinary dribbling. The MRI showed an intradural extramedullary mass extending downwards from the L3-4 level. He underwent an L3-S2 laminoplasty. The surgically resected mass was marked by sheets of cells with large nuclei and prominent nucleoli. The tumor cells stained with antibodies to synaptophysin and CAM5.2, and showed no immunoreactivity to INI-1 antibody. He was diagnosed with a World Health Organization Grade IV AT/RT. There was no mutation detected in the SMARCB1 gene on a comprehensive analysis of his blood. The boy is currently being treated according to the Medical University of Vienna AT/RT protocol, with no evidence of tumor recurrence 8 months after surgery. To our knowledge, this is the only report of a lumbar AT/RT in an African American child.

Lumbar spinal atypical teratoid rhabdoid tumor.

The utility of radiosurgery for pediatric brain tumors is not well known. For children, radiosurgery may have an important role for treating unresectable tumors, residual disease, or tumors in the recurrent setting that have received prior radiotherapy. The available evidence demonstrates utility for some children with primary brain tumors resulting in good local control. Radiosurgery can be considered for limited residual disease or focal recurrences. However, the potential toxicities are unique and not insignificant. Therefore, prospective studies need to be performed to develop guidelines for indications and treatment for children and reduce toxicity in this population. 

Radiosurgery for Pediatric Brain Tumors.

Cortical herniation through subdural membrane formation is a rare complication of chronic subdural fluid collections and may occur following subdural shunting. The authors present a unique case of progressive cortical herniation through a compressive subdural membrane that occurred concomitant with a functioning subdural-peritoneal shunt.

Cortical herniation through compressive subdural membrane in an infant with a history of a large bihemispheric subdural hematoma and subdural-peritoneal shunt: case report.

There have been various effective surgical procedures for the treatment of non-syndromic sagittal craniosynostosis, but no definitive guidelines for management have been established. We conducted a study to elucidate the current state of practice and establish a warranted standard of care. An Internet-based study was sent to 180 pediatric neurosurgeons across the country and 102 craniofacial plastic surgeons in fourteen different countries, to collect data for primary indication for surgical management, preference for timing and choice of surgery, and pre-, peri-, and post-operative management options. The overall response rate from both groups was 32% (n=90/284). Skull deformity was the primary indication for surgical treatment in patients without signs of hydrocephalus for both neurosurgeons and craniofacial surgeons (80% and 63%, respectively). Open surgical management was most commonly performed at six months of age by neurosurgeons (46%) and also by craniofacial surgeons (35%). Open surgical approach was favored for patients younger than four months of age by neurosurgeons (50%), but endoscopic approach was favored by craniofacial surgeons (35%). When performing an open surgical intervention, most neurosurgeons preferred pi or reversed pi procedure (27%), whereas total cranial vault remodeling was the most commonly performed procedure by craniofacial surgeons (37%). The data demonstrated a discrepancy in the treatment options for non-syndromic sagittal craniosynostosis. By conducting/comparing a wide survey to collect consolidative data from both groups of pediatric neurosurgeons and craniofacial plastic surgeons, we can attempt to facilitate the establishment of standard of care.

Management options of non-syndromic sagittal craniosynostosis.

Pyogenic ventriculitis is a rare but severe post-neurosurgical complication. The infection is often resistant to antibiotic treatment alone. Continuous intraventricular irrigation has been suggested but the technique is cumbersome, increases the risk for secondary infection, and is inadequate in removing adherent purulence. We used a novel neuroendoscopic approach assisted with a side-cutting aspiration device to treat four cases of post-neurosurgical pyogenic ventriculitis. Ventricular empyema was cleared in all patients and three of the four patients had favorable outcomes.

Neuroendoscopic evacuation of intraventricular empyema using a side-cutting aspiration device.

Autologous bone continues to represent the first choice for reconstruction of calvarial defects. However, unanswered questions remain on the natural history of the graft and the influence of patient-related risk factors. This study investigated the outcomes of skull reconstruction with split calvarial bone graft, examining the natural history and stratifying the risk of unfavorable results.

Reconstruction of Secondary Calvarial Defects with Ex Situ Split Calvarial Bone Grafts: Long-Term Evaluation of Outcomes.

Cranial vault surgery in children with ventricular shunts is more complex due to the possible interference of shunt location with surgical planning and increased risk of shunt related complications. The study evaluated the management of ventricular shunts during cranial vault remodeling (CVR) and subsequent outcomes and complications following CVR.

Cranial Vault Remodeling in Children With Ventricular Shunts.

Glioblastoma (GBM) is the most common primary brain tumor with a dismal prognosis. The inherent cellular diversity and interactions within tumor microenvironments represent significant challenges to effective treatment. Traditional culture methods such as adherent or sphere cultures may mask such complexities whereas three-dimensional (3D) organoid culture systems derived from patient cancer stem cells (CSCs) can preserve cellular complexity and microenvironments. The objective of this study was to determine if GBM organoids may offer a platform, complimentary to traditional sphere culture methods, to recapitulate patterns of clinical drug resistance arising from 3D growth.

Article	Year
Use of a minimally invasive tubular retraction system for deep-seated tumors in pediatric patients. Journal of neurosurgery. Pediatrics\| PubMed ID: 21529192	2011
Papillary tumor of the pineal region in a 15-month-old boy. Journal of neurosurgery. Pediatrics\| PubMed ID: 21529195	2011
Poland syndrome with extracorporeal intercostal liver herniation and thoracic myelomeningocele. Journal of pediatric surgery\| PubMed ID: 22244430	2012
Surgical briefings, checklists, and the creation of an environment of safety in the neurosurgical intraoperative magnetic resonance imaging suite. Neurosurgical focus\| PubMed ID: 23116092	2012
Use of high-field intraoperative magnetic resonance imaging to enhance the extent of resection of enhancing and nonenhancing gliomas. Neurosurgery\| PubMed ID: 24368543	2014
Hyperosmolar and methotrexate therapy avoiding surgery in the acute presentation of primary central nervous system lymphoma. Surgical neurology international\| PubMed ID: 25184099	2014
Lumbar spinal atypical teratoid rhabdoid tumor. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia\| PubMed ID: 26234633	2015
Radiosurgery for Pediatric Brain Tumors. Pediatric blood & cancer\| PubMed ID: 26536284	2016
Cortical herniation through compressive subdural membrane in an infant with a history of a large bihemispheric subdural hematoma and subdural-peritoneal shunt: case report. Journal of neurosurgery. Pediatrics\| PubMed ID: 27885943	2017
Management options of non-syndromic sagittal craniosynostosis. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia\| PubMed ID: 28279556	2017
Neuroendoscopic evacuation of intraventricular empyema using a side-cutting aspiration device. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia\| PubMed ID: 29066241	2018
Reconstruction of Secondary Calvarial Defects with Ex Situ Split Calvarial Bone Grafts: Long-Term Evaluation of Outcomes. Plastic and reconstructive surgery\| PubMed ID: 30589797	2019
Cranial Vault Remodeling in Children With Ventricular Shunts. The Journal of craniofacial surgery\| PubMed ID: 32195842	2020
Three-dimensional organoid culture unveils resistance to clinical therapies in adult and pediatric glioblastoma. Translational oncology\| PubMed ID: 34700192	2022

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