Endoscopy-assisted removal of periorbital inclusion cysts in children

Surgical treatment for periorbital inclusion cysts typically involves a brow, pterional, or partial bicoronal scalp incision for sufficient exposure. The authors have recently employed an endoscopy-assisted technique as an alternative approach intended to minimize the length of the skin incision and avoid scarring in the brow. Children having typical clinical findings of a dermoid cyst located on the hairless forehead were selected to undergo endoscopy-assisted cyst removal. For suspected intradiploic lesions, MR imaging was used to assess osseous involvement. After induction of general anesthesia, a 1–2-cm curvilinear incision was made posterior to the hairline. A 30°-angled endoscope (4 mm) was then used for dissection in the subgaleal compartment. Subgaleal dissection was followed by a circumferential periosteal incision in which the authors used an angled needle-tip unipolar cautery. For lesions within the diploe, a high-speed air drill was used to expose the lesion. Complete removal was accomplished with curettage of either the skull or dural surface. Eight patients (5–33 months of age) underwent outpatient endoscopic resection. Seven cysts were extracranial, and 1 cyst extended through the inner table. In all patients complete excision of the cyst was achieved. There was negligible blood loss, no dural violation, and no postoperative infection. There have been no recurrences at a mean follow-up of 15 months. Endoscopy-assisted resection of inclusion cysts of the scalp and calvaria is a safe and effective surgical approach. The technique results in negligible incisions with less apparent scarring compared with previously described incisions. This limited-access technique does not appear to be associated with a higher incidence of cyst recurrence

Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells

Diffuse intrinsic pontine glioma (DIPG) is a devastating disease with an extremely poor prognosis. Recent studies have shown that platelet-derived growth factor receptor (PDGFR) and its downstream effector pathway, PI3K/AKT/mTOR, are frequently amplified in DIPG, and potential therapies targeting this pathway have emerged. However, the addition of targeted single agents has not been found to improve clinical outcomes in DIPG, and targeting this pathway alone has produced insufficient clinical responses in multiple malignancies investigated, including lung, endometrial, and bladder cancers. Acquired resistance also seems inevitable. Activation of the Ras/Raf/MEK/ERK pathway, which shares many nodes of cross talk with the PI3K/AKT pathway, has been implicated in the development of resistance. In the present study, perifosine, a PI3K/AKT pathway inhibitor, and trametinib, a MEK inhibitor, were combined, and their therapeutic efficacy on DIPG cells was assessed. Growth delay assays were performed with each drug individually or in combination. Here, we show that dual inhibition of PI3K/AKT and MEK/ERK pathways synergistically reduced cell viability. We also reveal that trametinib induced AKT phosphorylation in DIPG cells that could not be effectively attenuated by the addition of perifosine, likely due to the activation of other compensatory mechanisms. The synergistic reduction in cell viability was through the pronounced induction of apoptosis, with some effect from cell cycle arrest. We conclude that the concurrent inhibition of the PI3K/AKT and MEK/ERK pathways may be a potential therapeutic strategy for DIPG

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents

Leptomeningeal dissemination in pediatric brain tumors

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors

Calculated Blood Loss and Transfusion Requirements in Primary Open Repair of Craniosynostosis

Background:. Open surgical correction is effective in the treatment of craniosynostosis but may result in significant blood loss and transfusions. This study seeks to compare surgeon estimated blood loss with calculated blood loss and provide contemporary data that objectively quantify blood loss and transfusion rate associated with open repair of craniosynostosis. Methods:. A retrospective review of patients undergoing primary open repair of craniosynostosis between May 2011 and November 2016 was performed. The medical records of 43 patients were reviewed to obtain the operative age, weight, affected suture, pre- and postoperative hematocrit, blood transfusion volume, estimated blood loss, and syndromic status. Estimated blood volume (EBV) and red cell mass were calculated for analysis. Results:. The median age and weight at the time of surgery were 9 months and 8.6 kg, respectively. Mean surgeon estimated blood loss was 207.4 mL (28.1% of EBV). Mean calculated blood loss was 318 mL (44.3% of EBV). The mean transfusion volume was 188 mL (26.5% of EBV). The mean transfusion as a percent of estimated red cell mass was 59.1%. Fourteen percent of patients did not require any transfusion. Conclusions:. We report intraoperative blood losses and transfusion requirements that are lower than those of many previous studies of open repair of craniosynostosis. Additionally, we found that calculated blood loss estimates may be more reliable than surgeon-derived estimated blood loss. We hope that these updated, objective data will be useful in comparisons of open repair to minimally invasive surgery or to new blood loss reducing procedures

Central nervous system tuberculoma mimicking a brain tumor: A case report

The central nervous system (CNS) is a rare but serious site of tuberculosis spread that manifests in three forms: meningitis, spinal arachnoiditis, and CNS tuberculoma. CNS tuberculoma, or intracranial tuberculous granuloma, is a caseating or non-caseating granulomatous reaction within the brain parenchyma that may mimic a brain tumor. We present the case of a 10-year-old male patient with a travel history to Western Africa who presented to our institution after his fourth tonic-clonic seizure over 2 months. MRI of the brain revealed a solitary cortical/subcortical enhancing intracranial mass with intralesional hemorrhage and mineralization, pathologically proven to represent a CNS tuberculoma. While rare, this etiology should be considered with the appropriate travel history and for which prompt treatment may improve outcomes in the pediatric population