Pediatric Traumatic Injuries Due to Agrarian Hay-Hole Falls.

Hay-holes are a design feature in many traditionally built barns that serve as a portal through which stored hay is passed to the lower level where animals are fed. Unfortunately, children sometimes fall through the hay-hole to the concrete or packed earth below. Available data on the frequency and types of hay-hole injuries is limited. The purpose of this study was to better characterize the resultant injuries and identify prognostic factors that predict outcomes from them. We performed a retrospective review of 53 children admitted to the Penn State Hershey Children's Hospital at the Penn State Hershey Medical Center with injuries due to a fall through a hay-hole over 15 years. Compared to urban trauma, hay-hole falls more frequently involve younger children and craniofacial injuries. Although they may result in significant injuries, they are rarely fatal. Greater fall height is associated with longer length of stay (LOS) but not with a greater frequency of intubation, intracranial hemorrhage, or skull fracture. A re-examination of barn design may help to reduce the frequency of this injury type.

Minimally Invasive Ventriculo-Cholecystic Shunt Placement Utilizing Combined Ultrasound and Fluoroscopic Guidance.

For the management of hydrocephalus with ventricular cerebrospinal fluid (CSF) shunting, multiple therapeutic options are available. Among these routes, the most commonly used are ventriculo-peritoneal, ventriculo-atrial, and ventriculo-pleural, while ventriculo-cholecystic is a less common option. Although ventriculo-peritoneal is accepted as the first option, ventriculo-cholecystic shunting may be performed in patients who are poor candidates for other routes of shunt placement. Open cholecystic shunt placement may be contraindicated in patients who have undergone previous surgeries or other comorbidities. Here, we present the case of a 25-year-old female with a complex medical history who presented with a posterior fossa intraparenchymal hemorrhage and subsequent hydrocephalus. She was unable to undergo a ventriculo-peritoneal, atrial, or pleural shunt placement, and thus, a cholecystic shunt placement was chosen. Due to a history of previous surgeries and comorbidities as well as a large volume of idiopathic and recurrent ascites, open placement was contraindicated in this patient. To the best of our knowledge, we present the first successful adult case of a minimally invasive ventriculo-cholecystic shunt placement under ultrasound and fluoroscopic guidance.

The Potential of Glioblastoma Patient Symptoms to Diagnose and Predict Survival.

Glioblastoma is a devastating malignancy with a dismal survival rate and median survival time of 14 months. Currently, the biomarkers for glioblastoma are mostly molecular and include EGFRvIII, ATRX, PTEN, IDH1, MGMT, and others. These prognostic tumor biomarkers are obtained through a surgical biopsy and thus are not easily attainable. Clinicians would benefit from a robust, non-invasive, and readily available indicator for early diagnosis and accurate prognostication for glioblastoma patients. In this study, we assessed whether specific patient symptoms could provide an early diagnosis of glioblastoma. Further, we also assessed if any patient symptomatology could provide clinicians with the ability to prognosticate patient survival more accurately. We retrospectively reviewed the clinical data for 218 patients. We determined whether symptoms including headache, weakness, seizure, memory loss/confusion, visual changes, speech changes, and loss of consciousness led to a patient being diagnosed earlier and if any of these symptoms predicted diminished patient survival. Our study determined that weakness and memory loss/confusion were the symptoms that predicted diminished survival, and weakness alone was the symptom that predicted an earlier diagnosis. This study further elucidates the complexities of glioblastoma and provides clinicians with more data for their patients when discussing prognostication after diagnosis of glioblastoma.

Spontaneous Hip Dislocation Complicating the Management of Malignant Peripheral Nerve Sheath Tumor Arising Within a Plexiform Neurofibroma.

Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders. It can cause plexiform neurofibromas, leading to diffuse enlargement of a nerve or nerves within the body. There are benign in general, however, can cause significant symptoms due to their size, including bony erosion, pain, and joint instability. Unfortunately, they also have the capacity to become malignant by internal transformation into a malignant peripheral nerve sheath tumor (MPNST). The case presented here is a 27-year-old male with NF1 that was followed for years with a pelvic girdle plexiform neurofibroma whose course was complicated by transformation to MPNST and a spontaneous hip dislocation. He underwent excision, Girdlestone procedure, chemotherapy, and radiation. Unfortunately, he subsequently developed lung metastases and is part of a clinical trial with an MDM2 inhibitor and pembrolizumab.

Aneurysmal and arteriovenous malformation hemorrhage during pregnancy: An update on the epidemiology, risk factors and prognosis.

INTRODUCTION: Intracranial hemorrhage (ICH) is a devastating condition with a high rate of morbidity and mortality. Aneurysm or arteriovenous malformation (AVM) rupture are two common etiologies leading to ICH. Here we provide an update on ICH during pregnancy with a focus on those caused by aneurysm or AVM rupture. METHODS: Here we systematically review 25 studies reported in the literature to provide an update on ICH during pregnancy focusing on aneurysm or AVM rupture. We also reviewed the prognosis of ICH during puerperium. RESULTS: Discrepancies exist between studies supporting or refuting the hypothesis of a higher rate of ICH during pregnancy, obscuring the overall rate of aneurysm and AVM rupture in pregnant ICH patients. However, risk factors such as maternal age and hypertension have shown to increase the frequency of ICH in pregnant patients. We also show increased morbidity and mortality in patients suffering from preeclampsia/eclampsia. DISCUSSION: ICH is rare, but the various studies demonstrating its increased frequency, morbidity, and mortality during pregnancy should raise our awareness of this condition. The management and treatment decisions for a pregnant ICH patient should follow the same principles as nonpregnant patients, but with the knowledge that not all medications are appropriate for use in the pregnant patient. Although there seems to be a higher frequency of AVM rupture, further research must be conducted in order to fully determine the effects of pregnancy on aneurysm and AVM ruptures.

Congenital Spinal Cysts: An Update and Review of the Literature.

Congenital spinal cysts are rare and encompass a wide variety of diseases including arachnoid, enterogenous, teratomatous, neurenteric, foregut, bronchogenic, epithelial, ependymal, dermoid, and epidermoid cysts. Here, we elucidate the epidemiology, pathology, pathogenesis, and diagnostic findings of the most common congenital spinal cysts, followed by a discussion of their presentation and treatment options. Differentiating the cause of each lesion is crucial for targeted clinical and surgical management for the patient. Our review describes how arachnoid cysts can be observed, fenestrated, percutaneously drained, or shunted; however, the primary goal for neurenteric, dermoid, and epidermoid cysts is removal. Further, we discuss how patient presentation is dependent on the rate of growth and location of compression on the spinal cord and nerve roots. However, although many of these lesions are discovered incidentally on imaging, the spectrum of possible symptoms include pain, weakness, ataxia, bladder incontinence, and progressive or acute neurologic deficits. We present and review the histology and imaging of a variety of cysts and discuss how although the goal of treatment is resection, the risks of surgery must be considered against the benefits of complete resection in each case.

A Unique Case of a High-Grade Neuroepithelial Tumor With EML4-ALK Fusion in a Five-Month-Old.

We present a unique and challenging case of a high-grade neuroepithelial tumor with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion in a five-month-old child. This tumor was difficult to classify, with glial and ependymal features, reinforcing the impact of a molecular-based diagnosis in correct classification and management. The patient had two tumor resections and underwent chemotherapy following the Head Start trial treatment regimen. The patient remains well, with no residual disease on MRI 15 months after initial resection. Further studies are needed to determine the frequency of EML4-ALK fusions in these types of tumors and to optimize therapeutic protocols for children and adults, alike, suffering from this disease.

Post-Laminectomy Kyphosis in Achondroplasia Patients: To Concurrently Fuse or Not.

The purpose of this review is to look at the incidence of post-laminectomy kyphosis in achondroplasia patients and to determine whether skeletal maturity and the number and location of laminectomies predict kyphosis in this patient population. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2019. After removing duplicates and checking for relevancy, the final number of articles yielded was eight. The results of this review summarize the incidence of post-laminectomy kyphosis in achondroplasia patients. In conclusion, we suggest fusion be considered in conjunction with multilevel laminectomies due to a high incidence of kyphosis with a need for stabilization in the pediatric achondroplastic patient population.

Suprasellar central nervous system ganglioneuroblastoma: a case in a 9-year-old child and review of the literature.

PURPOSE: Intracranial ganglioneuroblastomas are incredibly rare neuroectodermal tumors with only 8 described cases total, 5 of those having imaging findings METHODS: Here we present a 9-year-old female patient with 4 months progressive headaches, personality changes, and vomiting. We also present a review of the current literature of intracranial ganglioneuroblastomas. RESULTS: Imaging demonstrated a partially calcified suprasellar mass measuring 4.6 × 6.3 × 5 cm composed of both solid and cystic components, diagnosed to be a ganglioneuroblastoma, with mass effect on the lateral and 3rd ventricles, with a midline shift of right to left of 6-7 mm. She was treated with subtotal surgical resection, an intensive chemotherapeutic regimen, and radiation and has no residual disease on imaging 1 year and 4 months status post-surgery. CONCLUSION: To our knowledge, this is the first case of a ganglioneuroblastoma to mimic a craniopharyngioma based upon imaging findings and suprasellar location. As these cases are extremely rare, an optimal therapeutic regimen has not been defined. However, a combination of surgical resection, chemotherapy, and radiation therapy can be effective, as shown here with successful treatment and no evidence of residual disease.

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity.

OBJECTIVE: BRAF V600E is a common oncogenic driver in a variety of primary brain tumors. Dual inhibitor therapy using dabrafenib (a selective oral inhibitor of several mutated forms of BRAF kinase) and trametinib (a reversible inhibitor of MEK1 and MEK2) has been used successfully for treatment of metastatic melanoma, anaplastic thyroid cancer, and other tumor types, but has been reported in only a few patients with primary brain tumors and none with pleomorphic xanthoastrocytoma. Here, the authors report on the substantial clinical response and reduction in cutaneous toxicity in a case series of BRAF V600E primary brain cancers treated with dual BRAF/MEK inhibitor therapy. METHODS: The authors treated 4 BRAF V600E patients, each with a different type of primary brain tumor (pilocytic astrocytoma, papillary craniopharyngioma, ganglioglioma, and pleomorphic xanthoastrocytoma) with the combination of dabrafenib and trametinib. RESULTS: The patients with pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and papillary craniopharyngioma experienced near-complete radiographic and complete clinical responses after 8 weeks of therapy. A substantial partial response (by RANO [Response Assessment in Neuro-Oncology] criteria) was observed in the patient with ganglioglioma. The patient with craniopharyngioma developed dramatic, diffuse verrucal keratosis within 2 weeks of starting dabrafenib. This completely resolved within 2 weeks of adding trametinib. CONCLUSIONS: Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events.

The Relative Location of the Major Femoral Nerve Motor Branches in the Thigh.

In peripheral nerve surgery, repair of the femoral nerve (FN) requires identification of normal nerve elements both proximal and distal to the level of the injury. We identified FN branches to the sartorius (SRT) and quadriceps muscles in 16 embalmed specimens and calculated the length of each branch to its point of entry into its respective muscle. The SRT and rectus femoris (RF) muscles were mobilized but not transected to mimic the surgical approach. Ratios of the length of each motor branch as a unit of the total length of the thigh, defined as the FN at the inguinal ligament to the superior margin of the patella were also calculated. The proximal branch to RF spanned a ratio of .19 ± .11 (mean ± standard deviation) from the FN at the inguinal ligament to its endpoint. The ratio of the distal branch to the RF was .29 ± .08. The ratio of the proximal SRT branch was .20 ± .05. The distal branch to SRT was located at a ratio of .43 ± .11. The proximal branch to vastus lateralis (VL) was .26 ± .08. The distal branch to VL was .39 ± .07. The ratio of the motor branch to vastus intermedius (VI) was .30 ± .05. Lastly, the branch to vastus medialis (VM) was .55 ± .06. The motor branch to SRT frequently emerged as a bifurcation of itself and saphenous nerve within the adductor canal. Knowledge of the relative location of the motor branches of the FN in the thigh can be helpful to surgeons during the nerve exploration and repair.

STEMI: rare initial presentation of a mediastinal mass supplied by the RCA.

In the setting of severe septic shock, a 70-year-old woman had an ST segment myocardial infarction with ST elevations in the inferolateral leads. On cardiac catheterisation, no obstructive pathology was noted. Chest imaging revealed a large mediastinal mass measuring 8.5×6.5×7.5 cm in the visceral compartment of the mediastinum, with contrast enhancement from the right coronary artery (RCA). A biopsy was preformed and cytology was consistent with a well-differentiated neuroendocrine neoplasm. On review of the cardiac catherisation, it was noted that the mass was deriving blood supply from the RCA. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare but well-documented phenomenon. In this case, MINOCA was caused by coronary steal syndrome in the setting of profound hypotension. Immediate management is with haemodynamic support; there is no role for coronary intervention.

Exosomes and their implications in central nervous system tumor biology.

Exosomes are 20-100 nm cellular derived vesicles that upon discovery, were thought to be a form of cellular recycling of intracellular contents. More recently, these vesicles are under investigation for their purported significant roles in intercellular communication in both healthy and diseased states. Herein, we focus on the secretion of exosomes associated with glioblastoma, as most exosome studies on brain tumors have been performed in this tumor type. However, we included exosomes secreted from other forms of brain tumors for comparison as available. Exosomes contain intracellular content that can be transferred to other cells in the tumor or to cells of the immune system and endothelial cells. These recipient cells may subsequently take on oncogenic properties, including therapeutic resistance, cancer progression, and angiogenesis. Genetic components (DNA, RNA and miRNA) of the cell of origin may be included in the secreted exosomes. The presence of genetic material in the exosomes could serve as a biomarker for mutations in tumors, potentially leading to novel treatment strategies. In the last decade, exosomes have been identified as having a major impact on multiple aspects of medicine and tumor biology, and appear to be primed for a critical position in cancer diagnosis, prognosis, and treatment.

Exosomes impact survival to radiation exposure in cell line models of nervous system cancer.

Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressive miR-516, miR-365, and multiple tumor-suppressive mRNAs. Ingenuity pathway analysis revealed the most represented networks included cell cycle, growth/survival. Upregulation of DNM2 correlated with increased exosome uptake. To analyze the property of exosome blockade, heparin and simvastatin were used to inhibit uptake of exosomes in recipient cells resulting in inhibited induction of proliferation and cellular survival. Because these agents have shown some success as cancer therapies, our data suggest their mechanism of action could be limiting exosome communication between cells. The results of our study identify a novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation.

Targeting IL-13Rα2 for effective treatment of malignant peripheral nerve sheath tumors in mouse models.

OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that harbor a high potential for metastasis and have a devastating prognosis. Combination chemoradiation aids in tumor control and decreases tumor recurrence but causes deleterious side effects and does not extend long-term survival. An effective treatment with limited toxicity and enhanced efficacy is critical for patients suffering from MPNSTs.METHODSThe authors recently identified that interleukin-13 receptor alpha 2 (IL-13Rα2) is overexpressed on MPNSTs and could serve as a precision-based target for delivery of chemotherapeutic agents. In the work reported here, a recombinant fusion molecule consisting of a mutant human IL-13 targeting moiety and a point mutant variant of Pseudomonas exotoxin A (IL-13.E13 K-PE4E) was utilized to treat MPNST in vitro in cell culture and in an in vivo murine model.RESULTSIL-13.E13 K-PE4E had a potent cytotoxic effect on MPNST cells in vitro. Furthermore, intratumoral administration of IL-13.E13 K-PE4E to orthotopically implanted MPNSTs decreased tumor burden 6-fold and 11-fold in late-stage and early-stage MPNST models, respectively. IL-13.E13 K-PE4E treatment also increased survival by 23 days in the early-stage MPNST model.CONCLUSIONSThe current MPNST treatment paradigm consists of 3 prongs: surgery, chemotherapy, and radiation, none of which, either singly or in combination, are curative or extend survival to a clinically meaningful degree. The results presented here provide the possibility of intratumoral therapy with a potent and highly tumor-specific cytotoxin as a fourth treatment prong with the potential to yield improved outcomes in patients with MPNSTs.

Utility of Early Postoperative Magnetic Resonance Imaging After Glioblastoma Resection: Implications on Patient Survival.

BACKGROUND: The standard of care for glioblastoma is surgical resection followed by combination temozolomide and radiation. Magnetic resonance imaging (MRI) is used preoperatively for tumor resection planning. In some instances, MRI is also obtained postoperatively to assess for any complications and to determine extent of resection. There is some question whether early routine postoperative imaging of patients after tumor resection is beneficial to long-term outcomes, especially with the increased scrutiny of increasing health care costs. METHODS: In this study we retrospectively analyze patients with glioblastoma treated at our institution, comparing the difference in overall survival and treatment regimens between patients who had early postoperative MRI versus patients who did not. RESULTS: We determine that in our cohort of 125 patients, those with early postoperative MRI had no statistically significant overall survival difference compared with patients with no early postoperative MRI (P = 0.996). The median survival for the group with postoperative MRI was 378 days (95% confidence interval [CI], 242-443 days), and the median survival for the group without postoperative MRI was 308 days (95% CI, 203-445 days). Early postoperative MRI also did not significantly alter therapeutic regimens. CONCLUSIONS: Although early postoperative MRI may not significantly affect patient overall survival from a statistical standpoint or therapeutic regimens, this type of imaging may be important to hone resident and attending skill. We encourage other institutions to perform similar analyses to determine the overall survival benefit of early postoperative imaging after glioma resection for patients with glioblastoma.

Intra-cerebrospinal fluid antibiotics to treat central nervous system infections: A review and update.

Central nervous system infections can be complications of neurosurgical procedures or can occur spontaneously, and occasionally lead to devastating neurological complications, increased rate of mortality, and lengthier stays in the hospital, subsequently increasing costs. The use of intrathecal antibiotics to bypass the blood brain barrier and provide effective concentrations to the central nervous system has been described as an adjunct treatment option. However, the regimens of antibiotics utilized intrathecally have not been standardized. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2017 and after removing duplicates and checking for relevancy, the final number of articles yielded was 200. This review summarizes the use of antibiotics intrathecally to treat CNS infections, the dosages, therapeutic efficacies, and highlights significant side effects. The current rates of mortality in patients suffering from CNS infections is high, thus intrathecal antibiotic therapy should be considered as a potential therapeutic strategy in this patient population. Multiple antibiotics have demonstrated safety and efficacy when used intrathecally, and further studies, including clinical trials, need to be performed to elucidate their full therapeutic potential and outline proper dosing regimens.

Intracranial malignant peripheral nerve sheath tumor variant: an unusual neurovascular phenotype sarcoma case invading through the petrous bone.

INTRODUCTION: Intracranial malignant peripheral nerve sheath tumor (MPNST) is exceedingly rare. Previously reported cases of intracranial MPNST have been associated with development within a prominent cranial nerve. METHODS: This is the first report of an MPNST with both nerve sheath and vascular phenotype that follows the neurovascular bundle, without arising in a major cranial nerve or in the setting of neurofibromatosis type 1 (NF1). RESULTS: The patient is a 14-year-old boy with a history of worsening headaches for the past several months, left-sided hearing loss, nausea, vomiting, and vertigo. MRI was performed that demonstrated a large extra-axial tumor compressing the left infratemporal posterior temporal region. The tumor was associated with significant destruction of the superior portion of the petrous bone and extension through the petrous into the upper posterior fossa, immediately below the tentorium. The patient underwent surgical debulking and adjuvant chemotherapy with doxorubicin and ifosfamide. Pathology demonstrated a variant malignant peripheral nerve sheath tumor with both nerve sheath and vascular phenotype by immunostains. The patient's symptoms improved following treatment. CONCLUSION: We present the first reported case of an intracranial MPNST variant that developed along the neurovascular bundle as a sarcoma with both nerve sheath and vascular phenotype through the petrous bone and not associated with a major cranial nerve or with stigmata of neurofibromatosis type 1 (NF1). Although this is an extremely unusual presentation due to location and lack of prominent cranial nerves in that location, it is not unusual for benign nerve sheath tumors to follow the neurovascular bundle through foramen of cortical long bone or pelvis. This case suggests that physicians should incorporate intracranial MPNST variant into their differential diagnosis in the cranium, even when tumor is not located near a prominent cranial nerve. Surgical debulking and adjuvant chemotherapy with doxorubicin and ifosfamide has led to improvement in patient symptoms.

MLN8237 treatment in an orthoxenograft murine model for malignant peripheral nerve sheath tumors.

OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas arising from peripheral nerves. MPNSTs have increased expression of the oncogene aurora kinase A, leading to enhanced cellular proliferation. This makes them extremely aggressive with high potential for metastasis and a devastating prognosis; 5-year survival estimates range from a dismal 15% to 60%. MPNSTs are currently treated with resection (sometimes requiring limb amputation) in combination with chemoradiation, both of which demonstrate limited effectiveness. The authors present the results of immunohistochemical, in vitro, and in vivo analyses of MLN8237 for the treatment of MPNSTs in an orthoxenograft murine model.METHODSImmunohistochemistry was performed on tumor sections to confirm the increased expression of aurora kinase A. Cytotoxicity analysis was then performed on an MPNST cell line (STS26T) to assess the efficacy of MLN8237 in vitro. A murine orthoxenograft MPNST model transfected to express luciferase was then developed to assess the efficacy of aurora kinase A inhibition in the treatment of MPNSTs in vivo. Mice with confirmed tumor on in vivo imaging were divided into 3 groups: 1) controls, 2) mice treated with MLN8237, and 3) mice treated with doxorubicin/ifosfamide. Treatment was carried out for 32 days, with imaging performed at weekly intervals until postinjection day 42. Average bioluminescence among groups was compared at weekly intervals using 1-way ANOVA. A survival analysis was performed using Kaplan-Meier curves.RESULTSImmunohistochemical analysis showed robust expression of aurora kinase A in tumor cells. Cytotoxicity analysis revealed STS26T susceptibility to MLN8237 in vitro. The group receiving treatment with MLN8237 showed a statistically significant difference in tumor size compared with the control group starting at postinjection day 21 and persisting until the end of the study. The MLN8237 group also showed decreased tumor size compared with the doxorubicin/ifosfamide group at the conclusion of the study (p = 0.036). Survival analysis revealed a significantly increased median survival in the MLN8237 group (83 days) compared with both the control (64 days) and doxorubicin/ifosfamide (67 days) groups. A hazard ratio comparing the 2 treatment groups showed a decreased hazard rate in the MLN8237 group compared with the doxorubicin/ifosfamide group (HR 2.945; p = 0.0134).CONCLUSIONSThe results of this study demonstrate that MLN8237 is superior to combination treatment with doxorubicin/ifosfamide in a preclinical orthoxenograft murine model. These data have major implications for the future of MPNST research by providing a robust murine model as well as providing evidence that MLN8237 may be an effective treatment for MPNSTs.

Craniopharyngiomas: A systematic review and evaluation of the current intratumoral treatment landscape.

Cushing once described craniopharyngiomas as the most forbidding tumor; and, despite surgical advances decades later, craniopharyngioma resection is still extremely complex due to its location and infiltration into local structures, making gross total resection challenging. Adjuvant treatments include radiation and chemotherapy, but intratumoral therapy may emerge as an adjuvant treatment for craniopharyngiomas. Here, we present a review of the literature on this treatment modality; and, summarize the available reported cases to underline usefulness and effectiveness of this treatment method. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from 1974 to 2017. All articles were assessed for relevancy before inclusion into this review. Although the role for intratumoral therapy is unclear, multiple studies have reported efficacy in the treatment of craniopharyngiomas, and current results are promising. Out of the intratumoral agents utilized, intratumoral alpha interferon seems to provide the best response and least side effects for the treatment of craniopharyngiomas. The use of intratumoral therapy has led to delay in treatment with definitive surgery or radiation, both of which are associated with significant morbidities, detrimental in developmental years of childhood. Out of the intratumoral agents utilized, intratumoral alpha interferon seems to provide the best response and least side effects for the treatment of craniopharyngiomas. These findings need to be explored further with randomized controlled trials, outlining a standard dosing regimen. Furthermore, trials in craniopharyngioma patients with these combination therapies must be performed to determine the optimal therapeutic regimen for the successful treatment of these patients.