A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. PATIENTS AND METHODS: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine. RESULTS: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM.

Intracranial myeloid sarcoma presentation in distant acute myeloid leukemia remission.

Intracranial myeloid sarcoma (IMS) is a rare central nervous system manifestation of hematopoietic neoplasms of myeloid origin. We report the first case of IMS treatment with an isocitrate dehydrogenase-2 (IDH-2) inhibitor, Enasidenib, following surgical resection, whole-brain radiation, and consolidation Etoposide/Cytarabine therapy. A 42-year-old female was diagnosed with IMS after a 10-year remission of her acute myeloid leukemia (AML). She underwent surgical debulking and had postoperative resolution of her visual symptoms. She received adjuvant radiation and medical management, and continues to show no evidence of recurrence or progression at 17 months postoperatively. This case is notable for an isolated IMS presentation in a patient with a very distant history of AML remission, and without evidence of concurrent bone marrow relapse. The goals of neurosurgical intervention should be symptomatic relief of mass effect and pathological diagnosis, due to the sensitivity of IMS to adjuvant radiation and medical management such as IDH-2 inhibitors.

Treatment Outcomes of Intracranial Myeloid Sarcomas: A Meta-Analysis.

OBJECTIVE: Intracranial myeloid sarcomas (IMS) are rare central nervous system manifestations of malignant hematopoietic neoplasms of myeloid origin such as acute myeloid leukemia and chronic myeloid leukemia. Reported cases in the literature are limited to primarily case reports. We present a systematic review of this rare central nervous system tumor, characterizing the clinical presentation, tumor location, histopathology, and available treatment modalities. We correlate these variables with mortality, recurrence, and complications to suggest optimal management strategies for IMS. METHODS: A systematic literature search was performed across Ovid MEDLINE, Scopus, and Embase using 14 search terms in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This systematic review examines variables such as patient age, tumor location, size, presenting symptoms, treatment modality, extent of resection, and mortality. We performed descriptive analyses to identify bivariate associations between patient characteristics, treatment, and outcomes. RESULTS: The mean age at diagnosis was 34.8 years, and the most common etiology was acute myeloid leukemia (68.8%). The most common presenting symptoms were headache (45.5%), vision complaints (27.3%), and weakness/motor symptoms (21.2%). IMS were most commonly located in the temporal lobe (10.1%), cerebellum (10.1%), or falcine/parasagittal (10.1%) region. Patients who received radiotherapy (P < 0.001) or chemotherapy (P < 0.001) had lower rates of mortality versus those who did not. Surgical treatment and extent of resection were not significantly associated with mortality (P > 0.05). CONCLUSION: The use of adjuvant radiotherapy or chemotherapy for IMS significantly reduces mortality, confirming IMS as a cranial manifestation of a systemic disease. Although surgical treatment is indicated for histopathologic diagnosis and to relieve mass effect, the extent of resection does not predict overall survival.

Pituitary stalk gangliogliomas: Case report and literature review.

INTRODUCTION: Gangliogliomas rarely occur in the sella or suprasellar region and are almost never seen in the pituitary stalk. Seven cases of gangliogliomas occurring in this region have been reported; only one case involved a tumor within the pituitary stalk. Of the six tumors external to the pituitary stalk, two occurred in the neurohypophysis, one was in the adenohypophysis, the location of one was unspecified, and two extensively invaded the optic chiasm, hypothalamus and brainstem. This is only the second reported case of a pituitary stalk ganglioglioma, and it is unique in its use of an extended endoscopic endonasal approach for biopsy. CASE REPORT: A 51-year old woman presented with an eleven-month history of polydipsia and polyuria leading to the diagnosis of diabetes insipidus. Magnetic Resonance Imaging of the brain revealed contrast-enhanced thickening and anterior bowing of the hypophyseal stalk. An extended endoscopic endonasal approach permitted midline removal of the tuberculum sella, opening of underlying dura, and exposure of the pituitary stalk. A firm, white, 4 mm diameter mass, integral to the right side of the enlarged pituitary stalk was seen and biopsied. Histopathological analysis was consistent with WHO grade 1 ganglioglioma. The patient tolerated the procedure well and required no endocrinologic treatment other than desmopressin. CONCLUSION: Pituitary stalk gangliogliomas are extremely rare. The diagnosis should be considered in patients with pituitary stalk enlargement. Endoscopic endonasal approach is a safe surgical approach to establish a tissue diagnosis which is essential for pathologic certainty given the wide differential diagnosis of stalk lesions.

Primary intraosseous meningioma of the calvarium: A systematic review.

BACKGROUND: Primary intraosseous meningiomas (PIM) of calvarial origin are a small subset of meningiomas that arise from and occur within the calvarial bone. Its definition is often confused with other forms of non-dural based intracranial meningiomas, which has made previously published retrospective reviews heterogenous, non-specific and sometimes inaccurate. We present a systematic review of calvarial PIM. METHODS: Using a systematic search protocol that included databases such as PubMed, Web of Science and Embase, we extracted all human studies on PIM published from inception to December 2017. This systematic review includes case reports and retrospective reviews that specifically described PIM. RESULTS: On review of 166 articles identified with the systematic search protocol, 69 articles were analyzed. These comprised of 64 case reports, 1 case series and 4 retrospective reviews. 111 patients with PIM of calvarial origin were analyzed, 58 % of which were females and 42 % males. The mean patient age was 51 years and the frontal bone was the most common tumor location, occurring in 26.1 % of the cases. Surgical resection was the predominant modality of treatment in 97.2 % of the cases, and gross total resection was achieved in 84 % of cases that reported extent of resection. There were no recurrences for grade I meningiomas. However, all grade III meningiomas recurred and 33.3 % of grade II meningiomas showed recurrence with a mean postoperative follow-up interval of 20 months. Statistical analysis using Fisher's exact test showed the recurrence rate to be strongly associated with WHO tumor grade (p-value <0.001). CONCLUSION: There is statistically significant increased recurrence rate for calvarial PIM of higher grades, and we recommend close follow-up in those cases. Surgical resection remains the overwhelming treatment of choice for calvarial PIM, and it has a high gross total resection rate and low risk of complications and mortality.

Subarachnoid fat dissemination secondary to intrathecal pump.

Implantable intrathecal infusion pumps (ITPs) are an effective pain management modality for patients who have failed non-operative options. We present the first report of asymptomatic intracranial subarachnoid fat dissemination secondary to an ITP. A 39-year-old who underwent implantation of an ITP for intractable pelvic pain developed altered mental status. CT and MRI revealed subarachnoid fat deposition without evidence of a dermoid or epidermoid cyst. She returned to her baseline mental status with her symptoms attributed to delirium. The rare possibility of subarachnoid fat dissemination following transdural spinal procedures should be considered as a potential complication of ITPs. Although fat may persist in the subarachnoid space for years, asymptomatic patients can be safely managed with observation alone.

Intracranial Hypertension Following Gunshot Wound to the Torcula: Case Report and Literature Review.

BACKGROUND: Elevation of bone for the treatment of depressed skull fractures overlying venous sinuses is rarely required or performed. The neurosurgical literature only describes a handful of cases of surgical intervention in which the posterior two-thirds of the superior sagittal sinus was involved. Clinical course is variable, signs and symptoms suggest increased intracranial pressure, and all conservative measures should be exhausted before proceeding with the surgical route. CASE DESCRIPTION: A 27-year-old man presented with a self-inflicted gunshot wound to posterior head. On presentation, there were no neurologic complaints. On imaging, the bullet fragment was associated with a comminuted anteriorly displaced fracture over the torcula. Vessel imaging showed tapering of the superior sagittal sinus and transverse sinuses near the torcula, suggesting narrowing due to mass effect. The patient did not respond to initial conservative management and developed worsening diplopia and papilledema concerning for increased intracranial pressure. Occipital/suboccipital craniectomy was performed with elevation of depressed skull fracture, decompression of dural venous sinus, removal of bullet, and mesh cranioplasty. Repeat ophthalmology examination postoperatively showed improvement in optic disc edema and diplopia. CONSLUSIONS: This case confirms that the approach of surgical management of superior sagittal venous sinus injuries associated with skull fractures described in the literature also can be used successfully for injuries over the torcula if conservative management does not help alleviate the symptoms and results in good outcome. It was felt that delayed surgery also plays an important role, as it gives time for scar tissue to form, which may help to protect the sinus from injury during surgery.

Salary Trends Across American Subspecialties in Academic Neurosurgery.

Enthusiasm for research and teaching are often the main reasons neurosurgical residents choose academic careers, and subspecialty choice usually stems from an interest in that particular field. However, recent salary data bring to light a work relative value unit-related trend in American academic neurosurgeon salaries, one that is similar to private practice, where compensation is strongly correlated with clinical productivity. In addition, there are significant disparities in how various subspecialties are remunerated in academic settings. For example, functional and pediatric specialists earn significantly lower salaries on average compared with their spine and endovascular colleagues. These trends have important implications both for neurosurgical trainees and for institutions in the United States.

Intraventricular metastases from rectal carcinoma: case report and literature review.

Intraventricular metastases are a rare occurrence, particularly from a primary colorectal malignancy. To our knowledge, this is the first report of intraventricular metastasis from rectal cancer. A 72-year-old male presented with a new diagnosis of multiple intraventricular lesions, an anterior mediastinal mass and a rectal mass. His workup revealed rectal adenocarcinoma with intraventricular metastases and an incidental thymoma. Ommaya reservoir placement was performed via an awake procedure rather than under general anesthesia due to airway concerns. Cerebrospinal fluid (CSF) cytology was positive for malignancy and consistent with adenocarcinoma. Two weeks postoperatively, the patient underwent whole brain radiation. Although rare, this diagnosis should always be considered in the differential for solitary or multiple intraventricular lesions. CSF sampling is a useful alternative to intraventricular biopsy for diagnosis of intraventricular metastases. Awake placement of Ommaya reservoir is a safe option in the management of patients with intraventricular metastases, especially those who cannot undergo general anesthesia.

Neoplastic Cerebral Aneurysm From Metastatic Nonsmall Cell Lung Carcinoma: Case Report and Literature Review.

BACKGROUND AND IMPORTANCE: Intracranial cerebral aneurysms secondary to neoplastic etiology are a very rare occurrence. There have only been 5 published reports of intracranial cerebral aneurysms secondary to metastatic lung cancer. Four of those five previously published reports have been secondary to nonsmall cell lung carcinoma, and only 1 case caused subarachnoid hemorrhage. To our knowledge, this is the first report of a lung cancer-associated superior cerebellar artery aneurysm. CLINICAL PRESENTATION: A 41-yr old male presented with right-sided cerebellar hemorrhage. Cerebral angiogram was negative, but he was noted to have an underlying nonsmall cell carcinoma. His workup revealed a left upper lobe mass consistent with a diagnosis of metastatic lung carcinoma. A few weeks later, the patient represented with subarachnoid hemorrhage from a left superior cerebellar artery aneurysm that was new in comparison with a magnetic resonance angiography 19 d earlier. The aneurysm was remote to the surgical site, and the patient had a negative infectious workup, making an iatrogenic pseudoaneurysm or mycotic aneurysm unlikely. In the setting of metastatic cancer, a neoplastic cerebral aneurysm was the presumptive diagnosis. CONCLUSION: Intracranial neoplastic cerebral aneurysms are extremely rare entities, and a rare cause of subarachnoid hemorrhage. This diagnosis should be considered in patients who present with concurrent metastatic cancer and cerebral aneurysm or aneurysmal subarachnoid hemorrhage. Early initiation of chemotherapy may be beneficial in reducing the risk of tumor-particle embolization, but more research needs to be conducted to better understand this rare phenomenon.

Factors Affecting the Obliteration Rate of Intracranial Aneurysms Treated with a Single Pipeline Embolization Device.

OBJECTIVE: To evaluate the clinical and angiographic outcomes of intracranial aneurysm treatment using a single Pipeline embolization device (PED), and to evaluate the factors affecting aneurysm obliteration rate. METHODS: The demographic characteristics and anatomic features of 58 aneurysms in 47 patients treated with a single PED were reviewed retrospectively. All aneurysms treated with a PED at a single center and with follow-up angiograms for at least 6 months were included in this study. RESULTS: The overall rate of complete and near-complete occlusion was 84% (49 of 58) after a mean follow-up period of 18.3 months. The rate of complete aneurysm obliteration was lower in aneurysms with an arterial branch arising from the aneurysm neck compared with aneurysms without an arterial branch (13% [1 of 8] vs. 68% [34 of 50]; P = 0.0075). The overall rate of complete and near-complete aneurysm occlusion was 90% (45 of 50) in aneurysms without an arterial branch arising from its neck. There were no statistically significant associations between obliteration rate and aneurysm neck width, size, or type, or history of previous coil embolization. CONCLUSIONS: Our data suggest that a single PED is sufficient to induce complete or near-complete obliteration of most aneurysms. The presence of a branching artery arising from the aneurysm neck is highly predictive of incomplete occlusion after treatment with a single PED.

Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras.

BACKGROUND & AIMS: Inflammatory cytokine polymorphisms are associated with gastric adenocarcinoma in Helicobacter pylori-infected patients in Europe and Asia. We investigated the cytokine profile in the Latino population, specifically Honduras, a high-incidence region, and the use of the combination prevalence of H pylori and genotypes in identifying high-risk populations. METHODS: A population-based case-control study identified 170 incident gastric cancer cases and 162 healthy village controls. Interleukin (IL)-Ibeta-511, IL-1RN, IL-10-1082, and tumor necrosis factor-alpha-308 genotypes were determined. We define the combination prevalence index (CPI) as the product of H pylori and IL-1beta-511T+ genotype prevalence in healthy subjects. Medline identified gastric cancer studies to facilitate country-specific CPI calculations. RESULTS: In healthy, population-based Honduran controls, IL-1beta-511T+ prevalence was 81% (95% confidence interval, 75%-87%; CT, 57%; TT, 25%), which was among the highest reported. IL-10-1082A+ prevalence was 93% (95% confidence interval, 88%-97%), mirroring Asian populations. Seventeen percent were homozygous for both proinflammatory cytokines (TT/AA), with increased risk among cases (odds ratio, 2.6; 95% confidence intervals, 1.0-6.8). Tumor necrosis factor-alpha polymorphisms were nearly absent. Endemic H pylori infection (85%) was confirmed. Importantly, the CPI association with country incidence is highly significant (P = .0057), based on 16 global populations and Honduras. Sensitivity analysis confirms a robust CPI. CONCLUSIONS: The CPI, based on IL-1beta genotypes, has a strong association with country-specific gastric cancer incidence. The CPI correlation supports the chronic inflammation carcinogenesis model, and may explain the geographic variation. We report a novel cytokine profile in Honduras that mirrors Asian populations and explains the high incidence rates. This may have dyspepsia management and screening implications for the growing US Latino population.