Kartik Kesavabhotla

Immunomonitoring in glioma immunotherapy: Current status and future perspectives

AbstractnGiven the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome. Current immunomonitoring assays assess delayed-type hypersensitivity, T cell proliferation, cytotoxic T-lymphocyte function, cytokine secretion profiles, antibody titers, and lymphocyte phenotypes. Yet, no single immunomonitoring technique can reliably predict outcomes, relegating immunological markers to exploratory endpoints. In response, the most recent immunomonitoring assays are incorporating emerging technologies and novel analysis techniques to approach the goal of identifying a competent immunological biomarker which predicts therapy responsiveness and clinical outcome. This review addresses the current status of immunomonitoring in glioma vaccine clinical trials with emphasis on correlations with clinical response.

Predictors of recurrence in the management of chordoid meningioma.

AbstractnManagement of chordoid meningiomas (CMs) is complicated by high rates of recurrence, particularly following subtotal resection. Optimal management is not established given the paucity of published experience. To identify prognostic factors for recurrence following resection, the authors conducted the largest systematic review of CMs to date. A comprehensive search on MEDLINE (OVID and Pubmed), Scopus, Embase, and Web of Science utilizing the search terms “chordoid” AND “meningioma” was performed to identify all reports of pathologically confirmed intracranial CMs. A total of 221 patients were included, comprising 120 females and 101 males. Mean age, MIB-1/Ki67, and tumor size was 45.5xa0years, 4.3xa0% (range 0.1–26.6xa0%), and 4.1xa0cm (range 0.8–10xa0cm), respectively. 5-, and 10- year progression free survival was 67.5 and 54.4xa0%, respectively. Gross total resection (GTR) and subtotal resection was achieved in 172 and 48 patients, respectively. Adjuvant radiotherapy (RT) was given to 30 patients. Multivariate analysis found GTR was strongly correlated with decreased recurrence rates (HR 0.04, pxa0=xa0<0.0001), while higher MIB-1 labeling index (≥5 vsxa0<5xa0%) was associated with increased recurrence (HR 7.08; pxa0=xa00.016). Adjuvant RT, age, gender, and tumor location were not associated with recurrence. GTR resection is the strongest predictor of tumor control, and should be the goal to minimize local progression. Additionally, higher MIB-1 labeling was associated with increased rates of tumor recurrence. Tumors that are subtotally resected or demonstrate higher MIB-1 are at greater recurrence and warrant consideration for RT and close long term follow up.

Prognostic factors for recurrence and complications in the surgical management of primary chordoid gliomas: A systematic review of literature

OBJECTIVEnChordoid gliomas (CG) are rare neoplasms which frequently arise within the third ventricle. Surgery remains the mainstay treatment for CG. The present study comprehensively reviews all reported cases of CG within the literature in order to identify risk factors for surgical complications and tumor recurrence.nnnMETHODSnA comprehensive search on MEDLINE (OVID and PubMed), Scopus, Embase, and Web of Science was conducted following PRISMA guidelines to identify all reported cases of CG.nnnRESULTSnA total of 81 patients met the study criteria which comprised of 33 males and 48 females. Median age at diagnosis was 48 years with a range from 5 to 72 years, and mean tumor size was 3.1cm. Biopsy, subtotal resection (STR), and gross total resection (GTR) were achieved in 8, 34, and 33 patients, respectively, with six cases not reporting extent of resection (EOR). Thirteen patients underwent adjuvant radiotherapy. Postoperative complications were noted in 30 cases (37%), with new onset diabetes insipidus being the most common. Postoperative morbidity was not associated with age, tumor size, or extent of resection. A trans-lamina terminalis approach demonstrated a strong trend towards decreased overall rates of postoperative morbidity compared to other approaches (p=0.051). GTR was associated with improved progression-free survival (PFS; p=0.028), while adjuvant radiotherapy, age, tumor size and proliferative index were not predictive of patient outcomes.nnnCONCLUSIONnGTR should be the primary goal for the management of CG, as it is associated with improved rates of tumor control without an increased rate of postoperative complications. Surgical approach was a stronger predictor of complication rates than extent of resection. Morbidity remains high, and future studies to further elaborate on factors predictive of postoperative complications are critical.

Clinical attributes and surgical outcomes of angiocentric gliomas

Angiocentric gliomas (AG) are exceedingly rare low-grade neoplasms which often present in the form of intractable epilepsy within younger patients. The current study extensively reviews all reported cases which were pathologically verified as AG in the literature to analyze clinical attributes and surgical outcomes of this neoplasm. There were 88 patients with AG reported in the literature consisting mostly of pediatric cases. The sex distribution consisted of 45 males and 36 females with the remaining seven cases not documenting sex. The average age of initial diagnosis was 16years with almost half of all diagnosed patients being within the first decade of life. In cases where extent of resection was reported, gross total resection (GTR) was achieved in 54 patients, subtotal resection (STR) in 16, and biopsy only in three. Post-operative complications were transient and only occurred in three patients with no reports of death following surgery. Only five cases reported tumor recurrence on follow-up. Eight patients had seizure recurrence post-operatively and GTR offered improved rates of seizure control when compared to STR (p=0.0005). Nearly half of the cases of AG are diagnosed within the first decade of life and they usually manifest with intractable seizures. GTR appears to offer better seizure control in the post-operative period. Surgical resection is the mainstay therapy for AG as post-operative complications and tumor recurrence remain uncommon. Since the number of reported cases is limited, future studies with longer follow-up periods will help elaborate more long-term outcomes.

Safety and outcomes of preoperative embolization of intracranial hemangioblastomas: A systematic review

INTRODUCTIONnWhile preoperative embolization is often reserved for large and highly vascular tumors in order to minimize blood loss, its safety and efficacy in the treatment of hemangioblastomas (HB) is unclear. We present the largest systematic review focusing on the safety and outcome of preoperative embolization of intracranial HB.nnnMATERIALS AND METHODSnTo identify all cases of preoperative embolization for HB, a literature search was conducted via Medline (OVID and PubMed), Scopus, Embase, and Web of Science. Studies that were in English, included intracranial hemangioblastomas treated with preoperative embolization and provided sufficient disaggregated clinical data for each patient were included. Historical control patients with non-embolized intracranial HB undergoing resection were similarly identified.nnnRESULTSnA total of 111 patients that underwent preoperative embolization of HB prior to planned resection were identified. Patient age ranged from 12 to 72 years, with a cohort of 63% males and 36% females. Nine studies comprising 392 non-embolized patients were included as controls. Gross total resection was achieved in 83.7% of embolized and 95.6% of non-embolized patients. Intraoperative blood transfusion was required in 15.3% of embolized and 0.51% of non-embolized controls, while rates of post-operative hemorrhage were 8.4% and 1.6%, respectively. Complication rates from embolization were 11.7% and following consequent surgery were 20.7%.nnnDISCUSSIONnEmbolization did not increase rates of gross total resection, decrease estimated blood loss, or decrease incidence of complications. Not only does embolization fail to mitigate surgical risks, the embolization procedure itself carries significant risk for complications. Embolization should not be standard of care for intracranial HB.

Predictors for Airway Complications Following Single- and Multi-level Anterior Cervical Discectomy and Fusion.

Study Design. A retrospective, multivariate analyses of a prospectively collected multicenter database. Objective. The aim of this study was to evaluate the risk factors for postoperative airway complications following single- and multilevel anterior cervical discectomy and fusion (ACDF). Summary of Background Data. Airway compromise following ACDF may result in catastrophic outcome. However, its predictors have not been identified by a multi-institutional study. Methods. Patients who underwent ACDF between 2011 and 2013 were selected from the American College of Surgeons National Surgical Quality Improvement Program database. Multiple logistic regression analysis was performed to identify the risk factors for airway compromise following ACDF. Results. Twelve thousand one hundred eighty-five patients were analyzed in this study. Our multivariate analysis identified older age, male gender, dependent functional status, chronic obstructive pulmonary disease, bleeding disorder, American Society of Anesthesiology class >2, Wound Class >2, and prolonged operative durations as significant predictors of postoperative airway compromise following ACDF. Surprisingly, multilevel and corpectomy procedures were not significant risk factors for airway complication following ACDF. Conclusion. We identified significant risk factors for airway compromise following ACDF procedures. While ACDF is considered a safe procedure, postoperative airway complication can lead to disastrous outcome. Continued efforts to elucidate preoperative risk factors and subsequent optimization are warranted to improve outcomes in ACDF. Level of Evidence: 3

Endoscopic Approach to Clival Chordomas: The Northwestern Experience

INTRODUCTIONnChordomas are rare primary bone tumors with a low-grade histology but an aggressive clinical behavior characterized by local invasion and recurrence. When occurring in the skull base, their treatment is limited by proximity to critical neurovascular structures. Open surgical approaches can carry high morbidity, making the development of alternative approaches desirable. We describe our experience with endoscopic endonasal approaches to clival chordomas over 13 years.nnnMETHODSnWe performed a retrospective chart review of patients diagnosed with clival chordomas and treated with an endoscopic endonasal approach between 2003 and 2015 at Northwestern Memorial Hospital. We reviewed presenting symptoms, tumor location and size, extent of resection, complications, recurrence, adjuvant treatment, retreatment, and follow-up duration.nnnRESULTSnA total of 23 charts were reviewed, with 17 included in our final review. Mean age was approximately 48 years. The most common presenting symptom was diplopia present in 70.6% of patients. Mean tumor volume was 20.2 cm3. Gross total resection was achieved in 52.9% of patients. With a mean follow-up period of 63.4 months, 5 patients had a recurrence. The most common complication was cerebrospinal fluid (CSF) leak, which was noted in 6 patients. Tumor volume was significantly higher in patients with CSF leak. No correlation between intradural extension and postoperative CSF leak was noted.nnnCONCLUSIONSnClival chordoma are challenging entities to treat. The best outcomes are achieved with gross total resection followed by adjuvant radiotherapy treatment. We show that the endonasal endoscopic corridor is a viable alternative approach to these lesions.

Impact of CrossFit-Related Spinal Injuries

INTRODUCTIONnExercise-related injuries (ERIs) are a common cause of nonfatal emergency department and hospital visits. CrossFit is a high-intensity workout regimen whose popularity has grown rapidly. However, ERIs due to CrossFit remained under investigated.nnnMETHODSnAll patients who presented to the main hospital at a major academic center complaining of an injury sustained performing CrossFit between June 2010 and June 2016 were identified. Injuries were classified by anatomical location (eg, knee, spine). For patients with spinal injuries, data were collected including age, sex, body mass index (BMI), CrossFit experience level, symptom duration, type of symptoms, type of clinic presentation, cause of injury, objective neurological examination findings, imaging type, number of clinic visits, and treatments prescribed.nnnRESULTSnFour hundred ninety-eight patients with 523 CrossFit-related injuries were identified. Spine injuries were the most common injuries identified, accounting for 20.9%. Among spine injuries, the most common location of injury was the lumbar spine (83.1%). Average symptom duration was 6.4 months ± 15.1, and radicular complaints were the most common symptom (53%). A total of 30 (32%) patients had positive findings on neurologic examination. Six patients (6.7%) required surgical intervention for treatment after failing an average of 9.66 months of conservative treatment. There was no difference in age, sex, BMI, or duration of symptoms of patients requiring surgery with those who did not.nnnCONCLUSIONSnCrossFit is a popular, high-intensity style workout with the potential to injure its participants. Spine injuries were the most common type of injury observed and frequently required surgical intervention.INTRODUCTIONnExercise-related injuries (ERIs) are a common cause of nonfatal emergency department and hospital visits. CrossFit is a high-intensity workout regimen whose popularity has grown rapidly. However, ERIs due to CrossFit remained under investigated.nnnMETHODSnAll patients who presented to the main hospital at a major academic center complaining of an injury sustained performing CrossFit between June 2010 and June 2016 were identified. Injuries were classified by anatomical location (eg, knee, spine). For patients with spinal injuries, data were collected including age, sex, body mass index (BMI), CrossFit experience level, symptom duration, type of symptoms, type of clinic presentation, cause of injury, objective neurological examination findings, imaging type, number of clinic visits, and treatments prescribed.nnnRESULTSnFour hundred ninety-eight patients with 523 CrossFit-related injuries were identified. Spine injuries were the most common injuries identified, accounting for 20.9%. Among spine injuries, the most common location of injury was the lumbar spine (83.1%). Average symptom duration was 6.4 months ± 15.1, and radicular complaints were the most common symptom (53%). A total of 30 (32%) patients had positive findings on neurologic examination. Six patients (6.7%) required surgical intervention for treatment after failing an average of 9.66 months of conservative treatment. There was no difference in age, sex, BMI, or duration of symptoms of patients requiring surgery with those who did not.nnnCONCLUSIONSnCrossFit is a popular, high-intensity style workout with the potential to injure its participants. Spine injuries were the most common type of injury observed and frequently required surgical intervention.

Erratum to: Predictors of recurrence in the management of chordoid meningioma.

Fig. 3 Kaplan–Meier curve for all patients included within the study. 3and 5-year PFS was 76.0 and 67.5 %, respectively Fig. 4 Kaplan–Meier analysis of recurrence free survival following either gross (GTR) to subtotal (STR) resection. Greater extent of surgery was associated with improved rates of tumor control. For GTR, 3and 5-year PFS was 85.3 and 80.8 %, respectively. For STR, 3and 5-year PFS was 50.7 and 33.8 %, respectively, p 0.001

Seeing Floaters: A Case Report and Literature Review of Intraventricular Migration of Silicone Oil Tamponade Material for Retinal Detachment

BACKGROUNDnIntraocular injection of silicone oil is commonly performed during vitrectomy to tamponade the retina in place for treatment of retinal detachment. Although rare, this intravitreal silicone can migrate through the optic nerve and chiasm and enter the cerebral ventricles.nnnCASE DESCRIPTIONnHere we present a case report of a patient presenting with headache and intraventricular hyperdensities on a computed tomography (CT) scan, raising a concern for intraventricular hemorrhage. However, the intraventricular hyperdensities were in a nondependent location and moved to a new nondependent location when repeat imaging was performed with the patient in the prone position. We provide a literature review of this phenomenon and discuss the relevant CT and magnetic resonance imaging findings.nnnCONCLUSIONSnIntraocular silicone can rarely migrate into the cerebral ventricular system. Careful review of the clinical history and imaging findings can help distinguish this from other, more dangerous intracranial pathologies.