Evolution of surgical treatment of metastatic spine tumors.

PURPOSE: The treatment of cancer has transformed over the past 40 years, with medical oncologists, radiation oncologists and surgeons working together to prolong survival times and minimize treatment related morbidity. With each advancement, the risk-benefit scale has been calibrated to provide an accurate assessment of surgical hazard. The goal of this review is to look back at how the role of surgery has evolved with each new medical advance, and to explore the role of surgeons in the future of cancer care. METHODS: A literature review was conducted, highlighting the key papers guiding surgical management of spinal metastatic lesions. CONCLUSION: The roles of surgery, medical therapy, and radiation have evolved over the past 40 years, with new advances requiring complex multidisciplinary care.

Existing clinical evidence on the use of cellular bone matrix grafts in spinal fusion: updated systematic review of the literature.

OBJECTIVE: Spinal fusion surgery is increasingly common; however, pseudarthrosis remains a common complication affecting as much as 15% of some patient populations. Currently, no clear consensus on the best bone graft materials to use exists. Recent advances have led to the development of cell-infused cellular bone matrices (CBMs), which contain living components such as mesenchymal stem cells (MSCs). Relatively few clinical outcome studies on the use of these grafts exist, although the number of such studies has increased in the last 5 years. In this study, the authors aimed to summarize and critically evaluate the existing clinical evidence on commercially available CBMs in spinal fusion and reported clinical outcomes. METHODS: The authors performed a systematic search of the MEDLINE and PubMed electronic databases for peer-reviewed, English-language original articles (1970-2020) in which the articles' authors studied the clinical outcomes of CBMs in spinal fusion. The US National Library of Medicine electronic clinical trials database (www.ClinicalTrials.gov) was also searched for relevant ongoing clinical trials. RESULTS: Twelve published studies of 6 different CBM products met inclusion criteria: 5 studies of Osteocel Plus/Osteocel (n = 354 unique patients), 3 of Trinity Evolution (n = 114), 2 of ViviGen (n = 171), 1 of map3 (n = 41), and 1 of VIA Graft (n = 75). All studies reported high radiographic fusion success rates (range 87%-100%) using these CBMs. However, this literature was overwhelmingly limited to single-center, noncomparative studies. Seven studies disclosed industry funding or conflicts of interest (COIs). There are 4 known trials of ViviGen (3 trials) and Bio4 (1 trial) that are ongoing. CONCLUSIONS: CBMs are a promising technology with the potential of improving outcome after spinal fusion. However, while the number of studies conducted in humans has tripled since 2014, there is still insufficient evidence in the literature to recommend for or against CBMs relative to cheaper alternative materials. Comparative, multicenter trials and outcome registries free from industry COIs are indicated.

Methylphenidate Reversal of Executive Dysfunction in a Patient with Bi-Frontal Lobe Glioblastoma.

An elderly man with advanced glioblastoma developed neuro-cognitive deficits that were reversed by methylphenidate. After tumor resection from the right frontal lobe, he received cranial irradiation, temozolomide and Tumor Treating Fields (TTFields). MRI afterwards showed enhancements near the resection cavity and the contralateral frontal lobe. The patient experienced mild executive dysfunction that was not limiting his activities. Adjuvant temozolomide was started along with TTFields. After 2 cycles, his brain MRI showed stable disease, but he exhibited significant executive dysfunction. Methylphenidate improved his neuro-cognitive slowing in cycles 3 and 4. His disease eventually progressed during the 5th cycle, and he experienced a marked decline in activities. Repeat head MRI revealed tumor progression and cerebral edema. Treatments were discontinued while dexamethasone improved his neurological functions and bevacizumab biosimilar was later added. This case demonstrates the activity of methylphenidate for managing executive dysfunction in patients with glioblastoma while minimizing the use of dexamethasone.

Metastatic cervical carcinoma to the brain masquerading as a butterfly glioma: A case report.

Background: Metastatic cervical cancer to the brain is a rare occurrence, representing approximately 1.5% of metastatic cases. We report a rare presentation of cervical cancer with brain metastasis to the corpus callosum. The patient was initially suspected to have a primary glioma but was diagnosed with a metastatic cervical carcinoma lesion through both stereotactic and then opens biopsy. Case Description: A 53-year-old female, with Stage III adenosquamous cervical carcinoma, presented with a large heterogeneously enhancing mass in the corpus callosum body with extension in the cingulate gyrus concerning for glioma. A stereotactic biopsy revealed hypercellular and gliotic brain tissue, while an open biopsy showed an epithelioid neoplasm consistent with metastatic cervical adenosquamous carcinoma. The patient underwent a craniotomy and recovered well and was discharged in stable condition. Conclusion: Brain metastases from cervical cancer are uncommon. We present a rare case of metastatic cervical carcinoma which appeared on imaging to mimic a butterfly glioma. The patient's history and histopathological examination were essential in determining the correct diagnosis and receiving timely treatment.

Time of Discharge and 30-Day Re-Presentation to an Acute Care Setting After Elective Lumbar Decompression Surgery.

BACKGROUND: Evidence regarding the consequence of efforts to increase patient throughput and decrease length of stay in the context of elective spine surgery is limited. OBJECTIVE: To evaluate whether early time of discharge results in increased rates of hospital readmission or return to emergency department for patients admitted after elective, posterior, lumbar decompression surgery. METHODS: We conducted a retrospective cohort study of 779 patients admitted to hospital after undergoing elective, posterior, lumbar decompression surgery. Multiple logistic regression evaluated the relationship between time of discharge and the primary outcome of return to acute care within 30 days, while controlling for sociodemographic, procedural, and discharge characteristics. RESULTS: In multiple logistic regression, time of discharge earlier in the day was not associated with increased odds of return to acute care within 30 days (odds ratio [OR] 1.18, 95% CI 0.92-1.52, P = .19). Weekend discharge (OR 1.99, 95% CI 1.04-3.79, P = .04) increased the likelihood of return to acute care. Surgeon experience (<1 year of attending practice, OR 0.43, 95% CI 0.19-1.00, P = .05 and 2-5 years of attending practice, OR 0.50, 95% CI 0.25-1.01, P = .054), weekend discharge (OR 0.49, 95% CI 0.27-0.89, P = .02), and physical therapy evaluation (OR 0.20, 95% CI 0.12-0.33, P < .001) decreased the likelihood of discharge before noon. CONCLUSION: Time of discharge is not associated with risk of readmission or presentation to the emergency department after elective lumbar decompression. Weekend discharge is independently associated with increased risk of readmission and decreased likelihood of prenoon discharge.

Patterns in Decompression and Fusion Procedures for Patients With Lumbar Stenosis After Major Clinical Trial Results, 2016 to 2019.

Importance: Use of lumbar fusion has increased substantially over the last 2 decades. For patients with lumbar stenosis and degenerative spondylolisthesis, 2 landmark prospective randomized clinical trials (RCTs) published in the New England Journal of Medicine in 2016 did not find clear evidence in favor of decompression with fusion over decompression alone in this population. Objective: To assess the national use of decompression with fusion vs decompression alone for the surgical treatment of lumbar stenosis and degenerative spondylolisthesis from 2016 to 2019. Design, Setting, and Participants: This retrospective cohort study included 121 745 hospitalized adult patients (aged ≥18 years) undergoing 1-level decompression alone or decompression with fusion for the management of lumbar stenosis and degenerative spondylolisthesis from January 1, 2016, to December 31, 2019. All data were obtained from the National Inpatient Sample (NIS). Analyses were conducted, reviewed, or updated on June 9, 2023. Main Outcome and Measure: The primary outcome of this study was the use of decompression with fusion vs decompression alone. For the secondary outcome, multivariable logistic regression analysis was used to evaluate factors associated with the decision to perform decompression with fusion vs decompression alone. Results: Among 121 745 eligible hospitalized patients (mean age, 65.2 years [95% CI, 65.0-65.4 years]; 96 645 of 117 640 [82.2%] non-Hispanic White) with lumbar stenosis and degenerative spondylolisthesis, 21 230 (17.4%) underwent decompression alone, and 100 515 (82.6%) underwent decompression with fusion. The proportion of patients undergoing decompression alone decreased from 2016 (7625 of 23 405 [32.6%]) to 2019 (3560 of 37 215 [9.6%]), whereas the proportion of patients undergoing decompression with fusion increased over the same period (from 15 780 of 23 405 [67.4%] in 2016 to 33 655 of 37 215 [90.4%] in 2019). In univariable analysis, patients undergoing decompression alone differed significantly from those undergoing decompression with fusion with regard to age (mean, 68.6 years [95% CI, 68.2-68.9 years] vs 64.5 years [95% CI, 64.3-64.7 years]; P < .001), insurance status (eg, Medicare: 13 725 of 21 205 [64.7%] vs 53 320 of 100 420 [53.1%]; P < .001), All Patient Refined Diagnosis Related Group risk of death (eg, minor risk: 16 900 [79.6%] vs 83 730 [83.3%]; P < .001), and hospital region of the country (eg, South: 7030 [33.1%] vs 38 905 [38.7%]; Midwest: 4470 [21.1%] vs 23 360 [23.2%]; P < .001 for both comparisons). In multivariable logistic regression analysis, older age (adjusted odds ratio [AOR], 0.96 per year; 95% CI, 0.95-0.96 per year), year after 2016 (AOR, 1.76 per year; 95% CI, 1.69-1.85 per year), self-pay insurance status (AOR, 0.59; 95% CI, 0.36-0.95), medium hospital size (AOR, 0.77; 95% CI, 0.67-0.89), large hospital size (AOR, 0.76; 95% CI, 0.67-0.86), and highest median income quartile by patient residence zip code (AOR, 0.79; 95% CI, 0.70-0.89) were associated with lower odds of undergoing decompression with fusion. Conversely, hospital region in the Midwest (AOR, 1.34; 95% CI, 1.14-1.57) or South (AOR, 1.32; 95% CI, 1.14-1.54) was associated with higher odds of undergoing decompression with fusion. Decompression with fusion vs decompression alone was associated with longer length of stay (mean, 2.96 days [95% CI, 2.92-3.01 days] vs 2.55 days [95% CI, 2.49-2.62 days]; P < .001), higher total admission costs (mean, $30 288 [95% CI, $29 386-$31 189] vs $16 190 [95% CI, $15 189-$17 191]; P < .001), and higher total admission charges (mean, $121 892 [95% CI, $119 566-$124 219] vs $82 197 [95% CI, $79 745-$84 648]; P < .001). Conclusions and Relevance: In this cohort study, despite 2 prospective RCTs that demonstrated the noninferiority of decompression alone compared with decompression with fusion, use of decompression with fusion relative to decompression alone increased from 2016 to 2019. A variety of patient- and hospital-level factors were associated with surgical procedure choice. These results suggest the findings of 2 major RCTs have not yet produced changes in surgical practice patterns and deserve renewed focus.

Impact of temozolomide on immune response during malignant glioma chemotherapy.

Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.

Development of posttraumatic frontal brain abscess in association with an orbital roof fracture and odontogenic abscess: A case report.

Background: Brain abscess is a potentially fatal condition. Orbital fractures caused by penetrating injury may be associated with intracranial infection. Such complication associated with blunt trauma, orbital roof fractures, and odontogenic abscesses is exceedingly rare. Case Description: We report the case of a 40-year-old transgender female with a frontal abscess presenting several weeks following a motor vehicle crash from which she suffered multiple facial fractures and an odontogenic abscess. On computed tomography scan, the patient had multiple right-sided facial fractures, including a medial orbital wall fracture and a right sphenoid fracture extending into the superior orbital roof. There was hemorrhage notable in the right frontal lobe. Communication with the ethmoid sinuses likely provided a conduit for bacterial spread through the orbit and into the intracranial and subdural spaces. Conclusion: Skull base fractures that communicate with a sinus, whether it be frontal, ethmoid, or sphenoid may increase the risk of brain abscess, especially in patients who develop an odontogenic abscess. Surgical repair of the defect is essential, and treating patients prophylactically with antibiotics may be beneficial.

Instrumentation choice and early radiographic outcome following lateral lumbar interbody fusion (LLIF): Lateral instrumentation versus posterior pedicle screw fixation.

Background: Lateral lumbar interbody fusion (LLIF) is a minimally invasive fusion procedure that may be performed with or without supplemental instrumentation. However, there is a paucity of evidence on the effect of supplemental instrumentation technique on perioperative morbidity and fusion rate in LLIF. Methods: A single-institutional retrospective review of patients who underwent LLIF for lumbar spondylosis was conducted. Patients were grouped according to supplemental instrumentation technique: stand-alone LLIF, LLIF with laterally placed instrumentation, or LLIF with posterior percutaneous pedicle screw fixation (PPSF). Outcomes included fusion rates, peri-operative complication, and reoperation; estimated blood loss (EBL); surgery duration; length of stay; and length of follow-up. Results: 82 patients underwent LLIF at 114 levels. 35 patients (42.7%) received supplemental lateral instrumentation, 30 (36.6%) received supplemental PPSF, and 17 (20.7%) underwent stand-alone LLIF. More patients in the lateral instrumentation group had prior lumbar fusion at adjacent levels (23/35, 65.71%) versus stand-alone (3/17, 17.6%) or PPSF (2/30, 6.67%) groups (p = 0.003). 4/17 patients (23.5%) with stand-alone LLIF and 4/35 patients (11.42%) with lateral instrumentation underwent reoperation, versus 0/30 with PPSF (p = 0.030). There was no difference in fusion rates between groups (p = 0.717). Operation duration was longer in patients with PPSF (p < 0.005) and length of follow-up was longer for PPSF than lateral instrumentation (p = 0.001). Choice of instrumentation group was a statistically significant predictor of reoperation. Conclusions: While rates of complete radiographic fusion on imaging follow-up didn't differ, patients receiving PPSF were less likely than stand-alone or lateral instrumentation groups to require reoperation, though operative time was significantly longer. Further study of choice of supplemental instrumentation with LLIF is indicated.

Awake, Transforaminal Endoscopic Lumbar Spine Surgery in Octogenarians: Case Series.

BACKGROUND: Optimal approaches for treating surgical spine pathology in very geriatric patients, such as those over the age of 80, remain unclear. OBJECTIVE: To describe outcomes of awake, transforaminal endoscopic surgical treatment for patients 80 years old and older presenting with lumbar radiculopathy. STUDY DESIGN: Retrospective case review. METHODS: The records of 52 consecutive patients who underwent awake transforaminal lumbar endoscopic decompression surgery performed by a single surgeon at a single institution between 2014 and 2019 were retrospectively reviewed. All included patients were followed for at least one year after surgery. RESULTS: Transforaminal surgeries performed were discectomies (21), foraminotomies (7), redo foraminotomies post-laminectomy (5), fusion explorations (13), facet cyst resections (3), spondylolisthesis decompressions (2), and a decompression for metastatic disease (1). Seven patients (13.5%) required repeat surgery at the treated level during the one-year follow-up. For the remaining 45 patients, at one-year follow-up, preoperative visual analog scale (VAS) for leg pain and Oswestry disability index (ODI) improved from 6.9 (± 1.4) and 40.5% (± 11.5) to 1.8 (± 1.4) and 12.0% (± 10.8), respectively. The only complication of the procedure was a single durotomy (2%). LIMITATIONS: Single-center, retrospective case review with a relatively small number of cases with diverse clinical pathology. A multi-center case study with a larger number of patients with a more homogeneous case pathology would be more revealing. CONCLUSIONS: Endoscopic spine surgery offers octogenarians a safe and effective option for the treatment of lumbar degenerative spine disease and may represent a valuable treatment strategy in a growing patient population.

Neighborhood-level socioeconomic status, extended length of stay, and discharge disposition following elective lumbar spine surgery.

Background: In the context of increased attention afforded to hospital efficiency and improved but safe patient throughput, decreasing unnecessary hospital length of stay (LOS) is imperative. Given that lumbar spine procedures may be among a hospital's most profitable services, identifying patients at risk of increased healthcare resource utilization prior to surgery is a valuable opportunity to develop targeted pre- and peri-operative intervention and quality improvement initiatives. The purpose of the present investigation was to examine patient factors that predict prolonged LOS as well as discharge disposition following elective, posterior, lumbar spine surgery. Methods: We employed a retrospective cohort analysis on 779 consecutive patients treated with lumbar surgery without fusion. Our primary outcome measures were extended LOS (three or more midnights) and discharge disposition. Patient sociodemographic, procedural, and discharge characteristics were adjusted for in our analysis. Sociodemographic variables included Area of Deprivation Index (ADI), a comprehensive metric of socioeconomic status, utilizing income, education, employment, and housing quality based on patient zip code. Multivariable logistic regression and ordinal logistic regression analyses were performed to assess whether covariates were independently predictive of extended LOS and discharge disposition, respectively. Results: 779 patients were studied, with a median age of 66 years (±15) and a median LOS of 1 midnight (range, 1-10 midnights). Patients in the most disadvantaged ADI quintile (adjusted odds ratio, aOR 2.48 95% CI 1.15-5.47), those who underwent a minimally-invasive or tubular retractor surgery (aOR 3.03 95% CI 1.02-8.56), those who had an intra-operative drain placed (aOR 4.46 95% CI 2.53-7.26), who had a cerebrospinal fluid leak (aOR 3.46 95% CI 1.55-7.58), who were discharged anywhere but home (aOR 17.11 95% CI 9.24-33.00), and those who were evaluated by physical therapy (aOR 7.23 95% CI 2.13-45.30) or OT (aOR 2.20 95% CI 1.13-4.22) had a significantly increased chance of an extended LOS. Preoperative opioid use was not associated with an increased LOS following surgery (aOR 1.12 95% CI 0.56-1.46). Extended LOS was not associated with post-discharge emergency department representation or unplanned readmission within 90 days following discharge (p=0.148). Patients who were older (aOR 1.99 95% CI 1.62-2.48), in higher quintiles on ADI (3rd quintile; aOR 1.90 95% CI 1.12-3.23, 4th quintile; aOR 1.79, 95% CI 1.05-3.05, 5th quintile; aOR 2.16 95% CI 1.26-3.75), who had a CSF leak (aOR 2.18 95% CI 1.22-3.86), or who had a longer procedure duration (aOR 1.38 95% CI 1.17-1.62) were more likely to require additional services or be sent to a subacute facility upon discharge. Conclusions: Patient sociodemographics, along with procedural factors, and discharge disposition were all associated with an increased likelihood of prolonged LOS and resource intensive discharges following elective lumbar spine surgery. Several of these factors could be reliably identified pre-operatively and may be amenable to targeted preoperative intervention. Improving discharge disposition planning in the peri-operative period may allow for more efficient use of hospitalization and inpatient and post-acute resources.

Influence of Time of Discharge and Length of Stay on 30-Day Outcomes After Elective Anterior Cervical Spine Surgery.

BACKGROUND: Encouraging early time of discharge (TOD) for medical inpatients is commonplace and may potentially improve patient throughput. It is unclear, however, whether early TOD after elective spine surgery achieves this goal without a consequent increase in re-presentations to the hospital. OBJECTIVE: To evaluate whether early TOD results in increased rates of hospital readmission or return to the emergency department after elective anterior cervical spine surgery. METHODS: We analyzed 686 patients who underwent elective uncomplicated anterior cervical spine surgery at a single institution. Logistic regression was used to evaluate the relationship between sociodemographic, procedural, and discharge characteristics, and the outcomes of readmission or return to the emergency department and TOD. RESULTS: In multiple logistic regression, TOD was not associated with increased risk of readmission or return to the emergency department within 30 days of surgery. Weekend discharge (odds ratio [OR] 0.33, 95% CI 0.21-0.53), physical therapy evaluation (OR 0.44, 95% CI 0.28-0.71), and occupational therapy evaluation (OR 0.32, 95% CI 0.17-0.63) were all significantly associated with decreased odds of discharge before noon. Disadvantaged status, as measured by area of deprivation index, was associated with increased odds of readmission or re-presentation (OR 1.86, 95% CI 0.95-3.66), although this result did not achieve statistical significance. CONCLUSION: There does not appear to be an association between readmission or return to the emergency department and early TOD after elective spine surgery. Overuse of inpatient physical and occupational therapy consultations may contribute to decreased patient throughput in surgical admissions.

Neighborhood-Level Socioeconomic Status Predicts Extended Length of Stay After Elective Anterior Cervical Spine Surgery.

BACKGROUND: A significant portion of health care spending is driven by a small percentage of the overall population. Understanding risk factors predisposing patients to disproportionate use of health care resources is critical. Our objective was to identify risk factors leading to a prolonged length of stay (LOS) after cervical spine surgery. METHODS: A single-center cohort analysis was performed on patients who underwent elective anterior spine surgery from 2015 to 2021. Multivariate logistic regression evaluated the effects of sociodemographic factors including Area of Deprivation Index (quantifies income, education, employment, and housing quality), procedural, and discharge characteristics on postoperative LOS. Extended LOS was defined as greater than the 90th percentile in midnights for the study population (≥3 midnights). RESULTS: A total of 686 patients were included in the study, with a mean age of 57 years (range, 26-92 years), median of 1 level (1-4) fused, and median LOS of 1 midnight (interquartile range, 1-2). After adjusting for confounders, patients had increased odds of extended LOS if they were highly disadvantaged on the Area of Deprivation Index (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.04-4.82; P = 0.039); had surgery on Thursday or Friday (OR, 1.94; 95% CI, 1.01-3.72; P = 0.046); had a corpectomy performed (OR, 2.81; 95% CI, 1.26-6.28; P = 0.012); or discharged not to home (OR, 8.24; 95% CI, 2.88-23.56; P < 0.001). Patients with extended LOS were more likely to present to the emergency department or be readmitted within 30 days after discharge (P = 0.024). CONCLUSIONS: After adjusting for potential cofounders, patients most disadvantaged on Area of Deprivation Index were more likely to have an extended LOS.

Endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection of frontoethmoidal osteoma causing tension pneumocephalus.

Tension pneumocephalus is an unusual, potentially life-threatening complication of frontal fossa tumors. We present an uncommon case of a frontoethmoidal osteoma causing a tension pneumocephalus and neurological deterioration prompting a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection. A 68-year-old man presented with a 1-week history of worsening headache, slowness of speech, and increasing confusion. Standard computed tomography scan revealed a marked tension pneumocephalus with ventricular air and 1-cm midline shift to the right. Further studies showed a calcified left ethmoid mass and a left anterior cranial-base defect. A team composed of neurosurgery and otolaryngology performed a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach to resect a large frontoethmoid bony tumor. No abscess or mucocele was identified. The skull base defect was repaired with the aid of a transnasal endoscopy, a titanium mesh, and a pedunculated pericranial flap. Postoperatively, the pneumocephalus and the patient's symptoms completely resolved. Pathology was consistent with a benign osteoma. This is an uncommon case of a frontoethmoidal osteoma associated with tension pneumocephalus. Recognition of this entity and timely diagnosis and treatment, consisting of an endonasal ethmoidectomy and a bifrontal craniotomy with craniofacial approach, may prevent potential life-threatening complications.

Glycogen synthase kinase 3 inhibition lowers PD-1 expression, promotes long-term survival and memory generation in antigen-specific CAR-T cells.

Successful remission in hematological cancers by CAR-T cell immunotherapy has yet to be replicated in solid tumors like GBM. A significant impediment of CAR-T immunotherapy in solid tumors is poor exposure of T cells to tumor antigens resulting in suboptimal CAR-T cell activation, which ultimately fails to induce a robust anti-tumor immune response. Costimulatory moieties in advanced-generation CARs, along with additional IL2 therapy has been shown to be insufficient to overcome this hurdle and have its cytotoxic limitations. GSK3 is constitutively active in naïve T cells and is transiently inactivated during T cell activation resulting in rapid T cell proliferation. Pharmacologic inhibition of GSK3 in GBM-specific CAR-T cells reduced FasL expression, increased T cell proliferation and reduced exhaustion by lowering PD-1 levels resulting in the development of CAR-T effector memory phenotype. Treatment with GSK3-inhibited CAR-T cells resulted in 100% tumor elimination during the tumor-rechallenge experiment in GBM-bearing animals and increased accumulation of memory CAR-T cells in secondary lymphoid organs. These adjuvant-like effects of GSK3 inhibition on activated CAR-T cells may be a valuable adjunct to a successful implementation of CAR-T immunotherapy against GBM and other solid tumors.

Posterior dynamic stabilization of the lumbar spine: pedicle based stabilization with the AccuFlex rod system.

Posterior dynamic stabilization in the lumbar spine is performed in an attempt to reduce loading across the intervertebral disc for the purpose of relieving pain and limiting degeneration while preserving motion. The AccuFlex rod system (Globus Medical, Inc.), a first-generation device, achieves this by changing the properties of the rod within the Protex pedicle screw-based rigid rod system. Helical cuts that have been created in the standard 6.5-mm rod allow for a limited range of motion while providing a posterior tension band that relieves a significant amount of disc loading. The AccuFlex rod system has been approved by the Food and Drug Administration for single-level fusion when used in conjunction with an interbody graft. In a study involving 170 patients who underwent fusion surgery for back pain, the 54 who received the AccuFlex construct had statistically similar fusion rates and outcomes (as assessed by visual analog scale and Short Form-16 scores) when compared with 116 patients treated with rigid rod fixation after 1 year of follow up. Future clinical studies will examine and provide information regarding the impact of AccuFlex on the incidence of adjacent-level disease. Information gained through the clinical experience with AccuFlex will serve as a foundation for the development of a stand-alone dynamic construct.

Stereotactic radiosurgery for functional disorders.

Stereotactic radiosurgery (SRS) with the Gamma Knife and linear accelerator has revolutionized neurosurgery over the past 20 years. The most common indications for radiosurgery today are tumors and arteriovenous malformations of the brain. Functional indications such as treatment of movement disorders or intractable pain only contribute a small percentage of treated patients. Although SRS is the only noninvasive form of treatment for functional disorders, it also has some limitations: neurophysiological confirmation of the target structure is not possible, and one therefore must rely exclusively on anatomical targeting. Furthermore, lesion sizes may vary, and shielding adjacent radiosensitive neural structures may be difficult or impossible. The most common indication for functional SRS is the treatment of trigeminal neuralgia. Radiosurgical treatment for epilepsy and certain psychiatric illnesses is performed in several centers as part of strict research protocols, and radiosurgical pallidotomy or medial thalamotomy is no longer recommended due to the high risk of complications. Radiosurgical ventrolateral thalamotomy for the treatment of tremor in patients with Parkinson disease or multiple sclerosis, as well as in the treatment of essential tremor, may be indicated for a select group of patients with advanced age, significant medical conditions that preclude treatment with open surgery, or patients who must receive anticoagulation therapy. A promising new application of SRS is high-dose radiosurgery delivered to the pituitary stalk. This treatment has already been successfully performed in several centers around the world to treat severe pain in patients with end-stage cancer.

Updates On Chimeric Antigen Receptor-Mediated Glioblastoma Immunotherapy.

Glioblastoma multiforme (GBM) is the most malignant of the primary central nervous system (CNS) neoplasms, accounting for nearly 80% of all primary brain tumors and is associated with high morbidity and mortality. Immunotherapy is proving to be a fertile ground for next-generation GBM therapy, with large translational research projects and clinical trials currently underway. One particularly promising area is the chimeric antigen receptors (CARs) in the context of lymphocyte adoptive cell therapy (ACT), which has achieved success in the treatment of hematological malignancies. In this review, we will discuss CARs and review current challenges facing their use in GBM therapy. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].

Esthesioneuroblastoma (olfactory neuroblastoma) with hemorrhage: an unusual presentation.

Esthesioneuroblastoma (olfactory neuroblastoma) is an uncommon neuroectodermal tumor. Its biological activity ranges from indolent growth to local recurrence and rapid widespread metastasis. Treatment options consist of surgical resection followed by radiation therapy for primary lesions and the addition of chemotherapy for advanced, recurrent, or metastatic lesions. Patients often present with nasal obstruction, rhinorrhea, recurrent epistaxis, hyposmia, or anosmia. However, we report the highly unusual case of a patient with an esthesioneuroblastoma who presented with atypical symptoms of headaches, sinus congestion, and fatigue before acutely losing consciousness. Imaging showed a large frontal skull-based tumor associated with intratumoral hemorrhage. The findings prompted an emergent combined anterior craniofacial resection with gross total resection of the tumor. Except for anosmia, the patient recovered almost completely. Postoperatively, she received adjuvant intensity-modulated radiation therapy and chemotherapy. This is the first reported case of an esthesioneuroblastoma presenting with hemorrhage and rapidly declining mental status, an acute neurological manifestation of which clinicians should be aware.

Cerebrospinal fluid (vascular endothelial growth factor) and serologic (recoverin) tumor markers for malignant glioma.

BACKGROUND: Clinically useful tumor markers have yet to be identified for malignant glioma. We report on two potential novel tumor markers, vascular endothelial growth factor (VEGF) and recoverin (protein A). VEGF is a highly specific endothelial cell activator that induces angiogenesis both in vivo and in vitro. Our study was designed to assess whether VEGF could be measured in the cerebrospinal fluid (CSF) of patients with cerebral neoplasms and used as a marker of particular tumors. We also studied serum recoverin levels in patients with various brain tumors and compared these to controls. Recoverin is a detectable serologic protein that is expressed in patients with cancer-associated retinopathy, a paraneoplastic syndrome. METHODS: In the VEGF arm, we used a solid-phase ELISA to determine the levels of VEGF. CSF samples from patients with anaplastic astrocytoma and glioblastoma multiforme (GBM) and with metastatic and nonastrocytic brain tumors were compared with nontumor control samples. In our recoverin study, an immunoenzymetric assay was used to measure the serum recoverin levels patients with glioma and compared with controls. RESULTS: In the VEGF arm, 89% of samples with malignant astrocytoma and 27% of nonastrocytoma samples had detectable levels of VEGF. VEGF was not detectable in normal CSF samples. The levels of VEGF were significantly higher in high-grade astrocytomas than in nonastrocytic tumors. Recoverin levels were 10-fold higher in patients with recurrent GBM relative to controls. In patients with low-grade glioma, anaplastic glioma, and GBM with no evidence of recurrence, a 3- to 5-fold increase was observed. CONCLUSIONS: VEGF is detectable in CSF and may be a potential marker for differentiating astrocytic from nonastrocytic tumors. Recoverin is detectable in serum and may be a useful glioma tumor marker, especially for recurrent active disease. These markers may have application for tumor diagnosis, surveillance, and treatment response.