The treatment for glioblastoma (GBM) has not seen significant improvement in over a decade. Immunotherapies target the immune system against tumor cells and have seen success in various cancer types. However, the efficacy of immunotherapies in GBM thus far has been limited. Systemic immunotherapies also carry with them concerns surrounding systemic toxicities as well as penetration of the blood-brain barrier. These concerns may potentially limit their efficacy in GBM and preclude the use of combinatorial immunotherapy, which may be needed to overcome the severe multidimensional immune suppression seen in GBM patients. The use of viral vectors to deliver immunotherapies directly to tumor cells has the potential to improve immunotherapy delivery to the CNS, reduce systemic toxicities, and increase treatment efficacy. Indeed, preclinical studies investigating the delivery of immunomodulators to GBM using viral vectors have demonstrated significant promise. In this review, the authors discuss previous studies investigating the delivery of local immunotherapy using viral vectors. They also discuss the future of these treatments, including the reasoning behind immunomodulator and vector selection, patient safety, personalized therapies, and the need for combinatorial treatment.
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Alexander F. Haddad, Jacob S. Young, and Manish K. Aghi
Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
OBJECTIVE
There is an increased recognition of disproportional lumbar lordosis (LL) and artificially high pelvic incidence (PI) as a cause for positive sagittal imbalance and spinal pelvic mismatch. For such cases, a sacral pedicle subtraction osteotomy (PSO) may be indicated, although its morbidity is not well described. In this study, the authors evaluate the specific complication risks associated with S1 PSO.
METHODS
A retrospective review of all adult spinal deformity patients who underwent a 3-column osteotomy (3CO) for thoracolumbar deformity from 2006 to 2019 was performed. Demographic, clinical baseline, and radiographic parameters were recorded. The primary outcome of interest was perioperative complications (surgical, neurological, and medical). Secondary outcomes of interest included case length, blood loss, and length of stay. Multivariate analysis was used to assess the risk of S1 PSO compared with 3CO at other levels.
RESULTS
A total of 405 patients underwent 3CO in the following locations: thoracic (n = 55), L1 (n = 25), L2 (n = 29), L3 (n = 141), L4 (n = 129), L5 (n = 17), and S1 (n = 9). After S1 PSO, there were significant improvements in the sagittal vertical axis (14.8 cm vs 6.7 cm, p = 0.004) and PI-LL mismatch (31.7° vs 9.6°, p = 0.025) due to decreased PI (80.3° vs 65.9°, p = 0.006). LL remained unchanged (48.7° vs 57.8°, p = 0.360). The overall complication rate was 27.4%; the surgical, neurological, and medical complication rates were 7.7%, 6.2%, and 20.0%, respectively. S1 PSO was associated with significantly higher rates of overall complications: thoracic (29.1%), L1 (32.0%), L2 (31.0%), L3 (19.9%), L4 (32.6%), L5 (11.8%), and S1 (66.7%) (p = 0.018). Similarly, an S1 PSO was associated with significantly higher rates of surgical (thoracic [9.1%], L1 [4.0%], L2 [6.9%], L3 [5.7%], L4 [10.9%], L5 [5.9%], and S1 [44.4%], p = 0.006) and neurological (thoracic [9.1%], L1 [0.0%], L2 [6.9%], L3 [2.8%], L4 [7.0%], L5 [5.9%], and S1 [44.4%], p < 0.001) complications. On multivariate analysis, S1 PSO was independently associated with higher odds of overall (OR 7.93, p = 0.013), surgical (OR 20.66, p = 0.010), and neurological (OR 14.75, p = 0.007) complications.
CONCLUSIONS
S1 PSO is a powerful technique for correction of rigid sagittal imbalance due to an artificially elevated PI in patients with rigid high-grade spondylolisthesis and chronic sacral fractures. However, the technique and intraoperative corrective maneuvers are challenging and associated with high surgical and neurological complications. Additional investigations into the learning curve associated with S1 PSO and complication prevention are needed.
Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
OBJECTIVE
Rigid multiplanar thoracolumbar adult spinal deformity (ASD) cases are challenging and many require a 3-column osteotomy (3CO), specifically asymmetrical pedicle subtraction osteotomy (APSO). The outcomes and additional risks of performing APSO for the correction of concurrent sagittal-coronal deformity have yet to be adequately studied.
METHODS
The authors performed a retrospective review of all ASD patients who underwent 3CO during the period from 2006 to 2019. All cases involved either isolated sagittal deformity (patients underwent standard PSO) or concurrent sagittal-coronal deformity (coronal vertical axis [CVA] ≥ 4.0 cm; patients underwent APSO). Perioperative and 2-year follow-up outcomes were compared between patients with isolated sagittal imbalance who underwent PSO and those with concurrent sagittal-coronal imbalance who underwent APSO.
RESULTS
A total of 390 patients were included: 338 who underwent PSO and 52 who underwent APSO. The mean patient age was 64.6 years, and 65.1% of patients were female. APSO patients required significantly more fusions with upper instrumented vertebrae (UIV) in the upper thoracic spine (63.5% vs 43.3%, p = 0.007). Radiographically, APSO patients had greater deformity with more severe preoperative sagittal and coronal imbalance: sagittal vertical axis (SVA) 13.0 versus 10.7 cm (p = 0.042) and CVA 6.1 versus 1.2 cm (p < 0.001). In APSO cases, significant correction and normalization were achieved (SVA 13.0–3.1 cm, CVA 6.1–2.0 cm, lumbar lordosis [LL] 26.3°–49.4°, pelvic tilt [PT] 38.0°–20.4°, and scoliosis 25.0°–10.4°, p < 0.001). The overall perioperative complication rate was 34.9%. There were no significant differences between PSO and APSO patients in rates of complications (overall 33.7% vs 42.3%, p = 0.227; neurological 5.9% vs 3.9%, p = 0.547; medical 20.7% vs 25.0%, p = 0.482; and surgical 6.5% vs 11.5%, p = 0.191, respectively). However, the APSO group required significantly longer stays in the ICU (3.1 vs 2.3 days, p = 0.047) and hospital (10.8 vs 8.3 days, p = 0.002). At the 2-year follow-up, there were no significant differences in mechanical complications, including proximal junctional kyphosis (p = 0.352), pseudarthrosis (p = 0.980), rod fracture (p = 0.852), and reoperation (p = 0.600).
CONCLUSIONS
ASD patients with significant coronal imbalance often have severe concurrent sagittal deformity. APSO is a powerful and effective technique to achieve multiplanar correction without higher risk of morbidity and complications compared with PSO for sagittal imbalance. However, APSO is associated with slightly longer ICU and hospital stays.
Qiunan Lyu, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
OBJECTIVE
The purpose of this study was to compare rod fracture (RF) rates among three types of rod constructs (RCs) following lumbar pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD).
METHODS
A retrospective review of consecutive patients with adult spinal deformity who were treated with lumbar PSO between 2007 and 2017 was performed. The minimum follow-up was 2 years. Three RCs were compared: standard (2 main rods), satellite (2 main rods with satellite rod), and nested (2 main rods and 2 short rods spanning osteotomy). Outcomes examined included RF rate, time to RF, pseudarthrosis, and reoperation. Multivariate analysis was used.
RESULTS
A total of 141 patients were included 55 with standard, 23 with satellite, and 63 with nested RCs. The mean age was 65.2 years and 34.8% of patients were male. Radiographic preoperative and postoperative results were as follows: sagittal vertical axis (11.0 vs 3.9 cm), lumbar lordosis (28.5° vs 57.1°), pelvic tilt (30.6° vs 21.0°), pelvic incidence (61.5° vs 60.0°), distance between central sacral vertical line and C7 plumb line (2.2 vs 1.5 cm), and scoliosis (18.9° vs 11.3°). The average time to RF was 12.4 months. Overall RF, bilateral RF, pseudarthrosis, and reoperation rates were 22.7%, 5.0%, 20.6%, and 17.7%, respectively. Standard RCs had a significantly higher RF (36.4% vs 13.0% vs 14.3%, p = 0.008), bilateral RF (35.0% vs 0.0% vs 0.0%, p = 0.021), pseudarthrosis (34.5% vs 8.7% vs 12.7%, p = 0.004), and reoperation (30.9% vs 4.3% vs 11.1%, p = 0.004) rates. Satellite RCs (OR 0.21, p = 0.015), nested RCs (OR 0.24, p = 0.003), and bone morphogenetic protein–2 (OR 0.28, p = 0.005) were independently associated with lower odds of RF.
CONCLUSIONS
Use of multiple rods in the satellite RC and nested RC groups was associated with lower rates of RF, pseudarthrosis, and reoperations following lumbar PSO. Bone morphogenetic protein–2 was associated with a reduction in RF rate as well.
Eric J. Chalif, Ramin A. Morshed, Jacob S. Young, Alexander F. Haddad, Saket Jain, and Manish K. Aghi
OBJECTIVE
Decision-making in how to manage pituitary adenomas (PAs) in the elderly (age ≥ 65 years) can be challenging given the benign nature of these tumors and concerns about surgical morbidity in these patients. In this study involving a large multicenter national registry, the authors examined treatment trends and surgical outcomes in elderly compared to nonelderly patients.
METHODS
The National Cancer Data Base (NCDB) was queried for adults aged ≥ 18 years with PA diagnosed by MRI (in observed cases) or pathology (in surgical cases) from 2004 to 2016. Univariate and multivariate logistic regressions were used to evaluate the prognostic impact of age and other covariates on 30- and 90-day postsurgical mortality (30M/90M), prolonged (≥ 5 days) length of inpatient hospital stay (LOS), and extent of resection.
RESULTS
A total of 96,399 cases met the study inclusion criteria, 27% of which were microadenomas and 73% of which were macroadenomas. Among these cases were 25,464 elderly patients with PA. Fifty-three percent of these elderly patients were treated with surgery, 1.9% underwent upfront radiotherapy, and 44.9% were observed without treatment. Factors associated with surgical treatment compared to observation included younger age, higher income, private insurance, higher Charlson-Deyo comorbidity (CD) score, larger tumor size, and receiving treatment at an academic hospital (each p ≤ 0.01). Elderly patients undergoing surgery had increased rates of 30M (1.4% vs 0.6%), 90M (2.8% vs 0.9%), prolonged LOS (26.1% vs 23.0%), and subtotal resection (27.2% vs 24.5%; each p ≤ 0.01) compared to those in nonelderly PA patients. On multivariate analysis, age, tumor size, and CD score were independently associated with worse postsurgical mortality. High-volume facilities (HVFs) had significantly better outcomes than low-volume facilities: 30M (0.9% vs 1.8%, p < 0.001), 90M (2.0% vs 3.5%, p < 0.001), and prolonged LOS (21.8% vs 30.3%, p < 0.001). A systematic literature review composed of 22 studies demonstrated an elderly PA patient mortality rate of 0.7%, which is dramatically lower than real-world NCDB outcomes and speaks to substantial selection bias in the previously published literature.
CONCLUSIONS
The study findings confirm that elderly patients with PA are at higher risk for postoperative mortality than younger patients. Surgical risk in this age group may have been previously underreported in the literature. Resection at HVFs better reflects these historical rates, which has important implications in elderly patients for whom surgery is being considered.
Ramin A. Morshed, Alexander F. Haddad, Kunal P. Raygor, Mary Jue Xu, Charles J. Limb, and Philip V. Theodosopoulos
Intravestibular schwannomas are rare tumors within the intralabyrinthine region and involve different management considerations compared to more common vestibular schwannomas. In this report, the authors review a case of a 52-year-old woman who presented with hearing loss and vestibular symptoms and was found to have a left intravestibular schwannoma. Given her debilitating vestibular symptoms, she underwent microsurgical resection. In this video, the authors review the relevant anatomy, surgical technique, and management considerations in these patients.
The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID2187
Alexander F. Haddad, Jacob S. Young, Ramin A. Morshed, S. Andrew Josephson, Soonmee Cha, and Mitchel S. Berger
BACKGROUND
Lower-grade insular gliomas often appear as expansile and infiltrative masses on magnetic resonance imaging (MRI). However, there are nonneoplastic lesions of the insula, such as demyelinating disease and vasculopathies, that can mimic insular gliomas.
OBSERVATIONS
The authors report two patients who presented with headaches and were found to have mass lesions concerning for lower-grade insular glioma based on MRI obtained at initial presentation. However, on the immediate preoperative MRI obtained a few weeks later, both patients had spontaneous and complete resolution of the insular lesions.
LESSONS
Tumor mimics should always be in the differential diagnosis of brain masses, including those involving the insula. The immediate preoperative MRI (within 24–48 hours of surgery) must be compared carefully with the initial presentation MRI to assess interval change that suggests tumor mimics to avoid unnecessary surgical intervention.
Alexander F. Haddad, Jacob S. Young, Jun Yeop Oh, Hideho Okada, and Manish K. Aghi
Low-grade gliomas (LGGs), which harbor an isocitrate dehydrogenase (IDH) mutation, have a better prognosis than their high-grade counterparts; nonetheless, they remain incurable and impart significant negative impacts on patients’ quality of life. Although immunotherapies represent a novel avenue of treatment for patients with LGGs, they have not yet been successful. Accurately selecting and evaluating immunotherapies requires a detailed understanding of LGG tumor immunology and the underlying tumor immune phenotype. A growing body of literature suggests that LGGs significantly differ in their immunology from high-grade gliomas, highlighting the importance of investigation into LGG immunology specifically. In this review, the authors aimed to discuss relevant research surrounding the LGG tumor immune microenvironment, including immune cell infiltration, tumor immunogenicity, checkpoint molecule expression, the impact of an IDH mutation, and implications for immunotherapies, while also briefly touching on current immunotherapy trials and future directions for LGG immunology research.
Risk factors for determining length of intensive care unit and hospital stays following correction of cervical deformity: evaluation of early severe adverse events
Presented at the 2020 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves
Rushikesh S. Joshi, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
OBJECTIVE
Correction of rigid cervical deformities can be associated with high complication rates and result in prolonged intensive care unit (ICU) and hospital stays. In this study, the authors aimed to examine the risk factors contributing to length of stay (LOS) in both the hospital and ICU following adult cervical deformity (ACD) surgery and to identify severe adverse events that occurred in this setting.
METHODS
A retrospective review of ACD patients who underwent posterior-based osteotomies for deformity correction from 2010 to 2019 was performed. Inclusion criteria were cervical kyphosis > 20° and/or cervical sagittal vertical axis (cSVA) > 4 cm. Multivariate analysis was used to identify risk factors independently associated with ICU and hospital LOS.
RESULTS
A total of 107 patients were included. The mean age was 63.5 years, and 61.7% were female. Over half (52.3%) underwent 3-column osteotomies, while 47.7% underwent posterior column osteotomies. There was significant correction of all cervical parameters: cSVA (6.0 vs 3.6 cm, p < 0.001), cervical lordosis (8.2° vs −5.3°, p < 0.001), cervical scoliosis (6.5° vs 2.2°, p < 0.001), and T1-slope (40.2° vs 34.5°, p < 0.001). There were also reciprocal changes to the distal spine: thoracic kyphosis (54.4° vs 46.4°, p < 0.001), lumbar lordosis (49.9° vs 45.8°, p = 0.003), and thoracolumbar scoliosis (13.9° vs 11.1°, p = 0.009). Overall, 4 patients (3.7%) suffered aspiration-related complications, 3 patients (2.8%) experienced dysphagia requiring a feeding tube, and 4 patients (3.7%) had compromised airways, with 1 resulting in death. The mean ICU and hospital LOS were 2.8 days and 7.9 days, respectively. Multivariate analysis identified three factors independently associated with longer ICU LOS: female sex (3.0 vs 2.4 days, p = 0.004), ≥ 12 segments fused (3.5 vs 1.9 days, p = 0.002), and postoperative complication (4.0 vs 1.9 days, p = 0.017). These same factors were independently associated with longer hospital LOS as well: female sex (8.3 vs 7.3 days, p = 0.013), ≥ 12 segments fused (9.4 vs 6.2 days, p = 0.001), and complication (9.7 vs 6.7 days, p = 0.026).
CONCLUSIONS
Posterior-based osteotomies are very effective for the correction of ACD, but postoperative hospital stays are relatively longer than those following surgery for degenerative disease. Risk factors for prolonged ICU and hospital LOS consist of both nonmodifiable (female sex) and modifiable (≥ 12 segments fused and presence of complication) risk factors. Additional multicenter prospective studies will be needed to validate these findings.
Qiunan Lyu, Darryl Lau, Alexander F. Haddad, Vedat Deviren, and Christopher P. Ames
OBJECTIVE
The purpose of this study was to compare rod fracture (RF) rates among three types of rod constructs (RCs) following lumbar pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD).
METHODS
A retrospective review of consecutive patients with adult spinal deformity who were treated with lumbar PSO between 2007 and 2017 was performed. The minimum follow-up was 2 years. Three RCs were compared: standard (2 main rods), satellite (2 main rods with satellite rod), and nested (2 main rods and 2 short rods spanning osteotomy). Outcomes examined included RF rate, time to RF, pseudarthrosis, and reoperation. Multivariate analysis was used.
RESULTS
A total of 141 patients were included 55 with standard, 23 with satellite, and 63 with nested RCs. The mean age was 65.2 years and 34.8% of patients were male. Radiographic preoperative and postoperative results were as follows: sagittal vertical axis (11.0 vs 3.9 cm), lumbar lordosis (28.5° vs 57.1°), pelvic tilt (30.6° vs 21.0°), pelvic incidence (61.5° vs 60.0°), distance between central sacral vertical line and C7 plumb line (2.2 vs 1.5 cm), and scoliosis (18.9° vs 11.3°). The average time to RF was 12.4 months. Overall RF, bilateral RF, pseudarthrosis, and reoperation rates were 22.7%, 5.0%, 20.6%, and 17.7%, respectively. Standard RCs had a significantly higher RF (36.4% vs 13.0% vs 14.3%, p = 0.008), bilateral RF (35.0% vs 0.0% vs 0.0%, p = 0.021), pseudarthrosis (34.5% vs 8.7% vs 12.7%, p = 0.004), and reoperation (30.9% vs 4.3% vs 11.1%, p = 0.004) rates. Satellite RCs (OR 0.21, p = 0.015), nested RCs (OR 0.24, p = 0.003), and bone morphogenetic protein–2 (OR 0.28, p = 0.005) were independently associated with lower odds of RF.
CONCLUSIONS
Use of multiple rods in the satellite RC and nested RC groups was associated with lower rates of RF, pseudarthrosis, and reoperations following lumbar PSO. Bone morphogenetic protein–2 was associated with a reduction in RF rate as well.
