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Oluwaseun O. Akinduro, Brandon A. Miller, Diogo C. Haussen, Gustavo Pradilla, and Faiz U. Ahmad

OBJECT

The authors’ aim in this paper was to review the intraoperative use of epidural steroids in lumbar discectomy surgery with a focus on surgical complications.

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A comprehensive literature search was done using PubMed, MEDLINE, and the Cochrane Central Registry of Controlled Trials. Relevant papers were retrieved and analyzed. The authors performed a meta-analysis of all available data. Search terms included epidural, steroids, discectomy, lumbar disc surgery, herniated lumbar disc, methylprednisolone, and perioperative.The primary outcome was surgical complications such as wound infection or need for reoperation. Secondary outcomes were pain and postoperative narcotic usage.

RESULTS

Sixteen trials and 1 retrospective study (a total of 1933 patients) were eligible for inclusion in this study. In all studies, steroids were added epidurally over the nerve root before closure in cases, and control patients underwent discectomy alone. The mean age (42.7 years vs 42.4 years; RR 0.30 [95% CI −0.30 to 0.90], p = 0.32), overall complication rates (2.69% vs 1.18%; RR 1.94 [95% CI 0.72–5.26], p = 0.19), and infectious complication rates (0.94% vs 0.08%; RR 4.58 [95% CI 0.75–27.95], p = 0.10) were similar between the steroid group and control group, respectively.

CONCLUSIONS

There is good evidence that epidural steroids can decrease pain in the short term and decrease the usage of postoperative narcotics after lumbar spinal surgery for degenerative spinal disease. The authors’ results demonstrate a trend toward increased infection with epidural steroid use, but there was not a statistically significant difference. More studies are needed to validate the long-term risk/benefit ratio of epidural steroids in lumbar discectomy.

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Oluwaseun O. Akinduro, Paola Suarez-Meade, McKinley Roberts, Stephany Y. Tzeng, Rachel Sarabia-Estrada, Paula Schiapparelli, Emily S. Norton, Ziya L. Gokaslan, Panos Z. Anastasiadis, Hugo Guerrero-Cázares, Jordan J. Green, and Alfredo Quiñones-Hinojosa

OBJECTIVE

The vertebral column is the most common site for skeletal metastasis, often leading to debilitating pain and weakness. Metastatic cancer has unique genetic drivers that potentiate tumorigenicity. There is an unmet need for novel targeted therapy in patients with spinal metastatic disease.

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The authors assessed the effect of verteporfin-induced yes-associated protein (YAP) inhibition on spine metastatic cell tumorigenicity and radiation sensitivity in vitro. Animal studies used a subcutaneous xenograft mouse model to assess the use of systemic intraperitoneal verteporfin (IP-VP) and intratumoral verteporfin microparticles (IT-VP) to inhibit the tumorigenicity of lung and breast spinal metastatic tumors from primary patient-derived tissue.

RESULTS

Verteporfin led to a dose-dependent decrease in migration, clonogenicity, and cell viability via inhibition of YAP and downstream effectors cyclin D1, CTGF, TOP2A, ANDRD1, MCL-1, FOSL2, KIF14, and KIF23. This was confirmed with knockdown of YAP. Verteporfin has an additive response when combined with radiation, and knockdown of YAP rendered cells more sensitive to radiation. The addition of verteporfin to YAP knockdown cells did not significantly alter migration, clonogenicity, or cell viability. IP-VP and IT-VP led to diminished tumor growth (p < 0.0001), especially when combined with radiation (p < 0.0001). Tissue analysis revealed diminished expression of YAP (p < 0.0001), MCL-1 (p < 0.0001), and Ki-67 (p < 0.0001) in tissue from verteporfin-treated tumors compared with vehicle-treated tumors.

CONCLUSIONS

This is the first study to demonstrate that verteporfin-mediated inhibition of YAP leads to diminished tumorigenicity in lung and breast spinal metastatic cancer cells. Targeting of YAP with verteporfin offers promising results that could be translated to human clinical trials.

Free access

Rohin Singh, Nicole M. De La Peña, Paola Suarez-Meade, Panagiotis Kerezoudis, Oluwaseun O. Akinduro, Kaisorn L. Chaichana, Alfredo Quiñones-Hinojosa, Bernard R. Bendok, Mohamad Bydon, Fredric B. Meyer, Robert J. Spinner, and David J. Daniels

Neurosurgical education is a continually developing field with an aim of training competent and compassionate surgeons who can care for the needs of their patients. The Mayo Clinic utilizes a unique mentorship model for neurosurgical training. In this paper, the authors detail the historical roots as well as the logistical and experiential characteristics of this teaching model.

This model was first established in the late 1890s by the Mayo brothers and then adopted by the Mayo Clinic Department of Neurological Surgery at its inception in 1919. It has since been implemented enterprise-wide at the Minnesota, Florida, and Arizona residency programs. The mentorship model is focused on honing resident skills through individualized attention and guidance from an attending physician. Each resident is closely mentored by a consultant during a 2- or 3-month rotation, which allows for exposure to more complex cases early in their training.

In this model, residents take ownership of their patients’ care, following them longitudinally during their hospital course with guided oversight from their mentors. During the chief year, residents have their own clinic, operating room (OR) schedule, and OR team and service nurse. In this model, chief residents conduct themselves more in the manner of an attending physician than a trainee but continue to have oversight from staff to provide a “safety net.” The longitudinal care of patients provided by the residents under the mentorship model is not only beneficial for the trainee and the hospital, but also has a positive impact on patient satisfaction and safety. The Mayo Clinic Mentorship Model is one of many educational models that has demonstrated itself to be an excellent approach for resident education.

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Andres Ramos-Fresnedo, Ricardo A. Domingo, Jesus E. Sanchez-Garavito, Carlos Perez-Vega, Oluwaseun O. Akinduro, Mark E. Jentoft, Sujay A. Vora, Paul D. Brown, Alyx B. Porter, Bernard R. Bendok, Michael J. Link, Erik H. Middlebrooks, Daniel M. Trifiletti, Kaisorn L. Chaichana, Alfredo Quiñones-Hinojosa, and Wendy J. Sherman

OBJECTIVE

多发性脑膜瘤(MMs)发生在多达18%of patients with meningioma, and data on progression-free survival (PFS) are scarce. The objective of this study was to explore the influence of the number of lesions and clinical characteristics on PFS in patients with WHO grade I meningiomas.

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The authors retrospectively reviewed the records of all adults diagnosed with a meningioma at their three main sites from January 2009 to May 2020. Progression was considered the time from diagnosis until radiographic growth of the originally resected meningioma. A secondary analysis was performed to evaluate the time of diagnosis until the time to second intervention (TTSI). Univariable and multivariable analyses were conducted to assess whether the number of lesions or any associated variables (age, sex, race, radiation treatment, tumor location, and extent of resection) had a significant impact on PFS and TTSI.

RESULTS

Eight hundred thirty-eight patients were included. Use of a log-rank test to evaluate PFS and TTSI between a single and multiple lesions showed a significantly shorter progression for MM (p < 0.001 and p < 0.001, respectively). Multivariable Cox regression analysis showed significantly inferior PFS on MM compared to a single lesion (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.392–3.677, p = 0.001) and a significantly inferior TTSI for patients with MM when compared to patients with a single meningioma (HR 2.377, 95% CI 1.617–3.494, p = 0.001). By testing the number of meningiomas as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350, 95% CI 1.074–1.698, p = 0.010) and TTSI was significantly inferior as well (HR 1.428, 95% CI 1.189–1.716, p < 0.001). African American patients had an inferior PFS when compared to non-Hispanic White patients (HR 3.472, 95% CI 1.083–11.129, p = 0.036).

CONCLUSIONS

The PFS of meningiomas appears to be influenced by the number of lesions present. Patients with MM also appear to be more prone to undergoing a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions. These results show a decreased PFS for each additional lesion present, as well as a shorter PFS for MM compared to a single lesion. When assessing associated risk factors, African American patients showed an inferior PFS, whereas older age and adjuvant therapy with radiation showed an improved PFS.

Free access

Tito Vivas-Buitrago, Ricardo A. Domingo, Shashwat Tripathi, Gaetano De Biase, Desmond Brown, Oluwaseun O. Akinduro, Andres Ramos-Fresnedo, David S. Sabsevitz, Bernard R. Bendok, Wendy Sherman, Ian F. Parney, Mark E. Jentoft, Erik H. Middlebrooks, Fredric B. Meyer, Kaisorn L. Chaichana, and Alfredo Quinones-Hinojosa

OBJECTIVE

The authors’ goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase–wild-type (IDH-wt) glioblastoma after gross-total resection (GTR).

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888例年龄≥18年的医疗记录s who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed.

RESULTS

In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01–2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13–1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27–0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52–0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98–0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35–0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45–1.21; p = 0.234).

CONCLUSIONS

SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

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Oluwaseun o . Akinduro•迪奥戈p·加西亚,多米尼克M. O. Higgins, Tito Vivas-Buitrago, Mark Jentoft, David A. Solomon, David J. Daniels, Zach Pennington, Wendy J. Sherman, Mychael Delgardo, Mohamad Bydon, Maziyar A. Kalani, George Zanazzi, Nadejda Tsankova, Bernard R. Bendok, Paul C. McCormick, Daniel M. Sciubba, Sheng-fu Larry Lo, Jennifer L. Clarke, Kingsley Abode-Iyamah, and Alfredo Quiñones-Hinojosa

OBJECTIVE

High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic.

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The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS).

RESULTS

Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19–76) years were included in the analysis. Eighteen patients had H3 K27M mutation–positive tumors, and 12 had H3 K27M mutation–negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation–positive tumors (p = 0.017).

CONCLUSIONS

Although H3 K27M mutant–positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant–positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant–negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

Free access

Shashwat Tripathi, Tito Vivas-Buitrago, Ricardo A. Domingo, Gaetano De Biase, Desmond Brown, Oluwaseun O. Akinduro, Andres Ramos-Fresnedo, Wendy Sherman, Vivek Gupta, Erik H. Middlebrooks, David S. Sabsevitz, Alyx B. Porter, Joon H. Uhm, Bernard R. Bendok, Ian Parney, Fredric B. Meyer, Kaisorn L. Chaichana, Kristin R. Swanson, and Alfredo Quiñones-Hinojosa

OBJECTIVE

Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH–wild-type glioblastoma (GBM) to further improve patients’ overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH–wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile).

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Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3× (6.106/[VT21/1− VT11/1])2, where VT2and VT1are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse.

RESULTS

A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98–0.99; p = 0.02; and HR 0.98, 95% CI 0.96–0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively.

CONCLUSIONS

患者在操作系统对于我的影响DH–wild-type GBM is influenced by the degree of tumor invasiveness. The authors’ results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH–wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

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