Publications by authors named "Ian F Dunn"

188 Publications

Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta-analysis.

Cancer Med 2021 Jun 3. Epub 2021 Jun 3.

Department of Neurosurgery, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA.

Introduction: IDH1/2 mutations are prevalent in cartilaginous tumors including chondrosarcoma. This meta-analysis using individual patient data (IPD) aimed to investigate the clinical and prognostic association of these mutations in chondrosarcoma patients.

Methods: Two electronic databases including PubMed and Web of Science were searched for relevant data. We included studies providing IPD of chondrosarcoma with available IDH1/2 mutational status for meta-analysis. Chi-square and t-test were performed to compare the groups with and without IDH1/2 mutations. For survival analysis, log-rank test, and Cox proportional hazards model were used to investigate the association of IDH mutations with patient outcomes.

Results: Fourteen studies with 488 patients were analyzed. IDH1 and IDH2 mutations were detected in 38.7% and 12.1% of cases, respectively. IDH1/2 mutations were significantly associated with an older age (p = 0.003), tumor origins (p < 0.001), tumor grades (p < 0.001), larger diameter (p = 0.003), relapse (p = 0.014), and patient mortality (p = 0.04). Multivariate Cox regression analysis adjusted for age, gender, tumor grade, and tumor sites confirmed the negative impact of IDH1/2 mutations on patient overall survival (HR = 1.90; 95% CI = 1.06-3.42; p = 0.03).

Conclusion: Our meta-analysis demonstrated the distinct characteristics of IDH1/2-mutated chondrosarcomas in comparison to those without mutations. These mutations could serve as an independent prognostic biomarker to better prognosticate patient outcomes and design appropriate treatment plans.
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http://dx.doi.org/10.1002/cam4.4019DOI Listing
June 2021

Surgical and Peri-Operative Considerations for Brain Metastases.

Front Oncol 2021 5;11:662943. Epub 2021 May 5.

Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Introduction: Brain metastases are the most common brain tumors in adults, whose management remains nuanced. Improved understanding of risk factors for surgical complications and mortality may guide treatment decisions.

Methods: A nationwide, multicenter analysis was conducted with a retrospective cohort. Adult patients in the 2012-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) databases who received a craniotomy for resection of brain metastasis were included.

Results: 3500 cases were analyzed, of which 17% were considered frail and 24% were infratentorial. The most common 30-day medical complications were venous thromboembolism (3%, median time-to-event [TTE] 4.5 days), pneumonia (4%, median TTE 6 days), and urinary tract infections (2%, median TTE 5 days). Reoperation and unplanned readmission occurred in 5% and 12% of patients, respectively. Infratentorial approach and frailty were associated with reoperation before discharge (OR 2.0 for both; p=0.01 and p=0.03 respectively), but not after discharge. Infratentorial approaches conferred heightened risk for readmission for hydrocephalus (OR 5.1, p=0.02) and reoperation for cerebrospinal fluid diversion (OR 7.1, p<0.001).Overall 30-day mortality was 4%, with nearly three-quarters occurring after discharge. Pre-frailty and frailty were associated with increased odds for post-discharge mortality (OR 1.7 and 2.7, p<0.05), but not pre-discharge mortality. We developed a model to identify pre-/peri-operative variables associated with death, including frailty, thrombocytopenia, and high American Society of Anesthesiologists score (AUROC 0.75).

Conclusions: Optimization of metrics contributing to patient frailty and heightened surveillance in patients with infratentorial metastases may be considered in the peri-operative period.
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http://dx.doi.org/10.3389/fonc.2021.662943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131835PMC
May 2021

Activity of PD-1 blockade with Nivolumab among patients with recurrent atypical/anaplastic meningioma: Phase II trial results.

Neuro Oncol 2021 May 20. Epub 2021 May 20.

Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Background: Programmed death-1 ligand (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death-1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.

Methods: Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.

Results: Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected AEs. PFS-6 was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was > 10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased post-treatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.

Conclusion: Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.
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http://dx.doi.org/10.1093/neuonc/noab118DOI Listing
May 2021

Consolidating the Hyams grading system in esthesioneuroblastoma - an individual participant data meta-analysis.

J Neurooncol 2021 May 26;153(1):15-22. Epub 2021 Mar 26.

Department of Neurosurgery, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA.

Introduction: Esthesioneuroblastoma (ENB) is an uncommon primary sinonasal tumor which can extend intracranially. Exactly how to classify them pathologically still remains discrepant; the Hyams grading system, for example, has not been universally adopted. This individual patient data (IPD) meta-analysis aimed to investigate the prognostic implication of each Hyams grade on patient outcomes.

Methods: We accessed two electronic databases including PubMed and Web of Science. Raw patient data from potential articles were extracted. To examine the associations of various clinicopathological factors with the Hyams grades, we utilized Chi-square, t-test, and Mann-Whitney, as appropriate. Log-rank test and Cox regression analysis were used to elucidate the impact of the Hyams grades on recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS) of ENB patients.

Results: We included 33 studies with 492 ENB patients. We found significant associations of Kadish stages, Dulguerov stages, rates of recurrence, metastasis, and patient mortality with Hyams grade. Log-rank tests and Cox regression models demonstrated significant differences in RFS and OS of Hyams grade I - II, grade III, and grade IV patients. There was no statistical difference in RFS and OS of Hyams grade I and II. Radiotherapy was only effective in grade III - IV ENBs and chemotherapy showed no benefits to patients.

Conclusion: We verify that the Hyams grading system appears to be a reliable prognostic indicator to assess ENB patient outcomes. Consolidating the Hyams grading system into a three-tier system based on similar clinical outcomes of grades I and II may simplify this classification schema.
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http://dx.doi.org/10.1007/s11060-021-03746-2DOI Listing
May 2021

Clinical significance of checkpoint regulator "Programmed death ligand-1 (PD-L1)" expression in meningioma: review of the current status.

J Neurooncol 2021 Feb 21;151(3):443-449. Epub 2021 Feb 21.

MacFeeters-Hamilton Center for Neuro-Oncology Research, Princess Margaret Cancer Center, 14-701, Toronto Medical Discovery Tower (TMDT), 101 College St, Toronto, ON, M5G 1L7, Canada.

Introduction: Meningioma is the most common primary brain tumor. Most meningiomas are benign; however, a subset of these tumors can be aggressive, presenting with early or multiple tumor recurrences that are refractory to neurosurgical resection and radiotherapy. There is no standard systemic therapy for these patients, and post-surgical management of these patients is usually complicated due to lack of accurate prediction for tumor progression.

Methods: In this review, we summarise the crucial immunosuppressive role of checkpoint regulators, including PD-1 and PD-L1 interacting in the tumor microenvironment, which has led to efforts aimed at targeting this axis.

Results: Since their discovery, checkpoint inhibitors have significantly improved the outcome in many types of cancers. Currently, targeted therapy for PD-1 and PD-L1 proteins are being tested in several ongoing clinical trials for brain tumors such as glioblastoma. More recently, there have been some reports implicating increased PD-L1 expression in high-grade (WHO grades II and III) meningiomas. Several clinical trials are underway to assess the efficacy of checkpoint inhibitors in the therapeutic management of patients with aggressive meningiomas. Here, we review the immune suppressive microenvironment in meningiomas, and then focus on clinical and pathological characterization and tumor heterogeneity with respect to PD-L1 expression as well as challenges associated with the assessment of PD-L1 expression in meningioma.

Conclusion: We conclude with a brief review of ongoing clinical trials using checkpoint inhibitors for the treatment of high-grade and refractory meningiomas.
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http://dx.doi.org/10.1007/s11060-020-03584-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897616PMC
February 2021

Immunophenotype of Vestibular Schwannomas.

Otol Neurotol 2020 12;41(10):e1290-e1296

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

Background: Vestibular schwannomas exhibit a uniquely variable natural history of growth, stability, or even spontaneous regression. We hypothesized that a transitory population of immune cells, or immunomodulation of tumors cells, may influence the growth pattern of schwannomas. We therefore sought to characterize the impact of the immune microenvironment on schwannoma behavior.

Methods: Forty-eight vestibular schwannomas with preoperative magnetic resonance imaging and 11 with serial imaging were evaluated for presence of immune infiltrates (including the pan-leukocyte marker Cluster of Differentiation (CD)45, CD4 and CD8 T-cell, and CD68 and CD163 macrophages) as well as expression of immunomodulatory regulators (Programmed Death Ligand 1 (PD-L1), Programmed Death Ligand 2 (PD-L2), LAG-3, TIM-3, V-domain Ig Suppressor of T cell Activation). Maximal diameter, volume, and recurrence were annotated.

Results: Vestibular schwannomas were characterized by diverse signatures of tumor infiltrating leukocytes and immunomodulatory markers. The median tumor volume was 4.7 cm (Interquartile Range (IQR) 1.0-13.0) and maximum diameter was 2.3 cm (IQR 1.5-3.2). Among tumors with serial imaging, the median volumetric growth was 0.04 cm/mo (IQR 0.01-0.18). Tumor volume and maximum diameter demonstrated strong concordance (R = 0.90; p < 0.001). Vestibular schwannoma volume was positively associated with CD4, CD68, and CD163, but not CD8, immune infiltration (all p < 0.05). Tumor growth was positively associated with CD163 and PD-L1 (both p < 0.05). Further, CD163 modified this effect: the relationship between PD-L1 and growth strengthened with increasing CD163 infiltration (R = 0.81, p = 0.007). No other immune cell types modified this relationship. These associations were inconsistently observed for maximum diameter and linear growth.

Conclusion: Vestibular schwannomas demonstrate variable expression of immune regulatory markers as well as immune infiltrates. Tumor size is associated with immune infiltrates and tumor growth is associated with PD-L1, especially in the presence of M2-subtype macrophages. Volumetric measures may associate with the biological signature more accurately than linear parameters. Future exploration of the role of immune modulation in select schwannomas will further enhance our understanding of the biology of these tumors and suggest potential therapeutic avenues for control of tumor growth.
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http://dx.doi.org/10.1097/MAO.0000000000002782DOI Listing
December 2020

Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression.

Pituitary 2021 Jun 25;24(3):359-373. Epub 2021 Jan 25.

Department of Neurosurgery, University of Oklahoma Health Sciences Center, HHDC Suite 4000, 1000 N. Lincoln Blvd, Oklahoma City, OK, 73104, USA.

Purpose: Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities.

Methods: 72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed.

Results: Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors.

Conclusion: Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.
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http://dx.doi.org/10.1007/s11102-020-01114-3DOI Listing
June 2021

Headache outcomes after surgery for pineal cyst without hydrocephalus: A systematic review.

Surg Neurol Int 2020 11;11:384. Epub 2020 Nov 11.

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, United States.

Background: Pineal cysts are common entities, with a reported prevalence between 10 and 54%. Management of pineal cysts has historically been expectant, with surgical treatment of these lesions usually reserved for patients with a symptomatic presentation secondary to mass effect. The appropriate management of pineal cysts in patients presenting with headache in the absence of hydrocephalus - often the most common clinical scenario - has been more ambiguous. Here, we report the results of a comprehensive systematic review of headache outcomes for surgically treated, non-hydrocephalic pineal cyst patients without signs of increased intracranial pressure (ICP).

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to construct a systematic review. A comprehensive search of the PubMed, Embase, Scopus, and Web of Science databases was conducted from through June 2020. Relevant English-language articles were identified using the search terms "pineal cyst" and "headache." The following eligibility criteria were applied: the inclusion of at least one surgically-treated, non-hydrocephalic pineal cyst patient presenting with headache in the absence of hemorrhage or signs and symptoms of increased ICP. Patient demographics and post-operative headache outcomes for the included studies were extracted and summarized.

Results: A total of 24 pineal cyst cases meeting our selection criteria were identified across 11 included studies. Postoperative improvement or resolution of headaches was reported for 23/24 patients. Our systematic review of the literature demonstrates that non-hydrocephalic patients with pineal cysts have a high rate of headache improvement following surgical intervention.

Conclusion: The results indicate a need for further investigation of the link between headache and pineal cysts in the non-hydrocephalic patient.
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http://dx.doi.org/10.25259/SNI_541_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771429PMC
November 2020

Bilateral occipital metastases: Visual deficits and management considerations.

Surg Neurol Int 2020 11;11:428. Epub 2020 Dec 11.

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma, United States.

Background: Metastases to the bilateral occipital lobes pose a difficult clinical scenario due to risk of debilitating visual loss. We sought to characterize clinical outcomes following different treatment modalities to help guide management in this challenging situation.

Methods: We retrospectively reviewed brain metastases patients treated at a single institution between 2008 and 2017 and assessed visual symptoms before and after treatment, the tumor and peritumoral edema volumes before treatment, and clinical outcomes including mortality.

Results: Eighteen patients with metastases affecting both occipital lobes were identified. Lung cancer represented the most common primary ( = 10). Visual deficits were present in 12 patients at the time of diagnosis of bilateral occipital metastases (67%). Patients received radiotherapy ( = 5) or combined surgical resection and radiotherapy ( = 13). Among symptomatic patients, two received radiation and 10 received combined surgery and radiation. Nine patients had improved visual symptoms after treatment with no new visual deficits reported as a result of treatment. Among asymptomatic patients, three were treated with radiation alone and three with resection and radiation. Three of these patients developed new visual symptoms following treatment, including one patient with Balint's syndrome.

Conclusion: Patients with symptomatic bilateral occipital lobe metastases may experience visual improvement following intervention, especially if symptoms stem from compression or edema. Those without visual symptoms are at risk of developing new visual deficits during treatment, which should be included in the decision-making process and when counseling patients. Visual deficits improved after surgery in the majority of patients, with no cases of immediate visual deterioration.
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http://dx.doi.org/10.25259/SNI_487_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749938PMC
December 2020

Risk factors for tumor recurrence and progression of spindle cell oncocytoma of the pituitary gland: a systematic review and pooled analysis.

Pituitary 2021 Jun 18;24(3):429-437. Epub 2020 Nov 18.

Department of Neurosurgery, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA.

Introduction: Spindle cell oncocytoma (SCO) is an extremely rare sellar neoplasm. No observational studies have been reported so far to investigate the prognostic factors of this tumor entity. This systematic review aimed to elucidate the risk factors for tumor recurrence/progression of SCO.

Methods: We searched for relevant articles in PubMed and Web of Science. Studies providing individual patient data with follow-up information of SCO cases were included. Pearson's Chi square and Fisher's exact test were used for categorical variables while t test or Mann-Whitney tests were applied for continuous variables, if applicable. We used the Cox regression model to assess the effects of suspected variables on progression-free survival (PFS).

Results: A total of 38 case reports and case series comprising of 67 SCOs were included for final analyses. Recurrent/progressive tumors were noted in 38.8% of cases. Among the clinicopathological factors, only the extent of surgery was a significant risk factor for tumor recurrence/progression. SCO patients with a subtotal resection had a significantly higher risk for tumor relapse in comparison with complete removal (HR 7.51; 95% CI 1.75-32.31; p = 0.007).

Conclusion: Our study demonstrated the characteristic clinicopathological features of SCOs with a high recurrence/progression rate and outlined the predictor for tumor relapse. Failure to achieve gross total resection is the only risk factor for tumor recurrence/progression.
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http://dx.doi.org/10.1007/s11102-020-01110-7DOI Listing
June 2021

Postoperative Day 1 Morning Cortisol Value as a Biomarker to Predict Long-term Remission of Cushing Disease.

J Clin Endocrinol Metab 2021 Jan;106(1):e94-e102

Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Context: Recurrence of Cushing disease (CD) can occur even decades after surgery. Biomarkers to predict recurrence of CD after surgery have been studied but are inconclusive.

Objective: The aim of our study was to identify specific biomarkers that can predict long-term remission after neurosurgery.

Design: Identification of specific biomarkers to predict long-term remission of CD was performed by logistic regression analysis followed by Kaplan-Meier survival analysis, using recurrence as the dependent variable.

Setting: A total of 260 patients with CD identified from our institutional research patient data registry search tool and from patients who presented to our longitudinal multidisciplinary clinic between May 2008 and May 2018 underwent statistical analysis.

Interventions: Data on clinical features, neuro-imaging study, pathology, biochemistry, and treatments were collected by reviewing digital chart records.

Main Outcome Measure: Postoperative cortisol as a biomarker to predict long-term remission after surgical treatment for CD.

Results: By logistic regression analysis, postoperative day 1 (POD1) morning (5-10 am) serum cortisol, female sex, and proliferative index had significant association with CD recurrence (odds ratio [OR] = 1.025, 95% CI: 1.002-1.048, P = .032). In contrast, the postoperative nadir cortisol (OR = 1.081, 95% CI: 0.989-1.181, P = .086), urinary free cortisol (OR = 1.032, 95% CI: 0.994-1.07, P = .098), and late night salivary cortisol (OR = 1.383, 95% CI: 0.841-2.274, P = .201) had no significant correlation with recurrence. A significant association between POD1 morning serum cortisol and long-term CD remission was verified by Kaplan-Meier analysis when using POD1 morning serum cortisol <5 μg/dL as the cut-off.

Conclusions: The POD1 morning serum cortisol level has a significant association with CD recurrence.
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http://dx.doi.org/10.1210/clinem/dgaa773DOI Listing
January 2021

An Evaluation of Neurosurgical Practices During the Coronavirus Disease 2019 Pandemic.

World Neurosurg 2021 02 13;146:e91-e99. Epub 2020 Oct 13.

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address:

Objective: We sought to understand how the coronavirus disease 2019 pandemic has affected the neurosurgical workforce.

Methods: We created a survey consisting of 22 questions to assess the respondent's operative experience, location, type of practice, subspecialty, changes in clinic and operative volumes, changes to staff, and changes to income since the pandemic began. The survey was distributed electronically to neurosurgeons throughout the United States and Puerto Rico.

Results: Of the 724 who opened the survey link, 457 completed the survey. The respondents were from throughout the United States and Puerto Rico and represented all practices types and subspecialties. Nearly all respondents reported hospital restrictions on elective surgeries. Most reported a decline in clinic and operative volume. Nearly 70% of respondents saw a decrease in the work hours of their ancillary providers, and almost one half (49.1%) of the respondents had had to downsize their practice staff, office assistants, nurses, schedulers, and other personnel. Overall, 43.6% of survey respondents had experienced a decline in income, and 27.4% expected a decline in income in the upcoming billing cycle. More senior neurosurgeons and those with a private practice, whether solo or as part of a group, were more likely to experience a decline in income as a result of the pandemic compared with their colleagues.

Conclusion: The coronavirus disease 2019 pandemic will likely have a lasting effect on the practice of medicine. Our survey results have described the early effects on the neurosurgical workforce. Nearly all neurosurgeons experienced a significant decline in clinical volume, which led to many downstream effects. Ultimately, analysis of the effects of such a pervasive pandemic will allow the neurosurgical workforce to be better prepared for similar events in the future.
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http://dx.doi.org/10.1016/j.wneu.2020.10.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550862PMC
February 2021

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis.

BMC Cancer 2020 Sep 21;20(1):897. Epub 2020 Sep 21.

Department of Neurosurgery, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA.

Background: There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients.

Methods: Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies.

Results: A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55-0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54-2.26; p-value < 0.001). TERT-mutated glioblastoma (GBM) patients with MGMT methylation benefited from temozolomide (TMZ) treatment (HR = 0.33; 95% CI = 0.23-0.47; p-value < 0.001). MGMT methylation was not related with any improvement in OS in TERT-wild type GBMs (HR = 0.80; 95% CI = 0.56-1.15; p-value = 0.23).

Conclusions: The prognostic value of TERT promoter mutation may be modulated by MGMT methylation status. Not all MGMT-methylated GBM patients may benefit from TMZ; it is possible that only TERT-mutated GBM with MGMT methylation, in particular, may respond.
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http://dx.doi.org/10.1186/s12885-020-07364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504655PMC
September 2020

Translational Windows in Chordoma: A Target Appraisal.

Front Neurol 2020 8;11:657. Epub 2020 Jul 8.

Center for Skull Base and Pituitary Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States.

Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in cell-cycle regulation and chromatin remodeling genes have been identified in chordomas, but their significance remains unknown. Investigation of the immune microenvironment of these tumors suggests that checkpoint protein expression may influence prognosis, and adjuvant immunotherapy may improve patient outcome. Finally, growing evidence supports aberrant growth factor signaling as potential pathogenic mechanisms in chordoma. In this review, we characterize the impact on treatment opportunities offered by the genomic and immunologic landscape of this tumor.
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http://dx.doi.org/10.3389/fneur.2020.00657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360834PMC
July 2020

Microscopic and Endoscopic Skull Base Approaches Hands-On Cadaver Course at 30: Historical Vignette.

World Neurosurg 2020 10 18;142:434-440. Epub 2020 Jul 18.

Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, United States; Semmes Murphey Neurologic & Spine Institute, Memphis, Tennessee, United States. Electronic address:

Laboratory-based cadaveric training is essential for the development and refinement of neurosurgical technical skills in the operating room and has become an integral training component around the world. Postresidency fellowship-the first pillar of skull base surgery training-includes both hands-on clinical care and surgery supervised by an experienced skull base surgeon. Time is spent in a skull base laboratory practicing approaches and developing anatomic mastery. The second pillar includes formal skull-base courses-institutional dissection laboratories provide continuous anatomic and surgical education while complementary annual or semiannual cadaver courses gather recognized experts to share their knowledge and experience in an essential 2- to 3-day setting. In this paper, we present the history of the longest running annual skull-base cadaver microsurgical course, which was started by Dr. Ossama Al-Mefty: Annual Surgical Approaches to the Skull Base Course. At the Microscopic and Endoscopic Hands-on Cadaver Workshop, held in St. Louis, Missouri, we celebrated its 30th anniversary in April 2019. We also present the impact this course has had on neurosurgery and skull base surgery and on the professional and scientific developments of its participants in particular.
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http://dx.doi.org/10.1016/j.wneu.2020.07.064DOI Listing
October 2020

Impact of insurance on hospital course and readmission after resection of benign meningioma.

J Neurooncol 2020 Aug 11;149(1):131-140. Epub 2020 Jul 11.

Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.

Introduction: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients' insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies.

Methods: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014-2015.

Results: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p > 0.05), 59% of Medicaid patients (OR 2.3, p < 0.001), and 49% of self-pay patients (OR 3.4, p < 0.001). Medicare (OR 1.5, p = 0.002) and Medicaid (OR 1.4, p = 0.035) were both associated with higher likelihood of 90-day readmission compared to private insurance. In comparison, 30-day analyses did not unveil this discrepancy between Medicaid and privately insured, highlighting the merit for longer-term outcomes analyses in value-based care. Patients readmitted within 30 days versus those with later readmissions possessed different characteristics.

Conclusions: Compared to patients with private insurance coverage, Medicaid and self-pay patients were significantly more likely to undergo non-elective resection of benign meningioma. Medicaid and Medicare insurance were associated with a higher likelihood of 90-day readmission; only Medicare was significant at 30 days. Both 30 and 90-day outcomes merit consideration given differences in readmitted populations.
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http://dx.doi.org/10.1007/s11060-020-03581-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484429PMC
August 2020

An Evaluation of Neurosurgical Resident Education and Sentiment During the Coronavirus Disease 2019 Pandemic: A North American Survey.

World Neurosurg 2020 08 5;140:e381-e386. Epub 2020 Jun 5.

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address:

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous impact on the healthcare system. Owing to restrictions in elective surgery and social distancing guidelines, the training curriculum for neurosurgical trainees has been rapidly evolving. This evolution could have significant long-term effects on the training of neurosurgery residents. The objective of the present study was to assess the effects of COVID-19 on neurosurgical training programs and residents.

Methods: A survey consisting of 31 questions assessing changes to resident clinical and educational workload and their sentiment regarding how these changes might affect their careers was distributed electronically to neurosurgery residents in the United States and Canada.

Results: The survey respondents were from 29 states and Canada and were relatively evenly spread across all levels of residency. Nearly 82% reported that the inpatient and outpatient volumes had been either greatly (44.0%) or moderately (37.8%) reduced. Greater than 91% reported that their work responsibilities or access to the hospital had been reduced, with a significant reduction in work hours and a significant increase in resident didactics (P < 0.001). Senior residents expressed concern about their educational experience and their future career prospects as a result of the pandemic.

Conclusion: Universally, residents have experienced reduced work hours and a reduction in their operative case volumes. Programs have adapted by increasing didactic time and using electronic platforms. It is quite possible that this remarkable period will prompt a critical reappraisal of the pre-COVID-19 adequacy of educational content in our training programs and that the enhanced educational efforts driven by this pandemic could be lasting.
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http://dx.doi.org/10.1016/j.wneu.2020.05.263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274118PMC
August 2020

GATA2 Regulates Constitutive PD-L1 and PD-L2 Expression in Brain Tumors.

Sci Rep 2020 06 3;10(1):9027. Epub 2020 Jun 3.

Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

Encouraging clinical results using immune checkpoint therapies to target the PD-1 axis in a variety of cancer types have paved the way for new immune therapy trials in brain tumor patients. However, the molecular mechanisms that regulate expression of the PD-1 pathway ligands, PD-L1 and PD-L2, remain poorly understood. To address this, we explored the cell-intrinsic mechanisms of constitutive PD-L1 and PD-L2 expression in brain tumors. PD-L1 and PD-L2 expression was assessed by flow cytometry and qRT-PCR in brain tumor cell lines and patient tumor-derived brain tumor-initiating cells (BTICs). Immunologic effects of PD-L2 overexpression were evaluated by IFN-γ ELISPOT. CD274 and PDCD1LG2 cis-regulatory regions were cloned from genomic DNA and assessed in full or by mutating and/or deleting regulatory elements by luciferase assays. Correlations between clinical responses and PD-L1 and PD-L2 expression status were evaluated in TCGA datasets in LGG and GBM patients. We found that a subset of brain tumor cell lines and BTICs expressed high constitutive levels of PD-L1 and PD-L2 and that PD-L2 overexpression inhibited neoantigen specific T cell IFN-γ production. Characterization of novel cis-regulatory regions in CD274 and PDCD1LG2 lead us to identify that GATA2 is sufficient to drive PD-L1 and PD-L2 expression and is necessary for PD-L2 expression. Importantly, in TCGA datasets, PD-L2 correlated with worse clinical outcomes in glioma patients.. By perturbing GATA2 biology, targeted therapies may be useful to decrease inhibitory effects of PD-L2 in the microenvironment.
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http://dx.doi.org/10.1038/s41598-020-65915-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271235PMC
June 2020

Is Falcine Meningioma a Diffuse Disease of the Falx? Case Series and Analysis of a "Grade Zero" Resection.

Neurosurgery 2020 10;87(5):900-909

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Falcine meningiomas have unique characteristics including their high rates of recurrence, association with high grade pathology, increased male prevalence, and potential for diffuse involvement of the falx.

Objective: To address these issues in a substantial series of falcine meningiomas and report on the impact of extent of resection for this distinct meningioma entity.

Methods: Retrospective analysis of characteristics and outcomes of 59 falcine meningioma patients who underwent surgery with the senior author. A "Grade Zero" category was used when an additional resection margin of 2 to 3 cm from the tumor insertion was achieved.

Results: For de novo falcine meningiomas, gross total resection (GTR) was associated with significantly decreased recurrence incidence compared with subtotal resection (P ≤ .0001). For recurrent falcine meningiomas, median progression-free survival (PFS) was significantly improved for GTR cases (37 mo vs 12 mo; P = .017, hazard ratio (HR) .243 (.077-.774)). "Grade Zero" resection demonstrated excellent durability for both de novo and recurrent cases, and PFS was significantly improved with "Grade Zero" resection for recurrent cases (P = .003, HR 1.544 (1.156-2.062)). The PFS benefit of "Grade Zero" resection did not achieve statistical significance over Simpson grade 1 during the limited follow-up period (mean 2.8 yr) for these groups.

Conclusion: The recurrence of falcine meningiomas is related to the diffuse presence of tumor between the leaflets of the falx. Increased extent of resection including, when possible, a clear margin of falx surrounding the tumor base was associated with the best long-term outcomes in our series, particularly for recurrent tumors.
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http://dx.doi.org/10.1093/neuros/nyaa038DOI Listing
October 2020

Perioperative nasal and paranasal sinus considerations in transsphenoidal surgery for pituitary disease.

Br J Neurosurg 2020 Jun 25;34(3):246-252. Epub 2020 Feb 25.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Endoscopic endonasal skull base surgery has emerged as the treatment modality of choice for a range of skull base lesions, particularly pituitary adenomas. However, navigation and manipulation of the nasal corridor and paranasal sinuses requires that surgeons are aware of effective techniques to maximize patient outcomes and avoid sinonasal morbidity postoperatively. This paper is a narrative review aimed to provide an updated and consolidated report on the perioperative management of the nasal corridor and paranasal sinuses in the setting of endoscopic skull base surgery for pituitary disease. Anatomic variants and common surgical techniques are discussed. Post-operative complications are evaluated in detail. Understanding the structural implications of the endonasal approach to the sphenoid is crucial to optimization of the surgical outcomes. We propose guidelines for perioperative management of endoscopic endonasal skull base surgery for pituitary diseases. Standardized treatment algorithms can improve patient satisfaction, and increase the comparability and the quality of reported information across research studies.
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http://dx.doi.org/10.1080/02688697.2020.1731424DOI Listing
June 2020

Brachytherapy with surgical resection as salvage treatment for recurrent high-grade meningiomas: a matched cohort study.

J Neurooncol 2020 Jan 19;146(1):111-120. Epub 2019 Nov 19.

Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, USA.

Purpose: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options.

Methods: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery.

Results: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort.

Conclusion: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.
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http://dx.doi.org/10.1007/s11060-019-03342-5DOI Listing
January 2020

Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease.

Clin Cancer Res 2020 03 19;26(5):1141-1151. Epub 2019 Nov 19.

Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina.

Purpose: Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of treatment-refractory recurrence. The frequent emergence of lymphocytic hypophysitis following checkpoint blockade for other cancers, as well as the expression of PD-L1 on pituitary adenomas, suggest a role for immunotherapy.

Experimental Design: This study confirms PD-L1 expression on functioning pituitary adenomas and is the first to evaluate the efficacy of checkpoint blockade (anti-PD-L1) therapy in a preclinical model of Cushing disease.

Results: Herein, treatment with anti-PD-L1 was successful in reducing adrenocorticotropic hormone plasma levels, decreasing tumor growth, and increasing survival in our model. Furthermore, tumor-infiltrating T cells demonstrated a pattern of checkpoint expression similar to other checkpoint blockade-susceptible tumors.

Conclusions: This suggests that immunotherapy, particularly blockade of the PD1/PD-L1 axis, may be a novel therapeutic option for refractory Cushing disease. Clinical investigation is encouraged.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809696PMC
March 2020

Venous Thromboembolism Prophylaxis: Safe, but Still Provocative?

Thromb Haemost 2019 11 30;119(11):1716-1718. Epub 2019 Oct 30.

Department of Neurosurgery, Stephenson Cancer Center, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, United States.

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http://dx.doi.org/10.1055/s-0039-1700564DOI Listing
November 2019

Atypical Histopathological Features and the Risk of Treatment Failure in Nonmalignant Meningiomas: A Multi-Institutional Analysis.

World Neurosurg 2020 Jan 9;133:e804-e812. Epub 2019 Oct 9.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address:

Background: Histopathological grading of meningiomas is insufficient for optimal risk stratification. The purpose of the present study was to determine the prognostic value of atypical histopathological features across all nonmalignant meningiomas (World Health Organization [WHO] grade I-II).

Methods: The data from 334 patients with WHO grade I (n = 275) and grade II (n = 59) meningiomas who had undergone surgical resection from 2001 to 2015 at 2 academic centers were pooled. Progression/recurrence (P/R) was determined radiographically and measured from the date of surgery.

Results: The median follow-up was 52 months. The patients were stratified by the number of atypical features: 0 (n = 151), 1 (n = 71), 2 (n = 66), 3 (n = 22), and 4 or 5 (n = 24). The risk of P/R increased with an increasing number of atypical features (log-rank test, P = 0.001). The 5-year actuarial rates of P/R stratified by the number of atypical features were as follows: 0, 16.3% (95% confidence interval [CI], 10.7-24.4); 1, 21.7% (95% CI, 12.8-35.2); 2, 28.2% (95% CI, 18.4-41.7); 3, 30.4% (95% CI, 13.8-58.7); and 4 or 5, 51.4% (95% CI, 31.7-74.5). On univariate analysis, the presence of high nuclear/cytoplasmic ratio (P = 0.007), prominent nucleoli (P = 0.007), and necrosis (P < 0.00005) were associated with an increased risk of P/R. On multivariate analysis, the number of atypical features (hazard ratio [HR], 1.30; 95% CI, 1.03-1.63; P = 0.03), ≥4 mitoses per high-power fields (HR, 2.45; 95% CI, 1.17-5.15; P = 0.02), subtotal resection (HR, 3.9; 95% CI, 2.5-6.3; P < 0.0005), and the lack of adjuvant radiotherapy (HR, 2.40; 95% CI, 1.19-4.80; P = 0.01) were associated with an increased risk of P/R.

Conclusions: An increased number of atypical features, ≥4 mitoses per 10 high-power fields, subtotal resection, and the lack of adjuvant radiotherapy were independently associated with P/R of WHO grade I-II meningiomas. Patients with these features might benefit from intensified therapy.
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http://dx.doi.org/10.1016/j.wneu.2019.10.002DOI Listing
January 2020

Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022.

Clin Breast Cancer 2020 04 22;20(2):145-151.e2. Epub 2019 Aug 22.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Purpose: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance.

Patients And Methods: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662.

Results: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples.

Conclusion: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.
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http://dx.doi.org/10.1016/j.clbc.2019.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035200PMC
April 2020

The Epigenomics of Pituitary Adenoma.

Front Endocrinol (Lausanne) 2019 14;10:290. Epub 2019 May 14.

Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.

The vast majority of pituitary tumors are benign and behave accordingly; however, a fraction are invasive and are more aggressive, with a very small fraction being frankly malignant. The cellular pathways that drive transformation in pituitary neoplasms are poorly characterized, and current classification methods are not reliable correlates of clinical behavior. Novel techniques in epigenetics, the study of alterations in gene expression without changes to the genetic code, provide a new dimension to characterize tumors, and may hold implications for prognostication and management. We conducted a review of primary epigenetic studies of pituitary tumors with a focus on histone modification, DNA methylation, and transcript modification. High levels of methylation have been identified in invasive and large pituitary tumors. DNA methyltransferase overexpression has been detected in pituitary tumors, especially in macroadenomas. Methylation differences at CpG sites in promoter regions may distinguish several types of tumors from normal pituitary tissue. Histone modifications have been linked to increased p53 expression and longer progression-free survival in pituitary tumors; sirtuins are expressed at higher values in GH-expressing compared to nonfunctional adenomas and correlate inversely with size in somatotrophs. Upregulation in citrullinating enzymes may be an early pathogenic marker of prolactinomas. Numerous genes involved with cell growth and signaling show altered methylation status for pituitary tumors, including cell cycle regulators, components of signal transduction pathways, apoptotic regulators, and pituitary developmental signals. The limited clinical predictive capacity of the current pituitary tumor classification system suggests that tumor subclasses likely remain to be discovered. Ongoing epigenetic studies could provide a basis for adding methylation and/or acetylation screening to standard pituitary tumor workups. Identifying robust correlations between tumor epigenetics and corresponding histological, radiographic, and clinical course information could ultimately inform clinical decision-making.
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http://dx.doi.org/10.3389/fendo.2019.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527758PMC
May 2019

Adverse Events After Microvascular Decompression: A National Surgical Quality Improvement Program Analysis.

World Neurosurg 2019 Aug 11;128:e884-e894. Epub 2019 May 11.

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Although microvascular decompression (MVD) is a durable treatment for medically refractory trigeminal neuralgia, hemifacial spasm, or glossopharyngeal neuralgia attributable to neurovascular conflict, few national studies have analyzed predictors of postoperative complications.

Objective: To determine the incidence and risk factors for adverse events after MVD.

Methods: Patients who underwent MVD were extracted from the prospectively collected National Surgical Quality Improvement Program registry (2006-2017). Multivariable logistic regression identified predictors of 30-day adverse events and unplanned readmission; multivariable linear regression analyzed predictors of a longer hospital stay.

Results: Among the 1005 patients evaluated, the mortality was 0.3%, major neurologic complication rate 0.4%, and 2.8% had a nonroutine hospital discharge. Patient age was not a predictor of any adverse events. Statistically significant independent predictors both of any adverse event (9.2%) and of a longer hospitalization were American Society of Anesthesiologists (ASA) classification III-IV designation and longer operative duration (P ≤ 0.03) The 30-day readmission rate was 6.8%, and the most common reasons were surgical site infections (22.4%) and cerebrospinal fluid leakage (14.3%). Higher ASA classification, diabetes mellitus, and operative time were predictors of readmission (P < 0.04).

Conclusions: In this National Surgical Quality Improvement Program analysis, postoperative morbidity and mortality after MVD was low. Patient age was not a predictor of postoperative complications, whereas higher ASA classification, diabetes mellitus, and longer operative duration were predictive of any adverse event and readmission. ASA classification provided superior risk stratification compared with the total number of patient comorbidities or laboratory values. These data can assist with preoperative patient counseling and risk stratification.
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http://dx.doi.org/10.1016/j.wneu.2019.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825526PMC
August 2019

Iatrogenic Inner Ear Dehiscence After Lateral Skull Base Surgery: Therapeutic Dilemma and Treatment Options.

Otol Neurotol 2019 04;40(4):e399-e404

Brigham and Women's Hospital, Division of Otolaryngology, Harvard Medical School, Boston, Massachusetts.

Objective: To describe a series of patients with iatrogenic inner ear dehiscence after lateral skull base surgery and discuss treatment options.

Patients: Three patients with history of recent lateral skull base surgery, symptoms consistent with inner ear dehiscence, and radiographically proven bony dehiscence on postoperative imaging.

Interventions: All patients were initially managed conservatively with serial outpatient visits. Two patients with large cochlear and vestibular dehiscences had round window reinforcement procedures. One patient had transmastoid resurfacing for repair of an iatrogenic posterior semicircular canal dehiscence.

Main Outcome Measures: Anatomical location of dehiscences; treatment options; subjective auditory and vestibular symptoms pre-dehiscence, post-dehiscence and after dehiscence repair; pre- and post-audiogram when available.

Results: Patient ages were 46, 52, and 60 with two of three being women. None of the patients had subjective auditory or vestibular symptoms of inner ear dehiscence before initial skull base surgery, but they all had development of these symptoms afterwards. All patients were initially managed conservatively, but all ultimately required a surgical procedure. The two patients who elected for round window reinforcements, and the one patient who required transmastoid resurfacing, had significant improvement of symptoms.

Conclusions: Iatrogenic inner ear dehiscence after skull base surgery is best dealt with and repaired intraoperatively. Should intraoperative repair not be possible, transcanal round window reinforcement is a minimally invasive option for medial otic capsule dehiscence, although long-term outcomes are unclear. For lateral otic capsule dehiscence, a transmastoid approach is recommended.

Level Of Evidence: IV.
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http://dx.doi.org/10.1097/MAO.0000000000002162DOI Listing
April 2019

Variation in Coding Practices for Vestibular Schwannoma Surgery.

J Neurol Surg B Skull Base 2019 Feb 16;80(1):96-102. Epub 2018 Jul 16.

Department of Neurosurgery, Center for Skull Base and Pituitary Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

 Nationwide databases are frequently used resources for assessing practice patterns and clinical outcomes. However, analyses based on billing codes may be limited by the inconsistent application of current procedural terminology (CPT) codes to specific operations. We investigated the variability among commonly used CPT codes for vestibular schwannomas resection and sought to identify factors that underlie this variation.  The surgical procedure for 274 cases of vestibular schwannoma resections from two institutions was reviewed and classified as retrosigmoid, translabyrinthine, or middle fossa approaches. We then assessed the CPT codes assigned to each case and analyzed their association with surgical approach, surgeons involved, the coding specialty, and year of surgery. We further compared the incidence of CPT codes assigned for vestibular schwannoma surgeries in the American College Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2010 to 2014.  The majority (65%) of vestibular schwannoma resections within the institutional cohort were billed with skull base approach and/or excision codes, whereas 76% of cases in NSQIP were associated with a single craniotomy for tumor code. The use of skull base codes over the past decade increased within our institutional cohort but remained relatively stable within NSQIP. CPT codes did not consistently reflect the operative approaches for vestibular schwannomas.  We observed significant variability in coding patterns for vestibular schwannoma surgeries within institutions, surgical practices, and national databases. These results call for discretion in interpretation of data from aggregated billing code-based nationwide databases and suggests a role for institutional standardization of CPT assignments for the same approaches.
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http://dx.doi.org/10.1055/s-0038-1667124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365234PMC
February 2019