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  • Berger, Mitchel S.  (7)
  • Theodosopoulos, Philip V.  (7)
  • 1
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), ( 2023-07-01), p. 1-10
    Abstract: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. This study examined genomic alterations found in brain metastases with the aim of identifying alterations associated with postoperative nLMD in the context of clinical and treatment factors. METHODS A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of 〉 500 oncogenes was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD. RESULTS The cohort comprised 101 patients with tumors originating from multiple cancer types. There were 15 patients with nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B codeletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazards analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (× 10 cm 3 ; HR 1.2, 95% CI 1.01–1.5; p = 0.04), CDKN2A/B codeletion (HR 5.3, 95% CI 1.7–16.9; p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1–14.4; p = 0.04) were associated with a decreased time to postoperative nLMD. CONCLUSIONS In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    RVK:
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    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2023
    detail.hit.zdb_id: 2026156-1
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  • 2
    In: Neurosurgical Focus, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 55, No. 2 ( 2023-08), p. E14-
    Abstract: Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection. METHODS All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models. RESULTS There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79–4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27–8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37–19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies. CONCLUSIONS CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.
    Type of Medium: Online Resource
    ISSN: 1092-0684
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2023
    detail.hit.zdb_id: 2026589-X
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  • 3
    In: Neurosurgical Focus, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 55, No. 2 ( 2023-08), p. E15-
    Abstract: The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery. METHODS This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses. RESULTS The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3–85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence ( RB1 : OR 13.6, 95% CI 2.0–92.39, p = 0.008; and CTNNB1 : OR 11.97, 95% CI 2.25–63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08–15.34, p = 0.039). CONCLUSIONS Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.
    Type of Medium: Online Resource
    ISSN: 1092-0684
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2023
    detail.hit.zdb_id: 2026589-X
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  • 4
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), ( 2023-01-01), p. 1-12
    Abstract: Resection of brain metastases (BMs) may be associated with increased risk of leptomeningeal disease (LMD). This study examined rates and predictors of LMD, including imaging subtypes, in patients who underwent resection of a BM followed by postoperative radiation. METHODS A retrospective, single-center study was conducted examining overall LMD, classic LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression, Cox proportional hazards, and random forest analyses were performed to identify risk factors associated with LMD. RESULTS Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD, with 19 cases (8.8%) of cLMD and 28 cases (12.9%) of nLMD. Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from the date of LMD diagnosis compared with nLMD (median 2.4 vs 6.9 months, p = 0.02, log-rank test). Cox proportional hazards analysis identified cerebellar/insular/occipital location (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.73–6.11, p = 0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27–4.88, p = 0.008), and ventricle contact (HR 2.82, 95% CI 1.5–5.3, p = 0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an area under the receiver operating characteristic curve of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. CONCLUSIONS Tumor location, absence of extracranial disease at the time of surgery, ventricle contact, and increased tumor volume were associated with LMD. Further work is needed to determine whether escalating therapies in patients at risk of LMD prevents disease dissemination.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    RVK:
    RVK:
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2023
    detail.hit.zdb_id: 2026156-1
    Location Call Number Limitation Availability
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  • 5
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 134, No. 5 ( 2021-05), p. 1386-1391
    Abstract: High-value medical care is described as care that leads to excellent patient outcomes, high patient satisfaction, and efficient costs. Neurosurgical care in particular can be expensive for the hospital, as substantial costs are accrued during the operation and throughout the postoperative stay. The authors developed a “Safe Transitions Pathway” (STP) model in which select patients went to the postanesthesia care unit (PACU) and then the neuro-transitional care unit (NTCU) rather than being directly admitted to the neurosciences intensive care unit (ICU) following a craniotomy. They sought to evaluate the clinical and financial outcomes as well as the impact on the patient experience for patients who participated in the STP and bypassed the ICU level of care. METHODS Patients were enrolled during the 2018 fiscal year (FY18; July 1, 2017, through June 30, 2018). The electronic medical record was reviewed for clinical information and the hospital cost accounting record was reviewed for financial information. Nurses and patients were given a satisfaction survey to assess their respective impressions of the hospital stay and of the recovery pathway. RESULTS No patients who proceeded to the NTCU postoperatively were upgraded to the ICU level of care postoperatively. There were no deaths in the STP group, and no patients required a return to the operating room during their hospitalization (95% CI 0%–3.9%). There was a trend toward fewer 30-day readmissions in the STP patients than in the standard pathway patients (1.2% [95% CI 0.0%–6.8%] vs 5.1% [95% CI 2.5%–9.1%] , p = 0.058). The mean number of ICU days saved per case was 1.20. The average postprocedure length of stay was reduced by 0.25 days for STP patients. Actual FY18 direct cost savings from 94 patients who went through the STP was $422,128. CONCLUSIONS Length of stay, direct cost per case, and ICU days were significantly less after the adoption of the STP, and ICU bed utilization was freed for acute admissions and transfers. There were no substantial complications or adverse patient outcomes in the STP group.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    RVK:
    RVK:
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2021
    detail.hit.zdb_id: 2026156-1
    Location Call Number Limitation Availability
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  • 6
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 135, No. 6 ( 2021-12), p. 1889-1897
    Abstract: Surgical site infection (SSI) is a complication linked to increased costs and length of hospital stay. Prevention of SSI is important to reduce its burden on individual patients and the healthcare system. The authors aimed to assess the efficacy of preoperative chlorhexidine gluconate (CHG) showers on SSI rates following cranial surgery. METHODS In November 2013, a preoperative CHG shower protocol was implemented at the authors’ institution. A total of 3126 surgical procedures were analyzed, encompassing a time frame from April 2012 to April 2016. Cohorts before and after implementation of the CHG shower protocol were evaluated for differences in SSI rates. RESULTS The overall SSI rate was 0.6%. No significant differences (p = 0.11) were observed between the rate of SSI of the 892 patients in the preimplementation cohort (0.2%) and that of the 2234 patients in the postimplementation cohort (0.8%). Following multivariable analysis, implementation of preoperative CHG showers was not associated with decreased SSI (adjusted OR 2.96, 95% CI 0.67–13.1; p = 0.15). CONCLUSIONS This is the largest study, according to sample size, to examine the association between CHG showers and SSI following craniotomy. CHG showers did not significantly alter the risk of SSI after a cranial procedure.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    RVK:
    RVK:
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2021
    detail.hit.zdb_id: 2026156-1
    Location Call Number Limitation Availability
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  • 7
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), ( 2023-06-01), p. 1-14
    Abstract: Maximal safe resection is the standard of care for patients presenting with lesions concerning for glioblastoma (GBM) on magnetic resonance imaging (MRI). Currently, there is no consensus on surgical urgency for patients with an excellent performance status, which complicates patient counseling and may increase patient anxiety. This study aims to assess the impact of time to surgery (TTS) on clinical and survival outcomes in patients with GBM. METHODS This is a retrospective study of 145 consecutive patients with newly diagnosed IDH–wild-type GBM who underwent initial resection at the University of California, San Francisco, between 2014 and 2016. Patients were grouped according to the time from diagnostic MRI to surgery (i.e., TTS): ≤ 7, 〉 7–21, and 〉 21 days. Contrast-enhancing tumor volumes (CETVs) were measured using software. Initial CETV (CETV1) and preoperative CETV (CETV2) were used to evaluate tumor growth represented as percent change (ΔCETV) and specific growth rate (SPGR; % growth/day). Overall survival (OS) and progression-free survival (PFS) were measured from the date of resection and were analyzed using the Kaplan-Meier method and Cox regression analyses. RESULTS Of the 145 patients (median TTS 10 days), 56 (39%), 53 (37%), and 36 (25%) underwent surgery ≤ 7, 〉 7–21, and 〉 21 days from initial imaging, respectively. Median OS and PFS among the study cohort were 15.5 and 10.3 months, respectively, and did not differ among the TTS groups (p = 0.81 and 0.17, respectively). Median CETV1 was 35.9, 15.7, and 10.2 cm 3 across the TTS groups, respectively (p 〈 0.001). Preoperative biopsy and presenting to an outside hospital emergency department were associated with an average 12.79-day increase and 9.09-day decrease in TTS, respectively. Distance from the treating facility (median 57.19 miles) did not affect TTS. In the growth cohort, TTS was associated with an average 2.21% increase in ΔCETV per day; however, there was no effect of TTS on SPGR, Karnofsky Performance Status (KPS), postoperative deficits, survival, discharge location, or hospital length of stay. Subgroup analyses did not identify any high-risk groups for which a shorter TTS may be beneficial. CONCLUSIONS An increased TTS for patients with imaging concerning for GBM did not impact clinical outcomes, and while there was a significant association with ΔCETV, SPGR remained unaffected. However, SPGR was associated with a worse preoperative KPS, which highlights the importance of tumor growth speed over TTS. Therefore, while it is ill advised to wait an unnecessarily long time after initial imaging studies, these patients do not require urgent/emergency surgery and can seek tertiary care opinions and/or arrange for additional preoperative support/resources. Future studies are needed to explore subgroups for whom TTS may impact clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    RVK:
    RVK:
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2023
    detail.hit.zdb_id: 2026156-1
    Location Call Number Limitation Availability
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