Combined neuromodulation and resection for functional cortex epilepsy: a case series.

OBJECTIVE: Medically refractory epilepsy (MRE) often requires resection of the seizure onset zone (SOZ) for effective treatment. However, when the SOZ is in functional cortex (FC), achieving complete and safe resection becomes difficult, due to the seizure network overlap with function. The authors aimed to assess the safety and outcomes of a combined approach involving partial resection combined with focal neuromodulation for FC refractory epilepsy. METHODS: The authors performed a retrospective analysis of individuals diagnosed with MRE who underwent surgical intervention from January 2015 to December 2022. Patients whose SOZ was located in FC and were treated with resection combined with simultaneous implantation of a focal neuromodulation device (responsive neurostimulation [RNS] device) with more than 12 months of follow-up data were included. All patients underwent a standard epilepsy preoperative assessment including intracranial electroencephalography and extraoperative stimulation mapping. Resections were performed under general anesthesia, followed by the concurrent implantation of an RNS device. RESULTS: Seven patients (4 males, median age 32.3 years, all right-handed) were included. The median interval from seizure onset to surgery was 17.4 years. The epileptogenic network included sensorimotor areas (cases 2, 3, and 6), visual cortex (case 1), language areas (cases 4 and 7), and the insula (case 5). The median follow-up was 3 years (range 1-5.8 years). No significant changes in neuropsychological tests were reported. One permanent nondisabling planned neurological deficit (left inferior quadrantanopia) was observed. Six patients had stimulation activated at a median of 4.7 months after resection. All patients achieved good seizure outcomes (5 with Engel class I and 2 with Engel class II outcomes). CONCLUSIONS: Maximal safe resection combined with focal neuromodulation presents a promising alternative to stand-alone resections for MRE epileptogenic zones overlapping with functional brain. This combined approach prioritizes the preservation of function while improving seizure outcomes.

Laser interstitial thermal therapy in neurosurgery: a single-surgeon experience of 313 patients.

OBJECTIVE: Real-time MRI-guided focused laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment choice for challenging intracranial lesions that are either resistant to conventional therapies or located in deep or critical areas of the brain. However, existing studies on LITT within surgical neuro-oncology are relatively small and have limited follow-up periods. The authors aimed to present a comprehensive analysis of their experiences with LITT in surgical neuro-oncology, with the intent to provide a clearer understanding of the safety and efficacy of this procedure. METHODS: This study was an exploratory cohort analysis encompassing all patients who underwent LITT for brain tumors at a single center between 2013 and 2023. The primary focus was extent of ablation (EOA), time to recurrence (TTR), and overall survival (OS). Secondary outcomes, including the rate of complications, were also evaluated. Comparative analyses were conducted based on lesion subtypes, and factors predicting outcomes were identified. RESULTS: Three hundred thirteen patients underwent LITT procedures. During a mean follow-up of 10.4 months, 66.8% of patients remained alive and 26.2% of the ablated lesions recurred. The mean age of the cohort was 60.4 ± 13.3 years (58.5% female). The lesion subtypes that were treated comprised metastases (30%), glioblastoma (GBM; 41.6%), low-grade glioma (9.1%), radiation necrosis (11.4%), and meningioma (2.2%). The permanent neurological deficit rate was 14% (n = 44), with 25 (8%) of them new-onset deficits and 19 deficits (6.1%) that were present preoperatively and did not resolve after LITT. The mean TTR and OS were 12.2 and 38.1 months, respectively. TTR and OS varied significantly by lesion subtype (p < 0.001, log-rank analysis). A high-grade lesion was identified as the single factor linked to tumor recurrence. Age, high-grade lesion, preoperative lesion volume, and readmission within 30 days were identified as factors significantly associated with OS in the multivariable Cox regression analysis. EOA > 100% predicted longer OS in metastases and GBM by log-rank analysis. CONCLUSIONS: LITT stands as a secure and feasible ablative treatment choice for intracranial lesions, potentially suitable for specific patient cases otherwise not amenable to surgical intervention. These findings further corroborate the safety of the procedure and its favorable outcomes, underscoring its potential significance in clinical practice.

Surgical Management of Brain Metastasis from Esophageal Cancer: A Systematic Review and Single-Center Experience.

BACKGROUND: Brain metastases from esophageal cancer (BMEC) are rare and aggressive, with limited literature on optimal treatment modalities and a standard of care yet to be established. The objective of this study was to systematically review existing literature and perform a retrospective analysis of our institution's patients to evaluate the influence of different treatment modalities on patient outcomes. METHODS: A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and a retrospective review of our institutional experience with BMEC were both conducted. Data based on mean survival,histology, metastasis location, and treatment modality were abstracted. RESULTS: A total of 48 studies representing 136 patients with BMEC were identified, in addition to the 11 patients treated at our institution. There were a total of 100 males (12 unreported), with a median age of 62.2 at diagnosis in our systematic review, along with 8 males with a median age of 62 in our institutional review. Collectively, survival rates observed based on histology were not similar (squamous cell carcinoma: 9.2 months, adenocarcinoma: 13.4 months), however, based on treatment modalities (surgery: 11.6 months, radiation: 10.4 months, chemotherapy: 12.3 months), and metastasis location (supratentorial: 10.5 months, infratentorial: 9.9 months), the survival times were comparable. CONCLUSIONS: Our review suggests that causes of death were often independent of brain metastases highlighting the need for further studies on early detection and prevention of primary esophageal cancer, as well as improved treatment modalities for BMECs.

The Effect of the Coronavirus Disease 2019 Pandemic on Pituitary Surgery.

OBJECTIVE: As the coronavirus disease 2019 (COVID-19) pandemic spread to the United States in 2020, there was an impetus toward postponing or ceasing nonurgent transsphenoidal pituitary surgeries to prevent the spread of the virus. Some centers encouraged transcranial approaches for patients with declining neurologic function. However, no large-scale data exist evaluating the effects that this situation had on national pituitary practice patterns. METHODS: Pituitary surgeries in the National Inpatient Sample were identified from 2017 to 2020. Surgeries in 2020 were compared with the 3 years previously to determine any differences in demographics, surgical trends/approaches, and perioperative outcomes. RESULTS: In 2020, there was a decline in overall pituitary surgeries (34.2 vs. 36.3%; odds ratio (OR), 0.88; P < 0.001) yet transsphenoidal approaches represented a higher proportion of interventions (69.0 vs. 64.9%; P < 0.001). Neurosurgical complications were higher (51.9 vs. 47.4%; OR, 1.13; P < 0.001) and patients were less likely to be discharged home (86.4 vs. 88.5%; OR, 0.84; P < 0.001). This finding was especially true in April 2020 during the first peak in COVID-19 cases, when transcranial approaches and odds of mortality/complications were highest. CONCLUSIONS: In 2020, transsphenoidal surgery remained the preferred approach for pituitary tumor resection despite initial recommendations against the approach to prevent COVID-19 spread. Pituitary surgeries had a higher risk of periprocedural complications despite accounting for preoperative comorbidities, COVID-19 infection status, and surgical approach, suggesting that an overwhelmed hospital system can negatively influence surgical outcomes in noninfected patients.

Minimally invasive keyhole approach for supramaximal frontal glioma resections: technical note.

OBJECTIVE: The authors aimed to review the frontal lobe's surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results. METHODS: Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis. RESULTS: Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months. CONCLUSIONS: Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

Chat-GPT on brain tumors: An examination of Artificial Intelligence/Machine Learning's ability to provide diagnoses and treatment plans for example neuro-oncology cases.

OBJECTIVE: Assess the capabilities of ChatGPT-3.5 and 4 to provide accurate diagnoses, treatment options, and treatment plans for brain tumors in example neuro-oncology cases. METHODS: ChatGPT-3.5 and 4 were provided with twenty example neuro-oncology cases of brain tumors, all selected from medical textbooks. The artificial intelligence programs were asked to give a diagnosis, treatment option, and treatment plan for each of these twenty example cases. Team members first determined in which cases ChatGPT-3.5 and 4 provided the correct diagnosis or treatment plan. Twenty neurosurgeons from the researchers' institution then independently rated the diagnoses, treatment options, and treatment plans provided by both artificial intelligence programs for each of the twenty example cases, on a scale of one to ten, with ten being the highest score. To determine whether the difference between the scores of ChatGPT-3.5 and 4 was statistically significant, a paired t-test was conducted for the average scores given to the programs for each example case. RESULTS: In the initial analysis of correct responses, ChatGPT-4 had an accuracy of 85% for its diagnoses of example brain tumors and an accuracy of 75% for its provided treatment plans, while ChatGPT-3.5 only had an accuracy of 65% and 10%, respectively. The average scores given by the twenty independent neurosurgeons to ChatGPT-4 for its accuracy of diagnosis, provided treatment options, and provided treatment plan were 8.3, 8.4, and 8.5 out of 10, respectively, while ChatGPT-3.5's average scores for these categories of assessment were 5.9, 5.7, and 5.7. These differences in average score are statistically significant on a paired t-test, with a p-value of less than 0.001 for each difference. CONCLUSIONS: ChatGPT-4 demonstrates great promise as a diagnostic tool for brain tumors in neuro-oncology, as attested to by the program's performance in this study and its assessment by surveyed neurosurgeon reviewers.

Infrasellar Nasopharyngeal Craniopharyngiomas: An Individual Participant Data Meta-Analysis and Review of the Literature.

BACKGROUND: Craniopharyngiomas are benign tumors of the anterior skull base arising from epithelial remnants of Rathke pouch. They mainly occur in the suprasellar space, can be incredibly debilitating, and remain difficult to resect as they frequently involve critical neurovascular structures. Although it is embryologically possible for craniopharyngiomas to arise extracranially along the entire migrational path of Rathke pouch, these remain exceedingly rare, especially among adults, and can be mistaken for nasopharyngeal cancer. As such, minimal data exist evaluating the management and outcomes of such lesions. We evaluated our institutional experience with purely infrasellar nasopharyngeal craniopharyngiomas and obtained individual patient data reported in the contemporary literature to better characterize the demographics, presentation, surgical management, and long-term outcomes of these lesions. METHODS: A systematic review of the literature was performed to identify previously published cases of purely infrasellar nasopharyngeal craniopharyngioma in 3 electronic databases: MEDLINE (PubMed), Embase, and Scopus. Search terms were "infrasellar craniopharyngioma" and "nasopharyngeal craniopharyngioma." RESULTS: We identified 25 cases, in which 72% of patients presented with symptoms of nasal obstruction, epistaxis, or headache. An endoscopic approach was performed in 40% of cases; 83.3% of all patients had gross total resection, with 60% having no recurrence at a median follow-up of 13 months. No postoperative complications were reported. Tumor location involving the cavernous sinus was associated with incomplete resection (100%) compared with tumors not involving the cavernous sinus (87%) (P = 0.033). CONCLUSIONS: While uncommon, infrasellar nasopharyngeal craniopharyngiomas appear to have better perioperative and long-term surgical outcomes than their suprasellar counterparts.

The Learning Curve and Clinical Outcomes With 250 Laser Ablations for Brain Tumors: A Pathway to Experience.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has gained popularity as a minimally invasive technique for treating brain tumors. Despite its proven safety profile, LITT is not yet widely available, and there is a lack of data on the learning curve required to achieve proficiency. This study analyzes a 250-patient cohort of laser-ablated tumors to describe changes in patient selection and clinical outcomes over time and experience, with the aim of providing insight into the learning curve for incorporating LITT into a neuro-oncology program and identifying a cutoff point that distinguishes novice from expert performance. METHODS: We retrospectively reviewed 250 patients with brain tumor who underwent LITT between 2013 and 2022. Demographic and clinical data were analyzed. Kaplan Meier curves were used for survival analysis. Operative time was evaluated using exponential curve-fit regression analysis to identify when consistent improvement began. RESULTS: The patients were divided into quartiles (Q) based on their date of surgery. Mean tumor volume increased over time (Q1 = 5.7 and Q4 = 11.9 cm3, P = .004), and newly diagnosed lesions were more frequently ablated (P = .0001). Mean operative time (Q1 v Q4 = 322.3 v 204.6 min, P < .0001) and neurosurgical readmission rate (Q1 v Q4 = 7.8% v 0%, P = .03) were reduced over time. The exponential curve-fit analysis showed a sustained decay in operative time after case #74. The extent of ablation (P = .69), the recurrence (P = .11), and the postoperative complication rate (P = .78) did not vary over time. CONCLUSION: After treating 74 patients, a downward trend in the operative time is observed. Patient selection is broadened as experience increases.

High-Volume Centers Provide Superior Value of Care in the Surgical Treatment of Malignant Brain Tumor.

BACKGROUND: Improved outcomes in surgical patients have been associated with increasing volume of cases. This has led to the development of centers that facilitate care for a specific patient population. This study aimed to evaluate associations of outcomes with hospital characteristics in patients undergoing resection of malignant brain tumors. METHODS: The 2016-2020 National Inpatient Sample was queried for patients undergoing resection of malignant brain tumors. Teaching hospitals with caseloads >2 standard deviations above the mean (140 cases) were categorized as high-volume centers (HVCs). Value of care was evaluated by adding one point for each of the following: short length of stay, low total charges, favorable discharge disposition, and lack of major comorbidity or complication. RESULTS: In 3009 hospitals, 118,390 patients underwent resection of malignant brain tumors. HVC criteria were met by 91 (3%) hospitals. HVCs were more likely to treat patients of younger age or higher socioeconomic status (P < 0.01 for all). The Mid-Atlantic and South Atlantic regions had the highest percentage of cases and number of HVCs. Value of care was higher at HVCs (P < 0.01). Care at HVCs was associated with decreased complications (P < 0.01 for all) and improved patient outcomes (P < 0.01 for all). CONCLUSIONS: Patients undergoing craniotomy for malignant brain neoplasms have superior outcomes in HVCs. Trends of centralization may reflect the benefits of multidisciplinary treatment, geographic preferences, publicity, and cultural impact. Improvement of access to care is an important consideration as this trend continues.

Predictors of clinical and structural outcomes after surgery for spinal nerve sheath tumor resection: a retrospective analysis.

OBJECTIVE: Resection of spinal nerve sheath tumors (SNSTs) typically necessitates laminectomy, often with facetectomy, for adequate exposure of tumor. While removal of bone affords a greater operative window and extent of resection, it places the patient at greater risk for spinal instability. Although studies have identified risk factors for fusion at the time of tumor resection, there has yet to be a study assessing long-term stability following SNST resection. In this study, the authors sought to identify preoperative and operative risk factors that predispose to long-term spinal instability and investigate clinical variables associated with greater risk for subsequent fusion in the time following initial SNST resection. METHODS: An institutional registry of spinal surgeries was queried at a single institution over a 20-year period. Demographic, clinical, and operative variables were recorded retrospectively and investigated for predictive value of several postoperative sequelae. RESULTS: A total of 122 SNST cases among 112 patients were included. At a mean follow-up time of 27.7 months, patients with a history of neurofibromatosis type 2 (NF2) (p = 0.014) and those who had undergone a laminectomy of ≥ 4 levels at the time of initial SNST resection (p = 0.028) were more likely to present with some degree of structural abnormality or neurological deficit following their initial surgery. The presence of facetectomy, degree of laminectomy, and level of spinal surgery were not found to be predictors of future instability. Ultimately, there was no significant predictor for true spinal instability following index surgery without fusion. A secondary analysis showed that an entirely extradural location (p = 0.044) and facetectomy at index surgery (p = 0.012) were predictive of fusion being performed at the time of tumor resection. Four of the 112 patients required fusion after their index SNST resection, 3 of whom underwent fusion for instability at the level of the index surgery. No variables were identified as predictive for future instrumentation. CONCLUSIONS: Ultimately, the authors conclude that resection of SNSTs does not always necessitate fusion, and good outcomes can be obtained with motion-preserving techniques and minimizing facetectomy when possible. Patients with a history of NF2 and those with SNSTs that required ≥ 4-level laminectomy were more likely to exhibit some degree of structural abnormality and/or neurological deficit localized to the index level defined as either new or worsening spinal instability and/or new or worsening neurological deficit at last follow-up; however, no variable was found to be predictive of true spinal instability. Furthermore, a complete facetectomy at initial SNST resection and entirely extradural tumor location were noted to be associated with fusion at index surgery. Lastly, the authors were unable to identify a clinical predictor for future instrumentation.

Exploring the Landscape of Machine Learning Applications in Neurosurgery: A Bibliometric Analysis and Narrative Review of Trends and Future Directions.

BACKGROUND: The field of neurosurgery has consistently represented an area of innovation and integration of technology since its inception. As such, machine learning (ML) has found its way into applications within neurosurgery relatively rapidly. Through this bibliometric review and cluster analysis, we seek to identify trends and emerging applications of ML within neurosurgery. METHODS: A bibliometric analysis was carried out in the Web of Science database on publications from January 2000 to March 2023. The full data set of the 200 most cited publications including title, author information, journal, citation count, keywords, and abstracts for each publication was evaluated in CiteSpace. CiteSpace was used to elucidate publication characteristics, trends, and topic clusters via collaborate network analysis using the Kamada-Kawai algorithm. RESULTS: The 25 most cited titles were included in our analysis. Harvard University and its affiliates represented the top institution, contributing nearly 25% of publications in the literature. WORLD NEUROSURGERY was the journal with the highest net citation count of 747 (29%). Collaborative network analysis generated 12 unique clusters, the largest of which was machine learning, followed by feature importance and deep brain stimulation. CONCLUSION: This review highlights the most impactful articles pertaining to ML in the field of neurosurgery. ML has been applied into several sub-specialties within neurosurgery to optimize patient care, with special attention to outcome predictors, patient selection, and surgical decision making.

Same-day discharge after craniotomy for brain tumor resection: enhancing patient selection through a prognostic scoring system.

OBJECTIVE: Neurosurgery, among other surgical fields, is amid a shift in patient management with enhanced recovery and same-day discharge (SDD) protocols slowly becoming more popular and feasible. While such protocols reduce the risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate. The authors aimed to better quantify selection criteria through a prospective follow-up study of patients undergoing brain tumor resection with SDD. METHODS: Three arms of analysis were carried out. First, clinical data of SDD patients were prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived. RESULTS: Over the duration of the study, 31 of 334 patients were selected for SDD while 59 qualified for SDD by previously defined criteria but were not selected at the surgeon's discretion. There was no difference in outcomes between the two groups, and there were no postoperative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (left-sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume ≤ 11.75 cm3) were included in a predictive scoring system for successful SDD. The scoring system was found to significantly predict high or low likelihood for successful SDD when tested on the mixed prospective cohort. CONCLUSIONS: This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. This clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.

Bilateral Laser Interstitial Thermal Therapy for Butterfly Gliomas Compared With Needle Biopsy: A Preliminary Survival Study.

BACKGROUND AND OBJECTIVES: Bilateral/butterfly glioblastoma (bGBM) has a poor prognosis. Resection of these tumors is limited due to severe comorbidities that arise from surgical procedures. Laser interstitial thermal therapy (LITT) offers a minimally invasive cytoreductive therapy for deep-seated tumors such as bGBM. The objective of this study was to evaluate the safety of bilateral LITT in patients with bGBM. METHODS: Medical records of all consecutive patients diagnosed with bGBM by a single surgeon at a single institution from January 2014 to August 2022 were reviewed. Clinical, safety, and radiographic volumetric data were obtained. In addition, an exploratory analysis of survival was performed. RESULTS: A total of 25 patients were included; 14 underwent biopsy only, and 11 underwent biopsy + LITT (7 underwent bilateral and 4 underwent unilateral LITT). No (0%) intraoperative or postoperative complications were recorded in the treatment group. Tumor volume negatively correlated with extent of treatment (r 2 = 0.44, P = .027). The median progression-free survival was 2.8 months in the biopsy-only group and 5.5 months in the biopsy + LITT group ( P = .026). The median overall survival was 4.3 months in the biopsy-only group and 10.3 months in the biopsy + LITT group ( P = .035). CONCLUSION: Bilateral LITT for bGBM can be safely performed and shows early improvement of the progression-free survival and long-term survival outcomes of these patients.

Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma With Long-term Survival and Disease Control.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor microenvironment is scarcely reported. Nonablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting immunogenic cell death. To understand the local immune response post-LITT, we performed longitudinal molecular profiling in a newly diagnosed glioblastoma and conducted a systematic review of anti-tumoral immune responses after LITT. A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent stereotactic needle biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. Our findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy.

Two-stage radiosurgery for large brain metastases: a systematic review and meta-analysis of clinical outcomes.

OBJECTIVE: Brain metastases (BMs) are the most common intracranial tumors. In several cases, they present as large masses, which are related to a worse prognosis and more complex therapeutic alternatives. Staged radiosurgery is reported to achieve local control with minimal radiation-related adverse events in BMs. However, no methodological consensus has been achieved in its use for large brain metastases (LBMs; > 2 cm). Therefore, the authors aimed to determine the effectiveness and safety of 2-stage Gamma Knife radiosurgery (GKRS) for LBMs, in order to optimize patients' postoperative course. METHODS: A systematic review of available literature was run in PubMed/MEDLINE, Scopus, Web of Science, Cochrane (OvidSP), and Google Scholar for works published up to December 14, 2022. Nonrandomized clinical trials, case series, and cohort studies were included. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) and Joanna Briggs Institute tools. Pooled mean difference and rates estimates were calculated by a random-effects model meta-analysis. The degree of heterogeneity was expressed using the I2 statistic. A subgroup analysis was performed. Ultimately, the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment. RESULTS: Fourteen studies met the eligibility criteria (cohorts, case series, and nonrandomized clinical trials), including 958 patients. A total pooled mean volume reduction of 6.27 cm3 (95% CI 5.67-6.88 cm3) and 54.36% (95% CI 39.92%-68.79%) after 2-stage GKRS was reported. Pooled rates of complete response (44.63%; 95% CI 26.50%-64.31%), neurological mortality (16.19%; 95% CI 7.68%-30.98%), and all-cause mortality (47.92%; 95% CI 28.04%-68.49%) were calculated. Overall certainty of evidence ranged from very low to moderate. CONCLUSIONS: Two-stage GKRS is an effective and safe approach for the treatment of LBMs. Nevertheless, the lack of available literature and the weak methodological approaches used determine a low to very low certainty of evidence and cannot provide robust evidence to recommend this intervention. Therefore, it is necessary to conduct higher-quality primary studies.

Surgical management of brain metastasis from ovarian cancer: a systematic review and case series.

OBJECTIVE: Ovarian cancer is a rare origin of brain metastasis (BM), with an incidence of only 1%-3%. Consequently, the literature is sparse, and no treatment consensus guideline is available for ovarian BM. The authors conducted a systematic review of ovarian BM and performed a combined pooled cohort survival analysis with their case series. METHODS: A systematic review of PubMed, Scopus, and Web of Science consistent with PRISMA guidelines along with an institutional retrospective chart review was conducted. Inclusion criteria for the systematic review included patients with confirmed BM and primary ovarian cancer, reported perioperative complications and outcomes, differentiated histology, and explicitly reported individual patient data. Reviews, commentaries, technical notes, and articles without English-language translations were excluded. The Newcastle-Ottawa Quality Assessment Scale was used independently by the first and second authors to assess the quality of each article. The authors performed univariate and multivariate analyses of several survival prognostic factors. Kaplan-Meier curves were generated for significant prognostic factors in the univariate analysis. RESULTS: A total of 48 patients with individual data across 34 studies and 8 patients from the authors' institution were included. All patients (n = 56) underwent resection for BM; 83.9% received adjuvant radiotherapy following surgery and 41.1% of patients received adjuvant chemotherapy. The median progression-free survival was 12 months (range 2-43 months). The median overall survival was 9 months (range 1-49 months). On univariate analysis, a single BM and no extracranial metastasis conferred a survival benefit, while clear cell carcinoma as the primary histology corresponded to worsened OS. Multivariable analysis showed that age > 50 years (p = 0.002) and > 1 BM (p < 0.001) were risk factors for poor prognosis. Protective factors included the addition of the following multimodal adjuvant therapy with surgery: radiotherapy (p = 0.002), chemotherapy and radiotherapy (p = 0.005), and stereotactic radiosurgery (p = 0.002). CONCLUSIONS: Although the scarcity of published individual patient data hinders the determination of optimal management, the authors' analysis highlights that multimodal therapies, a single cranial lesion, and age < 50 years are associated with increased survival for patients with ovarian BMs.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Nitric oxide synthase inhibitors as potential therapeutic agents for gliomas: A systematic review.

INTRODUCTION: Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data. METHODS: Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells. RESULTS: Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing. CONCLUSION: Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors.

Development of an enhanced recovery protocol after laser ablation surgery protocol: a preliminary analysis.

Background: Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Methods: Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. Results: The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. Conclusions: This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.