Laser interstitial thermal therapy for deep-seated perivascular brain tumors is not associated with distal ischemia.

PURPOSE: Laser interstitial thermal therapy (LITT) is a minimally invasive cytoreductive treatment option for brain tumors with a risk of vascular injury from catheter placement or thermal energy. This may be of concern with deep-seated tumors that have surrounding end-artery perforators and critical microvasculature. The purpose of this study was to assess the risk of distal ischemia following LITT for deep-seated perivascular brain tumors. METHODS: A retrospective review of a multi-institution database was used to identify patients who underwent LITT between 2013 and 2022 for tumors located within the insula, thalamus, basal ganglia, and anterior perforated substance. Demographic, clinical and volumetric tumor characteristics were collected. The primary outcome was radiographic evidence of distal ischemia on post-ablation magnetic resonance imaging (MRI). RESULTS: 61 LITT ablations for deep-seated perivascular brain tumors were performed. Of the tumors treated, 24 (39%) were low-grade gliomas, 32 (52%) were high-grade gliomas, and 5 (8%) were metastatic. The principal location included 31 (51%) insular, 14 (23%) thalamic, 13 (21%) basal ganglia, and 3 (5%) anterior perforated substance tumors. The average tumor size was 19.6 cm3 with a mean ablation volume of 11.1 cm3. The median extent of ablation was 92% (IQR 30%, 100%). Two patients developed symptomatic intracerebral hemorrhage after LITT. No patient had radiographic evidence of distal ischemia on post-operative diffusion weighted imaging. CONCLUSION: We demonstrate that LITT for deep-seated perivascular brain tumors has minimal ischemic risks and is a feasible cytoreductive treatment option for otherwise difficult to access intracranial tumors.

Structure and Dynamics of the Central Lipid Pool and Proteins of the Bacterial Holo-Translocon.

The bacterial Sec translocon, SecYEG, associates with accessory proteins YidC and the SecDF-YajC subcomplex to form the bacterial holo-translocon (HTL). The HTL is a dynamic and flexible protein transport machine capable of coordinating protein secretion across the membrane and efficient lateral insertion of nascent membrane proteins. It has been hypothesized that a central lipid core facilitates the controlled passage of membrane proteins into the bilayer, ensuring the efficient formation of their native state. By performing small-angle neutron scattering on protein solubilized in "match-out" deuterated detergent, we have been able to interrogate a "naked" HTL complex, with the scattering contribution of the surrounding detergent micelle rendered invisible. Such an approach has allowed the confirmation of a lipid core within the HTL, which accommodates between 8 and 29 lipids. Coarse-grained molecular dynamics simulations of the HTL also demonstrate a dynamic, central pool of lipids. An opening at this lipid-rich region between YidC and the SecY lateral gate may provide an exit gateway for newly synthesized, correctly oriented, membrane protein helices, or even small bundles of helices, to emerge from the HTL.

Identification of High-risk Cryptic CRLF2 Rearrangements in B-Cell Acute Lymphoblastic Leukemia Utilizing an FGFR3/IGH Dual-Color Dual-Fusion DNA Probe Set.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy with gene rearrangements involving the IGH locus occurring in ∼5% of cases. Fluorescence in situ hybridization (FISH) probes targeting the IGH locus are not included in the standard children's oncology group (COG) fluorescence in situ hybridization panel. At our institute, we incorporated the use of FGFR3/IGH dual-color dual-fusion DNA probes for confirmation of aneuploidy 4 and 14 in diagnostic B-ALL specimens. Subsequently we have identified 4 B-ALL cases with cryptic CRLF2-IGH translocations that would otherwise have gone undetected. Detection of genetic alterations in B-ALL, such as CRLF2 rearrangements, may enhance patient risk stratification and therapy options in pediatric B-ALL.

A single center's approach to discriminating donor versus host origin of renal neoplasia in the allograft kidney.

Renal cell carcinoma (RCC) in the allograft of kidney transplant recipient (KTR) patients is rare and may represent a de novo process arising from the transplanted organ or metastasis from a clinically undetectable host primary. Determination of host versus donor origin is important for staging and management. We report our experience utilizing Penta-C (PC) and Penta-D (PD) short-tandem repeat (STR) microsatellite analysis to discriminate between host and donor origin of RCC identified in renal allografts. We identified 5 KTR patients with RCC in the allograft kidney. The PC and PD microsatellite analysis was applied to tumor, host, and donor formalin-fixed, paraffin-embedded tissue sections and/or fresh blood leukocytes to identify the origin of the neoplastic cells. The PC and PD microsatellite alleles were robustly amplified in all samples. Each case showed one or more informative alleles indicating that the neoplastic cells originate from donor tissue. Allele frequency data indicate that by using both PC and PD markers, we will be able to discriminate between host and donor cell of origin in over 99% of cases. The PC and PD microsatellite analysis is a convenient, robust, and efficient strategy to determine donor versus host origin or RCC in transplant kidney specimens.

Further evidence for a pain pathway involving the cingulate gyrus: a case of chronic cluster headache cured by glioblastoma.

The authors report a case of a 49-year-old man with long-standing, chronic cluster headache (CH) refractory to medical therapy and occipital nerve stimulation that resolved a few weeks prior to the diagnosis of glioblastoma involving primarily the right cingulate gyrus. An attempt to explore the underlying role of the cingulate cortex in pain modulation by appraising the current literature is presented. This report suggests that the cingulate gyri could be a potential target for neuromodulation in patients with medically refractory chronic CH.

Through the patient's eyes: the value of a comprehensive brain tumor center.

Since the founding of the Tumor Section of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) in 1984 much in neurosurgical oncology has changed. More than 40,000 papers have been published on glioma since the arrival of the AANS/CNS Tumor Section. Increasingly, research is focusing on more patient-centered care and quality of life. Preliminary work suggests that a greater emphasis on the patient and caregiver's experience of disease is crucial. Also, the provision of hope and appropriate information and communication with health care providers helps to lessen anxiety and promote improved quality of life. Lastly, our patients need a mechanism for continued symptom control and psychosocial support throughout their experience of this disease. An excellent venue for providing these facets of neurooncological patient care is the multidisciplinary brain tumor board and symptom management team. Herein, we present the philosophy and practice of the Hermelin Brain Tumor Center at the Henry Ford Health System as one type of approach to caring for the patient with a malignant glioma. The authors are aware of several brain tumor centers that share our philosophy and approach to patient care. Our comments are not meant to be exclusive to our experience and should be interpreted as representative of the growing movement in neurosurgery to provide comprehensive, multidisciplinary, patient-centered care.

Through the patient's eyes: an emphasis on patient-centered values in operative decision making in the management of malignant glioma.

The Joint Section on Tumors of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons is now in its 30th year. In many ways its growth and development has paralleled neurosurgery and medicine as a whole. This is most evident in our endeavor towards more patient-centered care and focus on quantity and quality of life. As the push towards evidence-based care continues, it is important to ensure that individualized care remains a guiding principle. Conscientious surgeons continue to refine techniques and develop technologies that push the boundaries of surgical efficacy while better defining the risks of surgery and the impacts of surgical complications. This article provides a review of the factors involved in minimizing risk and obtaining maximal outcomes for patients through insightful patient selection and evidence-based surgical decision-making. Herein, we present the philosophy and practice of the Hermelin Brain Tumor Center at the Henry Ford Health System as one type of approach to caring for the patient with a malignant glioma.

New technique for open placement of paddle-type spinal cord stimulator electrode in presence of epidural scar tissue.

OBJECTIVES: The objective of this study is to present a novel surgical technique for safe placement of paddle-type spinal cord stimulation (SCS) electrode in the presence of epidural scar tissue. MATERIALS AND METHODS: We developed a new surgical technique for placement of paddle-type SCS electrode in presence of epidural scar tissue when conventional placement methods had failed. The technique involves creating a laminotomy trough to provide an adequate window for dissection of scar tissue to ensure safe placement of the electrode. We have applied this technique in eight patients. RESULTS: Safe placement of SCS electrode was achieved in all eight patients without any complications. All electrodes were placed between T8 and T10 levels, and we were able to place the electrodes in the midline and achieve adequate coverage in all cases. CONCLUSION: SCS is a widely accepted treatment modality for chronic neuropathic pain. Placement of paddle electrode can be challenging, usually because of the presence of epidural scar tissue. There have been reported cases of spinal cord injury related to paddle electrode placement. We present a novel technique that allows for safe placement of a paddle-type SCS electrode in more challenging surgical circumstances, including the presence of epidural scar tissue.

Laser interstitial thermal therapy for first-line treatment of insular glioma.

OBJECTIVE: Insular gliomas pose a significant surgical challenge due to the complex surrounding functional and vascular anatomy. The authors report their experience using a novel framework for the treatment of insular gliomas with laser interstitial thermal therapy (LITT) and provide representative case examples emphasizing indications, rationale, and technical pearls. METHODS: A prospectively gathered institutional database was used to identify patients with newly diagnosed insular gliomas who underwent LITT between 2015 and 2023. The proposed framework of insular glioma management is guided by tumor size and extent of extra-insular tumor involvement. Patients with tumors localized to the insula (insula-only) were treated with single-session or staged LITT. Patients with insular tumors with frontotemporal involvement (insular+) were treated with insular LITT and standard frontotemporal resection of extra-insular tumor. Clinical and volumetric lesional characteristics were analyzed, with particular emphasis on extent of cytoreductive treatment and safety. RESULTS: Of the 261 patients treated at the authors' institution with LITT between 2015 and 2023, 33 LITT procedures were identified involving 22 unique patients with treatment-naive insular gliomas. Of the 22 patients, 12 had insular-only tumors and were treated with LITT alone, while 10 patients had insular+ lesions and were treated with LITT and resection. The median tumor volume for insular-only tumors was 13.4 cm3 (IQR 10.6, 26.3 cm3), with a median extent of treatment of 100% (IQR 92.1%, 100%). Insular+ lesions were significantly larger, with a median volume of 81.2 cm3 (IQR 51.9, 97 cm3) and median extent of treatment of 96.6% (IQR 93.7%, 100%). All patients with insular-only tumors were discharged the day after ablation, while insular+ patients had significantly longer hospital stays, with 50% staying more than 3 days. Overall, 8% of insular-only patients had permanent neurological deficits compared with 33% of insular+ patients. Two patients' tumors progressed during follow-up: one patient with WHO grade 4 astrocytoma and the other with diffuse glioma not otherwise specified. Patients with grade 4 tumors had the highest rate of permanent neurological deficit (43%) and a larger decline in postoperative Karnofsky Performance Status score (p = 0.046). CONCLUSIONS: The authors present their experience using a novel insular glioma treatment paradigm that incorporates LITT into the broader framework of insular glioma surgery. Their findings suggest that insular LITT is feasible and may allow for high rates of cytoreduction while potentially ameliorating the risks of conventional insular glioma surgery.

Augmented Reality Registration System for Visualization of Skull Landmarks.

BACKGROUND: Augmented reality (AR) is an emerging technology in neurosurgery with the potential to become a strategic tool in the delivery of care and education for trainees. Advances in technology have demonstrated promising use for improving visualization and spatial awareness of critical neuroanatomic structures. In this report, we employ a novel AR registration system for the visualization and targeting of skull landmarks. METHODS: A markerless AR system was used to register 3-dimensional reconstructions of suture lines onto the head via a head-mounted display. Participants were required to identify craniometric points with and without AR assistance. Targeting error was measured as the Euclidian distance between the user-defined location and the true craniometric point on the subjects' heads. RESULTS: All participants successfully registered 3-dimensional reconstructions onto the subjects' heads. Targeting accuracy was significantly improved with AR (3.59 ± 1.29 mm). Across all target points, AR increased accuracy by an average of 19.96 ± 3.80 mm. Posttest surveys revealed that participants felt the technology increased their confidence in identifying landmarks (4.6/5) and that the technology will be useful for clinical care (4.2/5). CONCLUSIONS: While several areas of improvement and innovation can further enhance the use of AR in neurosurgery, this report demonstrates the feasibility of a markerless headset-based AR system for visualizing craniometric points on the skull. As the technology continues to advance, AR is expected to play an increasingly significant role in neurosurgery, transforming how surgeries are performed and improving patient care.

Pathologic, immunologic, and clinical analysis of the microsatellite instability phenotype in endometrial carcinoma.

The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS) and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves (MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.

Hypertrophic olivary degeneration and palatal myoclonus from a Streptococcus intermedius infection of the brain: illustrative case.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition that can occur after disruption of the Guillain-Mollaret triangle. Clinically, HOD can present with palatal myoclonus with or without oculopalatal tremor, which sometimes results in symptomatic dysphagia and/or speech abnormalities. This condition is commonly associated with vascular lesions, with only three prior reported cases of HOD resulting from intracranial abscess. OBSERVATIONS: An otherwise healthy patient developed multiple intracranial abscesses. Biopsy showed gram-positive cocci; however, culture findings were negative. Polymerase chain reaction (PCR) identified Streptococcus intermedius. The patient demonstrated palatal myoclonus and vertical nystagmus, which resulted in persistent mild dysphagia and altered speech intonation. After appropriate antimicrobial therapy with resolution of the enhancing lesions, symptoms persisted. Follow-up imaging demonstrated progressive hypertrophy of the right olive with persistent disruption of the right-sided rubro-olivo fiber pathways. LESSONS: Although HOD classically occurs after vascular insult, it can also be seen as a postinfectious sequela. Despite eradication of the infection, palatal myoclonus and oculopalatal tremor may have a persistent impact on quality of life due to impaired speech and swallowing. This case emphasizes the utility of universal PCR in detecting fastidious organisms as well as diffusion tensor imaging for characterization of disrupted fiber pathways.

Clinically useful tumor fluorescence greater than 24 hours after 5-aminolevulinic acid administration.

Background: 5-aminolevulinic acid (5-ALA) is a valuable surgical adjuvant used for the resection of glioblastoma multiforme (GBM). Since Food and Drug Administration approval in 2017, 5-ALA has been used in over 37,000 cases. The current recommendation for peak efficacy and intraoperative fluorescence is within 4 h after administration. This narrow time window imposes a perioperative time constraint which may complicate or preclude the use of 5-ALA in GBM surgery. Case Description: This case report describes the prolonged activity of 5-ALA in a 66-year-old patient with a newly diagnosed GBM lesion within the left supramarginal gyrus. An awake craniotomy with language and sensorimotor mapping was planned along with 5-ALA fluorescence guidance. Shortly, after receiving the preoperative 5-ALA dose, the patient developed a fever. Surgery was postponed for an infectious disease workup which proved negative. The patient was taken to surgery the following day, 36 h after 5-ALA administration. Despite the delay, intraoperative fluorescence within the tumor remained and was sufficient to guide resection. Postoperative imaging confirmed a gross total resection of the tumor. Conclusion: The use of 5-ALA as an intraoperative adjuvant may still be effective for patients beyond the recommended 4-h window after initial administration. Reconsideration of current use of 5-ALA is warranted.

Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair.

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.

Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort.

BACKGROUND: Laser interstitial thermal therapy (LITT) for glioblastoma (GBM) has been reserved for poor surgical candidates and deep "inoperable" lesions. We present the first reported series of LITT for surgically accessible recurrent GBM (rGBM) that would otherwise be treated with surgical resection. OBJECTIVE: To evaluate the use of LITT for unifocal, lobar, first-time rGBM compared with a similar surgical cohort. METHODS: A retrospective institutional database was used to identify patients with unifocal, lobar, first-time rGBM who underwent LITT or resection between 2013 and 2020. Clinical and volumetric lesional characteristics were compared between cohorts. Subgroup analysis of patients with lesions ≤20 cm 3 was also completed. Primary outcomes were overall survival and progression-free survival. RESULTS: Of the 744 patients with rGBM treated from 2013 to 2020, a LITT cohort of 17 patients were compared with 23 similar surgical patients. There were no differences in baseline characteristics, although lesions were larger in the surgical cohort (7.54 vs 4.37 cm 3 , P = .017). Despite differences in lesion size, both cohorts had similar extents of ablation/resection (90.7% vs 95.1%, P = .739). Overall survival (14.1 vs 13.8 months, P = .578) and progression-free survival (3.7 vs 3.3 months, P = 0. 495) were similar. LITT patients had significantly shorter hospital stays (2.2 vs 3.0 days, P = .004). Subgroup analysis of patients with lesions ≤20 cm 3 showed similar outcomes, with LITT allowing for significantly shorter hospital stays. CONCLUSION: We found no difference in survival outcomes or morbidity between LITT and repeat surgery for surgically accessible rGBM while LITT resulted in shorter hospital stays and more efficient postoperative care.

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration.

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2-4 h prior to induction to anesthesia. Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data. Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented. Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4. Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.

Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs.

BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P < .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns.

A serum-based DNA methylation assay provides accurate detection of glioma.

BACKGROUND: The detection of somatic mutations in cell-free DNA (cfDNA) from liquid biopsy has emerged as a noninvasive tool to monitor the follow-up of cancer patients. However, the significance of cfDNA clinical utility remains uncertain in patients with brain tumors, primarily because of the limited sensitivity cfDNA has to detect real tumor-specific somatic mutations. This unresolved challenge has prevented accurate follow-up of glioma patients with noninvasive approaches. METHODS: Genome-wide DNA methylation profiling of tumor tissue and serum cfDNA of glioma patients. RESULTS: Here, we developed a noninvasive approach to profile the DNA methylation status in the serum of patients with gliomas and identified a cfDNA-derived methylation signature that is associated with the presence of gliomas and related immune features. By testing the signature in an independent discovery and validation cohorts, we developed and verified a score metric (the "glioma-epigenetic liquid biopsy score" or GeLB) that optimally distinguished patients with or without glioma (sensitivity: 100%, specificity: 97.78%). Furthermore, we found that changes in GeLB score reflected clinicopathological changes during surveillance (eg, progression, pseudoprogression, and response to standard or experimental treatment). CONCLUSIONS: Our results suggest that the GeLB score can be used as a complementary approach to diagnose and follow up patients with glioma.