Pediatric neuroblastoma with intraspinal extension: the role of surgical management.

OBJECTIVE: Neuroblastoma with spinal involvement accounts for up to 30% of pediatric spinal tumors and can cause profound neurological deficits. Chemotherapy is the preferred treatment option, but in select patients resection may be indicated. The goal of this study was to identify preoperative factors that led to early surgical intervention, with a specific emphasis on identifying differences on long-term neurological function and spinal deformity in the recent treatment era. METHODS: A retrospective chart review was performed on all children diagnosed with neuroblastoma at a single institution from 2007 to 2020. Patient demographics, symptoms (motor deficit and sphincter dysfunction), and tumor characteristics (e.g., 123I metaiodobenzylguanidine [MIBG] avidity, MYCN amplification, chromosomal abnormality, pathology, catecholamine secretion, and stage) were recorded. Spine involvement included neural or vertebral extension, spinal cord compression, and/or T2 signal change on MRI. Survival, neurological status (motor deficit, sphincter dysfunction), and spine deformity at last follow-up were compared using univariate and multivariate analyses. The variables that contributed to neurological and deformity outcome were assessed with binomial logistic and linear regression models using R software. RESULTS: Seventy-seven of the 160 patients with neuroblastoma had spinal neuroblastoma, meaning either bone metastases alone (n = 43) or intraspinal extension with or without neurological deficit (n= 34). Most patients with spinal neuroblastoma were treated with chemotherapy and/or radiation therapy (97% and 57%, respectively). Resection of the spinal tumor was performed in 14 (18%) patients, all of whom also received chemotherapy. Between the surgical and nonsurgical patients, no baseline demographic differences were found. However, surgical patients were more likely to present with either motor deficits (50% vs 5%, p = 0.0011) or bladder/bowel dysfunction (14% vs 0%, p 0.035), and a shorter median time to onset of neurological symptoms (33 vs 80 days, p = 0.0096). Surgical patients also had a significantly shorter median overall survival (33.0 vs 54 months, p = 0.014). Of the 14 patients who underwent spine surgery, 2 patients underwent surgery at the time of diagnosis while the remaining 12 underwent initial chemotherapy followed later by resection. The 2 patients who underwent initial surgery had excellent outcomes, with neither long-term motor or bowel/bladder deficits nor spinal deformity. CONCLUSIONS: Surgical patients had shorter overall survival. However, the 2 patients with radiographic evidence of cord compression and acute neurological symptom onset who underwent initial, immediate surgery within 3 days of diagnosis had fewer long-term neurological deficits than surgical patients who underwent initial trials of chemotherapy. Thus, acute decompression may provide benefit in carefully selected patients with acute neurological deficits and cord compression on imaging.

Neurosurgical Outcomes for Pediatric Central Nervous System Tumors in the United States.

BACKGROUND: Limited data exist on pediatric central nervous system (CNS) tumors, and the results from the National Cancer Database, the largest multicenter national cancer registry, have not previously been comprehensively reported. OBJECTIVE: To capture pediatric neurosurgical outcomes and investigate possible disparities of care. METHODS: The National Cancer Database was queried for pediatric patients who were diagnosed with CNS tumors from 2004 to 2018. Primary outcomes included 30/90 days postoperative mortality (30M/90M), readmission within 30 days of discharge (30R), and length of inpatient stay (LOS). RESULTS: Twenty four thousand nine hundred thirty cases met the inclusion criteria, of which were 4753 (19.1%) juvenile pilocytic astrocytomas, 3262 (13.1%) medulloblastomas, 2200 (8.8%) neuronal/mixed neuronal-glial tumors, and 2135 (8.6%) ependymal tumors. Patients aged 0 to 4 years had significantly poorer outcomes than patients in older age groups (90M: 3.5% vs 0.7%-0.9%; 30R: 6.5% vs 3.6%-4.8%; LOS: 12.0 days vs 6.0-8.9 days). Tumor size was a strong predictor of poor outcomes with each additional cm in diameter conferring a 26%, 7%, and 23% increased risk of 90M, 30R, and prolonged LOS, respectively. Data over the study period demonstrated year over year improvements of 4%, 3%, and 2%, respectively, for 90M, 30R, and prolonged LOS. Facilities with a high volume of pediatric tumor cases had improved 90M (1.1% vs 1.5%, P = .041) and LOS (7.6 vs 8.6 days, P < .001). Patients with private health insurance had better outcomes than patients with government insurance. CONCLUSION: There is substantial variability in surgical morbidity and mortality of pediatric CNS tumors. Additional investigation is warranted to reduce outcome differences that may be based on socioeconomic factors.

Correlation between tumor volume and serum prolactin and its effect on surgical outcomes in a cohort of 219 prolactinoma patients.

OBJECTIVE: Prolactinoma is the most common pituitary adenoma and can be managed medically or surgically. The authors assessed the correlation between tumor volume and prolactin level and its effect on surgical outcomes. METHODS: The authors reviewed 219 patients who underwent transsphenoidal prolactinoma resection at a single institution from 2012 to 2019. Outcomes were compared between patients with and without biochemical remission. Tumor volumes were quantified with BrainLab Smartbrush. Correlation analysis and linear regression were used to examine the association between tumor volume and serum prolactin level. Volume-adjusted prolactin level was defined as serum prolactin level divided by tumor volume. The authors utilized receiver operating characteristic (ROC) curve analysis to determine the thresholds for predicting biochemical remission status. RESULTS: The mean tumor volume was 5.66 cm3, and the mean preoperative prolactin level was 752.3 µg/L. Men had larger prolactinomas than women (mean volume 11.32 vs 2.54 cm3; p < 0.001), and women had a greater volume-adjusted prolactin level (mean 412.5 vs 175.9 µg/L/cm3, p < 0.001). In total, 66.7% of surgical patients achieved biochemical remission 6 weeks after surgery, whereas a similar cohort of medically treated patients during the same time frame demonstrated a 69.4% remission rate. Pearson correlation and linear regression analysis revealed a strong association between preoperative tumor volume and prolactin levels, with an increase in serum prolactin level of 101.31 µg/L per 1-cm3 increase in tumor volume (p < 0.001). This held true for men (R = 0.601, p < 0.001) and women (R = 0.935, p < 0.001), with women demonstrating a greater increase in prolactin level per 1-cm3 increase in volume (185.70 vs 79.77 µg/L, p < 0.001). Patients who achieved remission exhibited a 66.08-µg/L increase in preoperative prolactin level per 1 cm3 of preoperative tumor volume (p < 0.001), which was less than the 111.46-µg/L increase per 1 cm3 in patients without remission (p < 0.001). Patients who failed to achieve remission had residual tumors with a 77.77-µg/L increase in prolactin per 1 cm3 of remaining tumor volume after resection (p < 0.001). ROC curve analysis revealed significant thresholds that optimally predicted lack of postoperative remission on the basis of preoperative prolactin and tumor volume. These thresholds were rendered nonsignificant in patients with documented Knosp grade ≥ 3. CONCLUSIONS: Although the authors found a correlation between prolactinoma volume and serum prolactin level, patients without remission had a greater increase in serum prolactin level per increase in preoperative tumor volume than those who achieved remission, suggesting unique tumor composition. The authors also identified prolactin and tumor volume thresholds that optimally predicted biochemical remission status. The authors hope that their results can be used to identify prolactinomas for which surgery could achieve remission as an alternative to medical management.

The Hybrid Operative Suite with Intraoperative Biplane Rotational Angiography in Pediatric Cerebrovascular Neurosurgery: Utility and Lessons Learned.

INTRODUCTION: The benefits of performing open and endovascular procedures in a hybrid neuroangiography surgical suite include confirmation of treatment results and reduction in number of procedures, leading to improved efficiency of care. Combined procedural suites are infrequently used in pediatric facilities due to technical and logistical limitations. We report the safety, utility, and lessons learned from a single-institution experience using a hybrid suite equipped with biplane rotational digital subtraction angiography and pan-surgical capabilities. METHODS: We conducted a retrospective review of consecutive cases performed at our institution that utilized the hybrid neuroangiography surgical suite from February 2020 to August 2021. Demographics, surgical metrics, and imaging results were collected from the electronic medical record. Outcomes, interventions, and nuances for optimizing preoperative/intraoperative setup and postoperative care were presented. RESULTS: Eighteen procedures were performed in 17 patients (mean age 13.4 years, range 6-19). Cases included 14 arteriovenous malformations (AVM; 85.7% ruptured), one dural arteriovenous fistula, one mycotic aneurysm, and one hemangioblastoma. The average operative time was 416 min (range 321-745). There were no intraoperative or postoperative complications. All patients were alive at follow-up (range 0.1-14.7 months). Five patients had anticipated postoperative deficits arising from their hemorrhage, and 12 returned to baseline neurological status. Four illustrative cases demonstrating specific, unique applications of the hybrid angiography suite are presented. CONCLUSION: The hybrid neuroangiography surgical suite is a safe option for pediatric cerebrovascular pathologies requiring combined surgical and endovascular intervention. Hybrid cases can be completed within the same anesthesia session and reduce the need for return to the operating room for resection or surveillance angiography. High-quality intraoperative angiography enables diagnostic confirmation under a single procedure, mitigating risk of morbidity and accelerating recovery. Effective multidisciplinary planning enables preoperative angiograms to be completed to inform the operative plan immediately prior to definitive resection.

C2 translaminar screw fixation in pediatric occipitocervical fusion.

PURPOSE: Rigid occipitocervical (O-C) instrumentation can reduce the anterior pathology and has a high fusion rate in children with craniovertebral instability. Typically, axis (C2) screw fixation utilizes C1-C2 transarticular screws or C2 pars screws. However, anatomic variation may preclude these screw types due to the size of fixation elements or by placing the vertebral artery at risk for injury. Pediatric C2 translaminar screw fixation has low risk of vertebral artery injury and may be used when the anatomy is otherwise unsuitable for C1-C2 transarticular screws or C2 pars screws. METHODS: We retrospectively reviewed a neurosurgical database at UCSF Benioff Children's Hospital Oakland for patients who had undergone a cervical spinal fusion that utilized translaminar screws for occipitocervical instrumentation between 2002 and 2020. We then reviewed the operative records to determine the parameters of C2 screw fixations performed. Demographic and all other relevant clinical data were then recorded. RESULTS: Twenty-five patients ranging from 2 to 18 years of age underwent O-C fusion, with a total of 43 translaminar screws at C2 placed. Twenty-three patients were fused (92%) after initial surgery with a mean follow-up of 43 months. Two patients, both with Down syndrome, had a nonunion. Another 2 patients had a superficial wound dehiscence that required wound revision. One patient died of unknown cause 7 months after surgery. One patient developed an adjacent-level kyphosis. CONCLUSION: When performing occipitocervical instrumentation in the pediatric population, C2 translaminar screw fixation is an effective option to other methods of C2 screw fixation dependent on anatomic feasibility.

Management of migrating intracranial bullet fragments in a 13-year-old female after firearm brain injury: technical and surgical nuances.

INTRODUCTION: We present the challenges and nuances of management in a rare case of multiple migrating intracranial fragments after pediatric gunshot wound to the head (GSWH). CASE PRESENTATION: A 13-year-old girl suffered left parietal GSWH, with new neurologic decline 3 days after initial debridement. Serial imaging showed the largest intracranial fragments had migrated into the left trigone, and descended further with head of bed (HOB) elevation. HOB was iteratively decreased, with concurrent intracranial pressure monitoring. After extubation, with an alert and stable neurologic exam, HOB was decreased to -15 degrees, allowing gravity-assisted migration of the fragments to an anatomically favorable position within the left occipital horn. The patient underwent occipital craniotomy for fragment retrieval on hospital day 27. Two large and >20 smaller fragments were retrieved using neuronavigation and intraoperative ultrasound. Forensics showed these to be .45 caliber handgun bullet fragments. The patient recovered well after 2-months of intensive inpatient rehabilitation. DISCUSSION: During new neurologic decline after GSWH, bullet migration must be considered and serial cranial imaging is requisite. Surgical retrieval of deep fragments requires judicious planning to minimize further injury. Tightly controlled HOB adjustments with gravity assistance for repositioning of fragments may have utility in optimizing anatomic favorability prior to surgery.

Identifying risk factors for postoperative diabetes insipidus in more than 2500 patients undergoing transsphenoidal surgery: a single-institution experience.

OBJECTIVE: Diabetes insipidus (DI) following transsphenoidal surgery can adversely impact quality of life and be difficult to manage. This study sought to characterize pre- and perioperative risk factors that may predispose patients to DI after pituitary surgery. METHODS: A retrospective review of patients treated at a single institution from 2007 to 2019 was conducted. DI was defined as postoperative sodium > 145 mEq/L and urine output > 300 ml/hr and/or postoperative desmopressin (ddAVP) use. DI was further characterized as transient or permanent. Uni- and multivariate analyses were performed to determine variables associated with postoperative DI. RESULTS: The authors identified 2529 patients who underwent transsphenoidal surgery at their institution. Overall, DI was observed in 270 (10.7%) of the 2529 patients, with 114 (4.5%) having permanent DI and 156 (6.2%) with transient symptoms. By pathology type, DI occurred in 31 (46.3%) of 67 craniopharyngiomas, 10 (14.3%) of 70 apoplexies, 46 (14.3%) of 322 Rathke's cleft cysts, 77 (7.7%) of 1004 nonfunctioning pituitary adenomas (NFPAs), and 62 (7.6%) of 811 functioning pituitary adenomas (FPAs). Final lesion pathology significantly affected DI rates (p < 0.001). Multivariate analysis across pathologies showed that younger age (odds ratio [OR] 0.97, p < 0.001), intraoperative CSF encounter (OR 2.74, p < 0.001), craniopharyngioma diagnosis (OR 8.22, p = 0.007), and postoperative hyponatremia (OR 1.50, p = 0.049) increased the risk of DI. Because surgery for each pathology created specific risk factors for DI, the analysis was then limited to the 1815 pituitary adenomas (PAs) in the series, comprising 1004 NFPAs and 811 FPAs. For PAs, younger age (PA: OR 0.97, p < 0.001; NFPA: OR 0.97, p < 0.001; FPA: OR 0.97, p = 0.028) and intraoperative CSF encounter (PA: OR 2.99, p < 0.001; NFPA: OR 2.93, p < 0.001; FPA: OR 3.06, p < 0.001) increased DI rates in multivariate analysis. Among all PAs, patients with DI experienced peak sodium levels later than those without DI (postoperative day 11 vs 2). Increasing tumor diameter increased the risk of DI in FPAs (OR 1.52, p = 0.008), but not in NFPAs (p = 0.564). CONCLUSIONS: In more than 2500 patients treated at a single institution, intraoperative CSF encounter, craniopharyngioma diagnosis, and young age all increased the risk of postoperative DI. Patients with postoperative hyponatremia exhibited higher rates of DI, suggesting possible bi- or triphasic patterns to DI. Greater vigilance should be maintained in patients meeting these criteria following transsphenoidal surgery to ensure early recognition and treatment of DI.

Multiple Tumor-Associated Intracranial Aneurysms Adjacent to a Suprasellar Germ Cell Tumor: Case Report and Review of Literature.

INTRODUCTION: Tumor-associated intracranial aneurysms are rare and not well understood. CASE PRESENTATION: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms. DISCUSSION: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.

A Case of Torticollis in an 8-Month-Old Infant Caused by Posterior Fossa Arachnoid Cyst: An Important Entity for Differential Diagnosis.

Torticollis is a clinical diagnosis with heterogeneous causes. We present an unusual case of acquired torticollis in an 8-month-old female infant with a large cerebellopontine angle arachnoid cyst. Symptoms resolved after surgical fenestration. Non-traumatic acquired or new-onset torticollis requires brain imaging, and posterior fossa lesions are an important entity in the differential for pediatric clinicians.

Plurihormonal PIT-1-Positive Pituitary Adenomas: A Systematic Review and Single-Center Series.

OBJECTIVE: The 2017 World Health Organization classification of pituitary adenomas identified the plurihormonal PIT-1-positive (PP1) adenoma as a distinct subtype. The reported data suggest that PP1 adenomas encompass the former class of silent subtype 3 (SS3) adenomas and might have an aggressive phenotype. In the present study, we summarized the current clinical data on PP1 and SS3 adenomas and compared the reported data with the data from a single institutional cohort. METHODS: Medline and Google Scholar were searched from 1990 to 2020 for clinical series of PP1 and SS3 adenomas in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included if they had reported pituitary pathology as PP1 or SS3 adenomas and had reported the clinical outcomes after surgical intervention. To better define the PP1 phenotype compared with non-PP1 adenomas, we also reviewed the adenomas treated surgically at our institution from 2012 to 2019. RESULTS: Of all the tumors reported in the studies as PP1 or SS3, 99% were macroadenomas and 18% were giant adenomas (>4 cm). Of the reported patients, 31.8% had received radiotherapy, and 22.9% had undergone multiple surgeries for their pituitary tumor. In our single-center experience, 20 patients had an adenoma that met the criteria for a PP1 adenoma. Compared with the 1146 non-PP1 tumors, the PP1 tumors did not show statistically significant differences in the extent of resection, size, number of previous surgeries, future reoperations, rate of radiotherapy, p53 staining, or MIB-1 labeling index. CONCLUSIONS: The findings from the present large, single-center study comparing PP1 and non-PP1 adenomas do not suggest that PP1 tumors are more aggressive. Further work is warranted to identify the pathologic subtypes of pituitary adenomas that are consistently more clinically aggressive.

A Type II Split Cord Malformation in an Adult Patient: An Operative Case Report.

BACKGROUND AND IMPORTANCE: Split cord malformations (SCMs) are rare conditions in which the spinal cord is split into two hemicords within either a single thecal sac or two separate thecal sacs. The hemicords are typically split by a bony or fibrous structure. We present an adult patient who presented with a type II SCM with tethered cord. This is the first case of such a presentation with an accompanying intraoperative video. Unusual features of the case were the presence of an incomplete fibrous septum and lack of a discrete filum terminale. CLINICAL PRESENTATION: A 50-yr-old woman presented with back pain, radiculopathy, urinary urgency, and episodic fecal incontinence. Her exam was notable for weakness of the right extensor hallicus longus. Imaging showed an SCM extending from L3 to S1, a fibrous septum located at L4-5, and a low-lying conus at S4. She was treated with a decompressive L3-S4 laminectomy and disconnection of all the dural attachment points. She required lumbar drain placement postoperatively and reoperation for wound dehiscence and persistent pseudomeningocele. At the time of last follow-up, she was neurologically intact with improvement in bowel/bladder function. CONCLUSION: SCM is an uncommon presentation in adults and is often accompanied by findings of skin stigmata, tethered cord, and other central nervous system/skeletal anomalies. Obtaining full multimodal imaging is critical to understanding subtle anatomic variations that can pose operative challenges. We report the treatment of an adult patient with type II SCM, and provide an intraoperative video demonstrating the removal of an incomplete midline fibrous septum.

Recurrent brainstem cavernous malformations following primary resection: blind spots, fine lines, and the right-angle method.

OBJECTIVE: Proximity of brainstem cavernous malformations (BSCMs) to tracts and cranial nerve nuclei make it costly to transgress normal tissue in accessing the lesion or disrupting normal tissue adjacent to the lesion in the separation plane. This interplay between tissue sensitivity and extreme eloquence makes it difficult to avoid leaving a remnant on occasion. Recurrences require operative intervention, which may increase morbidity, lengthen recovery, and add to overall costs. An approximately 20-year experience with patients with recurrent BSCM lesions following primary microsurgical resection was reviewed. METHODS: A prospectively maintained database of 802 patients who underwent microsurgical resection of cerebral cavernous malformations during 1997-2018 was queried to identify 213 patients with BSCMs. A retrospective chart review was conducted for patients with recurrent BSCM after primary resection who required a second surgery. RESULTS: Fourteen of 213 patients (6.6%) underwent repeat resection for recurrent BSCM. Thirty-four hemorrhagic events were observed among these 14 patients over 576 patient-years (recurrent hemorrhage rate, 5.9% per year; median discrete hemorrhagic events, 2; median time to rehemorrhage, 897 days). BSCM occurred in the pons in 10 cases, midbrain in 2 cases, and medulla in 2 cases. A blind spot in the operative corridor was the most common cause of residual BSCM (9 patients). All recurrent BSCMs were removed completely, although 2 patients each required 2 operations to treat recurrence. Twelve patients had unchanged or improved modified Rankin Scale scores at last clinical evaluation compared with admission, and 2 patients had worse scores. Recurrence was more common among patients who were operated on in the first versus the second half of the series (8.5% vs 4.7%). CONCLUSIONS: The 6.6% rate of BSCM recurrence requiring reoperation reflects the fine lines between complete resection and recurrence and between safe and harmful surgery. The detection of remnants is difficult postoperatively and remains so even at 6 months when the resection bed has healed. The 5.9% annual hemorrhage risk associated with recurrent BSCM in this experience is consistent with that reported for unoperated BSCMs. The right-angle method helps to anticipate blind spots and meticulously inspect the resection cavity for residual BSCM during surgery. A low percentage of recurrent BSCM (5%-10%) ensures ongoing effort toward an acceptable balance of safety and completeness.

Clinical characteristics and outcomes in elderly patients undergoing transsphenoidal surgery for nonfunctioning pituitary adenoma.

OBJECTIVE: Life expectancy has increased over the past century, causing a shift in the demographic distribution toward older age groups. Elderly patients comprise up to 14% of all patients with pituitary tumors, with most lesions being nonfunctioning pituitary adenomas (NFPAs). Here, the authors evaluated demographics, outcomes, and postoperative complications between nonelderly adult and elderly NFPA patients. METHODS: A retrospective review of 908 patients undergoing transsphenoidal surgery (TSS) for NFPA at a single institution from 2007 to 2019 was conducted. Clinical and surgical outcomes and postoperative complications were compared between nonelderly adult (age ≥ 18 and ≤ 65 years) and elderly patients (age > 65 years). RESULTS: There were 614 and 294 patients in the nonelderly and elderly groups, respectively. Both groups were similar in sex (57.3% vs 60.5% males; p = 0.4), tumor size (2.56 vs 2.46 cm; p = 0.2), and cavernous sinus invasion (35.8% vs 33.7%; p = 0.6). Regarding postoperative outcomes, length of stay (1 vs 2 days; p = 0.5), extent of resection (59.8% vs 64.8% gross-total resection; p = 0.2), CSF leak requiring surgical revision (4.3% vs 1.4%; p = 0.06), 30-day readmission (8.1% vs 7.3%; p = 0.7), infection (3.1% vs 2.0%; p = 0.5), and new hypopituitarism (13.9% vs 12.0%; p = 0.3) were similar between both groups. Elderly patients were less likely to receive adjuvant radiation (8.7% vs 16.3%; p = 0.009), undergo future reoperation (3.8% vs 9.5%; p = 0.003), and experience postoperative diabetes insipidus (DI) (3.7% vs 9.4%; p = 0.002), and more likely to have postoperative hyponatremia (26.7% vs 16.4%; p < 0.001) and new cranial nerve deficit (1.9% vs 0.0%; p = 0.01). Subanalysis of elderly patients showed that patients with higher Charlson Comorbidity Index scores had comparable outcomes other than higher DI rates (8.1% vs 0.0%; p = 0.006). Elderly patients' postoperative sodium peaked and troughed on postoperative day 3 (POD3) (mean 138.7 mEq/L) and POD9 (mean 130.8 mEq/L), respectively, compared with nonelderly patients (peak POD2: mean 139.9 mEq/L; trough POD8: mean 131.3 mEq/L). CONCLUSIONS: The authors' analysis revealed that TSS for NFPA in elderly patients is safe with low complication rates. In this cohort, more elderly patients experienced postoperative hyponatremia, while more nonelderly patients experienced postoperative DI. These findings, combined with the observation of higher DI in patients with more comorbidities and elderly patients experiencing later peaks and troughs in serum sodium, suggest age-related differences in sodium regulation after NFPA resection. The authors hope that their results will help guide discussions with elderly patients regarding risks and outcomes of TSS.

Higher cytolytic score correlates with an immunosuppressive tumor microenvironment and reduced survival in glioblastoma.

Cytolytic score (CYT), calculated from mRNA expression levels of granzyme and perforin, positively correlates with CD8+ T cell infiltration/activity in a variety of cancers. Unlike other cancers, higher CYT has been associated with worse prognosis in glioblastoma (GBM). To address this discrepancy, we sought to investigate the relationship between CYT and immune checkpoint gene score (ICGscore), as well as their correlation with patient survival and tumor immune cell infiltration. Clinical and RNA-sequencing data for patients with newly diagnosed GBM were obtained from The Cancer Genome Atlas. Maximally-selected rank statistics was used to dichotomize subgroups. CIBERSORT was used to estimate abudence of immune cell-types. Spearman correlation was used to characterize the relationship between CYT and ICGscore. Kaplan-Meier curves were generated for survival analysis. Overall, 28/151 patients had high CYT. High CYT was associated with a mesenchymal subtype (p < 0.001) and worse survival (7.45 vs. 12.2 months, p < 0.001). There were no differences in patient demographics, IDH/MGMT mutation status, or treatment. On subgroup analysis, patients with high CYT/ICGscore had significantly increased CD8+ infiltration (p < 0.001), as expected, and worse survival (HR 0.445, p < 0.01). Furthermore, CYT strongly correlated with ICGscore (RS = 0.675, p < 0.001). The high CYT/ICGscore subgroup was associated with greater infiltration of M2 macrophages (p = 0.011) and neutrophils (p = 0.055). Our study highlights a multidimensional immunosuppressive GBM microenvironment in patients with higher CYT and potentially identifies patients with high CYT/ICGscore as a subgroup that may particularly benefit from multi-faceted immunotherapies, given their already elevated tumor CD8+ T cell levels.

Ventriculoperitoneal shunt infection rates using a standard surgical technique, including topical and intraventricular vancomycin: the Children's Hospital Oakland experience.

OBJECTIVE: Ventriculoperitoneal (VP) shunt infections are common complications after shunt operations. Despite the use of intravenous antibiotics, the incidence of infections remains high. Though antibiotic-impregnated catheters (AICs) are commonly used, another method of infection prophylaxis is the use of intraventricular (IVT) antibiotics. The authors describe their single-institution experience with a standard shunt protocol utilizing prophylactic IVT and topical vancomycin administration and report the incidence of pediatric shunt infections. METHODS: Three hundred two patients undergoing VP shunt procedures with IVT and topical vancomycin between 2006 and 2016 were included. Patients were excluded if their age at surgery was greater than 18 years. Shunt operations were performed at a single institution following a standard shunt protocol implementing IVT and topical vancomycin. No AICs were used. Clinical data were retrospectively collected from the electronic health records. RESULTS: Over the 11-year study period, 593 VP shunt operations were performed with IVT and topical vancomycin, and a total of 19 infections occurred (incidence 3.2% per procedure). The majority of infections (n = 10, 52.6%) were caused by Staphylococcus epidermidis. The median time to shunt infection was 3.7 weeks. On multivariate analysis, the presence of a CSF leak (OR 31.5 [95% CI 8.8-112.6]) and age less than 6 months (OR 3.6 [95% CI 1.2-10.7]) were statistically significantly associated with the development of a shunt infection. A post hoc analysis comparing infection rates after procedures that adhered to the shunt protocol and those that did not administer IVT and topical vancomycin, plus historical controls, revealed a difference in infection rates (3.2% vs 6.9%, p = 0.03). CONCLUSIONS: The use of a standardized shunt operation technique that includes IVT and topical vancomycin is associated with a total shunt infection incidence of 3.2% per procedure, which compares favorably with the reported rates of shunt infection in the literature. The majority of infections occurred within 2 months of surgery and the most common causative organism was S. epidermidis. Young age (< 6 months) at the time of surgery and the presence of a postoperative CSF leak were statistically significantly associated with postoperative shunt infection on multivariate analysis. The results are hypothesis generating, and the authors propose that IVT and topical administration of vancomycin as part of a standardized shunt operation protocol may be an appropriate option for preventing pediatric shunt infections.

Clinical characteristics and outcomes of null-cell versus silent gonadotroph adenomas in a series of 1166 pituitary adenomas from a single institution.

OBJECTIVE: Nonfunctioning pituitary adenomas present without biochemical or clinical signs of hormone excess and are the second most common type of pituitary adenomas. The 2017 WHO classification scheme of pituitary adenomas differentiates null-cell adenomas (NCAs) and silent gonadotroph adenomas (SGAs). The present study sought to highlight the differences in patient characteristics and clinical outcomes between NCAs and SGAs. METHODS: The records of 1166 patients who underwent transsphenoidal surgery for pituitary adenoma between 2012 and 2019 at a single institution were retrospectively reviewed. Patient demographics and clinical outcomes were collected. RESULTS: Of the overall pituitary adenoma cohort, 12.8% (n = 149) were SGAs and 9.2% (n = 107) NCAs. NCAs were significantly more common in female patients than SGAs (61.7% vs 26.8%, p < 0.001). There were no differences in patient demographics, initial tumor size, or perioperative and short-term clinical outcomes. There was no significant difference in the amount of follow-up between patients with NCAs and those with SGAs (33.8 months vs 29.1 months, p = 0.237). Patients with NCAs had significantly higher recurrence (p = 0.021), adjuvant radiation therapy usage (p = 0.002), and postoperative diabetes insipidus (p = 0.028). NCA pathology was independently associated with tumor recurrence (HR 3.64, 95% CI 1.07-12.30; p = 0.038), as were cavernous sinus invasion (HR 3.97, 95% CI 1.04-15.14; p = 0.043) and anteroposterior dimension of the tumor (HR 2.23, 95% CI 1.09-4.59; p = 0.030). CONCLUSIONS: This study supports the definition of NCAs and SGAs as separate subgroups of nonfunctioning pituitary adenomas, and it highlights significant differences in long-term clinical outcomes, including tumor recurrence and the associated need for adjuvant radiation therapy, as well as postoperative diabetes insipidus. The authors also provide insight into independent risk factors for these outcomes in the adenoma population studied, providing clinicians with additional predictors of patient outcomes. Follow-up studies will hopefully uncover mechanisms of biological aggressiveness in NCAs and associated molecular targets.

A middle cerebral artery ischemic stroke occurring in a child with a large prolactinoma.

Pituitary adenomas are rare in children, and often present with symptoms of headache, nausea or emesis, visual disturbance, or hormonal hypersecretion. With large tumors, mass effect from the lesion can lead to severe endocrinopathy and compression of intracranial neurovascular structures. In this case report, we describe an unusual presentation of an ischemic stroke in the territory of the right middle cerebral artery resulting from a prolactin-secreting macroadenoma. The patient's primary symptoms were headache, left facial droop, and left hemibody weakness. She was successfully managed with cabergoline, a dopamine agonist, with a reduction in the size of the tumor and normalization of serum prolactin levels. She remained clinically stable throughout her hospitalization, and was safely discharged without surgical intervention. In her recent 2-year follow-up, her tumor and prolactin levels were stable and she had dramatic improvements in her left-sided muscle strength.

Cone Beam Intraoperative Computed Tomography-based Image Guidance for Minimally Invasive Transforaminal Interbody Fusion.

Transforaminal lumbar interbody fusion (TLIF) is commonly used for the treatment of spinal stenosis, degenerative disc disease, and spondylolisthesis. Minimally invasive surgery (MIS) approaches have been applied to this technique with an associated decrease in estimated blood loss (EBL), length of hospital stay, and infection rates, while preserving outcomes with traditional open surgery. Previous MIS TLIF techniques involve significant fluoroscopy that subjects the patient, surgeon, and operating room staff to non-trivial levels of radiation exposure, particularly for complex multi-level procedures. We present a technique that utilizes an intraoperative computed tomography (CT) scan to aid in placement of pedicle screws, followed by traditional fluoroscopy for confirmation of cage placement. Patients are positioned in the standard fashion and a reference arc is placed in the posterior superior iliac spine (PSIS) followed by intraoperative CT scan. This allows for image-guidance-based placement of pedicle screws through a one-inch skin incision on each side. Unlike traditional MIS-TLIF that requires significant fluoroscopic imaging during this stage, the operation can now be performed without any additional radiation exposure to the patient or operating room staff. After completion of the facetectomy and discectomy, final TLIF cage placement is confirmed with fluoroscopy. This technique has the potential to decrease operative time and minimize total radiation exposure.