Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Clival Chordomas in the Endoscopic Endonasal Era: Comparison With Management With Open Skull Base Approaches.

BACKGROUND: The most significant paradigm shift in surgical management of skull base chordomas has been the adoption of the endoscopic endonasal approach, but the impact on patient outcomes compared with open skull base approaches remains unclear. OBJECTIVE: To compare a large series of patients treated by a single surgeon using primarily endoscopic endonasal approaches with previously published outcomes by the same surgeon using open skull base approaches. METHODS: Between 2006 and 2020, 68 patients with skull base chordoma underwent resection using primarily endoscopic endonasal approaches. Outcomes and complications were compared with previously published results of resection of chordomas from 1991 to 2005 using open skull base approaches. RESULTS: Compared with the prior cohort, the current principally endoscopic cohort demonstrated similar rates of OS ( P = .86) and progression-free survival ( P = .56), but patients undergoing first-time resection had significantly higher rates of radical resection (82.9% compared with 64.3%, P = .05) and required fewer staged surgeries (9.8% compared with 33.3%, P = .01). CONCLUSION: There was no difference in survival rates for patients treated in the current era, primarily using endoscopic endonasal techniques, compared with previously published results using open skull-base approaches by the same surgeon. Although use of endoscopic endonasal approach resulted in higher rates of radical resection, patients undergoing first-time resection and fewer staged surgeries were required.

Clival Chordomas in the Endoscopic Endonasal Era: Clinical Management, Outcomes, and Complications.

BACKGROUND: Surgical management of skull base chordomas has changed significantly in the past 2 decades, most notably with use of the endoscopic endonasal approach (EEA), although high quality outcome data using these modern approaches remain scarce. OBJECTIVE: To evaluate outcomes in a large series of patients treated by a single surgeon, using primarily the EEA. METHODS: Between 2006 and 2020, 68 patients with skull base chordoma underwent resection using mostly the EEA. Complications, outcomes, and potential contributing factors were evaluated using Kaplan-Meier survival analysis and univariable and multivariable Cox proportional hazards models. RESULTS: Overall 5-year survival was 76.3% (95% CI 61.5%-86.0%), and 5-year progression-free survival was 55.9% (95% CI 40.0%-69.0%). In multivariable analysis, radical resection was associated with significant reduction in risk of death (hazard ratio [HR] 0.04, 95% CI 0.005-0.33, P = .003) and disease progression (HR 0.05, 95% CI 0.01-0.18, P < .001). Better preoperative function status reduced risk of death (HR 0.42 per 10-point increase in Karnofsky Performance Scale, 95% CI 0.28-0.63, P < .001) and progression (HR 0.60 per 10-point increase in Karnofsky Performance Scale, 95% CI 0.45-0.78, P < .001). Localization at the clivus reduced risk of death (HR 0.02, 95% CI 0.002-0.15, P < .001) and progression (HR 0.24, 95% CI 0.09-0.68, P = .007) compared with tumors at the craniovertebral junction. CONCLUSION: In multivariable analysis, overall survival and progression-free survival of chordoma resection was most positively affected by radical resection, better preoperative functional status, and tumor location at the clivus rather than craniovertebral junction.

Safety Analysis of a New Portable Electrical Drill With a Smart Autostop Mechanism for Bedside Cranial Procedures.

BACKGROUND AND OBJECTIVES: Bedside procedures are often helpful for neurosurgical patients, especially in neurocritical care. Portable drills with technological advancements may bring more safety and efficiency to the bedside. In this study, we compared the safety and efficiency of a new cordless electric drill with smart autostop ("HD"-Hubly Cranial Drill, Hubly Surgical) with those of a well-established standard traditional electrical neurosurgical perforator ("ST"). METHODS: A cadaveric study was conducted using both drills to perform several burr holes in the fronto-temporo-parietal region of the skull. An evaluation was performed on the number of dura plunges, and complete burr hole success rates were compared. RESULTS: A total of 174 craniotomies using the HD and 36 burr holes using the ST perforator were performed. Despite significantly exceeding intended drill bit tolerance by multiple uses of a single-use disposable HD, autostop engaged in 100% of the 174 craniotomies and before violating dura in 99.4% of the 174 craniotomies, with the single dura penetration occurring on craniotomy no. 128 after the single-use drill bit had significantly dulled beyond its single-use tolerance. Autostop engaged before dura penetration for 100% of the 36 burr holes drilled with the ST perforator ( P = .610). All the perforations were complete using the HD after resuming drilling. An autostop mechanism in a cranial drill is not commonly available for portable bedside perforators. In the operating room, most use a mechanical method to stop the rotation after losing bone resistance. This new drill uses an electrical mechanism (smart autostop) to stop drilling, making it a single-use cranial drill with advanced features for safety and efficiency at the bedside. CONCLUSION: There was no difference in the safety and efficacy of the new cordless electric drill with smart autostop when performing craniotomies compared with a traditional well-established electric cranial perforator with mechanical autostop on a cadaveric model.

Malignant Transformation of an Intracranial Epidermoid Cyst 25 Years After Initial Surgery: A Case Report and Systematic Review.

OBJECTIVE: We report a unique case of a suspected recurrent intracranial epidermoid cyst (EDC) that was found on pathology to have undergone malignant transformation to squamous cell carcinoma (SCC) approximately 25 years after initial resection. Additionally, we performed a systematic review including 94 studies reporting intracranial EDC to SCC transformation. METHODS: Ninety-four studies were included in our systematic review. PubMed, Scopus, Cochrane Central, and EMBASE were searched in April 2020 for studies regarding histologically confirmed SCC arising within an EDC. Kaplan-Meier estimations were used to estimate time to event including survival, and log rank tests were used to test for significance. All analyses were conducted using STATA 14.1 (StataCorp, College Station, Texas, USA); tests were two-sided, and statistical significance was defined using the alpha threshold of 0.05. RESULTS: The overall median time to transformation was 60 months (95% confidence interval {CI}, 12-96). Transformation time was significantly shorter in the no surgery group (10 months, 95% CI undefined) versus the other 2 groups (60 months, 95% CI, 12-72 in surgery only and 70 months, 95% CI, 9-180 in surgery + adjuvant therapy group, both P < 0.01). Overall survival was significantly longer in the surgery + adjuvant therapy group (13 months, 95% CI, 9-24) versus the other 2 groups (3 months, 95% CI, 1-7 in surgery only and 6 months, 95% CI, 1-12 in the no surgery group, both P < 0.01). CONCLUSIONS: We report a rare case of delayed malignant transformation of an intracranial EDC to SCC, occurring nearly 25 years after initial resection. Transformation time in the no-surgery group was statistically significantly shorter as compared to the surgery only and surgery + adjuvant therapy groups. Overall survival was statistically significantly higher in the surgery + adjuvant therapy group as compared to the surgery only and no surgery groups.

Robotic-assisted stereotactic percutaneous balloon compression for trigeminal neuralgia treatment.

Trigeminal neuralgia (TN) is a facial pain disorder that can be a source of significant disability. Percutaneous balloon compression (PBC) has low cost, high efficacy, and minimal invasiveness. Complications can occur due to the balloon inflation or the needle placement itself. In this paper, we describe for the first time the clinical use of robotic-assistance to perform a PBC for TN, presenting our experience in two patients. The stereotactic planning targeted the foramen ovale (FO) establishing a safe and seamless needle trajectory. This yielded a streamlined, single pass needle placement and eliminated the need to "search" for the FO. There were no immediate complications and post-operatively both patients improved their symptoms. Robotic assistance is potentially a useful tool to reduce needle placement related complications, radiation exposure and PBC learning curve.

Volumetric growth rates of untreated cavernous sinus meningiomas.

OBJECTIVE: Meningiomas that arise primarily within the cavernous sinus are often believed to be more indolent in their growth pattern. Despite this perceived growth pattern, disabling symptoms can arise even with small tumors. While research has been done on cavernous sinus meningiomas (CSMs) and their treatment, very little is known about their natural growth rates. With a better understanding of the growth rate of CSM, patient treatment and guidance can be can optimized and individualized. The goal of this study was to determine volumetric growth rates of untreated CSMs. METHODS: Thirty-seven patients with 166 MR images obtained between May 2004 and September 2019 were reviewed, with a range of 2-13 MR images per patient (average of 4.5 MR images per patient). These scans were obtained over an average follow-up period of 45.9 months (median 33.8, range 2.8-136.9 months). All imaging prior to any intervention was included in this analysis. Volumetric measurements were performed and assessed over time. RESULTS: The estimated volumetric growth rate was 23.3% per year (95% CI 10.2%-38.0%, p < 0.001), which is equivalent to an estimated volume doubling time (VDT) of 3.3 years (95% CI 2.1-7.1 years). There was no significant relationship between growth rate and patient age (p = 0.09) or between growth rate and patient sex (p = 0.78). The median absolute growth rate was 41% with a range of -1% to 1793%. With a definition of "growth" as an increase of greater than 20% during the observed period, 65% of tumors demonstrated growth within their observation interval. Growth rates for each tumor were calculated and tumors were segmented based on growth rate. Of 37 patients, 22% (8) demonstrated no growth (< 5% annual growth, equivalent to a VDT > 13.9 years), 32% (12) were designated as slow growth (annual growth rate 5%-20%, VDT 3.5-13.9 years), 38% (14) were found to have medium growth (annual growth rate 20%-100%, VDT 0.7-3.5 years), and 8% were considered fast growing (annual growth rate > 100%, VDT < 0.7 years). CONCLUSIONS: This study evaluated CSM volumetric growth rates. A deeper understanding of the natural history of untreated CSMs allows for better counseling and management of patients.

Survival and outcomes in patients with ≥ 25 cumulative brain metastases treated with stereotactic radiosurgery.

OBJECTIVE: In the era in which more patients with greater numbers of brain metastases (BMs) are being treated with stereotactic radiosurgery (SRS) alone, it is critical to understand how patient, tumor, and treatment factors affect functional status and overall survival (OS). The authors examined the survival outcomes and dosimetry to critical structures in patients treated with Gamma Knife radiosurgery (GKRS) for ≥ 25 metastases in a single session or cumulatively over the course of their disease. METHODS: A retrospective analysis was conducted at a single institution. The institution's prospective Gamma Knife (GK) SRS registry was queried to identify patients treated with GKRS for ≥ 25 cumulative BMs between June 2013 and April 2020. Ninety-five patients were identified, and their data were used for analysis. Treatment plans for dosimetric analysis were available for 89 patients. Patient, tumor, and treatment characteristics were identified, and outcomes and OS were evaluated. RESULTS: The authors identified 1132 patients with BMs in their institutional registry. Ninety-five patients were treated for ≥ 25 cumulative metastases, resulting in a total of 3596 tumors treated during 373 separate treatment sessions. The median number of SRS sessions per patient was 3 (range 1-12 SRS sessions), with nearly all patients (n = 93, 98%) having > 1 session. On univariate analysis, factors affecting OS in a statistically significant manner included histology, tumor volume, tumor number, diagnosis-specific graded prognostic assessment (DS-GPA), brain metastasis velocity (BMV), and need for subsequent whole-brain radiation therapy (WBRT). The median of the mean WB dose was 4.07 Gy (range 1.39-10.15 Gy). In the top quartile for both the highest cumulative number and highest cumulative volume of treated metastases, the median of the mean WB dose was 6.14 Gy (range 4.02-10.15 Gy). Seventy-nine patients (83%) had all treated tumors controlled at last follow-up, reflecting the high and durable control rate. Corticosteroids for tumor- or treatment-related effects were prescribed in just over one-quarter of the patients. Of the patients with radiographically proven adverse radiation effects (AREs; 15%), 4 were symptomatic. Four patients required subsequent craniotomy for hemorrhage, progression, or AREs. CONCLUSIONS: In selected patients with a large number of cumulative BMs, multiple courses of SRS are feasible and safe. Together with new systemic therapies, the study results demonstrate that the achieved survival rates compare favorably to those of larger contemporary cohorts, while avoiding WBRT in the majority of patients. Therefore, along with the findings of other series, this study supports SRS as a standard practice in selected patients with larger numbers of BMs.

Combined Use of Diffusion Tractography and Advanced Intraoperative Imaging for Resection of Cervical Intramedullary Spinal Cord Neoplasms: A Case Series and Technical Note.

BACKGROUND: Intramedullary spinal cord neoplasms (ISCN) pose significant management challenges. Advances in magnetic resonance imaging (MRI) (such as diffusion tensor imaging, DTI) have been utilized to determine the infiltrative nature and resectability of ISCN. However, this has not been applied to intraoperative decision making. OBJECTIVE: To present a case series of 2 patients with ISCN, the first to combine use of DTI, pre- and intraoperative 3-dimensional (3D) virtual reality imaging, and microscope integrated navigation with heads-up display. METHODS: Two patients who underwent surgery for ISCN were included. DTI images were obtained and 3D images were created using Surgical Theater (Surgical Theater SRP, Version 7.4.0, Cleveland, Ohio). Fiducials were used to achieve accurate surface registration to C4. Navigation confirmed the levels of laminectomy necessary. The microscope was integrated with Brainlab (Brainlab AG Version 3.0.5, Feldkirchen, Germany) and the tumor projected in the heads-up display. Surgical Theater was integrated with Brainlab to allow for real time evaluation of the 3D tractography. RESULTS: Case 1: All tracts were pushed away from the tumor, suggesting it was not infiltrative. Surgical Theater and Brainlab assisted in confirming midline despite the abnormal swelling of the cord so the myelotomy could be performed. The heads-up display outline demonstrated excellent correlation to the tumor. Gross total resection was achieved. Diagnosis of ependymoma was confirmed. Case 2: Some tracts were going through the tumor itself, suggesting an infiltrative process. Surgical Theater and Brainlab again allowed for confirmation of the midline raphe. Near total resection of the enhancing portion was achieved. Diagnosis of glioblastoma was confirmed. CONCLUSION: This is a proof of concept application where multi-modal imaging technology was utilized for safest maximal ISCN resection.

Postoperative cerebral venous sinus thrombosis in the setting of surgery adjacent to the major dural venous sinuses.

OBJECTIVECerebral venous sinus thrombosis (CVST) is a known complication of surgeries near the major dural venous sinuses. While the majority of CVSTs are asymptomatic, severe sinus thromboses can have devastating consequences. The objective of this study was to prospectively evaluate the true incidence and risk factors associated with postoperative CVST and comment on management strategies.METHODSA prospective study of 74 patients who underwent a retrosigmoid, translabyrinthine, or suboccipital approach for posterior fossa tumors, or a supratentorial craniotomy for parasagittal/falcine tumors, was performed. All patients underwent pre- and postoperative imaging to evaluate sinus patency. Demographic, clinical, and operative data were collected. Statistical analysis was performed to identify incidence and risk factors.RESULTSTwenty-four (32.4%) of 74 patients had postoperative MR venograms confirming CVST, and all were asymptomatic. No risk factors, including age (p = 0.352), BMI (p = 0.454), sex (p = 0.955), surgical approach (p = 0.909), length of surgery (p = 0.785), fluid balance (p = 0.943), mannitol use (p = 0.136), tumor type (p = 0.46, p = 0.321), or extent of resection (p = 0.253), were statistically correlated with thrombosis. All patients were treated conservatively, with only 1 patient receiving intravenous fluids. There were no instances of venous infarctions, hemorrhages, or neurological deficits. The rate of CSF leakage was significantly higher in the thrombosis group than in the nonthrombosis group (p = 0.01).CONCLUSIONSThis prospective study shows that the radiographic incidence of postoperative CVST is higher than that previously reported in retrospective studies. In the absence of symptoms, these thromboses can be treated conservatively. While no risk factors were identified, there may be an association between postoperative CVST and CSF leak.

C-2 arteriovenous fistula presenting as a pathologic hangman's fracture: case report.

The authors report on an 81-year-old woman with a pathologic hangman's fracture secondary to a complex arteriovenous fistula (AVF). The patient presented with severe, unremitting neck pain and was found to have fractures bilaterally through the pars interarticularis of C-2 with significant anterior subluxation of C-2 over C-3 along with widening of the left transverse foramen. Due to an abnormally appearing left vertebral artery (VA) on CT angiography, the patient underwent conventional angiography, which revealed a complex AVF stemming from the left VA at the level of C-2 with dilated posterior cervical veins and a large venous varix. Given the radiographic evidence of bone remodeling and the chronicity of the AVF, it is believed that the C-2 vertebra was weakened over time by the pulsatile and compressive force of the vascular malformation eventually leading to fracture with minimal stress. Coil embolization of the AVF was performed followed by surgical fixation of C-1 to C-4. This case highlights the importance of investigating an underlying disease process in patients who present with significant spinal fractures in the absence of trauma.

In utero exposure to di-(2-ethylhexyl) phthalate exerts both short-term and long-lasting suppressive effects on testosterone production in the rat.

We examined the effects of fetal exposure to a wide range of di-(2-ethylhexyl) phthalate (DEHP) doses on fetal, neonatal, and adult testosterone production. Pregnant rats were administered DEHP from Gestational Day (GD) 14 to the day of parturition (Postnatal Day 0). Exposure to between 234 and 1250 mg/kg/day of DEHP resulted in increases in the absolute volumes of Leydig cells per adult testis. Despite this, adult serum testosterone levels were reduced significantly compared to those of controls at all DEHP doses. Organ cultures of testes from GD20 rats exposed in utero to DEHP showed dose-dependent reductions in basal testosterone production. Surprisingly, however, no significant effect of DEHP was found on hCG-induced testosterone production by GD20 testes, suggesting that the inhibition of basal steroidogenesis resulted from the alteration of molecular events upstream of the steroidogenic enzymes. Reduced fetal and adult testosterone production in response to in utero DEHP exposure appeared to be unrelated to changes in testosterone metabolism. In view of the DEHP-induced reductions in adult testosterone levels, a decrease in the expression of steroidogenesis-related genes was anticipated. Surprisingly, however, significant increases were seen in the expression of Cyp11a1, Cy17a1, Star, and Tspo transcripts, suggesting that decreased testosterone production after birth could not be explained by decreases in steroidogenic enzymes as seen at GD20. These changes may reflect an increased number of Leydig cells in adult testes exposed in utero to DEHP rather than increased gene expression in individual Leydig cells, but this remains uncertain. Taken together, these results demonstrate that in utero DEHP exposure exerts both short-term and long-lasting effects on testicular steroidogenesis that might involve distinct molecular targets in fetal and adult Leydig cells.