Silent corticotroph pituitary adenomas: clinical characteristics, long-term outcomes, and management of disease recurrence.

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a distinct subtype of nonfunctioning pituitary adenomas (NFAs) that demonstrate positive immunohistochemistry for adrenocorticotropic hormone (ACTH) without causing Cushing's disease. SCAs are hypothesized to exhibit more aggressive behavior than standard NFAs. The authors analyzed their institution's surgical experience with SCAs in an effort to characterize rates of invasion, postoperative clinical outcomes, and patterns of disease recurrence and progression. The secondary objectives were to define the best treatment strategies in the event of tumor recurrence and progression. METHODS: A retrospective analysis of patients treated at the authors' institution identified 100 patients with SCAs and 841 patients with NFAs of other subtypes who were treated surgically from 2000 to 2019. Patient demographics, tumor characteristics, surgical and neuroimaging data, rates of endocrinopathy, and neurological outcomes were recorded. Cohorts of patients with SCAs and patients with standard NFAs were compared with regard to these characteristics and outcomes. RESULTS: The SCA cohort presented with cranial neuropathy (13% vs 5.7%, p = 0.0051) and headache (53% vs 42.3%, p = 0.042) compared to the NFA cohort, despite similar rates of apoplexy. The SCA cohort included a higher proportion of women (SCA 60% vs NFA 45.8%, p = 0.0071) and younger age at presentation (SCA 50.5 ± 13.3 vs NFA 54.6 ± 14.9 years of age, p = 0.0082). Reoperations were comparable between the cohorts (SCA 16% vs NFA 15.7%, p = 0.98). Preoperative pituitary function was comparable between the cohorts with the exception of higher rates of preoperative panhypopituitarism in NFA patients (2% vs 6.1%, respectively; p = 0.0033). The mean tumor diameter in SCA patients was 24 ± 10.8 mm compared to 26 ± 11.3 mm in NFA patients (p = 0.05). Rates of cavernous sinus invasion were higher in the SCA group (56% vs 49.7%), although this result did not reach statistical significance. There were no significant differences in extent of resection, intraoperative CSF leak rates, endocrine or neurological outcomes, or postoperative complications. Ki-67 rates were significantly increased in the SCA cohort (2.88 ± 2.79) compared to the NFA cohort (1.94 ± 1.99) (p = 0.015). Although no differences in overall rates of progression or recurrence were noted, SCAs had a significantly lower progression-free survival (24.5 vs 51.1 months, p = 0.0011). Among the SCA cohort, progression was noted despite the use of adjuvant radiosurgery in 33% (n = 4/12) of treated tumors. Adequate tumor control was not achieved in half (n = 6) of the SCA progression cohort despite radiosurgery or multiple resections. CONCLUSIONS: In this study, to the authors' knowledge the largest surgical series to assess outcomes in SCAs to date, the findings suggest that SCAs are more biologically aggressive tumors than standard NFAs. The progression-free survival duration of patients with SCAs is only about half that of patients with other NFAs. Therefore, close neuroimaging and clinical follow-up are warranted in patients with SCAs, and residual disease should be considered for early postoperative adjuvant radiosurgery, particularly in younger patients.

Enhanced Recovery After Surgery-Based Perioperative Protocol for Head and Neck Free Flap Reconstruction.

OBJECTIVES: Evaluate an enhanced recovery after surgery (ERAS)-based free flap management protocol implemented at our center. STUDY DESIGN: Prospective cohort study of patients after implementation of an ERAS-based perioperative care protocol for patients undergoing free flap reconstruction of the head and neck as compared with a historical control group. SETTING: Tertiary care academic medical center. PARTICIPANTS AND METHODS: All patients undergoing free flap reconstruction were prospectively enrolled in the ERAS protocol group. A retrospective control group was identified by randomly selecting an equivalent number of patients from a records search of those undergoing free flap surgery between 2009 and 2015. Blood transfusion, complications, 30-day readmission rates, intensive care unit (ICU) and hospital length of stay, and costs of hospitalization were compared. RESULTS: Sixty-one patients were included in each group. Patients in the ERAS group underwent less frequent flap monitoring by physicians and had lower rates of intraoperative (70.5% vs 86.8%, P = .04) and postoperative (49.2% vs 27.2%, P = .026) blood transfusion, were more likely to be off vasopressors (98.3% vs 50.8%, P < .01) and ventilator support (63.9% vs 9.8%, P < .01) at the conclusion of surgery, and had shorter ICU stays (2.11 vs 3.39 days, P = .017). Length of stay, readmissions, and complication rates did not significantly differ between groups. CONCLUSION: ERAS-based perioperative practices for head and neck free flap reconstruction can reduce time on the ventilator and in the ICU and the need for vasopressors, blood transfusions, and labor-intensive flap monitoring, without adverse effects on outcomes.

Intentional Subtotal Resection of Vestibular Schwannoma: A Reexamination.

Background Treatment of vestibular schwannomas (VS) remains controversial. Historical surgical series prioritized gross total resections (GTR); however, near total resections (NTR) and intentional subtotal resections (STR) aiming at improving cranial nerve outcomes are becoming more popular. Objective The main purpose of this article is to assess the tumor control and facial nerve outcomes in VS patients treated with STR or NTR. Methods VS patients undergoing STR or NTR at our institution between 1984 and 2016 were retrospectively reviewed. Patient demographics, extent of tumor resection, facial nerve injury, tumor recurrence, and need for Gamma Knife radiosurgery were analyzed. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor regrowth was defined by the San Francisco criteria. Results Four-hundred fifty-seven VS resections were performed in a 32-year period. Sixty cases met inclusion criteria. The mean (range) follow-up duration was 30.9 (12-103) months. The STR cohort ( n = 33) demonstrated regrowth in 12 patients (36.3%) at an average of 23.6 months. The NTR cohort ( n = 27) did not experience tumor recurrence. Risk of tumor recurrence was positively correlated with preoperative tumor size ( p = 0.002), size of residual tumor ( p < 0.001), and STR ( p < 0.001). Facial nerve outcomes of HB1-2 were observed in the majority of patients in both cohorts (74.1% NTR, 56% STR), though NTR was associated with a higher likelihood of facial nerve recovery ( p = 0.003). Conclusion GTR remains the gold standard as long as facial nerve outcomes remain acceptable. NTR achieved superior tumor control and higher likelihood of facial nerve recovery compared with STR.

Discrepancy in Neurologic Outcomes Following Aneurysmal Subarachnoid Hemorrhage as a Function of Socioeconomic Class.

OBJECTIVE: To investigate potential health care discrepancies in patients with ruptured cerebral aneurysms undergoing microsurgical intervention. METHODS: We retrospectively reviewed patients with ruptured intracranial aneurysms treated at our tertiary referral university hospital (UH) and safety net county hospital (CH) from 2010 to 2015. We identified 73 UH patients and 58 CH patients. RESULTS: UH patients had shorter time duration between rupture and intervention (P < 0.001) and higher rates of intubation on admission (P = 0.01). Verapamil was more frequently used for clinical vasospasm in UH patients, at 0.13 (95% confidence interval [CI], 0.09-0.18) treatments per patient per day versus 0.077 (95% CI, 0.047-0.12) treatments per patient per day in CH patients, though there was no difference in delayed cerebral ischemia (P = 0.15). The majority of the CH cohort was uninsured (26.3%; UH 0%) or had Medicaid (59.7%; UH 35.2%) (P < 0.001). The UH had more dispositions to home or rehabilitation centers than the CH (82% vs. 67.3%; P = 0.04). After adjusting for disease severity, hospital stay, and insurance status, CH patients were 3.73 (95% CI, 1.25-12.14) times more likely to be discharged with a poor modified Rankin Scale score and 3.08 (95% CI, 1.04-9.61) times more likely to be discharged with a poor Glasgow Outcome Scale score compared with UH patients (P = 0.02 and P = 0.04, respectively). CONCLUSIONS: Limited resource availability in a safety net hospital system could be a major driving force behind the health care discrepancy identified in our ruptured cerebral aneurysm population. Reallocation of resources to supplement advanced inpatient acute care technologies and, more importantly, post-acute care environments can narrow the outcomes gap.

The Use of a Novel Perfusion-Based Human Cadaveric Model for Simulation of Dural Venous Sinus Injury and Repair.

BACKGROUND: Dural sinus injuries are potentially serious complications associated with acute blood loss. It is imperative that neurosurgery trainees are able to recognize and manage this challenging scenario. OBJECTIVE: To assess the feasibility of a novel perfusion-based cadaveric simulation model to provide the fundamentals of dural sinus repair to neurosurgical trainees. METHODS: A total of 10 perfusion-based human cadaveric models underwent superior sagittal sinus (SSS) laceration. Neurosurgery residents were instructed to achieve hemostasis by any method in the first trial and then repeated the trial after watching the instructional dural flap technique video. Trials were timed until hemostasis and control of the region of injury was achieved. Pre- and post-trial questionnaires were administered to assess trainee confidence levels. RESULTS: The high-flow extravasation of the perfusion-based cadaveric model mimicked similar conditions and challenges encountered during acute SSS injury. Mean ± standard deviation time to hemostasis was 341.3 ± 65 s in the first trial and 196.9 ± 41.8 s in the second trial (P < .0001). Mean trainee improvement time was 144.4 s (42.3%). Of the least-experienced trainees with longest repair times in the initial trial, a mean improvement time of 188.3 s (44.8%) was recorded. All participants reported increased confidence on post-trial questionnaires following the simulation (median pretrial confidence of 2 vs post-trial confidence of 4, P = .002). CONCLUSION: A perfusion-based human cadaveric model accurately simulates acute dural venous sinus injury, affording neurosurgical trainees the opportunity to hone management skills in a simulated and realistic environment.

Comparison of Referral Pathways in Otolaryngology at a Public Versus Private Academic Center.

OBJECTIVE: Delayed medical care may be costly and dangerous. Examining referral pathways may provide insight into ways to reduce delays in care. We sought to compare time between initial referral and first clinic visit and referral and surgical intervention for index otolaryngologic procedures between a public safety net hospital (PSNH) and tertiary-care academic center (TAC). METHODS: Retrospective cohort study of eligible adult patients undergoing one of several general otolaryngologic procedures at a PSNH (n = 216) and a TAC (n = 161) over a 2-year time period. RESULTS: PSNH patients were younger, less likely to have comorbidities and more likely to be female, Hispanic or Asian, and to lack insurance. Time between referral and first clinic visit was shorter at the PSNH than the TAC (Mean 35.8 ± 47.7 vs 48.3 ± 60.3 days; P = .03). Time between referral and surgical intervention did not differ between groups (129 ± 90 for PSNH vs 141 ± 130 days for TAC, P = .30). On multivariate analysis, the TAC had more patient-related delays in care than the PSNH (OR: 3.75, P < .001). Time from referral to surgery at a PSNH was associated with age, source of referral, type of surgery, diagnostic workup and comorbidities, and at a TAC was associated with gender and type of surgery and comorbidities. CONCLUSIONS: Sociodemographic differences between PSNH and TAC patients, as well as differences in referral pathways between the types of institutions, influence progression of surgical care in otolaryngology. These differences may be targets for interventions to streamline care. LEVEL OF EVIDENCE: 2c.

Effectiveness of Gamma Knife Radiosurgery in the Treatment of Refractory Trigeminal Neuralgia: A Case Series.

BACKGROUND: Medical management is the first line of treatment for trigeminal neuralgia (TN). Patients with medically refractory TN may undergo a variety of invasive surgical interventions with varying success rates. Management of TN refractory to both medical and surgical intervention remains somewhat controversial. OBJECTIVE: To assess the effectiveness of Gamma Knife radiosurgery (GKRS; Elekta Instruments AB) for medically refractory TN. METHODS: A retrospective review was conducted for 57 cases (47 patients) who underwent GKRS for refractory TN at our institution between 2005 and 2018. TN pain outcomes were evaluated using the Barrow Neurological Institute (BNI) Pain Scale. A good outcome was defined by post-GKRS BNI score of I-III, whereas treatment failure was defined BNI score IV-V. RESULTS: Of the total 57 GKRS procedures, 47 (82.5%) had good outcomes. A total of 22 patients (46.8%) experienced complete pain relief off medications (BNI I). The average time to pain relief was 30 d (range 1-120 d). Prior invasive surgical treatment for TN was not found to have a significant impact on GKRS outcomes (P = .32). Target and treatment volumes were not found to correlate significantly with GKRS outcomes (.47 and .47, respectively). Complications included 2 cases (4.2%) of facial numbness. A total of 37 patients (78.7%) did not have any additional invasive surgical interventions following GKRS treatment. CONCLUSION: GKRS is a safe and effective treatment modality for both medically and surgically refractory TN. Complete symptom relief was possible in patients with prior surgical or GKRS treatments. Recurrent symptoms following surgery or GKRS should not exclude a patient from future GKRS consideration.

Clinical utility of routine postoperative morning cortisol monitoring in detecting new hypothalamic-pituitary-adrenal axis insufficiency following endoscopic transsphenoidal surgery for sellar lesions.

OBJECTIVE: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a well-documented complication of transsphenoidal craniotomy (TSC) for sellar lesions. The authors aimed to assess their multidisciplinary approach to the diagnosis and treatment of postoperative hypocortisolemia utilizing conservative screening methods. METHODS: The authors performed a retrospective review of 257 patients who underwent TSC for pituitary adenoma (PA) or Rathke cleft cyst (RCC) at the University of Southern California between 2012 and 2017. Patients with preoperative adrenal insufficiency, Cushing's disease, or < 3 months of postoperative follow-up were excluded. Patient demographics, pathology, tumor characteristics, and complications were recorded. Postoperative day 1 (POD1) morning serum cortisol was assessed in all patients. Hypocortisolemia on POD1 (serum cortisol < 5 µg/dl) prompted a 7 am cortisol level measurement on POD 2 (POD2). Clinical signs and symptoms of hypocortisolemia were consistently monitored. After two serum cortisol levels < 5 µg/dl, or one serum level < 5 µg/dl plus a high clinical suspicion for HPA dysfunction, high-risk patients received glucocorticoid supplementation. RESULTS: Data on 165 patients were included in the analysis; there were 101 women (61.2%) and 64 men (38.7%). Preoperative diagnoses included nonfunctional adenoma (n = 97, 58.7%), growth hormone-secreting adenoma (n = 37, 22.4%), RCC (n = 18, 10.9%), prolactinoma (n = 8, 4.8%), and other (n = 5, 3.0%). One hundred thirty-eight patients (63.0%) had either suprasellar extension or cavernous sinus invasion. POD1 hypocortisolemia was diagnosed in 8 patients (4.8%). Of these patients, 2 (1.2%) were clinically asymptomatic and had normalized POD2 cortisol levels. Six patients (3.6%) had clinical symptoms and POD2 cortisol levels confirming HPA axis deficiency. Of these 6 patients treated with early glucocorticoid replacement, 2 patients recovered HPA axis function during follow-up, making the incidence of new, permanent HPA axis deficiency 2.5%. CONCLUSIONS: In the authors' institutional review, all patients warranting postoperative glucocorticoid replacement had both complicated surgical courses and associated clinical symptoms of hypocortisolemia. The authors' algorithm of withholding steroids until patients demonstrate clear evidence of postoperative hypocortisolemia is safe and clinically efficacious. Their data further suggest that routine postoperative cortisol screening may not be necessary following an uncomplicated operative resection, with gland preservation and the absence of clinical symptoms indicative of HPA dysfunction.