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Anna Jackanich, Sherwin Tavakol, Ben A. Strickland, Martin Rutkowski, Dina Kamel, John D. Carmichael, Martin Weiss and Gabriel Zada

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.

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Kyohei Itamura, Ki-Eun Chang, Joshua Lucas, Daniel A. Donoho, Steven Giannotta and Gabriel Zada

OBJECTIVE

The present study aims to assess the clinical utility of a previously validated intraoperative meningioma consistency grading scale and its association with extent of resection (EOR) and various surgical outcomes.

METHODS

The previously validated grading system was prospectively assessed in 127 consecutive patients undergoing open craniotomy for meningioma by multiple neurosurgeons at two high-volume academic hospitals from 2013 to 2016. Consistency grading scores ranging from 1 (soft) to 5 (firm/calcified) were retrospectively analyzed to test for association with surgical outcomes and EOR, categorized as gross-total resection (GTR) or subtotal resection, defined by postoperative MRI.

RESULTS

One hundred twenty-seven patients were included in the analysis with a tumor consistency distribution as follows: grade 1, 3.1%; grade 2, 14.2%; grade 3, 44.1%; grade 4, 32.3%; and grade 5, 6.3%. The mean tumor diameter was 3.6 ± 1.7 cm. Tumor consistency grades were grouped into soft (grades 1 and 2), average (grade 3), and firm (grades 4 and 5) groups for statistical analysis with distributions of 17.3%, 44.1%, and 38.6%, respectively. There was no association between meningioma consistency and maximal tumor diameter, or location. Mean duration of surgery was longer for tumors with higher consistency: grades 1 and 2, 186 minutes; grade 3, 219 minutes; and grades 4 and 5, 299 minutes (p = 0.000028). There was a trend toward higher perioperative complication rates for tumors of increased consistency: grades 1 and 2, 4.5%; grade 3, 7.0%; and grades 4 and 5, 20.8% (p = 0.047). The proportion of GTR for each consistency group was as follows: grades 1 and 2, 77%; grade 3, 68%; and grades 4 and 5, 43% (p = 0.0062).

CONCLUSIONS

In addition to other important meningioma characteristics such as invasiveness, tumor consistency is a key determinant of surgical outcomes, including operative duration and EOR. Future studies predicting tumor consistency based on preoperative neuroimaging will help considerably with preoperative planning for meningiomas.

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Matthew S. Agam, Michelle A. Wedemeyer, Bozena Wrobel, Martin H. Weiss, John D. Carmichael and Gabriel Zada

OBJECTIVE

Pituitary adenomas (PAs) are benign neoplasms that are frequently encountered during workup for endocrinopathy, headache, or visual loss. Transsphenoidal surgery remains the first-line approach for PA resection. The authors retrospectively assessed complication rates associated with transsphenoidal PA resection from an institutional database.

METHODS

A retrospective analysis of 1153 consecutive transsphenoidal pituitary adenoma resections performed at the Keck Hospital of USC between November 1992 and March 2017 was conducted. Microscopic transsphenoidal resection was performed in 85.3% of cases, and endoscopic transsphenoidal resection was performed in 14.7%. Analysis of perioperative complications and patient and tumor risk factors was conducted.

RESULTS

The overall median hospital stay was 3 days. There was 1 perioperative death (0.1%). Surgical complications included postoperative cerebrospinal fluid leak (2.6%), epistaxis (1.1%), postoperative hematoma (1.1%), meningitis (1.0%), cranial nerve paresis (0.8%), hydrocephalus (0.8%), vision loss (0.6%), stroke (0.3%), abdominal hematoma or infection (0.2%), carotid artery injury (0.1%), and vegetative state (0.2%). Perioperative medical complications included bacteremia/sepsis (0.5%), pneumonia (0.3%), myocardial infarction (0.3%), and deep venous thrombosis/pulmonary embolism (0.1%). Endocrine complications were the most frequent, including transient diabetes insipidus (4.3%), symptomatic hyponatremia (4.2%), new hypopituitarism (any axis) (3.6%), permanent diabetes insipidus (0.3%), and adrenal insufficiency (0.2%). There were no significant differences between microscopic and endoscopic approaches with regard to surgical complications (6.4% vs 8.8%, p = 0.247) or endocrine complications (11.4 vs 11.8%, p = 0.888). Risk factors for surgical complications included prior transsphenoidal surgery (11.4% vs 6.8%, p = 0.025), preoperative vision loss (10.3% vs 6.8%, p = 0.002), and presence of PA invasion on MRI (8.5% vs 4.4%, p = 0.007).

CONCLUSIONS

In this single tertiary center study assessing complications associated with transsphenoidal PA resection, the rate of death or major disability was 0.26%. Risk factors for complications included prior surgical treatment and PA invasion. No differences in complication rates between endoscopic and microscopic surgery were observed. When performed at experienced pituitary centers, transsphenoidal surgery for PAs may be performed with a high degree of safety.

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Justin Seltzer, Michelle A. Wedemeyer, Phillip A. Bonney, John D. Carmichael, Martin Weiss and Gabriel Zada

OBJECTIVE

Incidental pituitary adenomas (IPAs) are commonly discovered during cranial imaging evaluations obtained for unrelated indications. The optimal management of IPA remains controversial. The authors investigated the outcomes and safety of the surgical treatment of IPAs at their institution.

METHODS

Clinical outcome data for 1692 patients surgically treated for pituitary adenomas at the Keck Medical Center of USC/USC Pituitary Center over a 17-year period (1999–2016) were reviewed to identify all cases with surgically managed IPAs. Clinical characteristics reviewed in this retrospective analysis included patient demographics, endocrine laboratory data, visual field examinations, and MRI results. Intraoperative data reviewed included requirement for CSF leak repair, surgical complications, and estimated extent of resection. Postoperative data collected included pathology results, length of stay, postoperative complications, endocrine outcomes, readmission rates, and long-term outcomes, including extent of resection noted on postoperative imaging studies and tumor progression and/or recurrence.

RESULTS

Fifty-two patients (3.1% of all cases) underwent transsphenoidal surgery for IPA. The median age at surgery was 61 years (range 31–86 years). The most common reasons for neuroimaging included trauma (19%), stroke/transient ischemic attack (15%), and sinonasal disease (15%). Visual field deficits were present in 15% of bedside examinations, and among the 22 patients sent for formal testing, 54.5% were noted to have deficits. Preoperative endocrine function was normal in 69% of patients, which includes 3 patients (5.8%) having isolated hyperprolactinemia consistent with a stalk effect without other hormonal dysfunction. The average maximal tumor diameter was 20.9 mm (8–50 mm; data available in 35 patients). The most common primary indication for surgery was compression of the chiasm or vision loss (52%); other major considerations included tumor growth, a young patient age, and identified endocrine abnormalities. Intraoperative CSF leak repair was performed in 56% of patients, and 1 patient (2%) developed postoperative CSF rhinorrhea treated with lumbar drainage. The median hospital stay was 2 days. There were no deaths or major complications. Three patients (5.8%) developed transient diabetes insipidus. Over a mean follow-up of 61 months, 4 patients (50.0%) reported improved headaches and 6 (54.5%) reported improvement in their visual deficits. Four patients (25%) had improved endocrine function, including one with resumption of menstruation and another with remission of acromegaly. One patient (2.4%) reported new postoperative headache, and none experienced worsened vision. Four patients (10.5%) developed new single-axis hypopituitarism and 1 (2.6%) developed new panhypopituitarism. The overall recurrence/progression rate on neuroimaging was 9.6% at a mean of 80 months.

CONCLUSIONS

Transsphenoidal resection of IPAs, when appropriate, can be performed safely at experienced treatment centers. Incidental pituitary adenomas should be evaluated and treated as indicated, especially in younger patients at risk for endocrine or visual dysfunction.

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Michelle Lin, Michelle A. Wedemeyer, Daniel Bradley, Daniel A. Donoho, Vance L. Fredrickson, Martin H. Weiss, John D. Carmichael and Gabriel Zada

OBJECTIVE

Rathke’s cleft cysts (RCCs) are benign epithelial lesions of the sellar region typically treated via a transsphenoidal approach with cyst fenestration and drainage. At present, there is limited evidence to guide patient selection for operative treatment. Furthermore, there is minimal literature describing factors contributing to cyst recurrence.

METHODS

The authors conducted a retrospective analysis of 109 consecutive cases of pathology-confirmed RCCs treated via a transsphenoidal approach at a single center from 1995 to 2016. The majority of cases (86.2%) involved cyst fenestration, drainage, and partial wall resection. Long-term outcomes were analyzed.

RESULTS

A total of 109 surgeries in 100 patients were included, with a mean follow-up duration of 67 months (range 3–220 months). The mean patient age was 44.6 years (range 12–82 years), and 73% were women. The mean maximal cyst diameter was 14.7 mm. Eighty-eight cases (80.7%) were primary operations, and 21 (19.3%) were reoperations. Intraoperative CSF leak repair was performed in 53% of cases and was more common in reoperation cases (71% vs 48%, p < 0.001). There were no new neurological deficits or perioperative deaths. Two patients (1.8%) developed postoperative CSF leaks. Transient diabetes insipidus (DI) developed in 24 cases (22%) and permanent DI developed in 6 (5.5%). Seven cases (6.4%) developed delayed postoperative hyponatremia. Of the 66 patients with preoperative headache, 27 (44.3%) of 61 reported postoperative improvement and 31 (50.8%) reported no change. Of 31 patients with preoperative vision loss, 13 (48.1%) reported subjective improvement and 12 (44.4%) reported unchanged vision. Initial postoperative MRI showed a residual cyst in 25% of cases and no evidence of RCC in 75% of cases. Imaging revealed evidence of RCC recurrence or progression in 29 cases (26.6%), with an average latency of 28.8 months. Of these, only 10 (9.2% of the total 109 cases) were symptomatic and underwent reoperation.

CONCLUSIONS

Transsphenoidal fenestration and drainage of RCCs is a safe and effective intervention for symptomatic lesions, with many patients experiencing improvement of headaches and vision. RCCs show an appreciable (although usually asymptomatic) recurrence rate, thereby mandating serial follow-up. Despite this, full RCC excision is typically not recommended due to risk of hypopituitarism, DI, and CSF leaks.

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Michelle Lin, Michelle A. Wedemeyer, Daniel Bradley, Daniel A. Donoho, Vance L. Fredrickson, Martin H. Weiss, John D. Carmichael and Gabriel Zada

OBJECTIVE

Rathke’s cleft cysts (RCCs) are benign epithelial lesions of the sellar region typically treated via a transsphenoidal approach with cyst fenestration and drainage. At present, there is limited evidence to guide patient selection for operative treatment. Furthermore, there is minimal literature describing factors contributing to cyst recurrence.

METHODS

The authors conducted a retrospective analysis of 109 consecutive cases of pathology-confirmed RCCs treated via a transsphenoidal approach at a single center from 1995 to 2016. The majority of cases (86.2%) involved cyst fenestration, drainage, and partial wall resection. Long-term outcomes were analyzed.

RESULTS

A total of 109 surgeries in 100 patients were included, with a mean follow-up duration of 67 months (range 3–220 months). The mean patient age was 44.6 years (range 12–82 years), and 73% were women. The mean maximal cyst diameter was 14.7 mm. Eighty-eight cases (80.7%) were primary operations, and 21 (19.3%) were reoperations. Intraoperative CSF leak repair was performed in 53% of cases and was more common in reoperation cases (71% vs 48%, p < 0.001). There were no new neurological deficits or perioperative deaths. Two patients (1.8%) developed postoperative CSF leaks. Transient diabetes insipidus (DI) developed in 24 cases (22%) and permanent DI developed in 6 (5.5%). Seven cases (6.4%) developed delayed postoperative hyponatremia. Of the 66 patients with preoperative headache, 27 (44.3%) of 61 reported postoperative improvement and 31 (50.8%) reported no change. Of 31 patients with preoperative vision loss, 13 (48.1%) reported subjective improvement and 12 (44.4%) reported unchanged vision. Initial postoperative MRI showed a residual cyst in 25% of cases and no evidence of RCC in 75% of cases. Imaging revealed evidence of RCC recurrence or progression in 29 cases (26.6%), with an average latency of 28.8 months. Of these, only 10 (9.2% of the total 109 cases) were symptomatic and underwent reoperation.

CONCLUSIONS

Transsphenoidal fenestration and drainage of RCCs is a safe and effective intervention for symptomatic lesions, with many patients experiencing improvement of headaches and vision. RCCs show an appreciable (although usually asymptomatic) recurrence rate, thereby mandating serial follow-up. Despite this, full RCC excision is typically not recommended due to risk of hypopituitarism, DI, and CSF leaks.

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Meng Law, Regina Wang, Chia-Shang J. Liu, Mark S. Shiroishi, John D. Carmichael, William J. Mack, Martin Weiss, Danny J. J. Wang, Arthur W. Toga and Gabriel Zada

Cushing’s disease is caused by adrenocorticotrophic hormone (ACTH)–secreting pituitary adenomas, which are often difficult to identify on standard 1.5-T or 3-T MRI, including dynamic contrast imaging. Inferior petrosal and cavernous sinus sampling remains the gold standard for MRI-negative Cushing’s disease.

The authors report on a 27-year-old woman with Cushing’s disease in whom the results of standard 1.5-T and 3-T MRI, including 1.5-T dynamic contrast imaging, were negative. Inferior petrosal sinus sampling showed a high central-to-peripheral ACTH ratio (148:1) as well as a right-to-left ACTH gradient (19:1), suggesting a right-sided pituitary microadenoma. The patient underwent 7-T MRI, which showed evidence of a right-sided pituitary lesion with focal hypoenhancement not visualized on 1.5-T or 3-T MRI. The patient underwent an endoscopic endonasal transsphenoidal operation, with resection of a right-sided pituitary mass. Postoperatively, she developed clinical symptoms suggestive of adrenal insufficiency and a nadir cortisol level of 1.6 μg/dl on postoperative day 3, and hydrocortisone therapy was initiated. Permanent histopathology specimens showed Crooke’s hyaline change and ACTH-positive cells suggestive of an adenoma.

MRI at 7 T may be beneficial in identifying pituitary microadenoma location in cases of standard 1.5-T and 3-T MRI-negative Cushing’s disease. In the future, 7-T MRI may preempt inferior petrosal sinus sampling and help in cases of standard and dynamic contrast 1.5-T and 3-T MRI-negative Cushing’s disease.

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Kevin Diao, Shelly X. Bian, David M. Routman, Cheng Yu, Paul E. Kim, Naveed A. Wagle, Michael K. Wong, Gabriel Zada and Eric L. Chang

OBJECTIVE

Tumor and edema volume changes of brain metastases after stereotactic radiosurgery (SRS) and ipilimumab are not well described, and there is concern regarding the safety of combination treatment. The authors evaluated tumor, edema, and adverse radiation-induced changes after SRS with and without ipilimumab and identified associated risk factors.

METHODS

This single-institution retrospective study included 72 patients with melanoma brain metastases treated consecutively with upfront SRS from 2006 to 2015. Concurrent ipilimumab was defined as ipilimumab treatment within 4 weeks of SRS. At baseline and during each follow-up, tumor and edema were measured in 3 orthogonal planes. The (length × width × height/2) formula was used to estimate tumor and edema volumes and was validated in the present study for estimation of edema volume. Tumor and edema volume changes from baseline were compared using the Kruskal-Wallis test. Local failure, lesion hemorrhage, and treatment-related imaging changes (TRICs) were analyzed with the Cox proportional hazards model.

RESULTS

Of 310 analyzed lesions, 91 were not treated with ipilimumab, 59 were treated with concurrent ipilimumab, and 160 were treated with nonconcurrent ipilimumab. Of 106 randomly selected lesions with measurable peritumoral edema, the mean edema volume by manual contouring was 7.45 cm3 and the mean volume by (length × width × height)/2 formula estimation was 7.79 cm3 with R2 = 0.99 and slope of 1.08 on line of best fit. At 6 months after SRS, the ipilimumab groups had greater tumor (p = 0.001) and edema (p = 0.005) volume reduction than the control group. The concurrent ipilimumab group had the highest rate of lesion response and lowest rate of lesion progression (p = 0.002). Within the concurrent ipilimumab group, SRS dose ≥ 20 Gy was associated with significantly greater median tumor volume reduction at 3 months (p = 0.01) and 6 months (p = 0.02). The concurrent ipilimumab group also had the highest rate of lesion hemorrhage (p = 0.01). Any ipilimumab was associated with higher incidence of symptomatic TRICs (p = 0.005). The overall incidence of pathologically confirmed radiation necrosis (RN) was 2%. In multivariate analysis, tumor and edema response at 3 months were the strongest predictors of local failure (HR 0.131 and HR 0.125) and lesion hemorrhage (HR 0.225 and HR 0.262). Tumor and edema response at 1.5 months were the strongest predictors of TRICs (HR 0.144 and HR 0.297).

CONCLUSIONS

The addition of ipilimumab improved tumor and edema volume reduction but was associated with a higher incidence of lesion hemorrhage and symptomatic TRICs. There may be a radiation dose-response relationship between SRS and ipilimumab when administered concurrently. Early tumor and edema response were excellent predictors of subsequent local failure, lesion hemorrhage, and TRICs. The incidence of pathologically proven RN was low, supporting the relative safety of ipilimumab in radiosurgery treatment.

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Eisha A. Christian, Joshua Bakhsheshian, Ben A. Strickland, Vance L. Fredrickson, Ian A. Buchanan, Martin H. Pham, Andrew Cervantes, Michael Minneti, Bozena B. Wrobel, Steven Giannotta and Gabriel Zada

OBJECTIVE

Competency in endoscopic endonasal approaches (EEAs) to repair high-flow cerebrospinal fluid (CSF) leaks is an essential component of the neurosurgical training process. The objective of this study was to demonstrate the feasibility of a simulation model for EEA repair of anterior skull base CSF leaks.

METHODS

Human cadaveric specimens were utilized with a perfusion system to simulate a high-flow CSF leak. Neurological surgery residents (postgraduate year 3 or greater) performed a standard EEA to repair a CSF leak using a combination of fat, fascia lata, and pedicled nasoseptal flaps. A standardized 5-point Likert questionnaire was used to assess the knowledge gained, techniques learned, degree of safety, benefit of CSF perfusion during repair, and pre- and posttraining confidence scores.

RESULTS

Intrathecal perfusion of fluorescein-infused saline into the ventricular/subarachnoid space was successful in 9 of 9 cases. The addition of CSF reconstitution offered the residents visual feedback for confirmation of intraoperative CSF leak repair. Residents gained new knowledge and a realistic simulation experience by rehearsing the psychomotor skills and techniques required to repair a CSF leak with fat and fascial grafts, as well as to prepare and rotate vascularized nasoseptal flaps. All trainees reported feeling safer with the procedure in a clinical setting and higher average posttraining confidence scores (pretraining 2.22 ± 0.83, posttraining 4.22 ± 0.44, p < 0.001).

CONCLUSIONS

Perfusion-based human cadaveric models can be utilized as a simulation training model for repairing CSF leaks during EEA.