Robert F. Dallapiazza

Long-term results of endonasal endoscopic transsphenoidal resection of nonfunctioning pituitary macroadenomas.

BACKGROUNDnSeveral studies report early results of endoscopic endonasal transsphenoidal surgery; however, none discuss long-term outcome measures such as tumor recurrence rates and the need for additional surgical procedures.nnnOBJECTIVEnTo discuss the long-term outcomes after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary macroadenomas.nnnMETHODSnThis is a retrospective study. Patients were included only if they had at least 5 years of clinical and imaging follow-up after surgery.nnnRESULTSnEighty patients met the study criteria. Grossly complete resection was achieved in 71% of patients. Knosp grade 0 to 2 tumors and tumor with volumes <10 cm were significantly more likely to have received a grossly complete resection. There were 7 recurrences (12%) in patients who had received grossly complete resections, with a mean time to recurrence of 53 months. Among the 23 patients who had subtotal resections, 11 (61%) progressed radiographically, and 3 (17%) had symptomatic progression. Knosp score, surgical and radiographic evidence of invasion, and preoperative visual deficits were predictive of recurrence in a univariate analysis, but Knosp grade was the only independent predictor in a multivariate analysis. Kaplan-Meier analysis projected a 10-year progression-free survival rate of 80% and 21% for patients with gross total resections and subtotal resections, respectively.nnnCONCLUSIONnAt the long-term follow-up, 12% of patients had recurrent tumors after grossly complete resection. Recurrent or residual tumors were treated with either repeat surgery or Gamma Knife radiosurgery. Rates of complete resection, postoperative surgical and endocrinological complications, and additional surgical procedures are similar to previously published reports after microscopic transsphenoidal surgery.

Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution

OBJECTnThe object of this study was to compare surgical outcomes and complications in a contemporaneous series of patients undergoing either microscopic or endoscopic transsphenoidal surgery for nonfunctioning pituitary macroadenomas without imaging evidence of cavernous sinus invasion.nnnMETHODSnThis is a retrospective analysis of a prospectively collected database from a single institution. Data were collected from patients whose surgery had occurred in the period from June 2010 to January 2013. Patients who underwent microscopic or endoscopic surgery for Knosp Grade 0, 1, or 2 nonfunctioning pituitary macroadenomas were included in the study. Patients who had clinically secreting or Knosp Grade 3 or 4 tumors and patients who were undergoing revision surgery were excluded from analysis. Eligible patient records were analyzed for outcomes and complications. Statistical analyses were performed on tumor volume, intraoperative factors, postoperative complications, and degree of resection on 1-year postoperative MRI. The results were used to compare the outcomes after microscopic and endoscopic approaches.nnnRESULTSnForty-three patients underwent microscopic transsphenoidal surgery, and 56 underwent endoscopic transsphenoidal surgery. There were no statistical differences in the intraoperative extent of resection or endocrinological complications. There were significantly more intraoperative CSF leaks in the endoscopic group (58% vs 16%); however, there was no difference in the incidence of postoperative CSF rhinorrhea (12% microscopic vs 7% endoscopic). Length of hospitalization was significantly shorter in patients undergoing an endoscopic approach (3.0 days vs 2.4 days). Two-month follow-up imaging was available in 95% of patients, and 75% of patients had 1-year follow-up imaging. At 2 months postprocedure, there was no evidence of residual tumor in 79% (31 of 39) and 85% (47 of 55) of patients in the microscopic and endoscopic groups, respectively. At 1 year postprocedure, 83% (25 of 30) of patients in the microscopic group had no evidence of residual tumor and 82% (36 of 44) of those in the endoscopic group had no evidence of residual tumor.nnnCONCLUSIONSnThe microscopic and endoscopic techniques provide similar outcomes in the surgical treatment of Knosp Grades 0-2 nonfunctioning pituitary macroadenomas.

132 A Randomized, Sham-Controlled Trial of Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Trial for the Treatment of Tremor-Dominant, Idiopathic Parkinson Disease.

INTRODUCTIONnTraditional stereotactic radiofrequency thalamotomy has been used with success in medication-refractory tremor-dominant Parkinson disease (PD). Recently, transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been used to successfully perform thalamotomy for essential tremor. We designed a double-blinded, randomized controlled trial to investigate the effectiveness of MRgFUS thalamotomy in tremor-dominant PD.nnnMETHODSnPatients with medication-refractory, tremor-dominant PD were enrolled in the 2-center study and randomly assigned 1:2 to receive either a sham procedure or treatment. After the 3-month blinded phase, the sham group was offered treatment. Outcome was measured with blinded Clinical Rating Scale for Tremor (CRST) and Unified Parkinsons Disease Rating Scale (UPDRS) ratings. The primary outcome compared improvement in hand tremor between the treatment and sham procedure at 3 months. Secondary outcomes were measured with UPDRS and hand tremor at 12 months. Safety was assessed with MRI, adverse events, and comprehensive neurocognitive assessment.nnnRESULTSnTwenty-seven patients were enrolled and 6 were randomly assigned to a sham procedure. For the primary outcome assessment, there was a mean 50% improvement in hand tremor from MRgFUS thalamotomy at 3 months compared with a 22% improvement from the sham procedures (P = .088). The 1-year tremor scores for all 19 patients treated with 1-year follow-up data (blinded and unblinded) showed a reduction in tremor scores of 40.6% (P = .0154) and a mean reduction in medicated UPDRS motor scores of 3.7 (32%, P = .033). Sham patients had a notable placebo effect with a mean 21.5% improvement in tremor scores at 3 months. Twenty-seven patients completed the primary analysis, 19 patients completed the 12-month assessment, 3 patients opted for deep brain stimulation, 3 were lost to follow-up, 1 patient opted for no treatment, and 1 is pending a 12-month evaluation.nnnCONCLUSIONnTranscranial MRgFUS demonstrates a trend toward improvement in hand tremor, and a clinically significant reduction in mean UPDRS. A significant placebo response was noted in the randomized trial.cause of intractable epilepsy in children. Seizure freedom following resection of FCD is determined by complete resection of the dysplastic cortical tissue.However, difficulty with intraoperative identification of the FCD lesion may limit the ability to achieve the surgical objective of complete extirpation of these lesions. The use of intraoperative magnetic resonance imaging (iMRI) may aid in real-time detection of these lesions and improve seizure control outcomes compared with traditional resective surgery.

Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound

OBJECTIVE Ultrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal. METHODS Ten Yorkshire swine ( Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage. RESULTS LIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (∼ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage. CONCLUSIONS These results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.

Early versus late Gamma Knife radiosurgery following transsphenoidal resection for nonfunctioning pituitary macroadenomas: a matched cohort study

OBJECT Gamma Knife radiosurgery (GKRS) is frequently employed to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of radiographic progression of tumor. METHODS This is a retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS between 1996 and 2013 at the University of Virginia Health System. Patients were stratified based on the interval between resection and radiosurgery. Operative results and imaging and clinical outcomes were compared across groups following early (≤ 6 months) or late (> 6 months) radiosurgery. RESULTS Sixty-four patients met the study criteria and were grouped based on early (n = 32) or late (n = 32) GKRS following transsphenoidal resection. There was a greater risk of tumor progression after GKRS in the late radiosurgical group (p = 0.027) over a median radiographic follow-up period of 68.5 months. Furthermore, there was a significantly higher occurrence of post-GKRS endocrinopathy in the late radiosurgical cohort (p = 0.041). Seventeen percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 64% in the late cohort (p = 0.036). This difference was primarily due to a significantly higher rate of tumor growth during the observation period of the late treatment cohort (p = 0.014). Of these patients with completely new endocrinopathies, radiation-associated pituitary insufficiency developed in 1 of 2 patients in the early group and in 3 of 7 (42.9%) patients in the late group. CONCLUSIONS Early treatment with GKRS appears to decrease the rate of radiographic and symptomatic progression of subtotally resected nonfunctioning pituitary macroadenomas compared with late GKRS treatment after a period of expectant management. Delaying radiosurgery may place the patient at increased risk for adenoma progression and endocrinopathy.

Primary versus revision transsphenoidal resection for nonfunctioning pituitary macroadenomas: matched cohort study

OBJECTIVE The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods. METHODS The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS). RESULTS The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test). CONCLUSIONS Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.

Microsurgical versus endoscopic transsphenoidal resection for acromegaly: a systematic review of outcomes and complications

PurposeThe aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly.MethodsA literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes.ResultsFifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (nxa0=xa03144) and 13 were endoscopic (nxa0=xa0940). Three studies compared microsurgical (nxa0=xa0111) to endoscopic TSR outcomes (nxa0=xa0180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively.ConclusionsBoth endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.

Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Pituitary Tumors in Pediatric Patients

Although pediatric pituitary and parasellar tumors are uncommon, they can produce significant disability and pose significant treatment challenges for pediatricians, endocrinologists, and neurosurgeons. Despite their rarity in pediatric patients, there are a wide range of lesions that affect the pituitary gland and parasellar region. Craniopharyngioma is the most common, followed by hormone-active pituitary tumors. Fortunately, most pituitary tumors in children are benign. However, given the location of these tumors, they can have a profound impact on hormonal regulation in growing children. Therefore, surgical interventions must be planned carefully in order to minimize operative morbidity and maximize functional recovery. As with adult pituitary lesions, the transsphenoidal corridor often is a surgical option for treating pituitary and parasellar tumors in children. In this chapter we discuss some of the surgical nuances of transsphenoidal surgery in pediatric patients. We then review the clinical presentation, operative considerations, and surgical outcomes for the most common pediatric pituitary tumors. Finally, we discuss complication avoidance and management.