Daniel M. S. Raper

Endoscopic vs Microsurgical Transsphenoidal Surgery for Acromegaly: Outcomes in a Concurrent Series of Patients Using Modern Criteria For Remission

CONTEXT It is unclear whether endoscopic transsphenoidal surgery (ETSS) or microsurgical transsphenoidal surgery (MTS) is a superior surgical approach for pituitary adenomas. OBJECTIVE The objective of the study was to compare the outcome of surgery with ETSS and MTS by experienced pituitary surgeons using criteria of remission using current consensus criteria for acromegaly. DESIGN AND SETTING This was a retrospective review of prospectively recorded outcomes. The study was conducted at a tertiary referral center. Patients, Interventions, and Outcome Measures: Remission was defined as a normal IGF-I level and either suppressed GH less than 0.4 ng/mL during an oral glucose tolerance test or random GH less than 1.0 ng/mL. The Youden indices were calculated to determine the optimal cutoffs for using immediate postoperative GH levels to predict the results of later testing for remission. RESULTS Preoperative demographics and tumor characteristics were not significantly different between patients undergoing ETSS (72 patients) or MTS (41 patients). Overall, postoperative remission was achieved in 20 of 23 microadenomas (87%) and 59 of 90 macroadenomas (66%). Remission rates and perioperative complications were not significantly different between ETSS and MTS groups, except for self-reported sinusitis and alterations in taste or smell, which were significantly higher in patients treated with ETSS. Preoperative variables predicting remission in multivariate analysis included GH less than 45 ng/mL [odds ratio (OR) 6.4, P = .010)] and Knosp score of 0-2 (OR 6.8, P < .001). Postoperative in-hospital GH less than 1.15 ng/mL provided the best predictor of remission (OR 7.7, P < .001; sensitivity of 73%, specificity of 85%) defined by follow-up testing. CONCLUSIONS Outcomes of transsphenoidal surgery for acromegaly by experienced pituitary surgeons do not differ between endoscopic and microscopic techniques. Regardless of the mode of resection, patients with high preoperative GH levels and Knosp scores are less likely to achieve remission. An immediate postoperative GH level of less than 1.15 ng/mL provides the best immediate predictor of remission, but long-term outcomes are indicated.

Endoscopic Endonasal Compared with Microscopic Transsphenoidal and Open Transcranial Resection of Craniopharyngiomas

OBJECTIVE Craniopharyngiomas have traditionally represented a challenge for open transcranial or transsphenoidal microscopic neurosurgery because of their anatomical location and proximity to vital neurovascular structures. The extended endoscopic endonasal transsphenoidal approach has been more recently developed as a potentially surgically aggressive, yet minimal access, alternative. To gain a more comprehensive assessment of the benefits and limitations of the various approaches to resection of craniopharyngiomas, we performed a systematic review of the available published reports after endoscope-assisted endonasal approaches and compared their results with transsphenoidal purely microscope-based or transcranial microscope-based techniques. METHODS We performed a MEDLINE search of the modern literature (1995-2010) to identify open and endoscopic surgical series for pediatric and adult craniopharyngiomas. Comparisons were made for patient and tumor characteristics as well as extent of resection, morbidity, and visual outcome. Statistical analyses of categorical variables were undertaken by the use of χ(2) and Fisher exact tests with post-hoc Bonferroni analysis to compare endoscopic, microsurgical transsphenoidal, and transcranial approaches. RESULTS Eighty eight studies, involving 3470 patients, were included. The endoscopic cohort had a significantly greater rate of gross total resection (66.9% vs. 48.3%; P < 0.003) and improved visual outcome (56.2% vs. 33.1%; P < 0.003) compared with the open cohort. The transsphenoidal cohort had similar outcomes to the endoscopic group. The rate of cerebrospinal fluid leakage was greater in the endoscopic (18.4%) and transsphenoidal (9.0%) than in the transcranial group (2.6%; P < 0.003), but the transcranial group had a greater rate of seizure (8.5%), which did not occur in the endonasal or transsphenoidal groups (P < 0.003). CONCLUSIONS The endoscopic endonasal approach is a safe and effective alternative for the treatment of certain craniopharyngiomas. Larger lesions with more lateral extension may be more suitable for an open approach, and further follow-up is needed to assess the long-term efficacy of this minimal access approach.

Endoscopic endonasal versus open transcranial resection of anterior midline skull base meningiomas.

OBJECTIVE To assess the advantages and limitations of the endoscopic endonasal approach to anterior skull base meningiomas, a minimally invasive approach that avoids extensive bone drilling, brain retraction, and manipulation of nerves and critical vessels, versus open transcranial surgery. METHODS A MEDLINE (2000-2010) search was performed to identify series for either olfactory groove meningiomas or tuberculum sellae (TS) or planum sphenoidale meningiomas. Statistical analyses of categorical variables such as extent of resection, morbidity, and visual outcome were performed using χ(2) and Fisher exact tests. RESULTS The literature review included 60 studies, involving 1426 patients. Open surgery achieved a higher rate of gross total resection (GTR) for both olfactory groove (P < 0.001) and TS and planum (P < 0.001) meningiomas. Postoperative cerebrospinal fluid (CSF) leak occurred more frequently in the endoscopic cohort (P < 0.001). Other postoperative complications occurred more frequently in the open cohort, although this difference was not statistically significant. There were no significant differences in postoperative visual outcome between the groups. CONCLUSIONS Based on the current literature, open transcranial approaches for olfactory groove and TS and planum sphenoidale meningiomas still result in higher rates of total resection with lower postoperative CSF leak rates. The endoscopic endonasal approach may be safe and effective for certain skull base meningiomas; careful patient selection and multilayer closure techniques are essential.

The Endoscope-Assisted Ventral Approach Compared with Open Microscope-Assisted Surgery for Clival Chordomas

BACKGROUND The current management paradigm for clival chordomas includes cytoreductive surgery with adjuvant radiotherapy. Surgical approaches have traditionally utilized the microscope to remove these lesions through approaches that require extensive bone drilling, brain retraction, and mobilization of normal anatomy to create a suitably large corridor. The endoscopic ventral approaches provide a direct route to the tumor using natural orifices. Little data exist comparing these 2 surgical strategies. We conducted a systematic review of case series and case reports in hope of furthering our understanding of the role of endoscopy in the management of these difficult cranial base lesions. METHODS We performed a MEDLINE (1950 to 2010) search to identify relevant studies. Statistical analyses of categorical variables such as extent of resection, morbidity, and visual outcome were carried out using chi-square and Fisher exact tests. RESULTS Thirty-seven studies, involving 766 patients, were included. Compared with the open surgery cohort, the endoscopic cohort had a significantly higher percentage of gross total resection (61.0% vs. 48.1%; P = 0.010), fewer cranial nerve deficits (1.3% vs. 24.2%, P < 0.001), fewer incidences of meningitis (0.9% vs. 5.9%, P = 0.029), less mortality (4.7% vs. 21.6%, P < 0.001), and fewer local recurrences (16.9% vs. 40.0%, P = 0.0001). There was no significant difference in the incidence of postoperative cerebrospinal fluid leak (P = 0.084). Follow-up was longer in the open compared with the endoscopic cohort (59.7 vs. 18.5 months, P < 0.001). CONCLUSIONS Our systematic analysis supports the endoscopic ventral approaches as a safe and effective alternative for the treatment of certain clival chordomas. Although the overall literature supports this technique in carefully selected patients, longer follow-up is needed to more definitively address therapeutic efficacy. Careful patient selection and meticulous multilayer closure are critical to obtaining maximal resection and acceptably low cerebrospinal fluid leak rates.

The role of radiosurgery to the tumor bed after resection of brain metastases.

BACKGROUND Optimal postoperative management paradigm for brain metastases remains controversial. OBJECTIVE To conduct a systematic review of the literature to understand the role of postoperative stereotactic radiosurgery after resection of brain metastases. METHODS We performed a MEDLINE search of the literature to identify series of patients with brain metastases treated with stereotactic radiosurgery after surgical resection. Outcomes including overall survival, local control, distant intracranial failure, and salvage therapy use were recorded. Patient, tumor, and treatment factors were correlated with outcomes through the use of the Pearson correlation and 2-way Student t test as appropriate. RESULTS Fourteen studies involving 629 patients were included. Median survival for all studies was 14 months. Local control was correlated with the median volume treated with radiosurgery (r = -0.766, P < .05) and with the rate of gross total resection (r = .728, P < .03). Mean crude local control was 83%; 1-year local control was 85%. Distant intracranial failure occurred in 49% of cases, and salvage whole-brain radiation therapy was required in 29% of cases. Use of a radiosurgical margin did not lead to increased local control or overall survival. CONCLUSION Our systematic review supports the use of radiosurgery as a safe and effective strategy for adjuvant treatment of brain metastases, particularly when gross total resection has been achieved. With all limitations of comparisons between studies, no increase in local recurrence or decrease in overall survival compared with rates with adjuvant whole-brain radiation therapy was found.

Case-specific protocol to reduce cerebrospinal fluid leakage after endonasal endoscopic surgery

OBJECT Endoscopic transsphenoidal surgery is expanding in acceptance, yet postoperative CSF leak rates remain a concern. This study presents the Cornell closure protocol, which has yielded significantly lower postoperative CSF leak rates compared with prior reports, as an algorithm that can be used by centers having difficulty with CSF leak. METHODS A single closure algorithm for endoscopic surgery has been used since January 2010 at Weill Cornell Medical College. A prospective database noting intraoperative CSF leak, closure technique, and postoperative CSF leak was reviewed. The authors used a MEDLINE search to identify similar studies and compared CSF leak rates to those of patients treated using the Cornell algorithm. RESULTS The retrospective study of a prospectively acquired database included 209 consecutive patients. In 84 patients (40%) there was no intraoperative CSF leak and no postoperative CSF leak. In the 125 patients (60%) with an intraoperative CSF leak, 35 of them with high-flow leaks, there were 0 (0%) postoperative CSF leaks. CONCLUSIONS It is possible to achieve a CSF leak rate of 0% by using this closure protocol. With proper experience, endoscopic skull base surgery should not be considered to have a higher CSF leak rate than open transcranial or microscopic transsphenoidal surgery.

Clinical features, management and recurrence of symptomatic Rathke's cleft cyst

Rathkes cleft cyst (RCC) is a rare lesion of the pituitary gland that is often asymptomatic. The objective of this study was to further characterise the presenting symptoms, endocrinopathy and potential for recurrence of this lesion in an Australian population. The files of 12 patients with pathologically confirmed RCCs were reviewed retrospectively. Common presentations included headache, endocrinopathy, and visual disturbance. Uncommon presentations included 1 patient with pituitary apoplexy. The cysts varied in size from 6 mm to 20 mm; 8 had a suprasellar component. 1 patient had evidence of a RCC with xanthogranulomatous change. RCC recurrence was noted on follow-up MRI in 5 patients. In conclusion, RCCs are rare lesions that can present with an array of clinical symptoms. The relatively high rate of recurrence may indicate a link between this pathology and craniopharyngioma, although many patients with recurrent RCC do not require repeat resection and remain asymptomatic.

Vascular Smooth Muscle Cells in Cerebral Aneurysm Pathogenesis

Vascular smooth muscle cells (SMC) maintain significant plasticity. Following environmental stimulation, SMC can alter their phenotype from one primarily concerned with contraction to a pro-inflammatory and matrix remodeling phenotype. This is a critical process behind peripheral vascular disease and atherosclerosis, a key element of cerebral aneurysm pathology. Evolving evidence demonstrates that SMCs and phenotypic modulation play a significant role in cerebral aneurysm formation and rupture. Pharmacological alteration of smooth muscle cell function and phenotypic modulation could provide a promising medical therapy to inhibit cerebral aneurysm progression. This study reviews vascular SMC function and its contribution to cerebral aneurysm pathophysiology.

Tumor Necrosis Factor-α Modulates Cerebral Aneurysm Formation and Rupture

Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment of macrophages, activation of chemotactic cytokines, upregulation of matrix remodeling genes, production of free radicals leading to oxidative stress, and ultimately cellular apoptosis. Recent studies have indicated that TNF-α may be a potential target for the development of novel medical therapies, but additional experimental data is needed to clarify the intricacies of TNF-α activation and its critical downstream targets in cerebral aneurysms. This review provides an update on the mechanisms underlying TNF-α-induced molecular modulation in cerebral aneurysms.

Endoscopic skull base surgery: a comprehensive comparison with open transcranial approaches

Abstract Little data exists comparing endoscopic endonasal approaches to pathology of the anterior skull base with more traditional transcranial and transsphenoidal microscopic approaches. In order to more fully characterize the role of endoscopy in the management of pathology of the anterior cranial base, we conducted a systematic review of case series and case reports documenting surgical and clinical outcomes. We found that for craniopharyngiomas, clival chordomas, esthesioneuroblastomas and giant pituitary adenomas, the endonasal endoscopic approach can result in equivalent or higher rates of gross total resection than open approaches. For meningiomas, however, open transcranial approaches are still able to achieve higher rates of total resection. CSF leak rates are higher for patients undergoing endoscopic surgery for meningiomas and craniopharyngiomas, but not for chordomas, esthesioneuroblastomas or giant pituitary adenomas. In certain patients, the endonasal endoscopic approach may be a safe and effective alternative for the treatment of a wide variety of skull base pathology, particularly those with small midline tumours.