Search

OBJECTIVE The utility and safety of intraoperative MRI (iMRI) for resection of pituitary adenomas is not clearly established in the context of advances in endoscopic approaches. The goal in this study was to evaluate the safety and efficacy of iMRI for pituitary adenoma resection, with endoscopic transsphenoidal (ETS) versus microscopic transsphenoidal (MTS) approaches. METHODS Radiographic and clinical outcomes of all pituitary adenomas resected using iMRI between 2008 and 2017 at a single institution were retrospectively evaluated. RESULTS Of 212 tumors treated, 131 (62%) underwent further resection based on iMRI findings, resulting in a significant increase in gross-total resection on postoperative MRI compared with iMRI (p = 0.0001) in both ETS and MTS groups. iMRI increased rates of gross-total resection for cavernous sinus invasion Knosp grades 1 and 2, but not in Knosp ≥ 3 across treatment groups (p < 0.0001). The extent of resection on postoperative MRI was significantly correlated with increased progression-free survival (p < 0.0001). Initial hormone remission off medical therapy was achieved in 64%, with a significantly higher rate of remission in tumors resected via the ETS approach (81%) compared with the MTS approach (55%) (p = 0.02). The rate of persistent new hormone deficit was low at 8%, including a 2.8% rate of permanent diabetes insipidus, and 45% of patients had improvement in preoperative hormone deficit following surgery. Serious postoperative complications including CSF leaks requiring reoperation were rare at 1%, with no postoperative infections. CONCLUSIONS These results suggest that iMRI is a safe and effective method of increasing the extent of resection for pituitary adenomas while preserving hormone function. When paired with the endoscope, iMRI may offer the ability to tailor more aggressive removal of tumors while optimizing pituitary function, resulting in high rates of secretory hormone remission. Secretory tumors and adenomas with Knosp grade < 3 cavernous sinus invasion may benefit most from the use of iMRI.

OBJECTIVEThe sylvian bridging veins between the brain and the dura on the inner surface of the sphenoid wing can restrict brain retraction for widening of the lateral retrocarotid space during clipping surgery for internal carotid artery (ICA)–posterior communicating artery (PCoA) and basilar apex (BX) aneurysms. In such cases, the authors perform extradural anterior clinoidectomy with peeling of the temporal dura propria from the periosteal dura and inner cavernous membrane around the superior orbital fissure, with the incision of the dura mater stretching from the base of the temporal side to just before the distal dural ring of the ICA (termed by the authors as the sphenoparietal sinus transposition [SPST] technique). This technique displaces the bridging segment of the sylvian vein posteriorly and enables widening of the surgical space without venous injury. In this study, the authors observed the operative nuances and investigated the usefulness of this technique.METHODSThe authors retrospectively reviewed the medical charts of 66 consecutive patients with ICA-PCoA and BX aneurysms between January 2016 and July 2018. This technique was performed in 8 patients (5 patients with PCoA aneurysms and 3 with BX aneurysms) in whom the bridging segments of the sylvian veins between the brain and the skull base restricted brain retraction for widening of the surgical space. The surface areas of the lateral retrocarotid space and the aneurysm were measured at the most visible working angle before and after the SPST technique was performed.RESULTSWith the use of the SPST technique, an adequate surgical space for aneurysm clipping was obtained with preservation of the bridging veins in all patients. The mean surface areas of the lateral retrocarotid space (p = 0.002) and aneurysm (p = 0.001) were significantly increased from 18.3 ± 18.8 and 2.8 ± 2.5 cm2 before to 64.2 ± 21.1 and 20.9 ± 20.6 cm2, respectively, after the SPST technique was performed.CONCLUSIONSThe SPST technique enables displacement of the bridging segments of the sylvian veins without venous injury and enables widening of the surgical space around the lateral retrocarotid area.

OBJECTIVEGamma 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.METHODSThis 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.RESULTSAfter 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).CONCLUSIONSIn 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.

OBJECTIVEParasellar tumors that extend far laterally beyond the internal carotid artery or that are fibrous and adhere firmly to critical structures are difficult to remove totally via the endoscopic transsphenoidal approach alone. In such cases, a combined transsphenoidal-transcranial approach is effective to achieve maximal resection in a single stage. In this paper, a new minimally invasive surgical technique for complicated parasellar lesions, a fully endoscopic combined transsphenoidal–supraorbital keyhole approach, is presented.METHODSA retrospective review of patients who had been treated via a fully endoscopic combined transsphenoidal–supraorbital keyhole approach for complicated parasellar lesions was performed. The data for resection rate, perioperative mortality and morbidity, and postoperative outcomes were analyzed.RESULTSA total of 12 fully endoscopic combined transsphenoidal–supraorbital keyhole approaches were performed from March 2013 to February 2016; 10 were for pituitary adenomas and 2 were for craniopharyngiomas. Gross-total resection or near-total resection was achieved in 7 of 12 cases. Among the 11 patients who had presented with preoperative visual disturbances, 7 had visual improvement. However, 1 patient showed deterioration in visual function. No patient experienced postoperative hemorrhage, needed additional surgical treatment, or had postoperative CSF leakage.CONCLUSIONSIn the combined transsphenoidal and transcranial approach, safe and effective cooperative manipulation with 2 surgical corridors can be performed for complicated parasellar lesions. The goal of this procedure is not to achieve gross-total resection, but to achieve safe resection. Moreover, this new surgical approach offers neurosurgeons a simpler operative field with less invasiveness than the conventional microscopic combined approach. The fully endoscopic combined endonasal–supraorbital keyhole approach is an efficacious procedure for complicated parasellar lesions with acceptable results.

OBJECTIVEMultiple approaches have been designed to reach the medial middle fossa (for lesions in Meckel’s cave, in particular), but an anterior approach through the greater wing of the sphenoid (transalisphenoid) has not been explored. In this study, the authors sought to assess the feasibility of and define the anatomical landmarks for an endoscopic anterior transmaxillary transalisphenoid (EATT) approach to Meckel’s cave and the middle cranial fossa.METHODSEndoscopic dissection was performed on 5 cadaver heads injected intravascularly with colored silicone bilaterally to develop the approach and define surgical landmarks. The authors then used this approach in 2 patients with tumors that involved Meckel’s cave and provide their illustrative clinical case reports.RESULTSThe EATT approach is divided into the following 4 stages: 1) entry into the maxillary sinus, 2) exposure of the greater wing of the sphenoid, 3) exposure of the medial middle fossa, and 4) exposure of Meckel’s cave and lateral wall of the cavernous sinus. The approach provided excellent surgical access to the anterior and lateral portions of Meckel’s cave and offered the possibility of expanding into the infratemporal fossa and lateral middle fossa and, in combination with an endonasal transpterygoid approach, accessing the anteromedial aspect of Meckel’s cave.CONCLUSIONSThe EATT approach to Meckel’s cave and the middle cranial fossa is technically feasible and confers certain advantages in specific clinical situations. The approach might complement current surgical approaches for lesions of Meckel’s cave and could be ideal for lesions that are lateral to the trigeminal ganglion in Meckel’s cave or extend from the maxillary sinus, infratemporal fossa, or pterygopalatine fossa into the middle cranial fossa, Meckel’s cave, and cavernous sinus, such as schwannomas, meningiomas, and sinonasal tumors and perineural spread of cutaneous malignancy.

OBJECTIVEEfficient allocation of resources in the healthcare system enables providers to care for more and needier patients. Identifying drivers of total charges for transsphenoidal surgery (TSS) for pituitary tumors, which are poorly understood, represents an opportunity for neurosurgeons to reduce waste and provide higher-quality care for their patients. In this study the authors used a large, national database to build machine learning (ML) ensembles that directly predict total charges in this patient population. They then interrogated the ensembles to identify variables that predict high charges.METHODSThe authors created a training data set of 15,487 patients who underwent TSS between 2002 and 2011 and were registered in the National Inpatient Sample. Thirty-two ML algorithms were trained to predict total charges from 71 collected variables, and the most predictive algorithms combined to form an ensemble model. The model was internally and externally validated to demonstrate generalizability. Permutation importance and partial dependence analyses were performed to identify the strongest drivers of total charges. Given the overwhelming influence of length of stay (LOS), a second ensemble excluding LOS as a predictor was built to identify additional drivers of total charges.RESULTSAn ensemble model comprising 3 gradient boosted tree classifiers best predicted total charges (root mean square logarithmic error = 0.446; 95% CI 0.439–0.453; holdout = 0.455). LOS was by far the strongest predictor of total charges, increasing total predicted charges by approximately $5000 per day.In the absence of LOS, the strongest predictors of total charges were admission type, hospital region, race, any postoperative complication, and hospital ownership type.CONCLUSIONSML ensembles predict total charges for TSS with good fidelity. The authors identified extended LOS, nonelective admission type, non-Southern hospital region, minority race, postoperative complication, and private investor hospital ownership as drivers of total charges and potential targets for cost-lowering interventions.

OBJECT With the increase in the average life expectancy, medical care of elderly patients with symptomatic pituitary adenoma (PA) will continue to grow. Little information exists in the literature about the surgical treatment of these patients. The aim of this study was to present the results of a single pituitary center in the surgical treatment of PAs in patients > 70 years of age. METHODS In this retrospective study, 55 consecutive elderly patients (age ≥ 70 years) with nonfunctioning PAs underwent endoscopic transsphenoidal surgery at the General Hospital of Fortaleza, Brazil, between May 2000 and December 2012. The clinical and radiological results in this group were compared with 2 groups of younger patients: < 60 years (n = 289) and 60–69 years old (n = 30). RESULTS Fifty-five patients ≥ 70 years of age (average age 72.5 years, range 70–84 years) underwent endoscopic surgery for treatment of PAs. The mean follow-up period was 50 months (range 12–144 months). The most common symptoms were visual impairment in 38 (69%) patients, headache in 16 (29%) patients, and complete ophthalmoplegia in 6 (10.9%). Elderly patients presented a higher incidence of ophthalmoplegia (p = 0.032) and a lower frequency of pituitary apoplexy before surgery (p < 0.05). Tumors with cavernous sinus invasion were treated surgically less frequently than in younger patients. Although patients with an American Society of Anesthesiologists score of 3 were more common in the elderly group (p < 0.05), no significant difference regarding surgical time, extent of resection, and hospitalization were observed. Elderly patients presented with more complications than patients < 60 years (32.7% vs 10%, p < 0.05). Complications observed in the elderly group included 5 CSF leaks (9%), 2 permanent diabetes insipidus cases (3.6%), 4 postoperative refractory hypertension cases (7.2%), 1 myocardial ischemia (1.8%), and 1 death (1.8%). Postoperative new anterior pituitary deficit was more common in the younger group (< 60 years old: 17.7%) than in the elderly (≥ 70 years old: 12.7%); however, there was no statistical difference. CONCLUSIONS Endoscopic transsphenoidal surgery for elderly patients with PAs may be associated with higher complication rates, especially secondary to early transitory complications, when compared with surgery performed in younger patients. Although the worst preoperative clinical status might be observed in this group, age alone is not associated with a worst final prognosis after endoscopic removal of nonfunctioning PAs.

OBJECT Extended endoscopic transnasal surgeries for skull base lesions have recently been performed. Some expert surgeons have attempted to remove tumors such as chordomas, meningiomas, and pituitary adenomas in the clival region using the transnasal approach and have reported abducens nerve injury as a common complication. There have been many microsurgical anatomical studies of the abducens nerve, but none of these studies has described an anatomical landmark of the abducens nerve in the transnasal approach. In this study the authors used cadaver dissections to describe Grüber's ligament as the most reliable landmark of the abducens nerve in the transnasal transclival view. METHODS The petroclival segment of the abducens nerve was dissected in the interdural space—which is also called Dorello's canal, the petroclival venous gulf, or the sphenopetroclival venous confluence—using the transnasal approach in 20 specimens obtained from 10 adult cadaveric heads. RESULTS The petroclival segment of the abducens nerve clearly crossed and attached to Grüber's ligament in the interdural space, as noted in the transnasal view. The average length of the dural porus to the intersection on the abducens nerve was 5.2 ± 1.0 mm. The length of the posterior clinoid process (PCP) to the intersection on Grüber's ligament was 6.4 ± 2.6 mm. The average width of Grüber's ligament at the midsection was 1.6 ± 0.5 mm. CONCLUSIONS Grüber's ligament is considered a useful landmark, and it is visible in most adults. Thus, surgeons can find the abducens nerve safely by visualizing inferolaterally along Grüber's ligament from the PCP.

OBJECTIVECerebrospinal fluid (CSF) rhinorrhea is among the most common complications following transsphenoidal surgery for sellar region lesions. The aim of this study was to review the authors’ institutional experience in identifying, repairing, and treating CSF leaks associated with direct endonasal transsphenoidal operations.METHODSThe authors performed a retrospective review of cases involving surgical treatment of pituitary adenomas and other sellar lesions at the University of Southern California between December 1995 and March 2016. Inclusion criteria included all pathology of the sellar region approached via a direct microscopic or endoscopic endonasal transsphenoidal approach. Demographics, pathology, intraoperative and postoperative CSF leak rates, and other complications were recorded and analyzed. A literature review of the incidence of CSF leaks associated with the direct endonasal transsphenoidal approach to pituitary lesions was conducted.RESULTSA total of 1002 patients met the inclusion criteria and their cases were subsequently analyzed. Preoperative diagnoses included pituitary adenomas in 855 cases (85.4%), Rathke’s cleft cyst in 94 (9.4%), and other sellar lesions in 53 (5.2%). Lesions with a diameter ≥ 1 cm made up 49% of the series. Intraoperative repair of an identified CSF leak was performed in 375 cases (37.4%) using autologous fat, fascia, or both. An additional 92 patients (9.2%) underwent empirical sellar reconstruction without evidence of an intraoperative CSF leak. Postoperative CSF leaks developed in 26 patients (2.6%), including 13 (1.3% of the overall group) in whom no intraoperative leak was identified. Among the 26 patients who developed a postoperative CSF leak, 13 were noted to have intraoperative leak and underwent sellar repair while the remaining 13 did not have an intraoperative leak or sellar repair. No patients who underwent empirical sellar repair without an intraoperative leak developed a postoperative leak. Eight patients underwent additional surgery (0.8% reoperation rate) for CSF leak repair, and 18 were successfully treated with lumbar drainage or lumbar puncture alone. The incidence of postoperative CSF rhinorrhea in this series was compared with that in 11 other reported series that met inclusion criteria, with incidence rates ranging between 0.6% and 12.1%.CONCLUSIONSIn this large series, half of the patients who developed postoperative CSF rhinorrhea had no evidence of intraoperative CSF leakage. Unidentified intraoperative CSF leaks and/or delayed development of CSF fistulas are equally important sources of postoperative CSF rhinorrhea as the lack of employing effective CSF leak repair methods. Empirical sellar reconstruction in the absence of an intraoperative CSF leak may be of benefit following resection of large tumors, especially if the arachnoid is thinned out and herniates into the sella.

OBJECTIVEPituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%–20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented.METHODSNineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2–4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression.RESULTSData from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance.CONCLUSIONSPituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

Object The authors devised an extended transsphenoidal approach involving a submucosal posterior ethmoidectomy that allows for adequate exposure of the cavernous sinus. To evaluate the adequacy of this approach for removal of adenomas invading the cavernous sinus, the authors retrospectively analyzed the surgical outcomes obtained in treated patients. Methods During a 9-year period, 36 patients with pituitary adenomas extending into the cavernous sinus underwent tumor removal at Kinki University Hospital. In the authors' technique of extended transsphenoidal surgery, the inferior wall of the affected cavernous sinus was entirely exposed, not only to permit safe removal of the tumor but also to secure the petrous portion of the internal carotid artery (ICA). For prevention of intraoperative injury to the cranial nerves, a low-profile pressure sensor was attached on the eyelid to detect eye movements in response to electrical stimulation of the cranial nerves. Results Total or subtotal tumor removal was achieved in 72% of 36 patients. In eight (67%) of 12 patients with growth hormone–secreting adenomas, hormonal remission was achieved postoperatively. Postoperative transient double vision was observed in 27% of the patients, but no serious complications, such as permanent cranial nerve palsy or ICA injury, occurred. Conclusions These reasonable surgical results obtained in the present series of patients suggest that the extended transsphenoidal approach is safe and effective for removal of adenomas within the cavernous sinus. These preliminary results may lead to a reevaluation of the role of surgery as the therapeutic strategy for invasive pituitary adenomas.

Object The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision and a microscope and have reported a significant risk of cerebrospinal fluid (CSF) leakage. The authors report on a series of purely endoscopic endonasal surgeries for resection of suprasellar supradiaphragmatic lesions above a normal-sized sella turcica with a low risk of CSF leakage. Methods A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (three tuberculum sellae and two planum sphenoidale meningiomas) and five were post-chiasmal (four craniopharyngiomas and one Rathke cleft cyst). The floor of the planum sphenoidale and the sella turcica was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was performed in only five cases. Complete resection of the lesions was achieved in all but one patient. The pituitary stalk was preserved in all but one patient, whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus (DI). Vision improved postoperatively in all patients with preoperative impairment. Six patients had temporary DI; in five, the DI became permanent. Four patients with craniopharyngiomas required cortisone and thyroid replacement. After a mean follow up of 10 months, there was only one transient CSF leak when a lumbar drain was clamped prematurely on postoperative Day 5. Conclusions A purely endoscopic endonasal approach to suprasellar supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leakage is low and lumbar drainage can be avoided. A larger series will be required to validate this approach.

✓ Gliosarcomas are bimorphic intraaxial tumors. Involvement of the skull base is highly unexpected. The authors present the case of a temporal lobe gliosarcoma with significant infratemporal fossa extension. This 55-year-old man presented with a 1-month history of severe progressive headache. Neurological examination was unremarkable except for bilateral papilledema. Magnetic resonance imaging revealed a 6-cm right temporal mass with extension into the infratemporal fossa. The patient underwent a right frontotemporal craniotomy together with drilling of the sphenoid ridge and middle fossa floor. The tumor consisted of intraaxial, intracranial as well as extradural, and extracranial components with extension to the posterolateral wall of the sphenoid sinus. It had a relatively well-circumscribed dissection plane. Gross-total resection was achieved, and the middle fossa floor was reconstructed using a rotated temporalis muscle flap. The postoperative course was uneventful except for hypesthesia in the distribution of the maxillary division of the right trigeminal nerve. The histopathological diagnosis was consistent with gliosarcoma. Radiotherapy and chemotherapy consisting of temozolomide were administered subsequently, and the patient was recurrence free 12 months after his initial diagnosis. In the presence of a mass lesion with both intraaxial and extracranial involvement, gliosarcoma should be considered among the differential diagnoses. Aggressive resection should be attempted, including the use of skull base surgical techniques to ensure an optimal outcome. The effect of skull base involvement to the overall treatment and outcome of patients with gliosarcomas would be difficult to determine given the rare occurrence of these lesions in such locations.

Object The authors report their experience with pituitary apoplexy and evaluate the clinical significance of sphenoid sinus mucosal thickening found on magnetic resonance (MR) imaging. Methods The cases of 28 patients (19 males and nine females) with pituitary apoplexy were reviewed retrospectively. The mean age of the patients was 50 years (range 16–83 years), and the mean follow-up duration was 32 months (range 1–104 months). Admission MR imaging demonstrated hemorrhage or infarction in a pituitary tumor in each patient. A clinical grading scale for apoplexy was devised as follows: Grade I, presence of acute headache and/or endocrine abnormality (12 patients); Grade II, presence of the foregoing symptoms as well as cranial nerve deficit (visual and/or oculomotor; 15 patients); and Grade III, presence of all of these symptoms and a decreased level of consciousness (one patient). Twenty-five patients (89%) underwent early transsphenoidal resection within 9 days (80% within 72 hours) of diagnosis. Headaches and oculomotor paresis resolved completely in 100%, visual function resolved completely in 44% and partially in 56%, and hypopituitarism was reversed in 25%. Twelve patients (43%) required long-term hormone replacement therapy. Two of the three patients who were treated conservatively had prolactin-secreting adenomas, which were treated with dopamine agonist therapy. Thickening of sphenoid sinus mucosa was present in 22 patients (79%). Fifty percent of patients in Grade I and 100% of those in Grades II and III, including all those with persistent hypopituitarism and residual visual deficits, had thickened sphenoid sinus mucosa on MR imaging. Patients with thickened sphenoid sinus mucosa had larger tumors that compressed the optic chiasm or cavernous sinus, and these individuals also had a higher rate of cranial nerve deficits at presentation than those without mucosal thickening (73% compared with 0%). Patients with thickened mucosa had a higher rate of hypopituitarism and subsequent long-term hormone replacement therapy than those without thickened mucosa (55% compared with 17%). Conclusions Thickened sphenoid sinus mucosa may correlate with higher grades of pituitary apoplexy and worse neurological and endocrinological outcomes.

✓ The transnasal transsphenoidal approach is the preferred route for removal of most lesions of the sella turcica. The concept of transnasal surgery traversing the sphenoid sinus to reach the sella has existed for nearly a century. A comprehensive historical overview of the evolution of transsphenoidal surgery has been reported previously. In the present vignette, the authors focus on transsphenoidal surgery in the early 1900s, particularly on the methods advocated by Harvey Cushing and Oskar Hirsch, two prominent pituitary surgeons who pioneered the transsphenoidal technique. Cushing championed the sublabial approach, whereas Hirsch was the master of the endonasal route. Coincidentally, both surgeons independently performed the submucous septal resection for the first time on June 4, 1910. Although Cushing's and Hirsch's approaches were predicated on the work of their predecessors, their transsphenoidal procedures became the two most popular techniques and, for future generations of pituitary surgeons, laid the foundation for modern transsphenoidal surgery. In this comparative analysis, the authors compare the operative nuances of the approaches of Cushing and Hirsch and describe the contributions of these pioneers to modern transsphenoidal surgery.

Diabetes insipidus (DI) is a common complication of transsphenoidal surgery. The purpose of this study was to elucidate patient- and surgery-specific risk factors for DI.The perioperative records of 881 patients who had undergone transsphenoidal microsurgery at the authors' institution between January 1995 and June 2001 were reviewed. Among 857 patients without preoperative DI, the overall incidence of immediate postoperative DI was 18.3%, with 12.4% of patients requiring treatment with desmopressin at some point during their hospitalization. Persistent DI requiring long-term treatment with desmopressin was noted in 2% of all patients. An observable intraoperative cerebrospinal fluid (CSF) leak was strongly associated with an increased incidence of both transient (33.3%) and persistent (4.4%) DI. Craniopharyngioma and Rathke cleft cyst (RCC) were also associated with an increased incidence of transient and persistent DI, whereas repeated operation was not. Among patients with pituitary adenomas, those with Cushing's disease had an increased risk of transient (22.2%), but not persistent, DI. Patients with a microadenoma were more likely to suffer transient DI than those harboring a macroadenoma (21.6 compared with 14.3%) but were not more likely to experience persistent DI.Diabetes insipidus remains a common complication of transsphenoidal surgery; however, it is most frequently transient in nature. Patients with an intraoperative CSF leak, a microadenoma, a craniopharyngioma, or an RCC appear to have an increased risk of transient DI. Risk factors for persistent DI include an intraoperative CSF leak, a craniopharyngioma, or an RCC.

Sphenoorbital meningiomas (SOMs) are complex tumors involving the sphenoid wing, orbit, and cavernous sinus, which makes their complete resection difficult or impossible. Sphenoidal hyperostosis that results in incomplete resection makes these tumors prone to high rates of recurrence with postoperative morbidity resulting in a nonfunctional globe. High-dose radiation therapy has often been described as the only treatment capable of achieving tumor control, although often at the expense of the patient's progressive visual deterioration.This series consisted of 25 patients who were retrospectively analyzed over a 12-year period. Visual function was evaluated pre- and postoperatively in all patients. A standardized surgical approach to a frontotemporal craniotomy and orbitozygomatic osteotomy with intra- and extradural drilling of the optic canal and all the hyperostotic bone was performed. Orbital and cranial reconstruction was performed in all patients. The follow-up period was 6 months to 12 years (average 5 years). The patients presented with the classic triad of SOM: proptosis (86%), visual impairment (78%), and ocular paresis (20%). A gross-total resection was achieved in 70% of patients with surgery limited by the superior orbital fissure and the cavernous sinus. Proptosis improved in 96% of patients with 87% improvement in visual function. Ocular paresis improved in 68%, although 20% of patients experienced a temporary ocular paresis postoperatively. There were no perioperative deaths or morbidity related to the surgical approach or reconstruction. Ninety-five percent of patients reported an improved functional orbit. There was tumor recurrence in 8% of patients; in one case recurrence was delayed for longer than 11 years.Sphenoorbital meningiomas are a distinct category of tumors complicated by potentially extensive hyperostosis of the skull base. Successful resection requires extensive intra- and extradural surgery, necessitating drilling of the optic canal and an orbital osteotomy within anatomical limitations. The bone resection requires reconstruction with autograft, allografts, or alloplast for improved orbital function. All aspects of the clinical triad improved. A radical resection can be achieved with low morbidity, providing a significantly improved clinical outcome in the long-term period.

Object. Drug delivery across the blood—brain barrier remains a significant challenge. Based on earlier findings, the authors hypothesized that parasympathetic innervation of the brain vasculature could be used to augment drug delivery to the brain. Methods. Using a craniotomy—cerebrospinal fluid superfusate paradigm in rats with an intravenous injection of tracer the authors demonstrated that stimulation of the postganglionic parasympathetic fibers of the sphenopalatine ganglion (SPG) increased the concentration of fluorescein isothiocyanate—dextran (4–250 kD) in the superfusate by two- to sixfold. A histological examination indicated the presence of dextran in the parenchyma. In another experiment the amount of Evans blue dye in the brain following SPG activation was similarly significantly elevated. The chemotherapeutic agents anti-HER2 monoclonal antibody and etoposide were also delivered to the brain and reached therapeutic concentrations. Brain homeostasis was not disturbed by this procedure; a measurement of nicotinamide adenine dinucleotide reduction did not show a decrease in the tissue metabolic state and brain water content did not increase significantly. Conclusions. Sphenopalatine ganglion activation demonstrates a promising potential for clinical use in the delivery of small and large molecules to the brain.

Object. The sphenopetroclival area is the border zone between the middle and posterior cranial fossa. Several authors have studied the microsurgical anatomy of this region and have furnished sometimes contradictory descriptions of this area, which still represents a great challenge for the neurosurgeon. On the basis of previous anatomical data reported in the literature, the authors undertook a new microanatomical analysis of the sphenopetroclival region and report their findings. Methods. Twenty human cadaveric heads were used to reproduce, in the laboratory, different skull base approaches to expose the petroclival area. Measurements were taken in 40 specimens. From this study has emerged the finding that the sphenopetroclival area is a venous space, which the authors have named the “sphenopetroclival venous gulf” (SPCVG). The SPCVG is filled anteriorly by blood from the cavernous sinus (lateral sellar compartment [LSC], medially by blood from the basilar plexus, and laterally by blood from the superior petrosal sinus; this venous gulf is drained by the inferior petrosal sinus. The SPCVG is comparable in shape to an irregular hedron figure. It contains the Dorello canal, the venous segment of the abducent nerve, and the superior sphenopetrosal (Gruber) ligament, the fibers of which are in anatomical continuity with those of the inferior sphenopetrosal (petrolingual) ligament, forming a “falciform ligament.” Conclusions. The structures defining the posterior surface of the SPCVG may represent a helpful surgical corridor through which it is possible to approach the LSC via the posterior fossa. This conceptualization of the SPCVG is an attempt to define univocally the microanatomy of the sphenopetroclival region in its entirety.

Object. Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission. Methods. The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery. The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 µg/dl (83 nmol/L) on postoperative Day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission. Conclusions. Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone—producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD.

✓ Ectopic pituitary adenomas (EPAs) are rare and their association with orthotopic corticotroph hyperplasia has not been published. The case of a 30-year-old woman with clinical and biochemical evidence of Cushing disease (CD) is reported. A magnetic resonance image obtained preoperatively revealed asymmetrical inhomogeneity of the pituitary gland, which was suggestive of localized adenoma. It also showed what was thought to be a small sphenoid polyp. Postoperatively the latter lesion was found to be an ectopic corticotroph adenoma. The pituitary gland, which was free from any tumor, exhibited diffuse unilateral corticotroph hyperplasia. Clinical, radiological, laboratory, and histopathological findings are presented. A review of the literature and a discussion of possible causes of this unique association between the ectopic corticotroph adenoma and the pituitary hyperplasia are provided.

Object. Giant prolactinomas are rare tumors whose treatment and outcome has only been addressed in isolated case reports. The authors document the long-term follow-up findings and clinical outcome in a group of patients with giant prolactinomas. Methods. This study is a retrospective chart and clinical review of more than 2000 cases of pituitary tumors treated at the authors' institution, of which 10 met the criteria for inclusion (prolactin level > 1000 ng/ml, diameter > 4 cm on neuroimaging studies, and clinical signs of hyperprolactinemia/mass effect). The average follow-up duration was 6.7 years after initial treatment with either bromocriptine or transsphenoidal resection. In more than 90% of the patients in this series the disease was controlled by medical treatment with bromocriptine alone; the other 10% required early surgery via transsphenoidal resection. All patients had improvement in visual symptoms. All tumors had extrasellar components, five of which exhibited frank invasion of the cavernous sinus. Tumor volume on magnetic resonance imaging was decreased on average by 69%; this occurred at a faster rate and in larger amounts when treated with bromocriptine than has been reported in the literature for macroprolactinomas. Conclusions. According to long-term follow-up findings, giant prolactinomas are exquisitely responsive to dopamine agonist therapy. In giant prolactinomas the prolactin level does not correlate with size. The main indication for early surgery is intratumoral hematoma, whereas our main indications for late surgery are cerebrospinal fluid leakage caused by medical treatment, or an increasing prolactin level despite medical therapy. Checking prolactin levels in suspicious sellar and/or suprasellar lesions may be diagnostic and prevent unnecessary surgery.

Object. Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of “recurrent” tumors. Methods. Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (≤ 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome. Conclusions. Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.

✓ Internal carotid artery (ICA) pseudoaneurysm formation following transsphenoidal surgery is a rare but potentially lethal complication. Direct surgical repair with preservation of the ICA may be difficult. The feasibility of endovascular coil embolization with parent artery preservation for an iatrogenic ICA pseudoaneurysm is undefined. A 40-year-old man was referred to the authors' institution after identification of a pseudoaneurysm of the left ICA following transsphenoidal resection of a pituitary macroadenoma. The pseudoaneurysm was treated via an endovascular approach that included stent-assisted coil embolization of the lesion. Follow-up angiographic studies obtained 1 year later demonstrated complete occlusion of the aneurysm, and the patient remains asymptomatic. Stent-assisted coil embolization of this iatrogenic pseudoaneurysm was successful in achieving complete, angiographically confirmed aneurysm obliteration, with preservation of the ICA and short-term prevention of hemorrhage or carotid—cavernous fistula. The endovascular method provided an effective, relatively low-risk treatment for this difficult lesion, and was an excellent alternative to direct surgical repair. Nonetheless, long-term follow-up review is required before definitive treatment recommendations can be made.

Object. The aim of this study was to evaluate whether intraoperative magnetic resonance (MR) imaging can increase the efficacy of transsphenoidal microsurgery, primarily in non—hormone-secreting intra- and suprasellar pituitary macroadenomas. Methods. Intraoperative imaging was performed using a 0.2-tesla MR imager, which was located in a specially designed operating room. The patient was placed supine on the sliding table of the MR imager, with the head placed near the 5-gauss line. A standard flexible coil was placed around the patient's forehead. Microsurgery was performed using MR-compatible instruments. Image acquisition was started after the sliding table had been moved into the center of the magnet. Coronal and sagittal T1-weighted images each required over 8 minutes to acquire, and T2-weighted images were obtained optionally. To assess the reliability of intraoperative evaluation of tumor resection, the intraoperative findings were compared with those on conventional postoperative 1.5-tesla MR images, which were obtained 2 to 3 months after surgery. Among 44 patients with large intra- and suprasellar pituitary adenomas that were mainly hormonally inactive, intraoperative MR imaging allowed an ultra-early evaluation of tumor resection in 73% of cases; such an evaluation is normally only possible 2 to 3 months after surgery. A second intraoperative examination of 24 patients for suspected tumor remnants led to additional resection in 15 patients (34%). Conclusions. Intraoperative MR imaging undoubtedly offers the option of a second look within the same surgical procedure, if incomplete tumor resection is suspected. Thus, the rate of procedures during which complete tumor removal is achieved can be improved. Furthermore, additional treatments for those patients in whom tumor removal was incomplete can be planned at an early stage, namely just after surgery.

✓ The authors report two patients with benign fibroosseous lesions involving the center of the skull base: a 15-year-old boy with repetitive meningitis and pneumocephalus and a 11-year-old boy with nasal obstruction and headache. The clinical diagnoses were ossifying fibroma and aneurysmal bone cyst, respectively. Lesions in both patients extended to the nasal cavity, the sphenoid and posterior ethmoid sinuses, and the skull base, where the planum sphenoidale, the sella turcica, the upper two-thirds of the clivus, and the medial portion of the middle cranial base were involved. The lesions were totally removed using an anterior craniofacial approach. Characteristics of these lesions and the surgical approach are discussed.

✓ Sphenopalatine neuralgia is a rare craniofacial pain syndrome that is characterized by unilateral pain in the orbit, mouth, nose, and posterior mastoid process. During attacks of pain, vasomotor activity often results in ipsilateral nasal drainage, eye irritation, and lacrimation. The authors present a patient with a 15-year history of sphenopalatine neuralgia who underwent stereotactic radiosurgery targeted at the sphenopalatine ganglion, with initial pain relief, and repeated radiosurgery 17 months later for partial pain recurrence. Two years following radiosurgery, the patient is pain free, no longer suffering from nasal discharge and eye irritation.

As tumors enlarge, they generally grow along paths of least resistance. For pituitary macroadenomas, extrasellar extension into the suprasellar region, cavernous sinus, or sphenoid sinus may occur. The sphenoid sinus is known to have a variable anatomical configuration, and the authors hypothesize that certain anatomical factors may resist tumor expansion into the sphenoid sinus, thereby directing tumor growth into the suprasellar space. In this paper the authors' goal was to determine if sphenoid anatomy influences pituitary tumor growth.The authors conducted a retrospective analysis of 106 consecutive surgical cases of pituitary macroadenoma. Patient demographics, suprasellar extension, sellar width, and features of the sphenoid intersinus septum were recorded on radiographic review. The chi-square test, t-test, logistic regression, and classification and regression tree analysis were used for statistical analysis.Of the 106 patients included in the study, 71 (67%) demonstrated suprasellar extension of their tumor. Patients with suprasellar tumor extension had significantly greater intersinus septum width (width1.27 mm: OR = 14.32; p = 0.0012) and were significantly older (age54 yrs: OR = 3.33; p = 0.0176). They also tended to be male and to have two or more sphenoid partitions (OR = 6.58; p = 0.0306). While patients with suprasellar extension tended to be more likely to have a midline partition and a larger sellar width than their counterparts, these differences did not reach statistical significance.Certain aspects of the sphenoid sinus anatomy may function to resist pituitary tumor growth into the sphenoid sinus. Progressive enlargement of pituitary macroadenomas may extend in a suprasellar direction, in part, as a consequence of the sphenoid sinus anatomy.

Giant pituitary adenomas (4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique.The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome.Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size, and intraventricular or posterior fossa extension did not influence the surgical outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1-114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up.Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

Endoscopy as a visual aid (endoscope assisted) or as the sole visual method (fully endoscopic) is increasingly used in pituitary adenoma surgery. Authors of this study assessed the value of endoscopic visualization for finding and removing residual adenoma after initial microscopic removal.Consecutive patients who underwent endoscope-assisted microsurgical removal of pituitary adenoma were included in this study. The utility of the endoscope in finding and removing residual adenoma not visualized by the microscope was noted intraoperatively. After maximal tumor removal under microscopic visualization, surgeries were categorized as to whether additional tumor was removed via endoscopy. Tumor removal and remission rates were also noted. Patients undergoing fully endoscopic tumor removal during this same period were excluded from the study.Over 3 years, 140 patients (41% women, mean age 50 years) underwent endoscope-assisted adenoma removal of 30 endocrine-active microadenomas and 110 macroadenomas (39 endocrine-active, 71 endocrine-inactive); 16% (23/140) of patients had prior surgery. After initial microscopic removal, endoscopy revealed residual tumor in 40% (56/140) of cases and the additional tumor was removed in 36% (50 cases) of these cases. Endoscopy facilitated additional tumor removal in 54% (36/67) of the adenomas measuring ≥ 2 cm in diameter and in 19% (14/73) of the adenomas smaller than 2 cm in diameter (p0.0001); additional tumor removal was achieved in 20% (6/30) of the microadenomas. Residual tumor was typically removed from the suprasellar extension and folds of the collapsed diaphragma sellae or along or within the medial cavernous sinus. Overall, 91% of endocrine-inactive tumors were gross-totally or near-totally removed, and 70% of endocrine-active adenomas had early remission.After microscope-based tumor removal, endoscopic visualization led to additional adenoma removal in over one-third of patients. The panoramic visualization of the endoscope appears to facilitate more complete tumor removal than is possible with the microscope alone. These findings further emphasize the utility of endoscopic visualization in pituitary adenoma surgery. Longer follow-ups and additional case series are needed to determine if endoscopic adenomectomy translates into higher long-term remission rates.

Postoperative CSF leakage can be a serious complication after a transsphenoidal surgical approach. An elevated body mass index (BMI) is a significant risk factor for spontaneous CSF leaks. However, there is no evidence correlating BMI with postoperative CSF leak after transsphenoidal surgery. The authors hypothesized that patients with elevated BMI would have a higher incidence of CSF leakage complications following transsphenoidal surgery.The authors conducted a retrospective review of 121 patients who, between August 2005 and March 2010, underwent endoscopic endonasal transsphenoidal surgeries for resection of primarily sellar masses. Patients requiring extended transsphenoidal approaches were excluded. A multivariate statistical analysis was performed to investigate the association of BMI and other risk factors with postoperative CSF leakage.In 92 patients, 96 endonasal endoscopic transsphenoidal surgeries were performed that met inclusion criteria. Thirteen postoperative leaks occurred and required subsequent treatment, including lumbar drainage and/or reoperation. The average BMI of patients with a postoperative CSF leak was significantly greater than that in patients with no postoperative CSF leak (39.2 vs 32.9 kg/m(2), p = 0.006). Multivariate analyses indicate that for every 5-kg/m(2) increase in BMI, patients undergoing a transsphenoidal approach for a primarily sellar mass have 1.61 times the odds (95% CI 1.10-2.29, p = 0.016, by multivariate logistic regression) of having a postoperative CSF leak.Elevated BMI is an independent predictor of postoperative CSF leak after an endonasal endoscopic transsphenoidal approach. The authors recommend that patients with BMI greater than 30 kg/m(2) have meticulous sellar reconstruction at surgery and close monitoring postoperatively.

Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18-36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0-2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10-36 hours after surgery despite prolonged and severe hypercortisolism.

Dural invasion by adrenocorticotropic hormone (ACTH)-secreting adenomas is a significant risk factor for incomplete resection and recurrence in Cushing disease (CD). Since ACTH-producing adenomas are often the smallest of the various types of pituitary tumors at the time of resection, examining their invasion provides the best opportunity to identify the precise sites of early dural invasion by pituitary adenomas. To characterize the incidence and anatomical distribution of dural invasion by ACTH-secreting adenomas, the authors prospectively and systematically analyzed features of dural invasion in patients with CD.The authors prospectively studied consecutive patients with CD undergoing the systematic removal of ACTH-secreting adenoma and histological analysis of the anterior sella dura as well as other sites of dural invasion that were evident at surgery. Clinical, imaging, histological, and operative findings were analyzed.Eighty-seven patients with CD (58 females and 29 males) were included in the study. Overall, dural invasion by an ACTH-positive adenoma was histologically confirmed in 30 patients (34%). Eighteen patients (60% of dural invasion cases, 21% of all patients) had evidence of cavernous sinus wall invasion (4 of these patients also had other contiguous sites of invasion), and 12 patients (40% of dural invasion cases) had invasion of the sella dura excluding the cavernous sinus wall. Eleven patients (13% all patients) had invasion of the routinely procured anterior sella dura specimen. Preoperative MR imaging revealed an adenoma in 64 patients (74%) but accurately predicted dural invasion in only 4 patients (22%) with cavernous sinus invasion and none of the patients with non-cavernous sinus invasion. Adenomas associated with dural invasion (mean ± SD, 10.9 ± 7.8 mm, range 2-37 mm) were significantly larger than those not associated with dural invasion (5.7 ± 2.1 mm, range 2.5-12 mm; p = 0.0006, Mann-Whitney test).Dural invasion by ACTH-producing adenomas preferentially occurs laterally into the wall of the cavernous sinus. Preoperative MR imaging infrequently detects dural invasion, including cavernous sinus invasion. Invasion is directly associated with tumor size. To provide a biochemical cure and avoid recurrence after resection, identification and removal of invaded sella dura, including the medial cavernous sinus wall, are necessary.

A considerable degree of variability exists in the anatomy of the sphenoid sinus, sella turcica, and surrounding skull base structures. The authors aimed to characterize neuroimaging and intraoperative variations in the sagittal and coronal surgical anatomy of healthy controls and patients with sellar lesions.Magnetic resonance imaging studies obtained in 100 healthy adults and 78 patients with sellar lesions were reviewed. The following measurements were made on midline sagittal images: sellar face, sellar prominence, sellar angle, tuberculum sellae angle, sellar-clival angle, length of planum sphenoidale, and length of clivus. The septal configuration of the sphenoid sinus was classified as either simple or complex, according to the number of septa, their symmetry, and their morphological features. The following measurements were made on coronal images: maximum width of the sphenoid sinus and sellar face, and the distance between the parasellar and midclivus internal carotid arteries. Neuroimaging results were correlated with intraoperative findings during endoscopic transsphenoidal surgery.Three sellar floor morphologies were defined in normal adults: prominent (sellar angle of90°) in 25%, curved (sellar angle 90-150°) in 63%, flat (sellar angle150°) in 11%, and no floor (conchal sphenoid) in 1%. In healthy adults, the following mean measurements were obtained: sellar face, 13.4 mm; sellar prominence, 3.0 mm; sellar angle, 112°; angle of tuberculum sellae, 112°; and sellar-clival angle, 117°. Compared with healthy adults, patients with sellar lesions were more likely to have prominent sellar types (43% vs 25%, p = 0.01), a more acute sellar angle (102° vs 112°, p = 0.03), a more prominent sellar floor (3.8 vs 3.0 mm, p0.005), and more acute tuberculum (105° vs 112°, p0.01) and sellar-clival (105° vs 117°, p0.003) angles. A flat sellar floor was more difficult to identify intraoperatively and more likely to require the use of a chisel or drill to expose (75% vs 25%, p = 0.01). A simple sphenoid sinus configuration (no septa, 1 vertical septum, or 2 symmetric vertical septa) was noted in 71% of studies, and the other 29% showed a complex configuration (2 or more asymmetrical septa, 3 or more septa of any kind, or the presence of a horizontal septum). Intraoperative correlation was more challenging in cases with complex sinus anatomy; the most reliable intraoperative midline markers were the vomer, superior sphenoid rostrum, and bilateral parasellar and clival carotid protuberances.Preoperative assessment of neuroimaging studies is critical for characterizing the morphological characteristics of the sphenoid sinus, sellar floor, tuberculum sellae, and clivus. The flat sellar type identified in 11% of people) or a complex sphenoid sinus configuration (in 29% of people) may make intraoperative correlation substantially more challenging. An understanding of the regional anatomy and its variability can improve the safety and accuracy of transsphenoidal and extended endoscopic skull base approaches.

Over the last several years minimally invasive surgical approaches to the sella turcica and parasellar regions have undergone significant change. The transsphenoidal approach to this region has evolved from a sublabial transnasal, to transnasal, to pure endonasal approaches with the increasing popularity of endoscopic over microscopic techniques. Endoscopic and microscopic techniques individually or in combination have their own unique advantages, and the preference of one over the other awaits further technological refinements and surgical experience. In parallel with this evolution in techniques for transsphenoidal surgery, the authors designed an adaptable versatile speculum for the endonasal/transnasal transsphenoidal approach to the sella turcica and parasellar regions that can be used equally effectively with a microscope or an endoscope. The development of this instrument and its unique features are described, and its initial clinical use is summarized. This transnasal transsphenoidal speculum has interchangeable blades, unique blade angulations, and independent blade opening mechanisms and allows safe, optimal exposure in all patients regardless of the size and anatomical aberrations of individual nasal and endonasal regions. An attached endoscope carrier further allows it to be used interchangeably with microscopic or endoscopic techniques without having to remove the speculum; likewise, a single surgeon can use both hands without need of an assistant. A forehead headrest component adds further stabilization. This device has been used successfully in 90 transsphenoidal procedures.

The transcranial approach has been the standard technique for removal of craniopharyngiomas for several decades. However, many reports of successful suprasellar craniopharyngioma removal accomplished using extended transsphenoidal surgery (TSS) have recently been published. In the present study, the authors describe their technique and the outcomes of removal of suprasellar craniopharyngiomas aided by the use of an operating microscope and an endoscope concurrently during extended TSS.Between 1999 and 2008, 18 patients with suprasellar craniopharyngiomas underwent TSS. Tumors that adhered to the optic nerve were safely dissected, and fine perforating vessels were precisely preserved with the aid of a magnified, detailed microscopic view. Portions of the tumor that could not be properly visualized with the microscope were visualized with the endoscope.Total resection was achieved in all patients, and all visual symptoms improved. Preoperative hypopituitarism improved in 2 patients but persisted postoperatively in 15 patients (hormonal outcome was not available in 1 patient). Diabetes insipidus was present in 16 patients postoperatively. Cerebrospinal fluid leakage developed in 3 patients in the conventional fascia lata graft group, whereas no CSF leakage occurred after the dural suture technique with a fascia lata graft was introduced. This technique could be more precisely applied when using a microscopic view. Tumor recurrence was documented for 1 patient 2 years after surgery.The authors achieved good results by using extended TSS for the removal of suprasellar craniopharyngiomas. Endoscopy-assisted microscopic extended TSS harnesses the advantages of a microscope as well as those of an endoscope. Surgeons should consider using the advantages of both surgical modalities to achieve the best result possible.

Rathke cleft cysts (RCCs) are benign lesions that can be diagnosed as an incidental finding associated with headaches, pituitary dysfunction, or vision deterioration. Typically, they occur in a sellar or suprasellar location. The aim of this study was to review the clinical presentation and outcomes associated with endoscopic endonasal resection of these lesions.The authors retrospectively reviewed a series of 35 patients with a diagnosis of RCC after endoscopic endonasal resection at the University of Pittsburgh between January 1998 and July 2008.All 35 patients underwent a purely endoscopic endonasal approach (EEA). The average patient age was 34 years (range 12-67 years), and the average follow-up was 19 months (range 1-60 months). Clinical follow-up data were available for 32 patients, and radiographic follow-up data were accessible for 33 patients. All of the patients underwent complete removal of the cyst contents, and according to radiography studies 2 patients had a recurrence, neither of which required reoperation. The mean cyst volume was 1052.7 mm(3) (range 114-6044 mm(3)). Headache was a presenting symptom in 26 (81.2%) of 32 patients, with 25 (96.1%) of 26 having postoperative improvement in their headaches. Fifteen (57.7%) of the 26 patients had complete pain resolution, and 10 (38.5%) had a50% reduction in their pain scores. Six (18.8%) of 32 patients initially presented with pituitary dysfunction, although 2 (33.3%) had postoperative improvement. Three (9.4%) of 32 patients had temporary pituitary dysfunction postoperatively, although there was no permanent pituitary dysfunction. Neither were there any intraoperative complications, postoperative CSF leaks, or new neurological deficits. The average hospital stay was 1.8 days (range 1-5 days).The EEA is a safe and effective approach in the treatment of RCCs. None of the patients in this study experienced any worsening of their preoperative symptoms or pituitary function, and 96% of the patients who had presented with headache experienced complete or significant pain relief following treatment.

The endoscopic endonasal approach has become the preferred technique for CSF leak and encephalocele repair of the anterior skull base. The purpose of this study is to identify patient characteristics; review adjunctive perioperative treatments, reconstruction techniques, and outcomes; and identify risk factors for failure in patients undergoing endoscopic endonasal repair of anterior skull base CSF leaks and encephaloceles.This is a prospective observational study of patients undergoing endoscopic endonasal repair of a CSF leak between October 2004 and May 2009. Twenty-eight consecutive patients underwent 32 procedures. Twenty-two of the patients were women, which represents a statistically significant trend toward the female sex (p0.05). The average body mass index (33.9) was significant for obesity. The origin of the skull base defect included the cribriform plate (in 9 cases), fovea ethmoidalis (in 7), combined fovea ethmoidalis/cribriform plate (in 2), lateral sphenoid sinus (in 6), sella (in 4), clivus (in 3), and frontal sinus (in 1).The overall endonasal closure rate was 93.8% (30 of 32 procedures). One failure occurred due to overaggressive postoperative debridement, while the other recurred along the posterior wall of the frontal sinus, and endoscopic repair would have occluded the recess.The endoscopic endonasal approach for the treatment of CSF leaks and encephaloceles of the anterior skull base is the preferred method of repair in the vast majority of cases. The authors' 93.8% closure rate in a variety of anatomical locations compares favorably with the transcranial approach and echoes the results of other endoscopic series.

Cerebrospinal fluid leaks may occur as a result of trauma or following surgery, and occasionally may also be spontaneous. Leakage of CSF from the lateral sphenoid recess is rare and challenging to treat. The authors present their experience with repairs of 10 CSF leaks that were confined to the lateral sphenoid recess and were treated at the Singapore General Hospital.A retrospective chart review was conducted for all patients who underwent operations for lateral sphenoid recess CSF leaks between 2001 and 2008.Ten repairs were performed in 8 patients by using a transpterygoid approach, with a 90% success rate. In 3 cases the transcranial approach had failed prior to endoscopic repair. "Sandwich reconstruction" under direct vision was performed in all cases, and was completed using cartilage or bone as a rigid support.This series demonstrates that CSF leakage can be managed safely and effectively by using an endoscopic transpterygoid approach in patients in whom both external and endoscopic attempts have failed. The transpterygoid approach used in all of the cases in this series provides wide exposure around the skull base defect, which is crucial for successful repair.

Pituitary adenomas represent a large proportion of brain tumors that are increasing in incidence because of improved imaging techniques. Headache is the primary symptom in patients with large tumors (macroadenomas), but is also a symptom in patients with small tumors (microadenomas, tumors1.0 cm). The prevalence and optimal treatment of headaches associated with pituitary tumors is still unclear, particularly in cases of microadenoma. If conventional medical management fails, transsphenoidal surgery (TSS) may be considered as an alternative treatment for intractable headaches.The authors conducted a retrospective review of 512 patients who underwent TSS at Oregon HealthScience University between 2001 and 2007; patients with Cushing disease were excluded. The authors identified 41 patients with small pituitary tumors who underwent TSS, and retrospectively evaluated the resolution and/or treatment of headache.Ninety percent of patients who presented with nonfunctioning microadenomas and Rathke cleft cysts experienced resolution or improvement in their headaches after TSS, and 56% of patients who presented with hyperfunctioning pituitary microadenomas had improvement in their headaches. There were no postoperative complications.In this retrospective study, the authors demonstrate the efficacy of TSS in the treatment of intractable headaches in patients who present with pituitary microadenomas (nonsecreting and hypersecretory) and Rathke cleft cysts.

Midline clival lesions, whether involving the clivus or simply situated anterior to the brainstem, present a technical challenge for adequate exposure and safe resection. The authors describe, as a minimally invasive technique, an anterior clivectomy performed via an expanded transsphenoidal approach coupled with the use of a neuronavigation on mobile head and endoscopic-assisted technique. Wide and direct exposure, with the ability to resect extra- and intradural tumors, was achieved without mortality and with a low rate of complications.Cadaveric dissections were performed to outline the landmarks and measure the window that is created by resecting the clivus anteriorly. The technique was used in 43 patients to resect tumors located at or invading the clivus. The initial exposure of the clivus was obtained via the sublabial transsphenoidal approach. The wall of the anterior maxilla, often on 1 side, was removed to allow a wide side-to-side opening of the nasal speculum. Using neuronavigation, the authors made clivectomy windows by drilling the clivus between anatomical landmarks. Bilateral intraoperative neurophysiological monitoring was used (somatosensory evoked potentials, brainstem auditory evoked responses, and cranial nerves VI-XII).Of the 43 patients, 26 were female and 17 were male, and they ranged in age from 3.5 to 76 years (mean 41.5 years). Thirty-eight patients harbored a chordoma and 5 a giant invasive pituitary adenoma. Gross-total resection of the tumor was achieved in 34 cases (79%). Nine patients (21%) had residual tumor unreachable through the anterior clivectomy, and this required a second-stage resection. Four patients developed new transient extraocular movement deficits. One patient developed a permanent cranial nerve VI palsy. Twenty-seven patients with chordoma underwent postoperative proton-beam radiotherapy. Tumor recurred in 19% of these cases. In 3 patients a cerebrospinal fluid leak developed during hospitalization and was treated successfully. Two other patients presented with a delayed cerebrospinal fluid leak after radiotherapy. Only 1 patient, who had previously undergone Gamma Knife surgery, experienced postoperative hemiparesis.A complete anterior clivectomy via a simple extension of the transsphenoidal approach allows the surgeon access to different lesions involving the clivus or situated anterior to the brainstem. The exposure is similar to that provided by more extensive transfacial approaches. Instrument manipulation is easy. Neuronavigation, endoscopy, and intraoperative monitoring are easily incorporated and enhance the capability and safety of this approach.

Object The authors compare the views afforded by the operating microscope and the endoscope in the direct endonasal extended transsphenoidal approach to the sellar, suprasellar, and parasellar regions. Methods Five formalin-fixed, silicone-injected adult cadaveric heads were studied. A direct endonasal transsphenoidal approach was performed via the right nostril, pushing aside the nasal septum. The approach was performed with the microscope first, then with the endoscope. For each step (sellar, suprasellar, and clival), the exposure afforded by direct microscopic view was measured and then compared with that obtained using the endoscope. The direct endonasal approach provides a slightly off-midline view. Although the microscope provides an adequate view of the mid-line structures and part of the contralateral parasellar areas, the addition of the endoscope allows for a more panoramic view and permits widening of the approach in all directions. Conclusions An adequate exposure of the sellar, suprasellar, and infrasellar/upper clival regions can be achieved via a simple, direct endonasal approach. From a direct endonasal route, there is a preferential visualization of the structures contralateral to the approach. The endoscope affords a more panoramic view that extends the area covered by the operating microscope.

✓ The authors describe a case of carotid-cavernous fistula that was not treatable by the standard interventional neuroradiological techniques of transarterial or transvenous occlusion of the fistula because access was blocked by prior trapping procedures. Access to the venous side of the fistula was gained by means of a transethmoidal transsphenoidal exposure, making it possible to embolize the lesion with coils. The details of this approach are described.