The oculomotor cistern and pituitary adenomas: anatomical and clinical study

J Neurosurg 142:766–776, 2025

Study Focus: The research investigates the oculomotor cistern (OMC) and its involvement with pituitary adenomas (PitNETs), aiming to provide a histomorphological description and analyze its clinical impact.

Methods: Ten hemisellae from formalin-fixed specimens were studied, and clinical data from patients undergoing endoscopic transsphenoidal surgery for PitNETs between 2014 and 2021 were analyzed.

Results: OMC involvement was graded as not compressed, compressed, and invaded. Significant associations were found between OMC involvement and PitNET dimensions, Knosp grade, and preoperative oculomotor palsy.

OMC Shape and Measurements: The OMC is elliptical with an average area of 3.1 mm² and a length of 5.5 mm. No points of weakness were identified in the histomorphological study.

Clinical Findings: OMC compression and invasion were recorded in 43.1% and 9.3% of patients, respectively. Preoperative CN III palsy was documented in compressed (11.3%) and invasive (26.1%) OMCs.

Surgical Implications: Endoscopic transsphenoidal surgery is effective in treating PitNETs with OMC involvement, though the choice between transcranial and endoscopic approaches remains debated.

Histological Observations: The study confirmed the OMC’s extension ends before the anterior clinoid process (ACP), with potential points of weakness at the CS roof and MWCS.

Conclusion: OMC involvement is significant in PitNETs, affecting patient outcomes. Detailed preoperative evaluation and postoperative follow-up are crucial for managing these cases.

Morphological Classification of Pituitary Tumors With Suprasellar Extension

Neurosurgery 94:1183–1190, 2024

The objective of this study was to study the association among various morphological parameters and surgical outcomes in pituitary macroadenomas with suprasellar extension.

METHODS: MRI studies of 160 patients undergoing endoscopic transsphenoidal resection of pituitary macroadenomas with suprasellar extension were reviewed. In the coronal plane, tumors were classified into Type 1 (dome-shaped, no constriction at the level of diaphragma sellae) and Type 2 (dumbbell-shaped, with constriction at the level of diaphragma sellae). Based on the dome-to-neck ratio (D/Nr), Type 2 tumors were further classified as Type 2A (wide neck; D/Nr >1 and <1.3) and Type 2B (narrow neck; D/Nr ≥1.3). Surgical outcomes and complications were analyzed using a logistic regression model. Overall extent of resection (EOR) and presence of residual sellar-suprasellar tumor was separately assessed in all patients with available postoperative MRI (n = 149).

RESULTS: There were 108 Type 1 tumors and 26 patients each in the Type 2A and Type 2B subgroups. Tumor subtype was significantly associated with tumor size (P < .001), intraoperative cerebrospinal fluid leak (P < .001), EOR (P < .001), postoperative suprasellar residual tumor (P < .001), and postoperative complications, including diabetes insipidus (P = .005) and visual worsening (P = .003). On multivariate analysis, after adjusting for confounders, Type 2B tumors were negatively associated with EOR (odds ratio [OR] 0.22; 95% CI 0.07-0.68; P = .008) and associated with the presence of postoperative suprasellar residual tumor (OR 18.08; 95% CI 5.20-62.89; P < .001), intraoperative cerebrospinal fluid leak (OR 5.33; 95% CI 1.89-14.99; P = .002), and postoperative diabetes insipidus (OR 4.89; 95% CI 1.67-14.35; P < .001).

CONCLUSION: Preoperative tumor classification based on D/Nr is clinically and surgically relevant, and Type 2B macroadenomas are significantly associated with lower rates of gross total resection and higher rates of postoperative complications after endoscopic transsphenoidal resection.

The “candy wrapper” of the pituitary gland: a road map to the parasellar ligaments and the medial wall of the cavernous sinus

Acta Neurochirurgica (2023) 165:3431–3444

The anatomy of the medial wall of the cavernous sinus (MWCS) and parasellar ligaments (PLs) has acquired increasing importance in endoscopic endonasal (EE) surgery of the cavernous sinus (CS), including resection of the MWCS in functioning pituitary adenomas (FPAs). Although anatomical studies have been published, it represents a debated topic due to their complex morphology. The aim is to offer a description of the PLs that originate from the MWCS and reach the lateral wall of the cavernous sinus (LWCS), proposing the “candy wrapper” model. The relationships between the neurovascular structures and histomorphological aspects were investigated.

Methods Forty-two CSs from twenty-one human heads were studied. Eleven specimens were used for EE dissection; five underwent a microscopic dissection. Five specimens were used for histomorphological analysis.

Results Two groups of PLs with a fan-shaped appearance were encountered. The anterior group included the periosteal ligament (55% sides) and the carotico-clinoid complex (100% sides), formed by the anterior horizontal and the carotico-clinoid ligaments. The posterior group was formed by the posterior horizontal (78% sides), and the inferior hypophyseal ligament (34% sides). The periosteal ligament originated inferiorly from the MWCS, reaching the periosteal dura. The anterior horizontal ligament was divided in a superior and inferior branch. The superior one continued as the carotid-oculomotor membrane, and the inferior branch reached the CN VI. The carotico-clinoid ligament between the middle and anterior clinoid was ossified in 3 sides. The posterior horizontal ligament was related to the posterior genu and ended at the LWCS. The inferior hypophyseal ligament followed the homonym artery. The ligaments related to the ICA form part of the adventitia. Conclusion The “candy wrapper” model adds further details to the previous descriptions of the PLs. Understanding this complex anatomy is essential for safe CS surgery, including MWCS resection for FPAs.

Formation of internal carotid artery aneurysms following gamma knife radiosurgery for pituitary adenomas

Acta Neurochirurgica (2023) 165:2257–2265

Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far.

Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic.

The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought.

Dumbbell-shaped pituitary adenomas: prognostic factors for prediction of tumor nondescent of the supradiaphragmal component from a multicenter series

J Neurosurg 137:609–617, 2022

Dumbbell-shaped pituitary adenomas (DSPAs) are a subgroup of macroadenomas with suprasellar extension that are characterized by a smaller diameter at the level of the diaphragma sellae opening compared with the supradiaphragmal tumor component (SDTC). Hence, DSPAs may be particularly prone to a nondescending suprasellar tumor component and risk for residual tumor or postoperative bleeding.

METHODS A multicenter retrospective cohort analysis of 99 patients with DSPA operated on via direct endoscopic endonasal transsphenoidal approach between 2011 and 2020 was conducted. Patient recruitment was performed at two tertiary care centers (Medical University of Vienna and University of Southern California) with expertise in endoscopic skull base surgery. DSPA was defined as having a smaller diameter at the level of the diaphragma sellae compared with the SDTC.

RESULTS On preoperative MRI, all DSPAs were macroadenomas (maximum diameter range 17–71 mm, volume range 2–88 cm 3 ). Tumor descent was found in 73 (74%) of 99 patients (group A), and nondescent in 26 (26%) of 99 patients (group B) intraoperatively. DSPAs in group A had a significantly smaller diameter (30 vs 42 mm, p < 0.001) and significantly smaller volume (10 vs 22 cm 3 , p < 0.001) than those in group B. The ratio of the minimum area at the level of the diaphragmal opening in comparison with the maximum area of the suprasellar tumor component (“neck-to-dome area”) was significantly lower in group A than in group B (1.7 vs 2.7, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.75 (95% CI 0.63–0.87). At a cutoff ratio of 1.9, the sensitivity and specificity for a nondescending suprasellar tumor component were 77% and 34%, respectively.

CONCLUSIONS In the present study, the neck-to-dome area ratio was of prognostic value for prediction of intraoperative tumor nondescent in DSPAs operated on via a direct endonasal endoscopic approach. Pituitary adenoma SDTC nondescent carried the inherent risk of hemorrhagic transformation in all cases.

Evaluation of early postoperative day 1 discharge after endoscopic endonasal pituitary adenoma resection

J Neurosurg 136:1337–1346, 2022

While multiple studies have evaluated the length of stay after endonasal transsphenoidal surgery (ETS) for pituitary adenoma, the potential for early discharge on postoperative day 1 (POD 1) remains unclear. The authors compared patients discharged on POD 1 with patients discharged on POD > 1 to better characterize factors that facilitate early discharge after ETS.

METHODS A retrospective chart review was performed for patients undergoing ETS for pituitary adenoma at a single tertiary care academic center from February 2005 to February 2020. Discharge on POD 1 was defined as a discharge within 24 hours of surgery.

RESULTS A total of 726 patients (mean age 55 years, 52% male) were identified, of whom 178 (24.5%) patients were discharged on POD 1. These patients were more likely to have pituitary incidentaloma (p = 0.001), require dural substitutes and DuraSeal (p = 0.0001), have fewer intraoperative CSF leaks (p = 0.02), and have lower postoperative complication rates (p = 0.006) compared with patients discharged on POD > 1. POD 1 patients also showed higher rates of macroadenomas (96.1% vs 91.4%, p = 0.03) and lower rates of functional tumors (p = 0.02). POD > 1 patients were more likely to have readmission within 30 days (p = 0.002), readmission after 30 days (p = 0.0001), nasal synechiae on follow-up (p = 0.003), diabetes insipidus (DI; 1.7% vs 9.8%, p = 0.0001), postoperative hypocortisolism (21.8% vs 12.1%, p = 0.01), and postoperative steroid usage (44.6% vs 59.7%, p = 0.003). The number of patients discharged on POD 1 significantly increased during each subsequent time epoch: 2005–2010, 2011–2015, and 2016–2020 (p = 0.0001). On multivariate analysis, DI (OR 7.02, 95% CI 2.01–24.57; p = 0.002) and intraoperative leak (OR 2.02, 95% CI 1.25–3.28; p = 0.004) were associated with increased risk for POD > 1 discharge, while operation epoch (OR 0.46, 95% CI 0.3–0.71; p = 0.0001) was associated with POD 1 discharge.

CONCLUSIONS This study demonstrates that discharge on POD 1 after ETS for pituitary adenomas was safe and feasible and without increased risk of 30-day readmission. On multivariate analysis, surgical epoch was associated with decreased risk of prolonged length of stay, while factors associated with increased risk of prolonged length of stay included DI and intraoperative CSF leak. These findings may help in selecting patients who are deemed reasonable for safe, early discharge after pituitary adenoma resection.

Diabetes Insipidus After Endoscopic Transsphenoidal Surgery

Neurosurgery 2020 DOI:10.1093/neuros/nyaa148

Diabetes insipidus (DI) is a recognized transient or permanent complication following transsphenoidal surgery (TSS) for pituitary tumors.

OBJECTIVE: To describe significant experience with the incidence of DI after TSS, identifying predictive characteristics and describing our diagnosis and management of postoperative DI.

METHODS: A retrospective analysis was performed of 700 patients who underwent endoscopic TSS for resection of pituitary adenoma (PA), Rathke cleft cyst (RCC), or craniopharyngioma. Inclusion criteria included at least 1 wk of follow-up for diagnosis of postoperative DI. Permanent DI was defined as DI symptoms and/or need for desmopressinmore than 1 yr postoperatively. All patients with at least 1 yr of follow-up (n=345) were included in analyses of permanent DI. Multivariable logistic regression models were constructed to identify predictors of transient or permanent postoperative DI.

RESULTS: The overall rate of any postoperative DI was 14.7% (103/700). Permanent DI developed in 4.6% (16/345). The median follow-up was 10.7mo (range: 0.2-136.6). Compared to patients with PA, patients with RCC (odds ratio [OR] = 2.2, 95% CI: 1.2-3.9; P = .009) and craniopharyngioma (OR = 7.0, 95% CI: 2.9-16.9; P ≤ .001) were more likely to develop postoperative DI. Furthermore, patients with RCC (OR = 6.1, 95% CI: 1.8-20.6; P = .004) or craniopharyngioma (OR = 18.8, 95% CI: 4.9-72.6; P ≤ .001) were more likely to develop permanent DI compared to those with PA.

CONCLUSION: Although transient DI is a relatively common complication of endoscopic and microscopic TSS, permanent DI is much less frequent. The underlying pathology is an important predictor of both occurrence and permanency of postoperative DI.

 

 

Quantitative assessment of secondary white matter injury in the visual pathway by pituitary adenomas: a multimodal study at 7-Tesla MRI

J Neurosurg 132:333–342, 2020

The objective of this study was to investigate microstructural damage caused by pituitary macroadenomas by performing probabilistic tractography of the optic tracts and radiations using 7-T diffusion-weighted MRI (DWI). These imaging findings were correlated with neuro-ophthalmological results to assess the utility of ultra–high-field MRI for objective evaluation of damage to the anterior and posterior visual pathways.
METHODS Probabilistic tractography employing 7-T DWI was used to reconstruct the optic tracts and radiations in 18 patients with adenomas and in 16 healthy volunteers. Optic chiasm compression was found in 66.7% of the patients and visual defects in 61.1%. Diffusion indices were calculated along the projections and correlated with tumor volumes and
results from neuro-ophthalmological examinations. Primary visual cortical thicknesses were also assessed.

RESULTS Fractional anisotropy was reduced by 21.9% in the optic tracts (p < 0.001) and 17.7% in the optic radiations (p< 0.001) in patients with adenomas. Patients showed an 8.5% increase in mean diffusivity of optic radiations compared with healthy controls (p < 0.001). Primary visual cortical thickness was reduced in adenoma patients. Diffusion indices of
the visual pathway showed significant correlations with neuro-ophthalmological examination findings.
CONCLUSIONS Imaging-based quantification of secondary neuronal damage from adenomas strongly correlated with neuro-ophthalmological findings. Diffusion characteristics enabled by ultra–high-field DWI may allow preoperative characterization of visual pathway damage in patients with chiasmatic compression and may inform prognosis for vision
recoverability.

Complications associated with microscopic and endoscopic transsphenoidal pituitary surgery: experience of 1153 consecutive cases treated at a single tertiary care pituitary center

J Neurosurg 130:1576–1583, 2019

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

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

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

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

 

Endoscopic endonasal transoculomotor triangle approach for adenomas invading the parapeduncular space

J Neurosurg 130:1304–1314, 2019

Pituitary adenomas may extend into the parapeduncular space by invading through the roof of the cavernous sinus. Currently, a transcranial approach is the preferred choice, with or without the combination of an endonasal approach. In this paper the authors present a novel surgical approach that takes advantage of the natural corridor provided by the tumor to further open the oculomotor triangle and resect tumor extension into the parapeduncular space.

METHODS Six injected specimens were used to demonstrate in detail the surgical anatomy related to the approach. Four cases in which the proposed approach was used were retrospectively reviewed.

RESULTS From a technical perspective, the first step involves accessing the superior compartment of the cavernous sinus. The interclinoid ligament should be identified and the dura forming the oculomotor triangle exposed. The oculomotor dural opening may be then extended posteriorly toward the posterior petroclinoidal ligament and inferolaterally toward the anterior petroclinoidal ligament. The oculomotor nerve should then be identified; in this series it was displaced superomedially in all 4 cases. The posterior communicating artery should also be identified to avoid its injury. In all 4 cases, the tumor invading the parapeduncular space was completely removed. There were no vascular injuries and only 1 patient had a partial oculomotor nerve palsy that completely resolved in 2 weeks.

CONCLUSIONS The endoscopic endonasal transoculomotor approach is an original alternative for removal of tumor extension into the parapeduncular space in a single procedure. The surgical corridor is increased by opening the dura of the oculomotor triangle and by working below and lateral to the cisternal segment of the oculomotor nerve.

 

Fully endoscopic combined transsphenoidal and supraorbital keyhole approach for parasellar lesions

J Neurosurg 128:685–694, 2018

Parasellar 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.

METHODS A 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.

RESULTS A 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.

CONCLUSIONS In 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.

 

Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

J Neurosurg 124:596–604, 2016

The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients.

Methods Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR.

Results Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm3 vs 0.20 cm3, p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different.

Conclusions A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm3. The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing’s disease

Cushing's disease

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing’s disease (CD).

Method We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 μg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery.

Results Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n=15), enlarged adenomectomy (n=21) and subtotal/hemihypophysectomy (n=17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 μg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6–18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 μg/dl in the 1st week after surgery was highly predictive of remission (p=0.001).

Conclusion ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

J Neurosurg 121:1166–1175, 2014

The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA.

Methods. Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible.

Results. Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years.

Conclusions. The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.

MicroRNAs as Biomarkers in Pituitary Tumors

MicroRNAs_as_Biomarkers_in_Pituitary_Tumors

Neurosurgery 75:181–189, 2014

The use of extracellular microRNAs (miRNAs) as circulating biomarkers is currently leading to relevant advances in the diagnosis and assessment of prognosis of several diseases.

Specific miRNAs have also been shown to play a role in the pathophysiology of many neoplastic and non-neoplastic diseases. A number of studies have demonstrated that miRNAs show differential expression in various tumors, such as in the prostate, ovary, lung, breast, brain, and pituitary.

Recent findings have built connections between miRNAs that are deregulated within the tumor and their presence in peripheral blood. MiRNAs have been shown to be stable in the blood where they are present in either free and/or uncomplexed form, as well as packed in microvesicles, exosomes, and apoptotic bodies, or bound to different proteins.

Because the pituitary is a highly vascularized organ that releases hormones into the circulation, miRNAs would be useful biomarkers for the diagnosis of pituitary tumors, as well as for predicting or detecting recurrence after surgery.

Here we review the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.

Avoidance of postoperative epistaxis and anosmia in endonasal endoscopic skull base surgery

Avoid anosmia and epistaxis in EEA

Acta Neurochir (2014) 156:1393–1401

Most endoscopic transsphenoidal approaches jeopardize the sphenopalatine artery and septal olfactory strip (SOS), increasing the risk of postoperative anosmia and epistaxis while precluding the ability to raise pedicled nasoseptal flaps (NSF). We describe a bilateral “rescue flap” technique that preserves the mucosa containing the nasal-septal vascular pedicles and the SOS. This approach can reduce the risk of postoperative complications, including epistaxis and anosmia.

Methods A retrospective analysis was conducted of all patients who underwent endoscopic transsphenoidal surgery with preservation of both sphenopalatine vascular pedicles and SOS. In a recent subset of patients, olfactory assessment was performed.

Results Of 174 consecutive operations performed in 161 patients, bilateral preservation of the sphenopalatine vascular pedicle and SOS was achieved in 139 (80 %) operations, including 31 (22 %) with prior transsphenoidal surgery. Of the remaining 35 operations, 18 had a planned formal NSF and 17 had prior surgery or extensive lesions precluding use of this technique. Of pituitary adenomas, RCCs or sellar arachnoid cysts, 118 (94 %) underwent this approach, including 91% of patients who had prior surgery. Preoperative olfaction function was maintained in 97 % of patients that were tested. None of the patients had postoperative arterial epistaxis.

Conclusion Preservation of bilateral sphenopalatine vascular pedicles and the SOS is feasible in over 90 % of patients undergoing endonasal endoscopic surgery for pituitary adenomas and RCCs. This approach, while not hindering exposure or limiting instrument maneuverability, preserves the nasoseptal vasculature for future NSF use if needed and appears to minimize the risks of postoperative arterial epistaxis and anosmia.

Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older

Pituitary adenomas patients aged 80

Neurosurg Rev (2014) 37:269–277

To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated.

From1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima and Hiroshima University hospitals in Japan. Ten (1.1 %) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients.

The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2–3 on American Society of Anesthesiologists’ Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered.

Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients’ general condition is well preserved and pituitary hormonal deficiency is adequately replaced.

The value of immediate postoperative MR imaging following endoscopic endonasal pituitary surgery

The value of immediate postoperative MR imaging following endoscopic endonasal pituitary surgery

Acta Neurochir (2014) 156:133–140

Although the value of early MR imaging has been justified for microscopic transphenoidal surgery, there is no literature evaluating immediate postoperative MR imaging following endoscopic endonasal resection of pituitary adenomas. We hypothesized that MRI of the pituitary gland performed on the first postoperative day is just as effective at detecting residual disease and/or reconstruction materials as the MRI at 3 months following surgery.

Methods We retrospectively evaluated 102 consecutive patients who underwent endoscopic endonasal surgery for presumed pituitary adenomas. Sixty-four patients met the inclusion criteria with immediate and 3 months MR imaging. Imaging was evaluated by two sets of observers. The following parameters were assessed: enhancement pattern of the pituitary gland, pituitary stalk, nodular enhancement (residual tumor) or linear enhancement (non-tumoral) and residual reconstruction/packing materials.

Results Gross total resection of the tumors with no cavernous sinus involvement was achieved in 49 out of 52 (94 %) patients. Eleven out of 12 remaining patients with cavernous sinus invasion had residual cavernous sinus component visible on both immediate and 3 month MR imaging. The pituitary gland, position of stalk, and nasoseptal flap could be identified on both post-operative MRIs in all patients. The sensitivity and specificity for residual tumor detection on immediate MRI was 100 % and 97.9 %, respectively. The kappa index evaluating interobserver agreement for identification of residual tumor and packing/reconstruction material on immediate MR was 0.83 and 0.72 indicating near perfect and substantial agreement, respectively.

Conclusion Immediate MR imaging performed following endoscopic endonasal resection of pituitary lesions provides accurate and reliable information regarding the presence of residual tumor compared to reconstruction and packing materials.

Early promising results for the endoscopic surgical treatment of Cushing’s disease

Endoscopic treatment of Cushing's disease

Neurosurg Rev (2014) 37:105–114

High levels of endogenous cortisol due to Cushing’s disease cause significant mortality and morbidity. Treatment of Cushing’s disease is challenging. For many years, transsphenoidal microsurgical resection of the adenoma has been the treatment of choice. However, recently, neuroendoscope has taken its place in the neurosurgeon’s armamentarium, and the endoscopic transsphenoidal resection of pituitary tumors has become a familiar approach.

Our aim was to present the results of pure endoscopic surgery in the treatment of corticotropinomas for comparison with the results of previous endoscopic and microsurgical series.

We present a retrospective analysis of 90 patients with diagnosis of Cushing’s disease who were operated between 2006 and 2012. Among 90 patients, a total of 81 (90.0%) had a remission (28 out of 29 macroadenomas (96.6 %) and 53 out of 61 microadenoma patients (86.9 %)). Of note is that 66 out of 69 (95.7 %) primary patients (i.e., those who were operated in our center) and 15 out of 21 (71.4 %) patients previously operated in other centers reached a hypo/eucortisolemic state. A remission rate comparable with previous endoscopic series was achieved. In nine patients, it was not possible to achieve remission at all. On the other hand, only four of our cases (5.6%) had a recurrence, andwith reoperation, all of these patients entered a re-remission. To our knowledge, our series is the largest series studying endoscopically operated adrenocorticotropic hormone-secreting adenomas. Our results suggest that the endoscopic approach has opened a new avenue in the treatment of Cushing’s disease, previously a therapeutic challenge for both the clinician and the neurosurgeon.

Endoscopic approach in the treatment of Cushing’s disease is clearly better for patients because of its low morbidity rates and short duration of hospital stay. On the other hand, long-term follow-up of our patients will show whether these favorable observations will persist.

Treatment of acromegaly by endoscopic transsphenoidal surgery

Treatment of acromegaly by endoscopic transsphenoidal surgery

J Neurosurg 119:1467–1477, 2013

Acromegaly is a disease that has significant morbidity and mortality related to high levels of growth hormone (GH) and insulin-like growth factor–I (IGF-I), and is usually caused by pituitary adenomas. The goal in this study was to investigate the role of endoscopic transsphenoidal surgery and surgical experience in the treatment of GH adenoma cases in relation to surgical results and hormonal cure rates, and to perform a review of the literature.

Methods. The authors present a retrospective analysis of 214 GH adenoma cases. Restoration of IGF-I levels to normal for age and sex, suppression of GH levels below 0.4 μg/L on the oral glucose tolerance test, and demonstration of the total removal of the tumor on MRI studies obtained after administration of contrast material at the 3-month postoperative follow-up visit were the criteria for cure.

Results. In total 214 patients with a mean age of 41.9 ± 12 years (range 17–75 years) and a male/female ratio of 106/108 were enrolled in the study. Cure was achieved in 134 (62.6%) of 214 patients. One hundred sixty-nine patients were primary cases, and of these 109 (64.5%) were cured, whereas 61 patients were previously operated cases and of these 25 (41%) were cured. With a 51.1% decrease in the 1st month postoperatively, IGF-I levels were found to be predictive of cure (74.4% sensitivity and 73.7% specificity). Cut-off values for GH levels in predicting cure for the 1st day, 1st week, and 1st month postoperatively were 2.33, 2.05, and 2.25 μg/L, respectively. The cut-off value for surgical experience was 57 for primary surgeries (58.5% cure rate before this cut-off value compared with 72.6% after it; p = 0.025) and 108 for all operations (45.8% vs 79.4%, p = 0.037). Although 28 patients were found to be in remission according to the criteria in 2000, they were not in remission according to the new consensus criteria. Nine of these cases (32.1%) had random GH levels < 1 μg/L at the 1-year follow-up. The 1-year IGF-I and GH levels in these 28 patients showed no significant difference when compared with the cases defined as cured according to the current criteria.

Conclusions. In acromegaly treatment, transsphenoidal endoscopic surgery performed by an expert senior surgeon and increased surgical experience are important for higher cure rates. Random GH levels < 2.33 μg/L after the 1st day postoperatively and a > 50% decrease in IGF-I levels after the 1st month postoperatively are predictive of cure. Moreover, there is no urgency for additional therapy in patients with GH levels of 0.4–1 μg/L and MRI sequences showing no tumor at the 3-month follow-up, because for these cases remission can be achieved at the 1-year follow-up.