Inherent Tumor Characteristics That Limit Effective and Safe Resection of Giant Nonfunctioning Pituitary Adenomas

doi:10.1016/j.wneu.2017.07.043

World Neurosurgery

Volume 106, October 2017, Pages 645-652

https://doi.org/10.1016/j.wneu.2017.07.043 Get rights and content

Background

Surgical treatment of giant pituitary adenomas is sometimes challenging. We present our surgical series of giant nonfunctioning adenomas to shed light on the limitations of effective and safe tumor resection.

Methods

The preoperative tumor characteristics, surgical approaches, outcome, and histology of giant nonfunctioning adenoma (>40 mm) in 128 consecutive surgical patients are reviewed. The follow-up period ranged from 19 to 113 months (mean 62.2 months).

Results

A transsphenoidal approach was used in the treatment of 109 patients and a combined transsphenoidal transcranial approach in 19 patients. A total of 93 patients (72.7%) underwent total resection or subtotal resection apart from the cavernous sinus (CS). The degree of tumor resection, excluding the marked CS invasion, was lower in tumors that were larger (P = 0.0107), showed massive intracranial extension (P = 0.0352), and had an irregular configuration (P = 0.0016). Permanent surgical complications developed in 28 patients (22.0%). Long-term tumor control was achieved in all patients by single surgery, including 43 patients with adjuvant radiotherapy. Most tumors were histologically benign, with a low MIB-1 index (<3.0%) beside a few tumors mainly silent adenomas of pituitary-specific transcription factor lineage.

Conclusions

Irrespective of the surgical approach, massive intracranial extension, an irregular configuration, and marked CS invasion are inherent factors that independently limit effective resection. These high-risk tumors require an individualized therapeutic strategy.

Introduction

Transsphenoidal surgery (TSS) has been the gold standard operative approach for nonfunctioning pituitary adenomas for decades. With the recent evolution of surgical techniques and instruments, including the endoscope, complete and safe resection is possible for many adenomas, and the ability to resect complex adenoma is evolving dramatically. However, several inherent tumor characteristics still limit effective and safe resection.1, 2, 3, 4, 5 Giant adenomas, usually defined as those with a maximum diameter >40 mm, may occasionally remain a therapeutic challenge because of their size, invasiveness, and irregular extrasellar extensions. Radical removal of giant adenomas has been achieved in fewer than one half of the cases described in the literature.2, 6, 7, 8, 9 Complex adenomas are not only difficult to resect but also have a greater risk of complications. Currently most pituitary surgeons favor endoscopic TSS in the surgical management of giant adenomas, although some tumors require an individualized surgical approach.6, 8, 10 Most giant adenomas are slow-growing and histologically benign tumors despite giant in size and troublesome to manage.11, 12, 13, 14 Here, we review the surgical outcome and histology of a large consecutive series of giant nonfunctioning adenomas to elucidate the factors that limit effective and safe resection. We also discuss current therapeutic strategies.

Section snippets

Patients

The cases of 128 consecutive patients with giant nonfunctioning adenoma, defined as tumors measuring ≥40 mm in their maximum diameter, surgically treated between 2008 and 2015 are reviewed herein. They made up 12.8% of the 1001 cases of surgical nonfunctioning adenoma managed during this period at our institute. The 71 men and 57 women ranged in age from 27 to 81 years (mean 48.1 years). Surgery was performed for the first time in 91 patients, whereas 37 patients (28.9%) had previously

Results

The maximum diameters and the intracranial extension index of the tumor ranged from 40.1 to 83.0 (48.1) mm and 0% to 90% (mean 41%), respectively. Marked CS invasion characterized 69 tumors (53.9%), irregular configuration 66 tumors (51.6%), and complete encasement of the subarachnoid arteries 13 tumors (10.2%). Tumor size correlated positively with marked CS invasion (P = 0.0005) and encasement of the subarachnoid arteries (P = 0.0047) but not with an irregular configuration. The intracranial

Histology of Giant Adenomas

Giant adenomas are mostly invasive and may be surgically challenging but most are slow growing, histologically benign, and gonadotrophic in their subtype.11, 12, 13, 14 The absence of a correlation between the MIB-1 index and tumor size has been demonstrated in several studies.11, 12, 13, 14, 17 In the present series, silent ACTH adenoma was diagnosed in 21.1% of the patients and Pit-1-lineage silent adenoma in 7.0%. Many authors have pointed out that the clinical features of these 2 uncommon

Conclusions

Endoscopic TSS, the extended approach, and the combined approach allowed total resection and subtotal resection apart from the CS of giant adenoma in 93 patients (72.7%). Most of the tumors were histologically benign, with a low MIB-1 index (<3.0%) beside a few tumors mainly silent adenomas of Pit-lineage. Irrespective of the surgical approach, massive intracranial extension, an irregular configuration, and marked CS invasion are inherent factors that independently limit effective resection.

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Cited by (32)

Predictive model of resection in endoscopic endonasal approach for pituitary adenomas based on anatomical limits
2023, Neurocirugia
The aim of this project is to study several anatomical-radiological features of pituitary adenomas obtained from preoperative radiological images and to analyze their relationship with the extent of resection achieved through the endoscopic endonasal approach. The second objective was to create a prediction model of the extent of resection.
We retrospectively evaluated 105 patients. Tumor volume, Knosp grade, suprasellar-diaphragm coefficient and invasion of the posterior compartment have been analyzed. The extent of resection was assessed by analyzing the postoperative magnetic resonance. We created the predictive scale using statistically independent variables.
When each of the variables has been studied individually, a statistically significant value of all of them is appreciated to obtain a complete resection. However, only the Knosp grade and the suprasellar-diaphragm coefficient had a statistically significant value as independent variables. The sum of the Odds Ratio obtained from the Knosp scale, and the suprasellar-diaphragm coefficient gives the probability of complete resection. A new set of cases was employed to validate the scale.
The cavernous sinus invasion and the newly designed suprasellar diaphragm coefficient are directly related to the extent of resection in pituitary adenoma surgery performed by a transellar endoscopic approach. Moreover, based on both radiologic factors, a predictive scale may predict the probability of complete resection in a series of patients.
El objetivo principal de este proyecto es estudiar diversas variables anatomo-radiológicas de los adenomas hipofisarios obtenidas a partir de imágenes radiológicas preoperatorias y analizar su relación con el grado de resección logrado mediante el abordaje endoscopio endonasal. El segundo objetivo ha sido crear un modelo de predicción del grado de resección tumoral.
Se ha evaluado retrospectivamente a 105 pacientes, analizando el volumen tumoral, el grado de Knosp, el coeficiente supraselar-diafragma y la invasión del compartimento posterior. El grado de resección se ha evaluado mediante el análisis de la resonancia magnética postoperatoria. Se ha creado la escala predictiva empleando variables estadísticamente independientes.
Al estudiar cada una de las variables de forma individual, se aprecia un valor estadísticamente significativo en cada una de ellas para obtener una resección completa. Sin embargo, tan solo el grado de Knosp y el coeficiente supraselar-diafragma tuvieron un valor estadísticamente significativo como variables independientes. Empleando la suma de la odds ratio obtenida de la escala Knosp y el coeficiente supraselar-diafragma, se ha obtenido la probabilidad de resección completa. Se ha empleado un nuevo conjunto de casos para validar la escala.
La invasión del seno cavernoso y el coeficiente supraselar-diafragma son variables que están directamente relacionadas con el grado de resección en la cirugía de adenoma hipofisario realizada mediante un abordaje endoscópico transellar. Además, basándose en ambos factores radiológicos, se ha creado una escala predictiva que permite predecir la probabilidad de resección completa en una serie de pacientes.
Endoscopic endonasal pituitary surgery: How we do it. Consensus statement on behalf of the EANS skull base section
2023, Brain and Spine
The use of an endoscope in skull base surgery provides a panoramic close-up view over the intracranial structures from multiple angles with excellent illumination, thus permitting greater extent of resection of tumors arising at sellar area, mostly represented by PitNet - Pituitary neuroendocrine tumors, with higher likelihood of preserving vital/intact gland tissue. For this refined specialty of neurosurgery, unique skills need to be acquired along a steep learning curve.
EANS (European Association of Neurosurgical Societies) skull base section panelists were enrolled and 11 completed the survey: the goal was to provide a consensus statement of the endoscopic endonasal approach for pituitary adenoma surgery.
The survey consisted of 44 questions covering demographics data (i.e., academic/non-academic center, case load, years of experience), surgical techniques (i.e., use of neuronavigation, preoperative imaging), and follow-up management.
In this paper we identified a series of tips and tricks at different phases of an endoscopic endonasal pituitary surgery procedure to underline the crucial steps to perform successful surgery and reduce complications: we took in consideration the principles of the surgical technique, the knowledge of the anatomy and its variations, and finally the importance of adjoining specialties experts.
Preoperative Magnetic Resonance Imaging Localization of the Normal Pituitary Gland in Nonfunctioning Pituitary Adenoma Patients Using the Radiological Sign of “Internal Carotid Artery Notch”
2022, World Neurosurgery
Asymmetric features of nonfunctioning pituitary adenoma (NFPA) are poorly understood. We investigated the asymmetry in NFPA on magnetic resonance imaging.
We reviewed preoperative magnetic resonance imaging findings of patients initially treated for NFPA. The internal carotid artery (ICA) often seemed to cause an indentation in the external shape of the tumor (i.e., the ICA notch).
Two cases with a normal pituitary gland located at the midline were excluded. The remaining 66 cases were examined. The side where the normal gland was located was defined as the normal pituitary side and the opposite side as the cavernous sinus side. The Knosp grade was significantly higher on the cavernous sinus side (P < 0.001), and the vertical distance of the ICA was significantly greater on the cavernous sinus side (P < 0.001). The ICA notch was found in 87.9% of all cases on the normal pituitary side, but in only 45.5% on the cavernous sinus side (P < 0.001). In cases with a single-side ICA notch (34 of 68), the ICA notch was found in 91.2% of cases and on the cavernous sinus side in 8.8% (P < 0.001).
Magnetic resonance imaging of NFPA frequently shows asymmetry. The tumor does not extend laterally on the normal pituitary side but extends laterally more freely on the cavernous sinus side. The ICA notch is often found on the normal pituitary side where the position of ICA does not move. This may be useful as a preoperative sign to indicate the normal pituitary side.
Simultaneous combined endoscopic endonasal and transcranial surgery for giant pituitary adenomas: Tips and traps in operative indication and procedure
2022, Clinical Neurology and Neurosurgery
Citation Excerpt :
Even now, when substantial advances in endoscopic endonasal surgery have been achieved, giant pituitary adenomas remain challenging to treat [1–6].
This retrospective analysis of patients treated with endoscopic endonasal transsphenoidal surgery (ETSS) alone or simultaneous combined surgery investigated imaging features suitable for surgical methods and pitfalls in simultaneous combined surgery for giant pituitary adenoma.
Ten patients with giant pituitary adenoma treated by ETSS alone or simultaneous combined endoscopic endonasal and transcranial surgery were enrolled. By analyzing tumor imaging features on magnetic resonance imaging (MRI), operative findings and clinical outcomes, we examined types of imaging features suitable for each surgical method.
Four patients received ETSS alone and six patients underwent simultaneous combined endonasal and transcranial surgery. Four patients treated by ETSS alone and three patients treated by combined surgery had high resection rates and good outcomes. The remaining three patients with combined surgery achieved partial resection and visual deterioration in one patient. MRI features suitable for ETSS included an enlarged sella, upward tumor extension, and round surface, whereas those for combined surgery included normal/enlarged sella, anterior and/or unilateral tumor extension, and a multilobulated surface. Tumors extending extensively bilaterally or upward and encasing neurovascular structures could not be effectively resected even under combined surgery.
Both ETSS alone and simultaneous combined endonasal and transcranial surgery showed good results for giant pituitary adenoma when the surgical methods matched suitable imaging features. Tumors with unilateral or anterior extension and a multilobulated surface were maximally resected without neurological deficit by combined surgery, but tumors showing extensive multi-directional extension and full encasement of neurovascular structures were not effectively resected even with combined surgery.
Giant Pituitary Adenoma – Special Considerations
2022, Otolaryngologic Clinics of North America
Citation Excerpt :
Nevertheless, it is important to note that the combined approach is logistically challenging and requires 2 surgical teams, operative fields, sets of operating instruments, and potentially operating microscopes.128 Eight case series encompassing 96 GPA patients have been published on using a combined surgical approach for GPA resection (Table 4).7,22,34,84,120,126,127,129 These case series have combined a TC procedure with the MT approach,7,120 the EET approach,22,84,126,129 or both transsphenoidal modalities.34,127
Surgical management of giant pituitary neuroendocrine tumors: Meta-analysis and consensus statement on behalf of the EANS skull base section
2022, Brain and Spine
The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated.
The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section.
We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts.
20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases
After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy.

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: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleInherent Tumor Characteristics That Limit Effective and Safe Resection of Giant Nonfunctioning Pituitary Adenomas

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Histology of Giant Adenomas

Conclusions

Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas: institutional experience and predictors of extent of resection

J Neurosurg

Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations

J Neurosurg

Simultaneous combined supra-infrasellar approach for giant/large multi-lobulated pituitary adenomas

World Neurosurg

The current role of transcranial surgery in the management of pituitary adenomas

Pituitary

Defining the “edge of the envelope”: patient selection in treating complex sellar-based neoplasms via transsphenoidal versus open craniotomy

J Neurosurg

Endonasal transsphenoidal surgery and multimodality treatment for giant pituitary adenomas

Clin Endocrinol

Giant pituitary tumors: a study based on surgical treatment of 118 cases

Surg Neurol

Giant pituitary adenomas: surgical outcomes of 50 cases operated on by the endonasal endoscopic approach

World Neurosurg

Recent evolution of endoscopic endonasal surgery for treatment of pituitary adenomas

Neurol Med Chir (Tokyo)

Size does not matter. The intrigue of giant adenomas: a true surgical challenge

Acta Neurochir (Wien)

Clinicopathological correlates of giant adenomas

J Clin Neurosci

Giant pituitary adenomas: pathologic-radiographic correlations and lack of role for p53 and MIB-1 labeling

Am J Surg Pathol

The complementary role of transcription factors in the accurate diagnosis of clinically nonfunctioning pituitary adenomas

Endocr Pathol

Correlation between histological subtypes and MRI findings in clinically nonfunctioning pituitary adenomas

Endocr Pathol

Original Article
Inherent Tumor Characteristics That Limit Effective and Safe Resection of Giant Nonfunctioning Pituitary Adenomas