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Artistic illustration demonstrating the square-based pyramid structure in the posterior area of the CS (left side). The upper surface is the posterior portion of the oculomotor triangle. Invasive pituitary adenomas often invade this structure through the medial wall of the CS (right side)
Source publication
We found a series of Knosp grade 3A-4 pituitary adenomas in the posterior areas of the cavernous sinus (CS), a triangular-like structure on axial MRI. In this study, we dissected the surrounding neurovascular structure, discussed the surgical approach, and analyzed outcomes for patients with this invasion into this area. Eight embalmed adult cadave...
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Background
Patients diagnosed with pituitary apoplexy and presenting with acute visual deterioration require urgent surgical resection. This is also commonly associated with pituitary hypopituitarism that requires hormonal replacement for correction. This study was undertaken to evaluate the clinical recovery of 45 patients diagnosed with symptomat...
Citations
... The residual tumor is responsible for the postoperative failure of endocrinological remission and high rate of tumor recurrence [12,13,20]. Therefore, cavernous sinus invasion (CSI) requires early recognition and diagnosis, and timely treated by expert teams [15,16,21]. However, the gold standard for the diagnosis of CSI is intraoperative observation. ...
... Crucially, the CNN model's identification site exhibits a commendable degree of precision, signifying its adeptness at extracting pertinent information instead of processing data indiscriminately. This inherent attribute of the CNN contributes to clinical practitioners' ability to enhance their evaluations of the extent of tumor invasion, thereby enriching the intuitive understanding of image features during educational sessions and fostering effective doctor-patient communication [9,15,21]. ...
Objective
Cavernous sinus invasion (CSI) plays a pivotal role in determining management in pituitary adenomas. The study aimed to develop a Convolutional Neural Network (CNN) model to diagnose CSI in multiple centers.
Methods
A total of 729 cases were retrospectively obtained in five medical centers with (n = 543) or without CSI (n = 186) from January 2011 to December 2021. The CNN model was trained using T1-enhanced MRI from two pituitary centers of excellence (n = 647). The other three municipal centers (n = 82) as the external testing set were imported to evaluate the model performance. The area-under-the-receiver-operating-characteristic-curve values (AUC-ROC) analyses were employed to evaluate predicted performance. Gradient-weighted class activation mapping (Grad-CAM) was used to determine models' regions of interest.
Results
The CNN model achieved high diagnostic accuracy (0.89) in identifying CSI in the external testing set, with an AUC-ROC value of 0.92 (95% CI, 0.88–0.97), better than CSI clinical predictor of diameter (AUC-ROC: 0.75), length (AUC-ROC: 0.80), and the three kinds of dichotomizations of the Knosp grading system (AUC-ROC: 0.70–0.82). In cases with Knosp grade 3A (n = 24, CSI rate, 0.35), the accuracy the model accounted for 0.78, with sensitivity and specificity values of 0.72 and 0.78, respectively. According to the Grad-CAM results, the views of the model were confirmed around the sellar region with CSI.
Conclusions
The deep learning model is capable of accurately identifying CSI and satisfactorily able to localize CSI in multicenters.
... Despite advancements in surgical equipment and techniques, the rates of GTR and BR after surgery are still unsatisfactory due to the complexity of growth patterns, especially in acromegaly patients with invasive somatotroph tumors. [34][35][36][37] Tumors may invade surrounding structures including the sphenoid sinus, CS, and clivus bone. 38,39 The Knosp grade for pituitary neuroendocrine tumors is the most widely used to evaluate tumor invasion and has been shown to correlate with the possibility of achieving GRT and BR. ...
... 38,39 The Knosp grade for pituitary neuroendocrine tumors is the most widely used to evaluate tumor invasion and has been shown to correlate with the possibility of achieving GRT and BR. 23,36,40,41 Knosp grade 3 or 4 tumors may invade the posterior and lateral areas of the CS and might be difficult to resect because of overlying and surrounding neurovascular structures and therefore result in residual tumor. 42 In addition, some Knosp grade 0-2 tumors may also be invasive and can infiltrate the sphenoid sinus or clivus bone, leading to postoperative nonremission despite achieving GTR. ...
... 42 In addition, some Knosp grade 0-2 tumors may also be invasive and can infiltrate the sphenoid sinus or clivus bone, leading to postoperative nonremission despite achieving GTR. 31,36 Therefore, Hardy grade III or IV tumors were also classified as invasive in this study. ...
OBJECTIVE
The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs.
METHODS
A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0–2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor–1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion.
RESULTS
Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm ³ vs 3.50 ± 4.02 cm ³ , p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = −0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001).
CONCLUSIONS
Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.
... We have previously conducted in-depth studies on the invasive corridors of PA, such as the CS, clivus, and diaphragma sellae from an anatomical perspective, but the study of the CS corridor did not involve the special growth corridor of OC extension [11,14,15,17]. In this study, we used the technique of epoxy sheet plastination to study the membranous anatomy surrounding the cisternal segment of the oculomotor nerve and speculate on the anatomical factors that may affect PA with OC extension. ...
... A special subset of PA with CS invasion, which invaded through the posterior area of the CS causing OC extension, mainly led to higher risks of oculomotor nerve function damage and a further extension to the parapeduncular space [5,15]. The most common manifestation in patients with PAs is visual impairment or endocrine dysfunction, but the classical symptom of PAs with OC extension is oculomotor nerve palsy [3]. ...
Background
The anatomical basis of pituitary adenomas (PAs) with oculomotor cistern (OC) extension as a growth corridor is overlooked in the literature. In this paper, the authors use the technique of epoxy sheet plastination to study the membranous structure of the OC and validate the results by retrospective analysis of patients with OC extension.
Methods
Eighteen specimens were used to study the membranous anatomy surrounding the OC using the epoxy sheet plastination technique. Thirty-four patients with OC extension were retrospectively reviewed.
Results
The OC consisted of two thin membranous layers. The inner layer was extended by the arachnoid layer from the posterior fossa, and the lateral layer consisted of the dura mater sinking from the roof of the cavernous sinus. The oculomotor nerve is more likely to displace with a superolateral trajectory due to the weakness of the posterior dura and the relatively large space in the medial and posterior trajectories, which is consistent with the intraoperative observations. Among the anatomical factors that affect the PA by OC extension, we found that the relative position of the internal carotid artery (ICA) and posterior clinoid process may lead to the narrowing of the OC. Of 34 cases, 28 patients achieved total resection. Among 24 preoperative patients with oculomotor nerve palsy, 16 cases were relieved to varying degrees postoperatively. There was no ICA injury or severe intracranial infection found in any of the patients.
Conclusions
Extension into the OC is influenced by two anatomical factors: a weak point in the dura in the posterior OC and a potential space beyond this region of the dura. Meticulous knowledge of the membranous anatomy in endoscopic endonasal surgery is required to safely and effectively resect PA with OC extension.
... At that point, a "salvage" transcranial route is necessary for reexploration whenever complications occur. Studies of EEA have recently reported successful resection of tumors extending into the oculomotor triangle (8) and posterior triangle (9), which offer choices for experienced centers. Nevertheless, the following problems can be faced in clinical practice: 1) From which part should the resection be initiated? ...
Objectives
To understand the different characteristics and growth corridors of knosp grade 4 pituitary adenomas (Knosp4PA) with cavernous sinus (CS) compartments penetration and intracranial extension, aiming to improve the safety, effectiveness, and total resection rate of surgery.
Methods
A case series of 120 Knosp4PA patients with 187 invaded compartments were retrospectively reviewed. A novel surgery-relevant grading system was proposed according to the CS penetrating features. The details of approach drafting, risk prediction, and complication avoidance were analyzed and integrated through illustrated cases.
Results
All enrolled tumor was Knosp4PA which was derived from Knosp subgrades 3A(62.5%) and 3B(37.5%). Based on the tumor growth pathway and its relevant features, five subclassifications of intracranial extension(n=98,81.7%) were classified, which derived from the superior (Dolenc’s and Oculomotor subtype, 5% and 24.2%), lateral (Parkinson’s subtype,18.3%), and posterior (cerebral peduncle and Dorello’s subtype, 5.8% and 1.7%) CS compartment penetration. The size of intracranial extension is assessed by Lou’s scale proposed here based on preoperative MRI characteristics. Under Lou’s scale, the gross total rate (GTR) decreased (82%, 53%, 22%, and 19%) with grades increased (grade 0,1,2,3, respectively), and presents significant difference between the four groups (p=0.000), as well as between single and multiple compartments involved (p=0.001). Preoperative cranial nerve deficits included the optic nerve (53%), oculomotor nerve (24.2%), and abducent nerve (4.2%), with an overall rate of visual function improvement in 68.1%. Postoperative complications of transient diabetes insipidus, cerebrospinal fluid (CSF) leakage, and cranial nerve deficits were 6.7%, 0.8%, and 0%. No new cranial nerve deficits occurred. The mortality rate was 0.8%.
Conclusion
The concept of “penetration” refines the extracavernous growth pattern, and the five intracranial subclassifications help to understand the potential extension corridors, enhancing adequate exposure and targeted resection of Knosp4PA. This grading system may benefit from its predictive and prognostic value, from which a higher GTR rate can be achieved.
... 15 The principle is choosing an approach following the tumor growth pathway. For type A tumors (Figure 2), the medial approach with the aid of angle scope was used for tumors in the sellar, posterosuperior compartment, and posterior area of CS. 16 The laterosuperior approach was used for tumor extended to the oculomotor triangle, parapeduncular region, and temporal region; anteriorly in the lateral compartment; and lateral to the a.gICA. For type B tumors, the AI approach was used for tumors in the anterosuperior and lateroinferior compartments ( Figure 3). ...
Background:
Understanding the growth pathway of Knosp grade 4 pituitary adenoma (KG4PA) has a direct impact on surgical planning and safety for tumor eviction.
Objective:
To analyze the different characteristics between KG4PAs with a focus on the tumor growth pathway and its relationship to the cavernous segment of internal carotid artery.
Methods:
Clinical data from 129 patients with KG4PAs who underwent endoscopic endonasal surgery were retrospectively reviewed. A subclassification scheme was proposed based on the tumor growth pathway and its relevant features. The clinical connotation of the subclassification on surgical outcomes was also analyzed.
Results:
The KG4PAs were classified into 3 types based on the tumor growth pathway and its relevant features: groups A, B, and AB. The gross total resection rate in group A (51.2%) was much lower than that in group B (87.5%) and AB (87%) with a significant difference between the 3 groups (P = .0004). The overall rate of visual function improvement, preoperative cranial nerve (CN) palsy improvement, and postoperative hormonal remission was 85.1%, 83.3%, and 85.7%, respectively. The rate of transient CN palsy, permanent CN palsy, permanent diabetes insipidus, panhypopituitarism, CSF leakage, and internal carotid artery injury was 7.8%, 3.9%, 4.7%, 2.3%, 1.5%, and 0.7%, respectively.
Conclusion:
The subclassification strengthens our understanding of KG4PAs on tumor growth corridors and topographic relations of tumor and cavernous segment of internal carotid artery. Furthermore, the distinction into groups 4A, 4B, and 4AB is of benefits for selecting approaches, predicting risk and avoiding complications, and generating more tailored individualized surgical strategies for KG4PAs with better outcomes.
... The most challenging types of skull base surgery involve pituitary tumors, one of the most common tumors in the sellar region and include invasive and noninvasive pituitary tumors. Moreover, CS invasion is associated with high surgical risks and recurrence rates, STR and endocrine remission, and the need for adjuvant therapy (18,19). To address these issues, Cushing suggested a transsphenoidal surgical approach in 1907 (20). ...
Objective
The development of skull base surgery in the past decade has been influenced by advances in visualization techniques; recently, due to such improvements, 3D endoscopes have been widely used. Herein, we address its effect for transnasal endoscopic skull base surgery.
Methods
A total of 63 patients who under endoscopic endonasal surgery (EES) with 3-D endoscope were retrospectively reviewed, including pituitary adenomas, craniopharyngiomas, meningiomas, Rathke’s cleft cysts, and chordomas. According to different lesions, transsellar approach (24 cases), transsphenoidal–transtuberculum approach (14 cases), transclival approach (6 cases), and transpterygoid approach (19 cases) were selected.
Results
Total removal of tumors was achieved in 56 patients (88.9%) and subtotal removal in 7 cases (11.1%). Complications included diabetes insipidus in seven patients (11.1%), cerebrospinal fluid (CSF) leakage in two patients (3.2%), major vascular injury occurred in one patient (1.6%), cranial nerve injury in nine patients (14.3%), and meningitis in two patients (3.2%). There was no mortality in the series. All patients recovered and were back to normal daily life, and no tumor recurrence or delayed CSF leakage was detected during the follow-up (2–13 months, mean 7.59 months).
Conclusions
Via 3D EES, it improved depth perception and preserved important neurovascular tissue when tumors were removed, which is important for improving the operative prognosis.
... (Table 1). In the "Mosaic sign" group, 22 cases had Knosp grade ≥3, and 19 cases had Hardy grade ≥C (This type of tumor is considered invasive (18,19)). Only subtotal resection was performed in 1 patient because the tumor enveloped the internal carotid artery and the adhesion was tight. ...
Purpose
Tumor consistency is important for pituitary neuroendocrine tumors (PitNETs) resection to improve surgical outcomes. In this study, we evaluated the T2-WI of PitNETs and defined a specific T2-WI signaling manifestation, the “Mosaic sign,” to predict tumor consistency and resection of PitNETs.
Design
A retrospective review of MRI and tumor histology of 137 consecutive patients who underwent endoscopic endonasal resection for PitNETs was performed.
Methods
The “Mosaic sign” was defined by the ratio of the tumor itself T2-WI signals, and characterized by multiple intratumor hyperintense dots. The degree of tumor resection was an assessment by postoperative MRI examination. The presence of the “Mosaic sign” was compared with patients' basic information, tumor consistency, tumor pathological staining, and surgical result. To determine whether the presence or absence of “Mosaic sign” could predict tumor consistency and guide surgical resection of tumors.
Results
Statistical analysis showed that the consistency of the tumor and the degree of resection were correlated with the “Mosaic sign”. In the 137 cases of T2-WI, 43 had “Mosaic sign”, 39 cases had soft tumor consistency, and 4 were classified as fibrous, of which 42 were completely resected and 1 was subtotal resected. Of the 94 patients without “Mosaic sign”, the consistency of tumor of 54 cases were classified as soft, the remaining 40 cases were fibrous, 80 cases were completely resected, and 14 cases were subtotal resected. Postoperative cerebrospinal fluid leakage occurred in 1 patient. The number of corticotroph adenomas in the group of “Mosaic sign” was higher, with the statistical difference between the two groups ( P = 0.0343).
Conclusions
The presence of the “Mosaic sign” in T2-WI may provide preoperative information for pituitary adenomas consistency and effectively guide surgical approaches.
... The standard EEA for PAs has been described previously (13,19,20). A 2-surgeon 4-handed technique with binostril access was employed as previously described (21,22). Briefly, in situations where the DS descended asymmetrically, care was taken to avoid tumor residue (23). ...
Objective
Suprasellar pituitary adenomas (PAs) can be located in either extradural or intradural spaces, which impacts surgical strategies and outcomes. This study determined how to distinguish these two different types of PAs and analyzed their corresponding surgical strategies and outcomes.
Methods
We retrospectively analyzed 389 patients who underwent surgery for PAs with suprasellar extension between 2016 to 2020 at our center. PAs were classified into two main grades according to tumor topography and their relationships to the diaphragm sellae (DS) and DS-attached residual pituitary gland (PG). Grade 1 tumors were located extradurally and further divided into grades 1a and 1b, while grade 2 tumors were located intradurally.
Results
Of 389 PAs, 292 (75.1%) were surrounded by a bilayer structure formed by the DS and the residual PG and classified as grade 1a, 63 (16.2%) had lobulated or daughter tumors resulting from the thinning or absence of the residual PG and subsequently rendering the bilayer weaker were classified as Grade 1b, and the remaining 34 (8.7%) PAs that broke through the DS or traversed the diaphragmic opening and encased suprasellar neurovascular structures were classified as Grade 2. We found that the gross total removal of the suprasellar part of grade 1a, 1b, and 2 PAs decreased with grading (88.4%, 71.4%, and 61.8%, respectively). The rate of major operative complications, including cerebrospinal fluid leakage, hemorrhage, and death, increased with grading.
Conclusions
It is essential to identify whether PAs with suprasellar extension are located extradurally or intradurally, which depends on whether the bilayer structure is intact. PAs with an intact bilayer structure were classified as grade 1. These were extradural and usually had good surgical outcomes and lower complications. PAs with no bilayer structure surrounding them were classified as grade 2. These were intradural, connected to the cranial cavity, and had increased surgical complications and a lower rate of gross total removal. Different surgical strategies should be adopted for extradural and intradural PAs.
... All operations were performed under intraoperative electrophysiological monitoring. The surgical approach and preparation process are described in a previous report (14). Two surgeons (four hands) performed the surgery via the binostril EEA. ...
Background
It is well known that the clivus is composed of abundant cancellous bone and is often invaded by pituitary adenoma (PA), but the range of these cancellous bone corridors is unknown. In addition, we found that PA with clivus invasion is sometimes accompanied by petrous apex invasion, so we speculated that the petrous apex tumor originated from the clivus cancellous bone corridor. The aim of this study was to test this hypothesis by investigating the bony anatomy associated with PA with clival invasion and its clinical significance.
Methods
Twenty-two cadaveric heads were used in the anatomical study to research the bony architecture of the clivus and petrous apex, including six injected specimens for microsurgical dissection and sixteen cadavers for epoxy sheet plastination. The surgical videos and outcomes of PA with clival invasion in our single center were also retrospectively reviewed.
Results
The hypoglossal canal and internal acoustic meatus are composed of bone canals surrounded by cortical bone. The cancellous corridor within clivus starts from the sellar or sphenoid sinus floor and extends downward, bypassing the hypoglossal canal and finally reaching the occipital condyle and the medial edge of the jugular foramen. Interestingly, we found that the cancellous bone of the clivus was connected with that of the petrous apex through petroclival fissure extending to the medial margin of the internal acoustic meatus instead of a separating cortical bone between them as it should be. It is satisfactory that the anatomical outcomes of the cancellous corridor and the path of PA with clival invasion observed intraoperatively are completely consistent. In the retrospective cohort of 49 PA patients, the clival component was completely resected in 44 (89.8%), and only five (10.2%) patients in the early-stage had partial residual cases in the inferior clivus.
Conclusion
The petrous apex invasion of PA is caused by the tumor invading the clivus and crossing the petroclival fissure along the cancellous bone corridor. PA invade the clivus along the cancellous bone corridor and can also cross the hypoglossal canal to the occipital condyle. This clival invasion pattern presented here deepens our understanding of the invasive characteristics of PA.
... With the recent, rapid development in transsphenoidal endoscopic techniques and advances made through in-depth study of the endoscopic anatomy of the CS (12,13), as well as the availability of intraoperative neuronavigation, doppler ultrasonography, and cranial nerve monitoring, it is worth reconsidering whether it is best to adopt a conservative or aggressive surgical strategy for grade 4 PAs. The current study provides the outcomes and complications of an aggressive surgical strategy for 102 patients with grade 4 PAs treated by transsphenoidal endoscopic surgery performed by the same surgeon. ...
Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P<0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P<0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.
