Clinical characteristics and therapeutic outcomes after endoscopic endonasal surgery for craniopharyngioma in the elderly.

OBJECTIVE: Craniopharyngiomas (CPs) in adults are rare benign epithelial tumors, and few contemporary studies have explored outcomes after surgical treatment in elderly patients, especially with regard to endoscopic endonasal surgery (EES). METHODS: A retrospective cohort study was conducted on patients aged ≥ 18 years with CP who were treated with EES from 2013 to 2022. The cohort was divided into nonelderly (18-64 years) and elderly (≥ 65 years) groups based on age. Various parameters, including patient and tumor characteristics, surgical outcomes, complications, and follow-up, were compared between the two age groups. RESULTS: A total of 193 patients met the inclusion criteria, with 161 (83.4%) patients in the nonelderly group and 32 (16.6%) patients in the elderly group. Preoperatively, older patients were more likely to have memory impairment (4.3% vs 18.8%, p = 0.010), fatigue or decreased energy (9.3% vs 34.4%, p = 0.001), hypopituitarism (68.7% vs 90.6%, p = 0.012), or hydrocephalus (18% vs 40.6%, p = 0.005), and they were more likely asymptomatic (1.2% vs 9.4%, p = 0.033) and less likely to experience headache (57.8% vs 31.3%, p = 0.006). Patients in the elderly group had a longer symptom duration (median [IQR] 5 [10] months vs 9.5 [13] months, p = 0.001) and higher comorbidity scores (p < 0.001). Postoperatively, gross-total resection was achieved in 145 (90.1%) and 28 (87.5%) patients in the nonelderly and elderly groups, respectively. Older patients were more likely to develop pneumonia (5% vs 21.9%, p = 0.004). There were no significant differences in the extent of resection (p = 0.541), pathological subtypes (88.2% vs 75.0% adamantinomatous, p = 0.089), operation time (mean ± SD 307.8 ± 68.3 minutes vs 323.5 ± 86.0 minutes, p = 0.257), estimated blood loss (median [IQR] 300 [200] ml vs 300 [238] ml, p = 0.594), length of stay (median [IQR] 15 [8] days vs 15 [22] days, p = 0.964), perioperative mortality (2.5% vs 3.1%, p > 0.99), or postoperative severe hypothalamic dysfunction (37.9% vs 50.0%, p = 0.237) between the groups. Multivariate Cox regression analysis demonstrated that tumor calcification (HR 3.406, 95% CI 1.859-27.233, p = 0.038) and preoperative hydrocephalus (HR 3.688, 95% CI 1.310-10.386, p = 0.013) were independently associated with decreased survival. The median follow-up period in the elderly group was shorter (71 months vs 44 months, p = 0.001), and no recurrence was observed (7.1% vs 0%, p = 0.132). CONCLUSIONS: This study demonstrates that EES is a viable treatment option for older CP patients. With appropriate perioperative management, EES does not significantly increase mortality and, in selected populations, is well tolerated by patients.

Extended Endoscopic Endonasal Approach for Giant Pediatric Craniopharyngiomas: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: Giant pediatric craniopharyngiomas are rare tumors whose clinical and surgical management is extremely challenging. A variety of open transcranial approaches has been used to resect these lesions. Although there has been an increasing acceptance of the endoscopic endonasal approach (EEA) for the resection of pediatric craniopharyngiomas in recent years, many surgeons continue to recommend against the use of the EEA for giant pediatric craniopharyngiomas. This study aimed to evaluate the feasibility of extended EEA for giant craniopharyngiomas in the pediatric population. METHODS: All consecutive pediatric patients with giant craniopharyngiomas (diameter >4 cm) who underwent endoscopic endonasal surgery at our institution were retrospectively reviewed. Data on demographic information, preoperative assessment, imaging features, surgical results, complications, and recurrences were recorded and analyzed. RESULTS: A total of 16 pediatric patients with an average age of 12 years were identified. The mean maximum diameter and volume of the tumors were 4.35 cm and 24.1 cm3, respectively. Gross total resection was achieved in 13 patients (81.3%) and subtotal resection in 3 patients (18.7%). Postoperatively, partial or complete anterior pituitary insufficiency occurred in 100% of patients, and 62.5% developed new-onset diabetes insipidus. Visual function improved in 9 patients (56.3%) and remained stable in 7 patients (43.7%). Postoperative cerebrospinal fluid leakage occurred in 2 patients and was successfully repaired through the EEA. During a mean follow-up of 44.3 months, 18.8% of patients had a >9% increase in body mass index, and 93.8% of patients successfully returned to school or work. Two patients (12.5%) suffered a recurrence. Disease control was achieved in 16 patients (100%) at final follow-up. CONCLUSION: The extended EEA allows adequate access to this challenging tumor and enables complete resection and visual improvement with a reasonable approach-related complication rate.

Sestrin2 provides cerebral protection through activation of Nrf2 signaling in microglia following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a neurological emergency characterized by dysfunctional inflammatory response. However, no effective therapeutic options have been reported so far. Microglia polarization has been proposed to exert an essential role in modulating inflammatory response after SAH. Sestrin2 is a stress response protein. Growing evidence has reported that sestrin2 could inhibit M1 microglia and promote M2 microglia polarization. The current study investigated the effects of sestrin2 on microglia phenotype switching and the subsequent brain injury and sought to elucidate the underlying mechanism. We conducted an endovascular perforation SAH model in mice. It was found that sestrin2 was significantly increased after SAH and was mainly distributed in neurons and microglia. Exogenous recombinant human sestrin2 (rh-sestrin2) evidently alleviated inflammatory insults and oxidative stress, and improved neurofunction after SAH. Moreover, rh-sestrin2 increased M2-like microglia polarization and suppressed the number of M1-like microglia after SAH. The protection by rh-sestrin2 was correlated with the activation of Nrf2 signaling. Nrf2 inhibition by ML385 abated the cerebroprotective effects of rh-sestrin2 against SAH and further manifested M1 microglia polarization. In conclusion, promoting microglia polarization from the M1 to M2 phenotype and inducing Nrf2 signaling might be the major mechanism by which sestrin2 protects against SAH insults. Sestrin2 might be a new molecular target for treating SAH.

Nomograms to Predict Endocrinological Deficiency in Patients With Surgically Treated Craniopharyngioma.

Objective: Postoperative hypopituitarism associated with increased risks of premature mobility and mortality is often encountered in craniopharyngioma patients. The aim of our study is to construct nomograms related to injury types of the hypothalamus-pituitary axis (HPA) to predict hypopituitarism 1 year after surgery. Methods: Craniopharyngioma patients undergoing initial endoscopic endonasal surgery between December 2012 and March 2021 in our center were retrospectively reviewed, and injury types of the HPA were categorized according to intraoperative endoscopic observation. Included patients were randomly divided into a training group and a validation group. Nomograms were established based on the results of multivariate logistic analysis. The predictive performance of the nomograms was evaluated in the training and validation groups. Results: A total of 183 patients with craniopharyngioma were enrolled, and seven injury types of the HPA were summarized. Relative to intact HPA, exclusive hypothalamus injury significantly increased the risk of anterior (OR, 194.174; 95% CI, 21.311-1769.253; p < 0.001) and posterior pituitary dysfunction (OR, 31.393; 95% CI, 6.319-155.964; p < 0.001) 1 year after surgery, while exclusively sacrificing stalk infiltrated by tumors did not significantly increase the risk of anterior (OR, 5.633; 95% CI, 0.753-42.133; p = 0.092) and posterior pituitary dysfunction (OR, 1.580; 95% CI, 0.257-9.707; p = 0.621) 1 year after surgery. In the training group, the AUCs of nomograms predicting anterior and posterior pituitary dysfunction 1 year after surgery were 0.921 and 0.885, respectively, compared with 0.921 and 0.880 in the validation group. Conclusions: Intact hypothalamus structure is critical in maintaining pituitary function. Moreover, our preliminary study suggests that the pituitary stalk infiltrated by craniopharyngioma could be sacrificed to achieve radical resection, without substantially rendering significantly worse endocrinological efficiency 1 year after surgery. The user-friendly nomograms can be used to predict hypopituitarism 1 year after surgery.

Endoscopic Endonasal Supraoptic and Infraoptic Approaches for Complex "Parasuprasellar" Lesions: Surgical Anatomy, Technique Nuances, and Case Series.

Objective: The surgical management of lesions involving the lateral area of the suprasellar region, including the lateral aspect of the planum sphenoidale and the tight junction region of the optic canal (OC), anterior clinoid process (ACP), and internal carotid artery (ICA) and its dural rings, is extremely challenging. Here, these regions, namely, the "parasuprasellar" area, are described from the endonasal perspective. Moreover, the authors introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area. Methods: Surgical simulation of the EESO and EEIO approaches to the parasuprasellar area was conducted in 5 silicon-injected specimens. The same techniques were applied in 12 patients with lesions involving the parasuprasellar area. Results: The EESO approach provided excellent surgical access to the lateral region of the planum sphenoidale, which corresponds to the orbital gyrus of the frontal lobe. With stepwise bone (OC, optic strut and ACP) removal, dissociation of the ophthalmic artery (OA) and optic nerve (ON), the EEIO approach enables access to the lateral region of the supraclinoidal ICA. These approaches can be used independently or in combination, but are more often employed as a complement to the endoscopic endonasal midline and transcavernous approaches. In clinical application, the EESO and EEIO approaches were successfully performed in 12 patients harboring tumors as well as multiple aneurysms involving the parasuprasellar area. Gross total and subtotal tumor resection were achieved in 9 patients and 1 patient, respectively. For two patients with multiple aneurysms, the lesions were clipped selectively according to location and size. Visual acuity improved in 7 patients, remained stable in 4, and deteriorated in only 1. No postoperative intracranial infection or ICA injury occurred in this series. Conclusions: The EESO and EEIO approaches offer original treatment options for well-selected lesions involving the parasuprasellar area. They can be combined with the endoscopic endonasal midline and transcavernous approaches to remove extensive pathologies involving the intrasellar, suprasellar, sphenoid, and cavernous sinuses and even the bifurcation of the ICA. This work for the first time pushes the boundary of the endoscopic endonasal approach lateral to the supraclinoidal ICA and ON.

Identification of the Extradural and Intradural Extension of Pituitary Adenomas to the Suprasellar Region: Classification, Surgical Strategies, and Outcomes.

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.

Invasive Corridor of Clivus Extension in Pituitary Adenoma: Bony Anatomic Consideration, Surgical Outcome and Technical Nuances.

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.

MMP12 is a potential therapeutic target for Adamantinomatous craniopharyngioma: Conclusions from bioinformatics analysis and in vitro experiments.

Adamantinomatous craniopharyngioma (ACP) is considered a benign intracranial tumor, but it can also exhibit aggressive characteristics. Due to its unique location in the suprasellar, which brings it close to important nerves and vascular structures, ACP can often lead to significant neuroendocrine diseases. The current treatments primarily include surgical intervention, radiation therapy or a combination of the two, but these can lead to serious complications and adversely affect the quality of life of patients. Thus, it is important to identify effective and safe alternatives. Recently, studies have focused on the tumor genome, transcriptome and proteome in an attempt to identify potential therapeutic targets for clinical use. However, studies on this region of the CP are limited; thus, the present study focused on this region. The GSE94349 and GSE68015 datasets were downloaded from the Gene Expression Omnibus database and analyzed. In the in vitro studies, the effect of the matrix metalloproteinase (MMP)12 inhibitor, MMP408, on cell proliferation and protein expression was assessed. The results demonstrated that MMP408 effectively inhibited cell proliferation and migration of ACP cells, and decreased the expression levels of the related proteins. Thus, MMP12 may be used as a potential therapeutic target for the treatment of ACP.

A novel technique to manage internal carotid artery injury in endoscopic endonasal skull base surgery in the premise of proximal and distal controls.

Intraoperative internal carotid artery injury is one of the most daunting complications in endoscopic skull base surgery. This paper proposed a novel technique to manage ICA injury after proximal and distal controls. The appropriate block sites together with the proximal and distal controls of ICA were demonstrated in six injected cadaveric specimens. The surgical outcomes of five patients with intraoperative ICA injury and managed with this concept were retrospectively reviewed. Five block sites for vascular control could be identified in all six specimens, including (1) distal to the distal dural ring, (2) proximal to the proximal dural ring, (3) anterior genu of the parasellar ICA, (4) the upper third of the paraclival ICA, and (5) just above the foramen lacerum. Both proximal and distal controls of ICA were achieved by using the block sites in combination. Gross tumor resection was achieved in all five cases after the intraoperative ICA injury was successfully managed. Three coping techniques were used, including direct coagulation to seal (three cases), endoscopic suture (one case), and coagulation to sacrifice (one case). Focal brainstem infarction occurred in one case, one patient died of intracranial infection, and the other three cases had no sequelae. No pseudoaneurysm occurred in all patients. Except the sacrificed ICA, the other ICA was intact during follow-up. It is technically feasible to manage ICA injuries after proximal and distal controls during EEA surgeries. The surgical outcomes from our case series supported the use of this novel technique.

Hypothalamic injury patterns after resection of craniopharyngiomas and correlation to tumor origin: A study based on endoscopic observation.

The precise understanding of hypothalamic injury (HI) patterns and their relationship with different craniopharyngioma (CP) classifications remains poorly addressed. Here, four HI patterns after CP resection based on endoscopic observation were introduced. A total of 131 CP cases treated with endoscopic endonasal approach (EEA) were reviewed retrospectively and divided into four HI patterns: no-HI, mild-HI, unilateral-HI and bilateral-HI, according to intraoperative findings. The outcomes were evaluated and compared between groups in terms of weight gain, endocrine status, electrolyte disturbance and neuropsychological function before and after surgery. A systematic correlation was found between CP origin and subsequent HI patterns. The majority of intrasellar and suprasellar stalk origins lead to a no-HI pattern, the central-type CP mainly develops a mild or bilateral HI pattern, and the majority of tumors with hypothalamic stalk origins result in unilateral HI and sometimes bilateral HI patterns. The proportion of tumors with a maximum diameter >3 cm in the no-HI group was higher than that in the mild-HI group, BMI and quality of life in the no-HI group showed better results than those in the other groups. The incidence of new-onset diabetes insipidus in the bilateral-HI group was significantly higher than that in the other groups. Memory difficulty was observed mainly in the unilateral-HI and bilateral-HI groups. However, the outcomes of electrolyte disturbance, sleep, and cognitive disorder in the unilateral-HI group were significantly better than those in the bilateral-HI group. This study suggests the possibility of using pre- and intraoperative observation of CP origin to predict four HI patterns and even subsequent outcomes after tumor removal.