Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization.

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

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.

Endoscopic Endonasal Internal Carotid Artery Transposition Technique in Tumor With Parasellar Extension: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Lateralization or mobilization of the internal carotid artery (ICA) during a midline approach is required to expose lesions behind or lateral to the ICA. However, there have been no published data regarding the surgical outcomes of the endoscopic endonasal internal carotid transposition technique (EEITT). This study aimed to analyze the relevant surgical anatomy around the ICA and propose a grading scheme of EEITT. METHODS: A retrospective review of patients who underwent EEITT at a single institution was performed. Based on structures that limited the ICA and intraoperative findings, an anatomically surgical grading scheme of EEITT was proposed. RESULTS: Forty-two patients (mean age 45.6 years, 57.1% female patients) were included. Of them, 29 cases (69.0%) were Knosp grade 4 pituitary adenoma, 6 cases (14.3%) were chordoma, 6 cases (14.3%) were meningioma, and a single case (2.4%) was meningeal IgG4-related disease. The EEITT was categorized into Grades 1, 2 and 3, which was used in 24 (57.1%), 12 (28.6%), and 6 (14.3%) cases, respectively. The most common symptom was visual disturbance (45.2%). The gross total resection rate in Grade 1 (79.2%) and Grade 2 (83.3%) was much higher than that in Grade 3 (66.6%). The overall rate of visual function improvement, preoperative cranial nerve (CN) palsy improvement, and postoperative hormonal remission was 89.4%, 85.7%, and 88.9%, respectively. The rate for the following morbidities was cerebrospinal fluid leakage, 2.4%; permanent diabetes insipidus, 4.8%; new transient CN palsy, 9.5%; permanent CN palsy, 4.7%; panhypopituitarism, 7.1%; and ICA injury, 2.4%. CONCLUSION: The EEITT is technically feasible and could be graded according to the extent of disconnection of limiting structures. For complex tumor with parasellar extensions, the distinction into Grades 1, 2, and 3 will be of benefit to clinicians in predicting risks, avoiding complications, and generating tailored individualized surgical strategies.

Predictors of the Spontaneous Resolution of Central Diabetes Insipidus Following Endoscopic Endonasal Surgery for Craniopharyngioma.

OBJECTIVE: Central diabetes insipidus (CDI) is the most common complication of endoscopic endonasal surgery (EES) for craniopharyngioma. However, some cases of CDI could spontaneously resolve during the follow-up period. Hence, this study aimed to determine the predictive factors for the spontaneous resolution of CDI. METHODS: Data of patients with CDI who underwent EES for craniopharyngioma between February 2009 and June 2021 were retrospectively reviewed. All patients were divided into 2 groups based on the resolution of CDI during follow-up: the recovery and no recovery groups. The baseline characteristic, surgical, and follow-up results of patients were compared. RESULTS: We identified 84 patients with CDI (35 in the recovery group and 49 in the no recovery group). A direct comparison showed that retaining the pituitary stalk (57.1% vs. 14.3%, P = 0.000) and no-hypothalamic injury (HI) (68.6% vs. 20.4%, P = 0.000) were more common in the recovery group, whereas hydrocephalus at diagnosis (8.6% vs. 46.9%, P = 0.000) was significantly more common in the no recovery group. Subsequently, we found through univariate and multivariate analysis that the spontaneous resolution of CDI was associated with hydrocephalus at diagnosis (yes vs. no: odds ratio [OR], 0.198; P = 0.045), pituitary stalk injury (retaining vs. sectioning: OR, 7.055; P = 0.004), and the Hong et al HI pattern (mild-HI vs. no-HI: OR, 0.183; P = 0.038; unilateral-HI vs. no-HI: OR, 0.147; P = 0.017; bilateral-HI vs. no-HI: OR, 0.154; P = 0.044). CONCLUSIONS: Hydrocephalus at diagnosis, pituitary stalk injury, and the Hong et al HI pattern might be predictors of the spontaneous resolution of CDI following EES for craniopharyngioma.

Subclassification of Knosp Grade 4 Pituitary Adenoma: Bringing Insights Into the Significance of Tumor Growth Pathways.

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 use of three-dimensional endoscope in transnasal skull base surgery: A single-center experience from China.

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.

Exploration of the causes of cerebrospinal fluid leakage after endoscopic endonasal surgery for sellar and suprasellar lesions and analysis of risk factors.

Objective: Postoperative cerebrospinal fluid (CSF) leakage following endoscopic endonasal surgery (EES) is a frequent complication. This study aims to identify potential risk factors of postoperative CSF leakage. Methods: A retrospective review of 360 patients who underwent EES was included. The associations between postoperative CSF leakage and patient demographics, medical history, tumor characteristics, and intraoperative repair techniques were analyzed; the diagnosis and repair of postoperative CSF leakage were also introduced. Results: Postoperative CSF leakage occurred in 14 patients (3.9%), 2 of them cured by lumbar cistern drainage, 12 underwent endoscopic repair. Among these 12 cases, 3 were repaired twice, and the rest were cured the first time. During the repair surgery, insufficient embedded fat was detected in one case detected, seven with breached inner artificial dura, three had vascularized pedicle nasoseptal flap (VP-NSF) displacement, two with VP-NSF perforation, two with VP-NSF inactivation, and one with imperfect adherence to VP-NSF to the skull base. Eight cases had intracranial infections. Excluding one case who died of severe intracranial infection, the rest were cured and discharged without obvious sequelae. Multivariate analysis revealed that the suprasellar lesion, subarachnoid invasion, and intraoperative grade 3 flow CSF leakage were the risk factors of CSF leakage after operation, while the bone flap was a protective factor. Conclusion: Bone flap combined with VP-NSF and iodoform gauze for skull base reconstruction is recommended in high-risk patients, while postoperative lumbar cistern drain remains dispensable.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.

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.

Deubiquitination of TNKS1 Regulates Wnt/ß-Catenin to Affect the Expression of USP25 to Promote the Progression of Glioma.

Objective: To explore the regulatory effect of ubiquitin specific protease 25 (USP25) on glioma cell proliferation, migration, invasion, and its underlying mechanism. Methods: The USP25-overexpressed and USP25-knockdown glioma cells were established on U251 and U87 cells, respectively. Glioma cell proliferation ability was evaluated by CCK-8 assay. Cell apoptosis and cell cycle were determined utilizing flow cytometry. The Transwell assay measured cell invasion with wound healing used for cell migration detection. Western blotting established key protein expression levels in the Wnt/ß-catenin pathway. The coimmunoprecipitation was used to check Thankyrase 1 (TNKS1) ubiquitination levels. Results: TNKS1 expression levels were found to be considerably repressed in USP25-knockdown glioma cells and elevated in USP25-overexpressed glioma cells, accompanied by Wnt/ß-catenin pathway key protein downregulation and upregulation, respectively. Glioma cell invasion, migration, and proliferation activity were dramatically inhibited in USP25-knockdown glioma cells and promoted in USP25-overexpressed glioma cells. TNKS1 ubiquitination level was knowingly increased in USP25-knockdown glioma cells and reduced in USP25-overexpressed glioma cells, suggesting TNKS1 ubiquitination levels were negatively regulated by USP25. Conclusion: USP25 facilitated glioma cell invasion, migration, and proliferation by regulating Wnt/ß-catenin through the deubiquitination on TNKS1.

Experience and modification of skull base reconstruction results in lower complications rates.

OBJECTIVES: To investigate the efficacy of nasal septum bone flap combined with vascularized pedicle nasoseptal flap (VP-NSF) in the treatment of high-flow cerebrospinal fluid (CSF) leakage in the endonasal endoscopic skull base surgery. METHODS: A total of 156 patients in group A used a multi-layer skull base reconstruction method of fat-absorbable artificial dura mater- fascia lata-VP-NSF, and were treated with drainage of the lumbar cistern after surgery, in addition, a total of 94 patients in group B used a multi-layer skull base reconstruction method of fat-absorbable artificial dura mater-nasal septal bone flap-VP-NSF, and no lumbar cistern drainage was performed after surgery. Analyzed and compared the differences of postoperative cerebrospinal fluid rhinorrhea, intracranial infection, re-repair, average bed rest time, pulmonary infection and deep venous thrombosis of lower extremities were analyzed and compared in the two groups. RESULTS: In group A, 11 cases of cerebrospinal fluid rhinorrhea occurred after operation. In addition, 15 cases developed intracranial infection. During this period, there were 20 cases of pulmonary infection and 3 cases of deep venous thrombosis of lower extremities. In group B, there were 1 case of cerebrospinal fluid rhinorrhea (P < 0.05), 2 cases of intracranial infection (P < 0.05), 2 cases of pulmonary infection (P < 0.05), and 0 case of deep venous thrombosis of lower extremities (P > 0.05). CONCLUSION: Nasal septum bone flap combined with VP-NSF is effective in the treatment of high-flow CSF leaks in the endonasal endoscopic skull base surgery, which can avoid postoperative lumbar cistern drainage and is worth popularizing.

The eagle sign: a new preoperative MRI-based tool for predicting topographic correlation between craniopharyngioma and hypothalamus.

PURPOSE: Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. MATERIALS AND METHODS: Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. RESULTS: A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. CONCLUSION: "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

A propensity-adjusted comparison of endoscopic endonasal surgery versus transcranial microsurgery for pediatric craniopharyngioma: a single-center study.

OBJECTIVE: When comparing endoscopic endonasal surgery (EES) and transcranial microsurgery (TCM) for adult and mixed-age population craniopharyngiomas, EES has become an alternative to TCM. To date, studies comparing EES and TCM for pediatric craniopharyngiomas are sparse. In this study, the authors aimed to compare postoperative complications and surgical outcomes between EES and TCM for pediatric craniopharyngiomas. METHODS: The data of pediatric patients with craniopharyngiomas who underwent surgery between February 2009 and June 2021 at a single center were retrospectively reviewed. All included cases were divided into EES and TCM groups according to the treatment modality received. The baseline characteristics of patients were compared between the groups, as well as surgical results, perioperative complications, and long-term outcomes. To control for confounding factors, propensity-adjusted analysis was performed. RESULTS: Overall, 51 pediatric craniopharyngioma surgeries were identified in 49 patients, among which 35 were treated with EES and 16 were treated with TCM. The proportion of gross-total resection (GTR) was similar between the groups (94.3% for EES vs 75% for TCM, p = 0.130). TCM was associated with a lower rate of hypogonadism (33.3% vs 64.7%, p = 0.042) and a higher rate of growth hormone deficiency (73.3% vs 26.5%, p = 0.002), permanent diabetes insipidus (DI) (60.0% vs 29.4%, p = 0.043), and panhypopituitarism (80.0% vs 47.1%, p = 0.032) at the last follow-up. CSF leakage only occurred in the EES group, with no significant difference observed between the groups (p > 0.99). TCM significantly increased the risk of worsened visual outcomes (25.0% vs 0.0%, p = 0.012). However, TCM was associated with a significantly longer median duration of follow-up (66.0 vs 40.5 months, p = 0.007) and a significantly lower rate of preoperative hypogonadism (18.8% vs 60.0%, p = 0.006). The propensity-adjusted analysis revealed no difference in the rate of recurrence, hypogonadism, or permanent DI. Additionally, EES was associated with a lower median gain in BMI (1.5 kg/m2 vs 7.5 kg/m2, p = 0.046) and better hypothalamic function (58.3% vs 8.3%, p = 0.027) at the last follow-up. CONCLUSIONS: Compared with TCM, EES was associated with a superior visual outcome, better endocrinological and hypothalamic function, and less BMI gain, but comparable rates of GTR, recurrence, and perioperative complications. These findings have indicated that EES is a safe and effective surgical modality and can be a viable alternative to TCM for pediatric midline craniopharyngiomas.

Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors.

BACKGROUND: Matrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes. METHODS: In this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan-Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes. RESULTS: MMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes. CONCLUSION: MMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.

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.

Outcomes and Complications of Aggressive Resection Strategy for Pituitary Adenomas in Knosp Grade 4 With Transsphenoidal Endoscopy.

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.

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.