Characterization and clinical implications of different malignant transformation patterns in diffuse low-grade gliomas.

Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2-2 (n = 81, 35.4%), group 2-3 (n = 91, 39.7%), and group 2-4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2-2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2-2 had the longest survival, followed by group 2-3 and then group 2-4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.

Suprasellar arachnoid cysts: systematic analysis of 247 cases with long-term follow-up.

At present, limited data exists to discuss the characteristics of suprasellar arachnoid cysts (SACs). The aim of this study is to elucidate the relationship between characteristics of cysts and outcomes, quantitatively analyze improvement in hydrocephalus, and evaluate the risk factors for the prognosis of SACs treated by endoscope. From June 2002 to 2017 December, 247 cases of SACs treated by endoscope in Beijing Tiantan Hospital were included in this study. The severity of hydrocephalus was evaluated by Evans' index (EI). The results showed that the slit-valve and the transparent/thin membrane were noted in 86.2% and 76.5% of overall patients, respectively, and the distribution differences among age-groups were statistically significant (p < 0.01). After a mean follow-up duration of 73.1 months, 18 patients underwent a reoperation. Ventriculocystostomy (VC) (hazard ratio (HR), 3.37; 95% confidence interval (CI), 1.2-9.47; p = 0.024) and history of treatment (HR, 3.98; 95% CI, 1.31-12.31; p = 0.015) were adverse factors for reoperation rate. MRI at 1-year follow-up revealed mean decreases of 78.4% and 9.13% in cyst size and EI. No paraventricular edema was an adverse factor associated with the improvement in hydrocephalus (HR, 11.22; 95% CI, 5.43-23.18; p < 0.01). These results indicated that ventriculocystocisternostomy (VCC) and no history of treatment is favorable factors for prognosis of SACs treated by endoscope. If feasible, VCC is the optimal choice for SACs. Slit-valve phenomenon and transparent/thin membrane are correlated with age but did not influence the outcomes of endoscopic fenestration. The mechanism for the expansion of cysts may be different between child and adult patients. Paraventricular edema is a favorable factor for the improvement in hydrocephalus after endoscopic surgery.

Suprasellar arachnoid cysts in adults: clinical presentations, radiological features, and treatment outcomes.

A tendency for suprasellar arachnoid cysts (SACs) to occur in young children is known. Data of adult SACs were rare in previous reports. The aim of this study is to discuss their clinical presentations, radiological features, and treatment outcomes based on 23 adult patients who underwent endoscopic fenestration in our hospital between January 2003 and December 2018. Preoperative cyst volume ranged from 12.3 to 72.5 cm3 (mean 39.8 ± 19.8). Endocrine disorders occurred in 7 (30.4%) patients. Hydrocephalus was observed in 20 patients. In the patients with hydrocephalus, the mean preoperative Evans' index (EI) (%) and frontooccipital horn ratio (FOHR) (%) were 44.8 (ranged 32.2-63.4) and 49.6 (ranged 36.7-59.8), respectively. A bivariate correlation showed significant positive association between preoperative cyst volume and preoperative EI or FOHR (Pearson correlation, r = 0.607, p = 0.005; r = 0.583, p = 0.007). The slit-valve phenomenon was observed in 13 (56.5%) patients. Pale/tenacious cyst walls were observed in 12 (52.2%) patients. Postoperatively, all patients achieved the improvement in clinical symptoms and a decrease in cyst size. The mean decreases in cyst volume, EI, and FOHR were 64.7%, 7.89%, and 5.8%, respectively. A bivariate correlation indicated the irrelevance between the postoperative cyst volume and postoperative EI or FOHR (Pearson correlation: r = 0.37, p = 0.11; r = 0.43, p = 0.054). These results reveal that there are a few differences in several aspects between adult patients and child patients. The severity of hydrocephalus is correlated with cyst size in adult patients. Additionally, the excellent outcomes in adult SACs can be obtained by endoscopic fenestration.

A good choice for the patients with prior failed ventriculoperitoneal shunt treatment of suprasellar arachnoid cysts: endoscopic fenestration.

To investigate the effectiveness of endoscopic fenestration in the patients with prior failed ventriculoperitoneal (VP) shunt treatment of suprasellar arachnoid cysts (SACs). Between 2012 and 2018, four pediatric patients of SACs with previous failed VP shunt treatment were surgically treated using endoscopic ventriculocystocisternostomy (VCC) in our hospital. The clinical symptoms, imaging data, and surgical outcomes were collected and analyzed retrospectively. A literature review is provided with regard to the reasons of shunt failure and surgical outcome of further endoscopic fenestration in the previously reported patients of SACs with prior failed VP shunt. For the 4 cases, the initial clinical symptoms relieved or even disappeared after shunt placement, but, respectively, recurred 2, 6, 11, and 6 months later. MR scans were conducted when the clinical symptoms reappeared and showed a cyst had greatly enlarged after shunt placement. Furthermore, VP shunt-related slit ventricle was also demonstrated in 3 cases. Clinical improvement and cysts shrinkage occurred in all 4 patients after VCC. Slit ventricle and hydrocephalus were also resolved. Three patients had their shunt apparatus removed after VCC, and another patient's guardian refused to remove the shunt apparatus. Subdural hematoma occurred in one case after shunt apparatus removal. Four patients have been stable during follow-up period (mean follow-up 26.5 months). All the three patients whose VP shunt were removed were shunt independence. There were 24 patients who underwent endoscopic fenestration as an alternative to the failed VP shunt treatment in the published reports. Added our 4 patients to the published group, the effective rate of endoscopic fenestration for SACs following previous failed VP shunt treatment was approximately 93% (26/28). Of the 24 patients, the shunt apparatuses were in situ or reimplantation in 9 patients due to shunt dependence. The correction to recognize the SAC is the first condition to select the optimal management philosophy. The analysis of the series suggests endoscopic operation is still an effective and safe option in the SAC patients with previous failed VP shunt, and the shunt apparatus can be removed for some patients. The short interval time between shunt operation and endoscopic fenestration is conductive to return patients to the shunt-free state.

Comparative analysis of outcomes following craniotomy and expanded endoscopic endonasal approach resection of tuberculum sellae meningiomas: a single-institution study.

Background: Traditionally, supratentorial craniotomy has been used to sever tuberculum sellae meningiomas (TSMs), but there has been a remarkably increasing tendency of extended endoscopic endonasal approach (EEEA) used to treat TSMs in the recent decade. Several documents have described the advantages and disadvantages of both approaches, but there is no consensus on whether one is superior to the other. Objective: This study aimed to compare surgical outcomes between craniotomy and EEEA for TSMS treated at our institution. Methods: From January 2015 to December 2021, a total of 84 cases of TSMs were included in this study. Cases were separated into two groups: the craniotomy group and the EEEA group. Their anamneses and surgical records were reviewed. Demographic data, presenting symptoms, tumor volume, extent of resection, visual outcomes, and follow-up data were tabulated. The Kaplan-Meier curves were constructed for the PFS for both cohorts. Results: Complete data were available for 84 surgeries; 39 cases were treated via craniotomy, and 45 were treated via EEEA. Patient demographic data, pre-operative symptoms, and tumor characteristics were similar between the two cohorts. The extent of resection was similar between the two groups (GTR: 91.11% EEEA vs. 87.18% craniotomy; STR 8.89 vs. 12.82%, p = 0.91). There was no difference in visual outcomes between both groups (92.1 vs. 84.84%, p = 0.46). An increased rate of cranial nerve injury was noted in the craniotomy group (0 vs. 10.25%, p = 0.04). Post-operative CSF leak rate occurred in one patient in the EEEA group. The PFS curves (p = 0.52) and recurrence/progression rates (13.33 vs. 20.51%, p = 0.39) were similar between the two groups. Conclusion: Both EEEA and craniotomy can successfully sever TSMs. The recurrence/progression rate and PFS appear to be similar between the two groups. Although there are no differences in EOR and visual outcomes between the two groups, there was a clear trend in the EEEA group to obtain a better outcome. CSF leakage was common in the EEEA cohort, whereas the rate of cranial nerve injury was found to be higher in the craniotomy cohort. We believe that our data support the conclusion that EEEA surgery is the preferred approach for the removal of TSMs.

The clinical application of intraoperative visual evoked potential in recurrent craniopharyngiomas resected by extended endoscopic endonasal surgery.

OBJECTIVE: The protection of visual function is a major challenge for recurrent craniopharyngioma due to the interface between tumor and surrounding structure (esp. optic nerve) is more unclear. Intraoperative visual evoked potential (VEP) has been integrated into transsphenoidal surgery for pituitary adenomas and primary craniopharyngiomas in the prediction of postoperative visual outcome. In the present study, we firstly analyzed the clinical value of the VEP in the prediction of postoperative visual outcome for recurrent craniopharyngiomas by extended endoscopic endonasal surgery (EEES). METHODS: Thirty-six patients with recurrent craniopharyngiomas who underwent EEES with intraoperative VEP monitoring were retrospectively reviewed. The association between the changes in the VEP amplitude and postoperative visual outcome was determined. In addition, other potential prognostic factors with regard to postoperative visual outcomes were also included in the analysis. RESULTS: Gross total resection (GTR) was achieved in 32 patients (88.9%). Reproducible and stable VEP was recorded in 72 eyes. We recorded that there were 29 eyes remained stable VEP amplitude intraoperation, 4 (13.8%) of which suffered new visual acuity (VA) and 5 (17.2%) suffered new visual field (VF) defects after surgery. A transient VEP decrease was recorded in 41 eyes, 8 (19.5%) of which suffered from visual deterioration. Of 2 eyes with a permanent VEP decrease, 2 (100%) experienced postoperative visual impairment. Clinical variable analyses revealed a significant correlation between recurrent craniopharyngioma and age, adhesion with optic nerve, postoperative VA, and intraoperative VEP amplitude. Unstable VEP amplitude during operation and tight adhesion were independent risk factors for postoperative VA. Tight adhesion and a larger tumor volume were independent risk factors for postoperative VF defects. CONCLUSIONS: EEES provides a unique view for the lesions under and behind the chiasm and achieve higher rates of GTR with improved visual outcomes. Tight adhesion and unstable VEP amplitude were strong predictors of postoperative visual impairment. Recurrent craniopharyngiomas are more likely to adhere to the optic nerve, VEP is more likely to be unstable during operation, and the improvement rate of postoperative visual function is lower than primary craniopharyngiomas. So intraoperative VEP is more necessary for recurrent craniopharyngiomas.

Fornix alterations induce the disruption of default mode network in patients with adamantinomatous craniopharyngiomas.

Adamantinomatous craniopharyngioma (ACPs) are rare embryonic tumors and often involve the hypothalamus. The underlying neural substrate of the hypothalamic involvement (HI)-related cognitive decline in patients with ACP is still unclear. We aimed to combine the multi-modal neuroimaging and histological characteristics of the ACP to explore the potential neural substrate of the HI-related cognitive decline. 45 patients with primary ACPs (invasive, 23; noninvasive, 22) and 52 healthy control subjects (HCs) were admitted to the cross-sectional study. No significant difference in cognitive domains was observed between HCs and patients with noninvasive ACPs (NACP). Patients with invasive ACPs (IACP) showed significantly lower working memory performance (WM, p = 0.002) than patients with NACP. The WM decline was correlated with the disruption of the medial temporal lobe (MTL) subsystem in the default mode network (DMN) (r = 0.45, p = 0.004). The increased radial diffusivity of the fornix, indicating demyelinating process, was correlated with the disruption of the MTL subsystem (r = -0.48, p = 0.002). Our study demonstrated that the fornix alterations link DMN disruption to HI-related cognitive decline in patients with ACPs. ACPs that invade the hypothalamus can provide a natural disease model to investigate the potential neural substrate of HI-related cognitive decline.

The predictive value of intraoperative visual evoked potential for visual outcome after extended endoscopic endonasal surgery for adult craniopharyngioma.

OBJECTIVE: Due to the proximity of craniopharyngioma to the optic apparatus, one of the most common complications after surgery is visual deterioration. Intraoperative visual evoked potential (VEP), as a means of real-time visual function monitoring, has been integrated into transsphenoidal surgery for pituitary adenoma to predict postoperative visual outcome. Compared with pituitary tumor, craniopharyngioma often adheres to optic nerves, with increased risk of postoperative visual impairment. Furthermore, extended endoscopic endonasal surgery (EEES) can provide direct visualization of the surgical plane between the craniopharyngioma and the optic nerves, which contributes to analysis of the mechanism of real-time VEP changes during surgery. Therefore, VEP monitoring applied during EEES for craniopharyngioma may have more clinical value. However, only 9 patients who underwent EEES with VEP monitoring for craniopharyngioma have been sporadically reported to date. In this paper, the authors present the largest series to date analyzing the clinical value of VEP to predict postoperative visual outcome in adult patients with craniopharyngioma. METHODS: Sixty-five adult patients who underwent EEES with intraoperative VEP monitoring for primary craniopharyngioma were retrospectively reviewed. The association between changes in VEP amplitude and postoperative visual outcome was determined. In addition, other potential prognostic factors with regard to postoperative visual outcomes were included in the analysis. RESULTS: Gross-total resection was achieved in 59 patients (90.8%). Reproducible and stable VEP was recorded in 128 of 130 eyes (98.5%). During surgery, VEP remained stable in 108 eyes, 10 (9.3%) of which had new visual acuity (VA) and/or visual field (VF) defects after surgery. Transient VEP decrease was recorded in 15 eyes, 4 (26.7%) of which had visual deterioration. Of the 5 eyes with permanent VEP decrease, 3 (60%) experienced postoperative visual impairment. Permanent VEP decrease (OR 19.868, p = 0.007) and tight adhesion (OR 6.104, p = 0.040) were independent adverse factors for postoperative VA deterioration. Tight adhesion (OR 7.150, p = 0.002) and larger tumor volume (OR 1.066, p = 0.001) were significant risk factors for postoperative VF defects. CONCLUSIONS: Intraoperative VEP monitoring can serve as a real-time warning to guide surgeons to avoid postoperative visual impairment. It effectively predicted VA changes in adult patients with craniopharyngioma after EEES. Tight adhesion and larger tumor volume were also strong predictors of postoperative visual impairment.

Prognostic Utility of Optical Coherence Tomography for Visual Outcome After Extended Endoscopic Endonasal Surgery for Adult Craniopharyngiomas.

INTRODUCTION: Owing to the close vicinity of the optic chiasma, visual dysfunction is known as one of the most common surgical indications and postoperative complications in adult patients with craniopharyngiomas, probably leading to poor quality of life. Historically, very few consistent predictive factors associated with the visual outcome are identified, which may not be helpful for patient counseling and preoperative decision making. Recently, optical coherence tomography (OCT) serving as a novel high-resolution imaging technique can assess the retinal morphology by measuring the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex thickness. However, few studies have examined the prognostic utility of OCT parameters for visual outcome after surgery for craniopharyngiomas. This study aims to use the largest series to evaluate the association between OCT parameters and visual outcome after extended endoscopic endonasal surgery (EEES) for primary craniopharyngiomas in adults. MATERIAL AND METHODS: From October 2018 to October 2020, one hundred and seventy eyes in 88 adult patients with newly confirmed craniopharyngiomas were retrospectively reviewed and pertinent prognostic factors were analyzed. RESULTS: Gross total resection was performed in 82 (93.2%) patients. The median postoperative follow-up time was 10.9 months. Multiple logistic regression analysis showed that increased temporal cpRNFL thickness was associated with higher odds of visual acuity (VA) improvement and maintenance (OR = 1.070; 95% CI, 1.005-1.140; p = 0.035), and greater inferior cpRNFL thickness was significantly associated with visual field (VF) improvement and maintenance (OR = 1.034; 95% CI, 1.001-1.068; p = 0.046). Furthermore, tight adhesion between optic nerves and craniopharyngiomas was demonstrated as an independent adverse factor for either postoperative VA or VF (p = 0.048, p = 0.030, respectively). The ROC results further verified the robustness of the prediction model either in VA (AUC = 0.843; 95% CI, 0.734-0.952; p < 0.001) or VF (AUC = 0.849; 95% CI, 0.741-0.958; p < 0.001). CONCLUSION: Preoperative OCT can effectively predict visual outcome after EEES for adult craniopharyngiomas. It can also serve as a reliable alternative to evaluate preoperative visual field defects, especially for patients with lower compliance. Tight adhesion was confirmed as an independent risk factor for postoperative visual outcome. The OCT-based multivariable prediction models developed in the present study may contribute to patient counseling on visual prognosis.

Predicting the location of the preoptic and anterior hypothalamic region by visualizing the thermoregulatory center on fMRI in craniopharyngioma using cold and warm stimuli.

Hypothalamic nuclei in the preoptic and anterior hypothalamic region (POAH) are critically involved in thermoregulation and neuroendocrine regulation and can be displaced by craniopharyngiomas (CPs). We aimed to locate the POAH by visualizing hypothalamic thermoregulation through task-related functional magnetic resonance imaging (fMRI) to guide hypothalamus protection intraoperatively. Nine adult healthy volunteers (HVs) and thirty-two adult primary CP patients underwent task-related fMRI for POAH localization by warm (60° C) and cold (0° C) cutaneous thermoreceptor stimulation. Approach selection and intraoperative POAH protection were performed based on preoperative POAH localization. In all HVs and patients, significant single positive blood oxygen level-dependent (BOLD) signal changes were located in the POAH. The BOLD activity was significantly greater for cold (P=0.03) and warm (P=0.03) stimuli in patients than in HVs. Gross total resection and near-total resection were achieved in 28 (87.5%) and 4 (12.5%) patients, respectively. New-onset diabetes insipidus and new-onset hypopituitarism occurred in 6 patients (18.8%) and 10 patients (31.3%), respectively. Our findings suggest that cutaneous thermoreceptor stimulation could accurately activate the hypothalamic thermoregulatory center and allow POAH localization through task-related fMRI. Preoperative POAH localization could help neurosurgeons protect hypothalamic function intraoperatively. The CP patients were more sensitive to thermal stimulation.

Non-Invasive Radiomics Approach Predict Invasiveness of Adamantinomatous Craniopharyngioma Before Surgery.

PURPOSE: Craniopharyngiomas (CPs) are benign tumors, complete tumor resection is considered to be the optimal treatment. However, although histologically benign, the local invasiveness of CPs commonly contributes to incomplete resection and a poor prognosis. At present, some advocate less aggressive surgery combined with radiotherapy as a more reasonable and effective means of protecting hypothalamus function and preventing recurrence in patients with tight tumor adhesion to the hypothalamus. Hence, if a method can be developed to predict the invasiveness of CP preoperatively, it will help in the development of a more personalized surgical strategy. The aim of the study was to report a radiomics-clinical nomogram for the individualized preoperative prediction of the invasiveness of adamantinomatous CP (ACPs) before surgery. METHODS: In total, 1,874 radiomics features were extracted from whole tumors on contrast-enhanced T1-weighted images. A support vector machine trained a predictive model that was validated using receiver operating characteristic (ROC) analysis on an independent test set. Moreover, a nomogram was constructed incorporating clinical characteristics and the radiomics signature for individual prediction. RESULTS: Eleven features associated with the invasiveness of ACPs were selected by using the least absolute shrinkage and selection operator (LASSO) method. These features yielded area under the curve (AUC) values of 79.09 and 73.5% for the training and test sets, respectively. The nomogram incorporating peritumoral edema and the radiomics signature yielded good calibration in the training and test sets with the AUCs of 84.79 and 76.48%, respectively. CONCLUSION: The developed model yields good performance, indicating that the invasiveness of APCs can be predicted using noninvasive radiological data. This reliable, noninvasive tool can help clinical decision making and improve patient prognosis.

Expression of SPRR3 is associated with tumor cell proliferation and invasion in glioblastoma multiforme.

Esophagin, also known as small proline-rich protein 3 (SPRR3), has been demonstrated to be important in the initiation and progression of numerous types of tumor, including colorectal and breast cancer. However, studies concerning the biological functions of SPRR3 in glioblastoma multiforme (GBM) are limited. Therefore, we aimed to identify the functions and molecular mechanisms underlying the role of SPRR3 in GBM. Hypomethylation of SPRR3 was observed and associated with a poor clinical outcome in GBM patients compared with healthy individuals by using gene methylation profiling. The present study was performed to investigate the expression status and effects of SPRR3 in GBM. The U251 cell line was used in the functional analyses. Cell growth was examined by MTT and colony formation assay. Cell invasion was measured using the Transwell invasion assay. The expression of SPRR3 in tissue samples was examined by immunohistochemistry. The results revealed that the overexpression of SPRR3 accelerates U251 cell proliferation and invasion. It was also observed that SPRR3 was markedly upregulated in 72.7% of GBM samples (24/33) compared with the normal tissue. These results suggest that an increased expression of SPRR3 is involved in tumorigenesis.