The minimally invasive transventricular endoscopic approach to third ventricular lesions in pediatric patients-all-rounder with limitations?

INTRODUCTION: The surgical management of third ventricular lesions poses unique challenges, requiring careful consideration of various approaches and techniques. This study focuses on the transventricular transforaminal endoscopic approach and aims to provide insights into its indications, limitations, technical nuances, and potential complications in pediatric patients. METHODS: A retrospective analysis was conducted using data from a 13-year period on pediatric patients who were subjected to transforaminal endoscopic surgery for third ventricular lesions. The study utilized a prospectively maintained internal database, extracting demographic data, preoperative assessment, surgical details, and postoperative follow-up information. The surgical technique is presented in detail, and exemplary case reports highlight relevant surgical considerations. RESULTS: Out of 578 endoscopic transforaminal procedures, 24 surgeries were performed on pediatric patients with third ventricular lesions. Performed procedures consisted of cyst resection (13 cases), solid tumor resection (4 cases), and tumor biopsies with CSF pathway restoration (7 cases). The mean age at the time of surgery was 7.6 years. Postoperatively, 14 patients showed transient nausea and vomiting (58.3%); 10 patients showed pneumocephalus on postoperative MRI (41.7%). No emergency postoperative re-interventions nor perioperative mortality were observed. CONCLUSION: The endoscopic transventricular transforaminal approach is a safe approach for lesion resection, CSF pathway restoration, and tumor biopsy in pediatric patients with third ventricle lesions. The author's results support the use of this minimally invasive technique as an alternative to more extensive approaches, particularly to the interforniceal interhemispheric approach. However, surgical success is highly dependent to the individual surgeon's experience and moreover to a suitable indication setting. Careful preoperative planning and knowledge of the approaches' pro and cons is mandatory for successful application of this approach.

Considerations on surgical strategies and associated risk profiles for endoscopic tumor biopsies within the third ventricle and periaqueductal region.

INTRODUCTION: Neuroendoscopic techniques have proven to be a successful and minimally-invasive technique for tumor biopsies within the third ventricle in pediatric patients. However, a comprehensive assessment of associated surgical strategies, techniques, and morbidity is essential to optimize patient outcomes. METHODS: This retrospective study analyzed full endoscopic tumor biopsies in pediatric patients with tumors in the third ventricle and periaqueductal region. Data from 1995 to 2022 were collected from medical records, imaging, and intraoperative video documentation. RESULTS: In this study, 16 shear endoscopic tumor biopsies were performed using the transventricular transforaminal approach. Tumors were located in the anterior or mid part of the third ventricle (50%) or in the periaqueductal and pineal recess region (50%). Preoperative hydrocephalus was seen in 81.25%. Tumor biopsies were harvested successfully in all cases. Simultaneous ETV was performed in 12 (75%) cases and additional septostomy in 3 (18.75%). Significant intraoperative bleeding occurred in 3 cases (18.75%). All bleeding situations could be successfully managed with continuous irrigation. Histopathology revealed astrocytoma as the predominant diagnosis (75%). No new neurologic deficits were observed, except for one case of transient oculomotor nerve paralysis after ETV. Hydrocephalus persisted in 18.6% of all cases with the need of urgent ventriculoperitoneal shunting in two patients. CONCLUSION: In conclusion, neuroendoscopy emerges as an effective technique for tumor biopsies within the third ventricle in pediatric patients, offering the added advantage of simultaneous treatment of obstructive hydrocephalus. However, it is essential to acknowledge the specific intra- and postoperative risks associated with various surgical strategies. The safe management and achievement of favorable clinical results demand extensive experience and expertise.

Image quality and related outcomes of the ShuntScope for catheter implantation in pediatric hydrocephalus-experience of 65 procedures.

PURPOSE: Ventricular catheter implantation in pediatric hydrocephalus can become a highly challenging task due to abnormal anatomical configuration or the need for trans-aqueductal stent placement. Transluminal endoscopy with the ShuntScope has been invented to increase the rate of successful catheter placements. This study aims to evaluate ShuntScope's image qualities and related surgical outcomes in the pediatric population. METHODS: A retrospective analysis of all pediatric patients undergoing ventricular catheter placement using the ShuntScope from 01/2012 to 01/2022 in the author's department was performed. Demographic, clinical, and radiological data were evaluated. The visualization quality of the intraoperative endoscopy was stratified into the categories of excellent, medium, and poor and compared to the postoperative catheter tip placement. Follow-up evaluation included the surgical revision rate due to proximal catheter occlusion. RESULTS: A total of 65 ShuntScope-assisted surgeries have been performed on 51 children. The mean age was 5.1 years. The most common underlying pathology was a tumor- or cyst-related hydrocephalus in 51%. Achieved image quality was excellent in 41.5%, medium in 43%, and poor in 15.5%. Ideal catheter placement was achieved in 77%. There were no intraoperative complications and no technique-related morbidity associated with the ShuntScope. The revision rate due to proximal occlusion was 4.61% during a mean follow-up period of 39.7 years. No statistical correlation between image grade and accuracy of catheter position was observed (p-value was 0.290). CONCLUSION: The ShuntScope can be considered a valuable addition to standard surgical tools in treating pediatric hydrocephalus. Even suboptimal visualization contributes to high rates of correct catheter placement and, thereby, to a favorable clinical outcome.

Endoscope-assisted resection of brainstem cavernous malformations.

Targeted surgical precision and minimally invasive techniques are of utmost importance for resectioning cavernous malformations involving the brainstem region. Minimisation of the surgical corridor is desirable but should not compromise the extent of resection. This study provides detailed information on the role of endoscopy in this challenging surgical task. A retrospective analysis of medical documentation, radiologic studies and detailed intraoperative video documentation was performed for all consecutive patients who underwent surgical resection of brainstem cavernous malformations between 2010 and 2020 at the authors' institution. A case-based volumetry of the corticotomy was performed and compared to cavernoma dimensions. A total of 20 procedures have been performed in 19 patients. Neuroendoscopy was implemented in all cases. The mean size of the lesion was 5.4 (± 5) mm3. The average size of the brainstem corticotomy was 4.5 × 3.7 (± 1.0 × 1.1) mm, with a median relation to the cavernoma's dimension of 9.99% (1.2-31.39%). Endoscopic 360° inspection of the resection cavity was feasible in all cases. There were no endoscopy-related complications. Mean follow-up was 27.8 (12-89) months. Gross-total resection was achieved in all but one case (95%). Sixteen procedures (80%) resulted in an improved or stable medical condition. Eleven patients (61.1%) showed further improvement 12 months after the initial surgery. With the experience provided, endoscopic techniques can be safely implemented in surgery for BSCM. A combination of neuroendoscopic visualisation and neuronavigation might enable a targeted size of brainstem corticotomy. Endoscopy can currently be considered a valuable additive tool to facilitate the preparation and resection of BSCM.

miRNA-26a expression influences the therapy response to carmustine wafer implantation in patients with glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme is the most frequent malignant brain tumor in adults being marked with a very poor prognosis. Therapy concept implies concomitant radio-chemotherapy and facultative implantation of carmustine-eluted wafer. Current literature suggests microRNA 26a expression in glioblastoma to interact with alkylating chemotherapy. Subsequently, the aim of this study was to investigate the correlation of miRNA-26a expression and carmustine wafer implantation and its potential usefulness as a predictive marker for therapy response. METHODS: In total, 229 patients with glioblastoma multiforme were included into the final analysis. Of them, 80 cases were recruited from the Saarland University Medical Center for a retrospective matched-pair analysis stratified after therapy regime: One group (carmustine wafer group; n=40) received concomitant radio-chemotherapy with carmustine wafer implantation. The other group (control group; n=40) only received concomitant radio-chemotherapy. The results were confirmed by comparing them with an independent dataset of 149 patients from the TCGA database. All tumor specimens were evaluated for miRNA-26a expression, MGMT promoter methylation, and IDH1 R132H mutation status, and the results were correlated with the clinical data. RESULTS: Twenty-three patients in the carmustine wafer group showed low expression of miRNA-26a, while 17 patients showed a high expression. In the control group, 28 patients showed low expression, while 12 patients showed a high expression. The patients with high miRNA-26a expression in the carmustine wafer group were characterized by a significantly longer overall (hazard ratio [HR] 2.750 [95% CI 1.352-5.593]; p=0.004) and progression-free survival (HR 3.091 [95% CI 1.436-6.657]; p=0.003) than patients with low miRNA-26a expression. The 17 patients in the carmustine wafer group with high miRNA-26a expression showed a significantly longer progression-free survival (p=0.013) and overall survival (p=0.007) compared with the control group. There were no such correlations identified within the control group. TCGA datasets supported these findings. CONCLUSIONS: MiRNA-26a expression turned out to be a promising predictor of therapy response and clinical outcome in glioblastoma patients treated with carmustine wafer implantation. For evaluation of the role of miRNA-26a in a combined therapy setting, further studies are needed in order to translate general findings to the patient's individual situation.

Epigenetic Characteristics in Primary and Recurrent Glioblastoma-Influence on the Clinical Course.

OBJECTIVE: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. METHODS: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of MGMT, p15, and p16 methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. RESULTS: Instability was observed in all examined epigenetic markers. MGMT methylation changed in 30% of patients, p15 methylation changed in 35%, and p16 methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. CONCLUSIONS: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.

Image Quality and Related Outcomes of the ShuntScope-Guided Catheter Implantation in Adult Hydrocephalus: Experience of 63 Procedures.

BACKGROUND: Ventricular catheter (VC) placement in the selected subset of adult hydrocephalus can be highly challenging due to abnormal anatomical configuration or the need for trans-aqueductal stent placement. Transluminal endoscopy with the ShuntScope has been invented to increase the success rate of catheter placement. This study evaluates the image qualities of ShuntScope and related surgical outcomes in adults. METHODS: A retrospective analysis of all adult patients undergoing VC placement using the ShuntScope from November 2011 to July 2022 in the authors' department was performed. Demographic, clinical, and radiologic data were evaluated. The visualization quality of the intraoperative endoscopy was stratified into excellent, medium, and poor, and compared to the postoperative catheter tip placement. Follow-up evaluation included the surgical revision rate due to proximal catheter misplacement. RESULTS: A total of 63 ShuntScope-assisted surgeries have been performed on 60 adults. The mean age of the patients was 48.43 years. The most common underlying pathology was a tumor- or cyst-related cerebrospinal fluid (CSF) impairment in 38.33%, followed by a pseudotumor cerebri in 21.66%. The achieved image quality was excellent in 39.68%, medium in 47.62%, and poor in 12.7%. Ideal catheter placement was achieved in 79.37%. There were no intraoperative complications associated with the use of the ShuntScope. The revision rate due to suboptimal proximal VC placement was 4.76% during a mean follow-up period of 27.75 months. A statistical correlation between the image quality and accuracy of the catheter position was observed (p < 0.001). CONCLUSION: The ShuntScope can be considered an important addition to standard surgical tools in treating a selected subset of adult hydrocephalus. Direct visualization might even help achieve correct placement of the catheter in the cases with blurred vision and limited visual overview.

From fixed-pressure paediGAV to programmable proGAV/proSA serial valves for pediatric hydrocephalus within the 1st year of life: a technical single-center analysis.

OBJECTIVE: Programmable valves have gained increasing popularity in the complex treatment of pediatric hydrocephalus. Over the last decade, adjustable serial valves have gradually replaced fixed-pressure valves in the authors' department. The present study investigates this development by analyzing shunt- and valve-related outcomes for this vulnerable population. METHODS: A retrospective analysis of all shunting procedures between January 2009 and January 2021 in children younger than 1 year of age was performed at the authors' single-center institution. Postoperative complications and surgical revisions were set as outcome parameters. Shunt and valve survival rates were evaluated. Statistical analysis compared children who underwent implantation of the Miethke proGAV/proSA programmable serial valves with those who underwent implantation of the fixed-pressure Miethke paediGAV system. RESULTS: Eighty-five procedures were evaluated. The paediGAV system was implanted in 39 cases and the proGAV/proSA in 46 cases. The mean ± SD follow-up was 247.7 ± 140 weeks. In 2009 and 2010, paediGAV valves were used exclusively, but by 2019, the use of proGAV/proSA had evolved into the first-line therapy. The paediGAV system was significantly more often revised (p < 0.05). The main indication for revision was proximal occlusion, with or without impairment to the valve. The valve and shunt survival rates of proGAV/proSA were significantly prolonged (p < 0.05). The surgery-free valve survival of proGAV/proSA was 90% after 1 year and 63% after 6 years. There were no overdrainage-related revisions of proGAV/proSA valves. CONCLUSIONS: Favorable shunt and valve survival validates the increasing use of programmable proGAV/proSA serial valves in this delicate population. Potential benefits in postoperative treatment should be addressed in prospective multicenter studies.

MiRNA-181d Expression Correlates in Tumor versus Plasma of Glioblastoma Patients-the Base of a Preoperative Stratification Tool for Local Carmustine Wafer Use.

OBJECTIVE: Patients with a low micro-RNA-181d (miRNA-181d) level in glioblastoma tissue benefit most of carmustine wafer use. The study compares preoperative miRNA-181d plasma and tumor expression. This may form the base to decide, from a preoperative blood test, if carmustine wafer implantation is recommendable. METHODS: A total of 60 patients suffering from glioblastoma treated between 2018 and 2020 were enrolled prospectively. Preoperatively, blood was drawn and the plasma was isolated. Tumor specimens were collected. Blood samples from 30 healthy individuals served as a reference. MiRNA-181d expression in plasma and tumor were acquired as fold change, using quantitative reverse transcription-polymerase chain reaction. Results were correlated with relevant demographic, clinical, and histopathologic aspects of the cohort. Further factors like tumor volume as well as blood panel results were considered. The Cancer Genome Atlas analysis was performed to investigate specific miRNA-181d-protein interactions to elude how miRNA-181 impact therapy response to carmustine. RESULTS: Patients with glioblastoma showed a significant overexpression of miRNA-181d compared with healthy individuals (P = 0.029). There was a significant correlation between miRNA-181d expression in tumor tissue and plasma (P = 0.001, R = 0.51). The sensitivity of low miRNA-181d expression in plasma predicting low miRNA-181d tumor expression was 76.6%. Tumor volume, preoperative medication, and items of blood panel analysis did not influence the prognostic value of plasma miRNA-181d expression. The Cancer Genome Atlas analysis revealed 8 potential protein targets to be regulated by miRNA-181d. CONCLUSION: miRNA-181d seems to be a potential molecular marker that can reliably be detected in blood samples of patients with glioblastoma. It should therefore prospectively be evaluated as a potential preoperative prognostic marker regarding carmustine wafer implantation.

The semisitting position in pediatric neurosurgery: pearls and pitfalls of a 10-year experience.

OBJECTIVE: The authors sought to investigate the pearls and pitfalls of using the semisitting position in pediatric neurosurgery, with special focus on related morbidity and surgical practicability. METHODS: All pediatric cases at a single institution were evaluated retrospectively. Those patients who underwent procedures in the semisitting position between December 2010 and December 2020 were included in the final analysis. Results were compared with all children who underwent surgery in the prone position for posterior fossa lesions within the same time frame. RESULTS: A total of 42 posterior fossa surgeries were performed in 38 children in the semisitting position between December 2010 and December 2020. The mean patient age at the time of surgery was 8.9 years (range 13 months-18 years). The data of 24 surgeries performed in the prone position in 22 children during the same time frame were analyzed in comparison. Three children (7.9%) were diagnosed with a persistent foramen ovale preoperatively. The surgery was completed in all cases. The incidence of venous air embolism (VAE) was 11.9%. There was no VAE-related hemodynamic instability, infarction, or death. Endoscopic techniques were applied safely in 14 cases (33.3%). Postoperative pneumocephalus occurred significantly more frequently in patients who had undergone procedures in the semisitting position (p < 0.05), but without the need for intervention. During 1 surgery (2.4%), the patient experienced a postoperative skull fracture and epidural bleeding due to the skull clamp application. Clinical status of the patients immediately after surgery was improved or stable in 33 of the 42 surgeries (78.6%) performed in the semisitting position. CONCLUSIONS: With attentive performance and an experienced surgical team, the semisitting position is a safe option for posterior fossa surgery in the pediatric population. With a comparable complication profile, the semisitting position offers excellent anatomical exposure, which is ideal for the application of endoscopic visualization. Careful skull clamp application and appropriate monitoring are highly recommended.

A New Clip Generation for Microsurgical Treatment of Intracranial Aneurysms-The First Case Series.

OBJECTIVE: Considerable effort has been made in order to reduce surgical invasiveness while maintaining optimal exploiting of the operative space in aneurysm surgery. One aspect of this evolution is represented by the Lazic (Peter Lazic GmbH, Tuttlingen, Germany) aneurysm clip system. The purpose of this study was to illustrate the new generation clip system in practiced aneurysm surgery. METHODS: A retrospective analysis of all aneurysm surgeries in our departments between December 2015 and January 2018 using the new D-Clip system was performed. Evaluation included standardized retrospective review of the main surgeon, the nursing staff, as well as an analysis of surgical video documentation by objective reviewers. RESULTS: Forty-five patients with 50 intracranial aneurysms underwent surgical clipping using the D-Clip system. A total of 64 permanent and 19 temporary D-Clips were applied. Nine clips needed to be replaced. All aneurysms could be occluded totally. Surgeons considered handling and manoeuvrability of clip application as feasible and good in all cases (100%), even under impaired visibility circumstances (14%). Objective video analysis revealed comparable results. Nursing staff scored handling and practicability of D-Clips equivalent to the preceding L-Clip generation. There were no intraoperative complications. Surgery-related postoperative morbidity was 6.7%. CONCLUSIONS: The new D-Clip system combines an attenuated design for minimally invasive clipping procedures with traditional mechanisms of common clip systems. It therefore appears to be highly versatile in the context of variable different aneurysm morphologies and locations while maintaining high standard surgical safety and efficacy.

The Influence of Distinct Regulatory miRNAs of the p15/p16/RB1/E2F Pathway on the Clinical Progression of Glioblastoma Multiforme.

OBJECTIVE: The microRNAs (miRNAs) -26a, -24, and -21 have been reported as regulators of the P15/P16/RB1/E2F pathway, which plays a major role in glioblastoma multiforme (GBM) progression. In the present study, their predictive marker for the progression of GBMs is evaluated and described. METHODS: The expression of miRNA-21, -24, and -26a was analyzed as fold change (FC) in tumor specimens of 104 patients with GBM and 8 specimen of non-neoplastic brain tissue as control group. The results were referred to the individual clinical data sets and evaluated statistically. RESULTS: The FC of miRNA-21, -24, and -26a was 1.51 ± 1.35, 0.75 ± 0.67, and 0.39 ± 0.24 in the tumor samples. Within the control group, FC of miRNA-21, -24, and -26a was 0.31 ± 0.51, 0.66 ± 0.33, and 0.18 ± 0.11, respectively. MiRNA-26a and -21 were significantly overexpressed in GBM samples compared with healthy brain tissue (miRNA-21: P < 0.001; miRNA-26a: P = 0.011). High expression ofmiRNA-24 trended for a prolonged overall survival (P = 0.07). Patients with high miRNA-26a expression showed a significantly prolonged progression-free survival (hazard ratio 0.21; 95% confidence interval 0.09-0.51], P < 0.001) and overall survival (hazard ratio 0.3; 95% confidence interval 0.136-0.682], P = 0.003). The effect of miRNA-26a was mediated via regulation of mRNA of RB1. There was a significant inverse correlation between mRNA-26a and mRNA expression of RB1. CONCLUSIONS: The expression levels of miRNA-26a and -24 turned out to be promising predictors of further clinical course in patients with GBM multiforme.