Stefan Linsler

Molecular biological determinations of meningioma progression and recurrence.

Meningiomas are tumors that arise from the coverings of the brain or spinal cord. 5% of the cases turn into malignant forms with aggressive clinical behavior and increased risk of tumor recurrence. One hundred and five patients with meningiomas were operated by open surgery. To investigate predictors of meningioma recurrence in total 124 samples of 105 patients were investigated by iFISH. Dual-probe hybridization was performed to access chromosomal alterations of chromosomes 1p-, 9p- and 22q. Additionally, methylation of TIMP3 and p16 was analyzed with MS-PCR. Of the 105 investigated tumors 59.1% (62/105) were WHO grade I, 33.3% (35/105) were WHO grade II and 7.7% (8/105) were anaplastic meningiomas (grade III), respectively. The histopathological data correlates with the recurrence rate of the investigated meningiomas. Hypermethylation of TIMP3 was detected in 13.3% of all meningiomas: 10.9% in WHO grade I meningiomas, 25.0% in grade II and 14.3% in grade III meningiomas, respectively. No correlation of TIMP3 hypermethylation with tumor recurrence or WHO grade (p = 0.2) was observed. Interestingly, deletion of 1p36 emerged as a significant predictor of shorter overall survival (log rank test, p<0.001), whereas TIMP3 promoter methylation had no significant effect on overall survival (log rank test, p = 0.799). The results of the current study support the finding that the deletion of chromosome 1p is an independent marker of meningioma recurrence and progression (p = 0.0097). Therefore the measurement of genetic aberrations in meningiomas allows in a combined histological approach a more precise assessment of the prognosis of meningiomas than histopathology alone.

Endoscopic Endonasal Transclival Resection of a Brainstem Cavernoma: A Detailed Account of Our Technique and Comparison with the Literature

OBJECTIVE To report a technique of endoscopic transclival resection of a hemorrhagic brainstem cavernous malformation manifesting in the ventral pons. METHODS A 29-year-old woman presented with numbness and tingling of the right arm and leg and loss of fine motor control. Magnetic resonance imaging revealed a cavernoma in the ventromedial brainstem on the ventral surface. A purely endoscopic, endonasal, transclival approach was used to resect this cavernoma. Computed tomography/magnetic resonance imaging merged navigation (StealthStation, Medtronic) was used. RESULTS The patient had no neurologic deficits postoperatively. The motor control loss and tingling disappeared. She did not experience any complications. Cerebrospinal fluid leakage appeared to result from using the very small opening of the skull base and dura mater and was the reason for the use of a lumbar drain for several days. At the 6-week follow-up examination, the patient was in excellent condition with no neurologic deficits and had returned to her full-time job. CONCLUSIONS Successful endoscopic, endonasal, transclival resection of a brainstem cavernous malformation was described. This patient experienced improvement in neurologic symptoms after surgery without morbidity. Technologic advances in endoscopic skull base approaches provide access to lesions of the brainstem that previously required more invasive approaches. The endonasal transclival approach provides the most direct route to ventral pontine lesions. Early intervention in brainstem cavernous malformation is indicated and should be performed with an individualized approach taking into consideration the possible complications.

Endoscopic endonasal transsphenoidal approach to sellar lesions: a detailed account of our mononostril technique.

Objective The endonasal endoscopic approach is currently under investigation for perisellar tumor surgery. A higher resection rate is to be expected and nasal complications should be minimized. Here, the authors report their technique of transnasal endoscopic neurosurgery after 218 procedures. Methods Between October 2000 and September 2011, 210 patients received 218 endoscopic endonasal transsphenoidal procedures for perisellar lesions. Procedures were video recorded. The surgical technique was carefully analyzed. These cases were prospectively followed. Results Standard technique was mononostril approach with 0-degree optics. 30-degree and-after availability-45-degree optics were used for assessment of radicality. On follow-up, magnetic resonance imaging revealed radical tumor resection in 94 out of 104 cases (90.3%). Recurrent tumor growth was observed in five younger patients (2.2%). There was no mortality and a low complication rate. Three patients (1.4%) complained postoperatively of nasal congestion or reduced nasal air flow; however, no complaints were considered to be severe. Conclusion In comparison with other literature reports, the results are comparable or even better with respect to surgical radicality. The very low rate of nasal complaints is particularly remarkable. The technique has been shown to be safe and successful with a high radicality and only minor complications.

Mononostril endoscopic transsphenoidal approach to sellar and peri-sellar lesions: Personal experience and literature review.

Abstract Objective. The endonasal endoscopic approach to skull base is still under investigation. The main goal is the minimal invasive approach to pathologies with a better rate of resection without retraction of the brain tissue. Here, the authors report their technique of transnasal endoscopic neurosurgery using a mononostril approach and its development. Methods. The supplementary video demonstrates the different steps of the mononostril approach and resection of a pituitary adenoma. All video-recorded procedures that were carried out between 2000 and 2013 using this technique were analysed. The patients were followed prospectively. Results. Visualization and handling were good in 246/251 (98%). In three cases, we had to switch to microscopy because of severe bleeding of the cavernous sinus. On follow-up, magnetic resonance imaging revealed radical tumour resection in 92% of all cases when intended. There was no mortality, and the low complication rate was remarkable. Conclusion. Our mononostril approach of transnasal transsphenoidal surgery shows better results compared with previously published reports in regards to radicality, low cerebrospinal fluid leaks and morbidity. The very low rate of nasal complains is particularly remarkable.

Clonal cytogenetic progression within intratumorally heterogeneous meningiomas predicts tumor recurrence

Meningiomas arise from the coverings of the brain or the spinal cord. They are mostly benign and can be surgically cured. However, in approximately 5% of the cases, they turn into malignant forms with aggressive clinical behavior and increased risk of tumor recurrence. Cytogenetically meningiomas are well characterized, with normal karyotype or monosomy of chromosome 22 in most tumors and clinically relevant secondary losses of other autosomes and sex chromosomes in a subset of anaplastic tumors. Statistical analyses were performed for 1064 karyotypes derived from 661 meningiomas with respect to progression, and recurrence of the tumor. The order of accumulating genetic aberrations has previously been biostatistically estimated with oncogenetic tree models, and a genetic progression score derived from these models was shown to be predictive for tumor recurrence. Although more homogeneous than other cancer types, meningiomas show considerable intratumoral cytogenetic heterogeneity, particularly in their anaplastic form. We observed different cytogenetic patterns in tumor cells of 224 out of 661 (33.4%) meningiomas. The present study demonstrates that it is not sufficient to consider only the most frequent cytogenetic pattern observed in a sufficient set of cells derived from the same tumor. Even a single cell with more advanced genetic progression may start a clone and indicates also clinical progression. Cox regression analysis reveals that the clone with most advanced progression is a leading marker for recurrence in meningiomas. The aim of this study was the analysis of genetic heterogeneity on single cell basis. Further we investigated if there is a substantial correlation between the intratumoral heterogeneity of a given meningioma and its recurrence risk. We were able to show that the selection of single genetically advanced cells improves the prediction of clinical meningioma progression in a more precise manner.

The use of intraoperative computed tomography navigation in pituitary surgery promises a better intraoperative orientation in special cases.

Objective: The safety of endoscopic skull base surgery can be enhanced by accurate navigation in preoperative computed tomography (CT) and magnetic resonance imaging (MRI). Here, we report our initial experience of real-time intraoperative CT-guided navigation surgery for pituitary tumors in childhood. Materials and Methods: We report the case of a 15-year-old girl with a huge growth hormone-secreting pituitary adenoma with supra- and perisellar extension. Furthermore, the skull base was infiltrated. In this case, we performed an endonasal transsphenoidal approach for debulking the adenoma and for chiasma decompression. We used an MRI neuronavigation (Medtronic Stealth Air System) which was registered via intraoperative CT scan (Siemens CT Somatom). Preexisting MRI studies (navigation protocol) were fused with the intraoperative CT scans to enable three-dimensional navigation based on MR and CT imaging data. Intraoperatively, we did a further CT scan for resection control. Results: The intraoperative accuracy of the neuronavigation was excellent. There was an adjustment of <1 mm. The navigation was very helpful for orientation on the destroyed skull base in the sphenoid sinus. After opening the sellar region and tumor debulking, we did a CT scan for resection control because the extent of resection was not credible evaluable in this huge infiltrating adenoma. Thereby, we were able to demonstrate a sufficient decompression of the chiasma and complete resection of the medial part of the adenoma in the intraoperative CT images. Conclusions: The use of intraoperative CT/MRI-guided neuronavigation for transsphenoidal surgery is a time-effective, safe, and technically beneficial technique for special cases.

Prognosis of meningiomas in the early 1970s and today

OBJECTIVE The benefit of the current strategy of diagnosis and treatment of meningiomas in contrast to the standard treatment in use before computer tomographic and magnetic resonance imaging and before the microsurgical era has not yet been determined. METHODS Two groups of patients were compared, those on which surgery was performed before the year of 1985, when computer tomographic (CT) imaging was not yet available in our clinic and those who were treated after at the Neurosurgical Department of Saarland University. Average follow-up time was 17.9±9.3years for group 1 and 9.2±4.3years for group 2. RESULTS The number of patients with advanced age who had surgical treatment was significantly increased in the second group, whereas the number of perioperative complications found was nearly equal in both groups (17.8% vs. 18.8%). Nevertheless, perioperative morbidity was reduced from 2.2% to 1.2%. The postoperative recurrence free time period could be revealed to be longer in the first collective (p<0.0001). Furthermore, this study shows a notable increase of the incidence of WHO grade II meningiomas in patients treated after 1985. CONCLUSIONS Based on the presented results, the overall prognosis for patients with meningiomas has changed from the 1960s until today, since over the last two decades there has been a prolonged progression free survival time in addition to a reduced perioperative mortality rate. In the postoperative management of these patients genetic aberrations and microbiological markers should be considered as prognostic factors for meningiomas in addition to histopathological grading.

Aqueductal stenting with an intra-catheter endoscope—a technical note

IntroductionAqueductoplasty as well as aqueductal stenting is an accepted therapy option in short-segment aqueductal stenosis and isolated fourth ventricle. Over the years, different techniques with only slight modifications by using a conventional neuroendoscope with a working sheath to introduce different instruments have been presented. In summary, the use of Fogarty balloon catheters or flexible endoscopes to pass the narrowed aqueduct is recommended.MethodsThis technical report describes a substantially new technique for this purpose. Six patients underwent aqueductal stenting with a new intracatheter endoscope.ResultsAqueductal stenting was possible in 4 out of 6 cases. No complications occurred. Handling of this new technique was good and easy without a prolonged learning curve. All four stents did work appropriately, and the procedure was considered to be successful. Of the two failures, the technique was abandoned and endoscopic third ventriculostomy (ETV) was performed in one. In the other case, suboccipital shunting was done.ConclusionThis technical report describes a substantially new technique for aqueductal stenting. The combination of an intracatheter miniature endoscope and a prepared ventricular catheter enables careful and elegant aqueductal stenting. Large or flexible endoscopes, balloons, or special instruments to place a stent have become completely obsolete in selected cases.

Prognosis of pituitary adenomas in the early 1970s and today—Is there a benefit of modern surgical techniques and treatment modalities?

OBJECTIVE Neurosurgical techniques for the treatment of sellar pathologies have been evolving continuously over the last decades. Additionally to the innovation of approaches and surgical techniques, this progress yielded to the application of modern intraoperative surgical tools as well as peri- and intraoperative imaging. Until now, no long-term analysis of the impact of new therapy concepts on the patients outcome exists. Aim of this study was to analyse the impact of new operative approaches on perioperative mortality and morbidity as well as the long-term outcome after pituitary surgery. PATIENTS AND METHODS Three groups of patients were compared in this retrospective analysis of surgically treated pituitary adenomas between the years of 1963 and 2014. Group A contains 93 patients, treated between 1963-1980 with a mean follow-up of 12.1 years (±14.3years), group B comprises 89 patients treated between 1990 and 2000 with a mean follow-up of 10.1 years (±8.1years) and group C consists of 95 patients treated between 2011-2014 with a mean follow-up of 3.4 years (±1.9years). RESULTS The surgical treatment was performed significantly earlier today on smaller tumors with less preoperative complaints (p<0.01). Panhypopituitarism was detected only in 9.5% of the cases in group C compared to 50.8% in group A (p<0.01). Also, the incidence of revision surgery (5.6 vs. 2% vs 0%), postoperative hemorrhage (10.8% vs. 3.4% vs. 1%) and diabetes insipidus (34.4% vs. 11.2% vs. 5.2%) was decreased (p<0.01). Moreover, a significant postoperative improvement of ophthalmological complaints was detected (p<0.001). The long-term follow-up showed 40% of the entire recurrence rate occurring after the ninth postoperative year. The progression-free survival time increased significantly from group A to group B (p<0.05). CONCLUSIONS The results demonstrate a benefit of the recent developments of pituitary surgery in the short-term results as well as in the long-term outcome. The prognosis of pituitary adenoma patients could be improved by the introduction of new surgical approaches and techniques in the last decades. Also the perioperative morbidity and mortality rate has been reduced clearly since the 1970s. Furthermore our results emphasise the necessity of lifelong follow-up of all patients with successfully treated pituitary adenomas.

Establishment of a molecular cytogenetic analysis for native tumor tissue of meningiomas-suitable for clinical application

BackgroundMeningiomas are mostly benign tumors which arise from the meninges. They are among the cytogenetically best-studied solid tumors, mostly displaying a normal karyotype or, as a typical primary aberration, monosomy of chromosome 22. Further secondary chromosomal aberrations, especially the deletion of chromosome 1p, are correlated with increasing biological aggressiveness up to malignancy. These data are derived from the cytogenetical characterization of 661 meningiomas, from which the genetic progression score (GPS) has been developed. Due to the high expenditure of time and the expert knowledge for the cytogenetical characterization, the aim of this work was to establish an equally reliable yet more rapid clinical diagnosis based on fluorescence in situ hybridization (FISH) on meningiomas. Thus a comparison between the native tumor tissue and the primary culture of the same tumor was done in order to determine the most efficient method for a molecular cytogenetic characterization. The diagnostic procedure has to deliver fast and robust results, since they must enable the attending physician to plan the appropriate follow-up regimens for the patients. All in all, preparations of native tumor tissue as well as preparations of cell culture of 22 meningiomas were tested with FISH for aberrations concerning the prognostically relevant chromosome regions 1p and 9p, and the chromosomes 10, 14, 18 and 22 in comparison with the particular karyotypes revealed by conventional karyotyping using G-banding.ResultsThe FISH examinations between native and cultured cells showed an accordance of 93.4%. The comparison of FISH data and karyotyping presented accordance to the greatest possible extent concerning the chromosomes 14, 18 and 22, but to detect the progression associated losses of 1p and 9p FISH is the most sensitive method.ConclusionsThe raised data reveal that both methods can be used for a significant analysis of chromosome aberrations on meningiomas. As a result of that the complex primary culture could also be avoided. Therefore a clinical diagnosis based on FISH on meningiomas is at hand for the assignment of patients to a suitable follow-up regimen.