Joachim Oertel

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.

Limitations of dorsal transpedicular stabilization in unstable fractures of the lower thoracic and lumbar spine: an analysis of 133 patients

SummaryThe optimal treatment of thoracic and lumbar fractures remains controversial. While many authors recommend dorsal instrumentation with an internal fixator, others favour an anterior approach. To evaluate the posterior approach and to identify conditions under which an anterior approach should be preferred, 133 patients with unstable thoracic and lumbar fractures of the spine who underwent dorsal instrumentation with an internal fixator were analyzed. Clinical data were recorded prospectively with respect to fracture type, neurological findings, operative complications, spinal deformation correction, and long-term outcome. All fractures were located between the 7th thoracic and the 5th lumbar vertebrae and were considered to be unstable with respect to the three column model. Seventy-six patients (57%) received surgery within the first seven days after the trauma. Postoperatively, 98% of patients with a radicular lesion or an incomplete transverse syndrome (47 patients, 35%) improved. Stable fracture consolidation after fixator removal was obtained in 98% (130 of 133 patients). The preoperative kyphosis angle decreased from an average of 10.1° to 7.4° at the three year follow up. Major operative complications consisted of two isolated nerve root lesions (1.5%), two deep wound infections with need of fixator removal (1.5%), and mallocation of two pedicle screws with need for another procedure in two patients (1.5%). Three patients (2%) suffered from insufficient bony fusion with increase of kyphotic deformation and required subsequent anterior stabilization. These three patients presented with an initial kyphosis or wedge angle of 20° or higher. In conclusion, dorsal stabilization with the internal fixator is a safe and reliable treatment for unstable fractures of the lower thoracic and lumbar spine. The authors recommend this procedure because of its low-invasiveness in conjunction with satisfactory reconstruction and stabilization. However, an anterior approach should be considered in fractures with initial kyphotic deformation or wedge angle of 20 or more degrees.

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.

Long-term follow-up of dual-portal endoscopic release of the transverse ligament in carpal tunnel syndrome: an analysis of 94 cases.

OBJECTIVEThe long-term efficacy of dual-portal endoscopic release of the transverse ligament in carpal tunnel syndrome is still being debated. In this study, the authors present 94 endoscopic carpal tunnel surgery cases with long-term follow-up data. METHODSThe study includes 72 patients aged 17 to 86 years (mean age, 53.4 years); bilateral surgery was performed in 22 of these patients. Seventy-two hands of female patients and 22 hands of male patients were included. All procedures were performed with a dual-portal set according to the Chow technique. All patients were examined 2 to 3 months after surgery. The long-term follow-up evaluation was based on telephone interviews 5 to 12 years (mean, 8.2 years) after surgery. RESULTSFrom a cohort of 214 cases that were treated surgically between 1995 and 2002, 94 cases (44%) could be evaluated for long-term follow-up. Four of these patients had to be excluded from long-term follow-up because of a switch to an open technique and early open revision (3–6 months after the first surgery), owing to persistent symptoms. A good to optimal postoperative outcome with improvement of neurological signs and subjective patient satisfaction was observed in 84 (93.3%) of the remaining 90 cases. There were no recurrences. CONCLUSIONThe study shows that dual-portal endoscopic release of the transverse ligament in carpal tunnel syndrome is a valuable technique that produces very good long-term results and high patient satisfaction and does not result in a significant recurrence rate.

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.

Neurocognitive status in patients with newly-diagnosed brain tumors in good neurological condition: The impact of tumor type, volume, and location

OBJECTIVE Neurocognitive function is of great importance in patients with brain tumors. Even patients in good neurological condition may suffer from neurocognitive dysfunction that affects their daily living. The purpose of the present study was to identify risk factors for neurocognitive dysfunction in patients suffering from common supratentorial brain tumors with minor neurological deficits. METHODS A prospective study evaluating neurocognitive dysfunction in patients with a newly-diagnosed brain tumor in good neurological condition was performed at a major German academic institution. Patients underwent extensive neurocognitive testing assessing perceptual speed, executive function, visual-spatial and verbal working memory, short- and long-term memory, verbal fluency, fluid intelligence, anxiety, and depression. For each patient, a healthy control was pair-matched based on age, sex, handedness, and profession. RESULTS A total of 46 patients and 46 healthy controls underwent neurocognitive testing. Patients suffered from glioblastoma multiforme (10), cerebral metastasis (10), pituitary adenoma (13), or meningioma (13). There was neither any difference in age, educational level, fluid intelligence, neurological deficits, and anxiety nor in any depression scores between tumor subgroups. Overall, neurocognitive performance was significantly worse in patients compared to healthy controls. Larger tumor volume, frontal location, and left/dominant hemisphere were associated with worse executive functioning and verbal fluency. Additionally, larger tumors and left/dominant location correlated with impairments on perceptual speed tasks. Frontal tumor location was related to worse performance in visual-spatial and short- and long-term memory. Tumor type, clinical presentation, and patient self-awareness were not associated with specific neurocognitive impairments. CONCLUSIONS Patients suffering from newly-diagnosed brain tumors presenting in good neurological condition display neurocognitive impairments in various domains. Larger tumor volumes, frontal location, and left/dominant hemisphere are important predictors for potential neurocognitive deficits. Tumor type, clinical presentation, or self-awareness are less significant at the time of diagnosis.

Smith-Robinson Procedure with an Autologous Iliac Crest for Degenerative Cervical Disc Disease: A 28-Year Follow-Up of 95 Patients

BACKGROUND Long-term clinical results after anterior cervical discectomy and fusion (ACDF) with an autologous iliac crest are rare. The purpose of this study was to assess this, with special focus on pain, functional outcome, and repeat surgery for adjacent segment disease (ASD). METHODS Hospital records of 212 patients who were affected by degenerative cervical disc disease and treated by the Smith-Robinson technique were reviewed. Information about diagnosis, surgery, pre- and postoperative clinical process, and complications was analyzed. Patients were reviewed with a standardized questionnaire including the current neurologic status, Neck Disability Index, EQ-5D, Patient Satisfaction Index, Odom criteria, and limitations in quality of life. RESULTS Ninety-five patients with a mean follow-up of 28 years were evaluated. ACDF was performed at 1 level in 67 and 2 levels in 28 patients. Ninety-two patients reported pain before surgery and 68 patients remained pain free and did not require second surgery. At follow-up, the mean Neck Disability Index was 14%, and mean EQ-5D score was 5. Postoperatively, 96.8% of patients were satisfied and 84.2% of patients reported good to excellent functional recovery. One patient had a hairline fracture at the iliac crest donor site. Fourteen patients underwent second surgery because of degenerative changes, including 11 at the symptomatic ASD. CONCLUSIONS ACDF yields significant decrease in pain, a significant increase in function, and a high degree of patient satisfaction. Overall prevalence for ASD was 12.0% after 25 years. Patients with reoperation had similar clinical outcome regarding pain, compared with patients without reoperation.

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.