Hans Christoph Bock

Untreated Glioblastoma Multiforme: Increased Myo-inositol and Glutamine Levels in the Contralateral Cerebral Hemisphere at Proton MR Spectroscopy

PURPOSE To use localized in vivo proton magnetic resonance (MR) spectroscopy of the contralateral hemisphere in patients with glioblastoma multiforme (GBM) to detect alterations in cerebral metabolites as potential markers of infiltrating GBM cells. MATERIALS AND METHODS The study was approved by the ethics committee, and written informed consent was obtained. Twenty-two patients with newly diagnosed and untreated GBM underwent in vivo single-voxel short echo time proton MR spectroscopy with a 3-T MR imaging system. Absolute metabolite concentrations in the hemisphere contralateral to the tumor were compared with data from five patients with low-grade gliomas (LGGs) and from a group of 14 age-matched control subjects by using analysis of variance and subsequent t tests or corresponding nonparametric tests. RESULTS In the contralateral hemisphere, MR spectroscopy revealed increased concentrations of myo-inositol and glutamine. Mean myo-inositol levels were significantly increased in patients with GBM (3.6 mmol/L +/- 0.8 [standard deviation]) relative to levels in control subjects (3.1 mmol/L +/- 0.6; P = .03) and tended to be higher relative to levels in patients with LGG (2.7 mmol/L +/- 0.8; P = .09). Mean glutamine concentrations in patients with GBM (3.4 mmol/L +/- 0.9) differed significantly from those in control subjects (2.7 mmol/L +/- 0.7; P = .01); mean concentrations in patients with GBM differed from those in patients with LGG (2.4 mmol/L +/- 0.5; P = .01). There were no significant differences between data in patients with LGG and in control subjects. CONCLUSION Increased concentrations of myo-inositol and glutamine in the contralateral normal-appearing white matter of GBM patients are consistent with mild astrocytosis and suggest the detectability of early neoplastic infiltration by using proton MR spectroscopy in vivo.

Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients.

OBJECTIVE The effect of concomitant and adjuvant temozolomide in glioblastoma patients above the age of 65 years lacks evidence. However, after combined treatment became standard at our center all patients were considered for combined therapy. We retrospectively analyzed the effect of temozolomide focused on elderly patients. METHODS 293 patients with newly diagnosed glioblastoma treated single-centered between 1998 and 2010, by radiation alone or concomitant and adjuvant radiochemotherapy, were included. Treatment groups were analyzed by multi- and univariate analysis. Matched pairs for age, by a 5-year-caliper, extent of resection and general state was generated for all patients and elderly subgroups. RESULTS 103 patients received radiation only and 190 combined treatment. Multivariate and matched pair analysis revealed a benefit due to combined temozolomide (HR 1.895 and 1.752, respectively). For patients older than 65 years median survival was 3.6 (95% CI 3.2-4.7) and 8.7 months (6.3-11.8) for radiotherapy only and combined treatment (HR 3.097, p<0.0001, n=90). Over the age of 70 and 75 years median survival was 3.2 (2.3-4.2) vs. 7.5 (5.1-10.9, HR 4.453, p<0.0001, n=62) and 3.2 (1.4-3.9) vs. 9.2 months (4.7-13.5; HR 9.037, p<0.0001, n=24), respectively. In 8/56 (14%) patients over the age of 70 years temozolomide was terminated due to toxicity. CONCLUSION Retrospective matched pair analysis gives class 2b evidence for prolonged survival due to concomitant and adjuvant temozolomide in elderly glioblastoma patients. Until prospective data for combined radiochemotherapy in elderly patients will be available concomitant and adjuvant temozolomide therapy should not be withheld.

High chromosomal instability in brain metastases of colorectal carcinoma

Information on structural chromosomal changes in brain metastases (BM) of colorectal carcinoma (CRC) is very limited. Therapeutic and diagnostic strategies to reduce the risk of BM have potential impact on cancer mortality. By using comparative genomic hybridization, the primary CRC of 11 patients and their corresponding 13 BM were analyzed. BM showed significantly more mean chromosomal aberrations than the primary CRC (13.6+/-2.1 vs. 7.9+/-1.9, P=0.03), significantly more chromosomal gains (7.2+/-0.9 vs. 3.5+/-0.9, P=0.01), and tended to have also more losses (6.1+/-1.4 vs. 4.0+/-1.1, P=0.29). Changes that occurred significantly more often in BM than in primary CRC were gains of 8q, 12p, 12q, and 20p, as well as losses of 5q. BM of CRC show a significantly higher chromosomal instability in comparison to primary tumors. The prevalently altered genomic regions in the metastases of this study are likely to harbor genes that play an important role in the genesis of brain-specific metastasis.

Diagnostic performance of whole brain volume perfusion CT in intra-axial brain tumors: Preoperative classification accuracy and histopathologic correlation

BACKGROUND To evaluate the preoperative diagnostic power and classification accuracy of perfusion parameters derived from whole brain volume perfusion CT (VPCT) in patients with cerebral tumors. METHODS Sixty-three patients (31 male, 32 female; mean age 55.6 ± 13.9 years), with MRI findings suspected of cerebral lesions, underwent VPCT. Two readers independently evaluated VPCT data. Volumes of interest (VOIs) were marked circumscript around the tumor according to maximum intensity projection volumes, and then mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability Ktrans perfusion datasets. A second VOI was placed in the contra lateral cortex, as control. Correlations among perfusion values, tumor grade, cerebral hemisphere and VOIs were evaluated. Moreover, the diagnostic power of VPCT parameters, by means of positive and negative predictive value, was analyzed. RESULTS Our cohort included 32 high-grade gliomas WHO III/IV, 18 low-grade I/II, 6 primary cerebral lymphomas, 4 metastases and 3 tumor-like lesions. Ktrans demonstrated the highest sensitivity, specificity and positive predictive value, with a cut-off point of 2.21 mL/100mL/min, for both the comparisons between high-grade versus low-grade and low-grade versus primary cerebral lymphomas. However, for the differentiation between high-grade and primary cerebral lymphomas, CBF and CBV proved to have 100% specificity and 100% positive predictive value, identifying preoperatively all the histopathologically proven high-grade gliomas. CONCLUSION Volumetric perfusion data enable the hemodynamic assessment of the entire tumor extent and provide a method of preoperative differentiation among intra-axial cerebral tumors with promising diagnostic accuracy.

Intra-osseous ultrasound for pedicle screw positioning in the subaxial cervical spine: an experimental study

BackgroundIn contrast to other regions of the human spine, dorsal fixation with rods and pedicle screws is comparatively rarely performed in the cervical spine. Although this technique provides a higher mechanical strength than the more frequently used lateral mass screws, many surgeons fear the relatively high rate of misplacements. This higher incidence is mainly due to the complex vertebral anatomy in this spinal segment. For correct screw placement, the availability of an immediate and efficient intra-operative imaging tool to ascertain the accuracy of the pedicle screw hole position would be beneficial. We have previously investigated the usefulness of an intraspinal, specifically, intra-osseous ultrasound technique in the lumbar spine. In this study its accuracy as a means of controlling intrapedicular screw hole positioning has been evaluated in the cervical spine.MethodsAn endovascular ultrasound transducer was used for the intra-luminal scanning of 54 pedicle screw holes in cadaveric human spine specimens. Twenty-three of these had been intentionally misplaced (cortex breached). The resulting image files were assessed by three investigators blinded to both the procedure and the corresponding CT findings.FindingsThe investigators differentiated correctly between adequately and poorly placed pedicle screw holes in 96% of cases. False negatives and false positives both occurred in no more than 1.8% of cases.ConclusionsIntrapedicular ultrasonography of pedicle screw holes in the cervical spine is a promising technique for the intra-operative assessment of bore hole placement and may increase operative safety and postoperative outcome in posterior cervical fusion surgery.

Early surgical management and long-term surgical outcome for intraventricular hemorrhage–related posthemorrhagic hydrocephalus in shunt-treated premature infants

OBJECTIVE Perinatal intraventricular hemorrhage (IVH) in premature neonates may lead to severe neurological disability and lifelong treatment requirement for consecutive posthemorrhagic hydrocephalus (PHHC). Early CSF diversion as a temporizing measure, or a permanent ventriculoperitoneal shunt (VPS), is the treatment of choice. Preterm neonates are not only at high risk for different perinatal but also for treatment-related complications. The authors reviewed their institutional neurosurgical management for preterm neonates with IVH-related PHHC and evaluated shunt-related surgical outcome for this particular hydrocephalus etiology after completion of a defined follow-up period of 5 years after initial shunt insertion. METHODS The authors retrospectively analyzed early surgical management for preterm newborns who presented with IVH and PHHC between 1995 and 2015. According to the guidelines, patients received implantation of a ventricular access device (VAD) for temporizing measures or direct VPS insertion as first-line surgical treatment. Surgical outcome was evaluated for a subgroup of 72 patients regarding time to first shunt revision and the mean number of shunt revisions during a time span of 5 years after initial shunt insertion. Gestational age (GA), extent of IVH, and timing and modality of initial surgical intervention were analyzed for potential impact on corresponding surgical outcome. RESULTS A total cohort of 99 preterm newborns with GAs ranging from 22 to 36 weeks (mean 28.3 weeks) with perinatal IVH-related PHHC and a median follow-up duration of 9.9 years postpartum could be selected for further investigation. Extent of perinatal IVH was defined as grade III or as periventricular hemorrhagic infarction in 75% of the patient cohort. Seventy-six patients (77%) underwent VAD insertion and temporizing measures as initial surgical treatment; for 72 (95%) of these a later conversion to permanent ventriculoperitoneal shunting was performed, and 23 patients received direct VPS insertion. Etiological and treatment-related variables revealed no significant impact on revision-free shunt survival but increased the mean numbers of shunt revisions after 5 years for low GA, higher-order IVH in the long term. CONCLUSIONS Low GA and higher-order IVH in preterm neonates with PHHC who are treated with VPSs show no significant impact on time to first shunt revision (i.e., revision-free shunt survival), but marked differences in mean revision rates evaluated after completion of 5 years of follow-up. Temporizing measures via a VAD represent a rational strategy to gain time and decision guidance in preterm patients with PHHC before permanent VPS insertion.

Comment on the Letter to the editor: Bock et al. Occlusion of surgical opening of the ventricular system with fibrinogen-coated collagen fleece: a case collection study. Acta Neurochir (2011) 153:533–539

Thank you for your interesting comments outlining the sufficiency of collagen-fleece sealing for ventricular defects after carmustine wafer implantation. The use of fibrinogencoated collagen fleeces for sealing and reconstructive procedures of ventricular defects in neurosurgery has not yet been analysed by randomised clinical trials, but their use for neurosurgical indication as a local hemostatic agent with potent prevention of cerebrospinal fluid fistula has been reported in the literature, e.g. Nistor et al. (Skull Base Surg 7:23-30, 1997). We used the fleece for several complex hemostatic and dural-reconstructive indications, including cerebral as well as spinal operative procedures. The sponge-like consistency allows comfortable and accurate modelling, with a fast adhesive effect after direct fluid contact. We share the opinion of the authors that welldesigned studies are needed to analyse the potential benefit of using this agent for different neurosurgical indications compared with other biomaterials for reconstructive and watertight sealing strategies.