Vertebral body replacement with PEEK-cages after anterior corpectomy in multilevel cervical spinal stenosis: a clinical and radiological evaluation

Introduction

A growing number of industrially manufactured implants have been developed in the last years for vertebral replacement in anterior cervical corpectomy and fusion (ACCF). Polyetheretherketone (PEEK)-cages are used in many centers, but outcome reports are scarce. This study assesses the clinical and radiological outcome after one- or two-level ACCF by the use of a PEEK-cage augmented by a plate–screw osteosynthesis.

Methods

A total of 21 patients received one-level (18 patients) or two-level (3 patients) ACCF by a PEEK-cage and plate–screw osteosynthesis for multilevel degenerative stenosis. The Visual Analogue Scale, Nurick Score, Neck Disability Index and European Myelopathy Score were used for clinical assessment. Radiological outcome—osseous fusion and loss of height—was evaluated by CT.

Results

The mean follow-up was 28 ± 12 months. In 19 patients, bony fusion was achieved after the primary operation. Graft failure that required surgical revision occurred in two patients. In these patients, osseous fusion was achieved after the second operation. Myelopathy improved significantly. The loss of height was 2.2 ± 2.3 and 5.3 ± 2.1 mm after one- and two-level ACCF, respectively.

Conclusion

Anterior corpectomy and fusion by a PEEK-cage and plate–screw osteosynthesis resulted in clinical improvement in all patients. Bony fusion was achieved in all patients in the long run. PEEK cages are allegedly less rigid than other xenografts. Similar to those, however, their use bears the risk of early cage-dislocation and subsidence. A comparison of industrial xenografts and autologous bone implants is required to challenge the different fusion techniques.     

Value of Transcranial Doppler,Perfusion-CT and Neurological Evaluation to Forecast Secondary Ischemia after Aneurysmal SAH

Introduction

This study was conducted to prospectively evaluate the diagnostic value of detailed neurological evaluation, transcranial Doppler sonography (TCD) and Perfusion-CT (PCT) to predict delayed vasospasm (DV) and delayed cerebral infarction (DCI) within the following 3 days in patients with aneurysmal subarachnoid hemorrhage (SAH).

Methods

A total of 61 patients with aneurysmal SAH were included in the study. All patients were amenable for neurological evaluation throughout the critical phase to develop secondary ischemia after SAH. The neurological status was assessed three times a day according to a detailed examination protocol. Mean flow velocities (MFV) in intracranial vessel trunks were measured daily by TCD. Native CT and PCT were routinely acquired at 3-day intervals and, in addition, whenever it was thought to be of diagnostic relevance. The predictive values of abnormal PCT and accelerations in TCD (MFV > 140 cm/s) to detect angiographic DV and DCI within the following 2 days were calculated and compared to the predictive value of delayed ischemic neurological deficits (DIND).

Results

The accuracy of TCD and PCT to predict DV or DCI was 0.65 and 0.63, respectively. In comparison, DIND predicted DV or DCI with an accuracy of 0.96. Pathological PCT findings had a higher sensitivity (0.93) and negative predictive value (0.98) than TCD (0.81 and 0.96).

Conclusion

Neurological assessment at close intervals is the most accurate parameter to detect DV and DCI in the following 3 days. However, DIND may not be reversible. The routine acquisition of PCT in addition to daily TCD examinations seems reasonable, particularly in patients who are not amenable to a detailed neurological examination since it has a higher sensitivity and negative predictive value than TCD and leaves a lower number of undetected cases of vasospasm and infarction.     

Pediatric dermatohistopathology – histopathology of skin diseases in newborns and infants

While neonatal skin physiology has been thoroughly examined using non‐invasive techniques in recent years, only few systematic studies and review articles addressing the histopathology of neonatal skin have been published thus far. In most cases, histopathological findings of dermatoses in neonatal skin do not significantly differ from those seen in adult skin. Nevertheless, a comprehensive knowledge of embryonic and fetal skin development as well as the microanatomical structure of neonatal skin can contribute to a better understanding of various dermatoses of infancy. In the first part of this review article, we present the histopathological features of such skin diseases, which, though generally rare, almost exclusively appear during the first weeks of life due to distinctive structural and functional features of neonatal skin. The second part is dedicated to classic dermatoses of infancy and their histopathological features.     

A complete compilation of matrix metalloproteinase expression in human malignant gliomas

Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases (MMPs) were found in glioblastoma (GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma (LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory data available. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.     

Favorable outcome of triploid neuroblastomas: a contribution to the special oncogenesis of neuroblastoma

There is a well-known association between patient outcome and tumor ploidy in neuroblastoma. To date, however, most clinical trials have not used this parameter for therapy stratification. Using conventional cytogenetics and fluorescence in situ hybridization (FISH), we investigated 36 tumors in terms of ploidy and chromosome 1 copy number (polysomy). In addition, interphase FISH for polysomy was performed on a second cohort of 440 neuroblastomas, together with the status of 1p, MYCN, and 11q. The main goals were as follows: (1) to assess the reliability of FISH to determine ploidy; (2) to illustrate associations between somy 1 and clinical/biologic factors; and (3) to investigate the role of somy 1 for predicting outcome. The comparison between karyotyping and FISH in the smaller cohort revealed 86% consistency between ploidy and polysomy (31/36). According to FISH, trisomic tumors in the second cohort showed structural chromosomal aberrations less frequently compared to di-/tetrasomic tumors (15 vs. 60%, P < 0.001). The portion of trisomic neuroblastomas was higher in stages 1, 2, and 4S versus stages 3 and 4 (55 vs. 24%, P < 0.001) and in children 18 months or younger versus those older than 18 months (55 vs. 19%, P < 0.001). Prognosis was significantly better for trisomic tumors versus di-/tetrasomic in the whole cohort [event-free (EFS) and overall survival (OS), P < 0.001]. In the subgroup without abnormalities of other molecular markers, EFS of trisomic neuroblastomas was better (P = 0.048), but was most likely due to an unequal stage distribution. In further subgroups, in terms of age and stage, significance between the somy groups was not reached, neither for EFS nor OS. The multivariate analyses including age, stage, chromosomal markers, and somy 1 confirmed the lack of independent prognostic power for the copy number of chromosome 1. This study demonstrates the following: (1) FISH is a practical alternative to other more labor-intensive techniques for determining ploidy; (2) trisomic tumors correlate with younger age at diagnosis, localized stage, and the lack of structural alterations; and (3) polysomy is not an independent prognostic marker. The sharp decline of trisomic tumors after the age of 18 months supports the idea of different genetic tumor entities.     

Proliferative Activity of Microvascular Cells in Glioblastomas does not Correlate with Time to Recurrence

The time to recurrence operation (TR) is a good growth parameter, in particular for glioblastomas. Recently, we have shown that Ki-67 labeling index (LI) of tumor cells has a high inverse correlation with this time interval. In the current study, the LI of microvascular cells (MVC) was examined in the same glioblastoma cases. The LI of MVC of primary and recurrent tumors had no relationship and did not show any correlation to TR. The growth fraction of MVC was significantly lower than that of tumor cells. The MVC in glioblastomas seems to have chaotical proliferation properties without any link to the tumor growth potential. This observation may have implications for anti-angiogenic therapy.     

MYCN-status in neuroblastoma: characteristics of tumours showing amplification, gain, and non-amplification

While the role of MYCN-amplification (MNA) for risk assessment in neuroblastoma is undisputed, the phenomenon of gene copy excess below the amplification threshold is rarely described. To discuss biological characteristics and the clinical impact of the so- called MYCN-gain versus amplified or non-amplified cases, we investigated the MYCN status of 659 patients uniformly analysed by fluorescence in situ hybridisation. The number of MYCN-amplified tumours in our cohort was 18% (116/659); an additional 38 tumours (6%) displayed MYCN-gain. Both alterations were associated with an advanced stage disease, an increased patient age and further chromosomal alterations. Most of the amplified neuroblastomas displayed 1p aberrations, whereas MYCN-gain tumours correlated with 11q alterations. In contrast to the amplified cases, tumours with gain displayed no increased MYCN RNA levels. MNA versus non-amplification discriminated between good and poor outcomes, independent of stage, age and the degree of amplification. However, patients with amplified tumours showed a significantly better outcome when this was combined with non-stage 4 disease and age <1 year versus stage 4 and age >1 year. Although MYCN-gain was associated with poor event-free-survival (EFS) in stages 1–3, 4S (P=0.005), this might be related to associated genetic aberrations and not to the MYCN-gain itself. A survival difference between neuroblastomas with gain and single copy MYCN could not be delineated. In conclusion, MNA predicts a poor outcome for neuroblastoma patients of all stages and age. MYCN-gain is also a characteristic feature of advanced stage tumours and older patients, but is not associated with higher MYCN expression and appears not to be discriminative in predicting patient outcome.     

Prognostic significance of preoperative electrophysiologic investigation for facial nerve outcome in acoustic neuroma surgery

The prognostic significance of transcranial magnetic stimulation and nasal muscle F-wave recording to predict postoperative facial nerve function was assessed in 24 patients with unilateral acoustic neuromas (mean diameter, 31 mm) and clinically intact facial nerve function. Latency of F waves and response to cortical magnetic stimulation, as well as F ratios, central motor conduction time, and the ratio of response latency to cortical and cisternal magnetic stimulation were significantly increased. Outcome analysis revealed no significant correlation between preoperative electrophysiologic changes and postoperative facial nerve function. However, a significant correlation with tumor diameter was detected. Thus, acoustic neuroma size seems to be the best predictor of facial nerve function after surgery.     

Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors

We investigated the variability in infectivity of cells in primary brain tumor samples from different patients using an HSV-1 amplicon vector. We studied the infectivity of HSV-1 amplicon vectors in tumor samples derived from neurosurgical resections of 20 patients. Cells were infected with a definite amount of HSV-1 amplicon vector HSV-GFP. Transduction efficiency in primary tumor cell cultures was compared to an established human glioma line. Moreover, duration of transgene expression was monitored in different tumor cell types. All primary cell cultures were infectable with HSV-GFP with variable transduction efficiencies ranging between 3.0 and 42.4% from reference human Gli36 Delta EGFR glioma cells. Transduction efficiency was significantly greater in anaplastic gliomas and meningiomas (26.7+/-17.4%) compared to more malignant tumor types (glioblastomas, metastases; 11.2+/-8.5%; P=0.05). To further investigate the possible underlying mechanism of this variability, nectin-1/HevC expression was analyzed and was found to contribute, at least in part, to this variability in infectability. The tumor cells expressed the exogenous gene for 7 to 61 days with significant shorter expression in glioblastomas (18+/-13 d) compared to anaplastic gliomas (42+/-24 d; P<0.05). Interindividual variability of infectivity by HSV-1 virions might explain, at least in part, why some patients enrolled in gene therapy for glioblastoma in the past exhibited a sustained response to HSV-1-based gene- and virus therapy. Infectivity of primary tumor samples from respective patients should be tested to enable the development of efficient and safe herpes vector-based gene and virus therapy for clinical application.