Clonal analysis in recurrent astrocytic, oligoastrocytic and oligodendroglial tumors implicates IDH1- mutation as common tumor initiating event.

BACKGROUND: To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas. METHODOLOGY/PRINCIPAL FINDINGS: To address intertumoral heterogeneity we investigated non-microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors. To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence, and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components. All tumors and tumor components were analyzed for allelic loss of 1p/19q (LOH 1p/19q), for TP53- mutations and for R132 mutations in the IDH1 gene. The investigation of non-microdissected tumor tissue revealed clonality in 75% (38/51). Aberrant molecular alterations upon recurrence were detected in 25% (13/51). 64% (9/14) of these were novel and associated with tumor progression. Loss of previously detected alterations was observed in 36% (5/14). One tumor pair (1/14; 7%) was significant for both. Intratumoral clonality was detected in 57% (4/7) of the microdissected tumor pairs and in 75% (3/4) of single microdissected tumors. 43% (3/7) of tumor pairs and one single tumor (25%) revealed intratumoral heterogeneity. While intratumoral heterogeneity affected both the TP53- mutational status and the LOH1p/19q status, all tumors with intratumoral heterogeneity shared the R132 IDH1- mutation as a common feature in both their microdissected components. CONCLUSIONS/SIGNIFICANCE: The majority of recurrent gliomas are of monoclonal origin. However, the detection of divertive tumor cell clones in morphological distinct tumor components sharing IDH1- mutations as early event may provide insight into the tumorigenesis of true mixed gliomas.

Collagen matrix in decompressive hemicraniectomy.

OBJECTIVE: Decompressive hemicraniectomy is an accepted treatment for otherwise untreatable intracranial hypertension. The aim of this prospective randomized study is to evaluate the benefit of application of collagen matrix as an onlay graft to reduce operating time during hemicraniectomy and to facilitate dural dissection during second-stage cranioplasty. METHODS: Thirty-four consecutive patients were randomized to receive collagen matrix during hemicraniectomy or to undergo the conventional procedure. Specific time points were recorded during hemicraniectomy and cranioplasty. Intra- and postoperative complications, time course of Glasgow Coma Scale, Barthel's, and Early Rehabilitation Indices were monitored. The surgeon had to rate the convenience of the procedure if collagen matrix was used. Cost implications are discussed. RESULTS: The use of collagen matrix during hemicraniectomy resulted in a reduction of combined operating time for hemicraniectomy and cranioplasty by an average of 19.7%. The rate of cerebrospinal fluid effusion during cranioplasty was 13% when collagen was used and 58% in the control group. None of the patients who received collagen developed cerebrospinal fluid effusion persisting longer than 1 week, compared with 33% of patients in the control group. A total of 85% of the surgeons rated the use of collagen matrix as being easier than usual; the rest did not see a difference. CONCLUSION: The use of collagen matrix to cover the dural defect during hemicraniectomy reduces operating time in hemicraniectomy and cranioplasty. The complication rate (cerebrospinal fluid effusion), total treatment time, and time on intensive care unit can be reduced, giving a potential for cost reduction. There was no difference in the rehabilitative outcome.