H treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H gas.
Object The objective in the present study was to evaluate the usefulness of cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative assessment of speech function during resection of brain tumors. Methods Intraoperative monitoring of CCEP was applied in 13 patients (mean age 34 ± 14 years) during the removal of neoplasms located within or close to language-related structures in the dominant cerebral hemisphere. For this purpose strip electrodes were positioned above the frontal language area (FLA) and temporal language area (TLA), which were identified with direct cortical stimulation and/or preliminary mapping with the use of implanted chronic subdural grid electrodes. The CCEP response was defined as the highest observed negative peak in either direction of stimulation. In 12 cases the tumor was resected during awake craniotomy. Results An intraoperative CCEP response was not obtained in one case because of technical problems. In the other patients it was identified from the FLA during stimulation of the TLA (7 cases) and from the TLA during stimulation of the FLA (5 cases), with a mean peak latency of 83 ± 15 msec. During tumor resection the CCEP response was unchanged in 5 cases, decreased in 4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or absent CCEP response after lesion removal experienced deterioration in speech function. In contrast, in 5 cases with an unchanged intraoperative CCEP response, speaking abilities after surgery were preserved at the preoperative level, except in one patient who experienced not dysphasia, but dysarthria due to pyramidal tract injury. This difference was statistically significant (p < 0.01). The time required to recover speech function was also significantly associated with the type of intraoperative change in CCEP recordings (p < 0.01) and was, on average, 1.8 ± 1.0, 5.5 ± 1.0, and 11.0 ± 3.6 months, respectively, if the response was unchanged, was decreased, or had disappeared. Conclusions Monitoring CCEP is feasible during the resection of brain tumors affecting language-related cerebral structures. In the intraoperative evaluation of speech function, it can be a helpful adjunct or can be used in its direct assessment with cortical and subcortical mapping during awake craniotomy. It can also be used to predict the prognosis of language disorders after surgery and decide on the optimal resection of a neoplasm.
OBJECTIVEIn this study on the effectiveness and safety of photodynamic therapy (PDT) using talaporfin sodium and a semiconductor laser, the long-term follow-up results of 11 patients with glioblastoma enrolled in the authors’ previous phase II clinical trial (March 2009–2012) and the clinical results of 19 consecutive patients with newly diagnosed glioblastoma prospectively enrolled in a postmarket surveillance (March 2014–December 2016) were analyzed and compared with those of 164 patients treated without PDT during the same period.METHODSThe main outcome measures were the median overall survival (OS) and progression-free survival (PFS) times. Moreover, the adverse events and radiological changes after PDT, as well as the patterns of recurrence, were analyzed and compared between the groups. Kaplan-Meier curves were created to assess the differences in OS and PFS between the groups. Univariate and multivariate analyses were performed to identify the prognostic factors, including PDT, among patients with newly diagnosed glioblastoma.RESULTSThe median PFS times of the PDT and control groups were 19.6 and 9.0 months, with 6-month PFS rates of 86.3% and 64.9%, respectively (p = 0.016). The median OS times were 27.4 and 22.1 months, with 1-year OS rates of 95.7% and 72.5%, respectively (p = 0.0327). Multivariate analyses found PDT, preoperative Karnofsky Performance Scale score, and IDH mutation to be significant independent prognostic factors for both OS and PFS. Eighteen of 30 patients in the PDT group experienced tumor recurrence, including local recurrence, distant recurrence, and dissemination in 10, 3, and 4 patients, respectively. Conversely, 141 of 164 patients in the control group experienced tumor recurrence, including 101 cases of local recurrence. The rate of local recurrence tended to be lower in the PDT group (p = 0.06).CONCLUSIONSThe results of the present study suggest that PDT with talaporfin sodium and a semiconductor laser provides excellent local control, with few adverse effects even in cases of multiple laser irradiations, as well as potential survival benefits for patients with newly diagnosed glioblastoma.
Bevacizumab (BV), a monoclonal antibody against vascular endothelial growth factor (VEGF), is currently used in the treatment of malignant glioma. To understand mechanisms of resistance to BV, we investigated morphological changes in tumor vessels and expression of angiogenic factors, such as VEGF, Flt-1, basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB), in four autopsied tumors after BV treatment. Three patients had glioblastomas; the fourth had a secondary glioblastoma that developed from a diffuse astrocytoma. BV was administered because of recurrence following the use of the Stupp regimen in these four patients. We compared the initial surgical specimen with that obtained after death following BV treatment. Immunohistochemical staining of the autopsied tumors showed that Flt-1 expression increased while VEGF expression was significantly reduced. Additionally, other angiogenic factors, particularly bFGF, were enhanced. Interestingly, the proliferation of endothelial cells was reduced, but remarkable proliferation of pericytes was observed. These results suggest that following BV treatment, glioblastomas can grow tumor vessels by expressing various angiogenic factors. These mechanisms might be important for rapid regrowth and blood brain barrier repair after BV treatment. Inhibition of multiple angiogenic factors will be required to control tumor vessels in glioblastoma.
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