Wolfgang J. Bock

Local inflammation and devascularization — in vivo mechanisms of the “bystander effect” in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma

Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with “bystander effects” after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome. Cancer Gene Therapy (2001) 8, 843–851

Continuous monitoring of cerebral tissue pressure in neurosurgical practice - experiences with 100 patients

The authors present their experience with the use of continuous monitoring of cerebral tissue pressure (CTP) in a neurosurgical intensive care unit. The CTP was monitored in 100 patients with a variety of neurosurgical diseases. In 13 patients simultaneous recording of the ventricular fluid pressure (VFP) was carried out for up to 134 h. In 21 patients intrahemispheric gradients of CTP were recorded and in 66 patients CTP alone was recorded (59 supratentorial, 7 infratentorial). In general CTP monitoring gave excellent results with no additional risk to the patient and low costs for the monitoring system. The behaviour of CTP in various clinical conditions and the indications and limitations of CTP monitoring compared with VFP or epidural pressure monitoring are outlined. The authors recommend monitoring of VFP as the method of choice in ICP supervision. Continuous monitoring of CTP is the preferred method in the posterior fossa, after large craniectomies, for postoperative supervision following open surgery and in cases of narrowed ventricles.

Adjuvant intraarterial chemotherapy with nimustine in the management of world health organization grade IV gliomas of the brain. Experience at the department of neurosurgery of Düsseldorf university

A protocol with postoperative adjuvant intraarterial (ia) chemotherapy using nimustine (ACNU) was followed at the University of Düsseldorf (Federal Republic of Germany) after histologic confirmation of malignant glioma of the brain. The first iaACNU procedure was performed within 10 days of surgery, and immediately before postoperative irradiation. After radiotherapy further iaACNU courses were given. The study population consisted of 35 primarily treated malignant gliomas World Health Organization (WHO) Grade IV, i.e., glioblastomas (NIV). Of these tumors 11 showed early progressive disease (PD) (NIVprimPD), whereas 24 had stable or responsive disease (NIVsd&rd). Seven patients with recurrent malignant gliomas WHO Grade IV (NIV recurrent) were also treated plus six patients with malignant gliomas WHO Grade III (NIII). Experience with 50 treated patients resulted from this study. The median survival time (MST) for the group NIV was 14.2 months; 41.0% of patients were long‐term survivors. The MST for the group NIV primPD was 7.8 months; 9.1% of patients were long‐term survivors. For the group NIVsd&rd a MST of 18.3 months and 66.7% of long‐term survivors were determined. Patients with recurrent tumors on this treatment protocol had an additional MST of 6.1 months. The total MST after first surgery was 16.2 months. The incidence of complications was low. Systemic complications were infrequent or rare. Retinal disturbances were seen in two patients; leukoencephalopathy was not seen in our patients. In 10% of patients cerebral complications were found, which were irreversible in 2% of patients. Complications could not be assigned unequivocally to the nitrosourea. These results compare favorably with what is reported in the literature, demonstrate the potential value of iaACNU in the treatment of malignant gliomas WHO Grade IV, and should encourage the initiation of a randomized clinical trial of adjuvant iaACNU in the therapy of these tumors. The authors propose iaACNU as a valuable approach in the management of primarily diagnosed malignant gliomas WHO Grade IV, but cannot recommend the delay of iaACNU until the recurrence of a brain tumor.

Tomographic studies of rCBF with [99mTc]-HM-PAO SPECT in patients with brain tumors: comparison with C15O2 continuous inhalation technique and PET

In 10 patients with malignant gliomas, the intracerebral distribution of [99mTc]–hexamethylpropyleneamine oxime ([99mTc]–HM-PAO) was studied with single photon emission computed tomography (SPECT) in comparison with C15O2 steady-state inhalation technique to measure cerebral blood flow using positron emission tomography (PET). In all instances, the cerebral [99mTc]–HM-PAO distribution was comparable with the regional pattern of cerebral blood flow (rCBF) observed with PET. This was confirmed by a significant correlation of tumor to cortex and tumor to white matter ratios between these two experimental methods. However, the contrast between high and low activity regions in the SPECT scans was significantly less than that in the PET scans. Contrast enhancement of the SPECT scans was accomplished using a correction formula proposed by Lassen.

Obstructive hydrocephalus caused by a growing, giant aneurysm on the upper basilar artery

We describe the case of a giant aneurysm on the basilar artery not treated surgically after the first subarachnoid hemorrhage causing obstructive hydrocephalus 12 years later by growing. The problems of pathogenesis of growing aneurysms are discussed.

Protein and amino acid metabolism after severe cerebral trauma

Fourteen patients (20–48 years) suffering from severe head injury were followed for changes in amino acid and protein metabolism during the first 8 days after trauma. All patients received a standardized intravenous nutrition containing 15.7 g of nitrogen per day and additional carbohydrates. Electrolytes, free water, and blood constitutuents were given as needed. Additional treatment included surgical decompression of space-occupying hematomas, high dose dexamethasone therapy, and controlled hyperventilation for at least 5 days. Gross changes of protein metabolism were observed particularly on the days 5 and 6. The duration and chronological sequence of these changes are different from those usually found in patients with multiple injuries.

Magnetic resonance imaging of colloid cysts of the third ventricle

SummaryTwo cases of colloid cyst of the third ventricle are reported. Their computed tomographic (CT), magnetic resonance (MR) and neuropathological features are presented. The MR findings were different in the two cases for reasons not yet fully explained, full biochemical and biophysical analyses of the cyst contents not being available. Neuropathologically, the only significant difference was the abundant presence of cholesterin crystals in the colloid of case 1 and their absence in case 2. One of our cases is also peculiar from a CT point of view, since it was primarily hypodense and did not enhance on intravenous contrast administration.

Gadolinium-DTPA-enhanced MRI and positron emission tomography of stereotactic laser-induced interstitial thermal therapy in cerebral gliomas

Stereotactic laser-induced interstitial thermal therapy (SLIITT) is a new method for inducing local hyperthermia in cerebral tumours. As pre- and early post-therapeutic evaluations in five patients with cerebral gliomas WHO grade II and III treated by SLIITT we performed ga-dolinium-DTPA-enhanced MRI and positron emission tomography (PET). We found that MRI is a sensitive tool for mapping the spatial and temporal distribution of laser-tissue interactions. PET studies using 2-(18F)fluoro-2-D-de-oxyglucose showed typical changes in glucose metabolism of the glioma. Both investigations seem to reveal irreversible laser effects in the centre of the tumour probably due to a coagulative necrosis and reversible effects at the tumour margin probably caused by reparative processes after SLIITT. It could be demonstrated that laser-tissue interactions progress with time, depending on laser energy and exposure time.

Interdisciplinary treatment in pediatric patients with malignant CNS tumors.

Abstract Despite sophisticated surgical methods only a few pediatric CNS tumors can be controlled by operation alone. Therefore multimodality treatment regimens are needed to improve quality of life and survival, which is most important in malignant neoplasms. Since 1998 we have treated 16 children with malignant CNS tumors. All 16 patients have been treated on an interdisciplinary basis and are therefore accompanied by a pediatric neuro-oncology group consisting of a neurosurgeon, pediatric oncologist, and radiotherapist. Depending on tumor histology, childs age, and extent of surgery, further adjuvant therapy is planned by this group. Newly diagnosed tumors are typically treated by a specific chemotherapy protocol according to a multi-institutional study. In recurrent tumors more individual treatment regimens are considered. Data concerning surgery, adjunctive treatment, complications, and outcome of all patients and four case reports are presented.

Delayed traumatic intracranial hematomas - clinical study of seven years

Since the first description of delayed intracranial hematomas related to preceding head injury vast differences in the reported incidence and assumed pathophysiology have been described (i 17). Only since CT scanning has become routinely available, more reliable information can be obtained. Nevertheless, even in the contemporary literature figures of incidence and clinical relevance largely depend on admission criteria, frequency of and indications for CT follow-up studies, time interval considered, definition of hematoma size and whether previous scans may show an abnormality.