Maxim Koslow

Improved long term survival after intracavitary interleukin‐2 and lymphokine‐activated killer cells for adults with recurrent malignant glioma

Background. The median survival for adults with glioblastoma multiforme (GBM) is 12 months, despite surgery, radiation, and chemotherapy. Regimens using interleukin‐2(IL‐2) plus lymphokine‐activated killer (LAK) cells have been beneficial against systemic cancers, albeit with significant toxicity.

A Correlative Study of p53 Protein Alteration and p53 Gene Mutation in Glioblastoma Multiforme

The p53 tumor suppressor gene is frequently mutated in glioblastomas. Mutations within the p53 gene often result in aberrant expression of the p53 protein leading to protein accumulation within the nucleus of the cells which can be detected by immunochemistry. Many studies have correlated alterations of p53 protein expression with p53 gene mutations. Positive staining of tumor cells for p53 protein has been widely assumed, perhaps incorrectly, to signify the presence of p53 gene mutations. This study compared the immunostaining patterns for p53 protein in 37 glioblastomas with the molecular genetic data obtained by the single strand conformation polymorphism assay. p53 gene mutations were detected in 46% (17 of 37) of glioblastomas, while 65% (24 of 37) of glioblastomas were positive for protein accumulation by immunohistochemistry. Although 30 of 37 glioblastomas analyzed showed concordance for p53 protein expression and p53 gene mutations, a subset of seven glioblastomas showed discordant accumulation of the p53 protein in the absence of any detectable p53 gene mutations. The mdm‐2 gene was assessed in 17 glioblastomas for gene rearrangements or amplification, but none were found. This result suggests that a mechanism other than p53 gene mutation can result in altered p53 protein expression.

Synaptophysin: A sensitive and specific marker for ganglion cells in central nervous system neoplasms

Synaptophysin, a 38-kilodalton glycoprotein found in synaptic vesicle membranes, has been shown to be a sensitive marker of neuroendocrine differentiation in non-central nervous system (CNS) tumors. We analyzed the patterns of synaptophysin immunoreactivity in CNS neoplasms in comparison with various normal CNS sites in biopsies. Normal gray matter structures all showed a diffuse punctate granular pattern of neuropil staining without staining of neuronal cell bodies. In contrast, neoplastic ganglion cells in 18 of 18 gangliogliomas/gangliocytomas showed intense immunoreactivity outlinging the borders of the cell bodies. Focal staining was also seen in five of 16 primitive neuroectodermal tumors and in one of three central neurocytomas, but these tumors had a finely granular neuropil pattern of immunoreactivity more like that of normal gray matter than like that of the gangliogliomas. All 35 examples of pure gliomas of various types showed no immunoreactivity. Our data highlight synaptophysin as a sensitive and specific marker of both neuronal lineage and neoplastic character in gangliogliomas.

Risk factors associated with postcraniotomy meningitis: Commentary

OBJECTIVEThe authors conducted a retrospective cohort study to determine the incidence, bacteriological features, and risk factors for postcraniotomy meningitis. METHODSPatients older than 18 years who underwent nonstereotactic craniotomies between January 1996 and March 2000 and who survived for more than 7 days were included. Operations for placement of burr holes and shunts were excluded. Records of the first 30 postoperative days were abstracted. Host factors, types of craniotomy, and pre- and postoperative variables were evaluated as risk factors for meningitis RESULTSAmong 453 patients, there were 25 cases of meningitis. Eight out of 12 culture-positive cases were the result of gram-positive cocci. Four hundred twenty (92%) patients received antibiotic prophylaxis, most commonly a first-generation cephalosporin. In multivariate analysis, the risk of meningitis was increased by surgery that entered a sinus (odds ratio [OR], 4.49; P = 0.018), an increase in the American Society of Anesthesiologists score (OR, 1.72; P = 0.023), and increases in the number of days of external ventricular drainage (OR, 1.21; P = 0.049) and intracranial pressure monitoring (OR, 1.24; P = 0.002). CONCLUSIONAccess of upper airway bacteria to the surgical wound, host factors as expressed by the American Society of Anesthesiologists score, and duration of device-related postoperative communication of the cerebrospinal fluid and the environment are major risk factors for postoperative meningitis after craniotomy.

Stereotactic surgical system controlled by computed tomography.

The three-dimensional data obtained by computed tomographic (CT) scanning offer an advantage in using this imaging technique for stereotactic surgical procedures. This requires interfacing of CT image data with a stereotactic guide. In the performance of functional procedures where the surgical target must be identified from brain landmarks, such as the anterior and posterior commissures, an image reconstruction technique that presents in an image high spatial resolution structural information must be used. The description of a fully hardware- and software-interfaced CT-directed stereotactic surgical system is presented. The logic of operation and examples of images reconstructed with a high spatial resolution algorithm are illustrated. The experimentally determined measurement of an electrode tip localization with this system is within 1 pixel or +/- 0.5 mm in any direction.

Propionibacterium as a cause of postneurosurgical infection in patients with dural allografts: report of three cases.

OBJECTIVE AND IMPORTANCE Although Propionibacterium acnes is a common inhabitant of human skin, it is an uncommon pathogen in postoperative infections. We report three cases of postoperative wound infection/osteomyelitis caused by P. acnes. CLINICAL PRESENTATION Three patients underwent craniotomy for a supratentorial meningioma and had a dural allograft at the time of closure. The patients presented several weeks after surgery with clinical evidence of a wound infection. INTERVENTION All patients were diagnosed with P. acnes infection and treated for this pathogen with appropriate antibiotics. The bone flap was removed in two patients. After antibiotic therapy, all patients demonstrated no further evidence of infection. CONCLUSION To our knowledge, this is the first published report of P. acnes infection in patients with a dural substitute. The source of infection cannot be confidently ascertained; however, two patients had strains of P. acnes from one brand of graft, which were indistinguishable by pulsed field gel electrophoresis typing.

Supraophthalmic intracarotid infusion of BCNU for malignant glioma.

We treated five patients with 11 supraophthalmic infusions of BCNU at 200 mg/m2 every 2 months. All three patients with residual tumors showed marked CT response after one infusion. Two patients with bilateral tumors had no response on the contralateral side. All four evaluable cases showed evidence of BCNU neurotoxicity. CT findings superficially resembled tumor recurrence, but white matter changes, nonspecific gyral enhancement, and delayed calcification were more indicative of neurotoxicity. There were no procedure-related complications. One autopsy suggested that direct parenchymal damage might be responsible for delayed neurotoxicity. Supraophthalmic BCNU infusion, at this dosage, is too toxic for cerebral tissue.

Neuroanatomical Digital Image Processing in CT-Guided Stereotactic Operations

In order to utilize computed tomography (CT) for functional neurosurgical procedures, a number of problems must be resolved. One such problem is the development of an appropriate technique for digital processing of neuroanatomical images. Our previous work concerned a numerical reproduction of a well-known stereotactic atlas and its three-dimensional manipulation. In order to efficiently utilize this information with CT images we propose a technique for data reduction that allows the reconstruction of anatomical structures from the atlas. The logic of implementing these data in CT-assisted stereotactic surgery is described.

A fully interfaced computerized tomographic-stereotactic surgical system.

A fully interfaced computerized tomographic system has been designed and constructed. A prototype Philips Medical Systems Inc. translate-rotate body scanner has been modified to accommodate a specially designed head holder and stereotactic guide. A high resolution partial scanning algorithm is used to achieve improved spatial resolution in comparison to conventional algorithms. Integration of scanning data with the geometry of the guide system is achieved with software control.

Biologic Response to Intracavitary Interleukin-2/Lymphokine Activated Killer (IAK) Cells in the Treatmemt of Primary Malignant Brain Tumors

A Phase I trial of intracavitary recombinant Cetus IL-2 and lymphokine-activated killer (IAK) cells was performed in 9 adult patients (pts) with recurrent glioma with Karnofsky scores ≦ 60; 8 pts Grade IV, 1 pt Grade III. Following leukapheresis, lymphocytes were activated ex vivo. Activated IAK and IL-2 were infused via an Ommaya reservoir implanted in the tumor cavity during reqperation. Repetitive bolus IL-2 was given MWF for two weeks (wks). This cycle was repeated 2 wks later and in similar 4 wk courses every 12 wks for pts with anti-tumor response or stable disease. Corticosteroid therapy was limited to treatment of IL-2 related CNS toxicity. There was no evidence of systemic toxicity, nor were changes observed in peripheral immunophenotypes. The reservoirs were aspirated prior to each infusion and analyzed. A progressive eosinophilia was noted in the aspirates in a cumulative IL-2 dose-dependent manner, with apparent priming between cycles. Lumbar CSF punctures obtained in two cases also demonstrated eosinophilia. Similarly, IL-2 levels increased in the aspirates in a cumulative dose related manner. Tissue specimens, obtained in 5 pts after therapy, demonstrated pericavitary necrosis with an eosinophilic infiltrate and perivascular mononuclear cells. There were two partial responses. The median survival for 8 pts with Grade IV tumors was >50 wks, with 3 pts still alive.