Surgical Resection Of Brain Tumors Research Articles

Trigonal and Peritrigonal Lesions of the Lateral Ventricle: Presurgical Tractographic Planning and Clinic Outcome Evaluation

Surgery of lesions within the atrium of the lateral ventricle remains a challenging procedure because of the deep location and the relationship to vascular structures. The aim of this study was to determine the usefulness of tractography to evaluate the position of white matter tracts located along the course of the surgical access to trigonal and peritrigonal lesions. Diffusion tensor imaging (DTI) was acquired in 19 patients. All patients underwent surgical resection of brain tumors. Pre- and postoperative clinical conditions were evaluated by a neurosurgeon, using the Karnofsky Performance Status Scale. The corticospinal tract, optic radiation, and arcuate fasciculum were reconstructed because of their location close to the trigonal region. Two neurosurgeons were asked to assess the surgical approach with and without tractography. According to the tractographic reconstructions, the surgical access was chosen from the middle temporal gyrus in 12 patients (63%) and the posterior parietal gyrus in 7 patients (37%), leading to an a priori change in the surgical approach in 14 patients (73%). Six patients (31%) showed new postsurgical transient symptoms, whereas in 2 patients (10%) the deficits were permanent. After 30 days, the Karnofsky Performance Status Scale evaluation showed an improvement or a substantial stability of symptoms in 90% of cases. In 2 patients, a worsening of 30% of clinical performance was appreciable. The use of DTI in preoperative planning of trigonal and peritrigonal lesions may help in description of the best surgical approach for patient; this technique allows to reach the tumors, saving the white matter tracts, when it is possible.

Monopolar 250–500 Hz language mapping: Results of 41 patients

ObjectivesTo determine whether high-frequency 250–500 Hz monopolar stimulation is effective for mapping cortical and subcortical language structures during brain tumor resection. MethodsUsing high-frequency monopolar stimulation, we mapped the speech areas of 41 awake patients undergoing brain tumor resection in the dominant hemisphere, subject to risk of lesions in the cortical and subcortical speech tracts. Patients were tested for object naming, semantic and other language tasks. ResultsMapping was positive in 22 out of 41 patients. Nine patients presented clinical worsening immediately after surgery. Only one patient did not recover after the 30-day follow-up. Nineteen patients showed negative mapping for language tracts, none of whom exhibited worsening of symptoms at the final evaluation. The applied method showed 89% sensitivity and 56% specificity rates. ConclusionsThe applied method was effective in identifying cortical and subcortical speech areas during the surgical resection of brain tumors. SignificanceDetermining whether monopolar high-frequency stimulation is effective for language mapping is important, since it may be very effective in infiltrating tumor areas and nearby edema region.

387 Ischemic Preconditioning Reduces the Incidence of Postoperative Ischemic Lesions in Patients Undergoing Surgical Resection of Brain Tumors

Abstract INTRODUCTION Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Previous clinical and experimental studies have shown that the application of a brief ischemic stimulus not only in the target organ but also in a remote tissue can prevent ischemia. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences. METHODS Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified after tumor type (glioma or metastasis) and previous treatment with radiotherapy. Remote ischemic preconditioning was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 minutes at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative MR images were evaluated blinded to randomization for the presence of ischemia and its volume. RESULTS >Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 (75.9%) had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (87.1%) (27/31) than in the rIPC group (63.0%) (17/27) (P = 0.03). The median infarct volume was 0.36 cm3 (IR: 0.0- 2.35) in the rIPC group compared with 1.30 cm3 (IR: 0.29- 3.66) in the control group (P = 0.09). CONCLUSION Application of rIPC significantly reduced the incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery.

Post-Surgical Language Reorganization Occurs in Tumors of the Dominant and Non-Dominant Hemisphere.

Surgical resection of brain tumors may shift the location of cortical language areas. Studies of language reorganization primarily investigated left-hemispheric tumors irrespective of hemispheric language dominance. We used functional magnetic resonance imaging (fMRI) to investigate how tumors influence post-surgical language reorganization in relation to the dominant language areas. A total of, 17 patients with brain tumors (16 gliomas, one metastasis) in the frontotemporal and lower parietal lobes planned for awake surgery underwent pre-surgical and post-surgical language fMRI. Language activation post-to-pre surgery was evaluated visually and quantitatively on the statistically thresholded images on patient-by-patient basis. Results were qualitatively compared between three patient groups: temporal, with tumors in the dominant temporal lobe, frontal, with tumors in the dominant frontal lobe and remote, with tumors in the non-dominant hemisphere. Post-to-pre-surgical distributions of activated voxels changed in all except the one patient with metastasis. Changes were more pronounced in the dominant hemisphere for all three groups, showing increased number of activated voxels and also new activation areas. Tumor resection in the dominant hemisphere (frontal and temporal) shifted the activation from frontal towards temporal, whereas tumor resection in the non-dominant hemisphere shifted the activation from temporal towards frontal dominant areas. Resection of gliomas in the dominant and in the non-dominant hemisphere induces postsurgical shifts and increase in language activation, indicating that infiltrating gliomas have a widespread influence on the language network. The dominant hemisphere gained most of the language activation irrespective of tumor localization, possibly reflecting recovery of pre-surgical tumor-induced suppression of these activations.

Awake craniotomy. A patient`s perspective.

Objective:To report the personal experiences of patients undergoing awake craniotomy for brain tumor resection.Methods:We carried out a qualitative descriptive survey of patients’ experiences with awake craniotomies for brain tumor resection. The survey was conducted through a standard questionnaire form after the patient was discharged from the hospital.Results:Of the 9 patients who met the inclusion criteria and underwent awake craniotomy, 3 of those patients reported no recollection of the operation. Five patients had auditory recollections from the operation. Two-thirds (6/9) reported that they did not perceive pain. Five patients remembered the head clamp fixation, and 2 of those patients classified the pain from the clamp as moderate. None of the patients reported that the surgery was more difficult than anticipated.Conclusion:Awake craniotomy for surgical resection of brain tumors was well tolerated by patients. Most patients reported that they do not recall feeling pain during the operation. However, we feel that further work and exploration are needed in order to achieve better control of pain and discomfort during these types of operations.

Self-care Agency and Quality of Life in Brain Tumor Patients after Surgery

Purpose: This study evaluated the levels of self-care agency and quality of life and identified the effect of self-care agency on quality of life in brain tumor patients who had undergone surgical resection of brain tumors. Methods: Data were collected from 131 patients who visited an outpatient clinic for postoperative regular check-ups. Self-care agency and quality of life were assessed via self-administered questionnaires. Data were analyzed with descriptive, univariate, and hierarchical regression analyses. Results: The average scores for self-care agency and quality of life were 4.58 (possible range: 1~6) and 3.87 (possible range: 1~5) respectively. Social and thinking functions were the lowest among quality of life sub-scales. Education level was a significant correlate of quality of life in univariate analyses but not in multivariate analysis. Self-care agency accounted for 29.0% of the total variance in quality of life, controlling for education level. Conclusion: Approaches focusing on enhancing self-care agency could potentially improve quality of life in postoperative brain tumor patients.

O5.08 * INTRA-OPERATIVE NEUROPHYSIOLOGICAL MONITORING AND SMALL CRANIOTOMIES: RESULTS IN A CONSECUTIVE SERIES OF 85 PATIENTS WITH BRAIN TUMORS

INTRODUCTION: Intra-operative neurophysiological monitoring and brain mapping techniques represent nowadays the gold standard for surgical resection of brain tumors. Brain mapping usually requires the exposure of a large area of brain cortex in order to identify the different eloquent sites (e.g. primary motor strip, speech arrest sites). Thus, relatively large classic fronto-temporal craniotomies are generally performed. Nevertheless, in recent years the use of small craniotomies targeted on the tumor has gained popularity thanks to Neuronavigation systems and to the low morbidity rates associated with shorter surgical procedures and reduced anesthestic drug administration. Aim of this study was to review our experience which combines extensive neurophysiological monitoring and small craniotomies. Length of surgical time, intra-operative and post-operative complications, length of stay, extent of resection rate and the neurological outcomes were assessed. PATIENTS AND METHODS: Eighty-five consecutive patients (54 Males, 31 Females; Median Age 55 years, range 12-77) underwent surgery with brain mapping and intra-operative neurophysiological monitoring for resection of a brain tumor in eloquent location under asleep-asleep (62 patients) or asleep-awake (23 patients) anesthesia. Pre- and post-operative assessment included in-depth neuropsychological evaluation and MRI. Tumor histologies were the following: 74 gliomas (60 HGG, 14 LGG), 6 metastases and 5 other tumor histologies (2 cavernomas, 2, meningiomas, 1 AVM). The bone flap was tailored to the size of the tumor; no cortex other than that which was strictly necessary for tumor resection was exposed. The intra-operative neurophysiological monitoring included: EEG, SSEP, transcranial MEP and/or cortical MEP, ECoG; direct electrical stimulation (DES) was performed using bipolar and monopolar probes. RESULTS: Median surgical time was 230 minutes (range 90-390). Intra-operative complications included 9 seizures (3 requiring pharmacological treatment, 6 regressing after cold irrigation) and 5 electrical seizure. Post-operative neurosurgical complications were the following: 8 seizures and 4 re-operation for hematoma. Seventy-three patients (86%) could be discharged home while 12 (14%) were transferred to rehabilitation. In only 3 patients (3.5%) a permanent new neurological deficit could be noted at 3-month follow-up. Median post-operative stay was 7 days (range 3-45). CONCLUSIONS: In our experience a small craniotomy supported by extensive neurophysiological monitoring and brain mapping permitted to achieve satisfactory results in terms of complications, hospitalization, and neurological outcomes.

Hypertrophic olivary degeneration after surgical resection of brain tumors

Hypertrophic olivary degeneration (HOD) can be seen as high signal intensity with enlargement of the inferior olivary nucleus (ION) on T2-weighted magnetic resonance (MR) images 4-6 months after injury of the Guillain-Mollaret triangle. To the best of our knowledge, there has been no systematic evaluation with regard to the relationship between neurosurgical intervention affecting this pathway and the appearance of HOD. To evaluate MR findings of HOD after surgical resection of brain tumors with the temporal evolution in focus. MR images of seven patients that showed signal changes in the ION after surgical resection of brain tumors in the posterior fossa were retrospectively reviewed. T1-weighted imaging with and without gadolinium (Gd) contrast enhancement and T2-weighted imaging were performed in all patients before and after surgery. Before surgery, no patient had a signal change in the ION. T2-high signal intensity of the ION initially appeared 5 days to 2.5 months after surgery. Five patients showed enlargement of the ION with T2-high signal intensity 11 days to 3.5 months after surgery: three patients showed the enlargement of the ION subsequent to the T2-signal change on serial follow-up MR images. On Gd-enhanced T1-weighted images, there was no enhancement at the ION in any patient. Each signal change of the ION was consistent with HOD, according to the relationship between the resection site of the tumor and the Guillain-Mollaret triangle on follow-up MRI. HOD can be caused after neurosurgical intervention of brain tumors involving the Guillain-Mollaret triangle. It is important for radiologists to distinguish HOD from tumor recurrence.

Artifacts in magnetic resonance imaging after surgical resection of brain tumors

BackgroundSince the advent of magnetic resonance imaging, metal artifacts have posed an important diagnostic problem in different fields of medicine. However, this has not been systematically studied in patients undergoing surgery for brain tumors. ObjectiveThis study was planned to assess whether metal artifacts can occur in patients undergoing brain surgery without metallic implants. MethodsOf 40 individuals who could be included because of having a pre- and postoperative MRI and a postoperative computed tomography (CT) scan or a conventional skull X-ray for the detection of metallic artifacts, 26 patients agreed to participate in this study and gave informed consent. ResultsTwenty-six subjects, 12 males and 14 females, with an age range of 12 to 54 years, were included in the study. Four patients were found to have gross metal particles in their postoperative brain CTs and were excluded. Of the remaining 22 subjects, 7 patients (31.8%) had metallic artifacts. ConclusionOur study showed that simple bone drilling or chiseling during surgical manipulation of skull bones may result in separation of very tiny metal particles which can remain in the surgical site and cause artifacts in postoperative MRIs. This finding appeared to be independent of factors such as age, sex, tumor/incision site, tumor size, pathologic tumor type, total radiation dose, operation–MRI time interval and sequence of MRI.

Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models

Multifrequency (0 to 0.3 mm(-1)), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼1.5 in reduced scattering coefficient for all wavelengths and was ∼1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors.

Development of a Safe and Pragmatic Awake Craniotomy Program at Maine Medical Center

Awake craniotomy offers an excellent means of performing intraoperative mapping and optimizing surgical resection of brain tumors. Awake craniotomy relies on a strong collaboration between anesthesiologists, neurosurgeons, and operating room staff. The authors recently introduced awake craniotomy for tumor resection at the Maine Medical Center and propose that it can be performed safely, effectively, and efficiently in a high-volume community hospital. We describe a practical approach to performing awake craniotomy involving streamlined anesthetic protocols and simplified intraoperative testing parameters in a carefully selected group of patients. Our first 25 patients are retrospectively reviewed with particular attention to the anesthetic protocol, the extent of resection, the operative time, post-operative complications, the length of hospitalization, and their functional status at follow-up. The authors established an anesthetic protocol based primarily on midazolam, fentanyl, propofol, and local anesthetic. The authors note that all but one patient was able to tolerate the awake procedure. Gross total resection was achieved in nearly 80% of patients with a glial tumor. Operative time was short, averaging 159 minutes of entire anesthesia care. Length of stay averaged 3.7 days. Persistent new post-operative deficits were noted in 2 of 25 patients. There was no substantial difference in total hospital charges for patients undergoing awake craniotomy when compared to a matched historical control. With attention focused on patient selection and a streamlined anesthetic protocol, the authors were able to successfully implement an awake craniotomy protocol in a community setting with satisfying results, including low operative morbidity, short operative times, low anesthetic complications, and excellent patient tolerance.

Intraoperative EMG monitoring for protection of the posterior cranial nerves nucleus

Objective In order to protect the posterior cranial nerves nucleus,the intraoperative EMG monintoring was used during the surgical resection of brain tumors related to the forth ventrical floor.Method 23 brain tumors were surgically removed in our hospital from February 2007 to April 2008, which including 8 case of medulloblastoms, 7 enpendymomas, 3 brain stem gliomas.All the tumors were microsurgical removed and intraoperative EMG monitoring was applied during the operation. The dates of the posterior cranial nerves function,the surgical procedure and EMG monitor changes were analyzed in order to find their relationship.Results 17 tumors were totally removed and 6 subtotally removed.The patients posterior cranial nerves function were protected well in 6 cases, 13 cases of slight dysfunction and 4 cases of moderate dysfunction.There was no serious damage in our group.The myoelectricity induced by the posterior cranial nerve nucleus stimulation could be recorded successfully under normal anesthesia condition.Conclusion The intraoperative EMG monitoring could avoid posterior cranial nerves nucleus damage and provide objective judgment for resection strategy of tumors related to the forth ventrical floor. Key words: Brain stem neoplasms; Microsurgery; Intraoperative EMG monitor

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl- N-nitrosourea (MNU), and N-ethyl- N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of “GSNO > DEA/NO > SNP” when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP) tumors, mean overestimations of 2 and 24 µm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages) and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon) and primary (Gli36 glioma) brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

Accurate Characterization of the Main Trunk of the Anterior Cerebral Artery by Means of Intraoperative Sononavigation With Doppler Sonography

Doppler sonography can be used for real-time intraoperative localization of arteries within or near brain tumors but is less useful for distinguishing between arteries with similar diameters, such as the main trunk and branches of the anterior cerebral artery (ACA). By contrast, sononavigation provides real-time information in alignment with magnetic resonance imaging scans and may be of use in characterizing the identity of individual arteries on Doppler sonographic images. The goal of this study was to determine whether sononavigation can distinguish the main trunk of the ACA from the branches of the ACA on Doppler sonographic images. Doppler sonography was used in 3 patients undergoing surgical resection of brain tumors involving the main trunk of the ACA. The location of the main trunk of the ACA was characterized by sononavigation. With these data, tumor resection was performed with preservation of the main trunk of the ACA. Gross total resection was achieved in 1 case. Intraoperative sononavigation with Doppler sonography accurately localized the main trunk of the ACA and enabled preservation of this structure during tumor resection. This method may be applicable to the characterization of other critical arteries and may allow tumor resection with decreased morbidity.

On-line flow cytometry for real-time surgical guidance.

This study tests the feasibility of using on-line analysis of tissue during surgical resection of brain tumors to provide biologically relevant information in a clinically relevant time frame to augment surgical decision making. For the purposes of establishing feasibility, we used measurement of deoxyribonucleic acid (DNA) content as the end point for analysis. We investigated the feasibility of interfacing an ultrasonic aspiration (USA) system with a flow cytometer (FC) capable of analyzing DNA content (DNA-FC). The sampling system design, tissue preparation requirements, and time requirements for each step of the on-line analysis system were determined using fresh beef brain tissue samples. We also compared DNA-FC measurements in 28 nonneoplastic human brain samples with DNA-FC measurements in specimens of 11 glioma patients obtained from central tumor regions and surgical margins after macroscopically gross total tumor removal to estimate the potential for analysis of a biological marker to influence surgical decision making. With minimal modification, modern FC systems are fully capable of real-time, intraoperative analysis of USA specimens. The total time required for on-line analysis of USA specimens varies between 36 and 63 seconds; this time includes delivery from the tip of the USA to complete analysis of the specimen. Approximately 60% of this time is required for equilibration of the DNA stain. When compared with values for nonneoplastic human brain samples, 50% of samples (10 of 20) from macroscopically normal glioma surgical margins contained DNA-FC abnormalities potentially indicating residual tumor. With an interface of existing technologies, DNA content of brain tissue samples can be analyzed in a meaningful time frame that has the potential to provide real-time information for surgical guidance. The identification of DNA content abnormalities in macroscopically normal tumor resection margins by DNA-FC supports the practical potential for on-line analysis of a tumor marker to guide surgical resections. The development of such a device would provide neurosurgeons with an objective method for intraoperative analysis of a clinically relevant biological parameter that can be measured in real time.

Changes in Peripheral Blood Levels and Pulse Frequencies of GnRH in Patients with Hypopituitarism

Pituitary dysfunction occasionally results from brain tumors or the surgical resection of brain tumors. The authors examined two patients with hypogonadotropic secondary amenorrhea, who had undergone surgical removal of brain tumors. Changes in immunoreactive gonadotropin-releasing hormone (GnRH) secretion are of interest in patients with a gonadotropin and gonadal steroid deficit, because both steroid and pituitary feedback systems are altered by tumors or tumor resection. The authors thus measured GnRH, luteinizing hormone, and follicle-stimulating hormone levels every 15 minutes for 4 hours by radioimmunoassay and investigated qualitative and quantitative changes in the pulsatile patterns of these hormones in two hypogonadotropic hypogonadism patients. They also performed similar multiple measurements of GnRH in two normal cycle women in follicular phase and two postmenopausal women. The concentration of plasma GnRH in two hypopituitarism patients was compared with that in two normal cycle women and two postmenopausal women. The study showed that the peripheral blood level of GnRH was significantly lower in two hypopituitarism patients than in both normal cycle and postmenopausal women, and that the pulsatile frequency was not different among these three groups. These findings suggest that alteration of feedback systems results in a decrease in the blood level of GnRH, and that pulses of GnRH maintain normal fluctuation despite the alteration of the hormonal circumstances in two hypogonadotropic hypogonadism patients.

A proposed preoperative grading scheme to assess risk for surgical resection of primary and secondary intraaxial supratentorial brain tumors

Although surgical resection of brain tumors has been performed for over a century, complications still occur with distressing frequency. The authors propose a simple preoperative grading scheme to assess surgical risk for resection of primary and secondary intraaxial supratentorial brain tumors. The authors retrospectively reviewed the clinical records, neuroimaging studies, and outcomes of 224 surgeries performed in 207 patients from January 1993 to December 1995 at the Cleveland Clinic Foundation Brain Tumor Center. Subsequently, they considered and statistically analyzed multiple variables related to the patients and their lesions. Surgical risk was defined as any complication occurring within 30 days postoperatively, and was divided into transient operative complications, transient medical complications, and new sustained neurological deficits. Length of stay was also recorded. The overall incidence of complications was 10.6% and the mortality rate was 2.7%, with a median hospital stay of 3 days. Patient age greater than 60 years (p < 0.001), preoperative Karnofsky Performance Scale scores of 50 or less (p < 0.03), previous irradiation (p < 0.001), tumor location in eloquent regions (p < 0.03), and depth of tumor invasion (p < 0.001) independently predicted complicated outcome or increased length of stay. Finally, the authors derived a simple five-tier grading scheme in which these patient risk factors are added together to obtain a grade of I to V that corresponds to outcome and length of hospital stay. This grading scheme may be used to identify patients at higher risk and facilitate comparison of results between institutions and individual surgeons.

Clinical pharmacology of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193).

A pharmacokinetic study of tiazofurin was carried out in 13 patients treated in a phase I clinical trial of the drug and in 7 patients undergoing surgical resection of brain tumor (in conjunction with studies on penetration of drug into central nervous system tumors). Tiazofurin was found to be rapidly eliminated from the plasma and red blood cell fraction of both groups of patients with kinetics consistent with a two-compartment model of elimination. Operative conditions did not significantly change the pharmacokinetics of tiazofurin in CNS patients. Pharmacokinetics were linear over the dose range 500-2700 mg/m2. The data suggest that there is only a small degree of tissue binding of drug and that the drug is not concentrated by tissues. Uptake into RBC was rapid and elimination from RBC was essentially parallel to drug elimination from plasma. There was no evidence that RBC sequestration of drug contributes to toxicity. Much of the drug was excreted unchanged in the urine, but there was little correlation between creatinine clearance and plasma pharmacokinetics of tiazofurin, suggesting that renal tubular secretion may be a more important method of elimination than is glomerular filtration. Patients with high AUC values and low plasma clearance values were particularly prone to develop toxicity.