Thiamine-deficient lactic acidosis with brain tumor treatment

1998 ◽  
Vol 89 (6) ◽  
pp. 1025-1028 ◽  
Author(s):  
Hiroshi Kuba ◽  
Takanori Inamura ◽  
Kiyonobu Ikezaki ◽  
Masatou Kawashima ◽  
Masashi Fukui

✓ Lactic acidosis due to thiamine deficiency is known to complicate chemotherapy and radiotherapy treatment of malignant extracranial tumors, but to the authors' knowledge, this complication has not been reported in patients treated for malignant brain tumors. They report three such cases, demonstrating that this complication can occur during treatment of brain tumors. In all patients, consciousness levels deteriorated within 1 to 2 days. Serum lactic acid levels increased to concentrations between 62 and 96.7 mg/dl, resulting in severe metabolic acidosis. A low blood thiamine level (9 ng/ml) was demonstrated at the onset in one case, and high-dose thiamine infusions dramatically improved lactic acidemia as well as impairment of consciousness in two cases. In the other case, hydrocephalus was suspected initially, resulting in a delay in thiamine supplementation. Clinical differentiation of this form of lactic acidosis from hydrocephalus or tumor progression can be very difficult in a patient undergoing treatment for a malignant brain tumor. Demand for thiamine is thought to be increased in patients with malignant brain tumors, and supplemental thiamine during treatment is necessary to prevent lactic acidosis. When this complication occurs, immediate treatment with sufficient thiamine is essential, together with normalization of pH by using sodium bicarbonate. With timely intervention, the level of consciousness can recover to the preacidotic state with no new neurological deficits.

2003 ◽  
Vol 99 (4) ◽  
pp. 738-745 ◽  
Author(s):  
Yoshitaka Yamada ◽  
Toshihiko Kuroiwa ◽  
Toshimasa Nakagawa ◽  
Yoshinaga Kajimoto ◽  
Takehiko Dohi ◽  
...  

Object. Survivin, one of the apoptosis inhibitor proteins, has been detected in most cancers in humans. In addition, two splice variants (survivin-2B and survivin-ΔEx3) have been identified. The authors investigated the transcription levels of survivin messenger (m)RNA and its splice variants in nine tumor cell lines, including gliomas, and in 25 brain tumor samples, by performing quantitative reverse transcription-polymerase chain reaction. The correlation between transcript expression levels and pathological findings were also analyzed. Methods. Transcription levels were measured using primer pairs specific for survivin and either of its splice variants and were normalized to the glyceraldehyde 6-phosphate dehydrogenase. Among the tumor cell lines tested, glioblastoma cell lines showed the highest levels of survivin expression. Among brain tumor samples studied, survivin was preferentially expressed in malignant brain tumors and gliomas. The relative expression level of survivin-ΔEx3/survivin was significantly higher in malignant than in benign brain tumor samples. Expression patterns were dominant for survivin-ΔEx3 in malignant brain tumors and dominant for survivin-2B in benign ones. A significant linear correlation between survivin mRNA expression and MIB-1 labeling index was demonstrated in all brain tumor samples. Conclusions. The authors' results indicate that quantifying the levels of survivin and its splice variants is useful for the prediction of the cell biological malignancy of gliomas, independent of their pathological features.


2004 ◽  
Vol 101 (6) ◽  
pp. 960-969 ◽  
Author(s):  
Alexander M. Gorbach ◽  
John D. Heiss ◽  
Leonid Kopylev ◽  
Edward H. Oldfield

Object. Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear. Methods. An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis—astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow. Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery. Conclusions. Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion.


1993 ◽  
Vol 79 (4) ◽  
pp. 562-568 ◽  
Author(s):  
Harry T. Whelan ◽  
Meic H. Schmidt ◽  
Annette D. Segura ◽  
Timothy L. McAuliffe ◽  
Dawn M. Bajic ◽  
...  

✓ Photodynamic therapy was studied in dogs with and without posterior fossa glioblastomas. This mode of therapy consisted of intravenous administration of Photofrin-II at doses ranging from 0.75 to 4 mg/kg 24 hours prior to laser light irradiation in the posterior fossa. Tissue levels of Photofrin-II were four times greater in the tumor than in the surrounding normal brain. Irradiation was performed using 1 hour of 500 mW laser light at a wavelength of 630 nm delivered through a fiberoptic catheter directly into the tumor bed via a burr hole. All animals receiving a high dose (4 or 2 mg/kg) of Photofrin-II developed serious brain-stem neurotoxicity resulting in death or significant residual neurological deficits. A lower dose (0.75 mg/kg) of Photofrin-II produced tumor kill without significant permanent brain-stem toxicity in either the control animals or the animals with cerebellar brain tumors receiving photodynamic therapy.


1987 ◽  
Vol 67 (6) ◽  
pp. 852-857 ◽  
Author(s):  
Douglas Kondziolka ◽  
Mark Bernstein ◽  
Lothar Resch ◽  
Charles H. Tator ◽  
J. F. Ross Fleming ◽  
...  

✓ A retrospective clinical and pathological review of 905 consecutive brain tumor cases (excluding pituitary adenoma and recurrent tumor) was conducted to identify cases in which intratumoral hemorrhage was confirmed grossly and/or pathologically. There were 132 cases so identified, for an overall tumor hemorrhage rate of 14.6%; of these, 5.4% were classified as macroscopic and 9.2% as microscopic. The presence of hemorrhage was correlated with the neurological presentation. The highest hemorrhage rate (70.0%) was found in patients with prior neurological history who experienced apoplectic deterioration (acute-on-chronic presentation). Only 57.1% of patients with acute deterioration in the absence of prior neurological symptoms had hemorrhages. The highest hemorrhage rate for primary brain tumors was 29.2% for mixed oligodendroglioma/astrocytoma, while the highest hemorrhage rate for any tumor type was 50% for metastatic melanoma. The clinical relevance of tumor hemorrhage is discussed.


1998 ◽  
Vol 89 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Raul A. Rodas ◽  
Robert A. Fenstermaker ◽  
Paul E. McKeever ◽  
Mila Blaivas ◽  
Lawrence D. Dickinson ◽  
...  

Object. Thrombotic complications (deep vein thrombosis and/or pulmonary embolization [DVT/PE]) occur in 18 to 50% of patients harboring brain tumors who undergo neurosurgical procedures. Such patients are at risk for DVT/PE because of immobility, paresis, hypovolemia, and lengthy surgery. The present study was undertaken to see whether tumor patients at highest risk for DVT/PE could be identified so that augmentation of prophylactic measures might be used to reduce the incidence of thrombotic complications. Methods. The authors conducted a retrospective analysis of 488 patients enrolled in their brain tumor registries between 1988 and 1995, identifying 57 patients (12%) with recorded symptomatic DVT, PE, or both postoperatively. In 24 of these 57 cases histological specimens were retrievable for review, allowing an in-depth analysis. Forty-five patients were lost to follow-up review, and the remaining 386 patients had no record of systemic thrombosis. Slides of pathological specimens were retrievable in 50 cases in which there was no DVT/PE. From these 50 cases, 25 were selected at random to represent the control group by a blinded observer. Seventeen (71%) of the 24 brain tumor specimens obtained in patients with DVT/PE stained positively for intraluminal thrombosis (ILT) after hematoxylin and eosin had been applied. The odds ratio associated with the presence of ILT was 17.8, with a confidence interval ranging from 4 to 79.3. No evidence of ILT was found in 22 patients (88%) within the control group (p < 0.0001, Fisher's exact test). Other factors that may predispose patients with brain tumors to DVT/PE—limb paresis, extent of tumor removal, and duration of the surgery—were also analyzed and found not to be statistically significant. Therefore, these factors were not the basis for differences seen between the study and control groups. Conclusions. These preliminary observations suggest that the presence of ILT within malignant glioma or glioblastoma tumor vessels may represent a marker of tumor-induced hypercoagulability.


1990 ◽  
Vol 73 (3) ◽  
pp. 396-400 ◽  
Author(s):  
Takafumi Nishizaki ◽  
Tetsuji Orita ◽  
Koji Kajiwara ◽  
Norio Ikeda ◽  
Noboru Ohshita ◽  
...  

✓ There are no previous reports correlating the in vitro bromodeoxyuridine (BUdR) labeling index (LI) with the clinical outcome in patients with brain tumors. The reliability of the LI as a predictor of patient survival or recurrence was examined in this study of 66 human brain tumors (19 gliomas, 18 meningiomas, and 29 others). Anti-BUdR staining was performed on surgically extirpated tumor tissue that had been treated with BUdR as previously described. Correlation of the BUdR LI with patient survival or tumor recurrence rate was carried out by the method of Kaplan and Meier. Deoxyribonucleic acid (DNA) aneuploidy was estimated in 52 cases. The results of this study indicate that BUdR LI values correlated well with the clinical course of patients with brain tumor. In comparison with patients with higher LI's, there was both a significantly higher survival rate for tumors other than meningiomas and a higher recurrence-free rate for meningiomas in patients with LI's of less than 4% and 1%, respectively. Although there was a tendency for patients without tumor aneuploidy to show better survival data than the others, no statistical difference was observed. These results suggest that the in vitro BUdR labeling method is reliable for prediction of a patient's prognosis, whereas prognosis on the basis of DNA aneuploidy alone is uncertain.


1983 ◽  
Vol 58 (5) ◽  
pp. 650-653 ◽  
Author(s):  
Nicholas J. Patronas ◽  
Javad Hekmatpanah ◽  
Kunio Doi

✓ Perfluorocarbon, a new tumor-seeking x-ray contrast agent, was injected into three rats with experimental brain tumors. After 1 to 3 days the rats were sacrificed, and the brains were removed and subjected to x-ray study. All showed dense radiopaque areas which correlated with the size and shape of the corresponding brain tumors. Conversely, none of the radiograms taken of the brain tumor in five rats receiving no perfluorocarbon (control animals) showed similar increased density. These findings suggest that perfluorocarbon may serve a useful role as a contrast medium for computerized tomography studies of brain tumors in man.


1993 ◽  
Vol 79 (3) ◽  
pp. 400-407 ◽  
Author(s):  
Zvi Ram ◽  
Kenneth W. Culver ◽  
Stuart Walbridge ◽  
Joseph A. Frank ◽  
R. Michael Blaese ◽  
...  

✓ Retroviral-mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene into malignant tumors confers drug susceptibility to the antiviral drug ganciclovir. The authors have recently shown that in situ transduction of the rat 9L brain tumor following HSVtk-producer cell implantation led to tumor regression after ganciclovir administration in treated rats. A wide spectrum of potential adverse effects may, however, be associated with the application of this approach to treat brain tumors, including dissemination of the retroviral vector to nontumoral tissues within or outside the central nervous system, proliferation of the injected murine vector-producer cells at the injection site, immune-mediated responses to the implantation of xenogeneic cells, and damage to the brain from toxic by-products of the HSVtk-ganciclovir interaction. These possibilities were investigated using intracerebral and systemic injections of retroviral vector-producer cells carrying the HSVtk or the lacZ gene in mice, rats, and nonhuman primates. Using the lacZ gene as a reporter gene, no evidence of β-galactosidase activity consistent with vector transduction was detected in any major body organ in the treated mice or rats. Similarly, the HSVtk gene transfer did not result in toxicity, with or without ganciclovir administration. In studies using rat and monkey models, no proliferation of the vector-producer cells occurred after intracerebral injection. Vector-producer cell survival was limited to 7 to 14 days. High-dose steroid therapy did not appear to extend the survival of these xenogeneic cells in rats. No significant inflammatory response was observed in the meninges or brain parenchyma. Endothelial cells were occasionally transduced in brain capillaries adjacent to the injected site of the vector-producer cells. Injection of producer cells into brain tissue elicited mild edema and reactive gliosis surrounding the injection site, which were probably the cause of a transient toxic response arising 4 to 5 days following injection of the producer cells; short-term administration of dexamethasone eliminated that response. No neurological deficits were observed in the rats or primates treated with the HSVtk vector-producer cells, with or without ganciclovir. In primates injected with producer cells, magnetic resonance imaging before, during, and after ganciclovir administration showed minimal and localized breakdown of the blood-brain barrier without significant edema or mass effect. Similarly, histological examination of the monkeys' brains showed no damage to neurons, astroglia, or myelin. Long-term clinical (> 9 months) and radiological (3 months) assessment of the primates has revealed no evidence of toxicity. The results of these studies indicate that intratumoral implantation of HSVtk-producer cells can be attempted for the treatment of brain tumors, without anticipating significant adverse toxicity to normal brain or remote proliferating tissues.


1971 ◽  
Vol 34 (3) ◽  
pp. 408-411 ◽  
Author(s):  
Sanford R. Weiss ◽  
Robert Raskind

✓ In view of the technical complexity of gas ventriculography and the physiologic hazards of water insoluble contrast media, methylglucamine iothalamate 60% (Conray) was used in the diagnosis of brain tumor or congenital malformation in 15 children 1 mos to 10 yrs of age. The method proved simple, reliable, and radiographically satisfactory. General or local anesthesia was used. It was not necessary to change the position of the head during study. The medium left the ventricular system within 5 to 10 min and was excreted in the urine within 24 hrs. No complications occurred.


1984 ◽  
Vol 60 (6) ◽  
pp. 1287-1290 ◽  
Author(s):  
Sanford Kempin ◽  
Narayan Sundaresan ◽  
William B. Shapiro ◽  
Zalmen Arlin

✓ Two patients with malignant brain tumors who developed acute nonlymphocytic leukemia after treatment with radiation and chemotherapy are described. Both patients survived more than 2 years after diagnosis of the brain tumor. Survival following the diagnosis of leukemia was short, and both patients died of hemorrhage secondary to thrombocytopenia. A review of the literature reveals that leukemia after combined-modality treatment of malignant brain tumors is rare. A prolonged survival period from diagnosis of the primary tumor, treatment with nitrosoureas and radiation, plus the development of a preleukemic myelodysplastic syndrome are all important features of therapy-related nonlymphocytic leukemia.


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