Complications following anterior cervical spine surgery for disc diseases: an analysis of ten years experience.

The purpose of this study is to define, analyse and discuss the incidence and severity of the complications associated with anterior cervical spine surgery for degenerative disc diseases. The results and the management of complications of anterior spine surgery are discussed in relation to numerous previous published reports: precise knowledge of all potential accidents and pitfalls related to the surgical approaches and of their aetiology may contribute to preventing failures. The most common complication was a recurrent laryngeal nerve injury that developed in 7.9% of the cases. Dysphagia occurred in 5.6%, hoarseness in 5.2%, transient sore throat in 4.8%, worsening of pre-existing myelopathy in 3%, graft extrusion in 1.7%; root injury, haematoma, and wound infection developed in 0.87%. There was one case of oesophageal injury (0.43%) and there were no deaths related to the surgical approach. The rate of complications in our series has been reduced in the past years by 1) better patients selection: all of the patients in fact had previously received conservative treatment for at least four weeks; 2) more care in correct positioning of the patient during the operation; 3) meticolous removal of all harmful structures.

CNS-85 trial: a cooperative pediatric CNS tumor study--results of treatment of medulloblastoma patients.

Between 1985 and 1989, 38 children with newly diagnosed medulloblastoma entered our therapeutic protocol. After surgery and postoperative staging assessments, patients were assigned to risk groups. Eleven with "standard-risk" (SR) tumors were treated with radiation therapy alone, while 27 with "high-risk" (HR) tumors received radiation therapy plus adjuvant chemotherapy with vincristine, methotrexate, VM-26, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). After a minimum follow-up of 5 years (range 5-9 years) 21/38 children had developed a recurrence or progression of their disease and 19/38 patients had died. Five-year event-free survival rates and 5-year total survival rates for all 38 patients were 47.4% and 50% respectively. The event-free survival rates at 5 years for SR and HR patients separately were 27.3% and 55.6%, respectively. The corresponding 5-year total survival rates were 27.3% and 59.3%. The differences were not statistically significant. Univariate analysis showed age at diagnosis to be the most important prognostic factor. Infants aged 5 years or less had a significantly shorter event-free survival time than older patients (P = 0.00897). Similar effects were found when total survival time was considered. There were significant differences in outcome in patients receiving different doses of radiation, suggesting a dose-response relationship. A Cox stepwise multivariate analysis showed age at diagnosis as the only independent prognostic factor. Variables relating to treatment entered the model, suggesting that chemotherapy could play an important role in determining outcome.

"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema.

The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Concentrations of VP16 and VM26 in human brain tumors.

VP16 and VM26 were determined by high pressure liquid chromatography in intracerebral tumors, adjacent normal brain tissue, plasma and CSF samples from 24 patients given the two drugs before surgical resection of the tumor. The drugs were administered at doses of 100-150 mg/m2 as a 1-hour i.v. infusion, between 1.5 and 12 hours before surgery. Concentrations of VP16 ranged between 1.05 and 3.28 micrograms/g in tumors in the series of patients who received the drug 1.5-3 hours before surgery and between less than 0.05 and 1.12 micrograms/g in four patients who received the drug 9-13 hours before surgery. Tumor concentrations of VM26 also varied, ranging from less than 0.05 to 1.68 micrograms/g between 1.5 and 12 hours before surgery. VP16 and VM26 in the apparently normal brain tissue surrounding the tumor were low or undetectable except in one patient who had received radiotherapy, in whom we found 3.1 micrograms/g.

Single versus multiple drug therapy in the combined treatment of malignant gliomas. A multicenter study.

The best treatment of malignant gliomas has been considered to be surgery followed by irradiation and chemotherapy with nitrosourea compounds. Our controlled and randomized trial was designed in 1982 to analyze the effectiveness of multiple-drug versus single-drug therapy in patients bearing malignant gliomas. After 3 weeks from surgery and histopathological diagnosis 173 patients were randomly assigned to receive one of the three chemotherapy regimens: CCNU alone, CCNU plus VM-26 or CCNU plus VM-26 plus 5-FU. Radiotherapy was administered whole-brain (40-45 Gy) and coned-down focal (15-20 Gy) irradiation for a total of 60 Gy (1700 rets) in conjunction with the first course of chemotherapy. 150/173 patients are evaluable. Statistical analysis of results shows a better quality of life and survival for patients treated with polychemotherapy using a three drug combination than two drug or single drug therapy (13.8 vs 14.7 vs 18.2 months MST; P less than 0.01) but with a higher incidence of toxicity problems. An analysis of prognostic factors and their distribution in each arm of the protocol will be made in the near future.

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience.

In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours. In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.

Cell kinetics aspects of human malignant neuroepithelial tumors: a follow-up study.

The prognostic value of proliferative activity and DNA distribution (ploidy), determined by flow cytometry (FCM), was evaluated in 38 cases of human malignant neuroepithelial tumors. No statistically significant correlation was found between flow cytometric data and clinical outcome. In particular, there was no significant difference between mean survival in cases with percentage of cells in S-phase lower and higher than 5%, respectively. In 21 cases with unimodal DNA distribution, the mean survival was 11.7 months; in 17 cases with bimodal DNA distribution, the mean survival was 12.5 months. The difference was not statistically significant. In our experience, proliferative activity and ploidy do not correlate well with the clinical course and survival of patients with malignant neuroepithelial tumors. However, application of FCM may provide, aside from histopathologic examination, additional biologic information that may be valuable in understanding the variation observed in the course of individual patients.

Recessive cancer genes in meningiomas? An analysis of 31 cases.

Cytogenetic studies on 31 human meningiomas revealed clonal abnormalities in 14 of them. Monosomy 22 was present in three cases as the only abnormality, and in five it was associated with monosomy 18, monosomy 14, loss of X, loss of Y, and trisomy 20, respectively. We found a number of rearrangements involving chromosome #22: an i psu dic(22)(pter----q11::q11----pter) in two cases and a t(18;22)(q12;q11) in another case. Two cases showed a complex translocation involving #7 and #14: t(2;7;14)(q23;q36;q22) and t(1;7;14)(q25;q32;q22), respectively. Other clonal chromosome abnormalities were del(1p) (present in two cases); der(9)t(9;?)(q34;?); der(7)t(7;?)(q31;?); der(22)t(22;?)(q11;?); and a 9p+ chromosome. The relevance for the pathogenesis of human meningiomas of these chromosome anomalies is also discussed with reference to the previous literature. The possible involvement of recessive cancer genes present on the long arm of chromosome #22 is also discussed.

Nitrosourea derivatives-induced pulmonary toxicity in patients treated for malignant brain tumors. Early subclinical detection and its prevention.

Nitrosourea derivatives, such as BCNU and CCNU, are considered useful chemotherapeutic agents in malignant brain tumors combined therapy. Pulmonary toxicity is one of the major side effects demonstrated both in experimental animal models and in human autoptic findings. Pulmonary fibrosis is the end point of progressive functional disorder of respiratory mechanism and alveolo-capillary gas exchanges. Authors present the results of a randomized, double-blind trial of 40 patients previously treated with surgery and radiotherapy and who subsequently underwent BCNU therapy for primary intracranial glioma. Patients underwent functional respiratory examinations at each chemotherapy course interval. Twenty patients received ambroxol (120 mg/day) for 40 days after chemotherapy course. Control patients received placebo with the same schedule and showed a significant reduction of pulmonary functional parameters (DLCO, MMEF, MEF 25%), whereas in the treated group there is no significant variation of these functional parameters. The mechanism of ambroxol is commonly related to the surfactant synthesis enhancement and to the action on bronchiolar pathways.

Ploidy and proliferative activity of human brain tumors. A flow cytofluorometric study.

Ploidy and proliferative characteristics were estimated by flow cytometry of the nuclear DNA content of 92 human brain tumors. Samples were frozen at -20 degrees C immediately after surgery and single cell suspensions were obtained with a mechanical dissociation technique. Propidium iodide was employed for nuclear DNA staining. Human normal brain tissue was used as internal diploid reference standard. 86% of benign tumors had unimodal DNA distribution with a DNA index (DNA I = modal channel of the G0/1 peak of the studied population/modal channel of the G0/1 peak of the normal brain) usually within the diploid or near-diploid range. 14.0% had aneuploidy, with an additional cell peak having a median DNA I of 1.60. Among malignant tumors, these figures were 61.2 and 38.8% (p less than 0.001). The percentage of S phase cells was higher in malignant (median = 3.6) than in benign tumors (median = 2.0, p less than 0.01), without correlation to histological tumor subtype. Flow cytometry appears to be a useful method for evaluating differences in DNA distribution in tumors of the central nervous system.

Enzymes related to energy metabolism in human gliomas.

The evaluation of the specific activity of some enzymes related to energy transduction was performed in 7 fresh samples of malignant gliomas and in 4 samples of normal brain tissue. Compared with normal brain tissue, the hexokinase, phosphofructokinase and citrate synthase activities are lower; the lactate dehydrogenase and succinate dehydrogenase are unchanged, while glucose-6-phosphate dehydrogenase and NADP+-isocitrate dehydrogenase activities are higher in gliomas.

Proliferative characteristics and ploidy of human brain tumors by DNA flow cytometry.

We studied nuclear DNA distribution by flow cytometry in 59 human brain tumors. Samples were frozen at -20 degrees C immediately after surgery and unicellular suspensions were obtained with a mechanical dissociation technique. Nuclear DNA was stained with propidium iodide. Normal human brain tissue was used as a diploid reference standard. In 86.3% of benign tumors an unimodal DNA distribution with a DNA index usually within the diploid range was found. Among malignant tumors, 64% had un unimodal DNA distribution with diploid or near-diploid modal DNA content. The remaining 36% showed an additional cell peak with a DNA index ranging from 1.15 to 1.92. The percentage of S-phase cells was higher in malignant (median = 3.8) than in benign tumors (median = 1.9) (p less than .001), without correlation to histological tumor subtype.

Ambroxol and pulmonary toxicity induced by antineoplastic drugs.

The authors describe the potential effects of ambroxol on the pulmonary disorders induced by antineoplastic agents (in particular, bleomycin and the nitrosureas). An experimental stage focussed attention on the early modifications occurring in the alveolar surfactant and in the afflux of inflammatory and immune-effector cells following bleomycin-induced lung fibrosis in the rat (by intratracheal instillation). The ambroxol-protected rats showed a slower drop of alveolar lecithins in the first few hours after bleomycin administration and a lower afflux of neutrophils, macrophages and lymphocytes. In the clinical stage, respiratory function was studied in two groups of cancer patients treated with nitrosureas or bleomycin. Preliminary findings indicate a rapid worsening of some functional parameters--maximal expiratory flow at 25% vital capacity, diffusing capacity for carbon monoxide and diffusing capacity/ventilation--in controls, while no such changes occurred in the ambroxol-protected subjects. The possible pathogenetic implications of these results and perspective for future investigations are discussed.

[Post-traumatic hydrocephalus]. / L'idrocefalo postraumatico.

Post-traumatic hydrocephalus is a complication of cranio-cerebral injuries and can manifest itself through different clinical syndromes. These include obtunding, a tetrad composed of psychomotory delay, memory loss, motility disturbances and sphincter incompetence, and unusual symptoms which comprehend emotional disturbances. Intracranial pressure monitoring, lombo-ventricular infusion test, in addition to neuroradiologic exams, are necessary in order to decide wether or not to derivate a post-traumatic hydrocephalus; neuropsychologic tests complete these investigational methods. The post-traumatic hydrocephalus bearer patient's recovery is always problematic when an important parenchimal damage exists. When a NPH (normal pressure hydrocephalus) is found the shunting operation is always indicated. However it is difficult to take a decision when the patient has a normal liquoral pressure but is too wounded to show a NPH or when he has an atypical clinical feature.

Chemotherapy plus immunotherapy for patients with primary and metastatic brain tumors.

The authors report two clinical trials concerning chemotherapy and immunotherapy combined in the treatment of primary and metastatic brain tumors. In the first study bacillus Calmette-Guerin (BCG) and in the second Levamisole (LMS) were utilized as immunostimulating agents. Chemotherapy was performed with BCNU or CCNU in association with surgery and/or radiotherapy. The immunological response was obtained but immunotherapy failed to demonstrate any significant effect on survival.

[Chemotherapy of malignant brain tumors in childhood]. / La chemioterapia dei tumori cerebrali maligni dell'infanzia.

The best conventional care for medulloblastoma and malignant ependymoma in children consists of surgery and radiotherapy. The preliminary observations of some authors suggested that chemotherapy could be useful in treating these tumors. The two major experiences in this field are those from SIOP and CCSG -RTOG trials which used chemotherapy as adjuvant to surgery and radiotherapy. In such studies chemotherapy appears to be effective mostly in high-risk patients. A study performed by Italian Child's Neurooncology Group ( ICNG ) confirms the preceding results.