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.

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.

"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)

Clinical toxicity of combined modality treatment with nitrosourea derivatives for central nervous system tumors.

Two nitrosourea compounds--1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)--have been used in the treatment of primary and metastatic brain tumors after operation and/or radiotherapy. Hematological and nonhematological toxicity were recorded in 272 patients treated between May 1973 and June 1978. BCNU was given to 135 patients (80 mg/m2 i.v. daily for 3 days) and CCNU was given to 137 patients (130 mg/m2 orally, single dose) every 8 weeks until progression of the primary disease process or for a total of 12 cycles. Radiation therapy (5500 +/- 500 rads in 6 to 7 weeks) was carried out after the first course of chemotherapy. BCNU and CCNU induced the same hematological and clinical toxicity. The bone marrow toxicity seemed to be dose-related, delayed, and cumulative. One case of acute nonlymphoblastic leukemia arising 2 months after the end of CCNU therapy is reported.

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.

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.

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.

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.

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.

[Steroid receptors in brain tumors]. / I recettori steroidei nei tumori cerebrali.

Recently the presence of steroid hormone receptors (SHR) have been reported in a series of nervous system human tumors, mainly in meningiomas. The possibility of characterizing brain tumors deserves attention because of the poor knowledge of endocrine-related behaviour of such tumors. The reliability of biochemical characterization of various receptor types should allow for better understanding of biological profile of primary and metastatic brain tumor, together with new avenues for combined modality treatment. In the future the highest priority might be assigned to the definition of the cut-off value of positivity for single receptors and to the receptor-endocrine modulation complex relationship for individual patients. A clear definition of the role of SHR in human brain tumors might improve our therapeutic potentials.

[Chemotherapy, immunotherapy and supportive therapy in cerebral metastases]. / Chemioterapia, immunoterapia, e terapia di supporto delle metastasi cerebrali.

When a malignant tumor spreads to the brain, its concurrent growth outside of the Central Nervous System (CNS) and the devastating effects of cerebral metastases offset often all therapeutic attempts. The disappointing results commonly achieved in the management of intracranial metastases are only partly explained by the low efficacy of available therapeutic modalities. Support therapy plays the major role in the management of patients harboring cerebral metastases. Corticosteroids and osmotic agents can rapidly improve neurological symptoms, allowing a rapid, even if frequently brief, amelioration of the quality of life. Immunotherapy cannot be considered as an effective therapeutic tool for metastatic brain tumors. For many years chemotherapy has been thought inadequate treatment for both controlling the growth of metastases and improving neurological impairment . However the new concepts of multimodality therapy of primary CNS tumors seem to be applicable even to intracranial metastases. In combination with corticosteroids and radiation therapy, nitrosourea compounds (BCNU and CCNU) proved to be effective in more than 1/3 of patients in prolonging survival. New possibilities of improving available results are expected from new antiproliferative drugs (cisplatin) and from new modalities of administering conventional cytotoxic agents (intra-arterial route).

[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.

[Chemotherapy and immunotherapy of intracranial malignant gliomas]. / Chemioterapia ed immunoterapia dei gliomi maligni endocranici.

Although in recent years a great attempt has been made in brain tumor chemotherapy, this therapeutic approach appears to be conditioned by a large number of problems such as cell kinetics, tumor growth modalities, and drug delivery. Therefore only a small number of drugs (BCNU, CCNU, streptozotocin, and procarbazine) clearly demonstrate effectiveness against these tumors. Immunotherapy raises the same and other problems. In fact, if immune reaction is quite possible inside the brain, unfortunately current immunostimulant methods are unable to produce significant improvements.

[Combined treatment for malignant primitive brain tumors in infants using CCNU, neurosurgery and radiotherapy (author's transl)]. / Trattamento combinato con CCNU, intervento chirurigico e radiumterapia delle neoplasie endocraniche primitive dell'infanzia

The preliminary data (13 cases) is used to make a comparison between the survival length from the beginning of chemotherapy of these pediatric neuro-oncotypes with that of adults bearing sovra-tentorial astrocytomas or glioblastomas given the same treatment. Approximating, by means of normal distributions, the experimental results the Authors also note that the clinical efficacy of CCNU is more or less the same for infants and adults.

[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.

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.

Radio-chemo-immunotherapy (CCNU plus levamisole) for treatment of metastatic brain tumors. A pilot study.

Thirty-one patients with metastatic brain tumors were treated with Radiotherapy (RT) and CCNU or with RT, CCNU and Levamisole (LMS) in a randomized clinical trial. Twenty-seven were evaluable. All patients were submitted to whole brain radiation (50 +/- 5 Gy) and CCNU (130 mg/m2 p.o. every 8 weeks). 15 also received Levamisole (2.5 mg/kg p.o. daily for 3 weeks in the first month, for 2 weeks in the second, and then once a week monthly until progression). Primary tumor was predominantly lung cancer (22/27) and brain lesions were generally multiple (24/27). The overall response rate was 35% in the RT plus CCNU treated group and 38% in the RT plus CCNU plus LMS treated group. The median survival time was similar and not statistically different in both groups (7 versus 6 months). No important side effects were observed either in the RT + CCNU or in the RT + CCNU + LMS treated groups. The absence of combined depression of T-cell levels and responsiveness of lymphocytes to mitogens suggests that thymus dependent immunity could be improved by LMS administration. However, such improvement had no impact on duration of survival in patients with metastatic brain tumors.

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.