Prognostic value of peritumoral edema and angiogenesis in intracranial meningioma surgery.

PURPOSE: In a series of 78 consecutive patients we analyzed the influence of peritumoral edema (PTE) and angiogenesis (vascular endothelial growth factor/ VEGF expression) on the prognosis of morbidity and postoperative complications after intracranial meningioma surgery. METHODS: A retrospective analysis was performed of clinical, neuroradiological and histological data of 78 microsurgically treated patients with intracranial supratentorial meningioma, with follow-up period of at least one year. RESULTS: The severity of PTE showed significant correlation with VEGF expression, and all patients with large PTE (>40 mm) had strong VEGF expression (>50%). Treatment outcome was significantly better in patients with low VEGF expression (p<0.05). All of the monitored postoperative complications were more frequent in the group with PTE.The duration of intensive care treatment in the group with PTE (mean 6.85 days) was significantly longer than in the group without PTE (mean 3.68 days) (p=0.003). In the group without PTE, the outcome was significantly better than in patients with PTE (p<0.01). CONCLUSION: PTE in intracranial meningiomas has significant influence on the prognosis in surgically treated patients in terms of increased risk of morbidity and postoperative complications. VEGF expression is strongly correlated with PTE formation, which also affects the outcome in the management of patients with intracranial meningioma.

Late relapse of pediatric medulloblastoma.

Medulloblastoma (MB), the most common malignant brain tumor of childhood, is classified according to pathomorphologic characteristics in the group of central nervous system embryonal tumors, but both its pathogenesis and biologic behavior remain unknown. In addition, the relationship of MB to other embryonal brain tumors is debated and response to therapy is difficult to predict. The authors report an uncommon case of unfavorable late relapse, local as well as distant, in a 26-year old male patient, who was free of disease and without treatment-related morbidity for fifteen years after combined therapy for pediatric MB.

[Predictive factors for recurrent haemorrhagies in patients with brain cavernoma].

Haemorrhage is most important sequelae of brain cavernoma, so the surgical treatment is very important for treatment that complication. There are two types of bleeding chronic subclinical microhaemorrhage and acute real haemorrhage. Pathophysiological factors wich are responsible for bleeding are not still understanding. The reason for this study is understanding of clinical curse of cavernomas and identification of factors of influence. This is retrospective and prospective study. We analised 36 patients with simpthomatic brain cavernoma, surgicaly treated in Institute of neurosurgery KCS in 10 years period (1987-1997). Female were dominant but without statistical significance (p > 0.05). Male patients were older (32,1:29,8), but without statistical significance (p > 0.05). Almost 75% lesions were supratentorial, 25% infratentorial (p < 0.05). Focal neurological deficite (FND) was dominant clinical presentation in 52.8%. FND was dominant in 52.6% female, but without statistical singnificans (p > 0.05). Clinical presentation according the age was not statisticaly significant (p > 0.05). Clinical presentation was very diferent according the size of lesion (p < 0.001). FND as a sign of bleeding was in 57.9% supratentorial cavernomas and in 42.1% infratentorial (p < 0.005). More than 1/3 patients have recurent bleeding with 21 atack of haemorrhage or almost 2 atack per patient. We find that dominant predictive factors for recurent haemorrhages are localisation and size of lesion.

[The effect of extent of tumor resection on the outcome of combined therapy in patients with glioblastoma multiforme]. / Uticaj obima resekcije tumora na ishod kombinovanog lecenja bolesnika s multiformnim glioblastomom.

INTRODUCTION: The importance of the extent of surgery as a prognostic factor in multiform glioblastoma has been investigated for years. Some studies could not establish its influence on survival of patients treated with surgery, postoperative radiotherapy, with or without chemotherapy. On the other hand, there are data suggesting benefit for patients treated with more aggressive surgical approach. The aim of this study was to investigate the influence of the extent of surgery on survival/progression-free survival of patients with multiform glioblastoma treated with two consecutive protocols of a combined approach. MATERIAL AND METHODS: Of 86 patients that entered this study, thirty-seven were treated with surgery, postoperative hyperfractionated radiotherapy using 1.2 Gy b.i.d. to a total tumour dose of 72 Gy in 60 fractions in 30 treatment days and adjuvant chemotherapy consisting of BCNU, vincristine, procarbazine and cisplatin for up to 6 cycles or until tumour progression. Forty-nine patients were treated with surgery and postoperative accelerated hyperfractionated radiotherapy using 1.5 Gy b.i.d. fractions to a total tumour dose of 66 Gy in 44 fractions during 22 treatment days. BCNU and hydroxyurea were given once weekly during the irradiation period. Surgery consisted of biopsy in 25 patients and subtotal or gross total tumour resection in 61 patients. Patients treated with a more radical surgery had longer median survival time and higher 1- and 2-year survival rates than those treated with biopsy (56 v.s. 29 weeks, respectively; 62% and 23% v.s. 16% and 0%, respectively; long rank, p = 0.0000) (Figure 1). They also had longer median time to tumour progression and higher 1-year progression-free survival rate than those treated with biopsy only (33 v.s. 21 weeks, respectively; 20% v.s. 0%, respectively; log rank, p = 0.00000) (Figure 2). Multivariate analyses using both survival and progression-free survival as endpoints confirmed that the extent of surgery was an independent prognostic factor, together with the age, tumour location, and interfraction interval (Tables 3 and 4). DISCUSSION: The benefit of a more radical surgery remains controversial in patients with multiform glioblastoma, although maximal tumour reduction should be supported from the cytokinetic point of view. Findings of various authors support this view. Results of this study add further evidence that the aggressive surgical approach carries significant benefit for patients with multiform glioblastoma regarding the survival and progression-free survival. These observations are confirmed with multivariate analyses that showed independent influence of this prognostic factor.

[Hyperfractionated radiotherapy and adjuvant chemotherapy in patients with malignant gliomas]. / Hiperfrakcionisana radioterapija i adjuvantna hemioterapija kod bolesnika s malignim gliomom.

INTRODUCTION: Malignant gliomas are the most common primary brain tumours in adults. Postoperative radiation therapy significantly improves survival when compared to surgery alone. It is occasionally followed by the adjuvant chemotherapy (CHT). Since this approach carries a significant hazard of local recurrence, new approaches have been tested in order to improve survival figures, hyperfractionated radiation therapy (HFX RT) and recent multiagent CHT. MATERIAL AND METHODS: Fourty eight adult patients with malignant glioma were treated with HFX RT to a total TD of 72 Gy in 60 fractions in 30 treatment days, 1.2 Gy b.i.d. fractions with an interfraction interval of 4.5-6.0 hr. Four weeks after HFX RT, CHT was introduced consisting of BCNU, Vincristine, Procarbazine, and Cisplatin. Six cycles were planned to be administered but CHT was stopped because of tumour progression. Toxicity criteria were made on the basis of joint RTOG/EORTC toxicity criteria. RESULTS: Median survival time in all 48 patients was 52 weeks, and 1-3 year survival time was 48%, 29%, and 29%, respectively. Median progression-free survival was 30.5 weeks. Patients with AA achieved better results than those with GBM, regarding the overall survival and progression-free survival (p = 0.0000). The univariate analysis revealed that the age, performance status, and extent of surgery were important prognostic factors influencing the overall survival and progression-free survival, as well as tumour location and interfraction interval. The multivariate analysis revealed that the performance status, tumour location, and interfraction interval were independent prognostic factors in patients with GBM. Toxicity of this treatment approach was generally considered as mild, with no late toxicity attributed to HFX RT. CHT-related toxicity was mostly haematological. DISCUSSION: The results of this study are in agreement with those using standard and various altered fractionated regimens in malignant glioma. They add evidence that this combined approach is feasible and well tolerated by the patients. Although there is some controversy about dose-escalation in HFX studies in the past, the studies reporting no significant improvement in survival for HFX RT were probably due to somewhat lower total doses used in them. Since this approach contributed to a 3-year survival of 83%, and 3-year progression-free survival of 70% in AA patients (all treated with 4.5 hr interfraction interval), they could serve as a basis for further studies measuring late effects as an endpoint, since there are data showing that aggressive treatment might be hazardous in patients with AA.

Accelerated hyperfractionated radiation therapy for malignant glioma. A phase II study.

Sixty-four adult patients with malignant glioma entered into a Phase II study on the use of accelerated hyperfractionated radiation therapy. Histology included anaplastic astrocytoma (AA) in 15 patients and glioblastoma multiforme (GBM) in 49 patients. Treatment consisted of radiation therapy doses of 66 Gy in 44 fractions in 22 treatment days in 4.5 weeks, fractions of 1.5 Gy, b.i.d. 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) 80 mg/m2 and hydroxyurea 800 mg/m2 were both given on treatment days 1, 6, 11, 16, and 21 during the irradiation course. Median survival time for all 64 patients is 61 weeks (range; 12-163 weeks) from the date of starting irradiation. Median time to tumor progression (MTP) for GBM patients is 31 weeks, and 1-year and 3-year progression-free survival (PFS) are 16% and 0%, respectively, while MTP for AA patients is not attained yet, and 1-year and 3-year PFS are 100% and 73%, respectively. On univariate analysis of prognostic factors for GBM patients, younger age, total or subtotal tumor removal, and frontal tumor location are associated with a better prognosis. A multivariate analysis confirmed the importance of the extent of surgery and tumor site and revealed the interfraction interval (4.5-5.0 hours vs 5.5-6.0 hours, p = .041) as an important prognostic factor. Acute and late toxicity is not increased. Longer follow-up and more patients are needed to evaluate tumor control and toxicity in AA patients.

Hyperfractionated radiation therapy (HFX RT) followed by multiagent chemotherapy (CHT) in patients with malignant glioma: a phase II study.

PURPOSE: Forty-eight patients with malignant glioma were treated with hyperfractionated radiation therapy followed by multiagent chemotherapy to explore feasibility and toxicity of such combined modality treatment. METHODS AND MATERIALS: There were 34 males and 14 females with a median age of 53 years (range, 32-74 years) and median Eastern Cooperative Oncology Group performance status score of 1 (range, 0-3). Histology included anaplastic astrocytoma in 11 patients and glioblastoma multiforme in 37 patients. Radiation was given at 1.2 Gy per fraction, two fractions per day, for a total dose of 72 Gy, with a reduction in field size after 52.8 Gy. Four weeks after completion of hyperfractionated radiation therapy multiagent chemotherapy was introduced with bischlorethyl nitrosourea (BCNU) 50 mg/m2, days 1-3, vincristine 1.4 mg/m2 (max. 2 mg), day 1, procarbazine 50 mg/m2, days 1-7 and cisplatin 20 mg/m2, days 1-3. Cycles were repeated every 4 weeks to a maximum of six cycles or until tumor progression was noted. RESULTS: Median survival time for all patients was 52 weeks (range, 16-185 weeks) and median time to tumor progression was 30.5 weeks (range, 12-131 weeks). Besides age, histology, performance status, and extent of surgery, interfraction interval and location of tumor influenced survival in glioblastoma multiforms patients on univariate analysis: Patients treated with shorter intervals (4.5-5 h) did better than those treated with longer intervals (5.5-6 h); also, glioblastoma multiforme patients with frontal tumors did better than those with tumors of the other locations. Multivariate analysis confirmed that the performance status, interfraction interval, and tumor location were significant prognostic factors in glioblastoma multiforme patients. Acute toxicity was mild. No cases of brain necroses were observed. CONCLUSION: Hyperfractionated radiation therapy followed by multiagent chemotherapy was well tolerated with mild acute and virtually no late toxicity. More patients and longer follow-up are needed for further evaluation of its activity and late effects in anaplastic astrocytoma patients.

[Treatment of severe craniocerebral injuries]. / Lecenje teskih kraniocerebralnih povreda.

During 1992. 19357 patients were examined at the Department for Neurosurgery of the Emergency Centre, Clinical Center of Serbia, out of which 15879 had head injury. In addition to those necessitating hospitalisation, there was also a large number of patients with mild head injury that were not admitted for hospital management and were sent home following initial first aid. The average incidence of these patients was 45 patients per day during 1992. During 1992. a total of 1,978 patients were hospitalised, out of which 1,520 (84%) were injured. A total of 633 patients (25%) were hospitalised due to injuries sustained in traffic accidents. All patients were examined and evaluated according to the standard protocol including GCS as well.

Influence of extent of surgery and tumor location on treatment outcome of patients with glioblastoma multiforme treated with combined modality approach.

Between 1988 and 1991, eighty-six patients with glioblastoma multiforme were evaluated in order to define the influence of extent of surgery and tumor location on treatment outcome. Patients underwent surgery followed by postoperative hyperfractionated radiotherapy and chemotherapy delivered according to one of two consecutive protocols. Surgery consisted of biopsy in 25 (29%) patients and subtotal or gross total tumor resection in 61 (71%) patients. Frontally located tumors were noted in 26 (30%) patients and other tumor locations were noted in 60 (70%) patients. Patients having more radical surgery had longer median survival time (MST) and higher 1- and 2-year survival rates than those with biopsy only (56 vs 29 weeks, respectively; 62% and 23% vs 16% and 0%, respectively; p = 0.00000). Patients having frontally located tumors had longer MST and higher 1- and 2-year survival rates than those with other tumor locations (101 vs 47 weeks, respectively; 76% and 44% vs 37% and 2.5%, respectively; p = 0.00001). Multivariate analysis confirmed that extent of surgery and tumor location were independent prognostic factors in patients with glioblastoma multiforme. Regarding progression-free survival, patients having more radical surgery had longer median time to tumor progression (MTP) than those with biopsy only (33 weeks vs 21 weeks, respectively). Also, progression-free survival at 1 year was higher in radically resected group than in biopsy only group (20% vs 0%, respectively; p = 0.00000). Patients with frontally located tumors had longer MTP (42 weeks) and higher progression-free survival at 1 year (42%) than those with other tumor location (28 weeks and 1.7%, respectively; p = 0.00002).(ABSTRACT TRUNCATED AT 250 WORDS)

[Radiotherapy of primary spinal cord tumors in adults]. / Radioterapija primarnih tumora kicmene mozdine odraslih osoba.

Between 1980 and 1985 we treated 21 patients with primary spinal cord tumors. There were two diffuse and ten localized ependymoma, six low grade astrocytoma and three malignant glioma. Surgery consisted of total resection in six patients, subtotal resection in three and biopsy in twelve patients. Radiation doses ranged 45-55 Gy. Median age was 55 years (34-70 years), and median follow-up after therapy was 5 years (1-9 years). For patients with localized ependymoma, overall survival and 5-year recurrence-free survival are 80%. Of two patients with diffuse ependymoma, one is alive with no evidence of disease 6 years after the initial diagnosis, while the other is dead. Overall survival and 5 years recurrence-free survival for patients with low grade astrocytoma are 83% and 67%, respectively. All three patients with malignant glioma died of local recurrence (one had diffuse craniospinal metastases, too) one year after the initial diagnosis. Radiotherapy is therapy of choice after surgery in primary spinal cord tumors in adults, although local recurrences remain the major problem.

Nerve transfer in brachial plexus traction injuries.

Brachial plexus palsy due to traction injury, especially spinal nerve-root avulsion, represents a severe handicap for the patient. Despite recent progress in diagnosis and microsurgical repair, the prognosis in such cases remains unfavorable. Nerve transfer is the only possibility for repair in cases of spinal nerve-root avulsion. This technique was analyzed in 37 patients with 64 reinnervation procedures of the musculocutaneous and/or axillary nerve using upper intercostal, spinal accessory, and regional nerves as donors. The most favorable results, with an 83.8% overall rate of useful functional recovery, were obtained in patients with upper brachial plexus palsy in which regional donor nerves, such as the medial pectoral, thoracodorsal, long thoracic, and subscapular nerves, had been used. The overall rates of recovery for the spinal accessory and upper intercostal nerves were 64.3% and 55.5%, respectively, which are significantly lower. The authors evaluate the results of nerve transfer and analyze different donor nerves as factors influencing the prognosis of surgical repair.

Reinnervation of avulsed brachial plexus using the spinal accessory nerve.

The use of the accessory nerve as a donor is one of the possibilities for the reinnervation of the brachial plexus in cases of paralysis due to root avulsion. In this paper, an analysis of the reinnervation of the musculocutaneous or axillary nerve using the spinal accessory nerve is made on 13 cases, 8 of total and 5 of upper partial avulsion. In all cases, Allieu's technique was used, but in seven cases reinnervation was supplemented by upper intercostal nerves when there was total avulsion and/or by the medial pectoral nerve when there was partial avulsion. The methods are discussed and compared with the intercostobrachial anastomosis.

Regional donor nerves in the reinnervation of brachial plexus palsy due to upper spinal roots avulsion.

The prognosis for surgical treatment in cases of upper brachial plexus palsy due to spinal roots avulsion is somewhat better than in cases of total palsy. The main reasons are better possibilities for surgical reinnervation using regional donors i.e. the medial pectoral and the thoracodorsal nerves, and a shorter time span for nerve regeneration. Regional donor nerves, alone or in combination with upper intercostals and/or the spinal accessory nerve, were used in 13 cases for the reinnervation of the musculocutaneous and/or the axillary nerves. The value of the regional donors is analysed and compared with that of the spinal accessory and intercostal nerves. The value is documented throughout the results of surgical treatment with a follow-up period of at least 18 months after surgery.

Donor nerves in the reinnervation of brachial plexus.

In cases of brachial plexus spinal root avulsions the only possibility for surgical treatment is reinnervation of plexus by cross-anastomosis with intact nerves. As donor nerves for reinnervation the adjoining (upper intercostal and spinal accessory) or regional intact nerves can be used. In this paper an analysis of these nerves on histological preparation from 15 autopsies and analysis of surgical results from 13 operated patients with total or partial spinal root avulsions are presented. The advantages of pure motor, especially regional, nerves and possibility of combined use of all donor nerves are emphasized.

Surgical treatment of craniopharyngiomas in adults.

Thirty-eight patients over the age of 21 were found to be suffering from craniopharyngiomas. According to the clinical symptoms, 8 tumours were of the juvenile type and 24 of the adult type. Thirty-four patients underwent direct surgery of the tumour. Ten were operated on unilaterally and then contra-laterally, as we were unable to remove the tumour in one go. Fifteen of the 24 adult type tumours were operated on radically, and five subtotally. Four patients were given an A-V shunt implant. The best results were obtained with subtotal excisions of adult suprasellar craniopharyngiomas.