Clinical Outcome of Supratentorial Astrocytoma WHO Grade II

Summary  Objective. There are divergent opinions about the prognostic value of the extent of surgery and of different histological subtypes in supratentorial astrocytomas WHO grade II.  Methods. We reviewed 75 consecutive patients (36 females, 39 males) with supratentorial astrocytomas WHO grade II (59 primary and 16 recurrent tumours) operated on between 1991 and 1995.  Results. Gross total resection could be achieved in 40 astrocytomas, subtotal resection (including biopsy) was performed in 35 cases. Histological assessment confirmed 60 fibrillary, 6 gemistocytic, 9 oligo-astrocytic and no protoplasmic astrocytomas. There were no postoperative deaths. Early outcome 6 to 12 weeks after surgery according to the Glasgow Outcome Scale was good in 46 patients, 24 patients had moderate, and 5 had severe neurological deficits. Survival rates 1, 2, 3, and 4 years following surgery were 100%, 96%, 96%, 96% for patients who underwent gross total tumour resection and 86%, 77%, 77%, 64% for patients with subtotal tumour resection. The cumulative recurrence or progression rates after 4 years were 26% after gross total resection and 80% after subtotal resection, and this result is statistically significant. Recurrences after gross total resection or progressions after subtotal resection occurred more often in gemistocytic astrocytomas (40% and 100%, respectively) than in other subtypes. Dedifferentiation to a more malignant tumour seems to be more prominent in the gemistocytic subtype.  Conclusion. Gross total resection should be the leading therapeutic option for patients with astrocytomas WHO grade II. For the gemistocytic subtype further studies will have to prove whether additional radiotherapy is of any benefit.     

Surgical management of spinal cord haemangioblastoma

Summary Background. The surgical management of spinal cord haemangioblastomas is distinct from that of other benign spinal cord tumours and optimal surgical strategy is still being determined because of the rarity of the condition. The aim of this study is to investigate factors that affect the outcome of surgical management. Patients and methods. We retrospectively analysed 24 operations for symptomatic spinal cord haemangioblastomas in 20 patients. Clinical features and surgical results were investigated by medical record review, telephone interviews, angiographic images, and magnetic resonance images (MRI). The mean follow-up period was 5.6 years (range 6 months to 13.6 years). Results. Patients with cystic components showed pre-operative motor weakness and sensory change more commonly than those without cystic components. Post-operative function scale had a positive correlation with pre-operative function (R ² = 0.727; p < 0.001) and no correlation with the extent of the surgery. All subtotally removed tumours recurred, whereas totally removed tumours recurred in only 3 patients. Conclusion. The cystic component of spinal cord haemangioblastomas is responsible for symptom generation and is helpful for dissecting tumours. Post-operative functional status is determined by pre-operative functional status. Total removal is feasible by using the correct surgical technique and is recommended to prevent recurrence. Correspondence: Do Heum Yoon, M.D., Ph.D., Department of Neurosurgery, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.     

An epidemiological survey of primary tumours of the brain and spinal cord in South East Wales

This survey is founded on 526 patients who presented with a primary tumour of the brain, spinal cord or their coverings over a seven year period. The patients resided in one of the three counties comprising South East Wales, which has a population of about 1.3 million. Each tumour type is classified according to age, sex and area of residence of the patient. Age and sex adjusted annual incidence rates were calculated for each tumour type. All types of glioma have a higher incidence in males, while meningiomas are twice as common in females. Gliomas are the most commonly occurring tumour with an average annual incidence of 3.6 per 100,000 and a peak incidence for malignant astrocytomas of 7.6 in the 55 to 64 year age group. The low grade astrocytoma is the most common tumour of childhood. Oligodendrogliomas occur most commonly in adults between the ages of 35 and 44 years. In this survey there is an unexplained relatively high incidence of oligodendrogliomas. The majority of primary tumours arose in the brain, but there were 24 tumours of the spinal cord, nerve sheath and meninges. Comment is made on the presence and possible aetiological significance of chemical industries within South East Wales.     

A less invasive surgical concept for the resection of spinal meningiomas

Summary   Background. The surgical strategy for spinal meningiomas usually consists of laminectomy, initial tumour debulking, identification of the interface between tumour and spinal cord, resection of the dura including the matrix of the tumour, and duroplasty. The objective of this study was to investigate whether a less invasive surgical strategy consisting of hemilaminectomy or laminectomy, tumour removal and coagulation of the tumour matrix allows comparable surgical and cinical results to be obtained, especially without an increase of the recurrence rate as reported in the literature. Patients and methods. Between 1990 and 2005, 61 patients (11 men, 50 women) underwent surgery for spinal meningioma. All patients were treated microsurgically by a posterior approach. In 56 of the 61 patients, the above outlined – less invasive – surgical technique with tumour removal and coagulation of the tumour matrix was performed. In 5 patients, dura resection and duroplasty was additionally performed. Electrophysiological monitoring was routinely used since 1996. Recurrence was defined as new onset or worsening of symptoms and radiological confirmation of tumour growth. The pre-and post-operative clinical status was measured by the Frankel grading system. Results. Pre-operatively, 40 patients were in Frankel grade D, 13 patients in grade C, 6 patients in grade E and 1 patient each in grade A and B. Following surgery no patient presented a permanent worsening of clinical symptoms. All patients who initially presented with a Frankel grades A–C (n = 15) recovered to a better grade at the time of follow-up. Patients who presented with Frankel grade D remained in stable condition (n = 27) or recovered to a better neurological status (n = 13). Two patients experienced a temporary worsening of their symptoms, but subsequently improved to a better state than pre-operatively. Two (3.3%) complications (pseudomeningocele, wound infection) requiring surgery, were encountered. The pseudomeningocele developed in a patient who underwent durotomy. During the follow-up period of 2 months to 10 years (mean 31.3 months), 3 patients (5%) required surgery for symptomatic recurrence: 1 patient had 2 recurrences that occured 4 and 7 years after first tumour removal and matrix coagulation, 1 recurrence occurred 1 year after tumour removal that was accompanied by matrix coagulation in a patient with a diffuse anterocranial tumour extension and 1 occured 3 years after tumour removal and durotomy. Two patients showed a small recurrence on MRI during follow-up after 2 and 5 years, respectively, without any symptoms requiring surgery. Conclusions. The high rate of favourable clinical results combined with the low rate of recurrences supports our less invasive surgical concept, which does not aim for resection of the dural matrix of the spinal meningioma. Correspondence: Azize Bostr?m, M.D., Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.     

Changes in lactate dehydrogenase isoenzyme patterns in patients with tumours of the central nervous system

Summary The total activities of lactate dehydrogenase (LD) and the LD isoenzyme distribution were determined on homogenates from 61 benign and malignant intracranial tumours, and in serum and cerebrospinal fluid from 45 and 28 of the tumour patients respectively.The LD activity and the LD isoenzyme distribution in serum were not changed in patients with intracranial tumours. The LD activity in the cerebrospinal fluid was raised in about 50% of the tumour patients, but without any significant differences between patients with benign and malignant tumours.Except for very low activities in acoustic schwannomas and in pituitary adenomas, the tumour tissue did not differ significantly from normal brain in total LD activity. The LD isoenzyme distribution showed a pronounced cathodal shift in the grade 3–4 astrocytomas and the metastatic carcinomas, but an anodal shift in the grade 1–2 astrocytomas and the oligodendrogliomas.The meningiomas and the acoustic schwannomas showed a midzone isoenzyme pattern with a dominant LD₃ fraction.Knowledge of the LD isoenzyme distribution can thus sometimes be a complement to the histological examination in the classification of brain tumours.     

Prognostic Value of Vascular Endothelial Growth Factor and its Receptors Flt-1 and Flk-1 in Astrocytic Tumours

Summary  Background. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) is an important regulator of angiogenesis and vascular permeability.  Method. We examined immunohistochemically expressions of VEGF and its corresponding receptors Flt-1 and Flk-1 in a series of 50 astrocytic tumours, and correlated their expressions with the degree of angiogenesis, brain edema and prognosis.  Findings. There were significant relationships between VEGF, Flk-1 expressions and glioma malignancy grading, intratumoural vascularity and peritumoural brain edema, respectively. Patients with VEGF positive low grade astrocytoma and glioblastoma multiforme had a significantly shorter mean overall survival time than those with negative tumours (P=0.0010 and 0.0180, respectively). Flk-1 is also a significant prognostic factor within each tumour grade, which has a negative impact on overall survival. Additionally, overexpression of VEGF and Flk-1 were significantly associated with earlier recurrence in patients with low grade astrocytomas (P=0.0018 and 0.0240, respectively).  Interpretation. It is possible to subcategorize each grade of astrocytic tumours based on their VEGF and Flk-1 staining pattern, which may be crucial in predicting the biological behavior of tumours and thus provide useful information with regard to adequate treatment.     

Management and outcome of paediatric testicular tumours – A 20 year experience

Objective: To report a 20-year experience highlighting management and outcome(s) of paediatric testicular tumours.Patients and Methods: All males (< 19 years) with an index diagnosis of testicular tumours during the era(s) 1998–2018 in North West England were identified. Data were collected regarding age at diagnosis, disease stage, surgical operations, tumour biology and outcome(s).Results: A total of 34 male patients were identified. Median age at primary diagnosis was 94 months (range: 0–229 months). Eighteen tumours were benign and 16 malignant. Twenty cases (59%) were recorded in pre pubertal children and 14 (41%) in post pubertal males . In the pre pubertal group (0–11 years) - 15 cases of germ cell tumours (unrelated to germ cell neoplasia in situ – non-GCNIS derived) were recorded, including six yolk sac lesions, eight teratomas and one mixed teratoma/yolk sac tumour (pre-pubertal type). Four males with sex cord-stromal tumours included one juvenile granulosa cell tumour, two Sertoli cell tumours and one Leydig cell tumour. One miscellaneous type tumour notably a papillary cyst adenoma was also identified. In the post pubertal male cohort (>12 years) (n = 14) – four non-GCNIS derived tumours were identified (3 epidermoid cysts and one teratoma), eight cases of germ cell tumour derived from germ cell neoplasia in situ (GCNIS derived) included one teratoma, six with mixed germ cell tumours and one embryonal carcinoma. Two males had sex cord stromal tumours: (Leydig cell and granulosa cell biology). Twenty-eight patients underwent high radical inguinal orchidectomy(s) with one male also requiring retroperitoneal surgery to clear distant locoregional disease and a further single case thoracotomy and metastasectomy. Six patients had lesions suitable for ‘testicular sparing’ surgery. Six patients had metastatic disease at presentation (18%). Overall study survival was 97%. A single fatality occurred in an adolescent male with a mixed GCT harbouring liver, lung and para-aortic disease who died 48 months after initiating treatment.Conclusion: We highlight one of the largest study series of paediatric testicular tumours in the UK and Europe. Non-GCNIS derived tumours accounted for the most common tumour biology (56%). Survival for paediatric testicular tumours is reassuringly generally excellent. Delayed presentation however with a malignant testicular tumour may be associated with poor outcome(s).     

Usefulness of Motor Functional MRI Correlated to Cortical Mapping in Rolandic Low-Grade Astrocytomas

Summary  The indications for surgery of slow growing tumours like low grade astrocytomas in eloquent areas are difficult. The timing and the benefit/risk ratio of the surgery must be evaluated, taking into account the potential post operative deficit. The purpose of this study was: a) to validate the data obtained with functional MRI (FMRI) by direct cortical stimulation in patients who are candidate for surgery; b) to demonstrate the usefulness of FMRI coupled with cortical brain mapping and 3D reconstructions of the surfaces of the brain in low grade astrocytoma. FMRI of the hand-motor cortex was performed in 8 patients with low grade astrocytomas. They subsenquently underwent direct cortical mapping to correlate the results of FMRI and resective surgery sparing the functional area. In the 8 cases, the results of direct cortical mapping in the precentral region matched accurately those obtained from FMRI. When surgical resection of low grade astrocytoma in the motor areas is considered, FMRI used with intra-operative cortical mapping can help the surgeon to spare functional areas during tumour removal.     

Spinal intradural tumours: Part II--Intramedullary

The results of surgical management in 54 patients with intramedullary spinal cord tumours are presented. Cervical tumours were most frequent (25/54) followed by thoracic (16/54) and then lumbar (14/54). Ependymomas and astrocytomas were the most common tumour types. Total tumour removal was possible in just over half of the cases. Surgical complications included: two deaths, six patients with CSF leaks and one with wound infection. Postoperatively three patients had worsening of their motor deficit (unable to walk) and three patients had worsening of urinary sphincter function. Conversely, three patients who were unable to walk preoperatively were able to walk postoperatively, whilst four patients with sphincter disturbance showed improvement. Total tumour removal was not associated with increased risk of postoperative neurological deficit. Long-term follow up (2-18 years) was possible in 40 patients; 90% were still independently mobile. Our results compare favourably with other European studies and data from the North American units which have pioneered this surgery.     

Surgical resection of gliomas WHO grade II and III located in the opercular region

Summary Background. Surgery in the opercular region especially in the dominant hemisphere impose a major challenge for the neurosurgeon due to the close vicinity to functional important motor and speech areas. The purpose of the present study is to analyse on a homogenous patient group pre- and postoperative functional deficits with regard to different speech qualities (e.g. aphasia, apraxia), and to correlate these data with MR and intraoperative monitoring results. Method. Fourteen patients with suspected low grade astrocytomas in the opercular region consecutively treated by surgery were eligible for this study (histology revealed 3 WHO grade III tumours). Degree and duration of postoperative deficits were retrospectively evaluated according to tumour location and boundaries on MR, intraoperative neuromonitoring results and extent of tumour resection. Findings. Postoperatively, 8 patients showed speech or language disturbances, in 4 patients combined with motor deficits mainly of the contralateral upper extremity. Fifty percent of the neuropsychologically tested patients exhibited speech apraxia while the other 50% had a true aphasic syndrome. Recovery of the latter deficits was in general faster and more complete. The severity and duration of postoperative deficits was in good correlation with the distance of the resection margin to the next positive stimulation point(s), and a distance of more than 0.5cm proved to avoid major impairments. The distribution of functional important stimulation points in relation to the tumour extension was not predictable, and – unexpectedly – up to 50% of these sites were found overlaying the tumour. Interpretation. Surgery for WHO grade II and III gliomas in the opercular region can result in speech apraxia or an aphasic syndrome with or without concomitant motor deficits. Intraoperative cortical electrical stimulation is essential in resecting tumours in the opercular region to avoid permanent morbidity.     

The impact of tumour volume and surgery on the outcome of adults with supratentorial WHO grade II astrocytomas and oligoastrocytomas

Summary Background. The study was performed to elucidate the impact of tumour volume and surgical resection on the long-term outcome of patients with supratentorial, diffuse, World Health Organization (WHO) grade II astrocytomas and oligo-astrocytomas.Method. After analysing 79 adult patients consecutively diagnosed between 1991 and 2000, we selected a group of 42 patients treated by surgery without adjuvant therapy. The tumour volume was defined as the whole region of T2-hyperintensity and measured interactively on pre- and postoperative and follow-up Magnetic Resonance Imaging (MRI) using a dedicated imaging software. Volumetric, clinical, and histological data were analysed for correlation with tumour progression (TP), malignant transformation (MT), drop in functional status (DKPS) and overall survival (OS).Findings. Pre- and postoperative tumour volumes, and the involvement of more than one lobe were strongly associated with worse outcome. Preoperative tumour volume was the strongest predictor of OS (p<0.01) and the only predictor of MT (p<0.05). The absolute and relative volumes of tumour removed by surgery were not significantly associated with outcome.Conclusions. Initial tumour volume, measured as the volume of T2-hyperintensity on MRI, and tumour extension are the strongest predictors of outcome in patients with supratentorial diffuse astrocytic WHO Grade II tumours. The potential benefit of aggressive tumour resection needs to be investigated in a prospective controlled trial.     

Brain tumours in children

Summary A considerable number of high risk brain tumours require an interdisciplinary approach with surgery, radiation and chemotherapy rather than one single therapeutic regimen. Children with a medulloblastoma must be subdivided into four different risk groups depending on the size of the tumour, on the age of the child and on cerebral spinal fluid cytology findings. The treatment protocol for ependymomas depends on the location of the tumour and on histological grading. Pineal region tumours can be successfully removed; further therapy depends on the type of the tumour. Children with hemispheric high grade astrocytomas gain substantially from local radiation therapy. The GPO (Gesellschaft für Pädiatrische Onkologie) has most recently taken the initiative to found a pediatric neuro-oncology working group in order to establish and to evaluate different treatment modalities.     

The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours

Summary The monoclonal antibody Ki-67 has been tested as a marker of proliferating cells in 52 stereotactic brain tumour biopsies. The antibody reacts with a nuclear protein expressed in G₁,S, G₂n and Mphases of the cell cycle. Using the immunoperoxidase technique on squash preparations the percentage of Ki-67 positive cells was determined as a fraction of the total number of tumour cells present. This Ki-67 index was in close correlation with the histological grade. Highest values were found in a pineal germinoma (46.3%) and in 3 primary cerebral non-Hodgkin lymphomas (mean 39.5%). Among the gliomas, the highest fraction of proliferating cells was seen in 2 anaplastic paediatric brain stem gliomas (mean 17.4%) and in an anaplastic ependymoma (12.5%). Anaplastic astrocytomas and glioblastomas varied considerably with mean values of 9.5% and 8%, respectively. To some extent this variability may reflect tumour heterogeneity which is more likely to manifest in small stereotactic samples than in large tissue specimens obtained during open surgery. Pilocytic astrocytomas, mixed gliomas and fibrillary astrocytomas had moderate to low percentages.Ki-67 staining of squash preparations can easily be performed on a rountine basis and is, in our experience, superior to frozen sections. This method allows the determination of the growth fraction of an individual tumour and could become an important additional criterion for the decision among alternative and potentially harmful therapeutic regimens.     

Minimally invasive transmuscular approach for the treatment of benign intradural extramedullary spinal cord tumours: Technical note and results

BackgroundMinimally invasive surgery has expanded over the past two decades and was initially used for the treatment of lumbar disc herniation. Later, this approach was used to treat other spine pathologies, as well as to perform spinal fusion and extended spinal decompression. In this study, we report our experience regarding the use of a minimal surgical approach in the treatment of intradural extramedullary spinal cord tumours.MethodsBetween January 2008 and July 2013, 18 patients with an intradural extramedullary tumour were included in the study (13 thoracic, 4 lumbar and one cervical tumours). The mean age was 59 years. We operated on 11 meningiomas, 6 neurinomas and one ependymoma. All patients underwent minimally invasive surgery using a tubular retractor system to perform a hemilaminectomy in order to access the spinal canal. Fifteen patients had a neurological deficit and 7 suffered from radicular pain prior to surgery.ResultsGross completed resection was performed in all patients. Mean time of surgery was 95 min. Blood loss was less than 200cc. Fifteen patients out of 18 were able to get up the day after surgery. Mean hospital stay was 6 days. There were no complications.ConclusionA minimal surgical approach using a tubular retractor permits an effective resection of intradural extramedullary tumours. This procedure may be a useful tool to decrease the risk of secondary spine instability and postoperative kyphosis, and could also be used for spinal junctions and in fragile patients.     

Intramedullary spinal cord tumors

Opinion statement The three most common types of intramedullary spinal cord tumors are low-grade astrocytomas, ependymomas, and high-grade astrocytomas. Surgical extirpation is the necessary and sufficient primary treatment for most intramedullary spinal cord tumors. Radiation therapy may also have a role in the management of persistent, recurrent, or progressive low-grade astrocytomas and ependymomas. The current treatment of spinal cord high-grade astrocytomas, which includes surgical debulking, radiation therapy, and possibly chemotherapy, is clearly inadequate. Chemotherapy may have a potential role for certain progressive spinal cord tumors, but the role is undefined at present. Recent reports have described the use of stereotactic radiosurgery for extramedullary spinal tumors, and stereotactic radiosurgery may someday be useful in the management of intramedullary spinal cord tumors. Rehabilitation programs are an important component of the multidisciplinary care of patients with spinal cord tumors. Finally, more work, especially the inclusion of adults and children with intramedullary spinal cord tumors into prospective clinical trials, is needed to improve the therapy of intramedullary spinal cord tumors and rehabilitation after diagnosis of a spinal cord tumor.     

Supratentorial astrocytic tumours of childhood: A clinicopathologic study of 41 cases

Summary Forty-one patients with ages from 0 to 16 years harbouring Supratentorial astrocytic tumours were treated between 1964 and 1986. Twenty-four of them were located in the cerebral hemisphere or in the ventricle, and 17 were in the basal ganglia, thalamus, and/ or optico-hypothalamic region. There were nine glioblastomas multiforme, four anaplastic astrocytomas, 11 fibrillary astrocytomas, 12 pilocytic astrocytomas, two pleomorphic xanthoastrocytomas, two subependymal giant cell astrocytomas and one primitive astrocytic tumour. Low grade tumours tended to occur in young subjects near the midline, and high grade ones in older patients in the hemisphere. Initial treatment in most the patients was a resection or biopsy followed by radiation therapy. Eleven patients were retreated for their recurrent tumours with combinations of surgical removal of the tumour, radiotherapy, and/or chemotherapy. After a follow-up of 3 months to 17 years, 51% of the patients survived with a median survival of 7 years. Outcome of the patients with Supratentorial astrocytomas correlated mostly with the histological grade of malignancy of the tumour, and to a lesser degree with the tumour location. The biological behaviour and treatment of supratentorial astrocytomas in childhood are discussed.     

Changes in the stage and surgical management of renal tumours during 1995-2005: an analysis of the Dutch national histopathology registry

OBJECTIVE

To evaluate changes in the pathological characteristics, stage of primary renal tumours and their surgical management in the Netherlands during the period 1995–2005.

METHODS

Extracts from the records of all patients who had surgery for primary renal tumours in the Netherlands during the period 1995–2005 were reviewed. Data were collected from PALGA, the nationwide network and archive of histocytopathology. The 2002 Tumour‐Node‐Metastasis and the three‐tier Fuhrman grade were used for staging and grading.

RESULTS

In all there were 12 471 operations for primary renal masses during the study period. The incidence of surgically removed renal cancers increased from 6.2 in 1995 to 7.5 cases per 100 000 inhabitants (P = 0.005) in 2005. The mean (sd , median) age of the patients was 63.3 (11.9, 65.0) years, with a male‐to‐female ratio of 3:2. The mean (sd ) tumour size of malignant tumours decreased from 7.3 (3.6) to 6.9 (3.7) cm (P = 0.301). The percentage of benign removed tumours remained relatively stable (P = 0.056), with a mean of 5.4% of all resected tumours. There was an increase of grade 1 tumours; the incidence of T1 tumours increased from 36.6% to 44.2%, and advanced tumours decreased from 46.4% to 33.7%, respectively. The percentage of nephron‐sparing surgery increased from 3.5% in 1995 to 10.1% (P = 0.003) in 2005, mainly in the T1a tumours.

CONCLUSIONS

During the last decade there was an increase in the incidence of surgically treated renal tumours in the Netherlands. Tumours with favourable histopathological characteristics, low stage and grade, accounted for most of this increase. The percentage of surgically removed benign tumours remained stable. The use of nephron‐sparing surgery increased during the last decade, especially in T1a tumours.     

Cell proliferation in serial biopsies through human malignant brain tumours: measurement using Ki67 antibody labelling

Cell proliferation was assessed in brain tumours using the monoclonal antibody Ki67 which recognizes a nuclear antigen expressed by proliferating cells. Using a novel stereotactic biopsy procedure, serial 1 cm biopsies were taken along a trajectory through six malignant brain tumours. Specimens were also obtained from 10 other brain tumours during conventional surgery. The percentage of Ki67 positive cells was determined as a fraction of the total number of tumour cells present. The Ki67 index for anaplastic astrocytomas and glioblastomas was significantly higher (Ki67 index range 11-18%) than that for benign or low grade tumours. Significant variation in proliferation was measured along the biopsy track through individual tumours (e.g. 0-12.3%) which correlated well with histological appearance. The Ki67 indices of normal brain were very low. In general the Ki67 indices increased with increasing histological grade and also appear to be a useful indicator of the active tumour volume and margin. This method provides spatial information about tumour proliferation which may be used to decide between different treatments and relate to prognosis.     

111Indium (DTPA-octreotide) scintigraphy in patients with cerebral gliomas

Summary Somatostatin receptors (SR) have been identified in vitro in normal brain tissue, in neuro-endocrine tumours and in cerebral gliomas WHO grade 1 or 2 by autoradiography or using somatostatin-gold conjugates. In vivo, SR detection has become possible by scintigraphy applying the somatostatin analogue octreotide, radio-labelled with¹¹¹Indium. It was supposed that expression of SR in cerebral gliomas corresponds to low grade tumour malignancy and that, in vivo, somatostatin receptor scintigraphy (SRS) could refine and improve the WHO grading system for cerebral gliomas.Nineteen patients with cerebral gliomas (grade 2: n=8, grade 3: n=3, grade4: n=8) were examined with¹¹¹In (DTPA-octreotide) to evaluate, whether SRS could improve the pre-operative estimation of tumour biology and the postoperative management. The results of SRS were related with the histological findings and with the in vitro demonstration of somatostatin-binding sites on cultured tumour cells incubated with a somatostatin-gold conjugate.In vivo, none of the patients with glioma grade 2 showed enhanced tracer uptake in the SRS, whereas in vitro SR were detected in cultured tumour tissue in 5 out of 5 cases. Every patient with glioma grade 3 or 4 demonstrated a high focal uptake of¹¹¹In (DTPA-octreotide), as shown by SRS. Three patients with glioma grade 4, additionally examined with 99mTc-DTPA, showed an increased tracer uptake within the tumour area when compared with results of SRS. In vitro, SR were detected on tumour cell surface in 5 out of 6 tissue samples from patients with gliomas grade 3 or 4. One patient harbouring a cerebral abscess presented with a high focal tracer uptake in the SRS but with absence of somatostatinbinding sites in vitro.We concluded, that in glioma patients enhanced tracer uptake in receptor scintigraphy with¹¹¹In (DTPA-octreotide) does not depend on the presence of SR in tumour tissue but on the dysfunction of the blood-brain barrier. Thus, SRS does not improve the preoperative glioma grading or postoperative management in patients with cerebral tumours of glial origin.The article is dedicated to Prof. H. Leonhardt on the occasion of his 75th birthday.     

Prognosis factors of survival time in patients with glioblastoma multiforme: a multivariate analysis of 340 patients

Summary Background. The prognosis of glioblastoma multiforme remains poor despite recent therapeutic advances. Several clinical and therapeutic factors as well as tumour characteristics have been reported as significant to survival. A more efficient determination of the prognostic factors is required to optimize individual therapeutic management. The aim of our study was to evaluate by univariate then multivariate analysis the factors that influence prognosis and particularly survival. Methods. Data of 340 patients with newly-diagnosed GBM were retrospectively analyzed. Univariate analysis of prognosis factors of survival time was performed. Factors that seemed determinant were evaluated by Kaplan–Meier survival curves. Finally, the significant factors found in univariate analysis were tested in multivariate analysis using the COX regression method. Findings. Using multivariate analysis, the following factors were found to influence survival: radiotherapy was the predominant factor followed by radical surgery, tumour location, age and chemotherapy. Patients treated with temozolomide had a markedly better survival rate than patients treated with other chemotherapies (Log-rank test P < 0.005). The values of GBM type (de novo or secondary), as well as repeated surgery and partial surgery (vs. simple biopsy) were suggested by univariate analysis but not confirmed by the COX regression method. After radical surgery, progression-free survival was correlated to overall survival (r = 0.87, P < 10e-5). Conclusions. The influence of radiotherapy on survival was greater than the influence of age, an argument supporting the proposition of radiotherapy for patients until at least age 70. In the case of recurrence, the correlation between overall survival and progression-free survival is an important factor when considering the therapeutic options. Initial radical surgery and repeated procedures dramatically influence survival. The benefit of partial surgery remains difficult to evaluate. Partial surgery could be used to decrease intracranial pressure and to minimize residual tumours in order to enable treatment by chemotherapy and radiotherapy. The value of temozolomide treatment was confirmed.