Present and potential future adjuvant issues in high-grade astrocytic glioma treatment.

Despite major advances in the management of malignant gliomas of which glioblastomas represent the ultimate grade of malignancy, they remain characterized by dismal prognoses. Glioblastoma patients have a median survival expectancy of only 14 months on the current standard treatment of surgical resection to the extent feasible, followed by adjuvant radiotherapy plus temozolomide, given concomitantly with and after radiotherapy. Malignant gliomas are associated with such dismal prognoses because glioma cells can actively migrate through the narrow extra-cellular spaces in the brain, often travelling relatively long distances, making them elusive targets for effective surgical management. Clinical and experimental data have demonstrated that invasive malignant glioma cells show a decrease in their proliferation rates and a relative resistance to apoptosis (type I programmed cell death) as compared to the highly cellular centre of the tumor, and this may contribute to their resistance to conventional pro-apoptotic chemotherapy and radiotherapy. Resistance to apoptosis results from changes at the genomic, transcriptional and post-transcriptional level of proteins, protein kinases and their transcriptional factor effectors. The PTEN/ PI3K/Akt/mTOR/NF-kappaB and the Ras/Raf/MEK/ERK signaling cascades play critical roles in the regulation of gene expression and prevention of apoptosis. Components of these pathways are mutated or aberrantly expressed in human cancer, notably glioblastomas. Monoclonal antibodies and low molecular-weight kinase inhibitors of these pathways are the most common classes of agents in targeted cancer treatment. However, most clinical trials of these agents as monotherapies have failed to demonstrate survival benefit. Despite resistance to apoptosis being closely linked to tumorigenesis, tumor cells can still be induced to die by non-apoptotic mechanisms such as necrosis, senescence, autophagy (type II programmed cell death) and mitotic catastrophe. Temozolomide brings significant therapeutic benefits in glioblastoma treatment. Part of temozolomide cytotoxic activity is exerted through pro-autophagic processes and also through the induction of late apoptosis. Autophagy, type II programmed cell death, represents an alternative mechanism to overcome, at least partly, the dramatic resistance of many cancers to pro-apoptotic-related therapies. Another way to potentially overcome apoptosis resistance is to decrease the migration of malignant glioma cells in the brain, which then should restore a level of sensitivity to pro-apoptotic drugs. Recent series of studies have supported the concept that malignant gliomas might be seen as an orchestration of cross-talks between cancer cells, microenvironment, vasculature and cancer stem cells. The present chapter focuses on (i) the major signaling pathways making glioblastomas resistant to apoptosis, (ii) the signaling pathways distinctly activated by pro-autophagic drugs as compared to pro-apoptotic ones, (iii) autophagic cell death as an alternative to combat malignant gliomas, (iv) the major scientific data already obtained by researchers to prove that temozolomide is actually a pro-autophagic and pro-apoptotic drug, (v) the molecular and cellular therapies and local drug delivery which could be used to complement conventional treatments, and a review of some of the currently ongoing clinical trials, (vi) the fact that reducing the levels of malignant glioma cell motility can restore pro-apoptotic drug sensitivity, (vii) the observation that inhibiting the sodium pump activity reduces both glioma cell proliferation and migration, (viii) the brain tumor stem cells as a target to complement conventional treatment.

Endovascular treatment of intracranial aneurysms with a branch arising from the sac.

BACKGROUND AND PURPOSE: The endovascular treatment (EVT) of intracranial aneurysms is no more limited by the presence of a branch at the neck or by the neck width. Saccular aneurysms with a branch arising from the sac, however, are mostly candidates for surgery rather than embolization. We prospectively evaluated the feasibility and safety of the EVT in such cases. METHODS: Between May and November 2004, 9 consecutive patients with a saccular aneurysm that presents a branch arising from the sac were treated by embolization. There were 7 women and 2 men (mean age, 58 years). Six patients presented with a subarachnoid hemorrhage (SAH), and 3 were asymptomatic. All patients were treated by selective coiling with (n = 6) or without (n = 3) the remodeling technique. Clinical outcome was assessed with a modified Glasgow Outcome Scale at 3 months. RESULTS: EVT was successfully performed in all patients and resulted in 7 excellent outcomes and 2 deaths related to SAH complications. The arterial branch could be preserved in 7 cases and intentionally occluded in 2. Neither embolic nor ischemic complication occurred in the vascular territory of the involved branch. Angiographic results showed 5 neck remnants, 2 incomplete occlusions, and 2 complete occlusions. No rebleeding occurred. CONCLUSION: Our study, though limited by its small patient population, suggests that saccular intracranial aneurysms with a branch arising from the sac may be treated by endovascular approach with excellent clinical results; however, larger series with long-term follow-up are mandatory to confirm these preliminary results mostly in terms of anatomic stability.

Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.

The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.

Characterization of astroglial versus oligodendroglial phenotypes in glioblastomas by means of quantitative morphonuclear variables generated by computer-assisted microscopy.

The current WHO classification places glioblastomas in the astrocytoma category. However, whether or not glioblastomas also show oligodendroglial differentiation remains a matter of controversy. This study investigates, at the morphonuclear level, the hypothesis that some glioblastomas (GBMs) may also represent the ultimate level of malignancy in the oligodendroglial lineage. Using a series of 164 GBMs, we sought to ascertain whether any of these GBMs exhibited phenotypical characteristics that were more closely related to oligodendroglial lineages than astrocytic lineages. Phenotypical features were quantitatively determined by means of the computer-assisted microscope analysis of Feulgen-stained nuclei, a process that made it possible to quantitatively describe the patterns of the cell nuclei (and, more specifically, of their chromatin) through 16 variables, and the distribution of the nuclear DNA content (DNA ploidy) through 8 variables. The phenotypical characteristics typical of astrocytic and oligodendroglial tumors were analyzed by means of Discriminant Analysis, a statistical multivariate analysis, performed on a series of 65 astrocytic and oligodendroglial tumors. This series consisted of 14 WHO grade II and 19 grade III astrocytomas and 24 WHO grade II and 8 grade III oligodendrogliomas. This multivariate analysis enabled an accurate model to be produced that distinguished between astrocytomas and oligodendrogliomas on the basis of 5 cytometry-generated variables. This model was used to characterize the phenotype of each of the 164 glioblastomas. The results show that of these 164 glioblastomas, 6 (about 3.5%) displayed phenotypes that were very similar to oligodendrogliomas, and 141 displayed phenotypes that were very similar to astrocytomas. The phenotypes of the 17 remaining GBMs were too ambiguous to be categorized as having a pure astrocytic or oligodendroglial lineage.

The combined determination of proliferative activity and cell density in the prognosis of adult patients with supratentorial high-grade astrocytic tumors.

Tumor growth represents the ratio between cell gain (number of mitoses per unit of time, i.e., proliferative activity) and cell loss (number of cell deaths during the same unit of time). While in adults, proliferative activity parallels the level of malignancy in astrocytic tumors and therefore represents a useful diagnostic marker, cell loss has never been concomitantly assessed in tumors of this type. We hypothesize that cell density assessable on histologic slides represents the ratio between cell gain and cell loss. This hypothesis concerns only the diffuse type of astrocytic tumors. Proliferative activity (assessed by MIB1 antigen immunostain) and cell density were thus quantitatively assessed by means of a cell image processor in a series of 54 supratentorial astrocytic tumors of adult patients, which included 15 astrocytomas (ASTs), 18 anaplastic astrocytomas (ANAs), and 21 glioblastomas (GBMs). The results show that proliferative activity and cell density were highly correlated (P = .003) and that both correlated with histopathologic grade. The patients with a high-grade astrocytic tumor (i.e., ANA or GBM) that exhibited a low level of proliferative activity but high cell density survived for significantly shorter periods than did patients with a tumor that exhibited low proliferative activity and low cell density (P = .002). The patients with a high-grade astrocytic tumor that exhibited high proliferative activity and high cell density survived for significantly less time than did the patients with a tumor that exhibited high proliferative activity but low cell density (P < .05). A marked difference in survival periods was observed between the patients with a high-grade astrocytic tumor that exhibited a low level of proliferative activity and low cell density and the patients with a tumor that exhibited a high level of proliferative activity and high cell density (P < .001). The concomitant determination of proliferative activity and cell density seems likely to enable determination of the few adult patients who have high-grade astrocytic tumors and who will survive for a considerable period (several years).

Gadolinium-enhanced MR in the evaluation of preoperative meningioma embolization.

PURPOSE: To evaluate the use of postembolization gadolinium-enhanced MR imaging as a means to judge the efficacy of tumor embolization. METHODS: Fifteen patients with meningiomas were prospectively studied. The following data were evaluated for each tumor: the percentage of vascular supply to the tumor arising from the internal and external carotid arteries; the percentage of the tumor embolized as judged by angiography, by MR imaging, and by CT scanning; the estimated blood loss according to the surgeon; and histologic evidence of necrosis as seen by the neuropathologist. RESULTS: The data reveal an excellent correlation between the amount of tumor embolized as estimated by MR and both the estimated blood loss at time of surgery and the presence of histological necrosis in the specimen. CONCLUSIONS: Postembolization gadolinium-enhanced MR is an excellent means to evaluate the efficacy of an embolization and offers certain advantages over CT and angiography. One important advantage of this technique lies in the fact that it can be performed immediately postembolization.

A survey of 65 tumors within the spinal cord: surgical results and the importance of preoperative magnetic resonance imaging.

Between January 1984 and December 1990, 65 intramedullary spinal cord tumors were diagnosed and operated on. In this series, all patients underwent magnetic resonance imaging investigations and were operated on with the Cavitron ultrasonic surgical aspirator whenever necessary. Major surgical difficulties have been found in patients previously treated by radiotherapy with or without biopsy. We found magnetic resonance imaging to be a highly sensitive imaging procedure and the method of choice for visualizing tumors within the spinal cord. Nevertheless, accurate diagnosis may only be suggested by magnetic resonance imaging, rather than made definitively. Surgery is necessary in every case in order to obtain a definite diagnosis. Radical surgery can be performed when a plane exists between the tumor and the normal spinal cord: biopsy or debulking with the Cavitron ultrasonic surgical aspirator should be performed when the tumor is infiltrative. We have performed 33 so-called total resections, 22 partial resections, and 10 biopsies, among which 5 were performed on lipomas. Surgical results were assessed at 3 months after surgery, showing 35 improvements (53%), 24 stabilizations (37%), and 6 deteriorations (10%).

Prognostic scoring in adult astrocytic tumors using patient age, histopathological grade, and DNA histogram type.

High-grade astrocytic tumors constitute the most serious as well as the most common group of primary brain tumors. Although several prognostic factors have been proposed, little is known about the prognostic value of deoxyribonucleic acid (DNA) ploidy in adult astrocytic tumors. In a series of 146 adult patients, aged 16 to 82 years, the individual prognostic values of six variables were studied, namely: tumor histopathological grade, treatment, patient age, extent of tumor, ploidy level, and DNA histogram type. Cox's proportional hazard model was then applied to the data to ascertain which factors might independently determine patient survival. Univariate analyses revealed that histopathological grade, age, and DNA histogram type were very powerful prognostic factors. The statistical significance of the influence of adjuvant radiotherapy and chemotherapy was at a borderline level, and the two remaining variables (tumor extent and ploidy level) had no prognostic relevance. Multivariate analyses showed that age, histopathological grade, and DNA histogram type were independent, statistically significant prognostic factors. A prognostic score was calculated from Cox's polynomial function in which those factors were introduced. The best score corresponded to a patient aged 16 years with a hypertriploid low-grade astrocytoma, while the worst score corresponded to a patient aged 82 years with a diploid high-grade astrocytoma. The worst score:best score ratio revealed a risk 71 times higher for a bad prognosis. It is concluded that patient age, histopathological grade, and DNA histogram type are very powerful prognostic factors for adult astrocytic tumors. A prognostic score including those factors could be used to characterize astrocytic tumor aggressiveness presurgically on fine-needle aspirates, and to monitor the patient's postsurgical evolution to define the appropriate therapy.

Nearest-neighbor classification for identification of aggressive versus nonaggressive low-grade astrocytic tumors by means of image cytometry-generated variables.

The authors investigated whether cytometry-related variables generated by means of computer-assisted microscopic analysis of Feulgen-stained nuclei can contribute significant information toward the characterization of low-grade astrocytic tumor aggressiveness. This investigation was conducted using the nearest-neighbor rule (a traditional classification method used in pattern recognition) to analyze a series of 250 supratentorial astrocytic tumors from adult patients. This series included 39 low-grade astrocytomas and 211 high-grade astrocytic tumors (including 47 anaplastic astrocytomas and 164 glioblastomas multiforme [GBMs]). The results show that the 3-nearest-neighbors rule enabled a subgroup of "atypical" astrocytomas to be distinguished from the "typical" tumors. The atypical astrocytoma species exhibited a DNA content (DNA ploidy level) and morphonuclear characteristics that were statistically more similar to the characteristics of GBMs than to those exhibited by the typical astrocytomas. An analysis of survival data revealed that patients with atypical astrocytomas survived for a significantly shorter period (p < 0.001) than patients with typical lesions of this kind. In fact, patients with atypical astrocytomas had a survival period similar to that of patients with anaplastic astrocytomas, whereas patients with typical astrocytomas had a survival period significantly longer (p < 0.0001) than those associated with anaplastic astrocytomas and GBMs.

[Subarachnoid hemorrhage of unknown origin. Apropos of 59 cases]. / Les hémorragies sous-arachnoïdiennes (H.S.A.) d'étiologie inconnue. A propos de 59 cas.

Fifty-nine subarachnoid hemorrhage with normal panangiography were reviewed (1982-1989). The mean age is 50 + 10. The grades at admission are compared following the Hunt and Hess and the World Federation Classification. Fifty cases (Hunt and Hess) or 45 (W.F.N.S.) are grade I or II. Compared with 278 cases of subarachnoid hemorrhage of aneurysmal etiology, 76% were in good grades versus 55% only for the aneurysms. Hypertension was present in 21 cases (35%) and represented a factor of gravity. Hydrocephaly is a rare complication in these cases and only 2 cases were shunted. The repetition of angiographic exploration seems to be unnecessary: all the examens remained negatives. The aspect on C.T. Scan was the same that the subarachnoid hemorrhage of aneurysmal origin. Angiography of 4 pedicles were performed in all cases and in the late 15 cases, external carotid explorations were added for exclusion of dural malformations. Seven suspected cases had had a secondary exploration between 12 days. The other cases were reexamined at 3 months. Three cases deceased from a second hemorrhage without aneurysm at autopsy. These cases confirm that subarachnoid hemorrhage of unknown etiology is of good prognosis. Low grades, rare complications, few rebleeding and good outcome scale are common. Etiology remains hypothetic.

[Lesions of the pineal and tentorial region. Occipito-parietal approach in three-quarter prone position with infrasagittal craniotomy]. / Lésions de la région pinéale et falco-tentorielle. Abord occipito-pariétal en trois-quarts ventral avec volet infra-sagittal.

Surgical treatment of pineal-tentorial region lesions remains a challenge. The difficulty in approaching the pineal region can be verified with the number of operative plans that have been proposed to reach this area: transcallosal, occipital transtentorial, infratentorial supracerebellar approaches and sitting, prone or Concorde positions. This emphasizes the surgeon's dissatisfaction with the surgical techniques described. Recently, a three-quarter prone position with the bone flap placed under the midline has been described (1, 3, 8). We have decided to test this approach that we have slightly modified and we report our results on 13 cases: 2 arachnoid cysts, 3 vascular malformations and 8 tumors (3 brainstem gliomas, 2 dysgerminomas, 1 quadrigeminal plate metastasis and 1 meningioma plus 1 metastasis of the falx). Keeping the table in a horizontal plane, risks of air embolus are eliminated. Using the natural effect of gravity, traction on the occipital lobe is no more necessary and hemianopsia no more occurs. We recommand the parieto-occipital route which is the shortest way to reach epiphysis and falco-tentorial notch. We confirm the results of american colleagues (1, 3, 8, 15) and we advise to use this approach which seems to us the best way to treat pineal-tentorial lesions.

[Subarachnoid hemorrhage in patients over 65 years of age. Retrospective study of 72 patients including 65 cases of aneurysmal origin]. / Les hémorragies sous-arachnoïdiennes (HSA) au-delà de 65 ans. Etude rétrospective d'une série de 72 patients dont 65 cas d'origine anévrismale.

For this study, we reviewed a series of 564 consecutive SAH among which 72 cases (12.7%) were older than 65 years. Etiology of SAH was: arterial aneurysms (65), arteriovenous malformations (1), unknown origin (6). Among the 65 aneurysms, 28 operated cases were between 65-69 years old. One year after surgery, the results are: GOS 1 and 2: 22 cases (57%); GOS 3: 4 cases; GOS 5: 13 cases. In the non operated group, 19 cases died (73%) and among the alive patients, one was GOS 2 (4%), 5 GOS 3 and 1 GOS 4. In the operated group, mortality is similar to other published series. In the non operated group, mortality is unsurprisingly higher (73%) than in the operated group, but also than in the literature. An explanation could be found with analyses of the income of our patient whose many are not referred cases from other hospital. Our analysis confirmed that the severity of SAH after 65 years is increasing. The raise of anterior communicating aneurysms location is demonstrated. Operative indication and timing are dependent of neurological grading, general condition and secondarily of the location and anatomy of the aneurysm.

[Diagnostic and/or prognostic value of the nuclear level determination of desoxyribonucleic acid (DNA) in nervous system tumors]. / Valeur diagnostique et/ou pronostique de la détermination du contenu nucléaire en acide désoxyribonucléique (ADN) dans les tumeurs du système nerveux.

The diagnostic and prognostic value of the DNA ploidy level (nuclear DNA content) was studied in a series of 847 tumours of the nervous system. This series included 93 nerve sheath tumours, 224 meningiomas, 389 neuro-epithelial tissue tumours, 46 primitive neuroectodermal tumours (retinoblastomas, medulloblastomas, neuroblastomas, etc.) and 95 brain metastases. The DNA ploidy level determination was carried out by means of the computer-assisted microscope analysis (digital cell image analysis) of Feulgen-stained nuclei. The results show that the DNA ploidy level does not contribute significant diagnostic information when tumours are analyzed individually. Indeed, some tumours which are definitely benign like certain schwannomas and meningiomas can exhibit very high levels of aneuploidy, while some highly malignant tumours like certain glioblastomas and neuroblastomas can be diploid. In contrast to its weak diagnostic value, the DNA ploidy level appears to be a powerful prognostic factor with respect to the supratentorial astrocytic tumours of the adult. Indeed, patients with hypertriploid astrocytic tumours exhibit a survival period which is significantly longer when compared to that of patients with non-hypertriploid astrocytic tumours. These hypertriploid astrocytic tumours could be involved in a process of biological degeneration when reference is made to their proliferation activity which is significantly weaker than that of non-hypertriploid tumours.

Co-expression/co-location of S100 proteins (S100B, S100A1 and S100A2) and protein kinase C (PKC-beta, -eta and -zeta) in a rat model of cerebral basilar artery vasospasm.

OBJECT: The cellular events leading to cerebral vasospasm after subarachnoid haemorrhages (SAH) involve a number of members of the protein kinase C (PKC) family. However, whereas calcium is thought to play a number of major roles in the pathophysiology of SAH, a number of PKCs function independently of calcium. We recently emphasized the potential role of the calcium-binding S100 proteins in a 'double haemorrhage' rat model of SAH-induced vasospasm. A number of S100 proteins are known to interfere directly with PKC, or indirectly with PKC substrates. We therefore investigated whether specific S100 proteins and PKCs are co-expressed/co-located in a rat model of SAH-induced vasospasm. METHODS AND RESULTS: SAH-induced vasospasm in rats (by means of a double cisternal injection of autologous blood from a rat femoral artery) distinctly modified the expression levels of calcium-dependent PKC-alpha and PKC-beta and calcium-independent PKC-eta and PKC-zeta in endothelial and smooth-muscle cells. The RNA levels of these four PKC isotypes were determined by quantitative RT-PCR. The present study reveals that, in endothelial cells, the S100B expression/location correlate well with those of PKC-eta, and those of S100A1 with PKC-beta. In smooth-muscle cells S100A2 expression/location correlate with those of PKC-eta, and those of S100B with PKC-zeta. CONCLUSION: The present data argue in favour of a joint action of the S100 protein network and the PKC signalling pathway during cerebral vasospasm.

Management of malignant brain tumors.

This review is made up of two parts. The first section describes techniques and methods used in the treatment of malignant brain tumors, stressing the most recent developments. The second part reviews the therapeutic modalities in malignant gliomas, where an attempt is made to consider separately glioblastomas, anaplastic astrocytomas and oligodendrogliomas, low-grade glioma, medulloblastoma, primary brain lymphoma, and brain metastases. A decision making algorithm is suggested for each tumor type.

Three-quarter prone approach to the pineal-tentorial region. Report of seven cases.

We report our preliminary results (seven cases) with a three-quarter prone approach to the pineal-tentorial region using an opening beneath the midline. The technique we have used eliminates the risk of air embolism because the head is just over the right atrium, the table remaining in an horizontal plane. Using the natural effect of gravity, it is no more necessary to use retraction on the occipital lobe. So, hemianopsia is eliminated. We confirm the results of other teams who have used this approach which seems to us to be the best way to treat any lesion in the pineal-tentorial area.

Intracranial meningiomas revealed by non-traumatic subdural haematomas: a series of four cases.

OBJECTIVE: A review of the literature shows 33 cases of ipsilateral subdural haematomas (SDH) associated with meningiomas. We suggest that physiopathological mechanisms could be primary haemorrhages from abnormal vessels in the tumours and the opening of the intratumoral haematomas into the subdural space. Our working hypothesis relies on a series of 300 meningiomas operated upon in our department since 1990; of these, 4 were revealed by SDH. CLINICAL PRESENTATION: The four patients surgically treated in our department had developed a progressive impairment of consciousness. There was no history of trauma, blood dyscrasia or anticoagulant therapy. After diagnosis, the SDH was drained, and the meningeal tumour was totally resected once it had been discovered. In one case, the presence of a tumour was demonstrated by magnetic resonance imaging (MRI) performed only after the evacuation of a recurrent SDH. INTERVENTION: In each case, an acute SDH showing signs of recent bleeding was evacuated. The meningeal tumour discovered proved to be the source of the haemorrhage because of the numerous fresh blood clots both around and inside it. HISTOLOGY: In the four cases histology showed fresh intratumoral haemorrhages (ITH), large blood vessels with thin endothelial linings and haemosiderin deposits. In this review, SDH is associated with other haemorrhage sites in 24 of 37 cases (33+our 4 cases). ITH was present in 14 cases (40%). CONCLUSION: The treatment should consist of the extirpation of the meningioma at the same time as the evacuation of the haematoma. If primary ITH from abnormal vessels is the source of SDH, complete meningioma resection should prevent the recurrence of SDH. Subdural membranes and haematomas should therefore be inspected for their intrinsic pathology, especially when there is no history of trauma.

The use of disharmonic motion curves in problems of the cervical spine.

Cervical spine motion was investigated by three-dimensional electrogoniometry in 257 asymptomatic volunteers and in 32 patients with cervical disc hernia or whiplash syndrome. Maximal ranges of main and coupled motions were considered. Motion curves were analysed qualitatively and using fitting of sixth degree polynomials. Motion ranges obtained were in agreement with previous observations. Significant differences between patients and volunteers concerned several primary and coupled components but not all. Qualitatively, patients displayed less harmonic curves, with irregularities and plateau-like appearances. Root mean square differences between data and fit were significantly modified in patients. Although cervical spine motion ranges may remain within normal limits in patients, motion patterns were altered qualitatively and quantitatively. Motion pattern analysis might prove a useful discrimination parameter in patients in whom anatomical lesions are not clearly identifiable.

Histopathologic grading and DNA ploidy in relation to survival among 206 adult astrocytic tumor patients.

BACKGROUND: The authors studied the benefit of performing histopathologic grading and DNA ploidy characterization with respect to patient survival in a series of 206 astrocytomas (AST) for which they obtained 134 complete clinical follow-ups. METHODS: The material analyzed came from archival material, i.e., formalin-fixed paraffin-embedded tissues. DNA ploidy was assessed by means of a cell image processor computing the integrated optical density (IOD) on Feulgen-stained nuclei. RESULTS: Results showed that histopathologic diagnosis in three grades, i.e., AST, anaplastic astrocytoma (ANA), and glioblastoma multiforme (GBM), had a significant prognostic value. Patients with AST showed a mean survival time (between histopathologic diagnosis and death) of more than 36 +/- 6 months (AST versus ANA or GBM) (P less than 0.001). Patients with ANA and GBM showed a mean survival time of 15 +/- 2 and 10 +/- 1 months, respectively, (ANA versus GBM) (P less than 0.05). Patient age strongly correlated with survival. Patients younger than 40 years of age had a mean survival time of 20 +/- 4 months. Patients between 41 and 60 years of age had a mean survival time of 12 +/- 2 months, and patients older than 60 years of age had a mean survival time of 11 +/- 1 months. CONCLUSIONS: Considering DNA ploidy characterization, the authors noticed that aneuploid ANA (DNA index [DI] more than 1.30) were associated with a significantly higher mean patient survival time compared with that associated with euploid ANA. In contrast, the authors did not find this in either of the groups with AST and GBM. Recognizing six DNA histogram types (diploid, triploid, tetraploid, hyperdiploid, hypertriploid, and polymorphic), the authors observed that hypertriploid tumors were associated with greater patient survival compared with what happened in the cases of the five other DNA histogram types. This was true with respect to the three AST histopathologic types. Thus, DNA ploidy determination seemed helpful in characterizing aggressiveness in adult AST.