Cerebral Gliomas of Different Localization: Hemorrhagic
Complications after Their Removal

V.G. Mikhailyuk, V.F. Melkishev

Polenov Research Neurosurgical Institute Saint Petersburg, Russia

 

Introduction

Cerebral gliomas account for 45.6-58% of all primary intracranial neoplasms in adults [7, 9, 12, 15]. Their surgical removal is a leading method in complex treatment of this category of patients. However, complications, which develop at an early postoperative period in 25-35% of cases, increase a period of rehabilitation, reduce life quality and sometimes (14.3-15.4%) become a cause of fatal outcomes [10, 16, 17, 24]. One of the complications, typical of an early postoperative period, is hemorrhage into a tumor bed and/or its residual part with formation of epi- or subdural hematomas. The rate of clinically important hemorrhagic complications is not very high, but they lead to a fatal outcome in 23.8% of cases [14]. Hemorrhages into a tumor remnant occupy the second place (15-26%) among other causes of mortality after intracranial interventions for cerebral tumors [2, 3, 6, 16].

The goal of the present study has been obtaining more exact information on a structure, rate, causes, risk factors, peculiarities of clinical manifestations and outcomes of hemorrhagic complications after removal of gliomas with different localization.

Materials and Methods

The study is based on the analysis of results of surgical treatment, watched in 481 cases with cerebral gliomas and operated in the clinic of the Polenov Research Neurosurgical Institute in 1996-2003. There were 265 males (55.1%) and 216 females (44.9%), aged 17-72. Glioma localization was as follows: cerebral hemispheres - 261 cases (54.3%), subcortical ganglia - 68 cases (14.1%), brain ventricles - 59 cases (12.3%), corpus callosum - 56 cases (11.6%), brain stem - 18 cases (3.8%), cerebellum - 16 cases (3.3%). Diffuse glioblastomatosis was diagnosed in 3 patients (0.6%). Malignant and benign gliomas were watched in 326 (67.8%) and 144 (30.0%) cases respectively. Diagnosis was not verified histologically in 11 patient (2.2%) because of performing decompressive operations. However, tumor localization (cerebral hemispheres, brain stem) and MRI findings allowed to qualify it as glioma. There were 174 gioblastomas (36.2%), 118 anaplastic astrocytomas (24.5%), 97 differentiated astrocytomas (20%), 37 mixed gliomas (7.7%), 26 ependymomas (5.4%) and 18 oligodendrogliomas (3.7%).

Total, subtotal and partial removal was performed in 116 (24.1%), 166 (34.5%) and 168 (34.9%) of patients respectively. Biopsy was performed in 20 cases (4.2%); 11 patients (2.3%) were subject to decompressive operations (internal decompression by resection of lobe poles, tentoriotomy). Radical resection of a tumor was dependent on its localization. Cerebellar gliomas were resected totally in 70% of cases. Total and subtotal resections of hemispheric and ventricular gliomas were made in 69.8% and 52.5% of patients respectively. Removal of neoplasms of corpus callosum and subcortical ganglia was either subtotal or partial. Biopsy and/or tentoriotomy were performed in 66.7% of cases with brain stem gliomas. Operation efficacy did not depend on a tumor histologic structure.

Complex examination of patients was carried out before and after operation. It was based on clinical-and-neurologic, biochemical, pathohistologic, pathomorphologic and neurovizualization methods. Clinical-and-neurologic examination allowed to estimate disease duration, a neurologic status before and after operation; use of Karnofsky's scale served the basis for distinguishing such 5 clinical stages of the disease, as compensation (a score of 100-80), subcompensation (a score of 70-60), moderate decompensation (a score of 50-40), marked decompensation (a score of 30-20) and a terminal stage (a score of 10). Preoperative distribution of cases according to the stages was as follows: compensation - 18.5%, subcompensation - 47.6%, moderate decompensation - 21.4%, marked decompensation - 10.7%, a terminal stage - 1.8%. On admission the stages of clinical subcompensation or compensation were watched in 86.7% and 81.5% of cases with hemispheric and ventricular gliomas respectively. A stage of clinical decompensation was typical of 39.1% and 65.2% of admitted patients with tumors of corpus callosum and subcortical ganglia respectively.

Development of a hemorrhagic complication, diagnosed on the basis of clinical data, was confirmed by CT findings (CTP-1010 apparatus), during reoperation and/or postmortem examination.

Results and Their Discussion

Hemorrhagic complications developed in 29 (6.0%) out of 481 patients with cerebral gliomas at an early postoperative period. They resulted in a fatal outcome in 6 of them (20.7%). Hemorrhage into a tumor bed or its residual part was observed in 26 patients (5.4%). Meningeal (subdural or epidural) hematoma was present in 3 cases (0.6%). The rate and structure of hemorrhagic complications were in compliance with literature data, according to which clinically important hemorrhages had been watched in 1.6-5% of patients after glioma removal [14, 16, 19, 23, 25]; hemorrhages into a tumor bed and/or its remnant had been diagnosed in 2-3.9% of them; meningeal hematomas had been present in 0.2-0.9% of cases and the rate of fatal outcomes had been 23.8%. It is 3.1% higher, than in our study.

The rate of hemorrhagic complications in males and females was practically the same: 6.4% (17) and 5.6% (12) respectively. As for patients, aged 60 and more, this index was two and more times higher (p<0.05), than in other age groups (Fig.1). To some extent, it was conditioned by accompanying cardiovascular pathology, which was often typical for elderly persons. G. Kh. Ernan [14] and K.D. Post [23] reported a higher rate of hemorrhages in hypertension and artherosclerosis, resulting in smaller elasticity of vessels and unstable hemodynamics. Our study demonstrated, that accompanying cardiovascular pathology increased a risk of hemorrhages by 50% (from 14.8% up to 22%).

High-grade gliomas are characterized by progessive vascular changes and marked foci of angiomatosis. Taking into account this fact and reports of some authors [13, 14, 20], one can expect the highest rate of hemorrhages in this pathlogy. As for our study, we watched the same rate of hemorrhagic complications in malignant and benign gliomas: 6.3% (9) and 6.1% (20) respectively. There was no reliable difference in various histologic types of a tumor as well. However, it should be noted, that hemorrhages were more frequent in ependymomas and mixed gliomas. Abundant blood supply of glioma was that very risk factor, which had an effect on development of hemorrhages into a tumor bed and/or its residual part and increased their rate from 11% up to 25% (p was very close to 0.05).

Table 1

The Rate of Development of Hemorrhage Complications and Its Dependence on a Histological Structure of Glioma

A Histological Structure of Tumor

A Number of Patinets with Hemorrhages

A Total Number of Patients

 

An Absolute Number

%

 

Benign astrocytoma

4

4.1

97

Malignant astrocytoma

6

5.1

118

Glioblastoma

11

6.3

174

Oligodendroglioma

1

5.6

18

Ependymoma

3

11.5

26

Mixed gliomas

4

10.8

37

Total

29

6.2

470 *

* Cases without histological confirmatiom of diagnosis were not included.

Intracranial hypertension played a rather important part in development of hemorrhagic complications. It was confirmed by their high rate in the following cases: a short history of a disease (p<0.05) with quick development of intracranial hypertension; the stage of pronounced clinical decompensation, characterized by marked hypertensive syndrome; intracranial hypertension, watched during the first postoperative days and against a background of postoperative edema. Thus, the longer a history, the smaller probability of hemorrhagic complications. When a disease duration did not exceed a year, hemorrhages developed in 24.5% of cases. If it was equal to 1-3 years, they were watched in 12.2% of patients. If it was more than 3 years, there were no hemorrhagic complications. In case of marked clinical decompensation, hemorrhages developed in 33.3% of cases. It was two times higher as compared to patients at the stage of clinical compensation, subcompensation and moderate decompensation (16.1%, 13.8% and 19.4% respectively). The rate of hemorrhagic complications increased from 16.7% up to 26.3% in hypertensive syndrome with dislocation signs, watched during the first postoperative days. We failed to find any information on this problem in available literature.

One more factor, causing development of hemorrhagic complications, was intervention efficacy. A smaller volume of resection resulted in their higher rate (p<0.05). It was more than 2 times higher in partial removal as compared to total and subtotal resection (Fig.2). There are several reports, containing similar information [4, 13, 14, 16, 20]. The explanation is as follows: a part of a tumor, which remains after its incomplete removal, has defective vessels and is a source of fibrinolysis proactivators [1, 5].

Many authors report, that changes in the system of hemostasis can be one of the causes of hemorrhagic complications; it especially concerns the first postoperative days [1, 5, 14, 18, 21, 22, 23]. These disorders result from a great amount of thromboplastin substances and fibrinolysis proactivators, delivered to blood during tumor removal; intraoperative complications (edema, bleeding), demanding massive infusion, hemotransfusion and use of diuretics; thrombocytopenia. We did not reveal such a direct dependence. However, the rate of hemorrhages was 50% higher in marked postoperative hypoproteinemia than without it; hemorrhages were more frequent in patients with a coagulogram shift in the direction of hypocoagulation (3 out of 7 cases) and in intraoperative development of local syndrome of disseminated intravascular coagulability (4 out of 7 cases), manifesting itself in diffuse tissue bleeding.

There was a reliable difference (p<0.05) in the rate of hemorrhagic complications in patients with various localization of tumors (Fig.3). The highest rate was watched in subcortical and ventricular gliomas,especially those of the IV and III ventricles (16.2% - 11 cases and 8.5% - 5 cases respectively). As for tumors of cerebral hemispheres, corpus calosum and brain stem, hemorrhages developed in 3.8% (10), 3.6% (2) and 5.6% (1) of patients respectively.

First of all, it was explained by a large proportion of partial removal of subcortical and ventricular gliomas, as well as by the fact, that many patients with tumors of subcortical ganglia were admitted in a state of marked clinical decompensation. Incomplete removal can be also an explanation of a high rate of hemorrhages in ependymomas and mixed gliomas. There were no hemorrhages in cerebellar gliomas, which were resected totally in the majority of cases. V.K. Zhestovsky [4] and G.Kh. Ernan [14] demonstrated more frequent development of hemorrhages in gliomas, localized in functionally eloquent areas (subcortical ganglia, the IV ventricle fundus); in their opinion, it was conditioned by incomplete removal of a tumor as well.

The overwhelming majority of cases (69% - 20) developed hemorrhagic complications during the first three postoperative days; they appeared on the 4-12 day in the rest patients (31% -9). A state deterioration of an apoplexy type and augmentation of symptoms during some hours were observed in 51.7% (14) and 48.3% (14) of cases respectively. Progradient deterioration of a state took place only during first two days after operation; revision of a postoperative wound revealed a source of bleeding in 6 of these patients (vessels of a tumor bed or its remnant; pial, dural or diploic vessels). It indicated, that imperfect hemostasis could be a possible cause of hemorrhage in such cases. Hemorrhage was preceded by blood pressure elevation with a state deterioration of an apoplexy type in 6 patients. Hypertension and imperfect hemostasis are mentioned as possible causes of hemorrhagic complications in reports by other authors [8, 13, 14, 16, 23, 25]. Patients with hemorrhagic complications, which developed during the first three days after operation, had imperfect hemostasis and a source of bleeding, revealed during reoperation (6); blood pressure elevation (5); intraoperative local disseminated intravascular syndrome (2) and a coagulogram shift in the direction of hypocoagulation (2); intracranial hypertension with dislocation signs, watched during the first postoperative day (2). Findings in hemorrhages, developing after 4 days, included disorders in coagulograms (2), intracranial hypertension (4), pyo-inflammatory respiratory complications (6). The latter promoted increase of intracranial pressure due to hampered venous outflow and hypoxemia, development of disorders in the system of hemostasis, caused by marked infectious intoxication.

Hypertension syndrome (91.3%) was the main clinical manifestation of hemorrhages. It was accompanied by psychomotor excitement in 2 cases (8.7%), consciousness disorders in 19 patients (82.6%), dislocation syndrome in 16 cases (70%) and diencephalic symptoms in 12 patients (52.2%). Focal neurologic disturbances, marked to this or that degree, and seizures were present in 82.6% and 4.3% of cases respectively. When gliomas, localized in subcortical ganglia and the IV ventricle fundus, infiltrated the stem, hemorrhages into a tumor remnant manifested themselves in disorders of vital functions with a rapid fatal outcome (20.7% of cases). Meningeal symptoms were present in 65% of cases (25).

Hemorrhagic complications were confirmed by CT-examination, during reoperation and autopsy in 21 (72.4%), 2 (6.9%) and 6 (20.7%) of cases respectively. Meningeal hematoma was diagnosed in 3 patients (10.3%); 16 cases (55.2%) had hemorrhages into a tumor remnant, which looked like imbibition (soaking) of glioma tissues with blood; hemorrhages into a tumor bed or its remnant with formation of intracerebral hematoma were watched in 10 cases (34.5%). A rush of blood into the ventricular system was observed in 13.8% of cases with gliomas, localized in the III ventricle or thalamus. It resulted in tamponade of this system in 6.9% of patients. According to G.Kh. Ernan [14] and V.V. Timigraz [11], blood in cerebral ventricles was detected only in 1-3.6% of the diseased.

Besides a hyperdense zone, corresponding to hemorrhage, CT-examination demonstrated perifocal changes, i.e. areas of diminished density, characterized by different spread and a mass-effect. This phenomenon was treated as edema. In case of imbibition-type hemorrhages, it was just spread of perifocal changes, which conditioned a state severity. If there were intracerebral and meningeal hematomas, clinical manifestations depended on their volume. Extensive perifocal changes (more than 2 lobes) and intracerebral hematomas of more than 50 ml were accompanied by development of hypertension-dislocation syndrome in all cases and were indications for revision of an operative wound (8 patients). All meningeal hematomas were more than 100 ml and caused development of dislocation syndrome. It should be noted, that they manifested themselves in progradient aggravation of a state during the first three postoperative days; revision of an operative wound allowed to find a source of bleeding. It showed, that imperfect hemostasis was the only cause of formation of meningeal hematomas. As for hemorrhages into a tumor bed and/or its remnant, which were of an inbibition type or led to formation of intracerebral hematoma, everything was dependent on a combination of the above factors.

There were 23 cases, who survived at the moment of hemorrhage. Drug therapy was used in 12 of them and 11 patient were subject to reoperation with hematoma removal. In case of diffuse perifocal changes and meningeal hematomas, intervention was supplemented by internal and external decompression respectively. The therapy led to rergession of general cerebral and focal symtoms in 10 out of 29 patients (34.5%); they remained unchanged in 10 cases (34.5%); 9 patients (31%) died. It should be noted, that the results of reoperation were better as compared to those of drug therapy. A number of patients with persistent neurologic symptoms was smaller (36.6% and 41.7 respectively) and the mortality rate was lower (9.1% and 16.6% respectively). A direct cause of death (7) was hemorrhage into a tumor remnant because of acute tamponade of ventricles by blood (2) and imbibition of that part of glioma, which infiltrated the stem (primarily or growing from subcortical ganglia and the IV ventricle). Massive gastrointestinal bleeding and pneumonia, watched against a background of a severe postoperative course, were causes of fatal outcomes in 2 cases.

The most severe course, slow restoration of functions and the worst results of treatment were typical of gliomas of subcortical ganglia and cerebral ventricles. In case of hemorrhage development, mortality reached 46% and 60% respectively. There were no fatal outcomes in gliomas, localized in cerebral hemispheres and corpus callosum.

Conclusions

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