Advances, problems and prospects of complex treatment of patients with cerebral tumors

Tigliev G.S.

Russian Polenov Neurosurgical Institute, Saint Petersburg, Russia

Brain tumors account for 1.8-2.3% of the total number of oncologic diseases. During the last quarter of the XXth century their rate in different countries varied from 2.5 up to 16.5 men per 100 000 adults. Brain tumors are more prevalent in some regions of the world (Scandinavia, the Pacific region). Considering a problem in its absolute sense, one should agree that an annual number of people, who develop this disease, is not a small value. According to incomplete data, it varies within the limits of 250-300 men in Saint Petersburg only. Besides, a growth of neurooncologic morbidity in other countries should be emphasized too. Etiologic factors are the first to be mentioned among other causes of this phenomenon; it is illustrated brightly by consequences of the Chernobyl catastrophe (fig.1). However, a growing morbidity rate is watched in some countries (for example, the USA) even without ecological disasters of the above type. It is connected partly with improved identification of this pathology, i.e. its diagnosis. An increase of a number of patients due to these or those causes is confirmed indirectly by dynamics of their admission to the Neurooncologic Department (fig.2) of the Russian Polenov Neurosurgical Institute (RPNI). The analysis shows, that a number of cases, treated at the Institute during the last 25 (1977-2001) and previous 50 years is identical in spite of constantly developing neurooncologic care and its growing volume in all regions of Russia.

It is known, that the last 10-15 years are characterized by considerable reduction of postoperative mortality (fig.3), more radical interventions and, what is more important, better quality of life of operated patients (fig.4). It became possible thanks to up-to-date diagnostic modalities (CT, MRI, MRA, PET), research in microsurgical anatomy, modification and development of new approaches, the latest microsurgical technologies (including endoscopic means), new systems of anesthesiologic support, intraoperative monitoring of a state of vital systems and cranial nerves, intensive care in a postoperative period, etc. In particular, during the last 5 years postoperative mortality in the RPNI Neurooncologic Department (a total number of patients equal to 1594) did not exceed 4.2%; it was 0.2% in some, for example subfrontal, meningiomas. It is undoubtedly a reflection of certain achievements in complex treatment of patients with cerebral tumors.

Gliomas are known to be prevalent among brain tumors. It is also confirmed by data, obtained in the RPNI (fig.5). The second place is occupied by meningiomas, which have a leading position in a group of extracerebral neoplasms. Taking these two largest groups of patients as an example, let us dwell briefly on those main "constituents", which ensured modern advances in treatment of patients with cerebral tumors.

Intracranial Meningiomas

Surgery of extracerebral tumors is one of the most complicated, but at the same time reassuring (both for a doctor and patient) sections of neurooncology. In order to obtain good results of surgical treatment, one should observe several conditions of principal importance. Correct position of a patient on an operating table is one of the significant factors, determining success of surgical intervention. Multiform localization of meningiomas conditions use of practically all known positions of a patient during their surgical treatment. To some degree, a patient's position on an operating table is a compromise between providing conditions for an approach to a tumor and adequate venous blood outflow from a head. The latter should be a bit higher, than auricles in any position of a patient. Sometimes a sitting position is preferable; it depends on tumor localization. However, some famous neurosurgeons do not use this position, as they consider it to be dangerous because of a risk of air embolism. Still, when a sitting position is used, a special attention should be paid to fixing a patient's body and Doppler control of possible development of air embolism. A position of a patient's head should always promote gravitation retraction of the brain with the purpose of ensuring easier access to a tumor.

One of the important conditions, determining successful surgical treatment of meningiomas and other extracerebral tumors, is monitoring of the brain functional state during an intervention. It allows a surgeon, anesthesiologist and physiologist to carry out timely correction of both adequacy of anesthesiologic support and tactics of tumor removal. It is based on estimation of EEG findings, CNS evoked potentials, i.e. acoustic stem evoked potentials (ASEVP), visual evoked potentials (VEVP), somatosensory evoked potentials (SSEVP). A general view of a patient's head with electrodes for recording ASEVP and EEG is represented in (fig.6). Evoked potentials can be studied with the help of Viking-IV and Bravo computer systems (Nicolet, USA), etc. (fig.7).

Successful removal of cerebral tumors in general and meningiomas in particular is extremely dependent on a choice and use of an adequate surgical approach. The latter should meet several requirements:

A diagrammatic picture of main requirements to be met by surgical approaches are given in (fig.8). It is quite clear, that there is no approach, capable of meeting these requirements completely. Nevertheless, a lower margin of a trephination window in approaches to tumors of the sphenoid bone planum and chiasm-sellar region should be as close to the base of the anterior cranial fossa as possible (fig.9). During the last decades different modifications of approaches were developed with the purpose of increasing an angle of operative activity and avoiding traction injuries of the brain in operations for tumors of basal peristem localization. They allowed to perform more extended resection of bones of the skull base with the help of high-speed microtrepans. Some of these accesses are presented in (fig.10). Owing to this fact, it became possible to remove basal peristem benign extracerebral tumors practically without traction injuries of the brain. Thus, there appeared important preconditions for removing even difficult-of-access peristem intracranial tumors, as well as neoplasms, causing extended lesions of bony structures of the skull base (A.N. Konovalov et al., 1996, 1998, 1999).

It should be emphasized, that efficacy of surgical treatment of extracerebral tumors is dependent on preservation of adequate cerebral circulation during an operation. It is of equal importance to ensure not only full-value arterial, but also venous blood circulation, which can be often impaired at the stage of an approach to a tumor.

Let us consider tumors of the upper sagittal sinus, leading to complete or almost complete occlusion in its middle or posterior third (fig.11). Stage-by-stage exclusion of vicariously dilated cerebral, cranial (diploic) and extracranial (cutaneous) paths of venous blood outflow is a pledge of successful operation. Ignoring this requirement can result in irretrievable tragic sequelae during skin incison or one-stage formation (sawing) and isolation of a bone graft from blood circulation. A clinical equivalent of such disorders of venous blood outflow due to erroneous actions, is, at best, severe neurologic deficit, manifesting itself in prolonged para- or tetraparesis of extremities.

An EEG-test with temporary compression of soft tissue veins of a head with a cuff, worked out and used in the RPNI (1976), allows to carry out preoperative estimation of changes of venous circulation and a degree of its compensation at the expense of the above vessels (fig.12). Appearance or aggravation of persistent local or diffuse changes of bioelectric activity is indicative of an undoubtedly significant role of these soft tissue veins in compensation of venous blood outflow. A surgical intervention in such cases is to be performed under EEG control. It is expedient to use S-shaped incisions with stage-by-stage formation and separation of dermal-aponeurotic flap for prevention of possible disorders of blood circulation (fig.13A). Sometimes marked functional importance of soft tissue veins of a head and diploic veins can lead to necessity of dividing an approach into several stages. Resection of a greater part of meningioma is followed by removal of its intrasinus fragment. This stage of an operation is performed in compliance with conventional methods and use of different modifications of the upper sagittal sinus plasty (W. Siger, 1978, 1984) (fig.13B). A shunting catheter with inflated balloons (A. Hakuba et al., 1974) (fig.13C) or occluding balloons (fig.13D) are used for prevention of cerebral ischemia and reduction of blood loss.

As for removal of meningiomas of the middle or posterior third of the falciform process, which do not involve the upper longitudinal sinus, special attention should be paid to integrity of ascending veins, which are dilated or compressed by a tumor rather often. It promotes restoration of, for example, visual fields after removal of even large meningiomas, affecting the occipital lobe (fig.14).

Necessity of preservation of "venous blood circulation" is an urgent problem even in those cases, when veins bear no direct relation to neoplasm, but are located "on the way" to it. A typical example is a routine bifrontal approach, envisaging ligation and dissection of the upper sagittal sinus near the cock's comb. As a rule, large veins of frontal poles, lying within ligation area, are found be "excluded" from blood circulation (fig.15). Thus, there appear causes for development and aggravation of traction damages of anterior segments of frontal lobes in approaches to subfrontal large and middle-sized meningiomas (fig.16A). The only exception is giant olfactory meningiomas with initial atrophy of frontal poles (fig.16B). This or that degree of psychomotor excitation, watched in the nearest postoperative period, is often typical of such patients. Their CT or MRI examination, carried out in 2-3 months, is indicative of cystic degeneration of the frontal pole, manifesting itself clinically as intellectual-mnestic disorders. In order to avoid this type of complications in preserved integrity of frontal lobes, it is expedient to use such an approach to the chiasm-sellar region, in which cutting off anterior segments of the upper sagittal sinus is performed near the cecal foramen after separation of dura mater duplication from the cock's comb (fig.17). Thanks to this, all veins of frontal poles remain intact; together with anterior segments of the sagittal sinus and frontal lobes they are lifted over orbital roofs as "a single block". It ensures a wide approach to the chiasm-sellar region.

Mobilization of Labbe vein along the length of 3-4 cm (fig.18) in supratentorial approaches to the Pachyon foramen permits to avoid marked neurologic deficit and to get a sufficient angle of operative activity.

While approaching a tumor, one should pay peculiar attention to preservation of anatomic and functional integrity of cranial nerves. It concerns not only "the whole family" of transpyramidal approaches (V.A. Khilko). Even nowadays many neurosurgeons, performing a bifrontal approach, are known to dissect olfactory tracts. Use of microsurgical mobilization of olfactory bulbs and tracts up to olfactory trigones (fig.19) allows to preserve olfaction in approximately 60% of patients subject to removal of tumors of the chiasm-sellar region. Of course, it does not concern cases, in whom these nervous structures were destructed by a growing tumor.

However, preservation of anatomic integrity and functional competence of brain structures, directly connected with neoplasm, cerebral vessels and cranial nerves is a rather serious problem in surgery of giant extracerebral tumors. Solution of this problem lies in not only an adequate approach to a tumor, but also tactics and surgical technique, used during an operation. Here one should stress importance of compulsory observation of a fragment-by-fragment removal principle, as well as necessity of close cooperation with a neurophysiologist and anesthesiologist during an intervention.

It is expedient to perform fragmentation of a tumor node after its complete (if it is possible) or partial separation from matrix, as it reduces bleeding from neoplasm parenchyma (fig.20). At first, fragmentation is performed within the limits of this node, then a capsule with small parts of a tumor is separated from different areas of the brain, cranial nerves and vessels. As a rule, meningiomas are characterized by "double" blood supply; thus, it is wise to block vessels of matrix and pia mater as early as possible. One should be very careful in order not to damage functionally important vessels, including, for example, short branches of the ICA supraclinoid part, going to the pituitary pedicle and fundus of the third ventricle (fig.20B), perforating branches of the basilar artery, going to the stem, branches of cerebellar arteries, etc. Necessity of exposure or separation of functionally important arteries is almost always accompanied by spasm development (fig.21), being a result of microsurgical manipulations and irritation of vessels adventitia. It can be eliminated quickly by applying cotton stripes, moistened with papaverine or novocainamide solution.

The experience shows, that excessive haste in removal of big tumors, which sometimes have a gross effect on diencephalic region and mesencephalic-bulbar segments of the stem, is fraught with their marked irritation (fig.22). Arising changes of cerebral blood flow and brain metabolism, as a rule, demand cessation of surgical manipulations for some small period of time with the purpose of restoring a normal functional state of brain stem structures. Such pauses in surgical manipulations or transition to other areas of an operative field make it possible to refuse from additional use of drugs. It has a favorable effect on a state of patients and allows them to recover from anesthesia on an operating table. The last circumstance is of great importance from the point of view of estimating a patient's state immediately after an intervention.

However, removal of giant meningiomas with, for example, sphenopetroclival localization, leading to marked dislocation of the brain stem, may cause such persistent signs of its irritation (due to its ischemia, severe metabolic changes), that an operation should be discontinued as it threatens a patient's life. It can necessitate division of an operation into 2-3 stages and use of mutually complementary combined approaches for tumor removal (fig.23).

It should be noted, that decompression of the brain stem, carried out as early as possible, is the most important tactical method, ensuring a stable state of a patient during neoplasm removal. In particular, it concerns cases with suprasubtentorial spread through the Pachyon foramen, when cerebellar tentorium is dissected from its free margin (fig.24), often "soldered" into a tumor.

While removing an extracerebral tumor, a neurosurgeon should concentrate his attention on preservation of the arachnoid, which separates a tumor capsule and the brain substance. It is just to the point to remind here the postulate by M.G. Yasargil, according to whom, "the basis of microneurosurgery is an arachnoid approach and dissection". However, "separation line" is often "lost" in places, where feeding or functionally important vessels, whose integrity is to be preserved, enter a tumor. It is precisely this fact, that explains why it is necessary to start separation of a tumor capsule from the brain substance in areas free of vessels, i.e. in places, where the above "separation line" is well-marked.

Possibility of total removal of a tumor is strongly dependent on its parenchyma density and a degree, to which neoplasm proper and its capsule are connected with functionally important cerebral vessels and other structures, especially those of the brain stem. It should be kept in mind, that functionally important cerebral vessels, going within a tumor, lose their elasticity and become vulnerable. That is why, exposure of vessels from meningiomas, possessing marked fibrillar structure and density, is difficult technically (fig.25), fraught with their inevitable damage and, as a rule, cannot be justified even when a neurosurgeon has microsurgical experience of long standing. It is better to forget about "surgical self-esteem" and to limit oneself to partial removal of neoplasm (fig.26A,B), than to lead a patient to disability or death. However, there is an alternative, which can be used in such situations, i.e. preliminary accumulation, arterial bypass (fig.26C,D), whose different modifications were developed by L. Shekhar et al. (1986, 1996, 1998).

Serious difficulties, limiting operation radicality, can be conditioned by partial or sometimes complete involvement of cranial nerves into a tumor (fig.27). It especially concerns the third, sixth, seventh cranial nerves, whose damage threatens with marked functional and sometimes cosmetic defect. In such situations it is expedient to exercise continuous audio-video control of nerves' functional state, direct or transcapsular dosed bipolar stimulation, which allows to get information on projection of a zone of their localization behind a capsule. These methods facilitate preservation of anatomic and functional integrity of cranial nerves in tumor removal. Examples of total resection of difficult-of-access meningiomas with good functional results are given in (fig.28) and (fig.29).

It should be noted, that surgical treatment of extracerebral tumors demands a greater variety of approaches and tactical methods in comparison with any other cerebral pathology. Despite one and the same localization different modifications of surgical interventions can be used. It depends on a tumor size, peculiarities of its spread, relationship between a capsule and eloquent and vital structures of the brain as well as cranial nerves and cerebral vessels, a general state of a patient and his age, a neurosurgeon's experience. Special emphasis in surgical treatment of extracerebral tumors should be laid on extreme importance of using all modern technical means.

Brain Gliomas

Data of different reports show, that gliomas account for 40-60% of all cerebral neoplasms. Their distribution according to histostructure and survival is given in table 1.

Table 1.

Cerebral gliomas (histostructure, rate and survival).

One can see, that more than a half of all gliomas is represented by glioblastomas; the rate of malignant gliomas together with anaplastic astrocytomas is 67%. An average period of survival does not exceed 5-10 months, despite complex treatment:

Today there is no uniform approach to treatment of gliomas. Some neurosurgeons consider surgical treatment of malignant neuroectodermal tumors to be inexpedient. It is quite clear, that this problem cannot be solved without knowing fundamentals of biological essence of gliomas. There are several modern theoretical and experimental developments, such as theory of cells, having a neoplastic origin; theory of mechanisms of genetic changes; theory of potential strategy of genetic therapy. However, they have not clarified the above biological essence completely. Still, there is reason to assert, that the brain does not consist of normal differentiated cells only, but it also contains a certain population of mature stem cells, capable of transformation into non-differentiated glial tumor cells. Besides, according to differentiation hypothesis, some cerebral cells possess a potential of enhanced growth, which is a source of tumor development. These tumors are capable of further mutation, resulting in malignant gliomas. Advances of molecular biology and molecular genetics of gliomas broadened our knowledge of genetic changes of oncogene and gene, suppressing tumor growth. Disappointing as it may be, research in this field is not of great importance for treatment of malignant gliomas.

A special emphasis should be laid on removal of malignant or "benign" glial tumor, being the most important stage of treatment.

Absence of valid MRI diagnostic criteria, indicative of such space-occupying cerebral lesions, as small glial tumors, demyelination foci, granulomas, infarctions, etc., causing no mass-effect, often persuades a doctor to carry out dynamic observation of a patient. In particular, it concerns cases in a compensated and stable state. This tactics is justified, especially if a surgeon has no positron-emission tomograph at his disposal. An origin of space-occupying foci is often determined with the help of stereotaxic biopsy. If glioma is diagnosed, either tumor resection, or radiation therapy, or chemotherapy, or combined treatment may be used; it depends on a surgeon's experience. If glioma spreads into cerebral ventricles and threatens with block of liquor-conducting tracts, tumor resection is compulsory (fig.30). Besides, active surgical tactics is to be used in marked mass-effect, i.e. compression and dislocation of the brain. It should be kept in mind, that tumor resection, leading to decrease of a number of tumor cells, changes cellular kinetics and, thus, ensures greater sensitivity of neoplasm remnants to radiation and chemotherapy. If neoplasm is localized in deep layers of cerebral cortex, one should use navigation systems, for example, ultrasononavigation (fig.31), which permits to minimize surgical trauma in transcortical approaches. It is especially typical of cases, when non-projection approaches to tumors, underlying eloquent areas of the brain, are used. Some modifications of approaches to hemispheric gliomas and permissible borders of lobe resection are given in (fig.32). Eloquent areas of the cortex (sensomotor , Broca and Vernike areas, a region of the calcarine fissure) should be preserved with the help of different methods of their marking. It should be taken into consideration, that many gliomas, which do not affect the cortex and are localized deeply within it near the midline, can be removed through the median fissure. Sometimes mobilization of large transit veins is necessary. In some cases preservation of eloquent cortical areas can be achieved thanks to an approach with retraction of the Sylvian fissure. When more or less total tumor resection is impossible, effective inner decompression is compulsory, as it allows to compensate a patient's state and to get some reserve of time for carrying out non-surgical treatment. External decompression, still used in some cases, should be consigned to oblivion, as it aggravates a patient's state. Tumor removal can be accompanied by photodynamic therapy (fig.33), applied to both a tumor bed area and foci of infiltration of pia mater and cortex, localized at some distance from the main neoplastic node.

Intraoperative MRI can be used for control of a degree of tumor resection. Satisfactory results can be achieved in applying ultrasonography; it is especially typical of hyperechogenic tumors. However, it is practically impossible to guarantee hundred-per-cent glioma removal, as the question of presence of disseminated tumor cells in the perifocal area of resected neoplasm is left open every time. That is why up-to-date treatment of gliomas should be complex. A combination of radio- and chemotherapy improves results of treatment of malignant cerebral gliomas to some extent (table 2).

Table 2.

Results of complex treatment of malignant cerebral gliomas.

Preliminary data of our clinic show, that even in primarily multiple glioblastomas of hemispheres maximum removal of neoplasm within the limits of macroscopically unchanged tissues and its combination with specific immuno- (fig.34), chemo- and radiotherapy allow to get a twofold increase of life duration. Taking this into account, one cannot agree with the opinion of some neurosurgeons, refusing to render surgical care to patients with malignant gliomas on the basis of data of stereotaxic biopsy even if there are prerequisites for total removal. There is no doubt, that surgical treatment cannot be expedient and justified in considerable lesions of subcortical ganglia and diffuse lesions of the brain stem, caused even by "benign" glioma, as well as in a severe somatic state of a patient. Treatment of "benign gliomas" should include neoplasm removal with subsequent radiotherapy. Pilocytic astrocytomas, resected within the limits of macroscopically unchanged tissues, are the only exception.

In conclusion it should be emphasized, that despite existing achievements problems of surgical treatment of cerebral tumors are far from their complete solution; it especially concerns basal peristem meningiomas. It should be acknowledged, that use of the most perfect methods of conventional microsurgery for removal of peristem meningiomas has come to a certain limit. Ways of exposure of cranial nerves from a tumor mass with preservation of their functions seem to be absolutely exhausted. A problem of preservation and reconstruction of functionally important vessels, in particular short branches of the basilar artery, has not been solved yet. One should give up any attempts of radical removal of meningioma under these conditions in order to preserve satisfactory quality of a patient's life. Every neurosurgeon should be well aware of that border, beyond which further efforts to remove a tumor can result in a patient's death or severe disability. However, the above-mentioned facts should not become a ground for pessimism. On the contrary, one should search for new possibilities of microsurgery development. One of them is use of microgravers capable of "reproducing pictures on a butt-end of a human hair between two heartbeats (!). It is quite probable, that a mutually complementary combination of endoscopic methods and conventional microsurgical technologies may turn out to be prospective. One more promising trend is combined use of microsurgery and the latest radiosurgical technologies (fig.35), capable of resulting in absolutely new quality of treatment of cerebral tumors in general and those difficult of access in particular. One can hope, that development of molecular genetics and genetic engineering of glial neoplasms especially will promote understanding of fundamentals of tumor growth biology.

There are some professional qualities, which are extremely important for obtaining good results in surgery of brain tumors. They are as follows: perfect mastering of microsurgical technique, ability for "three-dimensional reconstruction" of a tumor in an operative wound on the basis of CT, MRI and angiographic findings (in the absence of navigation systems), ability for constant preservation of a dry operative field, compulsory continuous visual control of each "surgical step" in combination with a gentle "surgical touch", ability of a surgeon to keep his self-control and presence of mind up to the "last stroke" of an operation.