A PATHOLÓGIA SZEREPE A SUGÁR AGYSEBÉSZET FEJLÖDÉSÉBEN

Dr. med.habil. Szeifert György
Országos Idegsebészeti Tudományos Intézet
Semmelweis Egyetem Idegsebészeti Tanszék

Stereotaxiás sugársebészet

• Célja: "a kóros, vagy normális sejteket tartalmazó meghatározott céltérfogat teljes és pontos megsemmisítése egyszeri, nagy dózisú sugárkezeléssel, a környezö szövetek károsítása nélkül."

Professor Lars Leksell (1907-1986)

Linearis accelerator (LINAC):mozgó sugárforrás és célpont

Gamma Kés:fixált sugárforrások + fixált célpont

Gamma Kés:Stockholm, 1968

CNS PROJECT for Radiosurgical Pathology

WHAT CAN WE LEARN FROM PATHOLOGY?

Leonardo da Vinci (1452-1519):first anatomical image collection

Andreas Vesalius (Brussels:1514-Jerusalem?:1564)

• First systematic anatomical lessons
• "De humani et corporis fabrica": 1543
• Totally based on human experience
• Teachings of Galenos was developed

Giovanni Battista Morgagni (1682-1771)

• Systematic human pathological-anatomy lessons
• "De sedibus et causis morborum�": 1761
• Founder of clinical pathology

Japanese anatomical studies

The basic histopathological lesion in radiosurgery

• Larsson, Leksell et al.: The High-energy Proton Beam as a Neurosurgical Tool. Nature 182; 1222-1223, 1958.
• In animal experiments "�with high-energy protons a sharply delimited lesion can be made at any desired site in the central nervous system."

The pathological effect of radiosurgery on the CNS tissue

• Degenerative changes (coagulation necrosis, endothelial destruction, apoptosis, hyaline degeneration)
• Proliferative changes (granulation tissue formation, proliferation of fibrocytes, fibroblasts, myofibroblasts, capillaries, inflammatory cells, collagen production)

Coagulation necrosis created by high energy irradiation

• Is within the target volume
• the boundary of the lesion is distinct according to the sharp radiation fall- off
• does not change in time

Radiosurgical pathology of vascular malformations

• Arteriovenous malformations
• Cavernomas
• (Capillary teleangiectasias,
• DVA: No surgery, no RS)

Incompletely obliterated AVMs

Angiographically complete AVM obliteration

Increased metabolic activity at the region of the AVM 7 years after RS

• "�increased enhancement of the nidus after contrast or gadolinium administration could persist even after obliteration of the AVM was angiographically confirmed�
• ...as long as 8 years after radiosurgery,"

Message of pathology

• Until thrombus organization has not been completed in the AVM vessels after radiosurgery, neovascularization may supply a potential source for re-bleeding.
• The role of PET examination should be considered to asses metabolic activity of AVMs after radiosurgery.

Cavernomas

40 Gy irradiated cavernoma(fractionated)

The message of pathology

• The irradiation evokes endothelial damage,
• granulation tissue and
• scar tissue production in cavernomas as well

Radiosurgical pathology for tumors

• Cerebral metastases
• Vestibular schwannomas
• Gliomas

Message of pathology

• Patchy, inhomogeneous contrast enhancement on CT and MR images reflects necrotic tumor areas, i.e. hypoxic neoplastic tissue.
• Lesions demonstrating a similar radiological pattern require higher doses (18Gy minimum or more) to obtain control.

Vestibular schwannoma

Message of pathology

• Supports the hypothesis that vascular endothelial cells are the principal targets of single high-dose irradiation.
• The loss of central contrast enhancement of tumor tissue following radiosurgery might be consequence of the vascular damage.

Malignant astrocytic tumor(C-11 Methionine PET)

Message of pathology

• Morphological re-differentiation can occur in malignant astrocytic tumor after radiosurgery.
• Radiosurgery may promote some degree of restoration of the p53 gene tumor suppressor function.

Experimental radiosurgical pathology

• Animal experiments
• Tissue culture studies

What can we learn from pathology?

• "The future of radiosurgery will be built on three foundations.
• First, a better understanding of the biologic effects of radiation will enable treatment of new disorders.
• Second, technologic advancements�
• Third, new clinical applications will derive from radiobiological knowledge�"

Radiosurgical pathology

• Is it a new subspeciality?
• Do we need it?
• Quo vadis?

"Mortui vivos docent"