Advances in neurosurgery allow entire brain tumors to be removed

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 Advances in neurosurgery allow the removal of brain tumors in their entirety

Photo: Photo courtesy View of the operating room during a fluorescence-guided surgery

One day last February, Amélie (fictitious name), aged 15, was struck by intense headaches that persisted despite taking acetaminophen. Two days later, her headaches cut her appetite and even made her vomit. Worried to see their daughter in this state which is nothing like her usual, Amélie's parents bring her to the emergency room of the CHU Sainte-Justine. After conventional inconclusive tests, it was decided to have him undergo a CT scan (scan), which then revealed a mass in the brain. Magnetic resonance imaging (MRI) then confirms that it is indeed a tumor located in the left hemisphere of the brain. Amélie's parents are then shocked, devastated.

But Dr Dominic Venne, neurosurgeon at CHU Sainte-Justine, reassures them. “He explained to us that this tumor required surgery, because there were no other treatments to cure our daughter.He presented us with the advantages and possible disadvantages of this operation, and told us that in principle, our daughter could return to her normal life after the surgery. He then offered to carry out this intervention as soon as the operating room was available”, says Amélie's father.

Dr Venne also told them that he would use a new technique. to remove all of the tumor tissue, which should increase the chances of survival.

A resounding success

The extraction finally takes place on February 16 last. After more than 10 hours in the operating room, the neurosurgeons inform the parents that the intervention was a great success.

This success was made possible thanks to two state-of-the-art techniques employed at the CHU Sainte-Justine: fluorescence-guided surgery and intraoperative physiological monitoring. For the past year, 5-aminolevulinic acid (5-ALA, trade name Gleolan) has been administered orally, four hours before general anesthesia, to young patients who are about to have an operation to a high-grade (i.e. very malignant and rapidly growing) malignant brain tumour. It is most often a glioma that has originated within the glial cells of the brain, these cells serving as support for neurons.

Once ingested, 5-ALA is absorbed specifically by malignant brain tumors and cancer cells that have invaded the surrounding tissue, which metabolize it into a substance which, when exposed to blue light, fluoresces either a red, pink or dark orange color.

< p>“The problem we have in neurosurgery is that brain tumors are not well demarcated, they don't have a capsule, no wall like in other tissues. The white light microscope with which we perform our surgeries allows us to see if the tissue is more solid or more friable, if it is more vascularized, if it has a different color, but there comes a time when everything becomes pearly white, and there the tumor becomes indistinguishable. It is then very difficult to differentiate between normal tissue and tumor, especially since high-grade tumors are very aggressive and often invade adjacent tissue. However, when the tumor merges into the normal brain tissue, the resection of the tumor [which we strive to do] often turns out to be partial or subtotal. It often happens that we think we have removed everything, but that the magnetic resonance examination that we do during the operation reveals to us that there is still some left, “explains Dr. Dominic Venne, head of the surgical department.

However, to change the prognosis, more than 95% of the tumor visible on magnetic resonance must be resected. “You have to remove as much tumor tissue as possible in the case of glial tumors so that then adjuvant treatments, such as chemotherapy or radiotherapy, are more effective,” he adds.

More complete resection

The use of 5-ALA greatly promotes the achievement of such an objective. Studies in adults have shown that it achieves a more complete resection in almost twice as many patients, almost 65% of them, compared to 36% with the standard technique, resulting in an increase survival at six months after diagnosis. “It's definitely not the perfect cure yet, but it buys us time, because right now research is moving very quickly in the neurosciences, especially for brain tumors in children. “, specifies the neurosurgeon.

“We always start the operation with white light, which allows us to see everything: the brain, which is a little pink, and the blood vessels, which are red. It's safer, because when you switch to blue light, everything becomes very dark, almost black. We must turn off all the lights in the room so that the surgeon's retina gets used to the darkness. Then suddenly the tumor tissues that have metabolized the Gleolan start emitting a dark red or pink light. It's very spectacular, “explains the specialist.

Working with blue light is therefore more delicate, there is the danger of damaging a blood vessel, for example, he points out. “For this reason, most of the resection is done with white light. Then, we switch to blue light for a few minutes to see the tumor residues that we have left, then we go back to white light. This alternates between blue light and white light. »

“When we operated on Amélie, Gleolan allowed us to excise the entire tumor. After resecting most of the tumor under the microscope with white light, I was sure I had removed everything, but when we switched to blue light, I realized that there were still some islands of tumor cells, which we saw in different places thanks to their pink fluorescence. We then continued the resection,” says Dr. Venne.

Strategic areas of the brain

The large tumor that threatened Amélie's life was located in the left hemisphere of the brain, where the language center is located, and deep below the motor cortex, which regulates the motor skills of the whole body. To ensure that these strategic areas of the brain were not damaged, we used intraoperative physiological monitoring (MPIA), the principle of which had been developed by Dr. Wilder Penfield, founder of the Montreal Neurological Institute.< /p>

We therefore placed electrodes on the entire surface of Amélie's brain, arms and legs which continuously recorded the nervous activity – electrical – circulating between her cerebral cortex and her limbs. These electrodes allowed the electrophysiologist to stimulate the muscles of different parts of the body and to collect the electrical signals triggered by these stimulations on the surface of the cortex. And conversely, to stimulate precise points of the cortex and to collect in the periphery the signals induced by these stimulations.

“We were thus able to know precisely which area of ​​the cortex controlled the motor skills of each of the parts of the body on the right side [because the motor cortex of the left hemisphere controls the opposite side of the body], which made it possible to delimit precisely Amélie's entire motor cortex before starting surgery. We were then able to open the brain in a safer area and reach the tumor without damaging the motor cortex,” says Dr. Venne.

During the operation, the MPIA system also alerted the surgeon if he got too close to a motor area or the center of language.

“It happens that after surgery, patients have muscle weakness, paresis (partial or slight paralysis) which can be corrected by physiotherapy. But thanks to the MPIA, we reduce these neurological deficits and, as a result, the average length of hospitalization,” emphasizes Dr. Venne.

After their operation, young patients now have access to “targeted chemotherapy which is much better tolerated and more effective”, adds Dr. Venne. “Pathologists used to give us a diagnosis [i.e. identify the type of tumor] after looking at the tumor under a microscope. Now, they go much further, they determine the molecular signature, or genomic, of the tumour, which allows the oncologist to choose more appropriate, even personalized chemotherapy. Targeted therapies for children are in full development. They are changing the way we work. Five or six years ago, spinal cord astrocytomas and optic pathway tumors were excised. Now, neuro-oncologists only ask for a biopsy to identify the type of tumor and determine the targeted therapy that corresponds to it. It is no longer necessary to remove the tumor, and it saves us from doing very big surgeries which are often very risky,” he says.

Twenty-four hours after waking up, Amélie was going already very well. “After the operation, I had lost control of the right side of my body a bit. Suddenly, I had a little trouble walking, because my right leg no longer worked as before. But I quickly recovered [thanks to physiotherapy] and I feel much better than before the operation,” says Amélie, who has returned to school and even found herself running spontaneously, for the biggest happiness of his parents.