What causes brain tumours?

The short answer is that no-one knows why brain tumours occur. There are many theories, some of which are scientifically sound, others being nothing more than speculation. Here are some of those theories. Please remember that no definitive cause has been found and therefore we should not draw any firm conclusions based on non-factual information:

GENETIC

Arguments for this theory are mostly based on the close association between some congenital syndromes and brain tumours. There is a condition called neurofibromatosis(NF) that is characterised by multiple soft tissue tumours. The abnormal chromosome has been localised to chromosome 22 and 17. Those with NF1 may suffer from tumours anywhere along the visual tract and those with NF2 get tumours of the vestibular nerve. Also, some people with brain tumours have an over-expression of certain growth factors (PDGF) and cancer genes (proto-oncogenes) and a depletion or mutation of tumour suppressor genes (p53). These genes and growth factors are found in many people without cancer.

IONISING RADIATION

Ironically, radiation that is given in limited doses to treat patients with malignant tumours, may also cause malignant brain tumours when given in higher doses.

ELECTROMAGNETIC RADIATION (EMR)

The Scandinavians first alerted us to the adverse effects of very low frequency EMR. They showed quite conclusively that people who lived close to high tensile electrical wires were at greater risk of developing cancers, including brain tumours. To extrapolate this data to other electrical appliances may be over-reacting but it is generally accepted that one should try to limit exposure. Mobile phones emit EMR. The International Agency for Research on Cancer (IARC) have classified mobile phones as potentially carcinogenic (Grade 2B). Furthermore, the INTERPHONE study, considered the most convincing to refute the link, actually demonstrated that high usage (>30 minutes/day) was associated with a 2 times higher chance of developing brain cancer on the side of usage.

IMMUNO-SUPPRESSION

The scientific community accepts unequivocally that the immune system plays an important role in the genesis and control of any malignancy. The relative importance is disputed. Some people with brain tumours do have deficiencies in their immune system, but the majority are not immunosuppressed. Dr Teo is a strong believer in the importance of keeping the immune system primed. This can be done with exercise, a diet rich in anti-oxidants, positive thought, reduced stress and laughter.

What is a primary brain tumour?
This is a tumour that has developed from normal brain cells such as astrocytes, ependyma and oligodendroglial cells. They are often referred to as intra-axial tumours.

What is a secondary brain tumour?
A secondary brain tumour has spread to the brain from a primary tumour elsewhere in the body. Secondary tumours (in any part of the body) are also known as metastases.

What is an intracranial tumour?
These are tumours arising from structures in and around the brain, but not the brain itself. Because they are so intimately connected to the brain, they are often (inaccurately) called brain tumours.

What are the most common kinds of brain Tumours?
The most common type of primary brain tumour is a glioma. The most common type of glioma is an astrocytoma, and unfortunately the most common type of astrocytoma is the malignant variety. All other gliomas are quite rare. The next most common brain tumour is one that has spread from elsewhere in the body. This is called a secondary or metastasis. If you include all intracranial tumours under the heading of “brain tumours”, the next most common tumour is the meningioma.

What is the most important thing for patients to know about a brain tumour?
For patients, the most important thing is not so much the name of the brain tumour, but its rate of growth or biological aggressiveness and its invasiveness. There are well documented cases of so called “benign” or low grade tumours, growing very rapidly and behaving like malignant tumours and conversely there are some tumours which look malignant under the microscope but behave like a benign tumour.

CLASSIFICATION I (Intra-axial)

 

WHAT IS BRAIN CANCER?

The term “tumour” simply refers to a lump of abnormal cells. If the cells are slow-growing and unlikely to spread elsewhere, the tumour is classified as “benign” or low grade. If the cells are rapidly growing and can spread to other parts of the organ or body the tumour is “malignant”.

Brain cancer may refer to any malignant tumour within the skull. However, it has become associated with a tumour made up of malignant astrocytes, given that this type is by far the most deadly and common. Unfortunately, when someone is diagnosed with brain cancer, they immediately assume that their prognosis is terrible and without a chance of cure when indeed, some malignant brain tumours are curable (medulloblastoma and chondrosarcoma are two such cancers).

WHAT ARE THE COMMON TYPES OF BRAIN CANCERS?

The most common is the Glioblastoma Multiforme (GBM). The cells are so bizarre and abnormal that it is sometimes impossible to ascertain from which cell line they originated. They are characterised by necrosis (seen on an MRI and under the microscope), abnormal blood vessels (an attempt to provide oxygen and nutrients to the rapidly growing tumour), a high rate of multiplication (measured by the number of cells seen dividing under the microscope and the proliferation index MIB/Ki67) and characteristic molecular signatures or biomarkers ( IDH wild-type, TERT positive etc.).

The next most common is the malignant astrocytoma or Grade 4 glioma. The cells are not as poorly differentiated and therefore more recognisable as astrocytes. They have a unique biomarker called the IDH mutation. The prognosis is slightly better but still not good.

The other types of brain cancers are rare. Gliosarcoma, anaplastic astrocytoma, medulloblastoma, malignant teratoma, germinoma etc. are just some.

WHAT ARE SLOW-GROWING OR LOW GRADE GLIOMAS?

A very rudimentary way of looking at primary intra-axial brain tumours is by classifying them as Grade 1 to 4. In general, the lower the grade the better the prognosis. Grade 1 and 2 gliomas are uncommon in adults and more common in children. There are some Grade 1 gliomas that are truly benign and curable such as the juvenile pilocytic astrocytoma (JPA), ganglioglioma and DNET. Unfortunately, many low grade gliomas transform into high grade gliomas (malignant/cancer). A longitudinal study out of Europe showed that the average time between diagnosis of a low grade glioma and malignant transformation is 5.4 years.

WHAT IS A BRAINSTEM GLIOMA?

The brainstem is that part of the brain that connects the brain to the spinal cord. Not only do all the fibres that control movement and sensation pass through this structure, but it also contains vital hubs that control breathing, swallowing, hearing, balance, eye and facial movement and consciousness. Believe it or not, it is only the thickness of your thumb, so any tumour within it, no matter how small, can cause devastating problems.

In general, tumours within the brainstem can be classified as either diffuse or focal. The distinction is very important, because diffuse tumours, with poorly defined margins and with normal fibres running through them, are truly inoperable, whereas a focal tumour can be removed and sometimes the patient can be cured with surgery alone.

  1. Diffuse: These are unfortunately the most common type and are often malignant. Surgery is recommended for obtaining tissue confirmation and tissue typing. This is important because our scientists are always discovering new treatments based on tailoring chemotherapy or immunotherapy to the molecular signature of the tumour. Symptoms and signs are multiple and occur with rapid onset. No definitive radiological criteria have been proposed and consequently, some patients with focal gliomas are misdiagnosed as having a diffuse glioma…a deadly mistake!!
  2. Focal: These can occur anywhere in the brainstem and may have a cystic component (fluid) or an exophytic component (bulging outside the brainstem borders). The symptoms have often been present for years and may be very specific e.g. choking on one’s food. Most of these tumours are low grade and not malignant like the diffuse variety. Surgery, although high risk, may be curative or at the least prolong life significantly. A subset of these focal tumours are the tectal gliomas which carry a particularly good prognosis.

WHAT IS AN OPTIC GLIOMA?
These are most commonly found in patients with neurofibromatosis, a rare condition characterised by multiple tumours under the skin, in the brain and in the spinal cord. The optic glioma is often very slow growing and may never cause symptoms or signs. They should be distinguished from the more aggressive and symptomatic glioma in the same area, the hypothalamic glioma.

 

CLASSIFICATION II (Extra-axial)

MENINGIOMA

These tumours grow from the covering of the brain and the inside layer of the skull. They are typically slow-growing and benign. The primary treatment is surgery which is usually curative. If they cannot be totally removed, usually because of their location in and amongst vital nerves and arteries, they may require repeat surgery or radiation therapy. Some surgeons believe radiation should be the absolute last resort. Dr Teo is one such surgeon.

ACOUSTIC NEUROMA

These are also benign but are very intimately connected to vital nerves and arteries. The term acoustic neuroma is actually incorrect, because they are neither acoustic in origin (they grow from the vestibular/balance nerve) nor neuroma in histology (they are schwannomas). They present with hearing loss and balance disturbance and may be treated effectively with either focused radiation (radiosurgery) or surgery. The success of surgery has been shown in many studies to be directly proportional to the experience of the surgeon. Surgery may destroy what hearing is left and rarely cause paralysis of the face muscles, a very disfiguring complication.

EPENDYMOMA

These tumours grow from ependymal cells that line the ventricles and surface of the brain. Although they are glial type tumours they are considered extra-axial because they grow from the outside of the brain or the inside of the ventricles and compress and invade normal brain tissue. Every article and every study has underscored the importance of a complete removal of these tumours to give the best chance of cure or long-term survival. It cannot be stressed more that the first operation is probably the only chance of achieving this total resection and hence the importance of comprehensive and honest pre-operative discussion warning the patient and the family of inevitable neurological complications, the price of life !!

PITUITARY ADENOMA

These are very interesting tumours that require a multi-disciplinary approach. Surprisingly, there are post-mortem studies that show almost 1 in 4 people have a pituitary adenoma !!! This means that once one of these tumours are seen it doesn’t mean that it needs to be treated. Reasons for treatment include, hormone imbalance (either too much of a hormone or too little), compression of surrounding normal tissue (these structures include the visual pathways, eye movement nerves and the normal pituitary gland), headache or pain between the eyes as a result of compression of the structure that lies over the gland (diaphragma sella), fear of the tumour bleeding (apoplexy) and rapid growth. The operation is performed through the nose !!

 

The skull base is that part of the skull that separates the brain above from the soft tissue of the neck below. Many nerves (the 12 cranial nerves) and arteries (carotid and vertebral) run through the skull base. It’s not hard to imagine that any tumour arising from or involving this area presents unique challenges. Hence, the sub-specialty of Skull Base Surgery that requires extra training, expertise and a multi-disciplinary approach.

DIAGNOSING A BRAIN TUMOUR?

Although we can make educated guesses when it comes to patients with brain tumours, definitive diagnosis depends on obtaining tissue. This can only be done through surgery. The least invasive technique is a needle biopsy performed through a small hole (“burr hole”). This is sometimes performed under local anaesthetic. The overall risk of complications occurring from a needle biopsy is less than 5%.

One important downside to the needle biopsy approach is the size of the sample of tissue, sometimes resulting in incorrect results. Secondly, there is the risk of bleeding, especially when the tumour is in an area rich in blood vessels e.g. the pineal region. Alternatively, the surgeon can choose to perform a total or subtotal excision of the tumour through a larger, more invasive, approach called a craniotomy. The risk is slightly higher but the tissue yield for diagnosis is much greater.

How does neurosurgery effect the symptoms of a brain tumour?
Palliation essentially means “making the patient feel better”. Some tumours can cause symptoms of headache and drowsiness because of their large size. This is called “mass effect”. Surgery to reduce the size of the tumour may relieve these symptoms. Also, reducing the size of the tumour or completely removing it can sometimes reverse neurological deficits such as weakness and visual disturbances. Unfortunately, the surgeon is unable to predict the “reversibility” of the deficits preoperatively, as some brain tumours invade the normal brain tissue. Alternatively other brain tumours push the normal tissue aside. A general rule is that patients who improve with preoperative steroids will likely improve with surgery.

What can be the down side of ‘successful’ brain tumour surgery?
It is important that patients (and their families) consider all the potential outcomes of surgery before deciding to go ahead. Despite the surgeons’ best efforts, sometimes things may go terribly wrong. Some potential complications of surgery include, but are not confined to…

Worsening of the pre-operative neurological condition. It’s a well-known dictum that if you are perfectly normal before surgery, then there is a good chance you will be normal after surgery. Conversely, if you have some problem before surgery, you are more likely to be transiently and possibly permanently worse after surgery. This makes sense because any deficit before surgery is either due to invasion of the normal brain by tumour cells or compromise of normal tissue by the size and location of the tumour.

You can be made worse by 2 other mechanisms. Sometimes the surgeon is forced to damage normal brain tissue with the approach to the tumour or by removing the tumour. Although this is sometimes unavoidable, the surgeon can try to lessen this happening by employing techniques such as pre-operative mapping of normal brain structures, intra-operative mapping in either an asleep or an awake patient, staying within the tumour and sometimes leaving a small amount of tumour behind, intra-operative MRI scanning and the use of dyes that are preferentially taken up by tumour cells and NOT normal brain cells.

Despite all of these techniques, damage to normal tissue can still occur. One of the most disturbing features of brain surgery is a concept called “brain shift”. No matter how accurate the mapping both before and during surgery, once the skull is opened and air is allowed in, the brain shifts and one loses accuracy of any technology that depends on pre-operative maps. Even doing an MRI during the operation doesn’t compensate fully for brain shift.

The other cause for unexpected neurological worsening after surgery is vascular injury. If a blood vessel is damaged either intentionally or by accident it can cause a stroke and complications. Sacrificing a blood vessel that is clearly supplying the tumour may cause a stroke if that vessel is also supplying normal brain tissue.

You must always be aware that even if your surgeon quotes only a 1% chance of a serious problem or death, that 1 in 100 people may sadly be you. It is very rarely due to poor surgery or a careless surgeon, it is the nature of brain surgery.

What is adjuvant therapy?
In patients with cancer, adjuvant therapy generally refers to the use of chemotherapy and radiotherapy to kill cancer cells, especially those remaining after surgical removal of the tumour.

What effect does neurosurgery have on adjuvant therapy?
Younger patients with aggressive (high grade) gliomas have shown improved outcomes if most of the tumour cells have already been surgically removed. This benefit is not as applicable to older patients. Advocates of surgery say that there may be less chance of malignant transformation of tumour cells if there are less cells to transform. Those who are against surgery for low grade gliomas claim that there is the same chance for malignant transformation if there are 10,000 cells or 10 million cells. Furthermore, they also fear that surgery may invoke malignant transformation. It is very important that each patient is individually assessed.

Why offer surgery before radiotherapy or chemotherapy?
One of the most commonly accepted principles of oncological (cancer) surgery is a concept called cytoreduction. This means that chemotherapy and radiotherapy will have more of a chance of working when the bulk of the tumour has been reduced. There a few exceptions to this rule e.g. tumours that are very vascular (contain a lot of blood vessels) may be more amenable to surgery once their blood supply has been reduced, or tumours that spread when manipulated may be modified with pre-operative chemo or radiotherapy so that this doesn’t happen at the time of surgery.

What are the treatment options for low grade gliomas?
This is a controversial area. Certainly, in children, there is little doubt that surgery is indicated because of the chance of cure, the re-establishment of the normal flow of spinal fluid and the improvement surgery gives to the child’s symptoms. Even in adults, surgery can result in cure, although this is less common. Advocates of surgery say that there may be less chance of malignant transformation if there are less cells to transform. Those who are against surgery for low grade gliomas claim that there is as much chance for malignant transformation if there are 10,000 cells or 10 million cells. Furthermore, they also fear that surgery may invoke malignant transformation. For these reasons, it is very important that patients be assessed individually before any decision to operate can be made.

Needle Biopsy

What is a needle biopsy? Accurate diagnosis of brain tumors generally relies upon the analysis of affected brain tissue. The least invasive technique used to collect a tissue sample from the brain is a needle biopsy. It is performed through a small hole drilled into the skull (“bur hole”). This is procedure is sometimes performed under local anaesthetic. The overall risk of complications occurring from a needle biopsy is less than 5%.

What are the possible problems associated with a needle biopsy? An important downside to the needle biopsy approach is the small size of the tissue sample, sometimes resulting in an incorrect diagnosis. There is also the risk of bleeding, especially when the tumor is in an area rich in blood vessels e.g. the pineal region.

What is an alternative to a needle biopsy? A neurosurgeon may choose to perform a total or subtotal excision of the tumour through a larger, more invasive, approach called a craniotomy. The risk is slightly higher than a needle biopsy, but the tissue yield for diagnosis is much greater.

IS NEUROSURGERY EVER CURATIVE?

Radical macroscopic removal of low grade gliomas in children can be curative. Also, most extra-axial tumours, such as meningiomas, craniopharyngiomas and pituitary adenomas can be cured if removed totally. This cannot be said for high grade tumours in children and adults. The feasibility of curative surgery for low grade gliomas in adults remains unknown.

Is there scientific evidence for the benefit of radical resection of primary brain tumours?

Low grade Gliomas:

Laws ER Jr. Resection of low-grade gliomas. J Neurosurg. 2001 Nov;95(5):p731-2.
“Clearly, the more cells at risk, the more likely a tumor is to undergo the series of genetic events that ultimately leads to a more aggressive or malignant glioma. (Therefore), based on what we currently believe, the strategy of recommending radical resection of gliomas of the brain is probably a sound one.”

Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas:

Department of Neurological Surgery, Brain Tumor Research Center, University of California San Francisco, 505 Parnassus Ave, Room M-779, San Francisco, CA 94143-0112, USA. jsmith1enator@gmail.com
PURPOSE: The prognostic role of extent of resection (EOR) of low-grade gliomas (LGGs) is a major controversy. We designed a retrospective study to assess the influence of EOR on long-term outcomes of LGGs. PATIENTS AND METHODS: The study population (N = 216) included adults undergoing initial resection of hemispheric LGG. Region-of-interest analysis was performed to measure tumor volumes based on fluid-attenuated inversion-recovery (FLAIR) imaging. RESULTS: Median preoperative and postoperative tumor volumes and EOR were 36.6 cm(3) (range, 0.7 to 246.1 cm(3)), 3.7 cm(3) (range, 0 to 197.8 cm(3)) and 88.0% (range, 5% to 100%), respectively. There was no operative mortality. New postoperative deficits were noted in 36 patients (17%); however, all but four had complete recovery. There were 34 deaths (16%; median follow-up, 4.4 years). Progression and malignant progression were identified in 95 (44%) and 44 (20%) cases, respectively. Patients with at least 90% EOR had 5- and 8-year overall survival (OS) rates of 97% and 91%, respectively, whereas patients with less than 90% EOR had 5- and 8-year OS rates of 76% and 60%, respectively. After adjusting each measure of tumor burden for age, Karnofsky performance score (KPS), tumor location, and tumor subtype, OS was predicted by EOR (hazard ratio [HR] = 0.972; 95% CI, 0.960 to 0.983; P < .001), log preoperative tumor volume (HR = 4.442; 95% CI, 1.601 to 12.320; P = .004), and postoperative tumor volume (HR = 1.010; 95% CI, 1.001 to 1.019; P = .03), progression-free survival was predicted by log preoperative tumor volume (HR = 2.711; 95% CI, 1.590 to 4.623; P <or= .001) and postoperative tumor volume (HR = 1.007; 95% CI, 1.001 to 1.014; P = .035), and malignant progression-free survival was predicted by EOR (HR = 0.983; 95% CI, 0.972 to 0.995; P = .005) and log preoperative tumor volume (HR = 3.826; 95% CI, 1.632 to 8.969; P = .002).

CONCLUSION: Improved outcome among adult patients with hemispheric LGG is predicted by greater EOR.

Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas:

Department of Neurosurgery, The Johns Hopkins School of Medicine, and Neuro-oncology Surgical Outcomes Research Laboratory, Baltimore, Maryland 21231, USA.
OBJECTIVE: It remains unknown whether the extent of surgical resection affects survival or disease progression in patients with supratentorial low-grade gliomas. METHODS: We conducted a retrospective cohort study (n = 170) between 1996 and 2007 at a single institution to determine whether increasing extent of surgical resection was associated with improved progression-free survival (PFS) and overall survival (OS). Surgical resection of gliomas defined as gross total resection (GTR) (complete resection of the preoperative fluid-attenuated inversion recovery signal abnormality), near total resection (NTR) (<3-mm thin residual fluid-attenuated inversion recovery signal abnormality around the rim of the resection cavity only), or subtotal resection (STR) (residual nodular fluid-attenuated inversion recovery signal abnormality) based on magnetic resonance imaging performed less than 48 hours after surgery. Our main outcome measures were OS, PFS, and malignant degeneration-free survival (conversion to high-grade glioma). RESULTS: One hundred thirty-two primary and 38 revision resections were performed for low-grade astrocytomas (n = 93) or oligodendrogliomas (n = 77). GTR, NTR, and STR were achieved in 65 (38%), 39 (23%), and 66 (39%) cases, respectively. GTR versus STR was independently associated with increased OS (hazard ratio, 0.36; 95% confidence interval, 0.16-0.84; P = 0.017) and PFS (HR, 0.56; 95% confidence interval, 0.32-0.98; P = 0.043) and a trend of increased malignant degeneration-free survival (hazard ratio, 0.46; 95% confidence interval, 0.20-1.03; P = 0.060). NTR versus STR was not independently associated with improved OS, PFS, or malignant degeneration-free survival. Five-year OS after GTR, NTR, and STR was 95, 80, 70%, respectively, and 10-year OS was 76, 57, and 49%, respectively. After GTR, NTR, and STR, median time to tumor progression was 7.0, 4.0, and 3.5 years, respectively. Median time to malignant degeneration after GTR, NTR, and STR was 12.5, 5.8, and 7 years, respectively.

CONCLUSION: GTR was associated with a delay in tumor progression and malignant degeneration as well as improved OS independent of age, degree of disability, histological subtype, or revision versus primary resection. GTR should be safely attempted when not limited by eloquent cortex.

Malignant Gliomas:

Lacroix M. et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001 Aug;95(2):p190-8.
“Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.”

Nitta T, Sato K. Prognostic implications of the extent of surgical resection in patients with intracranial malignant gliomas. Cancer 1995 Jun 1;75(11):p2727-31.
“The favorable prognosis of patients with malignant gliomas depends upon the total resection of these tumors.”

Chandler KL et al. Long-term survival in patients with glioblastoma multiforme. Neurosurgery 1993 May;32(5):p716-20.
“Among patients with glioblastoma multiforme, long-term survival is most likely for those who have a long disease-free interval after the initial diagnosis and receive multimodal therapy, including aggressive tumor removal.”

Why do people with brain tumours need steroids?
Steroids, in the form of dexamethasone, are extremely effective in reducing the swelling that results from the tumour. They do NOT reduce the size of the tumour itself (the only exception being primary lymphoma of the brain). Some tumours cause more swelling than others e.g. malignant gliomas and meningiomas seem to create an extraordinary amount of vasogenic oedema (swelling). Once the tumour has been removed the steroids can be stopped. The prescription of dexamethasone does not replace a deficiency in the patients own steroid production.

Can steroids be stopped “cold turkey”?
The short answer is yes but there are 3 situations where they need to be tapered slowly. If the patient has been on steroids for any length of time, usually more than 2 weeks, the body gets a little lazy and stops production of its own (intrinsic) steroids (cortisol). Of course, the body will sense the need to secrete its own cortisol eventually, but this may take a few days. The longer the patient takes extrinsic steroids, the longer it takes to return to normal cortisol production. The second situation is when there is residual tumour. Even small amounts of tumour can generate enormous degrees of swelling resulting in a worsening of symptoms such as headache when the steroids are stopped. Finally, tumours that involve the pituitary gland may destroy cortisol production, and similarly, surgery to remove tumours from the pituitary region may result in diminished ability or total inability to secrete cortisol. To determine the ability of the body to resume cortisol production requires special tests and consultation by an endocrinologist.

Why can’t a patient with a brain tumour take steroids indefinitely?
Unfortunately, steroids have many bad side effects apart from the obvious one of depressing intrinsic cortisol production. They reduce the ability of the brain to recover from an insult. This is called “plasticity”. They suppress the immune system resulting in more chance of infection. They worsen and sometimes “cause” diabetes. In high doses they can cause Cushing’s Syndrome. This is a condition that is characterised by protein wasting, fat redistribution causing a fat face and abdomen, thinning of the skin, osteoporosis, bruising, acne, psychosis etc.

Pineal cysts are benign fluid filled cysts of the pineal gland. Their etiology is unknown but is thought to be a form of degeneration of normal pineal tissue. They are a common finding in the normal population. Occasionally they grow and may cause pressure on surrounding neural structures. If they compress the underlying “aqueduct of Sylvius” they may result in hydrocephalus and subsequent raised pressure. If they compress the underlying tectal plate, they may cause problems with eye movement resulting in double vision and blurred vision. Uncommonly they may cause other symptoms related to compression of other parts of the brain in close proximity to the pineal gland. These symptoms vary tremendously from sensory disturbance to fluctuations in level of consciousness.

It has always been contentious whether pineal cysts have the potential to cause headache and symptoms of pressure without CT or MRI evidence of hydrocephalus. Those who believe they can presume that the cysts cause intermittent CSF obstruction especially with changes in posture or any activity that might result in distension of the cerebral veins (…which are in close proximity to the pineal gland). Those who don’t believe that pineal cysts can cause headache are in the majority of neurosurgeons and neurologists.

The only valid way of knowing if someone’s symptoms are related to the pineal cyst is by removing it. Unfortunately this is easier said than done. Access to the pineal region is difficult and treacherous. Very few neurosurgeons have had a lot of experience operating in this delicate area. Some surgeons have proposed an operation to bypass the aqueduct called an endoscopic third ventriculostomy (ETV). This would address the symptoms if they were due to intermittent CSF obstruction but we know from other pathologies that headache may also be due to local pressure effect which would not be helped by an ETV.

This article published in the Journal of Neurosurgery highlights the excellent results seen after resection of pineal cysts in a very select group of patients. Before surgery was contemplated the patient had to be seen by a neurologist to exclude other causes of headache, the MRI had to show partial obstruction of the aqueduct and the symptoms had to strongly suggest intermittent compression of structures around the pineal gland. The article was rejected for many years and for very good reason. Unfortunately we did not have objective evidence of success. Without this objectivity the apparent success may have been due to the placebo effect. Furthermore, the assessment of success was initially made by our team, which could have added subjective bias. It was eventually accepted because every year for the last 4 years separate and unbiased physicians have reviewed the results and all have concurred that they are authentic. Furthermore, placebo is unlikely to have a lasting and consistent effect.

The greatest fear from this publication is that neurosurgeons inexperienced in surgery for pineal lesions will offer surgery to desperate patients with devastating outcomes. Complications from surgery in this region are typically very severe. They include death, short-term memory loss, paralysis, sensory disturbance, temporary and permanent eye movement paralysis, coma etc. etc.

Any patient who believes that they have a symptomatic pineal cyst should make an appointment to see Dr Teo for a personal consultation.

Once you are diagnosed with a brain tumour your whole world turns upside down and inside out. You go though the emotional reactions of “why me”, “what did I do wrong” and “who do I trust”. It’s a roller coaster ride that you don’t wish upon your worse enemy.

Here are some helpful tips on how to navigate the minefield….

DON’T READ DR GOOGLE… and if you do, don’t trust everything you read or hear. Remember that information on the internet is not peer-reviewed and often anecdotal.

GET A SECOND OPINION….. one of my beloved patients wrote a book called “Three quotes from a plumber” which documented her journey after diagnosis when she innocently trusted her first and only opinion and was mislead, had inadequate surgery and paid a terrible price for not getting a second opinion which would have been diametrically opposite to the first.

ASK CONFRONTING QUESTIONS?…. many patients are too scared to challenge their doctors. There is no harm in asking about their experience with your type of condition. There is no harm is bringing up alternative treatment options. Indeed, if a surgeon is offended by a confronting question, such as “what do you think about Dr X or this different approach” then it invariably means that he/she is threatened. That means insecurity about his/her own talents or knowledge…..a RED FLAG!!

CHOOSE THE DOCTOR WITH WHOM YOU HAVE UTMOST FAITH AND CONFIDENCE…. if you feel immediate comfort and trust with your surgeon, then that is arguably the most important step in your journey. Remember, if things go wrong, you need to be able to find solace that it was your choice and you were “hoping for the best, prepared for the worst”.

A doctor cannot and should not make idle and unsubstantiated claims of their results. It is incumbent on a surgeon to publish their results showing honest evaluation of how their results compare with the standard outcomes. It is also imperative for a surgeon to report their bad outcomes, no matter how difficult this is to do.

The following are a few of Professor Teo’s publications in peer-reviewed journals comparing his results with the average:

CRANIOPHARYNGIOMA

Teo C “Application of endoscopy to the surgical management of craniopharyngioma” Childs Nerv Syst 21:696-700, 2005                        This paper demonstrated a clear advantage of a keyhole eyebrow approach for the radical and curative resection of craniopharyngiomas. There were NO hypothalamic complications in “virgin” patients. Unfortunately, it showed a 95% incidence of post-op DI and some very poor outcomes with repeat surgery after previous radioRx.

 

TRIGEMINAL NEURALGIA

Teo C, Nakaji P, and Mobbs RJ. “Endoscope-assisted microvascular decompression for trigeminal neuralgia”. Neurosurgery 59(2):ONS-489, 2006.              This small series of only 150 patients showed a higher than average successful microvascular decompression rate with the use of a 30 degree endoscope to examine the CPA. This paper was reviewed by Jannetta himself who conceded that the higher success rate was likely due to the identification of offending vessels that were seen with the endoscope but were hidden from the microscope.

 

COLLOID CYSTS

Greenlee JD, Teo C, Ghahreman A, Kwok B “Purely endoscopic resection of colloid cysts” Neurosurgery 62:51-55, 2008                        This is one of the largest series of endoscopic resection of colloid cysts that shows that you don’t have to accept a lower complete resection rate when compared to open resection. We have only had 2 recurrences in 88 patients followed for an average of 7 years.

 

BRAINSTEM GLIOMAS

Teo C, Siu TL. “Radical resection of focal brainstem gliomas: is it worth doing?Childs Nerv Syst Nov;24(11):1307-14, 2008

In this paper there is a Kaplan-Meyer curve showing excellent long-term survival with radical total removal of focal brainstem gliomas with excellent clinical outcomes. Most patients fell into the excellent or good outcome categories

Faulkner H, Arnaout O, Hoshide R, Young IM, Yeung JT, Sughrue ME, Teo C.” The Surgical Resection of Brainstem Glioma: Outcomes and Prognostic Factors.” World Neurosurg. 2:S1878-8750(20)32349-4. Feb 202

This is the largest series of surgical patients with brainstem gliomas showing excellent results.

 

INOPERABLE TUMOURS

Teo C, Broggi M. “Surgical outcome of patients considered to have “inoperable” tumors by specialized pediatric neuro-oncological multidisciplinary teams” Childs Nerv Syst 26(9): 1219-1225; 2010                       

This is the small but impressive series of 47 patients all having been sent home to die with “inoperable” tumours. Some were in extremis/close to death. Of the 47 patients 32 were alive and well after surgery. Some have since died but there are over 20 who were cured !!!

 

PINEAL TUMOURS

Broggi M, Darbar A, Teo C “The value of endoscopy in the total removal of pineocytomas” Neurosurgery 67[ONS Suppl 1]:159-165, Sept, 2010

The OS in this series is greater than in any other published series of pineocytomas….100% !!!! Not a single patient had post-op radio or chemoRx. I believe the results were due to minimally invasive endoscopic-assisted resections ie. NO residual tumour within or hidden by the deep vein complex.

Of the patients who died, not a single one regretted having the surgery despite one of them only living an extra 6 weeks.

 

POSTERIOR FOSSA TUMOURS

Wait S, Gazzeri R, Galarza M, Teo C “Simple, Effective Supine Positioning for the Retrosigmoid Approach” Minim Invas Neurosurg 54:196-198, 2011                       

This paper looked at our series of 890 keyhole retro-sigmoid craniotomies for various pathologies. We only had 2 clinically-significant post-op collections and only a single case of post-PF craniotomy headache cf. 10% in the literature.

 

PITUITARY ADENOMAS

Teo C, Wait S “Endonasal Approach to Tumors of the Pituitary Fossa; a shift in the treatment paradigm” Clin Neurosurgery 58: 79-83, 2011                        

This was presented at the CNS in 2011 and was the first to show that cavernous sinus invasion by non-malignant pituitary adenomas does not confer a negative prognosis if one uses the extended endonasal approach. This has since been reproduced by the Chinese (Tiantan Hospital in Beijing). It’s all about the ability to look into the CS with angled endoscopes and instruments.

 

CEREBRAL METASTASES

Gazzeri R, Nalavenkata S, Teo C “Minimally invasive key-hole approach for the surgical treatment of single and multiple brain metastases” Clin Neurol and Neurosurgery 123;117–126, 2014

This was not a very impressive paper because numbers were small, but it did show that most patients were discharged within 24 hours of surgery, whether there were single or multiple lesions removed.

 

RECURRENT BRAIN CANCER

Sughrue M, Sheean T, Bonney P, Maurer A, Teo C. “Aggressive Repeat Surgery for Focally Recurrent Primary Glioblastoma: Outcomes and Theoretical Framework” Neurosurgical Focus 38-3, Page E11, 2015

This series is the MOST important for supporting the practice of offering surgery to those patients with recurrent malignant tumours who are facing certain death invariably within days to weeks of being diagnosed with their recurrence. The old dictum of second surgery only buying you half the time as the first surgery is incorrect. Aggressive, pro-active surgical management of recurrent GBM is worthwhile. What is NOT clear is which patient will benefit and in which patient it will be futile.

 

THE ADVANTAGE OF A KEYHOLE APPROACH

Sughrue ME, Bonney PA, Choi L, Teo C. “Early Discharge After Surgery for Intra-Axial Brain Tumors” World Neurosurg;84(2):505-10, Aug, 2015

This is a simple paper that demonstrates that rapid discharge after uncomplicated craniotomy is feasible. Our average LOS is 1.5 days !!!

 

INSULAR GLIOMAS

Sughrue ME, Othman J, Mills SA, Bonney PA, Maurer AJ, Teo C. “Keyhole Transsylvian Resection of Infiltrative Insular Gliomas: Technique and Anatomic Results” Turk Neurosurg; 26(4):475-83, 2016

This is one of the largest series of insular gliomas in the literature. Although my complication rate is higher than Dufau and Berger, 8% vs 3%, my complete resection rate is significantly higher. If you include all the insular gliomas that I have done at AIIMS in Delhi, NUH in Singapore and Duke in the USA, it is the largest in the world.

Sughrue M, Bonney PA, Burks JD, Othman J, Baker C, Glenn CA, Teo C. Multilobar Insular-Involving Gliomas: Results with Hyperaggressive Resection. Cureus;9(8):e1623. Aug 2017

This shows the same results in a larger series.

 

GLIOMAS OF ALL GRADES

Hoshide R, Teo C Neuroendoscopy to Achieve Superior Glioma Resection Outcomes. Neurosurgery 1;64(CN_suppl_1):139-143; Sept 2017

This is a technical/feasibility paper showing that complete resection rates are better than the published literature, using endoscopic assisted techniques

 

ACOUSTIC NEUROMA

Hoshide R, Faulkner H, Teo M, Teo C. Keyhole retrosigmoid approach for large vestibular schwannomas: strategies to improve outcomes. Neurosurg Focus;44(3): Mar 2018

This paper was researched and written by my fellow, who worked with some of the best acoustic neuroma surgeons and thought my technique was good. When he asked me to review my results, I reluctantly agreed thinking it might show inferior results. This series looked at facial preservation rates and degree of resection rates for large acoustics >3cm. Our facial preservation rate was better than Samii’s !!! ALL surgeries were done through a keyhole (<2cm diameter opening) retrosigmoid approach.

 

OLIGODENDROGLIOMAS

Profyris C, Chen E, Young IM, Chendeb K, Ahsan SA, Briggs RG, Sughrue ME, Teo C. “Anaplastic Oligodendroglioma – Is Adjuvant Radiotherapy Mandatory following Maximal Surgical Resection? Grade 3 Oligo Radiotherapy”. Clin Neurol Neurosurg;200:106303. Jan 2021

This series is probably the one of which I am most proud. For the last 20 years I have had a percentage of patients who are philosophically opposed to radiotherapy and who elect to be treated with surgery alone, which is against all recommended guidelines. Rather than coerce them to have adjuvant therapy, I have supported their decision and have offered repeat surgery for recurrence multiple times in several patients. This paper shows very clearly that with aggressive and accurate surgery, the long-term survival is as good as and arguably better than BST (best standard treatment). They do not have the quality-of-life issues of patients who have had radiotherapy and the Kaplan-Meir curve in this series shows that most are still alive and functional at the current time. Therefore, survival curves will likely show OS (overall survival) figures better than BST.

 

MALIGNANT SKULL BASE TUMOURS

Yeung JT, Caminer DM, Young IM, Sughrue ME, Teo C. “Radical exenteration of the skull base for end-stage, locally advanced sinonasal malignancies: Challenging the dictum of unresectability.” World Neurosurg. 26:S1878-8750(21)00285-0. Feb 2021

This series ianswers the question “how worthy is surgery in the management of futile cases that MDT’s have determined are inoperable?”. It showed that there is a role for surgery but with a predictable associated greater risk of complications and even peri-operative death.

 

PINEAL CYSTS

Yeung JT, Young IM, Profyris C, Katsos K, Sughrue ME, Teo C. Resection of Symptomatic Pineal Cysts Provides Durable Clinical Improvement: A Breakdown of Presenting Symptoms and Lessons Learned. World Neurosurg. 23:S1878-8750(21)00457-5. Mar 2021

This is the second publication on the efficacy of surgery for pineal cysts. It is the largest series in the world and demonstrates the same excellent results with minimal morbidity. It is likely to change the management paradigm for this controversial disease entity