Unit 14 Week 4: Brain tumour

Question 1

What is the use of TNM scale in cancers?

Answer 1

Pathological staging - general state of the tumour right now
Tumour size - 1 to 4 (large)
Regional lymph node involvement - 0 to 3
Distant metastasis - 0 or 1.
Can be further scored using a/b/c - norm specific to cancer type.

Question 2

What are the different stages of cancer?

Answer 2

Stage I - small and contain in starting organ
Stage II - large than in stage 1, may spread into nearby lymph nodes
Stage III - larger, spread into surrounding tissues and nearby lymph nodes
Stage IV - metastasis cancer.

Question 3

What is the TPM scheme of Nottinghal staging scheme of cancer?

Answer 3

In breast cancer:
Tubular differentiation - the proportion of cells that still resemble differentiated glands
Nuclear Pleomorphism - varing shape and size
Mitotic cell count - proliferation rate
Each section scored 1-3, added up to give total score

Question 4

What are the features of grade 1 tumours by the TPM scale?

Answer 4

Combined score of 3-5
T - more than 75% form glnands
N - uniform, small nuclei similar in shape and size to non-cancerous
M - normal or slightly elevated

Question 5

What are the features of Grade 2 breast cancer via TPM grading?

Answer 5

T - 10-75% glandular
P = moderate variability, vesicular nuclei, prominent nucleoli
M = 8 to 10 mitosis per 10 high power fields.

Question 6

What are the features of grade 3 breast cancer via TPM?

Answer 6

T - less than 10% cell form glands
P - vesicular nuclei, prominent nucleoli, varied in shape and size
M - more than 16 mitosies per 10 high power fields.

Question 7

What is the mechanism of action of trastuzumab in breast cancer?

Answer 7

Clinical: HER2 positive breast cancer
Chem: humanized monoclonal antibody.
Pharm: non-competitive inhibitor of the extracellular domain of TKR Her2.
Physio: Prevent dimerisation and phosphorylation/cleavage of Her2.
Inhibits the Ras signalling pathway - no cell proliferation
inhibits the PI13 AKT pathway - no cell growth (Protein synthesis, lipid synthesis)
Reduces cancer cell growth

Also drives antibody-dependent cell-mediated cytotoxicity and Her2 endocytosis and degradation.

Question 8

What are some different drug treatment options for breast cancer?

Answer 8

Pharmacology: HER2 inhibitors (trastuzumab), Antibody-drug conjugates (T-DM1), TKI (lapatinib).

Question 9

How is local radiotherapy used to treat breast cancer?

Answer 9

Local radiotherapy - CT/MRI/PET to image cancer, high energy rays from machine directed to cancer, ROS cause oxidative damage, DNA damage disrupts cell function - cell cycle arrest or apoptosis

Question 10

What is the usefulness of systemic chemotherapy to treat breast cancer?

Answer 10

Targets micro-metastases and distant metastases
Often adjuvent to surgery and radiotherapy
Use of drug based on cancer stage, subtype and treatment goals
General: disruption of DNA synthesis and mitosis, induction of apoptosis

Question 11

What is the use of dexamethasone in the treatment of brain tumours?

Answer 11

Chem - steroid, hydrophobic
Class - glucorticoid
Pharm - Insignificant mineralocorticoid activity​
Significant glucocorticoid activity​ - cytoplasmic GR– heterodimerizes – dissociated from heat shock proteins – translocate to nucleus – acts as transcription factor at GRE:​
Trans repression – COX-2, iNOS, PLA2, TNFalpha, VEGF​
Transactivation – Annexin A1, IL-10
Physiology:​
Decrease blood vessel permeability = maintained BBB integrity -> reduce cerebral oedema. ​
Reduce immune cell migration – reduce indirect inflammatory damage to brain region surrounding the tumour.
Clinical: Iv injection then oral - treat cerebral odema association with brain tumour.

Question 12

What is the process underpinning the headache pain sensation?

Answer 12

headache - from raised ICP in meninges which have nociceptive innervation (Brain parenchyma does not)
Trigeminal nerve - innervates the anterior and middle cranial fossa
Vagus nerve - innervates the posterior cranial fossa
All project to the trigeminal sensory nucleus in the brainstem.
Trigeminal leminiscus axons desicate to the contralateral side in the brainstem
Project and synapse in the ventromedial nucleus of the thalamus
Thalamocortical projections to S1.

Question 13

What is important about the gustatory neuroantaomy?

Answer 13

Three different cranial nerve inputs, the facial nerve (7) for anterior 2/3 the glassopharangyeal nerve post 1/3 and the vagus for the larynx,
All project to the nucleus of the solitary tract in the brainstem.
Project to the VPM nucleus of the thalamus
Project to the gustatory cortex in the insular lobe.
With some projections to the gustatory cortex in the frontal lobe.

Question 14

What are the roles of the association motor cortexes?

Answer 14

BA6 Supplementary motor area - concerned with internally generated movements
Ba6 -The premotor area - concerned with externally generated movements
Responsible for intention of motor activity.

BA8 - Frontal eye fields - directs eye movement
BA44/45 Brocas area - language production/speech.

Question 15

What can be seen on a MRI of a brain tumour?

Answer 15

Check for midline shift
Mass effect - compression of nearby structures (particularly the ventricles of soft tissue, due to a space occupying lesion and inc ICP.
Evidence of odema - vasogenic odema halo.

Question 16

What is the actual cause of a headache sensation?

Answer 16

Raised ICP
Pain due to increased pressure on the meninges.

Question 17

What are the different ways that ICP can be raised?

Answer 17

• Impaired lymphatic drainage
• Venous sinus stenosis - results in increase venous sinus pressure - confounding reduced drainage of CSF across arachnoid granulations
• Increased CSF production at the choroid plexus
• Obesity (adipokeines), female sex hormones, and other thomrbophilic of inflammatory factors can increase the risk of this.

Question 18

What are some consequences of raised ICP that can be identified on a MRI?

Answer 18

a. Empty sella turcica
b. Distention of the optic nerve sheath
c. Hypoplastic transvre sinus
d. Flattening of posterior globes (eyeballs)

Occur due to raised ICP - increase pressure on the meninges

Question 19

What are the different types of cerebral odema?

Answer 19

Cytotoxic oedema - cell swelling due to raised ICF, norm due to cellular injury of dysfunction e,g stroke or trauma
Ionic oedema - accumulation in ECF, osmotic shift due to ion imbalance, may be due to damage to BBB e,g tumour
Vasogenic oedma - disruption of BBB, extravasation of serum proteins and fluid into brain parencyhma e.g tumours. .

Question 20

Herniation, is a severe consequence of rasied ICP. What are the different types of herniation?

Answer 20

Transcalvarial (out of skull) - depdent on area
Subfalcine (under falx cerebri) - can affect gustatory cortex and M1, often contralateral leg weakness
Transtenotorial or uncal - affect eye movements, affect CN3
Tonsilar - heart rate and respiratory rate abnormalities

Question 21

What is a wide local area excision for breast cancer?

Answer 21

When a tumour or lesions is removed alongside surrounding normal tissue
Norm check histopathology to ensure clear marging around tumour to see if repeat needed (radial margin - distatnce of disease to the excision edge of the specimen)

Question 22

What is the practicality of an image guided needle core biopsy for beast cancer?

Answer 22

Imaging - US, MRI or X-ray
Core needle biospy - hollow needel to take out piece of breast tissue may be spring loaded or vaccuma-assisted.

Question 23

What is a mammogram?

Answer 23

X-ray of the breast - often from oblique and craniocaudal view.
Sensitivity is age dependent - less effective in younger women with denser breast tissue
Used in Breast cancer screening - every 3 years between 50 and 71yrs for females.
Stereotactic breast biopsy - combines images from different angles to use to target impalpable breast lumps for biopsy.

Question 24

Why are some headaches worse in the morning?

Answer 24

respiratory depression during sleep means raised pCO2 and less oxygen to brain parenchyma -> vasodilation of cerebral vessels -> increase cerebral odema -> hence worse headache as more pressure on meninges.

Question 25

What different regions in the brain can be affected by a lesion to cause symptoms?

Answer 25

Insula - taste
Parietal lobe - sensation
Frontal - movement (M1), brocas, congitive process
Temporal - wernicks area, auditroy cortex,
Occipital - vision
Smell -olfactory bulb, pressure from overlying frontal cortex

Question 26

What are some key symtpoms of raised ICP?

Answer 26

Seizures
Nausea/vomit
Confusion
Headaches
Visual disturbances

Question 27

What are the symptoms of lesions in the cerebellum?

Answer 27

Dysdiadochokinesia (difficulty performing rapidly alternating movements), dysmetria (inability to control the range of movements accurately)
Ataxia (lack of coordination of voluntary movement)
Nystagmus (involuntary rhythmic eye movements)
Intention tremor
Slurred speach
Hypotonia

Question 28

What is the role of the hospice at home team?

Answer 28

End of life care offered at home
GP can arrange for communities nurse to come to patient homes, also specialist care from community palliative care nurses
Provide:
Pain and symptom management
Personal care - bathing and dressing
Emotional support - counselling and therapy
Medication management - organising and adminstrating
Practical support - meal prep an house keeping