Pharyngeal carcinoma

Source: OHCS pg 570

• Often advanced at presentation.
• M:F = 5:1.
• Histologically, 85% are squamous.
• Typical pt: Elderly smoker with sore throat, sensation of a lump, referred otalgia, and local irritation by hot and cold foods.
• Risk factors:
  - Chewing or smoking tobacco.
  - Alcohol alone is not a risk factor but is synergistic with smoking.
  - Oral HPV (especially HPV-16) infection.
• 30% of pharyngeal SCCs will have a second primary within 10y.
• 20% are LN positive at presentation.
• Hypopharyngeal tumours may give dysphagia, voice alteration, otalgia, stridor, throat pain; trismus is a late sign.
• Note any sign of premalignant conditions:
  - Leukoplakia.
  - Paterson-Kelly-Brown syndrome (Plummer-Vinson): Pharyngeal web associated with iron deficiency, glossitis, koilonychia: 2% risk post-cricoid ca.
• Imaging: MRI with STIR (short tau inversion recovery), contrast-enhanced CT.
• Rx: Surgery, sometimes with:
  - Jejunal flaps.
  - Tubed skin flaps (e.g. radial forearm or anterolateral thigh flaps).
  - Gastric pull-ups.
• Rx: Radiotherapy (e.g. intensity-modulated) may be used first line if the tumour is small. i.e. T1 (less than 2cm) or T2 (less than 4cm).
• T3 = >4cm, T4 = beyond oropharynx.

Inhalational agents

These are volatile liquids which readily vaporise, permitting administration by inhalation in oxygen-enriched air or an O2/N2O mix.They help maintain anaesthesia and decrease awareness (by an unclear mechanism).

Halothane

A colourless, pleasant-smelling gas (which, unlike the other agents, is not an ether). First used as an anaesthetic in the 1950s. It has little analgesic effect, but decreases cardiac output (vagal tone increased, leading to bradycardia, vasodilation, hypotension. It sensitises the myocardium to catecholamines (beware in patients with arrhythmias and in surgical infiltration with local anaesthetic and adrenaline). Halothane has now been replaced by safer inhalational agents due to the rare but serious complication of post-op hepatitis (uo to 1 in 4,000 for multiple exposures).

Isoflurane

A halogenated ether. Theoretically induction should be quick, but isoflurane is irritant, so coughing, laryngospasm, or breath-holding may complicate the onset of anaesthesia.

Sevoflurane

Well-tolerated halogenated ether. Agent of choice for inhalation induction of general anaesthesia with low blood:gas solubility.

Desflurane

Another halogenated ether with a pungent smell, rapid onset of anaesthesia and quick recovery.

All can cause malignant hyperthermia.

Post-operative N&V

Anaesthesia SE experienced by at least 25% of patients.

Vomiting is initiated in the vomiting centre of the medulla, which itself receives input from higher centres, the chemoreceptor trigger zone (CTZ), afferent somatic and visceral fibres, and the vestibular apparatus of the middle and inner ear. Of these, the CTZ in the area postrema (floor of 4th ventricle) is probably the most important.

Complications:

Dehydration

Electrolyte imbalance

Metabolic imbalance (metabolic alkalosis)

Pulmonary aspiration

Hernia formation

Damage to site of surgery (direct e.g. ENT or indirect e.g. neurosurgery).

Inability to take oral medication.

Delayed discharge.

Risk factors:

• Patient: Female, younger than 16y, Hx, obesity, motion sickness, pre-op anxiety.
• Anaesthetic agents: Opioids, N2O nitrous oxide, etomidate, ketamine.
• Surgery: GI, GU, neurosurgery, middle ear, ophthalmic.
• Post-op: Dehydration, hypotension, hypoxia, early oral intake.

Entiemetics:

• H1: Cyclizine (GI causes), cinnarizine (Vestibular causes).
• D2: Metoclopramide (GI causes, prokinetic), domperidone (prokinetic), prochlorperazine (vestibular/GI causes), haloperidol (chemical causes e.g. opioids).
• 5HT3: Ondansetron - doses can be high e.g. for emetogenic chemotherapy.
• Others:
  • Hyoscine hydrobromide (antimuscarinic therefore also antispasmodic and antisecretory - don't prescribe with a prokinetic).
  • Dexamethasone (unknown mode of action).
  • Midazolam (unknown mode of action; anti-emetic effect outlasts sedative effect).

  
  
  
  

Premedication

• Analgesia: Pre-emptive analgesia aims to dampen the pain pathways before the signals starts to arrive. It is not often used, and effects are hard to determine as few studies are in agreement and there are many variables.
• Antacid: For reflux either ranitidine 150mg PO or omeprazole 40mg PO/IV the night before and then 2h pre-op. Ranitidine reduces both gastric pH and volume. High risk of aspiration in: Emergency surgery, pregnancy, DM, hiatus hernia.
• Anti-emesis
• Antibiotics: Depends on surgery e.g. cefuroxime + metronidazole for colorectal or biliary surgery.
• Anti-autonomic: B-blockers can be used to reduce risk of perioperative ischaemia.
• Steroids: Minor operations 25-50mg hydrocortisone IV at induction, major operations 50mg at induction then repeat 3 times 8 hourly before restarting oral. Ditto if adrenal insufficieny or adrenal surgery, or >10mg prednisolone/day over last 3m.
• Bronchodilators: E.g. salbutamol nebuliser.
• Anxiolytics and Amnesia: Amnesia may add to the unpleasantness of the experience, though it can be useful in those not wanting to know, and children.
  • The most common agents used are benzodiazepines. E.g. lorazepam 2mp PO, temazepam 10-30mg PO, diazepam 5mg PO. Some anaesthetists still use morphine 10mg IM (SE dysphoria) or atropine 0.6mg IM.
  • Children: Midazolam 0.5mg/kg (tastes bitter so often put in Calpol).
    Local anaesthetic creams for children: Tetracaine 4% applied 45min before inserting IVI.
    The presence of a parent at induction is more powerful than any premedication in reducing anxiety.

The patient should be aware of what will happen, where she will wake and how she will feel. Premedication aims to to allay anxiety and contribute to a smooth induction of anaesthesia by decreasing secretions (much less important than when ether was used), promoting amnesia and analgesia, and decreasing vagal reflexes.

Timing: 2h pre-op for oral drugs, 1h pre-op if IM.

Where does the oculomotor nerve like to get squashed?

Berry aneurysm at the junction between the posterior communicating artery and the internal carotid artery is an important cause of oculomotor nerve palsy.

The oculomotor nerve runs through the lateral wall of the cavernous sinus superiorly. It enters the cavernous sinus just above the petroclinoid ligament and inferior to the interclinoid ligament. Masses invading the cavernous sinus from within the sella are most likely to cause third cranial nerve dysfunction prior to involvement of the other cranial nerves in the cavernous sinus. This is probably because of the oculomotor nerve's close proximity to the unyielding interclinoid ligament above and the petroclinoid ligament below.

The axons for most of the muscles are uncrossed from the nucleus to the eye, but there are 2 exceptions: (1) Axons for the levator palpebrae come from both sides of the central caudal subnucleus via crossed and uncrossed pathways. (2) Those for the superior rectus muscle come from the superior rectus subnucleus on the contralateral side.

The pupillomotor and ciliary muscle neurons derive from the Edinger-Westphal subnucleus, which is in the midline in the most rostral and anterior part of the oculomotor nerve nucleus. These autonomic pathways are all ipsilateral or uncrossed.

From emedicine.

Kernig's sign

Positive when the leg is bent at the hip and knee at 90 degree angles, and subsequent further extension in the knee is painful (leading to resistance).

SAH

Rx: Renounce raw conceit; find notes, morphine and pennies.

Refer neurosurgery

Reexamine CNS often

Chart BP, pupils, GCS

Fluids: SBP >160 (HHT = hypertensive hypervolaemic therapy... because hypotension causes vasospasm).

Nimodipine. Start by day 4 (asap on diagnosis!) till day 21 - three weeks.

Morphine + laxatives (opiates cause constipation).

Angiography: Sensitivity: 4 vessel angiography > CTA > MRA

Procedures: Clipping (craniotomy) or coiling (endovascular).

Tests

• Angiogram: Sensitivity - 4 vessel angiography > CTA > MRA. CT detects >90% of SAHs.
• LP: If CT negative and no c/i >12h after headache onset.
  Early CSF uniformly bloody; later CSF shows xanthochromia.

S&S

• Thunderclap headache, vomiting, collapse, seizures, coma, neck stiffness, Kernig's sign, retinal or subhyaloid haemorrhage.
• Focal signs at presentation may suggest site of aneurysm (e.g. pupil change suggests CNIII palsy suggests PCA aneurysm).
• Sentinal headache due to small warning leak from the offending aneurysm.

DD of thunderclap headache = D SUMMIT V

Dissection of carotid/vertebral artery

SAH

Unknwon cause

Meningitis

Migraine

Intracerebral bleed

Thrombosis cortical vein

Valsalva maneuvre

Complications

1. Rebleed.
2. Vasospasm à stroke.
3. Hydrocephalus.
4. Hyponatraemia.

Prognosis

⅓ die immediately.

⅓ die within 1m from vasospasm or rebleed.

⅓ survive with or without neurological problems.

Grade I = No signs = 0% mortality.

Grade II = Necks stiffness, CN palsies = 11%.

Grade III = Drowsiness = 37%.

Grade IV = Drowsiness + hemiplegia = 71%.

Grade V = Prolonged coma = 100%.

Causes

Aneurysm rupture 80%.

AVM.

Unknown.

Risk factors

Smoking, hypertension, mycotic aneurysm, alcohol, bleeding disorder, low oestrogen (post-menopause).

Berry aneurysms are associated with:

1. Polycystic kidneys.
2. Coarctation of aorta.
3. Ehlers-Danlos syndrome.

Headache history

D SOAP TALC PFF

Duration (+ continuous/intermittent)

Straining

Onset (tempo) slow ~ migraine

Analgesia ICP headache responds to analgesia

Pulsatile

Time (of day) On waking ~ ICP

Associated symptoms - Vomiting LOV, gait apraxia, photophobia, phonophobia...

Location Hemicranial ~ migraine

Coughing

Posture

Frequency

First attack

MND

Amyotrophic lateral sclerosis ALS (50% - Stephen Hawking)

• Lesion: Motor cortex and ant horn spinal cord
• U or L: Both
• Muscles: All, distal and proximal.
• Pyramidal features: May predominate.

Progressive bulbar palsy PBP (10%)

• Lesion: CN 9-12. Often progresses to ALS.
• U or L: --
• Muscles: Tongue, palate, pharyngeal.
• Pyramidal features: May be present.

Progressive muscular atrophy PMA (10%)

• Lesion: Ant horn cells only
• U or L: LMN only
• Muscles: Distal limb muscles before proximal.
• Pyramidal features: --

Primary lateral sclerosis PLS

• Lesion: Betz cells in the motor cortex.
• U or L: Mainly UMN.
• Muscles: Spastic leg weakness and pseudobulbar.
• Pyramidal features: --

Seizure tests

DIET BEM

Drug levels

Ictal SPECT/PET/MEG

EEG +/- video EEG

Toxicology/drugs screen: Tricyclics, cocaine, alcohol, tramadol, theophylline.

Biochemistry profile: Glucose, Na, Ca, phosphate, urea.

Exclude infection - CMC, RPR, meningitis, encephalitis...

MRI/CT

Seizure History

Witness = PAM DICCI FEJ

Pulse

Associated symptoms (palpitations, angina, dyspnoea, light-headed)

Movement

Duration

Injury

Consciousness

Complexion (cyanosis suggests epilepsy)

Incontinence

Frothing

Eyes open or closed

Jacksonian features

Before

Precipitants - what was she doing?

Warning?

Can she prevent attacks?

After = STAMP C

Sleepiness

Tongue sore

Amnesia

Muscle ache

Paralysis/dysphasia

Confusion

Background

Frequency

First episode - date

Fx

Sleepiness (narcolepsy)

Otitis media

Otoscopic findings of the TM: MOBEE

- Mobility decreased on pneumatic otoscopy.

- Opacity.

- Bulging.

- Erythrma.

- Effusion of the middle ear (MEE).

OM with effusion (OME), formerly termed serous OM or secretory OM, is MEE of any duration that lacks the associated signs and symptoms of infection (eg, fever, otalgia, irritability). OME usually follows an episode of AOM.

Chronic suppurative OM is a chronic inflammation of the middle ear that persists at least 6 weeks and is associated with otorrhea through a perforated TM, an indwelling tympanostomy tube (TT; see image below), or a surgical myringotomy.

Neuroimaging in stroke

Source: http://www.ferne.org/Lectures/neuroimaging%200501.htm

The non-contrast head CT scan remains the first-line imaging study in suspected stroke patients due to its ubiquity and exquisite sensitivity for the detection of blood. On the initial emergency CT scan, overt nonstroke processes must be confidently excluded. These “stroke mimics” include tumor, subdural or epidural hematoma, SAH, and intraparenchymal hemorrhage.

Since thrombolytic therapy may produce lethal bleeding in patients with intracranial hemorrhage, exclusion of hemorrhage has been the key criterion in the major thrombolytic trials. While detection of hemorrhage is the most fundamental and critical step in the evaluation of the head CT, the ECASS trial demonstrated that early signs of major cerebral infarction (e.g. sulcal effacement, mass effect, edema, and loss of the insular ribbon) are also important features to look for, since they are associated with an increased risk for intracerebral hemorrhage in patients who receive thrombolytic therapy. Some guidelines have incorporated these more subtle signs into recommendations against thrombolytics when present. The NINDs trial, however, did not use these CT criteria for making decisions regarding thrombolysis.

There are three possible classes of CT diagnoses when a patient presents with an acute neurologic deficit:

I. Non-ischemic stroke lesion:

A: Hemorrhagic:

1. SDH

2. EDH

3. SAH

4. Intracerebral hemorrhage (cortical, subcortical, cerebellar, and brainstem)

B: Non-hemorrhagic:

1. Tumor

2. Abscess

II. Ischemic Stroke Signs:

A. Hyperdense Artery Sign

B. Loss of Insular Ribbon (“Insular ribbon sign”)

C. Loss of cortical gray-white differentiation

D. Mass effect

III. Normal CT

Non-ischemic stroke lesions

Fundamental to cranial CT interpretation in potential stroke cases is the identification of non-stroke lesions, particularly hemorrhage. Acute hemorrhage will usually appear hyperdense (whiter, like bone) to gray matter, and have a heterogeneous appearance. It also tends to have less mass effect than would be predicted for the size of the lesion. All hyperdensities, however, are not necessarily acute hemorrhage. Calcification, proteinaceous material, and lesions with a high nucleocytoplasmic ratio (e.g. GBM) can all appear hyperdense to normal brain.

Epidural hematoma (lens shaped/ do not cross suture lines), subdural hematoma (falx shaped/ can cross suture lines) and intraparenchymal hematoma (supra/infratentorial) are all clinical possibilities which are usually readily apparent on CT scanning. Subarachnoid hemorrhage can be more difficult to diagnose. SAH typically appears as a hyperdense (white) collection, most commonly in the basal cisterns (including circummesencephalic, suprasellar, sylvian, and quadrigeminal). The ability to diagnose a SAH on CT scan depends on the volume of blood present and the duration of its presence. Typically, CT scan loses sensitivity for detecting subarachnoid hemorrhage as time from the SAH ictus increases.

Tumor and abscess can have similar appearances on non-contrasted scans. Both can demonstrate mixed densities within them, and both are frequently associated with edema in the surrounding brain matter.

Normal CT Scan

Even with state-of-the-art 3rd and 4th generation scanners, most ischemic strokes will go undetected for the first few hours. Hence, the “Normal CT Scan” is perfectly compatible with acute ischemic stroke. Unfortunately, a normal scan is also perfectly compatible with seizure, metabolic disease (hypoglycemia, hyponatremia), and TIA as etiologies for a neurologic deficit.

In general, gray matter is more susceptible to ischemia than white matter, as it is more metabolically active. Hence, loss of gray-white differentiation due to the influx of edema into the gray matter is the earliest change to be noted. Subtle edema has been detected as early as 46 minutes from the ictus, but changes this early are the exception. By 6 hours from the ictus, ¾ of patients with MCA strokes will show early edema in the insular cortex. After 6-12 hours, additional edema is recruited into the area, making the lesion more conspicuous on CT imaging. Early on, it is NOT POSSIBLE to distinguish between ischemia and frank infarction by imaging techniques.

Ischemic Stroke Signs

The Hyperdense Artery Sign:

When an artery (typically MCA, PCA, or ACA) appears hyperdense, this is indicative of a major occlusion of the vessel with thrombus formation. The specificity of the hyperdense MCA (HMCAS) is 98%. False-positives can occur in the case of unilateral calcification of the MCA trunk. The sensitivity of the HMCAS, however, is only about 50%. Variability in blood volume and composition of the thrombus are responsible for the frequent false-negative findings. The hyperdense artery sign suggests that a major cerebral vessel is occluded and that this vessel’s territory is at risk for hypoperfusion. ICA and MCA trunk occlusions have more serious clinical implications than occlusions of the MCA branches, the PCA, or the ACA because the threatened territory is larger. Whether the affected territory will undergo ischemic necrosis is a matter of collateral blood supply. Therefore, this is not an infarct sign, rather it indicates volume of tissue that will die if the collateral blood supply fails and recanalization is not achieved. Clinically, ischemic stroke patients with an HMCAS have a poorer prognosis than those without this radiographic finding.

The Insular Ribbon Sign

The insular ribbon is an area of extreme gray-white differentiation that is readily examined on the CT scan. Located between the Sylvian fissure and the basal ganglia, it is supplied by small perforating branches of the MCA. Loss of the insular stripe is one of the more subtle early indications of MCA stroke. The normal insular cortex appears as a thin white line (gray-matter) adjacent to a darker gray subcortical area (white-matter). With ischemia, the metabolically active gray matter is effected first, resulting of intracellular edema, with resulting hypodensity. Thus, the insular ribbon or stripe is lost, and a homogeneous appearance is noted. This finding alone is not an exclusion criterion for intravenous thrombolytic therapy.

Mass Effect

Brain swelling is very subtle during the first hours after arterial occlusion. Swelling of brain tissue is assessed on CT scans by looking for compression of CSF spaces and asymmetry of cortical sulci. Swelling visible within the first 6 hours indicates severe edema and indicates a poor prognosis for the majority of patients.

A retrospective evaluation of CTs from the ECASS study suggested that if ischemic changes were present in greater than 1/3 of the MCA territory, the patient was at increased risk of hemorrhage. Other studies have supported this conclusion, but it has been demonstrated that the interobserver variability for identifying greater that 1/3 of the MCA distribution is very poor. For this reason, this criterion is difficult to rely on for clinical decision making, even when the CT is interpreted by a neuroradiologist.

Future Trends in Stroke Imaging

While CT is the current brain-imaging method of choice for determining qualification for thrombolysis, this may change in the future. MRI, especially diffusion-weighted and perfusion-weighted MRI are exquisitely sensitive to early pathologic changes of ischemic infarction and subtle brain edema. These techniques are superior to CT in that they can detect abnormalities much sooner than a conventional non-contrast CT scan. The major limitation of MRI remains its relative insensitivity to detecting hemorrhage, which is the key neuroimaging branch point in a clinical protocol. PET scanning, Xenon CT scanning, and cranial doppler are all being investigated in the stroke arena, but are all currently considered to be experimental.16,18

Outcome of a case:

You interpret the cranial CT correctly as demonstrating an early stroke in the left MCA distribution with obscuration of the insular ribbon on that side. Unfortunately for the patient, however, you also identify a right frontal mass lesion with significant edema surrounding it. You wisely withhold tPA in the presence of the presumed tumor. The patient is transferred to a nearby tertiary care center with neurosurgical expertise, where he undergoes craniotomy. A diagnosis of Astrocytoma is made, and the patient is ultimately discharged to a rehabilitation hospital.

Questions

1. NINDs CT scan criteria for exclusion from thrombolysis included:

A. Dense MCA sign

B. Hemorrhage

C. Edema in > 1/3 of MCA distribution

D. A&C

E. All of the above

2. Current treatment guidelines specify that the cranial CT must be read by a:

A. Neuroradiologist

B. Neurologist

C. Radiologist

D. Physician skilled in cranial CT interpretation

3. The normal cranial CT scan:

A. Is incompatible with acute stroke

B. Is pathognomonic of acute stroke

C. Is compatible with the diagnosis of acute stroke

Answers

1. Answer b.

2. Answer d.

3. Answer c.

Comparing decerebrate and decortical posture

Image from: http://www.wrongdiagnosis.com/symptoms/rigidity/book-causes-13b.htm

Brain coverings

Cerebrovascular territories

Image from: http://missinglink.ucsf.edu/lm/ids_104_cerebrovasc_neuropath/Case3/Case3Images/CerArtDistBlum1.jpg