Role of viruses and vaccines in head and neck malignancies

Introduction:
Oncovirus is a virus that causes cancer. Majority of viruses dont cause tumors due to their long evolutional history and coexistance with the human host. It has been estimated that about 20% of all malignant lesions are caused by oncogenic viruses. These oncogenic viruses can either be a RNA virus or DNA virus. Oncogenic tumors can hence be prevented by developing vaccines against appropriate oncoviruses.

Characteristics of oncogenic viruses:

1. The oncogenic viruses doesn't obey Koch's postulates
2. These viruses cause little or no symptoms after infection
3. Oncoviruses can either be DNA virus or RNA virus

Bradford Hill criteria is usually used to ascertain the association between oncogenic viruses and causation of tumors since oncogenic viruses don't fullfill Koch's criteria.

Hill criteria:

1. Strength – Also known as strength of assoication. A small association doesn't mean that it is not a causal effect. Larger the association more likely it is to be causal.
2. Consistency – Consistent findings observed by different examiners from different locations strengthens the likelihood of causal effect
3. Specificity – More specific the association between a factor and an effect the higher the probablity of causal relationship
4. Temporality – The effect has to occur after the cause
5. Biological gradient – Greater exposure leads to greater incidence of the effect
6. Plausibility – Plausible mechanism between cause and effect is helpful
7. Coherence – Between epidemiological and laboratory findings increases the likelihood of the effect
8. Experiment – If possible experimental evidence should be sought
9. Analogy – Effect of similar factors should always be considered

Classification of oncoviruses:

1. Viruses with DNA genome – Adenoviruses
2. Viruses with RNA genome – Hepatitis C virus
3. Retroviruses having both DNA and RNA genome – Human T lymphotrophic virus / Hepatitis B virus
4. Viruses that present as Eisomes / plasmids with an ability to replicate separately from host cell DNA e.g. Epstein Barr virus and Kaposi sarcoma associated herpes virus.

Mechanism of viral tumerogenecity:

1. Direct mechanism which involves insertion of oncogenetic material to the host cell
2. Enhancing already present oncogenetic genes (proto oncogenes) in the genome



Direct tumor viruses should atleast have one virus copy in each tumor cell. This viral genome is capable of expressing atleast one protein / RNA. These cells express surface viral antigens to which immune mechanism can be sensitized. In normal individuals the immune mechanism is capable of destroying these cells in a targetted manner. These type of viruses hence commonly cause tumors in patients who are immunosuppressed.

Common viruses causing Head and Neck malignancies:

1. Human papilloma viruses (Squamous cell carcinoma of oropharynx)
2. Epstein Barr virus (Nasopharyngeal carcinoma)
3. Kaposi sarcoma associated Herpes virus (Kaposi sarcoma)

Role of vaccines in preventing virus induced head and neck malignancies:

Most commonly available vaccine is HPV vaccine (Human Papilloma virus vaccine). It is of two types containing serotypes 16 and 18.

Hepatitis B and Hepatitis C vaccines are also commonly used to prevent Hepatitis B and C infections.

Another vaccine which is undergoing extensive clinical trial is the Epstein Barr virus vaccine. This again holds much promise.

Fat myringoplasty

Introduction:

Various graft materials have been used to close tympanic membrane perforations. The commonly used being temporalis fascia. Among the other graft materials used Fat fits the billing appropriately. Ringenberg was the first to use fat tissue to seal ear drum perforations.

Advantages of using fat graft:

The surgical procedure is rather simple. It can be inserted through the perforation after freshening the edges. Fat tissue available in the lobule of the ear can be utilized for this purpose. It is really wonderful to use fat to seal small perforations of ear drum.
Fat from ear lobe is considered to be better than that present in the abdomen / buttock area by Ringenberg as it is more dense and exhibits better scafolding for epithelial and mucosal overgrowth over the perforation.

Fat plugging does not require support at the level of anterior annulus which is actually a bane in conventional temporalis fascia myringoplasty.

Fat is actually a highly active material which could promote scarring and revascularization of adjcent areas.

Role of physiological saline in the management of patulous eustachean tube

Introduction:
The pharyngeal end of eustachean tube is normally closed. It usually opens temporarily during swallowing and yawning during which time middle ear drainage and pressure equalisation takes place. Abnormalities involving this opening mechanism may lead to middle ear pathologies like otitis media with effusion.

Patulous eustachean tube is a difficult entity to treat. The phenomenon of autophony which is caused by this condition is a difficult entity to treat. Patients have been driven to sucide because of this problem.

Patulous eustachean tube can be identified by the presence of the following features:

Aural fullness
Autophony
Hearing of self breathing

Sonotubometry is used to identify this condition.

Causes of patulous eustachean tube:

1. Weight loss (chronic)
2. Wasting disorders
3. Chronic inflammation followed by tissue atrophy at the pharyngeal end of eustachean tube

Management:

Various surgical modalities have been attempted with very little success.

Role of nasal topical instillation of physiological saline:

Instillation of physiological saline has been proved to be beneficial in nearly 60% of these patients. This therapy can be continued till there is sufficient weight gain which could obviate the need for this medication. Instillation of saline in the pharyngeal end of eustachean tube may cause it to close. This effect should be considered to be purely temporarly till normal saline is present close to the pharyngeal end of eustachean tube. The same can be instilled again if symptoms recur. Physiological saline administration can be continued till there is spontaneous recovery which is also common. Simple weight gain can obviate the symptoms.

Thyroid storm

Introduction:

This condition is also known as thyrotoxic crisis caused by hypermetabolic state induced by excessive secretion and release of thyroid hormones in individuals with thyrotoxicosis. In children this could be the initial presentation of thyrotoxicosis. This is more so in neonates.

Clinical manifestations:

1. Marked hypermetabolism
2. Excessive adrenergic response
3. Hyperpyrexia (reliable finding)
4. Flushing / sweating / tachycardia /atrial fibrillations / elevated pulse pressure / cardiac failure
5. CNS symptoms include – agitation / psychosis / restlessness / delirium / coma.
6. GI symptoms include – diarrhoea / jaundice
7. Hypertension may be present. * Normal blood pressure doesn't rule out thyroid strom.
8. Elderly patients may manifest atypical symptoms like (apathetic thryoid strom).
9. Heat intolerance

Diagnosis is primarly made on clinical grounds, as no specific lab test is going to clinch the diagnosis.


Triggering factors include:

1. Thyroid surgery
2. Radio active iodine therapy
3. Pregnancy / during delivery
4. Acute iodine load
5. Trauma
6. Acute infection
7. Drug reaction
8. Trauma
9. Myocardial infarction (rare)
10. Graves disease

Incidence:

It is 5 times more common in women than in men.
It is more common in prepeubertal children.
Common in children born to mothers with Graves disease.
More common in adolescents.

Pathophysiology:

Thyroid crisis is the most extreme state of thyrotoxicosis. It should be considered to be a decompensated state of thyroid hormone. Studies have shown that there is no clear evidence that increased secretion of thyroid hormones lead to thyroid strom. Increased levels of catecholamines and increased sensitivity of catecholamine receptors have been suggested to play a role. Decreased binding to thyroid binding globulin can also play a vital role as this would lead to a relative increase in the risk of increasing levels of serum T3 and T4.

Management:

All patients with suspected thyroid strom should be managed only in an ICU setup.

Treatment should be considered to be a triangular one.

Iv life line is to be started.
Dextrose is to be administered because of the increasing biological demand for glucose.
Serum electrolytes should be estimated and abnormalities if any should be corrected.
Cardiac arrythmias if present should be treated aggressively.
Hyperthermia can be managed by ice packs / acetaminophen 15 mg/kg orally.
Propranalol should be administered to block sympathomimetic effects of thyroxine.
Anti thyroid medications are to be administered. High dose of propyl thiouracil is preferred because it blocks peripheral conversion of T4 to T3. Hepatic parameters should be monitored while administering propylthiouracil.
Administration of Lugol's iodine will help by blocking the release of thyroid hormones. Lugol's iodinee is preferred.
Glucocorticoids are also administered in order to reduce peripheral conversion of T4 to T3.
Plasma pheresis can be resorted to in cases of accidental / suicidal ingestion of large doses of thyroxine.
Underlying cause should be looked for and treated.

Theories explaining thyroid strom:

1. These patientts have relatively high levels of thryoid hormones than normal controls. This may not be the case always.
2. Adrenergic receptor activation theory. Sympathetic nerves are supposed to innervate thyroid gland. Increased sympathetic stimulation causes an increase in thyroid hormone synthesis and secretion. This increase in thyroid hormone levels increase the density of beta receptors.
3. Excess hormones could be liberated when the gland is manipulated during surgery.
4. Rapid reduction in the levels of thyroid binding globulin levels cause increased levels of thyroid hormones
5. Alterations in tissue tolerance to thyroid hormones.


Differential diagnosis:

1. Anxiety disorder
2. Cardiac failure
3. Hypertension
4. Hyperthyroidism
5. Phaeochromocytoma
6. Atrial tachycardia / fibrillation