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Tumor Markers in ENT (Head and Neck)

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1. Thyroid Malignancies

Thyroglobulin (Tg)

• Tumor: Differentiated thyroid carcinoma (papillary and follicular)
• Use: Post-thyroidectomy surveillance marker; undetectable levels = disease free; rising levels = recurrence
• Used in combination with neck ultrasound - patients considered disease free only when both Tg is undetectable AND neck US is negative
• Normal: <33 ng/mL; post-total thyroidectomy: <2 ng/mL
• Pitfall: Anti-thyroglobulin antibodies (TgAb) can falsely lower Tg readings

Calcitonin

• Tumor: Medullary thyroid carcinoma (MTC) - produced by parafollicular C-cells
• Use: Diagnosis, preoperative staging, post-surgical surveillance, and screening of family members (MEN 2A, MEN 2B)
• Elevated calcitonin level is essentially diagnostic of MTC
• Stimulated calcitonin (pentagastrin or calcium infusion test) used for early/occult MTC

CEA (Carcinoembryonic Antigen)

• Also elevated in medullary thyroid carcinoma
• Used alongside calcitonin for MTC follow-up; a rising CEA with stable/falling calcitonin suggests dedifferentiation ("calcitonin escape")

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2. Nasopharyngeal Carcinoma (NPC)

EBV (Epstein-Barr Virus) Markers

• IgA antibodies to EBV VCA (Viral Capsid Antigen) - most widely used serological marker
• IgA antibodies to EBV EA (Early Antigen) - correlates with tumor burden
• Cell-free plasma EBV DNA - highly sensitive and specific; used for:
  • Screening in endemic populations (Southeast Asia, Southern China)
  • Monitoring disease response during radiotherapy
  • Detecting residual disease and predicting relapse
• Classified as an exogenous viral marker - EBV-coded RNA (EBER) detectable in tumor tissue

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3. Squamous Cell Carcinoma (SCC) of Head & Neck (HNSCC)

SCC Antigen (SCC-Ag)

• Glycoprotein from SCC cells; most relevant to laryngeal, pharyngeal, and oral cavity SCC
• Elevated levels correlate with tumor mass, lymph node metastasis, and stage
• Used for monitoring treatment response and detecting recurrence
• Also elevated in cervical SCC (hence sometimes listed under gynecology)

CYFRA 21-1 (Cytokeratin 19 Fragment)

• Reflects epithelial cell turnover; elevated in HNSCC
• Correlates with tumor stage and poor prognosis
• Useful alongside SCC-Ag for overall HNSCC monitoring
• Patients with high CYFRA 21-1 dying within 24 months had significantly elevated levels vs. survivors (p<0.05)

CEA (Carcinoembryonic Antigen)

• Non-specific; elevated in oral cavity and pharyngeal SCC
• Normal: <2.5 ng/mL (non-smokers), <5 ng/mL (smokers)
• CEA >100 ng/mL generally indicates metastatic disease

LDH (Lactate Dehydrogenase)

• Non-specific but significant in HNSCC grading
• High serum LDH correlates with moderately differentiated SCC
• Indicator of tumor grade and treatment prognosis

TPS (Tissue Polypeptide Specific Antigen)

• Marker of proliferation; elevated in advanced HNSCC
• Used alongside other markers for survival prediction (distinguishes alive vs. dead at 24 months with p<0.05)

sIL-2R (Soluble Interleukin-2 Receptor)

• Immune marker associated with aggressive HNSCC
• Elevated levels correlate with poor survival outcomes

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4. HPV and Molecular Markers in HNSCC

p16 / HPV

• p16 (INK4a) is the surrogate immunohistochemical marker for high-risk HPV (especially HPV-16)
• Used for oropharyngeal SCC staging and prognosis
• HPV-positive OPSCC has a markedly better prognosis than HPV-negative
• p16 testing is standard in oropharyngeal cancer staging (AJCC 8th edition creates a separate staging system for p16+ OPSCC)
• From Cummings Otolaryngology: "Testing for HPV or the p16 tumor suppressor gene, its surrogate marker, enable accurate tumor staging and treatment planning"

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5. Salivary Gland Tumors

Molecular/Prognostic Markers

• Ki-67 - proliferation marker; high Ki-67 + low p27 = worse prognosis in salivary gland malignancies. Considered a more accurate marker of proliferating cells than other markers
• HER-2/neu (ERBB2) - overexpressed in ~1/3 of mucoepidermoid carcinomas (MECs) and especially in salivary duct carcinoma; overexpression correlates with poorer prognosis and guides targeted therapy (trastuzumab)
• MECT1-MAMLI translocation t(11;19) - found in up to 70% of MECs; associated with lower-grade tumor
• CDKN2A/p27 - low expression = worse prognosis (cyclin-dependent kinase inhibitor)
• These are primarily tissue/IHC markers; none are in routine clinical serum use yet

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6. Other Relevant ENT-Associated Markers

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Summary Table

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Local Anaesthesia in ENT

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1. Mechanism of Action

• Non-ionized form crosses the lipid membrane barrier to reach the intracellular site of action
• In infected tissue (low pH), more drug is ionized - less penetrates the membrane - hence LA fails in infected fields. The solution: block nerves proximally in healthy tissue
• All clinically useful agents are diffusible, reversible, predictable, water soluble, and non-irritating to local tissue

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2. Classification

Structure: Three-part molecule

Three determinants of activity:

1. Lipid solubility - determines potency and duration
2. Degree of ionization (pKa) - lower pKa = more non-ionized form = better penetrance
3. Protein binding - higher binding = longer duration

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3. Individual Agents Used in ENT

Aminoester Agents

Aminoamide Agents

Miscellaneous

• Cyclonine: Neither ester nor amide - excellent topical (0.5%, 300 mg max); useful when allergy to both classes documented
• Cetacaine: Combination (benzocaine + butyl aminobenzoate + tetracaine); mucosal anesthesia; onset 30 seconds; max 2 sprays

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4. Vasoconstrictors (Additives)

• Concentrations: 1:100,000 (1 mg/100 mL) or 1:200,000 (1 mg/200 mL)
• Benefits:
  • Prolongs nerve block duration
  • Reduces systemic absorption (increases safety margin)
  • Decreases operative blood loss (critical in nasal surgery, tonsillectomy)
• Side effects: Tachycardia, hypertension - treat with esmolol
• Avoid in patients on tricyclic antidepressants (TCAs) or MAO inhibitors (hypertensive crisis risk)

• Adding NaHCO₃ (1:10 dilution - 1 mL bicarb to 10 mL lidocaine) reduces acidity of LA solution
• Significantly reduces burning pain on injection - routinely used for nasal blocks

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5. ENT-Specific Applications and Nerve Blocks

A. Nasal Surgery (Septoplasty, Rhinoplasty, FESS, Fracture Reduction)

1. Cotton pledgets soaked with 4% cocaine or 0.05% oxymetazoline + 4% topical lidocaine placed to cover branches of:
   • Anterior and posterior ethmoid nerves
   • Sphenopalatine nerve
   • Nasopalatine nerve
   • Leave for 5-10 minutes
2. Then 1% lidocaine with 1:100,000 epinephrine injected along:
   • Septum and lateral nasal walls
   • Floor of nasal cavity
3. External nasal nerve block - intercartilaginous injection from rhinion to supratip
4. Infraorbital nerve block - needle through vestibule to just below midportion of orbital rim
5. Nasopalatine nerve block - injection at base of columella and nasal tip
6. Pledgets replaced posteriorly for 5 more minutes

• Buffer lidocaine with NaHCO₃ (1:10)
• Use 27-gauge or smaller needle
• Inject slowly within mucosal-submucosal plane
• EMLA cream applied 1 hour before provides similar anesthesia with less discomfort than needle infiltration

B. Ear (Otology)

• External auditory canal (EAC): Innervated by auriculotemporal nerve (V3), Arnold's nerve (vagus), greater auricular nerve (C2/C3)
• Circumferential injection of LA at bony-cartilaginous junction for myringotomy, cerumen removal, small EAC procedures
• Tympanic membrane: EMLA cream applied topically; used for myringotomy under LA in adults
• Cotton wicks soaked in LA placed in EAC

C. Pharynx / Tonsil / Oropharynx

• Glossopharyngeal nerve block: Exits jugular foramen; gives off pharyngeal, tonsillar, and lingual branches
  • Blocked by injection into the base of the anterior tonsillar pillar (peritonsillar block)
  • Used for peritonsillar abscess drainage
• Sphenopalatine ganglion (SPG) block:
  • Large autonomic ganglion accessible intranasally
  • Cotton-tipped applicators soaked in LA (4% lidocaine or 10% cocaine) directed to posterior middle meatus just anterior to the posterior wall
  • Topical intranasal approach is most common and well-tolerated
  • Also injectable via greater palatine canal or transnasal needle
  • Used for: cluster headaches, migraines, facial pain, post-rhinoplasty analgesia, FESS analgesia

D. Larynx / Trachea

• Innervates supraglottic mucosa (internal branch - sensory) and cricothyroid muscle (external branch - motor)
• Technique: Inject LA lateral to the thyroid cartilage at the level of the hyoid, directing needle to pierce thyrohyoid membrane
• Bilateral block required for awake intubation

• Palpate cricothyroid membrane
• Insert 22- or 20-gauge needle, advance until air aspirated
• Inject 4 mL of 4% lidocaine rapidly - induces coughing which disperses LA throughout trachea/subglottis
• Contraindication: Direct infiltration of the recurrent laryngeal nerve is contraindicated (supplies all intrinsic laryngeal muscles except cricothyroid - may cause bilateral vocal cord paralysis and airway obstruction)

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6. Toxicity

CNS Toxicity (dose-dependent, sequential):

1. Perioral/circumoral paresthesias
2. Tinnitus, dizziness
3. Mental status changes
4. Tonic-clonic seizures
5. Coma, respiratory arrest

Cardiovascular Toxicity:

• Diminished myocardial contractility + reduced peripheral vascular tone
• Bupivacaine: Cardiac toxicity precedes CNS toxicity - unique danger
• Rapid cardiovascular collapse possible

• ACLS immediately
• 20% Intralipid (lipid emulsion rescue):
  • Initial: 1.5 mL/kg IV bolus
  • Maintenance: 0.5 mL/kg/min infusion
  • Maximum: 10 mL/kg over 30 minutes
  • Works for both CNS and cardiac toxicity
  • See: lipidrescue.org

Methemoglobinemia:

• Caused by prilocaine (≥600 mg) and benzocaine
• Pulse oximetry unreliable - reads ~85% regardless of actual saturation
• Higher risk in G6PD deficiency
• Treatment: 1% methylene blue IV, 1-2 mg/kg

Allergy:

• True allergic reactions: <1% of all adverse reactions
• Usually due to methylparaben or metabisulfite preservatives (not the LA itself)
• More common with esters (PABA derivatives); extremely rare with amides
• Cross-reactivity exists within the ester class (not between ester and amide)
• Management: provocative intradermal testing (with resuscitation ready) OR use opposite class

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7. Pharmacokinetics Summary

• Laryngeal and tracheal mucosa: Rapid absorption approaching IV injection levels - highest risk site in ENT
• Metabolism:
  • Amides: Hepatic (CYP450 + carboxylesterases)
  • Esters: Plasma cholinesterase (+ liver)
  • Both compromised in parenchymal liver disease
  • Both excreted renally
• Important: Ester drugs (procaine, chloroprocaine) inhibit plasma cholinesterase and may prolong succinylcholine effects

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8. Quick Reference Summary

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Local Anaesthesia Techniques & Applications in ENT

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I. Techniques of Administration

1. Topical Anaesthesia

Important: Laryngeal and tracheal mucosa absorb LA at near-IV rates. Total lidocaine dose for airway topicalisation is debated - sources cite 4-9 mg/kg. Monitor for LAST (tinnitus, perioral tingling, metallic taste, sedation).

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2. Infiltration Anaesthesia

• Buffer with NaHCO₃ 1:10 (1 mL bicarb per 10 mL lidocaine) - reduces acidity
• Use fine needle (27-gauge or smaller)
• Inject slowly within the submucosal/subdermal plane
• Warm LA to body temperature before injection
• Inject through already-anaesthetised tissue where possible

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3. Nerve Block Anaesthesia

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II. ENT Site-Specific Applications

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A. EAR (Otology)

Nerve Supply of the External Ear

CN VII and CN IX innervate the concha and middle ear mucosa but are not amenable to regional block. Their distributions are reached by local infiltration of the EAC and topical anaesthesia to the middle ear.

Auriculotemporal Nerve Block

• Landmark: Superficial temporal artery palpated as it crosses the zygoma; inject between this point and the incisura, near the root of the zygoma
• Volume: 2-3 mL of LA
• Effect: Anaesthesia of anterior EAC, tragus, anterior auricle

Greater Auricular Nerve Block

• Landmark (proximal technique): Identify the midline of the sternocleidomastoid (SCM); draw a line from the inferior edge of the EAC 6.5 cm inferiorly to meet this midpoint; inject here
• Landmark (distal/mastoid technique): Posterior border of SCM origin at skull base; insert needle posteromedially toward calvarium; withdraw slightly; aspirate (avoid occipital artery); inject
• Volume: 2-3 mL of LA
• Effect: Lower third of ear, lower postauricular skin

Lesser Occipital Nerve Block

• Landmark: Posterior border of SCM at base of skull; inject slightly cephalad
• Effect: Upper posterior auricle

Vagus Nerve (Arnold's Nerve) Block

• Landmark: Where it exits the skull base between the mastoid process and the tympanic plate
• Often caught incidentally during postauricular infiltration

Circumferential 'Ring' EAC Block

• Inject 1-2 mL of 1% lidocaine + 1:100,000 adrenaline at the bony-cartilaginous junction (4-quadrant circumferential technique)
• Used for: myringotomy, grommets in adults, foreign body removal, cerumen removal, EAC procedures

Tympanic Membrane - Topical

• EMLA cream applied to TM under otoscopy for 30-60 minutes
• Provides adequate anaesthesia for myringotomy/grommet insertion under LA in cooperative adults

Applications in Ear Surgery Under LA

• Tympanoplasty (type I-III)
• Stapedotomy / stapedectomy
• Ossiculoplasty
• Mastoidectomy (modified radical / canal wall down) - with sedation
• Auroplasty (prominent ear correction)
• EAC exostosis removal

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B. NOSE (Rhinology)

Nerve Supply of the Nasal Cavity

The Standard Combined Technique (Nasal Surgery)

• Cotton pledgets soaked in 4% cocaine OR 0.05% oxymetazoline + 4% lidocaine placed to cover all major nerve territories
• Leave in situ 5-10 minutes
• Targets: anterior ethmoid nerve (dorsal nasal surface, toward cribriform plate), sphenopalatine nerve (posterior middle meatus), nasopalatine nerve (septum/floor junction)

• 1% lidocaine + 1:100,000 adrenaline injected along septum, lateral nasal walls, and floor
• Allow 15 minutes for haemostatic effect before incision

• Infraorbital nerve block: Through nasal vestibule, needle to just below midpoint of orbital rim; anaesthetises nasal tip, ala, and columella skin
• Anterior ethmoidal nerve block: Cotton applicator along dorsal nasal surface to anterior cribriform plate; selective block after 5-10 min
• External nasal nerve block: Intercartilaginous injection along nasal dorsum from rhinion to supratip
• Nasopalatine nerve block: Injection at base of columella just inside nasal sill

• Pledgets replaced posteriorly for 5 more minutes to maximise deep block

Applications in Nasal Surgery

• Septoplasty / submucous resection (SMR)
• FESS (functional endoscopic sinus surgery)
• Rhinoplasty (+ tumescent for scalp)
• Closed reduction of nasal fractures
• Nasal polyp removal
• Turbinoplasty / inferior turbinate reduction
• Nasal endoscopy and biopsy

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C. THROAT / PHARYNX (Laryngology & Pharyngology)

Glossopharyngeal Nerve Block

• Tongue displaced medially with a tongue blade, exposing the glossogingival groove ("gutter")
• 25-gauge spinal needle inserted at base of anterior tonsillar pillar, just lateral to base of tongue, to depth of 0.5 cm
• Aspirate (avoid ICA); inject 2 mL of 2% lidocaine
• Repeat on contralateral side

• Cotton-tipped applicators soaked in 4% lidocaine held at base of anterior tonsillar pillar for 5 minutes - achieves comparable block without injection

• Peritonsillar abscess (quinsy) drainage
• Awake fiberoptic intubation (abolish gag reflex)
• Rigid laryngoscopy under LA
• Tonsillar biopsy
• Nasopharyngoscopy in sensitive patients

Sphenopalatine Ganglion (SPG) Block

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D. LARYNX & TRACHEA

Sequence for Complete Laryngotracheal Anaesthesia

1. Glycopyrrolate 0.2 mg IM/IV (antisialogogue) - reduces secretions that dilute topical LA
2. Spray oropharynx with 20% benzocaine (Cetacaine) - gargle and swallow
3. Nebulize 5 mL of 2% plain lidocaine if time allows
4. Transnasal: spray with oxymetazoline 0.05% then 4% lidocaine pledgets between inferior turbinate and septum (5 min before scope)

Superior Laryngeal Nerve (SLN) Block

• Volume: 1.5-2 mL of 2% lidocaine each side (bilateral block required)
• Effect: Anaesthesia of supraglottis, glottis, aryepiglottic folds
• Complication: Inadvertent internal carotid artery injection - always aspirate first

Transtracheal (Translaryngeal) Block

1. Patient in neck extension; identify CTM (between thyroid cartilage above and cricoid below, in midline)
2. 20-22 gauge needle attached to 5 mL syringe; advance posteriorly and slightly caudally
3. Free aspiration of air confirms intratracheal position
4. Inject 4 mL of 2% or 4% lidocaine rapidly on expiration
5. Patient coughs immediately - this disperses LA upward to vocal cords and downward into trachea
6. Optionally: thread catheter over needle first to reduce trauma, then inject through catheter

Critical warning: NEVER directly infiltrate the RLN. The RLN supplies all intrinsic laryngeal muscles (except cricothyroid). Bilateral damage = immediate bilateral vocal cord paralysis = acute life-threatening airway obstruction.

Spray-as-you-go (SAYGO)

• 2-4% lidocaine injected in 1-2 mL aliquots through suction/working channel of fiberoptic scope
• Applied at each level as scope advances: nasopharynx → oropharynx → supraglottis → glottis → trachea
• Cumulative dose must be tracked carefully (4-9 mg/kg maximum for airway)

Applications for Laryngotracheal LA

• Awake fiberoptic intubation (AFOI) - difficult airway
• Awake direct laryngoscopy
• Laryngeal biopsy under LA
• Vocal cord injection (fat, hyaluronate)
• Microlaryngoscopy in high-risk GA patients
• Rigid bronchoscopy preparation

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E. NECK

Cervical Plexus Block

• Superficial cervical plexus: injected along posterior border of SCM at its midpoint (Erb's point)
• Provides anaesthesia to the lateral/anterior neck, postauricular region, clavicle
• Used for: neck dissection supplementation, thyroidectomy under LA, parotidectomy

Facial Nerve Branches (Head & Neck)

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III. Sedation Adjuncts

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IV. Technique Selection by Procedure

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