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DNB ENT — 10-Mark Answers

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Question 1: Radiotherapy

a) How does radiotherapy act? [3]

1. Direct effect: High-energy photons or particles directly break phosphodiester bonds, causing single-strand breaks (SSB) or, more critically, double-strand breaks (DSB) in DNA. DSBs are lethal as they cannot be faithfully repaired.
2. Indirect effect (dominant — 70%): Radiation interacts with intracellular water molecules, generating highly reactive free radicals (especially hydroxyl radical •OH). These diffuse to DNA and cause the same strand breaks.
3. Cell cycle effect: Radiation is most effective in G2 and M phases (mitosis) and least effective in S phase (DNA synthesis). Rapidly dividing tumour cells are more radiosensitive than most surrounding normal tissue.
4. Fractionation biology (4 Rs):
   • Repair — normal cells repair sublethal damage between fractions better than tumour cells
   • Redistribution — cells redistribute into more sensitive cell-cycle phases
   • Repopulation — normal tissues repopulate faster
   • Reoxygenation — hypoxic tumour cells (radioresistant) become oxygenated between fractions

b) Discuss dose delivery methods (normal and various modifications to increase effectiveness and decrease toxicity) [4]

• External Beam Radiotherapy (EBRT): Megavoltage linear accelerator (LINAC) delivering photon beams. Standard fractionation: 1.8–2 Gy/fraction, 5 days/week, total 60–70 Gy over 6–7 weeks for head & neck SCC.

• IMRT with parotid sparing — reduces xerostomia
• Amifostine: Cytoprotective agent protecting salivary glands and mucosa
• Spacers/shields: Physical blocking of critical structures

c) Briefly discuss the clinical features of radiation toxicity [3]

• Mucositis: Erythema → pseudomembranous ulceration; painful, impairs swallowing; peaks at week 3–4
• Xerostomia: Parotid gland damage → reduced saliva → dental caries risk
• Dermatitis: Erythema → dry desquamation → moist desquamation → healing
• Dysphagia/odynophagia: Due to oropharyngeal mucositis
• Hoarseness: Laryngeal mucosal oedema
• Fatigue, nausea: Systemic effects

• Xerostomia: Most common; permanent parotid fibrosis
• Osteoradionecrosis (ORN): Mandibular bone necrosis due to endarteritis obliterans; requires hyperbaric oxygen ± surgery
• Trismus: Fibrosis of masticatory muscles/TMJ
• Hypothyroidism: In ~25% of cases with neck irradiation
• Radiation-induced malignancy: Secondary tumours after 10–20 years
• Carotid blowout / carotid stenosis
• Chondronecrosis of larynx
• Radiation neuropathy: Brachial plexus, lower cranial nerves
• Lymphoedema
• Cataracts if eyes are in field

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Question 2: Gene Mapping and Gene Therapy

a) What is gene mapping? [1]

• Genetic linkage mapping: Based on recombination frequencies between genes
• Physical mapping: Determines actual physical location in base pairs on chromosomal DNA

b) Enumerate the various strategies employed for gene mapping [3]

1. Restriction Fragment Length Polymorphism (RFLP): Uses restriction enzymes to identify DNA polymorphisms that serve as chromosomal markers
2. Linkage analysis: Studies co-inheritance of markers with disease genes in families; calculates LOD (logarithm of odds) score
3. Positional cloning: Identifies disease gene purely based on chromosomal position without knowledge of function
4. Somatic cell hybridization: Fusion of human and rodent cells; human chromosomes are progressively lost, allowing gene-to-chromosome assignment
5. Fluorescence In Situ Hybridization (FISH): Fluorescent probes hybridize to specific chromosomal locations
6. Comparative genomic hybridization (CGH): Detects chromosomal gains and losses across the entire genome
7. Whole-genome sequencing (WGS) / Next-generation sequencing (NGS): Current gold standard for complete physical mapping
8. Chromosome walking and chromosome jumping: Sequential cloning of overlapping DNA fragments to traverse large chromosomal regions

c) Enumerate the viral vectors used for gene therapy [2]

d) What are the various approaches used in gene therapy? [4]

• RNA interference (RNAi): siRNA/shRNA to silence dominant-negative mutations
• Antisense oligonucleotides: Block mRNA translation

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Question 3: Gamma Knife Stereotactic Radiosurgery

a) Enumerate the basic principles of gamma knife stereotactic radiosurgery [4]

1. Stereotaxy: A rigid stereotactic frame (Leksell frame) is fixed to the skull under local anaesthesia. This provides a 3D coordinate system for precise target localization.
2. Cobalt-60 sources: 192 fixed Co-60 radioactive sources arranged in a hemispherical array. Each source emits a narrow gamma-ray beam.
3. Convergent beams: All 192 beams converge on a single focal point (isocenter). Each individual beam carries a subtherapeutic dose; the cumulative dose at the isocenter is lethal.
4. Steep dose gradient: Rapid dose falloff outside the target (up to 50% per mm). This spares adjacent critical structures.
5. Collimation: Collimator helmets (4, 8, 14, 18 mm diameter) shape beam size to match target dimensions. Multiple isocenters can be combined to treat irregular shapes.
6. Radiobiological effect: High single fraction causes irreversible DNA double-strand breaks; for vascular lesions (AVMs), causes progressive thrombosis and obliteration over months to years.
7. Treatment planning: MRI/CT fusion; dose prescription to the margin (isodose line); conformity and selectivity indices calculated.
8. No general anaesthesia required; outpatient procedure.

b) Mention the various steps involved in treating a patient with this technique [4]

1. Patient selection & imaging: MRI brain (with gadolinium) ± CT/angiography for lesion characterization
2. Frame application: Leksell stereotactic frame fixed to skull under local anaesthesia + sedation
3. Stereotactic imaging: MRI/CT with stereotactic localizer box attached; volumetric sequences (VIBE, MPRAGE)
4. Treatment planning: Neurosurgeon + radiation oncologist + physicist define target volume (GTV) and organs at risk (cochlea, brainstem, optic apparatus)
5. Dose prescription: Typically 11–13 Gy marginal dose for vestibular schwannoma; 12–14 Gy for meningioma
6. Quality assurance: Dosimetry verification
7. Treatment delivery: Patient positioned in treatment unit; automated beam sequencing; duration 20–90 minutes
8. Post-treatment: Frame removal; 2–4 hours observation; discharge same day; MRI follow-up at 6 months, then annually

c) What are the limitations of this modality? [2]

1. Size limitation: Effective only for lesions ≤3 cm (≤3.5 cm); larger tumours require microsurgery or fractionated RT
2. Intracranial restriction: Classic Leksell Gamma Knife treats only intracranial targets; cannot treat extracranial head & neck lesions (Cyberknife/LINAC-SRS can)
3. Radiation necrosis: Risk of symptomatic radionecrosis; latency 6–24 months
4. Delayed response: Tumour control/obliteration takes 2–3 years; not suitable for acute mass effect
5. Cranial nerve toxicity: Risk of facial palsy, hearing loss, trigeminal neuropathy
6. Re-treatment uncertainty: Reirradiation risks poorly defined
7. Frame-based system: Invasive frame; not tolerated in some patients; Extend system partially addresses this
8. No pathological confirmation: Treats based on imaging diagnosis

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Question 4: Midline Neck Swelling

a) Enumerate the differential diagnosis of a midline neck swelling [4]

1. Thyroglossal duct cyst — most common midline neck swelling in children
2. Dermoid cyst / epidermoid cyst
3. Plunging ranula (from floor of mouth, presents submental/midline)
4. Cervical thymic cyst (rare)
5. Lymphatic malformation (cystic hygroma) — more often lateral but can be midline

b) Briefly discuss the clinical presentation of a patient with thyroglossal cyst [2]

• Age: Most common in children; 50% present before age 20
• Site: 80% subhyoid; 15% at hyoid; 5% suprahyoid
• Swelling: Smooth, cystic, non-tender midline swelling usually 1–3 cm
• Pathognomonic sign: Moves upward on swallowing and on protrusion of the tongue (because tract is attached to foramen caecum via hyoid)
• Skin: Overlying skin normal unless infected
• Infection: Can become acutely inflamed; forms fluctuant abscess with discharging sinus if repeatedly infected
• Transillumination: Present (cystic)
• Thyroglossal fistula: May develop after spontaneous rupture or inadequate surgery
• Malignancy: Rare (1%); papillary carcinoma most common type

c) Differences between ectopic and aberrant thyroid [4]

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Question 5: Neck Secondaries

a) What are the sites for putative biopsies in a case of an unknown primary with neck secondaries? [2]

1. Nasopharynx: Bilateral biopsies from fossa of Rosenmüller (most common occult primary; especially upper neck nodes)
2. Base of tongue: Bilateral biopsies including lingual tonsil (most common in oropharyngeal HPV+ cancers)
3. Palatine tonsil: Tonsillectomy (not just biopsy) — yields primary in ~20% of cases; bilateral if contralateral tonsil normal
4. Pyriform sinus / hypopharynx: Direct laryngoscopy ± biopsy
5. Supraglottis / larynx: During panendoscopy
6. Floor of mouth and oral cavity: Visual inspection under GA

b) Describe the various levels of lymph nodes in neck [4]

c) Discuss the various types of neck lymph node dissections [4]

• Removes levels I–V
• Sacrifices: SCM, internal jugular vein (IJV), spinal accessory nerve (SAN/CN XI)
• Indication: Bulky N2/N3 disease with involvement of SAN or IJV
• Complications: Shoulder drop/dysfunction (SAN sacrifice), facial oedema (bilateral IJV sacrifice is contraindicated)

• Removes levels I–V
• Preserves one or more non-lymphatic structures (SAN, IJV, SCM)
  • Type I: SAN preserved
  • Type II: SAN + IJV preserved
  • Type III (functional neck dissection): SAN + IJV + SCM preserved
• Indication: N1–N2 disease without fixation

• Removes only specific levels at risk based on primary site
  • Supraomohyoid ND (levels I–III): Oral cavity primaries
  • Lateral ND (levels II–IV): Oropharynx, larynx, hypopharynx
  • Posterolateral ND (levels II–V + suboccipital): Posterior scalp, posterior neck
  • Central ND / Anterior compartment ND (level VI): Thyroid, parathyroid
• Indication: Elective ND for N0 neck with >15–20% occult metastasis risk

• Includes structures beyond standard RND: parotid, parapharyngeal nodes, mediastinal nodes, carotid artery, hypoglossal nerve
• Indication: Extensive disease with involvement of adjacent structures

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Question 6: Chemotherapy in Head and Neck Malignancies

a) Classify chemotherapeutic agents according to their mechanism of action [6]

• Nitrogen mustards: Cyclophosphamide, Ifosfamide
• Platinum compounds: Cisplatin, Carboplatin, Oxaliplatin (most widely used in HNC)
• Nitrosoureas: BCNU, CCNU

• Folate antagonists: Methotrexate (first-line palliative in HNC)
• Pyrimidine analogues: 5-Fluorouracil (5-FU), Capecitabine, Gemcitabine
• Purine analogues: 6-mercaptopurine, Cladribine

• Anthracyclines: Doxorubicin (adriamycin), Epirubicin
• Bleomycin (causes DNA strand breaks via free radical generation)
• Mitomycin C (bifunctional alkylator)
• Actinomycin D

• Vincristine, Vinblastine, Vinorelbine

• Paclitaxel, Docetaxel — key in TPF induction regimen

• Topo I inhibitors: Irinotecan, Topotecan
• Topo II inhibitors: Etoposide, Teniposide

• Cetuximab (chimeric anti-EGFR IgG1 monoclonal antibody): Inhibits EGFR tyrosine kinase signalling → anti-proliferative, pro-apoptotic; approved for HNSCC with RT and in recurrent/metastatic disease
• Pembrolizumab, Nivolumab (PD-1 inhibitors / immune checkpoint inhibitors): First-line in recurrent/metastatic HNC (KEYNOTE-048)
• Bevacizumab: Anti-VEGF; anti-angiogenic

b) What are the various chemotherapy strategies used in head and neck malignancies? [4]

• Given before definitive surgery or RT
• TPF regimen (Docetaxel + Cisplatin + 5-FU): Highest response rates; improves larynx preservation
• Goal: Tumour downsizing, assess chemosensitivity, treat micrometastases
• TAX 323 and TAX 324 trials established TPF superiority over PF

• Chemotherapy given simultaneously with RT as radiosensitizer
• Concurrent cisplatin (100 mg/m² every 3 weeks) is gold standard
• Mechanism: Inhibits DNA repair of RT-induced damage; synchronizes cell cycle into radiosensitive phases
• Used in: Locally advanced oropharynx, larynx preservation, nasopharynx carcinoma
• MACH-NC meta-analysis: 6.5% absolute survival benefit at 5 years

• After surgery in high-risk features (positive margins, extranodal extension)
• Concurrent cisplatin with PORT (Peters/Bernier trial)

• Cetuximab + Platinum + 5-FU (EXTREME regimen): First-line R/M HNSCC
• Pembrolizumab ± platinum-5FU (KEYNOTE-048): First-line; pembrolizumab monotherapy for CPS ≥1
• Methotrexate: Single agent palliative

• VA Laryngeal Cancer Study: Induction PF → RT allows larynx preservation in ~64% without compromising survival
• RTOG 91-11: Concurrent CCRT superior to sequential for larynx preservation

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Question 7: PET / SUV / PET-CT in Head and Neck

a) Briefly describe the principles of PET (positron emission tomography) [3]

1. A positron-emitting radiopharmaceutical is administered IV — most commonly 18F-FDG (fluorodeoxyglucose, a glucose analogue labelled with fluorine-18, T½ = 110 min)
2. FDG is taken up by metabolically active cells (tumours, brain, inflammation) via GLUT transporters; phosphorylated by hexokinase to FDG-6-phosphate → metabolically trapped (cannot be further metabolized)
3. F-18 undergoes positron (β+) decay: emits a positron that travels ~1–2 mm before annihilating with an electron
4. Annihilation produces two 511 keV gamma photons travelling in exactly opposite directions (180°)
5. Coincidence detection: Two opposing detectors simultaneously detect both photons — defines a line of response (LOR)
6. Thousands of LORs are back-projected to reconstruct a 3D image of metabolic activity

• CT provides anatomical localization; PET provides functional/metabolic data
• CT also used for attenuation correction of PET signal
• Acquired in same session on hybrid scanner

b) What is SUV in relation to PET? [2]

SUV = (Tissue activity in Bq/mL) / (Injected dose in Bq / Body weight in grams)

• Normal tissue: SUV < 2.5
• Malignant lesion: SUV typically ≥ 2.5 (conventional threshold); many HNSCCs show SUV 6–15
• SUVmax: Maximum voxel value within ROI; most widely used in clinical practice
• SUVmean: Average of all voxels; less susceptible to noise
• Clinical relevance: Higher SUVmax correlates with higher grade, worse prognosis, and predicts poor response to chemoradiation in HNC

c) Enumerate the oncological indications of PET-CT in head and neck [5]

1. Initial staging of HNSCC: Particularly for detecting occult nodal metastases (superior to CT/MRI for N0 neck), distant metastases (lung, liver, bone), and synchronous second primary tumours
2. Unknown primary with cervical metastasis: PET-CT detects primary in 25–40% of cases missed on conventional imaging; guides biopsy site (especially base of tongue, tonsillar fossa)
3. Post-treatment response assessment: Performed at 12 weeks after completing chemoradiotherapy; negative predictive value >90% for residual disease — avoids unnecessary planned neck dissection (PET-NECK trial)
4. Surveillance for recurrence: Detection of loco-regional recurrence or distant metastasis in symptomatic patients or rising tumour markers
5. Thyroid cancer: Detection of recurrent/metastatic differentiated thyroid cancer (especially dedifferentiated FDG-avid disease); medullary thyroid carcinoma staging
6. Skull base and parapharyngeal tumours: Perineural spread, bone marrow involvement not visible on CT/MRI
7. Radiotherapy planning (biological target volume, BTV): FDG-PET defines metabolically active tumour; avoids geographic miss; allows dose painting/escalation to FDG-avid sub-volumes
8. Salivary gland tumours: Distinguishing benign (Warthin's — hot) from malignant; staging of carcinoma
9. Lymphoma staging (including ENT lymphomas — Waldeyer's ring): Staging and response assessment (Deauville criteria)

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Question 8: Lignocaine (Lidocaine)

a) What is the mechanism of action of lignocaine? [2]

1. Voltage-gated sodium channel blockade: Lignocaine diffuses across the nerve cell membrane in its uncharged (lipid-soluble) base form, then becomes protonated intracellularly. The charged cationic form binds to the intracellular aspect of voltage-gated Na⁺ channels (specifically the α-subunit at the DII-DIV S6 transmembrane segments) → stabilizes the channel in its inactivated (closed) state.
2. Use-dependent (phasic) block: Block is greater in rapidly firing nerves because lignocaine preferentially binds open/inactivated channels. This is clinically advantageous — more active pain fibres are blocked preferentially.
3. Effect on nerve fibres: Blocks small myelinated Aδ fibres (sharp pain, temperature) and unmyelinated C fibres (dull pain) more readily than large myelinated Aβ fibres (touch, motor). Order of block: autonomic > pain > temperature > touch > motor.
4. Lignocaine also stabilizes cardiac cell membranes (Class Ib antiarrhythmic).

b) What is the maximum safe dose of lignocaine infiltration? [2]

• Note: In a 70 kg adult, plain lignocaine: max 3×70 = 210 mg = 21 mL of 1% or 10.5 mL of 2%
• With adrenaline: max 7×70 = 490 mg ≈ 49 mL of 1%
• Topical lignocaine (4% spray, laryngotracheal): max 4 mg/kg (absorbed rapidly from mucosa)

c) Enumerate the adverse drug reactions associated with its usage [3]

• Early: Perioral numbness, tinnitus, light-headedness, visual disturbances, metallic taste, restlessness
• Intermediate: Slurred speech, nystagmus, muscle twitching
• Severe: Generalised tonic-clonic seizures
• Terminal: CNS depression, respiratory arrest, coma

• Bradycardia, hypotension
• PR prolongation, QRS widening
• Ventricular arrhythmias (less than bupivacaine)
• Cardiovascular collapse

• Urticaria, angioedema, anaphylaxis
• Usually due to methylparaben preservative, not the drug itself

• Tachycardia, hypertension, anxiety, tremor
• Tissue ischaemia if inadvertently injected in terminal arteries (fingers, penis, nose)

d) What is Plester's technique of local anaesthesia for ear surgeries? [3]

1. Preparation: Patient supine, head turned to opposite side. Use lignocaine 1–2% with adrenaline 1:100,000–1:200,000 (vasoconstriction reduces bleeding and prolongs anaesthesia)
2. Four injection points (quadrant block):
   • 12 o'clock (superior): Injection at the superior margin of the bony external auditory canal (EAC) at the level of the linea temporalis / spine of Henle
   • 6 o'clock (inferior): At inferior margin of EAC
   • 3 o'clock (anterior): At anterior EAC wall (raises a bleb between skin and cartilage)
   • 9 o'clock (posterior): At posterior EAC wall / postauricular sulcus
3. Postauricular injection: Additional infiltration in the postauricular crease/hairline for postauricular approach
4. Meatal injections: 4 points (vascular strip areas) — anterior, posterior, superior, inferior — just deep to the bony-cartilaginous junction to anaesthetize the tympanomeatal flap
5. Volume: 0.5–1 mL per injection point; total 4–6 mL
6. Wait time: 10–15 minutes for full vasoconstriction effect before incision

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Question 9: Dysplasia of the Larynx

a) Enumerate the cytological features of dysplasia [3]

1. Increased nuclear-cytoplasmic (N:C) ratio — hallmark of dysplasia
2. Nuclear enlargement (anisonucleosis)
3. Nuclear pleomorphism — variation in size and shape
4. Hyperchromatism — darkly staining nuclei due to increased DNA content
5. Irregular nuclear membrane (membrane irregularity, angulation)
6. Abnormal chromatin pattern — coarse, clumped, irregular distribution
7. Prominent nucleoli — especially in higher grades
8. Increased mitotic activity — including abnormal mitotic figures

b) What are the grades of dysplasia? [3]

• Squamous cell hyperplasia → Basal/parabasal cell hyperplasia → Atypical hyperplasia → CIS

• Low-grade dysplasia: Includes mild + moderate dysplasia
• High-grade dysplasia: Severe dysplasia + CIS

• Mild: ~5–10% → carcinoma
• Moderate: ~20–30%
• Severe/CIS: ~30–40%
• CIS: Up to 65% if untreated

c) Briefly discuss the management of carcinoma in situ of glottis [4]

• Direct laryngoscopy + biopsy (under GA, microlaryngoscopy)
• NBI (narrow band imaging) endoscopy to delineate extent
• CT scan to exclude invasion (though CIS has no invasion)

• Cold steel stripping / cordectomy (Kleinsasser Type I–III) or CO₂ laser cordectomy
• Complete excision with free margins
• Achieves diagnosis + treatment simultaneously
• Voice results acceptable if only superficial layer removed
• ELS (European Laryngological Society) classification guides extent of laser cordectomy

• 60–66 Gy in conventional fractionation
• Excellent local control rates (>90%)
• Preferred when: multifocal disease, bilateral vocal cord involvement, patients who cannot tolerate surgery
• Advantage: Better voice quality than extensive cordectomy
• Disadvantage: Resource-intensive; delays detection of transformation; re-irradiation difficult

• Photosensitizer (porfimer sodium/ALA) + laser activation
• Used for extensive/multifocal CIS not amenable to complete resection
• Complications: Skin photosensitivity, laryngeal oedema

• Close endoscopic surveillance every 3 months initially (NBI-guided)
• Repeat biopsy if progression suspected
• Transformation to invasive carcinoma must be detected early

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Question 10: Floor of Mouth Reconstruction / Nasolabial Flap

a) What are the various reconstruction options following floor of mouth resection surgeries? [6]

• Small defects (<2 cm); suitable after limited excision
• Risk: Tongue tethering, restricted tongue mobility
• Only used for small peripheral defects

• Suitable for superficial, small-to-moderate defects where mandible periosteum is intact
• Disadvantage: Contraction, poor durability in a moist environment

• Workhorse for large FOM defects, especially with mandibular resection
• Based on thoracoacromial artery (pectoral branch)
• Reliable, large volume; but bulky, limited reach, chest donor morbidity
• Best for: Large defects, salvage surgery, irradiated fields

• Small (<3 cm): Local flap (nasolabial, submental)
• Medium: PMMF or RFFF
• Large / composite (with mandible): Fibula free flap
• Total glossectomy + FOM: ALT or rectus abdominis

b) Enumerate the blood supply and uses of nasolabial flap [4]

1. Superiorly based flap: Supplied by facial artery and its angular/lateral nasal branches; angular artery (terminal branch of facial artery) — more reliable blood supply
2. Inferiorly based flap: Supplied by facial artery and inferior labial branches; less reliable pedicle
3. Angular artery (a branch of the facial artery): The dominant vessel for the superiorly based pedicle

• Superiorly pedicled: Rotates into nasal lining, alar defects, medial cheek defects
• Inferiorly pedicled (tunnelled): Tunnelled under the cheek into the oral cavity for floor of mouth, soft palate, buccal mucosa

1. Floor of mouth reconstruction: After small-to-moderate resections; tunnelled inferiorly based flap
2. Buccal mucosa defects: Post-resection reconstruction
3. Soft palate: Small palatal defects
4. Alveolar reconstruction
5. Retromolar trigone

• Excellent skin colour and texture match for facial defects
• Reliable vascularity
• Simple technique; minimal donor site morbidity (scar hidden in nasolabial fold)
• Thin and pliable — suitable for intraoral lining
• Can be used as single-stage (tunnelled) or two-stage (divided at 3 weeks)

• Limited reach (regional flap)
• May be hair-bearing in males (problem for intraoral use)
• Scar visible if poorly placed
• Not suitable for large defects

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