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DNB Question Paper — Model Answers

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QUESTION 1 (10 Marks)

a) How does radiotherapy act? [3]

1. Repair — sublethal damage repair between fractions
2. Redistribution — cycling cells move into sensitive phases
3. Repopulation — tumor and normal cells repopulate between fractions
4. Reoxygenation — hypoxic cells become oxygenated after fractionation, increasing sensitivity

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

• Multiple small fractions (1.1–1.2 Gy) given 2–3× daily (≥6 hr apart)
• Allows a higher total dose with equivalent late toxicity
• Exploits differential repair: late-reacting normal tissues repair better between small fractions (low α/β ratio ~3) than tumor (high α/β ratio ~10)
• Example: RTOG 9003 showed improved locoregional control in H&N SCC

• Standard dose per fraction but given over a shorter total time to overcome tumor repopulation
• Subtypes: pure acceleration, accelerated with concomitant boost
• CHART (Continuous Hyperfractionated Accelerated Radiotherapy): 54 Gy in 36 fractions over 12 days

• Larger dose per fraction (>2 Gy), fewer fractions
• Shortens overall treatment time
• Used in palliative settings or SBRT (stereotactic body radiation therapy)
• Suitable for tumors with low α/β ratio (e.g., prostate cancer)

• Boost dose given to primary tumor during last 2 weeks while standard dose continues to wider field
• Reduces total treatment time without excessive toxicity

• Computer-generated dose sculpting to spare organs at risk (parotid glands, spinal cord, optic nerves)
• Reduces xerostomia, osteoradionecrosis
• IMRT → parotid-sparing → reduced xerostomia (PARSPORT trial)

• Daily imaging (CBCT) to reduce set-up error, enables tighter margins → smaller normal tissue volume irradiated

• Protons — Bragg peak allows precise dose deposition at tumor depth, minimal exit dose
• Neutrons — high LET (linear energy transfer), less oxygen-dependent

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

• Mucositis: painful erythema → pseudomembrane formation → ulceration; grade 3–4 requires hospitalization, feeding tube
• Dermatitis: erythema, dry then moist desquamation, skin breakdown
• Xerostomia: parotid gland injury (threshold dose ~26 Gy mean), reduced saliva
• Odynophagia/dysphagia: mucosal injury, edema
• Dysgeusia: altered/lost taste (recovery variable)
• Fatigue, myelosuppression (especially if concurrent chemotherapy)

• Xerostomia: permanent if parotid dose >40 Gy (major glands), dental caries
• Osteoradionecrosis (ORN): mandible most common; hypoxic-hypovascular-hypocellular tissue → bone necrosis after trauma/extraction; treated with HBO + surgery
• Trismus: fibrosis of pterygoid muscles/TMJ; >35 Gy
• Hypothyroidism: dose >45 Gy to thyroid; check TSH at 6 months post-RT
• Radiation-induced neuropathy: cranial nerve palsy, brachial plexopathy
• Carotid blowout syndrome: rare but catastrophic
• Secondary malignancy: sarcoma in radiation field; latency 5–10 years
• Lymphedema: external and pharyngeal

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QUESTION 2 (10 Marks)

a) What is gene mapping? [1]

• Genetic (linkage) mapping: based on recombination frequencies during meiosis; measured in centimorgans (cM); 1 cM = 1% chance of recombination
• Physical mapping: determines actual physical distances in base pairs (bp) using molecular techniques

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

1. Linkage Analysis: Co-segregation of genes with known markers in families; RFLP (restriction fragment length polymorphism) analysis
2. Somatic Cell Hybridization: Human-rodent hybrid cells retain specific human chromosomes; genes assigned to chromosomes by correlation with retained chromosomes
3. In-Situ Hybridization (FISH): Fluorescent probes hybridize to specific chromosomal loci on metaphase spreads; direct physical localization
4. Deletion Mapping: Identifying genes absent in patients with chromosomal deletions
5. Radiation Hybrid Mapping: Human chromosomes fragmented by radiation, fused to hamster cells; co-retention frequency used to estimate physical distance
6. Restriction Mapping: Restriction enzymes cut DNA at specific sequences; fragment sizes reveal gene organization
7. Contig Mapping/STS Mapping: Sequence-tagged sites anchored to YAC/BAC libraries
8. Comparative Genomic Hybridization (CGH): Identifies chromosomal gains/losses in tumor cells vs. normal genome
9. SNP Mapping (Genome-Wide Association Studies): High-density SNP arrays identify disease-associated loci

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

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

• Replace mutant gene with functional copy (e.g., CFTR in cystic fibrosis, p53 replacement in H&N cancer)
• Advexin (Ad-p53) — adenoviral p53 in H&N SCC

• Introduce new/exogenous gene not naturally present to produce therapeutic protein
• E.g., cytokine genes (IL-2, TNF-α) to stimulate anti-tumor immunity

• Antisense oligonucleotides, siRNA, shRNA, miRNA-based approaches
• Silence overexpressed oncogenes (e.g., EGFR, Bcl-2)

• Genetically engineered viruses that selectively replicate in and lyse tumor cells
• ONYX-015 — adenovirus with deleted E1B gene; replicates only in p53-deficient tumor cells

• HSV thymidine kinase (TK) gene inserted into tumor cells; ganciclovir converted to toxic form only in TK-expressing cells; bystander effect

• Transfect tumor cells with immunostimulatory genes (IL-2, GM-CSF, B7 co-stimulatory molecules) to enhance anti-tumor immune response
• Dendritic cell-based vaccination

• Deliver genes encoding anti-angiogenic factors (endostatin, angiostatin) to tumor microenvironment

• Restore function of inactivated tumor suppressors (p53, Rb, p16/CDKN2A) — frequently deleted in H&N SCC

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QUESTION 3 (10 Marks)

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

1. Stereotaxis: A rigid stereotactic frame is fixed to the skull under local anesthesia, providing a 3D coordinate reference system. This allows millimeter-precise targeting.
2. Multiple Convergent Beams: 201 (original Leksell) or 192 (Icon model) cobalt-60 (⁶⁰Co) sources arranged in a hemispheric array. Each individual beam carries a subtherapeutic dose. All beams converge on the isocenter (target), producing a therapeutically lethal dose at focus while surrounding normal tissue receives a small fraction of that dose.
3. Collimation: Each source has a collimator system; four collimator sizes (4, 8, 14, 18 mm) shape the radiation field to match target geometry. Multiple isocenters can be used for irregular or large targets.
4. High Dose Rate at Isocenter: Typical single-session dose: 12–16 Gy to arteriovenous malformations, 12–14 Gy to vestibular schwannoma, 20–24 Gy to brain metastases
5. Radiobiological Basis: High dose per fraction causes catastrophic DNA damage; exploits linear-quadratic model. Also causes direct vascular damage (endothelial injury, thrombosis) — especially important in AVMs.
6. Sharp Dose Gradient: 50% isodose line typically at tumor margin; ≥80% fall-off within a few mm outside target — key safety feature.
7. Immobilization: Rigid frame prevents any patient movement during treatment.
8. Treatment Planning: MRI/CT fusion-based 3D planning (GammaPlan software); dose-volume histograms optimize coverage and minimize critical structure doses.

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

• Patient placed supine; local anesthesia (lignocaine) at four fixation points (2 frontal, 2 occipital)
• Leksell stereotactic frame secured rigidly to skull with fixation screws
• Frame coordinates are now linked to the patient's anatomy

• Fiducial indicator box (FIB) attached to frame for imaging
• MRI (with gadolinium): best for soft tissue targets (VS, meningioma, AVM)
• CT: for bony lesions, pacemaker patients, claustrophobia
• MR Angiography for AVMs
• Images exported to GammaPlan workstation

• Neurosurgeon, radiation oncologist, and medical physicist collaborate
• Target volume delineated on fused images
• Prescription dose, collimator size, number of isocenters decided
• Dose constraints for critical structures set (optic chiasm <8 Gy, brainstem <12 Gy)
• Dose-volume histogram reviewed

• Frame attached to treatment couch adapter
• Patient positioned; frame coordinates verified

• Patient moves automatically into unit (helmet with collimators)
• Treatment delivered; time per shot = minutes to hours depending on dose
• Patient awake throughout, no anesthesia needed for adults

• Frame removed; patient observed 1–2 hours
• Dexamethasone prescribed if edema anticipated
• Discharged same day (outpatient procedure for most patients)
• Follow-up MRI at 6 months, then annually

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

1. Intracranial use only — the rigid frame system limits it to head; cannot treat extracranial sites (CyberKnife/LINAC-based SBRT used instead)
2. Size limitation — optimal for targets ≤3–3.5 cm diameter; larger tumors have poor dose gradient, risk of radiation necrosis
3. Eloquent cortex proximity — cannot treat tumors intimately involving optic chiasm (<2 mm), brainstem, without risk of serious toxicity
4. Single session only (single isocenter approach) — fractionated SRS (FSRS) requires repeated frame applications or mask-based systems
5. Radiation necrosis — occurs in 2–5%; mimics tumor recurrence on imaging (MRI perfusion/PET-CT needed for differentiation)
6. Delayed response — tumor shrinkage takes months to years; not for rapidly expanding lesions requiring urgent decompression
7. No tissue diagnosis — no histological confirmation unless prior biopsy
8. ⁶⁰Co source decay — cobalt sources need periodic replacement (half-life 5.27 years)
9. Lack of direct vision/surgeon's "feel" for intraoperative bleeding, CSF fistula, etc.

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QUESTION 4 (10 Marks)

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

1. Thyroglossal duct cyst (most common midline neck cyst — 70%)
2. Dermoid/epidermoid cyst
3. Plunging ranula (sublingual gland retention cyst)
4. Anterior cervical hygroma (cystic hygroma midline)
5. Median ectopic thyroid

• Submental/suprahyoid midline: dermoid, epidermoid, submental lymph node
• Hyoid level: thyroglossal cyst (most common here), subhyoid bursa
• Infrahyoid/pretracheal: thyroid isthmus lesion, delphian node, laryngocele, thymic cyst

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

• Age: Most common in children <10 years; can present at any age
• Location: 65% at or just below hyoid bone (subhyoid); 20% at thyrohyoid membrane; 15% at base of tongue (intralingual)
• Character: Smooth, soft, cystic, non-tender, midline or just off-midline (slightly left); transilluminates
• Pathognomonic sign: Moves upward with tongue protrusion and swallowing (attached to hyoid bone and tract)
• Size: Usually 1–4 cm

• Infection/abscess: most common reason for acute presentation; warm, tender, fluctuant swelling; may discharge spontaneously
• Thyroglossal sinus: after spontaneous/surgical drainage of infected cyst
• Dysphagia/dyspnoea: large or lingual thyroglossal cysts
• Thyroglossal duct carcinoma: 1% risk; usually papillary carcinoma; suspect if solid areas, cervical lymphadenopathy, or rapid enlargement

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c) Differences between ectopic and aberrant thyroid [4]

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QUESTION 5 (10 Marks)

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

1. Nasopharynx (bilateral) — most common occult primary; level II nodes, especially lateral retropharyngeal
2. Tongue base (bilateral) — blind biopsies bilaterally; HPV-related oropharyngeal SCC common
3. Tonsils/tonsillar fossae (bilateral) — tonsillectomy (not just biopsy) — increases detection rate of occult primary from 10% to 25–45%
4. Pyriform sinus (bilateral) — level II–IV nodes
5. Postcricoid/hypopharynx
6. Supraglottic larynx

• Level I nodes → oral cavity (floor of mouth, gingiva)
• Level V / posterior triangle → nasopharynx, thyroid, skin
• Supraclavicular (level IV/VB) → subglottic, thyroid, lung, esophagus, breast

• EBER (EBV-encoded RNA) in-situ hybridization for nasopharyngeal origin
• p16 IHC + HPV PCR for oropharyngeal origin (now directs targeted oropharyngeal workup)

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

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

• Gold standard; removes levels I–V
• Non-lymphatic structures sacrificed: SCM, internal jugular vein (IJV), spinal accessory nerve (CN XI)
• Indicated: massive cervical metastases with involvement of these structures
• Morbidity: shoulder drop/weakness (CN XI), neck deformity, facial edema (bilateral RND → bilateral IJV loss)

• Levels I–V preserved but one or more non-lymphatic structures preserved
• Type I MRND: IJV and SCM removed; CN XI preserved
• Type II MRND: IJV removed; CN XI and SCM preserved
• Type III MRND (Functional/Bocca's): All three structures (CN XI, IJV, SCM) preserved
• Most common type today; equivalent oncological outcomes to RND in N1-N2 disease

• Fewer than all five node groups removed; tailored to primary tumor drainage
• Supraomohyoid ND (SOHND): Levels I–III — oral cavity SCC
• Anterolateral ND: Levels I–IV — oropharynx, hypopharynx, larynx
• Lateral ND: Levels II–IV — oropharynx, hypopharynx, larynx (N0 neck)
• Posterolateral ND: Levels II–V + retroauricular + suboccipital — posterior scalp/neck melanoma
• Central Compartment ND: Level VI ± VII — thyroid carcinoma

• RND plus additional structures (carotid artery, hypoglossal nerve, vagus, skin, parotid)
• Reserved for exceptional cases with direct tumor extension

• Sentinel lymph node biopsy (SLNB): emerging for oral cavity T1-T2 N0; radioguided technique
• END (elective ND) for clinically N0 neck with >20% occult metastasis risk
• Bilateral ND for midline tumors (tongue base, supraglottic larynx, hypopharynx)

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QUESTION 6 (10 Marks)

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

• Nitrogen mustards: Cyclophosphamide, Ifosfamide, Mechlorethamine, Melphalan, Chlorambucil
• Nitrosoureas: Carmustine (BCNU), Lomustine (CCNU), Streptozocin (lipid-soluble; cross BBB)
• Alkyl sulfonates: Busulfan
• Triazines: Dacarbazine, Temozolomide
• Platinum compounds: Cisplatin, Carboplatin, Oxaliplatin (form intrastrand/interstrand DNA crosslinks)

• Folate antagonists: Methotrexate (inhibits DHFR, thymidylate synthesis)
• Purine analogues: 6-Mercaptopurine, 6-Thioguanine, Fludarabine, Cladribine
• Pyrimidine analogues: 5-Fluorouracil (5-FU; inhibits thymidylate synthase), Capecitabine, Gemcitabine, Cytarabine

• Topoisomerase I inhibitors: Irinotecan, Topotecan (camptothecin derivatives; cause single-strand breaks)
• Topoisomerase II inhibitors:
  • Epipodophyllotoxins: Etoposide, Teniposide
  • Anthracyclines: Doxorubicin, Daunorubicin, Epirubicin, Idarubicin (also intercalate DNA)

• Vinca alkaloids (inhibit polymerization): Vincristine, Vinblastine, Vinorelbine
• Taxanes (inhibit depolymerization): Paclitaxel, Docetaxel
• Estramustine

• Intercalating: Actinomycin D (dactinomycin), Bleomycin (causes DNA strand breaks + free radicals)
• Anthracyclines: Doxorubicin (intercalation + Topo II inhibition)

• Monoclonal antibodies:
  • Anti-EGFR: Cetuximab (chimeric IgG1), Panitumumab
  • Anti-HER2: Trastuzumab
  • Anti-VEGF: Bevacizumab
  • Anti-PD-1: Pembrolizumab, Nivolumab (immune checkpoint inhibitors)
• Tyrosine kinase inhibitors (TKI): Erlotinib, Gefitinib (EGFR-TKI), Lapatinib
• mTOR inhibitors: Everolimus, Temsirolimus
• BCR-ABL inhibitors: Imatinib (CML)
• Proteasome inhibitors: Bortezomib (multiple myeloma)
• CDK4/6 inhibitors: Palbociclib

• Antiestrogens: Tamoxifen, Fulvestrant
• Aromatase inhibitors: Anastrozole, Letrozole
• Antiandrogens: Enzalutamide, Bicalutamide
• LHRH agonists: Leuprolide, Goserelin

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

• Given before definitive surgery or radiotherapy
• Goals: tumor downstaging, early treatment of micrometastases, assess chemosensitivity
• TPF regimen: Docetaxel + Cisplatin + 5-FU (TAX 323/TAX 324 trials) — superior to PF; used for organ preservation in larynx/hypopharynx
• PF regimen: Cisplatin + 5-FU
• Used to preserve larynx/hypopharynx function; if good response → definitive RT; if poor → surgery

• Chemotherapy given simultaneously with radiation to act as radiosensitizer
• Most important strategy in H&N SCC; improves locoregional control and overall survival
• Cisplatin (100 mg/m²) every 3 weeks concurrent with RT — standard of care
• Weekly cisplatin (40 mg/m²) — better tolerated, used in low-resource settings
• Cetuximab + RT (Bonner trial) — alternative for cisplatin-ineligible patients; improved OS vs RT alone
• Used for: locally advanced oropharyngeal, laryngeal, hypopharyngeal, nasopharyngeal SCC (post-op CCRT for high-risk features: positive margins, ENE)

• After surgery; limited role in H&N SCC
• Post-operative CCRT (cisplatin + RT) for high-risk pathological features: positive margins, extranodal extension (RTOG 9501 / EORTC 22931)

• For recurrent/metastatic disease not amenable to surgery or RT
• EXTREME protocol (first-line): Cetuximab + Cisplatin/Carboplatin + 5-FU (Vermorken et al.) — significantly improved OS
• KEYNOTE-048: Pembrolizumab ± chemotherapy for R/M H&N SCC with CPS ≥1
  • Pembrolizumab + Platin/5-FU → new standard first-line for CPS ≥1
  • Pembrolizumab monotherapy for CPS ≥20
• Nivolumab (CheckMate 141) — second-line after platinum failure

• Nasopharyngeal carcinoma: Induction TPF → concurrent cisplatin-RT (Al-Sarraf protocol: cisplatin-RT → adjuvant PF)
• Salivary gland tumors: Cyclophosphamide + Doxorubicin + Cisplatin (CAP) for advanced/metastatic; anti-HER2 (trastuzumab) for HER2+ tumors
• Thyroid (anaplastic): Doxorubicin + cisplatin; lenvatinib; pembrolizumab

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QUESTION 7 (10 Marks)

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

• Tracer: Most commonly ¹⁸F-FDG (fluorodeoxyglucose) — glucose analogue labeled with ¹⁸F (positron emitter, half-life 110 min)
• Uptake: FDG enters cells via GLUT transporters (upregulated in cancer), is phosphorylated by hexokinase to FDG-6-phosphate, which is metabolically trapped (cannot undergo glycolysis further) — metabolic trapping
• Positron emission: ¹⁸F decays by emitting a positron (β+)
• Annihilation: Positron travels 1–2 mm, then annihilates with an electron, producing two 511 keV gamma photons traveling in exactly opposite directions (180°)
• Coincidence detection: Two opposed detector rings simultaneously detect both gamma photons → line of response (LOR) drawn between them; thousands of LORs reconstruct a 3D image of metabolic activity
• Biological basis of cancer imaging: Cancer cells have Warburg effect — preferential aerobic glycolysis → increased GLUT expression and hexokinase activity → high FDG uptake relative to most normal tissues

• Attenuation correction (from CT component of PET-CT)
• Spatial resolution: ~4–6 mm (FDG-PET), improving with new digital detectors
• Image reconstruction: filtered back-projection or iterative algorithms (OSEM)

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

SUV = [Tissue radioactivity concentration (kBq/mL)] / [Injected dose (kBq) / Body weight (g)]

• SUV = 1.0: Uptake equal to the average in the body (uniform distribution)
• SUV >2.5: Generally considered suspicious for malignancy in most tissues
• SUVmax: Maximum voxel value in the ROI — most commonly reported; less affected by partial volume effects than mean SUV
• SUVpeak: Average of 1 cm³ around the hottest voxel — more robust, less noisy

• Differentiate malignant from benign lesions (threshold typically SUVmax ≥2.5)
• Prognostication: Higher SUVmax correlates with worse prognosis in H&N SCC
• Response assessment: decrease in SUVmax after treatment indicates response (PERCIST criteria)
• Limitation: SUV is affected by blood glucose level, time between injection and scan (60–90 min standard), body composition, scanner calibration — hence "standardized" conditions essential

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

• Detection of nodal metastases (sensitivity 80%, specificity 90% for N+ disease)
• Detection of distant metastases (lung, liver, bone, mediastinum) — changes management in ~10–15% cases
• Identification of synchronous primary tumors (H&N cancer has 3–5% synchronous second primary rate)

• CUP with neck metastases: PET-CT has sensitivity ~55% for identifying occult primary
• Combined with panendoscopy and directed biopsies (HPV-guided)
• Detects primaries in tongue base, tonsil (highest yield when combined with DWIBS-MRI)

• Gold standard: FDG-PET 12 weeks after completion of chemoradiotherapy for H&N SCC
• High negative predictive value (NPV >90%) for neck — if PET-CT negative, observation safe without planned neck dissection (PETNECK trial: NPV 93%)
• Identifies residual/recurrent disease in primary site

• Post-treatment surveillance in high-risk patients
• PET-CT 3–6 months post-treatment detects recurrence earlier than CT/clinical exam alone

• Biological target volume (BTV): FDG-avid subvolumes within gross tumor for dose escalation (dose painting)
• Better GTV delineation in difficult anatomical regions (skull base, oropharynx)

• ¹²³I/¹³¹I scintigraphy is primary modality
• FDG-PET: For radioiodine-negative metastatic differentiated thyroid cancer (thyroglobulin-elevated, iodine-scan negative — TENIS syndrome)
• Medullary thyroid carcinoma staging: ⁶⁸Ga-DOTATATE PET/CT

• Staging, post-treatment assessment, detection of distant metastases

• Waldeyer's ring lymphoma, HL/NHL — staging (Lugano classification), interim response, end-of-treatment response (Deauville 5-point scale)

• Limited role for FDG; Ga-68 PSMA PET emerging for ACC (adenoid cystic carcinoma)

• Searching for occult malignancy

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QUESTION 8 (10 Marks)

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

• Lignocaine binds to the α-subunit of voltage-gated Na⁺ channels in the inner vestibule (intracellular side) of the channel
• It preferentially binds to channels in the open or inactivated state (use-dependent/frequency-dependent block) — explains why it works better on rapidly firing neurons
• Binding prevents Na⁺ influx → membrane cannot depolarize → action potential propagation blocked
• Result: reversible blockade of nerve conduction in the sequence: autonomic > sensory (pain/temp first, then touch, proprioception) > motor

• At higher concentrations: stabilizes cardiac membranes (Class 1B antiarrhythmic — also blocks fast Na⁺ channels in myocardium; accelerates repolarization)
• Inhibits G-protein-coupled receptors and reduces inflammatory mediator release at local level

• pKa 7.9 → at physiologic pH, ~25% un-ionized (active membrane-permeable form) — onset ~3 min
• Ester vs amide: metabolized by hepatic microsomal enzymes (CYP1A2, CYP3A4) → active metabolite monoethylglycinexylidide (MEGX)
• No metabolic inactivation by plasma pseudocholinesterase (unlike esters)

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

• 1% lignocaine = 10 mg/mL → max volume of 1% plain = 20–30 mL (for 70 kg patient = 210 mg)
• 2% lignocaine with epinephrine: 7 mg/kg → 70 kg → 490 mg → ~24 mL of 2%

• Site of injection: Highly vascular sites (intercostal > caudal > epidural > brachial plexus > subcutaneous) absorb faster → lower safe dose
• Patient: Hepatic disease, cardiac disease, extremes of age, pregnancy — reduce dose
• Epinephrine → vasoconstriction → slows absorption → safe dose increases

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

• Pain at injection site, hematoma
• Infection (from injection technique)
• Neurotoxicity: peripheral nerve damage if injected intraneural

• Early (excitatory): Perioral/tongue numbness, tinnitus, lightheadedness, visual disturbances, restlessness, anxiety, dysarthria
• Intermediate: Tremors, muscle twitching
• Late (inhibitory/severe): Grand mal seizures, unconsciousness, respiratory arrest
• Threshold: CNS toxicity at ~5 µg/mL plasma; convulsions at 10 µg/mL

• Bradycardia, hypotension
• Widening QRS, prolonged PR interval
• Ventricular arrhythmias (VF, VT) — especially with inadvertent IV injection
• Cardiac arrest
• "All or nothing" cardiovascular collapse (less common than bupivacaine)

• True allergy to amide LAs is rare (<1%)
• More commonly reaction to methylparaben preservative (in multidose vials) or epinephrine additive
• Anaphylaxis possible but uncommon

• High doses especially with EMLA (prilocaine component), benzocaine; rare with lignocaine
• Presents as cyanosis unresponsive to oxygen; treat with methylene blue

• Transient neurological symptoms (TNS) — post-spinal lignocaine (now largely replaced by bupivacaine for spinal)
• Cauda equina syndrome (hyperbaric spinal) — rare

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

• The ear canal and pinna receive innervation from:
  • Auriculotemporal nerve (V3 — anterosuperior canal)
  • Great auricular nerve (C2, C3 — posteroinferior/lobule)
  • Auricular branch of vagus (Arnold's nerve — posterior wall)
  • Facial nerve branch (small contribution)

1. 12 o'clock (12 o'clock position — superior canal wall): Injection at the bone-cartilage junction of the anterosuperior canal wall — blocks auriculotemporal nerve
2. 3 o'clock (or 9 o'clock — anterior canal wall): At bone-cartilage junction anteriorly
3. 6 o'clock (inferior canal wall/floor): At bone-cartilage junction inferiorly — blocks great auricular nerve
4. 9 o'clock (or 3 o'clock — posterior canal wall): At bone-cartilage junction posteriorly — blocks Arnold's nerve

• 1–2% lignocaine with 1:80,000–1:200,000 adrenaline used
• Injections made at the bony-cartilaginous junction (not deep into canal) — 4 quadrant injections, 0.3–0.5 mL each
• Additional injection: Postauricular (posterior auricular nerve) — 1–2 mL behind pinna along postauricular fold
• Anterior tragal injection (vascular supply/anterior pinna)
• Total volume: 2–4 mL
• Adrenaline achieves vasoconstriction → bloodless field crucial for microsurgery

• Allows tympanoplasty, myringoplasty, grommet insertion under LA with sedation
• Excellent hemostasis due to epinephrine
• Avoids general anesthesia risks
• Allows intraoperative patient cooperation (hearing assessment during ossiculoplasty)

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QUESTION 9 (10 Marks)

a) Enumerate the cytological features of dysplasia [3]

1. Nuclear enlargement — increased nuclear size, nuclear:cytoplasmic (N:C) ratio >0.5
2. Nuclear pleomorphism — variation in nuclear shape and size (anisokaryosis)
3. Hyperchromasia — increased nuclear staining due to increased DNA content
4. Irregular nuclear membrane — scalloped, indented, or angulated nuclei
5. Prominent/abnormal nucleoli — enlarged, irregular, multiple nucleoli
6. Increased mitotic figures — especially abnormal (tripolar, ring) mitoses
7. Abnormal chromatin pattern — coarsely clumped chromatin, parachromatin clearing

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

• Architectural and cytological changes confined to the lower third (basal layer) of the epithelium
• Low risk of malignant transformation (~5%)

• Changes extend to the middle third of the epithelium
• Intermediate risk (~10–15%)

• Changes extend to the upper third but basal orientation remains
• High risk (20–30%)

• Full-thickness cytological and architectural changes with complete loss of maturation
• Basement membrane intact (no invasion)
• Very high risk (>30–50%)

• Low-grade intraepithelial lesion (LGIL): squamous hyperplasia + mild/moderate dysplasia
• High-grade intraepithelial lesion (HGIL): severe dysplasia + CIS

• Grade I (mild): Hyperplasia of basal cells, slight atypia
• Grade II (moderate): Atypical cells middle third
• Grade III (severe): Atypical cells upper third
• CIS: Full-thickness dysplasia

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

• Microlaryngoscopy + biopsy (operative); narrow band imaging (NBI) to delineate margins
• CT/MRI not required for CIS (no invasion); assess contralateral cord, anterior commissure involvement

• Cold knife or microdebrider excision of diseased mucosa (epithelium only)
• Preferred for limited CIS (unilateral, not involving AC)
• Submucous resection: excision of epithelium + superficial lamina propria; preserves thyroarytenoid muscle
• Allows histological examination of entire specimen (vs. laser — charred margins)
• Recurrence rate: 10–30%; repeat excision feasible

• Most widely used; European Laryngological Society (ELS) Classification:
  • Type I (subepithelial cordectomy): Epithelium only removed — appropriate for CIS
  • Type II: Subligamental; Type III: Transmuscular; Type IV: Total; Type V: Extended
• Hemostasis excellent; outpatient or day-care procedure
• Limitation: charred margins may complicate histology assessment

• Delivers 60–66 Gy in 30–33 fractions over 6–6.5 weeks
• Excellent local control (~90% at 5 years) and voice quality preservation
• Preferred in: bilateral CIS, anterior commissure involvement, recurrent CIS after multiple endoscopic procedures, patient unable/unwilling to undergo endoscopy
• Toxicity: temporary dysphonia, edema; late: radiation changes, fibrosis, risk of radionecrosis

• Porfimer sodium (Photofrin) administered IV; activates with 630 nm laser
• Selective destruction of dysplastic tissue
• Limited availability; risk of photosensitivity

• Microlaryngoscopy at 3–6 months after treatment
• Frequent surveillance (3-monthly initially) for 2 years; annually thereafter
• NBI/contact endoscopy supplements white light endoscopy for residual/recurrent disease

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QUESTION 10 (10 Marks)

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

• Small (T1–T2, <3 cm): Primary closure or split-thickness skin graft (STSG)
• Moderate (3–5 cm): Locoregional flap
• Large (>5 cm, with mandible/tongue involvement): Free flap

• Only for very small anterior FOM defects
• Risk: tethering of tongue → restricted mobility, impaired speech/swallowing

• For small-moderate defects with adequate bed (no bone exposure)
• Provides epithelial cover; no bulk
• Contracts → tongue tethering remains a risk
• Best for elderly patients unfit for free flap

• Tongue flap (dorsal or tip): Small anterior FOM defects; reliable; donor site on tongue
• Buccal mucosal advancement flap: Small posterior FOM defects

• Submental island flap:
  • Pedicled on submental artery (branch of facial artery)
  • Skin + platysma from submental region
  • Thin, pliable; excellent for FOM; good color match
  • Caution: oncological contraindication if level IA nodes are positive; pedicle passes through at-risk nodal territory
• Nasolabial flap: Pedicled on angular/facial artery; used for small FOM defects; two-stage if oral tunneling needed
• PMMC (Pectoralis Major Myocutaneous Flap):
  • Pedicled on thoracoacromial artery
  • Reliable, large volume; good for simultaneous FOM + mandible bar coverage
  • Limitations: bulky, hair-bearing in males, restricted reach, poor voice outcomes, donor site morbidity (shoulder), ptosis
  • Still widely used in salvage/post-RT situations, elderly patients, resource-limited settings

• T1–T2, no mandible: RFFF (preferred) or submental flap
• With marginal mandibulectomy: RFFF or ALT + plate reconstruction
• With segmental mandibulectomy: Fibula osteocutaneous free flap
• Salvage/post-RT/elderly: PMMC (reliable, no microsurgery needed)

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

• Angular artery (terminal branch of facial artery) → enters the pedicle superiorly
• Contributions from: infraorbital artery (branch of maxillary/internal maxillary artery) and transverse facial artery (branch of superficial temporal artery)
• The superior flap has a true axial pattern based on the angular artery

• Facial artery and its labial branches
• Submental artery contributions
• More reliable for submandibular/floor of mouth rotation

• Facial vein, angular vein → to internal jugular vein

• Based on perforators from facial artery; allows a more inferiorly placed pivot point

1. Floor of mouth reconstruction — small to moderate anterior FOM defects; two-stage (intraoral tunneling)
2. Buccal mucosal defects — after excision of buccal SCC; pedicled into mouth through buccal tunnel
3. Alveolar/gingival defects — small defects along alveolar ridge
4. Lip reconstruction — lower lip defects <1/3 (Abbe-Estlander variant)
5. Partial glossectomy defects — small anterior tongue defects (one-stage if skin paddle folded into mouth)

• Abundant, well-vascularized tissue in the cheek
• Thin, pliable skin with good color match for facial reconstruction
• Donor scar concealed in nasolabial fold (cosmetically acceptable)
• Can be raised as one-stage or two-stage procedure
• No microsurgery required

• Hair-bearing skin in males (may require epilation/shaving within oral cavity)
• Limited reach (regional flap; cannot reach posterior oral cavity)
• Two-stage procedure needed for intraoral use (first stage: inset flap with pedicle; second stage: divide pedicle at 3 weeks)
• Relatively small paddle — not suitable for large defects
• Risk of facial asymmetry/depression at donor site