Comprehensive Management of Head and Neck Cancer Narayana Subramaniam, Sivakumar Vidhyadharan, Samskruthi P Murthy
INDEX
Page numbers followed by f refer to figure, fc refer to flowchart, and t refer to table.
A
Abscess 46
Acetone 23
Acidosis, respiratory 452
Acinic cell carcinoma 109
Acquired immunodeficiency syndrome 359
Acral-lentiginous melanoma 275
Activator protein 1 127
Active osteoclastic reaction 115
Activities of daily living 408
Acute hypoparathyroidism
signs of 352t
symptoms of 352t
Acute pain 586
management of 587
Adenocarcinoma 26, 98, 109, 191, 192, 197, 215, 253, 506f
polymorphous 253
low-grade 109
Adenoid 219
cystic carcinoma 109, 110, 192, 202, 253, 383
Adenoma
benign 305
pleomorphic 251, 254
re-recurrent pleomorphic 251f
Adenomatoid odontogenic
fibromas 468
tumor 465
Adenosine deaminase 292
Adequate soft tissue bulk 516
Adjuvant radiotherapy after surgery 111
Adjuvant therapy 326
role of 138, 234
Adrenocorticotropic hormone 328
Advanced gingivobuccal cancer
compartmental resection of 502f
reconstruction of 502f
Afatinib 403, 426
Airway
anesthetizing 40
disorders 382
evaluation 38
fires 44
invasion of 320
management of 39, 45
obstruction
acute 385
palliation of 334
protection 170
Alcohol 103, 149, 175
cessation 33, 34
consumption 149, 175
exposure 175
Allogenic dura 515
Alpha emitters 431
Alveolar foramen, inferior 206
Alveolar nerve canal, inferior 22
Alveolar ridge 107109
Alveolar soft part sarcoma 359
Alveolar vessels, inferior 115
Ameloblastoma 464
desmoplastic 466
in situ 464
invasive 464
malignant 467
microinvasive 464
peripheral 466
American Cancer Society Scale 564
American Dietetic Association 555
American Joint Committee on Cancer 105, 106t, 132, 181, 182t, 222, 223t, 287, 287t, 288t, 293, 295t, 331t, 384
American Society of Anesthesiologists 481
American Thyroid Association
High-Risk Category 316
Intermediate-Risk Category 315
Low-Risk Patients 315
Amifostine 377
Amino acid 53, 435
Amitriptyline 589
Anaplastic thyroid carcinoma 324, 333
Androgen receptor 256
Androgenetic deprivation therapy 256
Anesthesia 38
maintenance of 41
Anesthetic optimization 484
Ang's prospective trial 112
Angiofibroma 204
juvenile 207
Angiogenesis 420
Angiography 269
Angioinvasion 305
Angiomatoid fibrous histiocytoma 359
Angiosarcoma 109, 365
Anhidrosis 392
Ankylosis 38
Anorexia 51
Anosmia 197, 198
Antebrachial flap 46
Anterior cranial fossa 201, 206
parts of 212f
Anterior skull base 195
reconstruction 516
tumors 205, 206
Anterolateral thigh 521
flap 487
Anthracycline 255
Antibiotic prophylaxis 42, 47
Antibody interference 318
Anticonvulsants 589
Antidiuretic hormone 203
Antiepidermal growth factor receptor 5
Antireflux treatment 79
Antisepsis 1
Antithrombotic agents 42
Antivascular endothelial growth factor 431
Anxiety 30, 335
disorders 30
Arizona 61
Arm
disabilities of 572
flap, lateral 493
quick disabilities of 572
Armamentaria 396
Arnold's nerve 104, 264
Arrhythmias 53
Arterial systems 229
Artery
pharyngeal 201
superior ethmoidal 200
supratrochlear 516
Aryepiglottic folds 150
Arytenoid 150
cartilage 16, 153
Asbestos 150, 191
Aspiration
rate of 143
risk 38
tracheal 46
Aspirin 70
Asthma 382
Ataxia telangiectasia 418f, 419, 425
Atypical mole syndrome 273
Autofluorescence endoscopy 77
Autologous grafts 386
Autosomal dominant 285, 324
Autosomal recessive 285, 324
Awake fiberoptic intubation 39
Axial fluid-attenuation inversion recovery 193
Axillo-bilateral breast approach 450
Azacytidine 428
B
Balance disease control 99
Balloon
brachytherapy technique 375
occlusion test 90
test occlusion 231
Barium swallow impairment profile, modified 553, 554
Baroreceptor damage 38
Basal cell
carcinoma 192, 284, 285, 290
nevus syndrome 285
Basaloid squamous cell carcinoma 26
Bazex-Dupré-Christol syndrome 285
B-cell lymphoma 220f
Beckwith-Wiedemann syndrome 358
Bell's palsy 534
Benzodiazepines 32
Beta-catenin 427
encoding gene 366
Beta-emitters 430
Bevacizumab 400
Bifrontal craniotomy 195
Bilateral axillo-breast approach 450, 451
Binimetinib 279
Biopsy 96, 132
Bioreductive agents 377
Bioreductive drugs 376
Bipolar Maryland forceps 137f
Bleeding 43
posterior 483
Bleomycin 474
topical 68
Blind finger dissection 252
Blood
biochemistry 192
flow 483
pressure monitoring, invasive 40
tinged saliva 104
transfusion 41
Bloom syndrome 285
Blowtorch scenario 45
Bocca's sign 177
Body
mass index 51
tissue, normal 23
Bone
anchored hearing aid 235
cancer treatment 230
cysts, aneurysmal 464
erosion 206
loss 578f
manifestations 344
marrow aspiration 192
resorption 354
tumors 360
tympanic 233
Borle's extension 209, 210f
Boron neutron capture therapy 376
Botryoidal odontogenic cysts 463
Botulinum toxin injection 588
Brachioradialis muscle 350
Brachytherapy 4
Brain 432
parenchyma 205, 208
Branchial arches 328
Breathlessness 335
Broder's grading system 28
Bronchitis 382
Bronchoscopy 384
Brow 536
Brown's classification 211f
Brush cytology 61
Buccal defects, classification of 501t
Buccal mucosa 107109, 116, 501
cross-section of 500f
reconstruction 500
Buccopharyngeal fascia 125
Bupropion 72
Burkitt's lymphoma cell 220
C
Cabozantinib 333
Cachexia 51
cancer of 51
Calcitonin 332
serum 329, 343
Calcitriol 342
Calcium 347
carbonate 352
channel blockers 41
dependent transmembrane adhesion 427
gluconate 352
homeostasis 342
normal 342
required doses of 350t
supplementation 347
Cancer 65
anterior skull base 197
cachexia, pathophysiology of 54f
cells 373
central molecular pathophysiology of 417
diagnosis of 30
hallmarks of 417
hypopharyngeal 89, 180, 186, 187, 375, 447
nonoropharyngeal 98
nonsquamous 109, 109t
postcricoid 177
promoting inflammation 420
recurrent laryngeal 169
second primary 593
signs of 51
stem cells 419
subglottic 161
supraglottic 159
traits 418f
Candida 103
Canine smile 533
Capecitabine 255
Capillary malformation 471, 474
Capsular invasion 305
Carbamazepine 589
Carbohydrate 51
Carbon ion radiotherapy 254
Carboplatin 397
Carcinoembryonic antigen 330
Carcinogen exposure 126
Carcinogenesis 62, 126, 284
human papillomavirus-induced 127fc
inhibition, antioxidants in 149
tobacco-induced 71fc
Carcinogenic volatile nitrosamines 221
Carcinoma 26t, 98
ameloblastic 467
anaplastic 301, 334, 335
epithelial myoepithelial 109
ex pleomorphic adenoma 109
hypopharyngeal 178
in situ 65
metastatic nasopharyngeal 224
mucoepidermoid 109
nonkeratinizing 220
odontogenic 466
postcricoid 175, 178, 179
recurrent nasopharyngeal 224
sebaceous 293
cyst 284
sinonasal undifferentiated 192, 193, 204
thyroid, left lobe follicular 25f
Cardiac failure, congestive 473
Carnoy's solution 462
Carotid 219
artery 13f, 84, 90, 139, 213, 391
balloon test 213
internal 15, 137, 201, 229, 230, 232, 391
involvement, management of 90
protection, lack of 251
stenosis 38
upper internal 214
blowout 379
body tumors 263, 270, 270fc, 271
bulb 137
canal 232
involvement 85
preoperative evaluation of 213
pulse 105
resection 392
sacrifice 213
sinus reflex 44
vascular involvement 15
vessels 14
Cartilage 518
Cartilaginous septum 191
Cataract 215
Cavernous sinus 222, 268f
coronal section of 199f
exposure of 268f
Cell cycle regulation 425
Cementoblastoma 465, 467
Central neck dissection technique 312
Central venous catheter 40
Cephalic vein 482f
Cerebrovascular accident 476
Cerebrovascular circulation 214
Cervical
approaches 311
esophageal cancers, upper 54
esophagus 167, 176, 184
exenteration 386
lymph node 82
metastases, incidence of 253t
lymphadenopathy 94, 104
plexus roots 46
trachea 384
Cetuximab 399, 403, 413, 426
containing combination therapy 399
intravenous 142
Charged particle radiotherapy 376
Charlson comorbidity index 409
Cheek defects 501
Chelators 431
Chemodectomas 262
Chemoimmunotherapy 397
Chemoluminescence 61
Chemoprevention 70, 70t, 79, 291
primary 69
secondary 69
Chemoradiotherapy 112, 133, 134, 184, 393
posterior 4
primary 98
Chemosis 198
Chemotherapy 5, 55, 133, 143, 196, 208, 254, 354, 364, 374, 397, 413, 596
administration 412
conventional 255
cytotoxic 402
drug 412
evolution of 5
meta-analysis of 136
neoadjuvant 412
nonhematological complications of 410
palliative 387
platinum-based 399, 413
role of 136, 412
single-agent 402
Chernobyl disaster 343
Chevalier Jackson's sign 177
Chinese-letter pattern 204
Chin-to-manubrium stitch stitch 386
Cholecalciferol 347
Chondrocalcinosis 343
Chondronecrosis 433
Chondrosarcoma 109, 194, 203, 207, 360, 368
Chordoma 203
Chromium 191
Chromogranin 203
Chronic hypoparathyroidism
signs of 352t
symptoms of 352t
Chronic obstructive pulmonary disease 382
Chyle leak 87
Circular total laryngopharyngectomy 187
Cis-diamminedichloroplatinum 224
Cisplatin 136, 139, 255, 413, 589
plus pemetrexed 400
Cisplatinum 224
Clamshell incision 385
Clear cell
carcinoma 109
sarcoma 359
Clinical scoring systems 572
Clonidine 41
Cobimetinib 279
Codman's triangle 367
Color-coded Doppler sonography 476
Combination cytotoxic chemotherapy 400
Combined positive score 398
Commissurotomy, anterior 158
Complete decongestive therapy 566
Composite tissue allotransplantation 6
Comprehensive geriatric assessment 408, 409t
Computed tomography 12, 581
role of 566
scan 531
Computer-aided surgery 584
Computerized tomography, contrast-enhanced 192
Concomitant boost accelerated schedule 134
Concurrent chemoradiotherapy 133, 134, 185, 413
role of 387
Concurrent chemotherapy 224
Condyle 252
Congenital vascular anomalies, management of 476fc
Conservative partial pharyngectomy 183
Constant-Murley shoulder outcome score 572
modified 572
Contact endoscopy 157
Continuous hyperfractionated accelerated radiation therapy 374
Contralateral fibula free flap 507
Conventional transcervical techniques 453
Cordectomy
subligamental 158
supepithelial 158
total 158
transmuscular 158
Corlett loop 482f
Cortical bone 193
involvement 14
Corticosteroids
dose of 183
use of 42
Costal cartilage 386
Costello syndrome 358
Cowden‘s syndrome 324
Cranial bone 518
Cranial fossa, middle 108, 206, 219
Cranial nerve 104
lower 262f
rehabilitation 516
resection 392
Craniocaudal movements 176
Craniofacial implant classification 583f
Craniofacial resection 38, 194, 208, 211
Craniotomy
middle 233
posterior 233
Cribriform plate 198, 209
coronal images of 193
erosion of 193
Cricohyoidoepiglottopexy 549
Cricoid cartilage 13f, 16, 152, 222, 382, 384
Cricopharyngeal myotomy 167
Cricopharyngeus muscle 176
Cricothyroid membrane 178
Cross-face nerve graft 539
Cumulative illness rating scale 409
Cupid's bow 501
Curcumin 69
Cushing's syndrome 328
Cutaneous squamous cell carcinoma 284, 286, 290
Cyclin-dependent kinase 127, 425
inhibitor 220f
Cyclophosphamide 255, 354, 368
Cyclopyrimidine dimers 285
Cysteine-rich domain 329
Cysts
lateral periodontal 463
malignant 95
nonodontogenic 464
odontogenic 461
periapical 461
residual 461
Cytokeratin 202, 203, 286
Cytosine, methylation of 427
Cytotoxic therapy 327
D
da Vinci single port 454
Dabrafenib 279
Dacarbazine 354
De Almeida's meta-analysis 445
Debulking tumor 42
Deep cervical fascia 183
Deep circumflex iliac artery flap 495
Deep soft tissue extension, assessment of 286
Delanian's radiation-induced fibrosis theory 581fc
Dental
amalgam 106
extraction 115
implant placement 584fc
after radiotherapy 584fc
primary 583f
lamina 461
oncology and maxillofacial prosthodontics, principles of 578
Dentigerous cyst 461
radiologic types of 472f
Deoxyribonucleic acid 126, 127, 129, 149, 176, 285, 417
damage response pathway 426
Depression 30
ICD-10 diagnostic criteria of 33
Dermatofibrosarcoma protuberans 292, 359
Device-assisted closure 483
Dexmedetomidine 41
Diabetes mellitus 481
DICER1 syndrome 324
Diethylenetriaminepentaacetic acid 434
Difficult Airway Society Extubation Guidelines 43fc
Difficult mask ventilation 38
Diffuse sclerosing variant 306
Diffusion-weighted imaging 12f
Digestive tract 102
Digital photography 565
Digital subtraction angiography 473
Dihydroxyphenylalanine 269
Diplopia 198
Direct laryngoscopy 155, 167
Direct nerve repair 537
Disease-free survival 139, 278
Disrupted endothelial surfaces 483
Distant metastases 104f, 156, 286, 319
management of 278, 327
Docetaxel 136, 224, 393, 397, 589
Donor sensory nerves 538
Doxorubicin 255, 354
Doxycycline 474
Dumbbell appearance 266
Durvalumab 402
Dynasplint trismus system 569
Dyskeratosis 28
congenita 285
Dysphagia 94, 104, 130, 177, 182, 223, 254, 359, 392, 396, 547, 548, 550, 557t, 596
following thyroidectomy 551
sideropenic 175
Dysplasia 77
epithelial 65
grade of 63
mild 77
mild to moderate 79
moderate 77
severe 65, 77, 79
Dyspnea 151, 359
E
Ear 373
ipsilateral 177
Earache 94
Early stage disease 110, 207
Eastern Cooperative Oncology Group 398
Ectropion 215
Edmonton symptom assessment system 30, 31f
eFACE 534
Eicosapentaenoic acid 51
Electrodiagnostic tests 571
Electrolaryngeal speech 550
Elemental calcium 352
Embolectomy, elimination of 485
Emphysema, subcutaneous 452
En bloc resection 232
Enamel epithelium 461
Encapsulated angioinvasive follicular carcinoma 306
Encorafenib 279
Endemic nasopharyngeal cancer 222
Endocrinopathies 342
Endolaryngeal soft tissues 151
Endoscope, robotic 443f, 452
Endoscopic approach 194, 208
Endoscopic surgery 207, 209, 226
Endoscopic thyroidectomy 451
classification of 450t
Endoscopic tumor resection 208
Endothelin receptor type B 220f
Endotracheal tube 45, 385
Endtidal carbon dioxide 45
analysis 44
Endtidal nitrogen 45
analysis 44
End-to-end anastomosis 386, 482
Enhanced recovery after surgery 47
Enophthalmos 392
Enzymes 299
Eosinophils 204
Epidermal growth factor 419
receptor 127, 256, 418f
pathway 419
Epidermodysplasia verruciformis 285
Epigenetic modification 421
Epiglottectomy, ipsilateral 447
Epiglottic reconstruction 549
Epiglottis 13f, 150, 178f
Epiphora 226
Epirubicin 255
Epithelial cell 420
types of 220
Epithelial dysplasia, human papillomavirus-associated 66
Epithelial membrane antigen 202, 286
Epithelium 151
Epstein-Barr virus 6, 219, 220, 220f, 221
Erlotinib 403
Eruption cyst 461, 462
Esmolol 41
Esophageal management 322
Esophageal speech 551
Esophagoscopy 179, 384
Esophagus 178
Esthesioneuroblastoma 192, 193, 213
diagnosis of 193
Esthetic rehabilitation 516
Estlander flap 503
Estrogen receptor 256
Ethmoid bone 201
Ethmoid sinus 198, 205, 211, 279
Ethmoidal arteries, inferior 200
Ethmoidectomy 211
Ethyl alcohol 23
European Cooperative Oncology Group 113
European Laryngological Society classification of endoscopic
cordectomies for glottic carcinoma 158t
supraglottic laryngectomy 160t
European Organization for Research and Treatment of Cancer System 564
European Society for Clinical Nutrition and Metabolism 552
Eustachian tube 219, 230
Ewing's sarcoma 359, 365, 368
Exfoliative cytology 25
External auditory canal 232, 233
External beam radiotherapy 168, 327, 331, 364
combined 326
role of 325
technique 168
External carotid artery 264
branches of 138
External lymphedema 564
grading system 564t
Extracapsular extension 159, 378
Extracellular-signal-regulated kinase 273
Extranodal disease 253
Extranodal extension 8385, 132, 144, 159, 182, 288, 319
presence of 83
prognostic value of 83
Extrapharyngeal extension 180f
Extrathyroidal extension 306
incidence of 319
Extubation plan 42
Eyelid
closure, regional muscle transfer for 542
lower 537
upper 536
Eyes
patches 535
protection of 40
F
Facial artery myomucosal flap 511
Facial degloving approach 209, 210f
Facial hypoesthesia 198
Facial nerve 229, 234, 266f, 529
danger zones of 531t
disorders 529, 542
Committee of American Academy of Otolaryngology 534
lower 540f
management of 233
monitoring 49
palsy 529, 540f
paralysis 265
grading systems 534
sacrifice 233
secretory function 231
sensory function 231
upper 540f
Facial neurovascular bundles, level of 191
Facial pain, ipsilateral 222
Facial palsy, etiology of 530
Fagerström test 34f
Familial head and neck paraganglioma syndromes 263t
Familial nonmedullary thyroid cancer syndromes 324, 324t
Fanconi anemia genes 419
Fascia lata 515
Fasciocutaneous anterolateral thigh flap 251f, 500f
Fast spin echo 11
Fatal complications 137
Fatty acids 53
Fear 335
Feeding jejunostomy 54
Feyh-Kastenbauer retractor system 447
F-fluorodeoxyglucose 222, 431
Fibroblast 360
growth factor 418f
receptor 418f, 419
Fibroma
ameloblastic 467
odontogenic 467
ossifying 204
Fibromyxoid sarcoma 359
Fibrosarcoma 109, 366
Fibrosis, postsurgical 64
Fibrous dysplasia 204, 207
Fibula free flap 583f
ipsilateral 507
Fibula osteocutaneous flap 494, 494f
Field cancerization 62, 103
Fine-needle aspiration 12, 26, 360
biopsy, ultrasound-guided 345
cytology 23, 95, 129, 301, 329
Fisch approaches 266f, 268f, 271
Fistula 95
arteriovenous 473, 482f
pharyngocutaneous 139, 187, 523
Flap
design and utilization 486, 487, 489, 491, 492
failure 523
parascapular system of 491
re-exploration and salvage 484
Flavin adenine dinucleotide 61
Flex robotic system 454
Flexner-Wintersteiner rosettes 203
Fluorescent in situ hybridization 26
Fluorescent visualization 27
Fluorine-18-dihydroxyphenylalanine 332
Fluorine-18-fluorodeoxyglucose 435
Fluoro-alpha-methyltyrosine 434
Fluorocholine positron emission tomography 345
Fluorodeoxyglucose 12, 155, 432
physiological uptake of 432
Fluorouracil 393, 394, 397, 399
Fogarty catheters 485
Foley's catheter 165
Follicular carcinoma, minimally invasive 306
Follicular cell 299
derived tumors, pathological features of 306t
Food and Drug Administration 295
Foramen ovale 219
Foramen spinosum 219
Forehead flap, lateral 512
Formaldehyde 191
Formalin 23
Fossa of Rosenmüller 219, 221
Fraction of inspired oxygen 44
Free deep inferior epigastric perforator 526
Free flap failure, absence of 187
Free flap surgery 411
Free-muscle transfer 540
Frontal sinus 198
part of 195
Frozen section analysis 27
Full-thickness skin graft 504
Fused protein, suppressor of 285
G
Gabapentin 589
Gadolinium 95
Galeopericranial flaps 517
Gallium-68 434
Gardner's syndrome 324, 358
Gasless unilateral axillary approach 451
Gastrinoma tumor 351
Gastroesophageal reflux
chronic 150
disease 150
Gastrointestinal bleeding 43
Gastrostomy tubes insertion 445
Gefitinib 402, 403
Gemcitabine 224, 255, 403
Gene mutation, high-risk 331
Genetic mutations 263
Genial muscles, divisions of 115
Genioglossus 125, 499
Genomic instability 420
Geriatric assessment scales and evaluation 408
Geriatric syndromes 408
Germanium-68 434
Gingiva 108, 115
Gingivobuccal complex cancers 102, 104
Gingivobuccal sinus cancers 500
Gingivobuccal sulcus 212f
Gingivolabial sulcus 311
Gland
identification of 348
visual confirmation of 348
Glandular odontogenic cyst 463
Glandular tissues 342
Glenoid fossa 230
Glomus jugulare 268
classification of 268t
tumors 264
Glomus tumors 262
Glomus tympanicojugular lesions 267
Glomus tympanicum 264, 268
classification of 268t
Glomus vagale 265
Glossectomy 24
total 500f
Glossopharyngeal nerve block 40, 588
Glottic cancers
advanced 159
early 151, 157, 157fc, 158
moderately advanced 159
Glottic carcinomas
classification of 158
early stage 448
Glottic tumors 152
Glottis 150
exposure of 161
larynx 178
Glucose
metabolism 61
transporter 1 431, 471
Glycemic control 42, 432
Glycolysis, anaerobic 420
Glycosylation 61
Gollicular tumor 306
Gothenburg trismus questionnaire 568
Granulocyte colony-stimulating factor 432
Graves’ disease 305, 433
Great saphenous vein 482
Greater auricular nerve 538
Gross tumor volume 135, 378
Growth
factor, insulin-like 418f
inhibitory signals 420
H
Hand
disabilities of 572
quick disabilities of 572
Harbor metastasis 84
Hard palate 13f, 107, 108, 109, 116
defect 582f
Hashimoto's thyroiditis 433
Haversian canals 230
Head and neck 373t, 432
anatomy of 13
bone sarcomas 361t
cancer 30, 377, 390, 407t, 529, 562, 586, 592, 594
chemoprevention of 70t
evaluation of 11
evolution of 2t
imaging 434
lymphedema 562
management of 57, 372, 407, 408
metastatic 396, 413
microvascular reconstruction in 481
molecular biology of 417
nuclear medicine in 430
radiological evaluation of 11
radiotherapy in 372
reconstruction in 479
recurrent 413
risk of 69
robotic surgery in 440
surgery 38, 411t
swallowing rehabilitation in 547
therapy 1, 51, 424
treatment 1
lymphedema 565t
melanomas of 273
neurogenic tumors of 262
nonmelanoma skin cancers of 284
oncology 6
specimens 24
osteosarcoma of 367fc
paragangliomas 263, 435
common sites of 262f
primary mucosal melanoma of 280t
recurrent sarcomas of 364t
region, nodal levels of 82t
sarcomas 358, 363fc
classification 359
clinical features 359
epidemiology 358
etiology 358
management of 358
pathology 360
principles of management 362
staging 360
surgery 363
soft tissue sarcomas, staging of 361t
squamous cell carcinoma 6, 28t, 83, 95, 128, 398fc, 417
conventional 28
non-human papillomavirus-associated 128t
pathology of 28
surgery 86
evolution of 1
swallowing function following surgery for cancer of 548
tumors
histopathology of 23
pathology of 23
vascular malformations of 471
Hearing and vestibular rehabilitation 234
Hearing voices 31
Heart failure, congestive 344, 473
Hemangioendotheliomas 472
Hemangioma
congenital 472
infantile 471, 472
noninvoluting congenital 473
rapidly involuting congenital 473
Hemangiopericytoma 366
Hematoma 483
Hemiglossectomy defect 141f
Hemilaryngopharyngectomy
supracricoid 183
supraglottic 183
Hemodilution
hypervolemic 41
normovolemic 41
Hemoptysis 94
Hemostasis 1
Heparan sulfate proteoglycans 127
Hering's nerve 264
Herpes simplex virus 535
Herpes virus 103
Heterozygosity, loss of 220f
Hirschsprung's disease 329t
Hirudo medicinalis 485
Hoarse voice 94
Hoarseness 177, 359
Hodgkin's lymphoma 203
Homer-Wright rosettes 203
Homodimeric glycol protein 299
Hormones, nonthyroid 300
Horner's syndrome 392
House-Brackmann grading system 534
Human epidermal growth factor receptor 256
Human immunodeficiency virus 128, 359
Human leukocyte antigen 221
Human papillomavirus 5, 66, 83, 103, 125129 132134, 144, 221, 285, 417, 445, 592
detection methods 129t
genetic alterations in 128t
infection, prevalence of 128
role of 80, 150, 176
testing 128
Human pathogenic herpes virus 220
Huriez syndrome 285
Hurthle cell
carcinoma 323
tumors 323
Hyam's grades 203
Hydroxyapatite cement 518
Hydroxyurea 5, 393
Hygienic voice therapy 551
Hyoglossus 499
muscles 125
Hyperbaric oxygen therapy 581
Hypercalcemia 347, 354
diagnosis of 343
malignancy-associated 342
mild 343
osteolytic 342
symptoms of 343
Hypercalciuria 347
hypercalcemia, familial 344
Hypercapnia 452
Hyperfractionated radiation 412
therapy 374, 412
Hyperglycemia 43
Hyperparathyroidism 329t, 342
development of 349
familial 350
lithium-induced 344
primary 342, 354
Hyperthermia 376, 377
Hypocalcemia 350, 352
acute 352
management 352
Hypoglossal canals 219
Hypomagnesemia 53
Hypoparathyroidism 351
causes of 352t
post-total thyroidectomy, management of 351
Hypopharyngeal cancers
advanced 170, 182, 184, 187
early 181
Hypopharynx 2, 14, 21, 83, 94, 96, 176, 390, 391
cancer of 175
carcinoma 89
structures of 152
Hypophosphatemia 53
Hypotension, moderate controlled 41
Hypothermia 47
Hypothyroidism 38, 314, 401
Hypoxia
chronic 374
life-threatening 43
Hypoxic cell radiosensitizers 376
I
Iatrogenic fracture, high risk of 118
Ifosfamide 5
Iliac bone grafts 517
Imatinib 366
Immune
enhancing nutrition 55
evasion 128
modulation 70
Immunohistochemistry 26, 202
expression 420
Immunotherapy 403, 596
Impaired swallowing 38
Implantology 3
In situ hybridization 129
Incidentalomas 304
Induction chemotherapy 5, 133, 134, 143, 169, 184, 224, 393
role of 136, 208
Inflammatory cells, reactive 363
Influence disease 412
Infraorbital canal 198
Infraorbital nerve 201
Infrastructural maxilla 209
Infratemporal fossa 108, 200, 206, 212, 222, 225, 230, 391, 501, 516
superior 267f
Inhalational induction 40
Inherited medullary thyroid carcinoma, management of 331
Injury, potential sites of 530
Insulin 432
Insulinoma tumor 351
Intensity modulated radiotherapy, era of 4
Interleukins 418f
Internal jugular vein ligation, bilateral 87
International Dysphagia Diet Standardization Initiative 555
International Society for Study of Vascular Anomalies Classification of Vascular Malformations 472t
Intestinal absorption 342
Intracapillary papillary capillary loops 157
Intractable cough 335
Intraepithelial papillary capillary loops 78
Intraoperative nerve monitoring, use of 310
Intrathecal drug delivery 588
Invasive localization methods 345
Invasive thyroid cancer
biology of 319
Shin's classification of 321f
Inverted papilloma 204
treatment of 194
Iodine deficiency 300
Ionizing radiation 150
Ipilimumab 278, 279
J
Jacobson's nerve 264
Jargon-free language 35
Jaw
cysts 463
opening devices 569
tumor syndrome 351
Jejunal free flap 522
Jugular bulb 263
Jugular foramen 219
Jugular vein, internal 13f, 42, 178f, 266, 346, 482
K
Kadish staging for olfactory neuroblastoma, modified 205
Kaposi's sarcoma 359, 365
Kaposiform hemangioendothelioma 473
Karapandzic flap 503f
Keratocyst, odontogenic 462
Keratosis 150
Kit protooncogene mutation 274
Koh's retractor 451
L
Labetalol 41
Labyrinthectomy 233
Labyrinthine 229
Lacrimatory nucleus 529
Lactate dehydrogenase 276
Lamina papyracea 198, 211
Lamina propria 151
Lapatinib 403
Laryngeal cancer 16, 77, 89, 149, 150, 154, 156t, 169, 169t, 186, 187t, 375, 424, 447
advanced 170, 180
development of 150
management of 149
pathways of spread of 151
risk of 149
Laryngeal carcinoma 155
Laryngeal cartilage 14, 178
involvement 16, 320
Laryngeal chondroradionecrosis 170
Laryngeal diseases 89
Laryngeal dysfunction, pretreatment 159
Laryngeal edema, internal 565f
Laryngeal inlet 178f
Laryngeal intraluminal involvement 321
Laryngeal mask airway 49, 385
Laryngeal nerve
anastomotic branch 309
palsy following thyroidectomy 573
Laryngeal reconstruction 520
Laryngeal stenosis 38
Laryngeal submucosa 346
Laryngeal surgery 3, 38
Laryngectomy 42
partial 157, 159, 162, 162t, 183, 549
plus 154
primary partial 184
supracricoid 160, 162, 163, 549
supraglottic 160, 162, 163, 165f, 442, 443, 549
supratracheal 160
total 153, 157, 159, 166, 184, 448, 550
Laryngohypopharyngeal cancer, advanced 394
Laryngopharyngeal defects, reconstruction of 521fc
Laryngopharyngectomy 24, 550
total 184
Laryngopharynx 176, 177
Laryngotracheal-esophageal complex, invasion of 320
Larynx 2, 14, 21, 83, 89, 94, 373, 390, 391
cancer of 149
carcinoma of 161
classification systems for premalignant lesions of 77t
function 4
lesions of 77
premalignant lesions of 77, 79t, 80
tumors of 383
Laser resistant endotracheal tubes 46t
Latissimus 516
dorsi flap 492, 526
Lectins targeting sialic acid 61
Left lateral border tongue, carcinoma of 578f
Left lower alveolar ulceroproliferative lesion 105f
Leiomyosarcoma 366
Lentigo maligna melanoma 275
Less invasive surgery 143
Lesser palatine nerve 131
Leukocyte common antigen 202
Leukoplakia 63, 63f, 65, 70, 77, 103, 150
diagnosis of 77
idiopathic 65
Lichen amyloidosis, cutaneous 329t
Lichen planus 105f
Lid weight implant 536
Li-Fraumeni syndrome 358
Ligament of Berry 309
Light therapy, low-level 567
Light-emitting diode 567
Lingual nerve 25f
Lip 107, 108, 109
reconstruction 501
total 503, 510
upper 504fc
split incisions 114f
squamous cell carcinoma of 17
Liposarcoma 109, 366
Lithium 314
Locoregional disease 396
advanced 113
Locoregional failure 378
Locoregional management 280
Lomustine 354
Lost skin cover, replacement of 515
Low iodine diet 314
Low molecular weight heparins 483
Lower cheek flap 113, 117f
Lower lid
ectropion 226
reconstruction 504fc
Lower motor neuron 530
palsy 530
Lozenges 72
Lugol's iodine 60
Lumbar drain placement 194
Lung
metastases 254
tumors of 383
Lyme disease 534
Lymph node 12f, 19, 19f, 85, 106, 132, 222
abnormal 18
density 83
hilum, evaluation of 19
hyperplasia 256
involvement 21, 180f
level of 82
metastasis 253, 305f
biological basis of 82
rate of 280
paratracheal 177
retropharyngeal 15, 18, 125, 449
staging 83
ultrasound assessment of 303
Lymphadenopathy 151, 198
Lymphatic drainage 168, 191
patterns 14t
Lymphatic malformation 471, 474
Lymphatic spread 230
Lymphatic system 562
Lymphatic vascular endothelial protein-1 82
Lymphedema 562, 596
internal 564
secondary 562
Lymphocytes 204
Lymphoepitheliomas 220
Lymphoid tissue 219
Lymphoma 95, 98, 192, 196, 203, 208, 223
management of 68
Lymphovascular invasion 275
Lynch's incision 209, 210f
M
Macrophages 204
Macroscopic nodal metastasis 306
Magnetic resonance 473
angiography 473
imaging 475, 532
role of 566
Malformation, arteriovenous 473, 475
Malignant diseases 103
Malignant fibrous histiocytoma 109, 366
Malignant peripheral nerve sheath tumor 109, 359
Malignant tracheal tumor
diagnosis of 382
pathology of 383t
Mallampati score
for airway assessment, modified 39f
modified 39
Malnutrition
preoperative 38
universal screening tool 51
for nutritional assessment 53fc
Mandible 13f, 25f, 581
osteoradionecrosis of 38
reconstruction 504
Mandibular defects, classification of 505t
Mandibular swing 140
Mandibulectomy 24, 141
segmental 104
Mandibulotomy 113, 114f, 117f
types of 115t
Mannose receptor 82
Manual lymphatic drainage 566
Manubrium resection 185
Marginal mandibulectomy 118, 118f, 505f
Marx's hypoxic hypocellular theory 580fc
Mastication 102
Masticator space 390
anatomy of 106f
Mastoidectomy 266f
Matrix metalloproteinases 63
Maxilla 25f, 504, 582
Maxillary antrostomy 195
Maxillary cancer, advanced 212f
Maxillary defects, classification of 505t
Maxillary nerve 201
branches of 201
Maxillary sinus
extensive 195
tumors of 375
Maxillectomy 38, 211
defect 582f
Brown's classification of 211f
incisions 210f
Maximum interincisor distance 568
Maxon approach 314
McCune-Albright syndrome 324
McGregor incision 114f
Hayter modification of 114f
MD Anderson Cancer Center Head and Neck Lymphedema 564, 565
MD Anderson Dysphagia Inventory 554
Mechanical exfoliation 25
Medial canthus misalignment 226
Medial labiomandibular glossotomy 141
Medial maxillectomy 211
Medial pterygoid 25f
muscle 138, 222
Medial sural artery perforator flap 490
Mediastinal nodal disease 179
Mediastinal tracheostomy 185
Mediastinum 170
Medullary thyroid
cancer 302, 434
carcinoma 328, 333, 435
temporomandibular joint staging for 331t
Melanocytic neoplasm 274t
Melanoma 98, 273, 280
cutaneous 273, 276t, 281
histology of 275
malignant 203
superficial spreading 275
Mendelsohn maneuver 557
Meningitis 215
Mental
foramen 115
health 30, 408, 409
nerves 451
Mercuric chloride 23
Merkel cell carcinoma 284, 294, 295
staging of 295t
Mesenchymal tumors 202, 230, 383
Metabolic tumor volume 433
Metaiodobenzylguanidine 332
Metal dusts 150
Metastasectomy 254
Metastatic cervical
cancer 94
lymph nodes 97
Metastatic disease 21, 155, 256, 365
treatment for 224
Metastatic lymph node, paratracheal 320
Metastatic node
imaging characteristics of 84
percentage of 83t
Methionine 434
Methotrexate 5, 354, 400, 402, 403
single-agent 400
Methylene blue 349
Metoprolol 41
Metronomic chemotherapy 403
Microcarcinoma 323
Microendoscopy 27
Micrometastatic disease, treatment of 213
Microsatellite metastases 276
Microsatellite tumor deposit 275
Microscopic nodal metastasis 306
Microscopic residual disease 325
Microvascular free flap reconstruction 481
Minimally invasive surgery 452
Minor salivary glands 14
adenoid cystic tumor of 17
Miosis 392
Mitogen-activated protein 419
kinase 273, 301, 327
Mitoxantrone 255
Moh's micrographic surgery 28, 290
Moisture meter D 566
Molecular biology 352
Molecular markers 301, 303
interpretation of 302
prognostic implications of 303
use of 302
Molecular studies 97
Molecular targets 70
Molecular testing 274
indications for 275
Molecular therapies 184
Motor nucleus 529
Motor root 529
Moure's lateral rhinotomy incision 209, 210f
Mouth
floor of 107, 108, 109, 116
malignancy, floor of 118f
opening 39
self-examination 60
Mucoepidermoid carcinoma
high-grade 253
intermediate-grade 253
low-grade 253
Mucosal irritation, chronic 150
Mucosal melanoma 110, 195, 279
primary 279, 280
Mucosectomy defect, left tongue base of 447f
Mucositis 254, 376, 412
Multidetector computed tomography 153
Multidisciplinary team 55, 589
Multigland disease 343
Multiorgan dysfunction 53
Multiple chemotherapy regimens 213
Multiple endocrine neoplasia syndrome 328, 350
Multivitamins 378
Muscle
direct neurotization of 538
invasion of 320
prevertebral 222
transposition 542
Mutator phenotype 420
Myocardial infarction 344
Myocardium 432
Myoepithelial carcinoma 26
Myofibroblastic spindle cells 204
Myofibroblasts 360
Myxoid liposarcoma 359
Myxomas, odontogenic 467
N
N-acetyl-cysteine 68
Narrow band imaging 78, 96, 157
Nasal bleeding 94
Nasal block 94, 197
Nasal cavity 14, 191, 196, 205, 209, 294, 373, 390
cancer of 191
lesions 192
malignant lesions of 192
tumors of 196, 375
Nasal discharge 197
Nasal mucosa 518
Nasal obstruction, ipsilateral 198
Nasal sprays 72
Nasal symptoms 198
Nasal vestibule 191
lesions 195
staging system for tumors of 192t
tumors of 192
Nasogastric tube 54, 549
insertion 42
Nasolabial cysts 464
Nasolabial flap 509
inferiorly based 510
Nasopalatine duct cysts 464
Nasopharyngeal cancer 97, 222, 223, 375, 448
Nasopharyngeal carcinoma 6, 17, 219, 221, 224, 391
advanced 5
landmark trials in 224t
pathogenesis of 220f
Nasopharyngeal epithelium, malignant transformation of 221fc
Nasopharyngeal reconstruction 526
Nasopharyngectomy 226, 443
robotic 448
Nasopharynx 14, 20, 96, 99, 108, 391
cancer of 219
exposure 268f
ipsilateral 225
National Cancer Data Base 390
National Cancer Institute 377
National Comprehensive Cancer Network 133, 134, 594
approach to evaluation of head and neck sarcomas 362t
margin recommendation in cutaneous melanoma 277t
National Dysphagia Diet 555
National Institutes of Health-Swallowing Safety Scale 554
National Tobacco Control Program 59
Nausea 42, 47
Near total laryngectomy 164, 166f, 549
Neck
clinical examination of 84
disability index 572
disease, recurrent 90
dissection 1, 38, 133, 134, 138, 233, 253, 363, 569
anterolateral 86
categories of 86
elective 87, 110
evolution of 85
functional 570
impairment index 572
lateral 86
role of 233
selective 289
supraomohyoid 453
surgical description of 86
therapeutic 252
elective management of 110t
malignancies 433
management of 82, 195, 277, 288
nodes, management of 312
squamous cell carcinoma 175, 289
swellings, management of 26
ultrasonography 344
Negative predictive value 302
Neoangiogenic microvascular abnormalities 157
Neodymium-doped yttrium aluminum garnet 475
Neoplasms
benign 193
high-grade 253
types of 149
Nephrocalcinosis 343
Nephrolithiasis 343
Nerve
grafts 538
choice of donor nerves for 538t
integrity monitor 48
prognostication of 310
Nervus intermedius 529
Neural complications 87
Neural crest cell 328
Neuroendocrine carcinoma 203
Neuroendocrine markers 203
Neuroendocrine tumors 26, 203, 383
imaging in 434
Neurofibromatosis 358
Neuromuscular electrical stimulation 554
Neuron specific enolase 202
Neutron radiotherapy 376
Neutropenia 393
Newer robotic surgery systems 454
Ni's classification of premalignant lesions of larynx based on narrow band imaging 78t
Nicardipine 41
Nicotinamide 154, 377
Nicotine 73
dependence 71
metabolite ratio 73
oral absorption 72
patch 72
replacement therapy 33, 72, 73
Nimotuzumab 413
Nitric acid 24
Nivolumab 278, 279, 401, 402
Nodal disease 84
early 112
nonsurgical treatment of 89
postoperative radiotherapy for 89
recurrent 319
surgical treatment of 85
Nodal metastasis 115, 130, 195, 223
contralateral 130
rate 312t
Nodal staging 18
anatomy 18
Nodal status 112
Nodular melanoma 275
Nonfluorodeoxyglucose tracers 434
Non-Hodgkin's lymphoma 203
Noninvasive follicular thyroid neoplasm 306
Nonmelanoma skin cancers 284, 285t, 287t, 288t, 290
prevention of 291
radiotherapy in 289
Nonmetastatic disease 113
Nonoropharyngeal origin 98
Nonrecurrent laryngeal nerve, course of 309t
Nonsquamous cell carcinoma pathology 223
Nonsteroidal anti-inflammatory drugs 69, 587f
Nonverbal communication 102
Nuclear imaging, role of 431
Nuclear medicine 430, 438
fundamentals of 430
Nucleic acids 129
Nutrition 408, 409
Nutritional support, types of 54
O
Obstructive sleep apnea 441
Occipital nerve block 588
Odontoameloblastoma 466
Odontogenic cyst, calcifying 463
Odontogenic epithelial remnants 464
Odontogenic lesions 461, 468
differential diagnosis of 468t
Odontogenic tumors
calcifying epithelial 466, 468
epithelial 464
origin of 465f
Odontoma 465
component 466
Odynophagia 104, 130
Olfactory nerve 191
Olfactory neuroblastoma 203, 207
Kadish staging for 205
Ollier and Maffucci syndrome 358
Omental free flap 517
Omohyoid 451
Open oropharyngeal approaches 142t
Ophthalmic veins, inferior 199
Optic atrophy 215
Optic nerve surgery 201
Oral calcium supplementation 352
Oral cancer 1, 59, 88, 105, 105f, 106, 107t, 116t, 117f, 437
carcinogenesis of 62
causation of 68
magnetic resonance imaging of 107
prevention 59
screening 60
surgery 1, 113
treatment, brachytherapy catheter placement for 111f
Oral cavity 2, 14, 20, 20f, 83, 88, 89, 104, 109, 373, 390, 499
cancer of 102
carcinoma 195
nonsquamous
cancers of 109
tumors of 110t
premalignant lesions of 62
reconstruction 507
general principles in 499
principles of 499, 501
surgical considerations 500
squamous cell carcinoma of 17
tumor, portals for 375
Oral celecoxib 291
Oral chemoprevention strategies 68fc
Oral epithelial dysplasia 66t
Oral erythroplakia 63
Oral examination, conventional 60
Oral hypoglycemic agents 432
Oral lesion, suspicious 67fc
Oral leukoplakia 63
diagnosis of 63
Oral lichen planus 65
Oral nicotinamide 291
Oral potentially malignant disorders 63
Oral premalignant lesion 71, 73
management of 68
Oral reconstruction, regional flaps for 508
Oral squamous cell carcinoma 102, 103, 109t
Oral stage exercises 557
Oral submucous fibrosis, classification of 64t
Oral surgery 548
Oral tongue 107, 109
primary 394
Orbit 108, 200
bony anatomy of 201f
management of 212
Orbital apex 199f
Orbital fissure, superior 206
Orbital invasion 16
Organ preservation
strategies, radiation-based 167, 185
therapy 5
Oropharyngeal cancer 6, 89, 97, 125, 126, 132, 137, 139, 141, 144, 444, 445
human papillomavirus-associated 133t
prevention strategies 144
risk of 126
treatment of 133
tumors, node, and metastasis staging in 133t
Oropharyngeal carcinoma 126
radiation dose-volumes in 136t
Oropharyngeal defects, reconstructive options in 525t
Oropharyngeal reconstruction 524, 526fc
Oropharyngeal retractors 441
Oropharyngeal surgery 548
Oropharyngeal swallow disorders 556t
Oropharyngeal tumors 131, 136
clinical stage of 133t
Oropharyngeal wall 126
Oropharyngectomy defect, left lateral 442f
Oropharynx 2, 14, 20, 20f, 83, 89, 94, 96, 125, 140, 141f, 222, 390, 391
cancer of 125
epidemiology of 126
lumen of 130
tumors of 383
Orthopantomogram 12, 15
Osmium tetroxide 23
Osseointegrated implants 583
Osseous destruction, secondary 362
Osteoblasts 580
Osteoclasts 580
Osteocytes 580
Osteomyelitis 204
Osteoradionecrosis 38, 118, 578, 580
Delanian's radiation-induced fibrosis theory 581fc
Marx's hypoxic hypocellular theory of 580fc
risk of 12, 118
Osteosarcoma 109, 204, 207, 360, 367
Osteotomy 233, 507
Osteradionecrosis 379
Otalgia 177
Otolaryngology 86
P
Paclitaxel 139, 224, 255, 397, 589
Paget's disease 358
Pain 586, 595
assessment of 587
chronic 586
etiology of 586
management of 47, 586
myofascial 46
neuropathic 46, 586
nociceptive 586
postchemotherapy 589
postradiotherapy 588
relief, principles of 588t
Palatal mucosal grafts 386
Palate 582
Palatine tonsils 125
Palatoglossus 125, 499
arch 137
Palbociclib 403, 425
Palliative care 586, 589
Palliative procedures 387
Palliative radiotherapy, palliative 255
Pamidronate 354
Pancytokeratin 222
Panendoscopy 96, 97, 155
Panitumumab 400
Papillae 305
Papillary carcinoma
nuclear features of 305
thyroid 302, 304f, 305f, 306, 324
Papilloma 193, 206
Papillomatosis 157
Papillomavirus 126
Paraffin 24
Paragangliomas 262, 269
adrenal 262
jugular 270fc
jugulotympanic 271
tympanic 263
Paralytic agents 385
Paramedian mandibulotomy 141, 141f
Paranasal sinus 14, 196, 198, 204, 208, 373, 390
cancer of 197
cross-sectional view of 200f
malignancies 193
tumors of 197
Paraneoplastic syndromes 203
Parapharyngeal space 13f, 221, 225, 251
Parascapular free flap system 491f
Parasymphysis 252
Parathyroid 311
adenoma 343, 344, 348f, 351353, 435
atypical 353
applied anatomy of 346
carcinoma 352, 353t, 354
cells 345
gland 344, 348, 349, 436
disorders of 342
embryology of 346
inferior 346, 348
superior 346
hormone 342, 352
disorders, management of 342
secretion 342
surgery 347, 348
minimally invasive 348f
tissue 349
Parathyroidectomy 344
failed 350
indications for 344
minimally invasive 348, 436
endoscopic 348
image-guided 348
Parenteral nutritional support 54
Parotid gland 96
management of 233
Parotid involvement 233
Parotid nodes 18
Paterson-Brown-Kelly syndrome 175
Patterson scale for measuring internal lymphedema 565t
Pectoralis major flap 522
Pectoralis muscle 350
Pediatric
salivary gland tumors 256
thyroid carcinoma 324
Pembrolizumab 278, 279, 397, 401
immunotherapy 397
single-agent 399
Penetration-aspiration scale 554
Pentoxifylline 377
Peptide receptor radioligand therapy 434
Percutaneous endoscopic gastrostomy tubes 54
Periapical cemento-osseous dysplasia 465
Perifacial nodes 191
Perineural invasion 206, 275
Perioperative fluid management 41, 47
Perioperative nutritional care 47
Peroxisome proliferator-activated receptor gamma, ligands of 70
Petrosal veins, inferior 199
Petrosectomy, subtotal 232
Pharmacotherapy 566
Pharyngeal and tracheal reconstruction, principles of 520
Pharyngeal artery, ascending 138
Pharyngeal diseases 89
Pharyngeal irritation 378
Pharyngeal mucosa 448
Pharyngeal obturator 582f
Pharyngeal phase 555
Pharyngeal plexus 177
Pharyngeal reconstruction, free jejunal transfer for 523f
Pharyngeal squamous cell cancers, metastatic infiltration of 449
Pharyngeal wall, lateral 176
Pharyngectomy 184
Pharyngoesophageal resection 170
Pharyngoesophageal segment 550, 551
Pharyngolaryngoesophagectomy 184
Pharyngostoma 46
Pharyngotomy, lateral 140
Pharynx 373
part of 219
Pheochromocytoma 262, 329t, 330, 331
Phoenix 61
Phosphatase 472
Phosphate levels 53
Phosphorus, serum 343
Photodynamic therapy 79, 289
Photon emitters 430
Physical therapy 569
Physiologic voice therapy 551
Picric acid 23
Pingyangmycin 475
Pittsburgh staging system for temporal bone malignancy, modified 231t
Planar dynamic imaging 437
Planar scintigraphy 430
Planning target volume 372
Plasma cells 204
Plasmacytoma 208, 223
Platinum 394, 399, 400
Platysma 13f
Plummer-Vinson syndrome 175, 176, 179
Pneumonitis 401
Polymerase chain reaction 129, 202, 302, 424
Polyphenols 68
Polypoidal mass 265
Polytetrafluoroethylene 463
Poor anastomotic flow 484
Porous polyethylene 518
Porphyrins 61
Port-wine stain 474
Positive lymph nodes, log odds of 83
Positive oropharyngeal cancer 132
Positive predictive value 302
Positron emission tomography 12, 96, 269, 436
Postauricular facelift approach 451
Posterior oropharyngeal wall 131, 178
Posterior pharyngeal wall 125, 126
defect 141f
Postoperative flap monitoring 47
Postoperative pain 587
management of 46
Postoperative pulmonary physical therapy 48
Postradical parotidectomy 251f
Poststyloid space injuries 252
Poststyloid styloid 252
Postsurgical excision 79
Post-thyroidectomy 352
Potassium dichromate 23
Pre- and post-therapy radioiodine scan 316
Pre-epiglottic fat invasion 16
Pre-epiglottic space 152, 447
Pregabalin 589
Pregnancy and thyroid cancer 322
Premalignant disease 103
progression of 104f
Premalignant epithelial lesions 78
Prevertebral fascia 16, 105, 312, 391
involvement 15
signs of 16
Prevertebral space 131
Primary intraosseous carcinoma
de novo 467
ex odontogenic cysts 466
Primary tumors 382
ultrasound assessment of 303
Progesterone receptor 256
Programmed cell death ligand 1 274, 398
Prophylactic central compartment, role of 312
Prophylactic neck dissection, role of 353
Proptosis 198
Propulsion 102
Prosthodontics 3
Proteins
melanogenesis-related 275
patched homolog 285
Proton therapy 4
intensity modulated 5
Psammoma bodies 306
Pseudotumors, inflammatory 204
Pterygoid 222
muscle 391
Pterygomandibular raphe 138
Pterygomaxillary fissure 391
Pterygopalatine fossa 108f, 200, 201f, 206, 222
Pterygopalatine ganglion 201
Ptosis, partial 392
Pulmonary function tests 159
Pyogenic granuloma 472, 474
Pyriform fossa 178
cancer 178f
carcinoma of 180f
tumors 177
Pyriform sinus 152, 177, 178, 185
carcinomas 179, 184
tumors 183
Pyrimidine 285
Q
Quadruple drug regimens 400
Quality of life 412, 594
and survival 597
assessment 170
questionnaires 554
R
Radial forearm 485
free flap 486f, 521
Radiation
caries 579
delivery 4
exposure 176
fractionation 373
reactions
signs of 377
symptoms of 377
therapy 79, 133, 289
intensity modulated 223, 326, 378, 568
oncology group 90, 564
role of 3, 133, 277
Radical brachytherapy 110
Radical chemoradiotherapy 578f
Radical external beam radiotherapy 111, 112
Radical neck dissection 178f, 507
specimen, left 178f
Radical parotidectomy 251
extensive 251
Radicular cyst 463
Radioactive iodine therapy 326
Radiobiology 373
Radioiodine
ablation 315
administration, dose of 313
therapy 313, 327
fundamentals of 313
Radionuclide 430
types of 430
Radioprotectors 376
Radiosensitizers 376
Radiotherapy 55, 133, 134, 157, 159, 208, 224, 253, 270, 378, 392, 596
adaptive 376
advantages of 412
diagnostic workup for 372
evolution of 3
image-guided 378
planning 433
postoperative 253
primary 185
role of 373t
technique 134, 375
choice of 379
timing of 379
Radiotracers 431
Rapamycin 426
Reactive cord edema 42
Receptor tyrosine kinase 426
Reconstruction
after transoral robotic surgery 139
principles of 504, 535
Reconstructive surgery 3
role of 234
Rectus abdominis flap 490, 516
Recurrent laryngeal nerve 309, 346, 551, 573
block 40
dissection 308
infiltrated 320
palsy
bilateral 574
unilateral 573
Recurrent tumors 193
management of 318
primary 318
Refeeding syndrome 53
Reflectance confocal microscopy 61
Rehabilitation 234, 581
Reinke's space 152, 158
Reirradiation
complications of 379
radiobiology of 378
Remote access thyroidectomy
advantages of 452
disadvantages of 452
operative techniques in 451
Renal cell carcinoma 192
Renal dysfunction 54
Renal function, normal 343
Resectable disease 288
Respiratory distress 44, 383
Rests of Malassez 461
Retroauricular facelift approach 451
Retromolar trigone 107109, 501
tumors 104
Retropharyngeal space 13f, 131, 176
Revision thyroidectomy, principles of 319
Rhabdomyosarcoma 202, 223, 358, 365
alveolar 359
Rhinosinusitis 197
Ribociclib 425
Ribonucleic acid 129, 149, 302
Right internal carotid artery, anatomy of 214f
Right vagus, schwannoma of 269f
Robotic and endoscopic thyroidectomy, classification of 450
Robotic lateral neck dissection 453
Robotic neck surgery 450
Robotic surgery 6, 440
milestones in 440f
section of 137
use of 441
Robotic thyroidectomy 451453
classification of 450t
Robson incision 114f
Rotation-advancement flaps 503
Rothmund-Thomson syndrome 358
Roux-Trotter incision 114f
Royal College of Pathologists Reporting of Nodal Specimens, summary of 85t
S
Saliva, pooling of 177
Salivary bypass tubes 524
Salivary duct carcinoma 109, 253, 255
Salivary flow test 534
Salivary gland 21, 192, 390
carcinomas 255
function 552
major 14, 373
neoplasms, treatment of 256
surgery 3
tumors 109, 110, 230, 253t, 255t, 256, 383
general guidelines for 110
metastatic major 17
Salivary tests 61
Salivation 102
Salivatory nucleus, superior 529
Salpingopharyngeus 176
Salvage
resections 449
surgery 187
Saphenous nerve 538
Sarcoidosis 342
Sarcomas 109, 110
radiation-induced 368
synovial 109, 359, 366
Saygo technique 40
Scalp, dermatofibrosarcoma of 360f
Scapula bone flap 496
Schirmer's test 533, 534
Schobinger staging system 475
Sclerotherapy 474
Seizures 53
Selective parathyroid venous sampling 346
Sensory innervation 125
Sensory root 529
Sentinel European node trial 84
Sentinel lymph node 82
biopsy 87, 437
current recommendations for 88
Septal bone 518
Serine-threonine kinase 301
Shaker exercises 557
Shamblin classification 264
Sharpey's fibers 367
Shin's classification 321f
Short tau inversion recovery 11, 12, 14
Shoulder
disabilities of 572
dysfunction 562, 569
pain and disability index 572
quick disabilities of 572
Sigmoid notch 391
Sigmoid sinus 266f
Simple shoulder test 572
Simultaneous integrated boost technique 134
Single-photon emission computed tomography 430
normal 90
Single-positron emission tomography 277
Sinonasal cancer, risk of 197
Sinonasal cavity 200
Sinonasal disease 194
Sinonasal endocrine carcinoma 213
Sinonasal malignancies 191, 197
Sinonasal tract 205
Sinuses 194
anterior wall of 191
Skin
anatomy of 284
cancers 284, 287, 295
classification of 284fc
epithelial 284
lesions, history of 94
squamous cell carcinoma of 17
toxicity 5
Skull-base defects 195
Skull-base reconstruction
alloplasts in 518
basic principles of 514
divisions of 515f
goals of 514
lateral 517
objectives of 515
posterior 517
principles of 514
Skull-base surgery 3, 518
complications of 514
Small cell
carcinoma 26, 203
tumors 203
Small molecule tyrosine kinase inhibitors 403
Smile
dynamic of 533
regional muscle transfer for 542
Snap and lid retraction test 533f
Sodium tetradecyl sulfate 474
Soft palate 13f, 108, 126, 375
defect 582f
Soft tissue sarcomas 359, 360, 361t, 363f
Solbiati index 132
Solitary fibrous tumor 207, 366
Solitary lesions, metastasectomy of 255
Somatic cells 421
Somatostatin 434
receptor 434
Southern blot test 128
Specialty tobacco clinic intervention 72
Spectroscopy 62
Speech 595
therapy after thyroidectomy 551
Sphenoethmoidectomy 194
Sphenoid
defects 518
sinus 191, 198, 199, 201, 211, 268f, 279
Sphenoidectomy 211
Sphenopalatine
artery 201
ganglion block 588
Spin echo 11
Spinal cord 376
myelopathy 379
Spinal nerve 46
Spindle cell mesenchymal malignancy 366
Spirometry 383
Spontaneous fracture, high risk of 118
Squamous cell
cancers 424
carcinoma 82, 94, 98, 161, 191, 197, 202, 219, 229, 290, 372, 390, 421, 431
oropharyngeal 103, 144
Squamous epithelium 125, 176
Squamous odontogenic tumor 466
Stable skeletal support, provision of 515
Standard anesthetic protocol 47
Stapedial reflex 534
Stellate ganglion block 588
Stem cell, hemangioma-derived 471
Stereolithographic modeling 507
Stereotactic body radiation therapy 378
Stereotactic radiosurgery 4, 270
Sternocleidomastoid 13f
muscle 451
Sternohyoid muscles 385
Sternothyroid muscles 385
Storz professional image enhancement system 157
Strap muscles 13f
Strenuous exercise 432
String sign 367
Stroke, Postoperative ischemic 231
Sturge-Weber syndrome 476
Stylomandibular ligament 252
Stylomastoid
arteries 229
foramen 206, 233
Stylopharyngeus muscle 125
Subjective objective management analytic system 564, 568
Sublingual gland 21, 252
Submandibular gland 21, 252
Submental flap 508
Submucosal disease 179
Subtotal temporal bone resection 233
Succinate dehydrogenase 263
complex subunit 263
Sulfuric acid fumes 150
Sulindac 366
Sun protection strategy 291
Sunitinib 403
Superficial circumflex iliac artery perforator flap 489, 489f
Superficial musculoaponeurotic system 500f, 531, 532f
Superficial temporal artery 214
Superior laryngeal nerve 177, 551
anatomy, classification of external branch of 308t
block 40
external branch of 308
injury 573
Supraclavicular flap 508
Supraclavicular nerve 538
Supraclavicular nodes 18
Supraglottic cancers, advanced 159, 159fc
Supraglottic larynx, structures of 152
Supraglottis 150
Suprahyoid
epiglottis 150
neck 13, 13f
Sural nerve 538
Surgery 596
Surgical wound dehiscence 215
Survivorship care guidelines 592, 593
Swallow
flexible endoscopic examination of 553
supraglottic 557
Swallowing 595
disorders 556t
function, normal 547
function, rehabilitation of 553
scale, functional outcome of 549
toxicity, dynamic imaging grade of 555
Sydney swallow questionnaire 554
Synaptophysin 203
Systemic chemotherapy, role of 139
Systemic therapy 281, 290
role of 281
T
Tamoxifen 366
Tape measurement 565
Tar products 150
Target organ manifestations 344
Tarsorrhaphy
lateral 536
temporary 535
Taste tasting 534
Taxane 394, 397, 400
Technetium-99m sestamibi scintigraphy 345
Technetium-99m-labeled pentavalent dimercaptosuccinic acid 435
Teeth, loosening of 104
Telomerase reverse transcriptase 285, 303
Telomere elongation helicase, regulator of 285
Temporal bone 230
cancer 229
routes of spread of 231f
malignant tumor types involving 230t
primary cancers of 229
resection 234
lateral 233
margins of 232f
tumors 230
Temporal fossa 516
Temporalis
contracture 38
fascia 518
muscle, part of 391
Temporomandibular joint 38, 233, 504, 531, 567
pseudoankylosis 38
Tension pneumocranium 515
Tensor fascia 488
Tensor veli palatine muscle 222
Textile dust 191
Therabite jaw motion rehabilitation system 569
Therapeutic central compartment dissection 312
Thermogenic adipose tissue 432
Thiamine 53
Thiazides 342
Thiazolidinediones 70
Thoracic
procedures 385
trachea 384, 385
veins, internal 346
Thoracodorsal nerve 538
Thromboembolism prophylaxis 47
Thrombolytic agents 485
Thyroarytenoid muscle 152
Thyroglobulin 299, 452
assay 317
elevated negative iodine scan 326
preoperative 304
serum 317
Thyroglossal cyst 322
Thyroid 94, 152, 299, 375, 388
arteries 346
inferior 176
superior 176
cancer 86, 299, 300, 304, 307t, 312t, 316, 319, 322, 325, 435
and mutation profiles 302t
imaging in 303
management of 303
molecular genetics in 301
radiation-induced 323
stages of 299
carcinoma 299, 306, 322
familial medullary 328
follicular 324
metastatic medullary 332
papillary 98, 306
cartilage 13f, 159
gland 373, 385
anatomy of 299
physiology of 299
hormone synthesis 299
laminae 152
lymphoma, primary 307
malignancies 299
management of 2
nodule 300, 305f
evaluation of 300
peroxidase 299
primary squamous cell carcinoma of 307
remnant ablation, principles of 315
sarcoma, primary 307, 334
stimulating hormone 300, 317, 318
surgery 2, 311
monitoring during 48
remote access 311
swelling 304f
tissue, assessment of 312
vein
left superior 346
right superior 346
Thyroidectomy, completeness of 310
Thyroiditis
chronic 433
subacute 305
Thyrolinguofacial trunk 482
Thyromental distance 39
Tinel's sign 539
Tissue
abnormal 78
characterization 202
subcutaneous 510
Titanium mesh 518
Tobacco 73, 103, 149, 175
cessation 33, 71
program 73
consumption 71
effects of 71
exposure 150, 175
smoke 149
Toluidine blue 60
Tongue 116
base 125
cancer 442
carcinoma 110
base of 131f, 135f
defects, reconstructive options in 500t
exercises, base of 557
reconstruction 499
Tonsil 125
cancer 442
clinical staging of 130f
Tonsillar pillar 108
Tonsillectomy 96
ipsilateral 96
Topognostic tests 533
Total thyroidectomy 25f, 308
surgical completeness of 452
Touch imprint cytology 27
Toxic effects 187
Trachea 178, 178f
invasion of 321
posterior 167
Tracheal lengthening maneuvers 386
Tracheal malignancy 382, 384t, 387
arterial supply 382
epidemiology 382
lymphatic drainage 383
outcomes in 388t
pathology 383
primary 382, 388
surgery 385
surgical anatomy 382
symptoms of 383
temporomandibular joint classification systems for 384t
treatment 384
Tracheal reconstruction 386, 526
after oncological resection 527fc
Tracheal resection 386f
contraindications for 387
Tracheal tumors, management of 385, 388
Tracheoesophageal prosthesis 167
Tracheoesophageal puncture 170
Tracheoesophageal speech 551
Tracheostoma 166, 169
Tracheostomy 187
care 48
elective 40
for respiration 182
temporary 42, 448
Tracheotomy cannula 46
Tractus solitarius, nucleus of 529
Trametinib 278, 279
Transforming growth factor-beta 285
pathway 420
Transfusion 1
Transnasal high-flow rapid insufflation ventilatory exchange 40
Transoral endoscopic thyroidectomy vestibular approach 311
Transoral laser microsurgery 97, 137, 161, 181, 182, 441
Transoral robotic surgery 5, 96, 97fc, 137, 139, 139t, 144, 251, 441, 443, 550
complications in 450
feasibility 444
margins in 444
oncologic outcomes of 138
suitability of 441
surgical procedure 441
treatment with 446
Transoral vestibular approach 451
Transpterygoid approach 226
Trendelenburg position 42
Tricyclic antidepressants 588
Trigeminal ganglion block 588
Trigeminal nerve 201
Tri-iodothyronine 314
Triple drug regimens 400
Triple innervation technique 540f
Trismus 567
rehabilitation of 562
Trotter's operation 141
Trotter's triad 222
Trunk melanoma 274
Tuberculosis 342
Tumors 25f
benign 252
biological classification of 465t
cells 61, 128, 153
central nervous system 98
central tongue base 137f
desmoid 366
epithelial 202, 230, 383
extralaryngeal 153
extraocular 293
factors 78, 289
high-grade 209, 362
human papillomavirus
negative 425
positive 425
hypopharyngeal 177
hypoxia 376
inflammatory myofibroblastic 204
invasive 304f
isolated subglottic 152
jugulotympanic 264
large-bulky 194
lymphoproliferative 203
markers, serum 329
mesenchymal odontogenic 467
nasopharyngeal 16, 391
necrosis factor receptor 425
node, and metastasis 182
nonchromaffin 262
nonepithelial 207
odontogenic 461, 464, 468
parapharyngeal 449
pathological classification of 202
perineural spread of 17
pharyngeal 14
second field 59f
sinonasal 16, 208, 212
size 14
skull-base 3
spread 17
routes of spread of 192, 222
subglottic 151, 152
superficial spreading 179
suppressor gene 128
supraglottic 151
thickness 275
tonsillar 130
transglottic 153
ulceration 275
upper esophageal 188
vascular 471
volume 181
Tyrosinase inhibitors 326
Tyrosine 434
kinase
activity 255
domain 329
inhibitors 301, 327
U
Ultrasonography 12
Ultrasound, high-resolution 566
Union for International Cancer Control Staging for
Nasopharyngeal Cancer 223t
Oral Cancer 106t
Unresectable nodal disease 90, 113
Upper aerodigestive tract 96, 103, 520
Upper cheek flap 113, 117f
Upper motor neuron 530
palsy 530
Urinary catheterization 48
Urogenital system 328
V
Vagal paragangliomas 270fc
Vagus, auricular branch of 104
Valsalva maneuver 43, 181
Vandetanib 333
Varenicline 72, 73
Vascular anomalies, management of 476fc
Vascular endothelial growth factor 82, 256
Vascular malformations 474, 477
characteristics of 473t
classification 471
Vemurafenib 278, 279
Venous air embolism 43, 45
management of 45fc
manifestations of 44fc
Venous malformation 471, 474, 475fc
Ventricles 150
Vermilion reconstruction 502
Vertical partial laryngectomy 162, 164f
classification of 165f
Vestibule, cancer of 191
Vestibuloplasty 583
Vidian nerve 201
Vimentin 202
Vinca alkaloids 589
Vincristine 368
Vinorelbine 255, 589
Viral gene expression 128
Viral genomes, transcriptions of 128
Viruses 150
Visceral flaps 187
Visor flap 113
Vitamin 69
B3 377
D 343, 347
supplementation, required doses of 350t
D3 342
doses of 53
Vocal cord
mobility 384
mucosa 79
palsy 38, 562
status 347
Vogelstein's model 103
Voice
handicap index 170
rehabilitation 524, 550
therapy, symptomatic 551
Vomiting 42, 47
W
Waldeyer's ring 125
Weber Ferguson incision
Borle's extension of 209
Dieffenbach's modification of 209, 210f
Weber Ferguson Longmire incision 209, 210f
Webster-Bernard flap 503f
Weight loss 254
Werner syndrome 285, 324, 358, 359
Wide field autofluorescence imaging 61
Widely invasive follicular carcinoma 306
Wood dust 191
World Health Organization 588, 594
Wound
care, postoperative 47
healing, delayed 38
X
Xeroderma pigmentosum 285
Xerophthalmia 215
Xerostomia 412, 595
Xylocaine spray 437
Z
Z incision, modified 114f
Zoledronic acid 354
Zygomatic implants 582
Zygomaticus major smile 533
×
Chapter Notes

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Head and Neck Cancer Treatment: Past, Present and FutureCHAPTER 1

Vijay Pillai
 
HISTORICAL ASPECTS
The evolution of head and neck surgery encapsulates the evolution of a specialty. From the confines of general surgery, otolaryngology, plastic and reconstructive surgery and maxillofacial surgery, the specialty has carved out a niche of its own.
The history of development of head and neck surgery also parallels the developments seen in medicine and surgery such as advances in anesthesia, antisepsis, transfusion and hemostasis; this had led to development of major extirpative procedures.
The brief description that follows is neither exhaustive nor all inclusive, but summarizes various key developments in head and neck cancer therapy.
The earliest mention of cancer dates back to the medical documents of the Edwin Smith Papyrus and the Ebers Papyrus. A description of an “eating ulcer on the gums” treated with a mixture of cinnamon, gum, honey and oil seems to be the first treatment described for oral cancer.1
The Greek Physician Hippocrates (460 bc) was the first to use the term carcinoma and describe skin cancers and its treatment with cautery and caustic pastes. Aurelius Cornelius Celsus (30 ad) treated cancer of the face and lip with excision. Galen in 200 ad advocated the humoral theory of disease and neoplasms due to excess black bile that needed to be treated with diet and purging.2
The medieval age was characterized by a general lack of progression of any scientific developments and it was with the Renaissance (1500–1760 ad) that knowledge started to develop with Vesalius’ anatomical studies. As the use of tobacco reached the European and American continents we find the mention of cancer and also its related treatments.
Table 1 summarizes key milestones and developments in the evolution of head and neck cancer.
 
EVOLUTION OF HEAD AND NECK SURGERY
 
Oral Cancer Surgery
As a better understanding of the biology and pathways of spread of oral cancer developed, contributions have been made to access and management of these tumors, which form the principles of current practice. In addition various studies demonstrated the involvement of the mandible in oral cancer and founded the principles of mandible resection in oral malignancies.
It is worthwhile mentioning the early pioneering surgeons and their contributions:
  • Lip-split approach with a mandibular division developed by von Langenbeck and Billroth
  • Wedge excision for tongue tumors with lingual artery control by von Langenbeck
  • Roux described the cervical approach to the oral cavity
  • Kocher cervical approach for oral cavity and lateral mandibular osteotomies
  • Theodore Billroth described bilateral mandibular osteotomies
 
Neck Dissection
Management of the neck is an integral part of head and neck surgery of any site. Neck dissection itself is an operation that evolved from a radical surgery (as proposed by Crile and Hayes Martin) to selective neck dissection (preserving function); we are now in the era of superselective neck dissection and sentinel lymph node biopsy.
George Crile was the first person to describe the enbloc resection of the cervical lymphatics in 1906.3 Hayes Martin reported his experience at the Memorial Sloan Kettering Cancer Center from 1928 to 1950 describing radical neck dissections. This was the procedure of choice for clinically positive necks with the sacrifice of the internal jugular vein, spinal accessory and sternomastoid muscle along with the clearance of levels I-V.2
Table 1   Key milestones and developments in the evolution of head and neck cancer.
Year
Contributor and role
1740
Jean Godinot established the first cancer hospital in Reims, France
1790
Onuigbo described nodal metastases: A sign of incurability
1801–1878
Johannes Müller and Alfred Donne did the pioneering work in histopathology
1805–1906
Manuel Garcia described indirect laryngoscopy
1815–1856
Horace Wells, William Morton and John Warren introduced general anesthesia
1821–1902
Rudolph Virchow developed the concept of cellular pathology putting aside Galen's humoral theory
1851
Gurdon Buck described laryngofissure, later reported by Cohen
1865–1867
Thiersch and Waldeyer proposed the origin of cancer from the epithelial surface and stromal invasion
1873
Billroth performed the first laryngectomy
1885–1893
General Grant's oropharyngeal cancer and President Cleveland's oral cancer gave impetus to the development of histopathologic examination
1895–1900
Description of frozen section by Nezelof and its popularization by Thomas Stephen Cullen
18th century
First reports of neck dissection and its importance in disease control: Butlin demonstrated efficacy of neck dissection for tongue cancer, Jawdynski from Poland performed a block dissection of the neck
1905–1906
George Crile described the block dissection of the neck popularized subsequently by Hayes Martin
1919
Coutard developed external beam irradiation
1922
Gluck and Soerensen standardized the technique of laryngectomy
1924
Giacomo Puccini an Italian opera artist received brachytherapy using the Columbia apparatus at Brussels
1938
Hayes Martin at Memorial Hospital described the commando operation
1939
Justo Alonso (Uruguay) performed horizontal partial laryngectomy
1965
Bakamjian introduced the two-stage pharyngoesophageal reconstruction with the deltopectoral flap
1979–1980
Stephen Ariyan described the pectoralis major myocutaneous flap
1983
Yang and David Soutar described the radial forearm flap
1989
Hidalgo described the free fibula flap first introduced by Taylor in 1977
2000
Anterolateral thigh flap first described by Song popularized by Wei and colleagues
He was not a proponent of prophylactic dissection of the clinically negative neck. Starting in 1938 at Memorial Sloan Kettering Cancer Center, the group published their results of 665 radical neck dissections performed in 599 patients in 1959.4 Due to the extensive morbidity of the removal of the nonlymphatic structures Suarez in 1952, described the modified radical neck dissection preserving the nonlymphatic structures.5 Ballantyne from the MD Anderson Cancer Center demonstrated comparable results of modified radical neck dissection with radical neck dissections with removal of only those lymph nodes having the highest risk of metastases.6 The concept of functional neck dissection developed with the work of Bocca and Suarez in the 1960s and 1970s.
The pioneering clinical evidence that changed the radicality of neck dissection toward a selective approach was the work of Byers from MD Anderson in 428 patients7 and the series of 1,081 patients by Shah from the Memorial Sloan Kettering Cancer Center that studied the progression of cervical metastasis from primaries of the oral cavity, oropharynx, larynx and hypopharynx.8
 
Thyroid Surgery
Thyroid surgery advances classically reflect the development of our specialty. Initially in the domain of the general surgeon, advances in understanding the anatomy of the parathyroids, the recurrent and external laryngeal nerve, techniques of intraoperative nerve monitoring, imaging and histology acquisition, with high-quality ultrasound, surgery has moved into the head and neck surgeon's armamentarium. From its earliest descriptions in 200 bc for goiter (gutter), with the first surgery being performed in 1646, significant advances and refinements have been made. Kocher, Billroth and Wells made significant contributions in the early century. Rapid strides have been made in the staging system with dynamic risk stratification and personalized approaches in the management of thyroid malignancies.9 Similarly, parathyroid surgery3 made rapid advances with the use of radioimmunometric assays and intraoperative delineation with radionuclide scans.10
 
Laryngeal Surgery
The initial total laryngectomies were considered highly morbid and thus the role of radiotherapy was envisaged as an excellent alternative. However, radiotherapy had its limitations in advanced cancer. Improvements in the understanding of the anatomy and the lymphatic drainage led Pressman to elaborate the importance of subtotal laryngectomies.11 Open cordectomy, vertical partial laryngectomy, supracricoid laryngectomy and supraglottic laryngectomy were less radical but were able to achieve cure.12,13 With the introduction of the CO2 laser in the 1970 it was demonstrated that oncologic cure rates similar to radiotherapy could be achieved in early lesions. Jako and colleagues from the United States,14 and Kleinsasser and Steiner15 from Germany developed endoscopic laser excision of laryngeal tumors thus creating a paradigm shift in the management approach. Robot-assisted supraglottic laryngectomy with and without CO2 laser has expanded the indication for transoral laryngeal cancer resection.16 Voice restoration after laryngectomy was first described by Singer and Blom in 1980. Tracheoesophageal puncture and valve prosthesis is the standard of care for voice rehabilitation after laryngectomy.17 The future hold exciting scope with the possibility of laryngeal transplantation.
 
Salivary Gland Surgery
Salivary gland surgery has developed with a better understanding of the anatomy of the facial nerve, intraoperative nerve monitoring, better rehabilitative measures for the paralyzed face (both dynamic and static), histology driven management of the primary and neck, and adjuvant treatment. The role of molecular profiling in recurrent tumors has enabled use of targeted agents. Surgical extirpation of advanced tumors necessitated the use of various lateral skull-base approaches.
 
Skull-base Surgery
Alfred Ketchum from the National Institute of Health was the first person to describe a craniofacial approach that permitted an enbloc resection of the cribriform plate with the ethmoid complex.18 Subsequently this concept was extended by Terz et al.19 Using the concepts of endoscopic sinus surgery, Kassam, Carrau and Synderman used these to develop transnasal approaches to the management of skull-base tumors.20 Lewis reported innovative techniques with hypotensive anesthesia, high speed drills and repair of the surgical defect reducing operative mortality to 5%.21 Lateral skull-base surgery was advanced by the development of the three Fisch approaches that gave access to lesions in the infratemporal space in relation to the petrous carotid, venous sinuses and the facial nerve.22
 
Reconstructive Surgery
In the last 40–50 years major strides have been made in reconstructive surgery as this was able to overcome the morbidity associated with extensive ablations, ensure timely commencement of adjuvant therapy and better quality of life and function. From the use of skin grafts, local flaps, diversion conduits, axial pattern flaps, the advent of pedicled flaps such as the deltopectoral and pectoralis major was a major hallmark in head and neck reconstruction.23,24 By the 1970s reconstructive microsurgery had developed as a specialty and was evident in the application of various free flaps in head and neck reconstruction.25-27 Currently, the reconstructive armamentarium is so extensive that one can choose from a reconstructive elevator rather than a reconstructive ladder.
 
Prosthodontics and Implantology
As the reconstructive armamentarium improved to include free flaps, osseous reconstruction has heralded a new finesse in final outcomes. The use of virtual planning, cutting guides and customized implants has significantly brought in precision, reduced surgical time and enables optimal functional rehabilitation. Primary dental implantation has also been proven to be safe in the settings of adjuvant radiotherapy. Craniofacial implants and obturators are the other aspects of rehabilitation.28
 
EVOLUTION OF RADIOTHERAPY
This brief description will give insights to the development of radiotherapy in head and neck along with different fractionation schedules and delivery modalities, the details of which will be covered in the relevant sections.
The role of radiation therapy in head and neck cancer emerged in the early 1900s with initially single fraction treatments with subsequent multifraction treatment schedules developed in Europe.29 Advancements were made in the field to incorporate radiation in the postoperative setting in the early 1950s by Fletcher and colleagues at MD Anderson and expanding it to the definitive setting by Million and colleagues (University of Florida) and Wang (Harvard) over the 1960s to 1980s.30 4Fletcher's work defined the indications for postoperative radiotherapy and its benefits in improving locoregional control. It also showed differences between aryepiglottic fold lesions and false vocal cord lesions and refined the techniques of radiation delivery, precise data recording and reporting, radiobiology and time-dose factors and preservation of larynx function. The development of protocols enabled its use in organ preservation protocols for tumors of the oropharynx, larynx, hypopharynx and nasopharynx.
The use of radiation was evaluated in different settings in well-designed randomized trials and meta-analysis.
  • Definitive setting: Evidence for use of radiotherapy with chemotherapy in the definitive setting was in organ preservation trials of appropriately selected patients with larynx and hypopharynx cancer. This was evidenced from the results of the RTOG 91-11 and EORTC HPX trials.31-33
  • Altered fractionation: Accelerated repopulation is known to cause locoregional failure in patients experiencing delay in commencement of treatment and in patients with extended overall radiation treatment times. Altered fractionation regimens can be either hyperfractionation or accelerated fractionation. The EORTC trial demonstrated that hyperfractionation in oropharynx improved local control with a strong trend toward improved survival and no difference in late effects.34 Similarly the Danish group (DAHANCA) also reported improved local control at 5 years by 10% for patients treated with 6 fractions per week, but with no difference in overall survival.35 The meta-analysis suggested that altered fractionation regimens delivered without chemotherapy improved locoregional control and survival (6.4% and 3.4%) at 5 years.36
  • Concomitant chemoradiation: MACH-NC demonstrated a 5-year 4.5% absolute survival benefit of adding chemotherapy to radiation which was most evident in the concurrent setting, with a 6.5% absolute benefit (HR 0.81, 95% CI 0.78–0.86).37
  • Postoperative chemoradiotherapy: Randomized trials conducted by the EORTC and RTOG demonstrated an improvement in local control, disease free survival and overall survival with the addition of cisplatin to postoperative radiotherapy. The presence of positive margins and extranodal extension of tumor were the common indications.38-40
 
Refinements in Radiation Delivery
From the initial two dimensional clinical and plain radiograph-based findings that would delineate the regions for risk to deliver radiotherapy, progress has been made to three dimensional CT-based conformal approaches. These use parallel opposed fields to deliver radiation.
Era of intensity modulated radiotherapy (IMRT): By modulating the intensity of the beam and allowing it to conform to the shape of the target tissue, it was possible to significantly reduce the dose to critical structures. By using multiple radiation beams from different directions with a steep dose gradient and highly conformal dose distribution it was possible to have better coverage of tumor and high risk target areas.
Inverse planning is used to define the target dose for the tumor. It allows for the delivery of simultaneous integrated boost without treatment field modifications.41,42 Variations have been developed in the delivery of IMRT such as step and shoot fields: Multileaf collimator (MLC) does not move, sliding window fields (MLC moves), volumetric arc therapy (VMAT: gantry and MLC move), tomotherapy (gantry, couch and MLC move).
Brachytherapy: Radioactive sources were placed within the tumor and combined with an external beam to boost the primary to a higher dose while still minimizing exposure to surrounding tissues. This was commonly employed for tumors of the lip, tongue, floor of mouth, recurrent nasopharyngeal cancers and recurrent tumors of the head and neck.43,44 This along with intraoperative radiotherapy (IORT) done with electrons or high dose rate low energy photon source allows steep dose fall-off sparing normal tissues.45
Stereotactic radiosurgery (SRS): A highly conformal form of radiotherapy allowing delivery of high dose radiation to the tumor in small fractions. First described for the palliation of skull-base recurrences, has been proven to be effective and well tolerated in the palliative setting.46 The Cyberknife (Accuracy Inc., Sunnyvale CA) is a smaller 6MV X-band accelerator mounted on a robotic arm allowing greater degrees of movement freedom. It can track implanted fiducial markers and has six degrees of freedom. It is mostly used for reradiation.
Proton therapy: Proton therapy aims at reducing the incidental dose to nontarget structures. This has a direct bearing on outcomes as the toxic effects follow a dose-response relationship. A focused beam created by a particle accelerator allows the protons to travel fast through the body with minimal interactions and then increase the interactions as the velocity is reduced with maximal energy deposited resulting in the “Bragg peak” and no exit dose. The dosimetric advantage can translate to clinical benefits. Treatment can be delivered by using5 passive or active scanning techniques. The active or intensity modulated proton therapy (IMPT) is the most commonly used. Skull-base chordomas, chondrosarcomas, paranasal malignancies are indications for proton therapy post-resection. The use of protons for oropharyngeal and nasopharyngeal cancers can minimize the treatment toxicity. Adenoid cystic carcinoma which are unresectable and periorbital tumors are also indications for proton therapy. Reirradiation is also another avenue for proton treatment. Reported toxicity includes reduced rate of feeding tube dependence, malnutrition, lower mucositis, nausea and dysgeusia though the skin toxicity is higher.47
 
EVOLUTION OF CHEMOTHERAPY
Dating back to the 1940s the first chemotherapeutic agents were developed from nitrogen mustard. Teropterin was the first folic acid antagonist to be used in advanced nasopharyngeal carcinoma. Gradually the role of platinum-based components came in as a radiosensitizer and predictor of radiosensitivity. The development of chemotherapy has been from a point when it was initially used in the palliative setting with intra-arterial methotrexate to neoadjuvant, concomitant with radiation and in the adjuvant settings. A variety of cytotoxic agents has been used, the common ones being cisplatin, carboplatin, paclitaxel, docetaxel, 5-fluorouracil, methotrexate, ifosfamide, hydroxyurea. Targeted agents that are in vogue are cetuximab [(antiepidermal growth factor receptor (EGFR)], imatinib, gefitinib and erlotinib, though the evidence of benefit for the latter two is lacking. The concept of metronomic chemotherapy is gaining significance in the recurrent and metastatic setting.48
 
Refinements in Chemotherapy
Platinum-based chemotherapeutic regimens are the cornerstone in the concomitant and adjuvant settings. Multiple phase 3 trials of induction chemotherapy followed by locoregional treatment compared to locoregional treatment alone have shown variable results with regards to survival and decreasing distant metastasis. A meta-analysis showed that induction chemotherapy conferred a nonsignificant survival improvement of 2% at 5 years (HR, 0.95 95% CI 0.88–1.01, p = 0.10).49 The addition of a taxane to cisplatin plus 5-flurouracil-based induction regimen has been shown to improve survival.50,51
 
Organ Preservation Therapy
The use of organ preservation therapy in head and neck cancer was introduced because of poor functional outcomes with surgery. Surgical organ preservation protocols use transoral robotic surgery (TORS) or transoral laser microsurgery (TLMS) or open partial laryngeal surgeries. However, this discussion would primarily be on nonsurgical options. Curative chemoradiotherapy has been established as the standard of care which showed an absolute decrease in 5-year mortality of 6.5% with decreased locoregional failures.37,52 RTOG 91-11 established concurrent chemoradiotherapy for locoregional control and organ preservation in patients with resectable Stage III or IV glottic or supraglottic disease.31,32 This modality is preferred in advanced laryngeal or hypopharyngeal cancers without cartilage involvement. High dose cisplatin (100 mg per square meter of body surface area) given intravenously every 21 days for 3 cycles concurrent with radiotherapy is the standard of care.37 Patients with poor performance status may have carboplatin substituted for cisplatin though it is less effective as definitive therapy.53
Bonner in 2006 showed that cetuximab with radiotherapy provided better locoregional control and overall survival compared to radiotherapy alone, however there was no comparison with cisplatin radiotherapy regimen. This has been borne out by the data from recent randomized trials.54-56
 
Induction Chemotherapy
The role of induction chemotherapy remains controversial and is recommended by the guidelines in a clinical trial setting. Taxane-based chemotherapy in the TAX 324 and EORTC TAX 323 trials showed improved survival but with higher toxic effects and treatment delays.50,51 However, there is significant heterogeneity in trial design which needs to be cautiously interpreted before it can be used before definitive chemoradiation. Toxic effects from induction chemotherapy can prevent 20–30% patients from completing definitive chemoradiation.57 Various single institution trials have looked at the role of induction chemotherapy in advanced oral cancer with borderline resectability, as a bioselection tool to guide treatment decision.
 
FUTURE AVENUES
 
Personalized Therapy
The treatment modalities of head and neck cancer include surgery, radiation, chemotherapy, and targeted therapy (most recently the checkpoint inhibitors). A common denominator for all these modalities is the toxicity profile. Biomarker driven treatment strategies are an exciting avenue of clinical research. Existing markers are for human papilloma virus (HPV)6 in oropharyngeal carcinoma, and Epstein-Barr virus (EBV) in nasopharyngeal carcinoma, in addition pathways and markers associated with EGFR downstream signaling abnormalities (PI3K/MTOR pathway and PTEN pathway) and immune checkpoint-related markers. Advances in digital genomic technologies, detection of circulating DNA from clinical specimens offer potential predictive biomarkers in head and neck squamous cell carcinoma (HNSCC) therapy.58 With both pembrolizumab and nivolumab getting accelerated approval by the FDA the future is likely drugs that are biomarker based, have a high clinical efficacy and durable response rate. With increased access to next-generation sequencing and with the TCGA tumor type agnostic therapy is a reality in clinical development and practice.
 
Vaccinations
Patient specific vaccinations will soon become a reality. With the availability of next generation sequencing, many neoantigens have been identified. The neoantigen with highest affinity are formulated into a peptide or dendritic cell vaccine and delivered as a patient specific vaccine to promote an antitumor response. The presence of neoantigen specific T cells in the blood are used to monitor response. Currently phase I clinical trials are ongoing for vaccines for glioblastoma, melanoma, colon cancer and breast cancer. Viral protein-based vaccines are used in HPV associated HNSCC namely the bivalent HPV 16/18 and the quadrivalent HPV 6/11/16/18.
 
Robotic Surgery
Transoral robotic surgery for head and neck cancer needs appropriate patient selection with outcomes similar to organ sparing techniques having been reported. It has widespread applications as in treatment of the unknown primary, oropharyngeal cancer (allowing for possible deintensification of treatment and better functional outcomes), supraglottic laryngectomy (with outcomes similar to patients treated by radiotherapy) and advanced applications in nasopharyngeal and parapharyngeal tumors.
 
Composite Tissue Allotransplantation and Tissue Engineering
There are various groups involved in research of tissue engineered regenerative medicine (TERM) using stem cells to develop bone regenerates. Similarly work is ongoing in the field of stem cell-based tissue engineered larynx and airway constructs and also complex face transplants have been performed.
 
CONCLUSION
Head and neck oncology has developed over the century with tremendous strides in surgical and nonsurgical modalities of care. From multiple worldwide associations to international cooperative and collaborative groups, the specialty has fostered dedicated training and also integration of multiple disciplines. The future holds exciting prospects in terms of personalized medicine, endoscopic and robotic surgeries and the expanding scope of regenerative medicine, all carving out a distinct niche for themselves in the specialty.
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