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Surgical Surgical ManagementManagement of of
Malignant TumorsMalignant Tumors
อ . พญ .ทพญ . นุ�ชดา ศรี ยารี�ณย
ภาควิ�ชาศ�ลยศาสตรี�ช�องปาก
คณะท�นุตแพทยศาสตรี� มหาวิ�ทยาล�ยเช ยงใหม�
Etiology and predisposing Etiology and predisposing factorsfactors
The exact cause of oral cancer is
unknown• Variations in incidence rates : differences in exposure to carcinogenic initiators
Risk factorsRisk factors
Genetic predispositionAtmospheric pollutionImmunosuppressionVirusesFungal infectionDietDental sepsis
TobaccoAlcohol
Tobacco Tobacco
24% of all male deaths in developed world7% of all female deathsSmoking is the cause of 45% of all cancer deaths95% of all lung cancer deaths85% of all oral cancer deaths
Tobacco Tobacco
Carcinogens of tobacco Benzopyrene tobacco specific nitrosamines
Act locally on keratinocyte stem cellsAffecting DNA replicationCausing mutation
AlcoholAlcohol
Pure ethanol is not carcinogenicNitrosamines and other impuritiesRising incidence of oral cancer linked to rising alcohol consumption
AlcoholAlcohol
Ethanol increases mucous membrane permeabilityEthanolmetabolised to acetaldehyde locally by bacterial alcohol dehydrogenases and can damage cells – poor oral hygieneAlcoholic liver disease reduces detoxification of carcinogensHigh calorie value suppresses nutrition and leads to nutritional deficiencies
Risk factorsRisk factors
Genetic predisposition ? - impaired capacity to metabolise carcinogens - DNA damage repair impaired
Atmospheric pollution - polycyclic aromatic hydrocarbons/nitrosamines/benzenes
Risk factorsRisk factors
Immunosuppression - organ transplant patients – lip cancer - no increased risk with AIDS of oral SCC
Viruses -HPV 16 and 18 viral oncogene deactivates p53 inhibit apoptosis
Risk factorsRisk factors
HPV and oral cancerPrevalence 0-100 % in OSCCBut only 40% of head and neck SCC with p53 mutations had high risk HPVOnly 40% of HPV positive tumors showed p53 mutationsHPV infection is pobably an early eventHigher prevalence in younger patients
Risk factorsRisk factors
Other viruses Herpes simplex Epstein-Barr virus Hepatitis virus no clear evidence of involvement in
oral cancer
Risk factorsRisk factors
Fungal infection - candida albicans – potential to promote nitrosation of dietary substrates
Diet -Protective effect of antioxidants Vit A, C, E and trace elements Zinc and selenium
Dental sepsis - poor oral hygiene-socioeconomic status
and nitrosating enzyme in plaque
Age and sexAge and sex
older age~ 95% occur in over 40 Yrs The average age at the time of Dx is about 60 Yrsmore frequent in males
Male : Female ~ 2 : 1
SitesSites
The Tongue is the most common site for oral cancer Floor of mouth
Histologic typesHistologic types
Carcinoma 96%Sarcoma 4%The most common type : squamous cell squamous cell carcinomacarcinomaMajor salivary gl. : malignant mixed tumorMinor salivary gl. : adenoid cystic CALymphomaMetastatic tumors to oral cavity
DiagnosisDiagnosis
Examination
• Inspection : oral cavity, neck, pharynx
• Palpation : neck , oral masses
Investigations
1. Surgical biopsy • oral cavity : local anesthesia • Small lesions excisional biopsy• Incisional biopsy is recommended in all cases
Surgical biopsy
The biopsy : suspicious area of the lesion and some normal adjacent mucosa
Avoid area of necrosis or gross infection
2. Toluidine blue test
The suspicious area is paint with 1% aqueous solution of toluidine blue for 10 sec.Rinsed with 1% solution of acetic acidThe toluidine blue binds to DNA present in the superficial cells and resists decoloration by acetic acid
Toluidine blue test
Dye binding is proportional to the amount of DNA present and the number and size of superficial nuclei in the tissuesfalse negativesguide
3. Fine needle aspiration biopsy
lumps in the neck (suspicious lymph nodes) percutaneous puncture of the mass with a fine needle and aspiration of material for cytological examination
FNAB
The node is fixed between finger and thumbPuncture by a 21 or 23 gauge needle on a
10 ml syringeA small amount of air is already in the syringe (2ml) before puncture
FNAB
moving the needle around different parts of the node the plunger is then released and the needle withdrawn through the skinThe tip of the needle must touch the slideSmear slide
FNAB
Wet fixed material: an alcoholic ‘spray fixed’
immediately, 10 minThinner film : air dryafter the aspiration, aspirate 2ml of 95% ethanol as fixative into the same syringe
FNAB
fast , almost painless, needs no specialised equipment and without complicationThe technique depends on 2 aspects:
- successful puncture of the node
- transfer of cells and stroma onto slide
FNAB
Frable and Young: 94.5% accuracy with head and neck lesionsmay avoid the need for open biopsyRisk of spreading malignant cells into the surrounding tissues
(Tumor implantation into the needle track, when large gauge needle has been used)
4. 4. RadiographyRadiography
Limited value 50% of calcified component of bone must be lost before any radiographic change Panthomography alveolar and antral involvementlungs and skeleton
5. Computerised 5. Computerised tomographytomography
Great benefit in head and neck• Primary tumor and lymph node Primary tumor and lymph node
metastasismetastasis• Value in the investigation of
metastasis in the lungs, liver and metastasis in the lungs, liver and skeletonskeleton
6. Radionuclide studies6. Radionuclide studies
Technetium pertechnetate bone scansNot specific
(increased uptake : increased metabolic activity in the bone) Detecting distant metastases
7. Magnetic resonance imaging 7. Magnetic resonance imaging (MRI) (MRI)
Highly contrasted image for soft tissue soft tissue lesionlesionBone is not imagedonly the marrow being directly visualized
8. Ultrasound8. Ultrasound
Noninvasive, readily available and cost effective
• Abdominal ultrasound : liver metastases• intra-oral tumors : high degree of
accuracy, demonstrating bone invasion (early stage)
• Regional LN
Precancerous Precancerous lesionlesion
LeukoplakiaErythroplakia
Location of leukoplakia/erythroplakiaLocation of leukoplakia/erythroplakia
Occurrence probability of dysplasia1. Buccal mucosa 1. Floor of mouth2. Mandibular vestibule 2. Tongue3. Maxillary gingiva 3. Lower lip4. Mandibular gingiva 4. mandibular gingiva5. Tongue 5. Buccal mucosa6. Floor of mouth 6. Mandibular vestibule7. Lower lip 7. Maxillary gingiva
Leukoplakia
Dysplasia
1. Mild Dysplasia 2. Moderate Dysplasia 3. Severe Dysplasia
Leukoplakia
MangementLooking for etiology factors
- stop smoking immediatelynon/mild dysplasia
- total excision - F/U 3-6 mo. when non total
excision
Leukoplakia
Moderate dysplasia - total excision - F/U 4-8 wk. when non total excision
Severe dysplasia - total excision - F/U every 4wk.
Erythroleukoplakia
Moderate dysplasia Management - total excision with 1 cm margin , extend in submucosa - F/U every 4wk.
Erythroplakia
Management - total excision with 1 cm margin , extend in submucosa - F/U every 4wk.
Spread of tumor
Local extensionLymphatic spread
- stepwise spreadHematogenous spread
Biology of metastasisBiology of metastasis
SCC : most to regional LN sometimes through blood (lung, brain, bone)
Biology of metastasisBiology of metastasis
Steps1. Invasion through basement membrane, between endothelial cell or blood vessel (collagenase, heparanase, stromelysin)2. Entrance into lymphatics or blood
vessel form tumor embolus3. Survival of cancer cell in lymphatics or
blood vessel
Biology of metastasisBiology of metastasis
4. Escape from circulation into new tissue (collagenase, heparanase, stromelysin)5. Implantation in new tissue area with
cloning require : angiogenic factors, GF to recruit
blood supply, stimulate self-replication, down regulate host cells, activate host cell (osteoclast)
Incidence of LN metastases
Depend on : - size - site - histological type of primary tumor
LN metastases
most commonly in the upper deep cervical and submandibular nodes on the same side of the primary tumorlower deep cervical nodes : rareContralateral node metastases : rare
Incidence of LN metastases
Site : - more posterior lesion in the mouth the more likely LN metastases Retromolar trigone : 45% Tongue : 35% Floor of mouth = lower alveolus : 30% buccal mucosa and hard palate, lower lip : 10-15%
Incidence of LN metastases
Histology SCC : The better differentiated, the less
metas. verrucous CA : low well diff. SCC : 26% moderated diff. SCC :33% poorly diff. SCC : 50%
Diagnosis of LN metastases
• Clinical examination• Imaging• Cytology• Histology
Imaging
CT - sensitivity similar to clinical exam.
sensitivity > 90% Node above 1 cm suspicious of
malinancy
Diagnosis of LN metastases
Ultrasound - simple, relative cheap - used to guide FNAB of impalpable
nodes
Diagnosis of LN metastases
Cytology (FNAB) - useful confirmatory test - accuracy is high - false-negative results
open biopsy
Lymphatic drainage
Superficial parotid LN submental LN
deep parotid LN submandibular LN
deep cervical LN
Lymphatic drainage
- anterior floor of mouth, anterior alveolar ridge, lower lip submental triangle LN
- Posterior floor of mouth, tongue, buccal mucosa, posterior alveolar ridge Submandibular LN
- Cancer of tongue node of Stahr- retromolar trigone, tonsillar fossa,
pharyngeal tongue jugulodigastric LN
Lymphatic drainage
- SCC Lung (multifocal) Oral Lung (venous system) - invasion into small vein - drain to larger vein - cancer emboli SVC - heart - pulmonary artery
Classification and Classification and stagingstaging
TNM classification
TNM classification
Pretreatment Clinical Classification (cTNM) - clinical, radiological, other investigation
Postsurgical Histopathological Classification (pTNM)
- by surgical findings and the examination of the therapeutically resected specimen
T – Primary Tumor TX Primary tumor cannot be assessed TIS Pre-invasive carcinoma (carcinoma-in-situ) T0 No evidence of primary tumor T1 Tumor size ≤ 2 cm T2 Tumor size > 2 but ≤ 4 cm T3 Tumor size > 4 cm T4 Massive tumor or Tumor invades adjacent structures e.g. through cortical bone, muscles (intrinsic) of tongue, muscle of mastication, maxillary sinus, skin
N – Regional Lymph Nodes
NX Regional LNcannot be assessed
N0 Noregional LN metastasisN1 single ipsilateral LN ≤ 3 cm
N2a ipsilateral LN >3 but ≤ 6 cmN2b multiple ipsilateral LN ≤ 6 cmN2c bilateral or contralateral LN ≤ 6
cm
N3 LN > 6 cm
M – Distant Metastases
MX distant metastasis can not assessedM0 no distant metastasisM1 metastasis present
Postsurgical histopathological classification uses the same categories for pT, pN and pM
The stage grouping in UICC classification
Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 T1, T2, T3 N1 M0 Stage IV T4 N0, N1 M0 Any T N2, N3 M0 Any T Any N M1
Histopathological Grading (G)
GX Grade of differentiation cannot be assessed
G1 Well differentiatedG2 Moderately differentiatedG3 Poorly differentiatedG4 Undifferentiated
The absence or presence of residual tumor after Tx. (R)
RX Presence of residual tumor cannot be assessed
R0 No residual tumorR1 Microscopic residual tumorR2 Macroscopic residual tumor
Basic aim of treatment Eradication of tumor with satisfactory physiological function : mastication, phonation, facial
expression and an acceptable cosmetic
appearance
Treatment of oral cancer
SurgeryRadiotherapyChemoradiotherapySurgery with adjuvant radiotherapy
Surgery : main of treatment Primary site is resected, cervical LN are removed
Radiotherapy can be primary Tx. or
combined with surgeryChemotherapy
not suitable as primary Tx. can be combined with
surgery and radiation
Team work
SurgeonRadiotherapistMedical oncologistPathologistSupportive team (nurse, prosthetist, speech therapist, psychiatrist, etc.)
PrognosisPrognosis
Factor• Site • Size (diameter, thickness , invasion)• Degree of histologic differentiation• Lymph node metastasis (Level,
number)• Extranodal spread• Distant metastasis
CA of oral cavity management of primary
tumor
Choice of treatment factors in deciding - site of origin - stage of disease - histology of the tumor - medical condition and lifestyle
Stage of diseaseStage of disease
Small lesion : surgery without deformity (1cm margin)
Large mass with invasion of bone : Surgery, low cure rates by radiotherapy
Lesions of intermediate stage (larger T1, most T2, early exophytic T3) :
controversial, similar survival rate (functional results and morbidity)
Stage of disease
Advanced as to be unresectable :Radiotherapy or chemotherapy• Previously irradiated tissue : relatively
radioresistant because of limited blood supply : not advisable to re-treat
Multiple primary tumors or extensive premalignant change : surgery
HistologyHistology
SCC : poorly differentiated ~ higher incidence
of lymphatic spread, worse prognosis
Verrucous CA in early stage (superficial exophytic lesion : local excision Adenoid cystic carcinoma of minor salivary gland : nerve resection, nerve canal
resection
Medical condition and lifestyle
Age : elderly, poor general condition,
with advanced disease irradiationAlcoholic patient, smoking : high risk of postradiation complication
Principles of resection
Palliative resectionCurative resection
Palliative resection
Aim improve quality of life • Reduction of the tumor size (when
compression of vital structure)• Debulking : control of tumor with
subsequent radiotherapy and/or chemotherapy
• To relieve pain (direct excision or surgical decompession
Curative resection
Remove tumor in one piece with margin of microscopically normal tissue
Frozen section Management of regional lymph nodes
Frozen section
Principle• Between surgery• Margin of resection tissue• residual
Neck dissection
‘Lymphatics and lymph node chain in the neck are contained in the cervical fascia and in fatty contents around the cervical fascia of the neck’
Cervical lymph node in level I-V
Level I
submental LN (submental triangle) laterally : two anterior bellies of digastric inferior : hyoid bone floor : mylohyoid
submandibular LN (digastric triangle)
superior : mandible anterior : anterior belly of digastric posterior : posterior belly of digastric floor : mylohyoid, hyoglossus
Level II
Upper internal jugular nodes caudal : carotid bifurcation or hyoid dorsal : dorsal of sternoclidomastoid
m. anterior : stylohyoid muscle
Level III
Mid internal jugular nodes cranial : hyoid and carotid bifurcation caudal : omohyoid m. anterior : sternohyoid m. posterior : dorsal of sternocleidomastoid
m.
Level IV
Lower internal jugular nodes cranial : omohyoid m. caudal : clavicular anterior : sternohyoid m. posterior : dorsal of sternocleidomastoid
m.
Level V
Spinal accessory, supraclavicular LNand posterior triangle anterior : dorsal of sternocleidomastoid m. posterior : trapezius m. inferior : clavicle
Types of neck dissection
Comprehensive neck dissection - radical
Selective neck dissection - functional sparing
Comprehensive neck dissection
Type Node level preserved
Radical ND I-V noneModified RND 1 I-V SANModified RND 2 I-V SAN, IJVModified RND 3 I-V SAN, IJV, SCM
Standard radical neck dissection
All LN are removed (level I-V) superiorly : from the level of mandible inferiorly : to the clavicle postriorly : from the trapezius m. anteriorly : to the midlineSacrificing : sternocleidomastiod m.,
internaljugular vein, spinal accessory n.
Indications for radical neck Indications for radical neck dissectiondissection
N3 neck disease where accessory nerve not preservablemultiple positive LN involving accessory n. or internal jugular v. Gross extranodal spreadResidual or recurrent disease after radiotherapy
Contraindications for radical Contraindications for radical neck dissectionneck dissection
Distant metastasesPoor general condition or high risk for GAFixed LN with skin infiltration or ulceration
Modified radical neck dissection
1. MRND – I preserves the accessory n.2. MRND – II preserves accessory n. and internal
jugular vein 3. MRND – III preserves accessory n., sternocleidomastoid m. and internal jugular vein
Indications for modified RNDIndications for modified RND
N+ neck where all nodal levels require dissectionWhere certained structures are involved by nodal metastases but others can be preserved. To preserve function especially the accessory n.Maintain IJV for microvascular anastomosis
Selective neck dissection
Some compartment or preserve structure
1. Submandibular triangle dissection 2. Suprahyoid ND (level I-II) 3. Supraomohyoid ND (level I, II, III)
Indications forIndications for supraomohyoid ND supraomohyoid ND
Oral cavity tumorsN0 neck Small N+ disease
Aims of neck Aims of neck dissectiondissection
Removed nodal metastases, manage disease in neckNode sampling for accurate pathological staging to direct further Tx. of the neck
Node disease and survivalNode disease and survival
Positive LN metastases are the single most important prognostic indicator for survivalSurvival is decreased by up to 50%
Oral cancerOral cancer
Tongue and floor of mouth 65% of all oral cancer
SCC : predominantly
The Tongue
20 –30% of oral cancerMajority : middle third of lateral margin, extending onto the ventral aspect and floor of the mouth25% on posterior 1/3 of the tongue20% on anterior 1/3 of the tongue4% on the dorsum (associated with syphilitic glossitis)
The tongue
Manifestation: exophytic with ulceration,
superficial ulceration with infiltrationEndophytic tumor
The Tongue Typical malignant ulcer:
Often several centimeters in diameterHard in consistency with heaped-up and
everted edgesFloor is granular, indurated and bleeds,
area of necrosis
The tongue
difficulty with speech and swollowing Pain : severe and constant, radiating to
the neck and ears LN metastases : common (relatively early) 12% may present with no symptoms other
than a lump in the neck
The Tongue
Treatment• Small lesion : intraoral excision Excision of less than 1/3: no
reconstruction• Exceeding 2 cm :
hemiglossectomy
The Tongue
Extensive tongue lesion involve floor of mouth and alveolus :
lip split and mandibulotomyTumors reach the alveolus : rim resection of the mandible, reconstruction with distant flapnot exceed 2/3 of tongue : radial forearm free flap with microvascular anastomosis
The Tongue
Large volume defect, total glossectomy, deeply infiltrating tumor :
resection extends to hyoid bone, pectoralis major muscle flap
When possible at least one hypoglossal n. should be preserved
The floor of the The floor of the mouthmouth
second most common site for oral cancerMost : anterior of the floor of mouth to
one side of the midlineIndurated massEarly stage : tongue and lingual aspect of the mandible become involved
The floor of the mouth
Early slurring of the speechLymphatic metastasis is less common, usually to submandibular and jugulodigastric nodes and may be bilateralAssociated with preexisting leukoplakia more commonly
Floor of the mouth
Treatmentsmall tumor : simple excision (1 cm margin)
• involve the under surface of tongue and lower alveolus :
surgical excision partial glossectomy and marginal resection of mandible, reconstructed with local or distant flap
The Gingiva and alveolar ridge
Predominantly in the premolar and molar regionsproliferative tissue at the gingival margins or superficial gingival ulcerationHx. of tooth extraction with subsequent failure of the socket to heal or sudden difficulty in wearing denturesEdentulous alveolar ridge : indolent superficial ulceration often adjacent to leukoplakia
The Gingiva and alveolar ridge
DDx :apical or periodontal abscessPyogenic granulomaPeripheral giant cell granulomaPregnancy granulomaPolypoidSessile fibroepithelial lesionDenture granuloma
The Gingiva and alveolar ridge
Invasion of the underlying bone 50% of cases (important consequences for treatment)Regional nodal metastasis is common
(30-84%)
Lower alveolus
Modality of choice : surgeryMarginal resectionExtensive invasion :
continuity resection and reconstruct with free corticocancellous graft (iliac, rib) or microvascular tissue transfer
The buccal mucosa
SCC mostly arise at the commissure or along the occlusal plane to the retromolar areamajority : situated posteriorlyExophytic, ulcero-infiltrative and verrucous typeSometimes presenting with trismus
(deep neoplastic infiltration into the buccinator muscle)
The buccal mucosa
LN metastasis : submental,submandibular, parotid and lateral pharyngeal
nodes
Buccal mucosa
Treatment• Lesion confined to buccal mucosa : wide excision include buccinator m. and split thickness skin graft• Small defects up to 3 x 5 cm : excision and closure with buccal fat pad• More extensive lesions : reconstruction with free radial fore arm flap, temporalis muscle flap
The hard palate, maxillary alveolar ridge and floor of antrum
Presenting symptom :Complaint of painful or ill-fitting denture CA in the floor of maxillary antrum often present as palatal tumors present with dental symptoms
early symptoms are non specific and mimic chronic sinusitis
The hard palate, maxillary alveolar ridge and floor of antrum
symptom :painless loose teeth failure of the sockets to heal after extractionswelling in the mucogingival foldpain, swelling or numbness of the faceLater symptoms : nasal obstruction, discharge or bleeding oro-antral fistula
The hard palate, maxillary alveolar ridge and floor of antrum
symptom :Occasionally localised or referred pain in the premolar or molar teeth : early infiltration of the posterior superior dental n.Trismus : tumors extend backwards into the pterygoid region
The hard palate, maxillary alveolar ridge and floor of antrum
LN metastasis from CA of the palate and floor of the antrum : late, poor prognosisInitially to submandibular nodes and then to the deep cervical chain
Hard palate and upper alveolus and
maxillary antrum Tumor of minor salivary gl. are more commonSCC arise from maxillary antrum
TreatmentTreatmentInvolve bone : surgeryRadiotherapy alone for small early superficial tumor
Hard palate and upper alveolus and maxillary antrum
Tumor in hard palate, upper alveolus, floor of antrum : partial maxillectomyMore extensive tumor confined to maxilla : total maxillectomyExposed through a Weber-Fergusson incision
Hard palate and upper alveolus and
maxillary antrum
Defect : reconstruction or obturator prosthesisReconstruction : local flap or free flapSmall posterior defect : buccal fat pad or masseter muscle flap
Carcinoma of the lip
SCCLower lip > upper lipGreater exposure of lower lip to sunlightUlcer, keratin crust covers ulcerRest of lip vermillion may show actinic change
Carcinoma of the lip
Up to 1/3 of lower lip can be removed Up to 1/4 of upper lip can be removed
V or W shaped excision with primary closure (up to 2 cm diameter)
large central defect of lower lip Step ladder approach of Johanson
Abbe or Estlander plastic
Retromolar trigone
Anterior surface of ascending ramusTumor invade the ascending ramusSpread to pterygomandibular space
Retromolar trigone
Surgery : lip split and mandibulotomySmall defect : reconstructed with masseter or temporalis muscle flapLarger defect : free flap