surgical management of malignant tumors อ. พญ. ทพญ. นุชดา...

Surgical Surgical ManagementManagement of of

Malignant TumorsMalignant Tumors

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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


Genetic predisposition ? - impaired capacity to metabolise carcinogens - DNA damage repair impaired

Atmospheric pollution - polycyclic aromatic hydrocarbons/nitrosamines/benzenes


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


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


Other viruses Herpes simplex Epstein-Barr virus Hepatitis virus no clear evidence of involvement in

oral cancer


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)


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


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


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%


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


Ultrasound - simple, relative cheap - used to guide FNAB of impalpable

nodes


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


DDx :apical or periodontal abscessPyogenic granulomaPeripheral giant cell granulomaPregnancy granulomaPolypoidSessile fibroepithelial lesionDenture granuloma


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


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


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


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

surgical management of malignant tumors อ. พญ. ทพญ. นุชดา...

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