lung cancer( 肺 癌 )

PrevalenceEpidemic report in 1999: 1,000, 000 new cases worldwidelyRapid increase in population of youth and femalesDeath rate: 1st in male cancer patients, 3 rd in female; In China, 3rd in cancer patients – 1st in urban, 4th in rural areaA report from WHO predict that lung cancer & AIDS are the first TWO of the most severe D in this century

Etiology & Mechanisms( 病因和发病机制 )

1. Smoking

One of the most important risk factorsSmoking closely related to squamous & small cell lung cancerof lung cancer patients: smokers have 10-13 times higher Death rate than nonsmokers The more the smoking, the longer the course, the earlier the initiation, the younger the deathThe passive smokers have even more impairment than active ones

Smoking & histological changes↓ Ciliary cellsEpithelial cells hyperplasiaMetaplasia to squamous cellAtypical hyperplasia

Industrial waste airTail gas excreted by autoPitchy waste on highwayBenzopyrene

2. Air pollution

3. Pollution in familypassive smokingIncomplete burning of coal Radon

4. Occupational factorsConfirmed by WHOExposure to asbestos, inorganic Arsenate, radon, Nickel, etc Other possible factors include acrylamidine, acrolein resin, chlorovynilic products, etc

5. Ionizing radiationLung is sensitiveOccurrence increased after atomic attacks in Japan and radiation therapyMore related to small cell carcinomaNosocomial radiation is much more, among which, 36.7% from X-rayNatural radiation in special area

6. Diets & NutritionDeficiency of vitamin A or its derivatives, vitamin C, B2 & E

Deficiency of selenium or zinc

Other factorsBronchial carcinoma may be related to chronic bronchitis, lung TB, or other chronic respiratory DTB scar tends to develop into Cancer Genetic correlation remains to be proven

Pathogenesis

Anatomic classificationCentral bronchial carcinoma: segmental or larger bronchi, account for ¾ cases, consist of squamous and small cell lung cancerPeripheral: small bronchi or bronchioles, account for ¼ cases ， adenocarcinoma is the main histological type

Histological classification (WHO) 1980

Squamous cell well, medium or badly differentiated Small undifferentiated cell lymphocyte-like ( avenine cell ) intermediate cell (fusiform cell, polyhedral cell, etc) Adenocarcinoma well, medium or badly differentiated, bronchoalveolar/papillary Large cell accompanied with mucus differentiation accompanied with multilamellar structure cytomegalic, megalocyte hyalocyte

Biobehavioral classification

Small cell lung cancer (SCLC): 25%Non-small cell lung cancer (NSCLC): 75%, including squamous lung cancer, adenocarcinoma, and adeno-squamous lung cancer

Clinical features

Small cell carcinomaOriginated from Kultschitzky (K cell) or argyrophilic cell in mucus gland of airwayEvidence from immunohistochemistry and special tumor markers indicate SCLC has characters of neuroendocrinal tissuesParaneoplastic syndrome: serotonin, histamine, kinin, catecholamine, etc Polymorphic: avenine, lymphoid, and fusiform

Accounts for 25% of all lung cancer cases, increase rapidly recentlyMost malignantOccur commonly at age of 40-50Closely related to history of smoking90% in a central locationSensitive to radiation & chemical therapy

Rapidly growth Earlier local infiltration: blood vessel, hilum of lung, or mediastinal lymph nodeEarlier metastasis: 22-28% in liver, 17-30% in bone marrow, 8-15% in CNS, 11% in postperitonum

Non-small cell lung carcinoma（非小细胞肺癌）

Squamous cell （鳞癌）Originated mainly from segmental or subsegmental bronchiIntraluminal growthCancerous cavity & abscess is more commonMedium or badly differentiated: cancerous nest, keratinization, intercellular bridgeNeural granule rarely seen

Commonly occurrenceIn the elder male personsClosely related to smokingMostly in a central locationSlow growth, late metastasis, more opportunity to be eradicatedInsensitive to radiation & chemical therapy

Adenocarcinoma ( 腺癌 )Acinar, papillary, mucoserous or mucus cell carcinomaOriginated from peripheral bronchiole mucoserous glandsPeripheral lung cancerExtraluminal growth

more commonly in FemalesIrrelevant to smokingEarly local infiltration & early metastasisInfiltrate to pleura→ pleural effusionMetastasis to liver, brain and bones

Bronchoalveolar cancer ( 细支气管肺泡癌 )A subtype of lung adenocarcinomaPeripheral regionSingle nodule, multiple nodule or diffused distributionSlow growth, especially for single noduleInfiltrates to several lobe for diffuse onesWell differentiated

Originated from Clara cell, type alveolar epitheliⅡal cells or mucus cells

Large cell lung cancerMegalocyte, polygonal or presented as clear cytoplasm, May be central, but more occurs peripherallyMalignantNeuroendocrinal granulesMetastasis is a little later than SCLC, so more opportunity for surgery

Clinical manifestations

Symptoms caused by primary tumors

coughhemoptysisgaspingDyspnea or short of breathLoss of body weightfever

CoughOne of the early symptomsStimulating Without sputum or with a little mucus sputumLarge quantity of sputum was seen in bronchoalveolar LCObstructive cough: persistent, high-pitch, metal-like soundExuberant purulent sputum seen in those accompanied with secondary infection

HemoptysisMore commonly in central LCA little amount of blood in sputum, large amount of bleeding is rare

Gasping or asthmaPartly obstruction of airway induced by tumorTypical presentation: localized gasping

Dyspnea, short of breathPossible mechanisms

1. Bronchial narrowing induced by intraluminal growth of tumor

2. Extraluminal oppression by Metastasis of hilar lymph node

3. Large amount of pleural effusion4. Large amount of pericardium effusion5. Diaphragmatic paralysis, obstruction of

superior cava vein, diffuse infiltration

Loss of body weightTumor toxinIncreased consumptionInfectionDyspepsia caused by unendurable pain

Fever

Tumor necrosis, lower than 38.5ºCSecondary infection

Symptoms caused by local infiltration

Chest pain: infiltrated to pleura, ribs or thoracic wallDyspnea: big airway oppressedDysphagia: esophagus infiltrated, or bronchoesophageal fistula Aphasia: recurrent laryngeal nerve infiltrated

Superior cava vein syndrome

Mechanism: Mediastinal infiltration →S. cava V oppressed →blood flow obstructedManifestations: Edema on face, neck and upper limbsVarices and haemostasis on chestHeadache and dizziness

Horner syndrome

Also termed as Pancoast tumor, superior sulcus tumorIn the apex or upper lobe near brachial plexus and cervical sympathetic ganglionOppression on the latter →ipsilateral drooped eyelid, myosis (retracted pupil), inward eyeball, little or no sweating on ipsilateral forehead and chestThe former oppressed →ipsilateral pain radiated to inside upper limb, exacerbated at night

Symptoms caused by distal metastasis

Metastasis to brain and CNSBoneLiverLymph node: such as supraclavicular ones

Paraneoplastic syndrome• In SCLC, Endocrinal disorders: serotonin,

histamine, kinin, catecholamine, etcMale mammary development caused by secretion of human chorionic gonadotrophin (hCG)Cushing syndrome caused by secretion of adrenocorticotrophic hormone (ACTH)

Secretion of anti-diuretic hormone (ADH)1. Diluted hyponatremia2. Dyspepsia3. Fatigue, somnolence

Hypercalcemia caused by parathyroid hormone- related hormone, more in squamous LC

Neuromuscular syndrome

Mechanism is not clear

More commonly in SCLC, but seen in all histological types of LC

Irrespective to site and metastasis

Characteristic manifestations: proximal limb muscle weakness & fatigue

Carcinoid syndrome

Excessive secretion of serotoninOccur in SCLC (avenine cell LC) and adenocarcinomaClinical manifestations:

1. Bronchial spasm →gasping or asthma2. Paroxysmal tachycardia3. Watery diarrhea

4. Skin flush

Digital clubbing & hypertrophic oesteoarthropathy

More commonly in squamous lung cancer, next is adenocarcinoma, least in SCLCDistal side of long bone of limbsAcropachy and oesteoarthropathyDisappear after successful surgery, but appear with recurrence of tumor

ImagingThoracic X-ray– most important examination

1. Thoracic perspective2. Posterioanterior and lateral X-RAY im

aging3. CT4. MRI

PA & lateral X-RAY imaging

Central LC1. Mass or shadow near to hilum with

irregular margin2. Multiple lobe3. Coexistent of atelectasis, obstructive

pneumonia & localized emphysema

Peripheral LC1. Bronchoalveolar LC2. Nodular or diffuse type

CT

Have advantage in diagnosis of LC in special sites: posterior to heart, near to spine, capitulum costae or diaphragm, on apexDiscern metastasis to hilar or mediastinal LNHelix CT: ＞ 3mm discernable

MRI

Compared with CT1. Have advantage in discern the infiltration to

large blood vessels2. But no advantage in the diagnosis of small

tumors

HistologySampling means

1. Bronchoscopy – most important ,90-93% sensitive to central LC

2. CT-guided subcutaneous needle aspiration3. Mediastinoscopy4. Biopsy in surgery5. Exfoliative cytology in sputum, more

sensitive for NSCLC, 70-80%

Scintigraphic Imaging

Tumorphilic chemicals labeled with Radioactive isotypesTumor marker-specific Ab labeled with Radioactive isotypes –radioimmunographyAdministered intravenously or by inhalation, image obtained with a gamma camera＜ 1cm LC or LN metastasis can be discerned by PET

Tumor markers in useCEA, NSE ( 神经原特异性烯醇化酶 ), SCC ( 麟癌细胞抗原 ), TPA ( 组织多肽抗原 )Not sensitive and specific enough

Diagnosis

1. > 40, longtime persistent heavy smokers (smoking index >400 per year)

2. Stimulant cough without prominent trigger, little or no response to therapy; Characters of cough Varied in patients with chronic respiratory D

3. Persistent or recurrent hemoptysis, not interpreted by other respiratory D

4. Recurrent localized pneumonia, esp. segmental pneumonia

5. Lung abscess, without toxic presentations, no exuberant purulent sputum, no inhalation of foreign body, no response to antibiotics

1. Limb articulate pains or acropachy2. Localized emphysema, or segmental,

lobar atelectasis3. Solitary round loci, ipsilateral hilar

enlargement 4. New alterations of Stable TB loci 5. Pleural effusion, especially

haemothorax with progressively increase of effusion

Differentiation DiagnosisLung TBPneumoniaLung abscessTubercular effusion pleurisy

Lung TBTB tuberculoma from central LC: more common in youth, asymptomatic, with clear margin & integral envelope, high density →calcified loci, invariable with follow-upsHilus TB from metastasis to hilar LN: more common in childhood & aging, well responded to tuberculocidesAcute miliary TB from peripheral bronchoalveolar LC: homogenous size, evenly distributed, low density; while the latter with uneven distributed loci, high density, progressively enlargement

Pneumonia

Abrupt onsetRespond well to antibioticsCurable, loci can completely disappear

Lung abscessPrimary Lung abscess: abrupt onset, fever, & other significant toxic symptoms, WBC & neutral granulocyte counting; thinner cavity wall with liquid plane & inflammatory changesCancerous cavity: centrifugal cavity within a cancerous mass, thick & rough wall. May complicated with secondary infection→ fever, production of purulent sputum

Tubercular effusion pleurisy

Malignant effusion: haemothorax, increase rapidlyCEA &LDHNo response to tuberculocidesCytology examine in pleural precipitates

Clinical stagingTNM staging standard for LC

Cryptic Tx N0 M0 (or invisible ) 0 Tis tumor in situ

Ⅰ T1N0M0 T2N0M0 Ⅱ T1N1M0 T2N1M0

Ⅲa T3N0M0 T3N1M0 T1-3N2M0 Ⅲb N3M0 with any T, T4 and M0 with any N Ⅳ M1 with any T, any N

Interpretations for TNM stagingT: primary tumor1. T0: no evidence of tumor2. Tx: cytology findings, but not confirmed by X-ray o

r bronchoscopy, termed as cryptic tumor3. Tis: tumor in situ4. T1: φ3cm, enveloped by lung tissue or visceral l

ayer of pleura, no infiltration to proximal lobar bronchi

5. T2: φ >3cm, or infiltrated to visceral layer of pleura, or obstructive pneumonia or atelectasis; hilar infiltration, but less than 2cm from carina;

6. T3 ： infiltration to chest wall, diaphragm, mediastinum, pleura or pericardium, hilar infiltration, more than 2cm from carina

7. T4: Invades heart, great vessels, esophagus, trachea, carina, vertebrae, or malignant effusion

N: infiltration to local LN1. N0: no infiltration findings2. N1: infiltration around bronchi, or ipsilateral

hilar infiltration, or bilateral infiltration3. N2: metastasis to ipsilateral mediastinal LN

or those below carina4. N3: metastasis to contralateral hilar, mediast

inal LN of the other side; ipsilateral or contralateral metastasis to supraclavicular or scalenus ( 斜角肌 ) LN

5. M: distal metastasisM0: no evidence; M1: proved metastasis

TreatmentNSCLC

1. Stage - a: surgery centered integral interⅠ Ⅲvention

2. Stage b: chemical therapy centered integrⅢal treatment

3. Stage : chemical therapy with supportive ⅣmeasurementsSCLC ： chemical therapy centered, assisted by surgery and/or radiationImmune regulationsTCM

Surgery

PneumonectomyLobectomyLimited resectionsCarinal resection & sleeve PneumonectomyMonitor, Supportive therapy & chemical therapy before & after operation

Chemical therapy

SCLC1. EP project: Etoposide + cisplatin2. CAO project: cytoxan +adriamycina +

vincristineNSCLC

1. EP project2. ICE project: ifosfamide + etoposide +

carboplatin

PrognosisGood prognosis benefits from early diagnosis and early interventionCryptic lung cancer is curableSquamous better than adenocarcinoma, the latter better than small cell undifferentiated cancer