OCCUPATIONAL CANCER Dr Majid Golabadi Occupational Medicine Specialist

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OCCUPATIONAL CANCER Dr. Majid Golabadi Occupational Medicine Specialist Isfahan University of Medical Sciences

OCCUPATIONAL CANCER Dr. Majid Golabadi Occupational Medicine Specialist Isfahan University of Medical Sciences

What Is Cancer? Cancer is a large group of diseases (over 200) characterized by

What Is Cancer? Cancer is a large group of diseases (over 200) characterized by uncontrolled growth and spread of abnormal cells.

 The majority of cancers in adults: Genetic factors Lifestyle Environmental and occupational exposure

The majority of cancers in adults: Genetic factors Lifestyle Environmental and occupational exposure

 Stress Sleep disturbances, Diet: high fat and low in fruits and vegetables Lack

Stress Sleep disturbances, Diet: high fat and low in fruits and vegetables Lack of exercise Chemicals In Foods Smoking – 30% of all cancer deaths, 87% of lung cancer deaths Obesity – 50% higher risk for breast cancer in postmenopausal women, 40% higher risk in colon cancer for men Viral Factors

 5 -10% of all human cancers are thought to be caused by occupational

5 -10% of all human cancers are thought to be caused by occupational exposure to carcinogens Carcinogen: Any chemical , physical or biologic agent present at the workplace which increases the risk of cancer among exposed workers

Stages in Tumor Development 1. Initiation Cancers come from an abnormal cell (mutation in

Stages in Tumor Development 1. Initiation Cancers come from an abnormal cell (mutation in DNA) 2. Promotion To a benign or preneoplastic tumor 3. Progression To a malignant tumor

Carcinogens Initiator Promoter Complete Carcinogens

Carcinogens Initiator Promoter Complete Carcinogens

 Medical surveillance : Occupational cancers are completely preventable Induction-latency period 3 -5 years

Medical surveillance : Occupational cancers are completely preventable Induction-latency period 3 -5 years for radiation or toxin induced leukemias 40 or more years for some cases of asbestos- induced mesothelioma For Solid tumors usually 10 -25 years There is controversy about the existence of threshold doses for carcinogenic agents

OCCUPATIONAL CANCER Avoid the use of chemical in IARC groups 1 and 2 A

OCCUPATIONAL CANCER Avoid the use of chemical in IARC groups 1 and 2 A Use agent in group 2 B only with very tight controls when there are no viable alternatives

OCCUPATIONAL HUMAN CARCINOGENS GROUP 1 (IARC) CLASSIFICATION Arsenic Asbestos Benzene Beryllium Lung, Skin, Liver

OCCUPATIONAL HUMAN CARCINOGENS GROUP 1 (IARC) CLASSIFICATION Arsenic Asbestos Benzene Beryllium Lung, Skin, Liver Pleura & peritoneum, Lung, Larynx, GI Leukemia Lung Cadmium Chromium Coal tar Mustard gas Nickel Solar radiation Lung Skin, Scrotum, Lung, Nasal sinus Skin Vinyl chloride Liver

Selected industrial processes causally associated with human cancer Industrial process Agent Cancer site Aluminum

Selected industrial processes causally associated with human cancer Industrial process Agent Cancer site Aluminum production Shoe manufacture Iron and steel founding PAH Lung, bladder Benzene Leukemia PAH, Silica lung Aromatic amines, solvents Bladder, leukemia Rubber industry

OCCUPATIONAL CANCER l LUNG l MESOTHELIOMA l NASAL CAVITY & SINUSES l LARYNX l

OCCUPATIONAL CANCER l LUNG l MESOTHELIOMA l NASAL CAVITY & SINUSES l LARYNX l BLADDER l LIVER l SKIN l HEMATOLOGIC

LUNG CANCER

LUNG CANCER

LUNG CANCER The currently accounts for almost 30% of all cancer deaths The most

LUNG CANCER The currently accounts for almost 30% of all cancer deaths The most preventable risk factor: cigarette smoking In occupations with high prevalence of smoking There is no one cell type that is pathognomonic of an occupationally related lung cancer

LUNG CANCER: Related carcinogens l Asbestos l Radon l. Chloromethyl ethers l PAHs l

LUNG CANCER: Related carcinogens l Asbestos l Radon l. Chloromethyl ethers l PAHs l Chromium l Nickel l Arsenic l Mustard

Asbestos (Asbestos miners, Textile, Insulation , filter, Shipyard)

Asbestos (Asbestos miners, Textile, Insulation , filter, Shipyard)

Blue asbestos (Crocidolyte) White asbestos (Chrysotile) Brown asbestos (Amosite)

Blue asbestos (Crocidolyte) White asbestos (Chrysotile) Brown asbestos (Amosite)

Asbestos The accounting for 20% of all deaths in asbestosexposed 7% of all lung

Asbestos The accounting for 20% of all deaths in asbestosexposed 7% of all lung cancer is attributable to asbestos exposure. A latency period: 20 years Synergic effect with Smoking Cigarette smoke: initiator Asbestos: promoter Adenocarcinoma

Radon (Uranium mining , Domestic exposure) Excessive lung cancer in uranium miners is independent

Radon (Uranium mining , Domestic exposure) Excessive lung cancer in uranium miners is independent of cigarette smoking, although exposure to both is synergistic

Polycyclic Aromatic Hydrocarbons (PAHs) From the incomplete combustion of coal tar, pitch, oil and

Polycyclic Aromatic Hydrocarbons (PAHs) From the incomplete combustion of coal tar, pitch, oil and coke The scrotal cancer in chimney sweeps (Dermal exposure to soot) Coke oven workers, Roofers, Printers, Truckers, Rubber plant workers, Asphalt workers

Chloromethyl Ethers Chloromethyl ether (CMME) Bischloromethyl ether (BCME) Bactericides, Pesticides, Dispersing agents, Water repellents,

Chloromethyl Ethers Chloromethyl ether (CMME) Bischloromethyl ether (BCME) Bactericides, Pesticides, Dispersing agents, Water repellents, Flame-proofing agents Small cell lung cancer

Arsenic (Organic Arsenic) Lead, Copper and Zinc smelting Pesticides Chromium Chromate production Nickel Soluble

Arsenic (Organic Arsenic) Lead, Copper and Zinc smelting Pesticides Chromium Chromate production Nickel Soluble forms

Probably Carcinogenic for lung cancer Acrilonitryl Beryllium Cadmium Vinyl chloride Formaldehyde Acid Sulfuric

Probably Carcinogenic for lung cancer Acrilonitryl Beryllium Cadmium Vinyl chloride Formaldehyde Acid Sulfuric

Medical monitoring in the workplace (Screening ) Periodic examination: History , Physical exam, smoke,

Medical monitoring in the workplace (Screening ) Periodic examination: History , Physical exam, smoke, training Symptoms: persistent cough, blood-streaked sputum, chest pain, Voice change Environmental monitoring Serial Chest Radiography and Sputum cytology (OSHA, NIOSH) CT Scan (spiral, …. . ), HRCT

Prevention Primary prevention: The most effective methods Complete avoidance of exposure to the carcinogen

Prevention Primary prevention: The most effective methods Complete avoidance of exposure to the carcinogen Identification of etiologic agents in the workplace Worker education

MESOTHELIOMA Asbestos l Asbestos miners l Textile manufacturing l Insulation and filter production l

MESOTHELIOMA Asbestos l Asbestos miners l Textile manufacturing l Insulation and filter production l Construction workers l Welders, Plumbers, electricians l Roofers l Shipyard workers

MESOTHELIOMA The latency period: 30 years or more Cigarette smoking dose not increase the

MESOTHELIOMA The latency period: 30 years or more Cigarette smoking dose not increase the risk of MM Symptoms: Persistent gnawing chest pain, dyspnea, dry cough, weight loss Pleural effusion, pleural thickening or nodularity, interstitial pulmonary fibrosis, pleural plaques, pleural calcification CXRay: Unilateral pleural effusion CT_Scan: Most sensitive test for pleural surface Sputum cytology Thoracentesis Thorachotomy and thoracoscopy

MESOTHELIOMA Treatment: Surgical Radiotherapy Chemotherapy Prognosis: 75% of patients die within 1 year after

MESOTHELIOMA Treatment: Surgical Radiotherapy Chemotherapy Prognosis: 75% of patients die within 1 year after diagnosis Pleura, peritoneal

NASAL CAVITY & SINUSES CANCER

NASAL CAVITY & SINUSES CANCER

NASAL CAVITY & SINUSES CANCER l. More frequent in men than women (2: 1)

NASAL CAVITY & SINUSES CANCER l. More frequent in men than women (2: 1) l. Usually squamous cell histology (50%), l. The disease is very uncommon in workers under 50 years of age, and rates increase with age

NASAL CAVITY & SINUSES CANCER l Wood and other dusts (Furniture, Textile, boot and

NASAL CAVITY & SINUSES CANCER l Wood and other dusts (Furniture, Textile, boot and shoe manufacturing, bakes ) l. Chromium (Nasal septum ulcer and perforation) (Chromate pigment production , metal plating ) l Nickel (Nickel refinery workers) l Isopropyl alcohol, Formaldehyde (laboratory workers , other industries ) • Owen workers, foundry workers, Radium, Radon, mustard

NASAL CAVITY & SINUSES CANCER l Symptoms: Unilateral nasal obstruction Non-healing ulcer Occasional bleeding

NASAL CAVITY & SINUSES CANCER l Symptoms: Unilateral nasal obstruction Non-healing ulcer Occasional bleeding A low-grade chronic infection, associated with discharge, obstruction , and minor intermittent bleeding

Wood and other organic dusts l. Chronic hypertrophic rhinitis l. Dry atrophic nasal mucosa

Wood and other organic dusts l. Chronic hypertrophic rhinitis l. Dry atrophic nasal mucosa l. Nasal polyps l. Almost Adenocarcinomas

Prevention Primary prevention: Complete avoidance of exposure to the carcinogen is the ultimate goal,

Prevention Primary prevention: Complete avoidance of exposure to the carcinogen is the ultimate goal, but this is not always possible Identification of etiologic agents in the workplace Worker education

CANCER OF THE LARYNX

CANCER OF THE LARYNX

CANCER OF THE LARYNX l. Laryngeal cancer is primarily a disease of older workers.

CANCER OF THE LARYNX l. Laryngeal cancer is primarily a disease of older workers. l. Cancer of the larynx is much more common than sinonasal cancer l. Cigarette smoking and alcohol abuse are the primary etiologic factors l. Much more frequent in men than women (4. 5: 1) , usually middle aged or older

CANCER OF THE LARYNX Asbestos l Asbestos miners l Textile manufacturing l Insulation and

CANCER OF THE LARYNX Asbestos l Asbestos miners l Textile manufacturing l Insulation and filter production l. Shipyard workers

CANCER OF THE LARYNX l Hoarseness is an early presenting symptom l Usually squamous

CANCER OF THE LARYNX l Hoarseness is an early presenting symptom l Usually squamous cell histology l At the time of diagnosis: 60% localized 30% regional spread 10% distance metastases l 40% supra-glottic, 59% glottic, 1% sub-glottic

Prevention Primary prevention: Complete avoidance of exposure to the carcinogen is the ultimate goal,

Prevention Primary prevention: Complete avoidance of exposure to the carcinogen is the ultimate goal, but this is not always possible Identification of etiologic agents in the workplace Worker education Periodic examination: History , Physical exam, smoke, training Environmental monitoring (limits)

BLADDER CANCER

BLADDER CANCER

BLADDER CANCER l 5% of all malignant tumors l M/F = 2/1 l Cigarette

BLADDER CANCER l 5% of all malignant tumors l M/F = 2/1 l Cigarette smoking is the most important etiologic factor (60%) l Water infected to pesticides and other chemicals l The latency period: mean of 20 years l Presenting complaints of hematuria and vesical irritability l Diagnosis by urine cytologic examination and cystoscopy

Aromatic Amins l Naphtylamine (Textile workers, Dye & pigment manufacture, Rubber manufacture) l 4

Aromatic Amins l Naphtylamine (Textile workers, Dye & pigment manufacture, Rubber manufacture) l 4 -Aminobiphenyl (Tire & Rubber manufacture) l Benzidine (Dye & pigment manufacture) l Chlornaphazine (leather worker) l O-toluidine (Painters, Textile workers , Bootblacks) l Phenastin (Petroleum workers, Hairdressers)

High exposed workers Textile workers, Dye & pigment manufacture, Tire & Rubber manufacture leather

High exposed workers Textile workers, Dye & pigment manufacture, Tire & Rubber manufacture leather worker Painters, Bootblacks Petroleum workers, Hairdressers

4 - Aminobiphenyl

4 - Aminobiphenyl

Chlornaphazine

Chlornaphazine

Benzidine

Benzidine

Pathogenesis & Pathology Body exposure via GI, Dermal or Respiratory Caused by contact of

Pathogenesis & Pathology Body exposure via GI, Dermal or Respiratory Caused by contact of the bladder epithelium with carcinogens in the urine The bladder is exposed to higher concentration of these materials than other body tissues Urothelial tumors: 90% transitional cell type 6 -8 % squamous cell 2% adenocarcinoma

Clinical findings The most common: Hematuria 80% Painless, gross, and intermittent 20%: the vesical

Clinical findings The most common: Hematuria 80% Painless, gross, and intermittent 20%: the vesical irritability alone, with increased frequency, dysuria, urgency and nocturia U/A: RBC, Blood Anemia, Uremia

Prognosis varies with the stage of the disease Superficial: The excellent 5 -year survival

Prognosis varies with the stage of the disease Superficial: The excellent 5 -year survival Muscle invasion: 40 -50% of patients 5 -year survival Local spread of disease in the pelvis: 10 -17% of patients survive 5 years

Screening Urine cytology and U/A: Screening tool Sensitivity (75%), specifity (99. 9%) Used to

Screening Urine cytology and U/A: Screening tool Sensitivity (75%), specifity (99. 9%) Used to screen only certain at risk occupations The screening of high-risk patients may result in a significant reduction of the stage of disease at diagnose, with improved long-term survival

LIVER CANCER l Vinyl chloride (PVC production) l Arsenic (Pesticide , Copper , Lead

LIVER CANCER l Vinyl chloride (PVC production) l Arsenic (Pesticide , Copper , Lead , Zinc smelting , Wine maker, Fowler) l Thorotrast

Hepatic Angiosarcoma of the liver is a rare tumor M/F: 4/1 Major exposure to

Hepatic Angiosarcoma of the liver is a rare tumor M/F: 4/1 Major exposure to vinyl chloride Sign & symptoms RUQ abdominal pain, weight loss Hepatomegaly on physical examination Diagonisis by hepatic arterogram and liver biopsy

Clinical Findings Non-specific: Fatigue, weakness, and weight loss are seen in 25 -50% of

Clinical Findings Non-specific: Fatigue, weakness, and weight loss are seen in 25 -50% of patients The some patients may be asymptomatic Abdominal pain is the most common symptom, usually in the RUQ Phx: Hepatomegaly with ascites Jaundice Splenomegaly , abdominal mass, tenderness

Laboratory findings A mild anemia, target cells and schistocytes Leukocytosis and thrombocytopenia (1/2 patients)

Laboratory findings A mild anemia, target cells and schistocytes Leukocytosis and thrombocytopenia (1/2 patients) Prolonged PT Almost all patients: abnormality of liver function testing ALT, AST and ALP

Screening tests Periodic testing: History and physical examination CBC, LFT (SGOT, SGPT, ALP)

Screening tests Periodic testing: History and physical examination CBC, LFT (SGOT, SGPT, ALP)

SKIN CANCER l UV radiation (Outdoor workers, welding arc) l PAHs (coal tar workers

SKIN CANCER l UV radiation (Outdoor workers, welding arc) l PAHs (coal tar workers , Electrode production , Pigment Industry , Roofers , Shale oil worker) l Ionizing radiation (Uranium miners, Health care workers, Military personnel) l Arsenic (Pesticide , Copper , Lead , Zinc smelting) l. Chronic inflamation

UV Radiation Major risk is ultraviolet radiation There are 4. 8 million outdoor workers

UV Radiation Major risk is ultraviolet radiation There are 4. 8 million outdoor workers in the USA (agriculture, …) The estimated 300000 workers are exposed to industrial radiation sources (welding arc, germicides and printing processors)

PAHs

PAHs

Ionizing radiation & skin cancer High risk: more than 1000 c. Gy Early radiation

Ionizing radiation & skin cancer High risk: more than 1000 c. Gy Early radiation workers with heavy exposure: Predominantly SCC The hands and feet and occasionally on the face More recently, basal cell cancers have been described following repeated occupational exposures

Arsenic Punctate keratoses of the palms and soles and hyperpigmentation are frequently seen

Arsenic Punctate keratoses of the palms and soles and hyperpigmentation are frequently seen

HEMATOLOGIC CANCER l Ionizing radiation (Nuclear power plant worker, Health care worker, Military personnel)

HEMATOLOGIC CANCER l Ionizing radiation (Nuclear power plant worker, Health care worker, Military personnel) l Benzene (Petrochemical and refinery worker , Rubber worker)

Ionizing radiation & aplastic anemia o Dose dependent o Large dose & long term

Ionizing radiation & aplastic anemia o Dose dependent o Large dose & long term (small amount) o Risk: n n Increased until 3 -5 years after exposure After which there is a marked decline in incidence o Treatment: n Bone marrow transplantation, hematopoietic growth factors

Benzene & leukemia o Benzene is a cyclic hydrocarbon obtained in distillation of petroleum

Benzene & leukemia o Benzene is a cyclic hydrocarbon obtained in distillation of petroleum and coal tar o It is used widely in chemical synthesis in many industries o Explosives, soap, perfums, Drugs, dyes, rubber, shoes

Benzene & leukemia o Workers exposed for 5 years or more had a 21

Benzene & leukemia o Workers exposed for 5 years or more had a 21 -fold increased risk of death from leukemia o Aplastic or hypoplastic anemia o Acute , chronic (30 years after exposure) o Exposure to 100 ppm cause cytopenia