Oxford Handbook of Occupational Health (2 edn)
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Hepatic angiosarcoma
Epidemiology
This otherwise very rare hepatic cancer occurs among workers exposed to VCM and, less frequently, pesticide-exposed agricultural workers. Reactor (autoclave) cleaners may be highly exposed to VCM, a genotoxic carcinogen. When this association was first recognized, VCM production workers showed 400× expected incidence of hepatic angiosarcoma. However, owing to improved exposure control, the disease is now very rare in developed countries.
Clinical features
Fatigue
Abdominal pain
Weight loss
Pyrexia
Jaundice
Ascites
Hepatosplenomegaly
Oesophageal varices.
Causal exposure/industries
Vinyl chloride monomer production in the plastics industry
Arsenic-containing pesticides used in vineyards.
Clinical assessment/diagnosis
Thrombocytopenia, anaemia, on full blood count
Abnormal liver function tests
CT/MRI scan:
CT scan may show a multifocal tumour with hypo-attenuation; hyper-attenuation to liver suggests haemorrhage into the tumour
angiosarcoma is hypo-intense to normal liver on T1-weighted MRI images
Liver biopsy: histology variable within a tumour. Vascular spaces, lined with tumour cells, may or may not be obvious.
Prognosis
Untreated, death occurs within months from hepatic encephalopathy or intra-abdominal bleeding.
Health surveillance
Long latent interval between exposure and presentation
Liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST)) identify hepatic impairment in VCM exposed workers
Hepatic ultrasound has been used to identify pre-symptomatic angiosarcoma.
Medical management
Hepatic resection and/or chemotherapy may prolong life in those with an operable tumour.
Prevention
Prevent by limiting exposure to VCM.
Compensation
Angiosarcoma of the liver is a prescribed disease (C24) for Industrial Injuries Disablement Benefit in those exposed to VCM in the manufacture of PVC.
Relevant legislation
COSHH Schedule 5: monitor employee breathing zone VCM exposure
COSHH Schedule 6: annual health surveillance by HSE appointed doctor
EH 40/2005 VCM, WEL 3ppm (8h TWA)
RIDDOR Regulations 1995: Angiosarcoma of the liver is a reportable disease among those exposed to VCM.
Hepatic cirrhosis
Epidemiology
Common causes of liver cirrhosis worldwide include HBV, HCV, and alcohol. Most cases of cirrhosis due to these agents are not work-related, but a small proportion may be due to occupational exposure. Other rare causes of cirrhosis include work with halogenated hydrocarbons.
Clinical features
Fatigue
Anorexia
Nausea
Spider naevi
Jaundice
Pruritus
Ascites
Bleeding/bruising
Finger clubbing
Portal hypertension
Oesophageal varices
Hepatocellular cancer
Hepatic encephalopathy.
Causal exposures/industries
Hepatitis B:
HCWs
Hepatitis C:
HCWs
Alcohol:
transport industry
publicans and bar staff
Organic solvents:
carbon tetrachloride
1,1,1-trichloroethane.
Clinical assessment/diagnosis
LFTs
Full blood count and clotting studies
Hepatitis B surface antigen
Hepatitis C antibody
Hepatic ultrasound
Liver biopsy.
Prognosis
Depends on the disease stage; once complications such as hepatic encephalopathy supervene, the prognosis is generally poor. A small proportion will develop primary carcinoma of the liver as a complication of cirrhosis.
Health surveillance
Biological monitoring of solvent-exposed workers using urinary metabolites or exhaled breath sampling may be indicated dependent on the risk assessment
HCWs and others at risk of hepatitis B should be immunized and their immune status confirmed by measuring hepatitis B surface antibody levels.
Medical management
Abstinence from alcohol in alcoholic cirrhosis
Liver transplant:
employment rates pre-operatively are lower for alcoholic liver disease than other indications for liver transplant. However, return to work rates post-transplant are similar
45–70% of transplant recipients will return to work
poor physical functioning and fatigue influence employment status post-transplant
some centres employ living donor hepatic lobe transplants. Limited evidence suggests donors have a mean work absence of about 3mths.
Prevention
Preventing exposure to human blood and body fluids—see 
p.
104, Human tissue and body fluids.
Compensation
Liver fibrosis is a prescribed disease for Industrial Injuries Disablement Benefit in those who have been exposed to VCM in the manufacture of PVC (C24d). Cirrhosis is prescribed in those who have been exposed to chlorinated naphthalenes (C13).
Acute hepatotoxicity
A number of chemicals are recognized as causing acute hepatotoxicity, although some of them are no longer used in the way that once led to workers suffering adverse effects. Hepatotoxicity due to occupational chemical exposure is now rarely reported in the UK.
Epidemiology
Common causes of hepatic insult
Alcohol
Metabolic syndrome
Drug reactions.
Clinical features
Fatigue
Weight loss
Right upper quadrant abdominal pain
Anorexia
Nausea
Jaundice
Impaired clotting.
Mild steatosis may be asymptomatic
Causal exposures/industries
Chemical industry including:
carbon tetrachloride (CCl4)
chlorinated napthalenes
dimethylformamide
chlordecone (kepone)
methylene dianiline
polychlorinated biphenyls
phosphorus
trinitrotoluene
Painting:
2-nitropropane
Dry cleaning:
perchloroethylene.
Mechanism of hepatotoxicity
Acute chemical hepatotoxicity may manifest itself in a number of ways:
Steatosis (fatty liver):
steatohepatitis if hepatic inflammation present
Acute hepatocellular injury (necrosis):
direct toxicity
idiosyncratic reaction (e.g. halothane)
Cholestasis (impaired bile flow).
Clinical assessment and diagnosis
Clinical examination looking for stigmata of chronic liver disease or alcohol misuse
Liver enzymes:
alkaline phosphatase (AlkPhos)
alanine aminotransferase (ALT)
gamma glutamyl transpeptidase (GGT)
Bilirubin
Carbohydrate deficient transferrin (CDT): in suspected alcohol misuse
Albumin
Full blood count
Clotting screen—prothrombin time
Hepatitis B surface antigen and core antibody
Hepatitis C antibodies
Liver ultrasound +/– biopsy: findings are dependent on the nature of the hepatic insult.
Prognosis
Dependent on the degree of hepatic injury but some cases will progress to cirrhosis.
Health surveillance
Biological monitoring may be indicated for some agents (e.g. solvents).
Medical management
Withdraw from exposure to hepatotoxin
Lifestyle changes:
abstinence from alcohol
weight loss if obese
Review workplace risk assessment—further controls may be required.
Compensation
Liver toxicity is prescribed for Industrial Injuries Disablement Benefit in those who are exposed to carbon tetrachloride (C26(a)) or trichloromethane (C27).
Relevant legislation
Hepatotoxicity is reportable under RIDDOR where it is due to poisoning by any of the chemicals listed in Schedule 3, part 1.
Gastrointestinal cancers
Epidemiology
Gastric cancer is the fourth most common cancer.
Adenocarcinoma is the most common gastric cancer
Gastric cancer is much more common in Asia (Japan and China) than in Europe
The annual incidence of gastric cancer is falling and is presently estimated at 870 000 cases/year worldwide
Men are at twice the risk of gastric cancer as women
Occupational exposures have been linked to an increased risk of gastric cancer
Most studies of pancreatic cancer have not found a link to occupation.
Clinical features
Gastric cancer
Weight loss
Abdominal pain
Dyspepsia
Dsyphagia
Anorexia.
Causal exposures
Nitrosamines (gastric cancer)
Phenoxy herbicides
Industries at risk
Industries at high risk:
tin mining
steel works
carpentry
Industries at increased risk:
chemical industry
coal mining
coke works
rubber industry
oil refining.
Clinical assessment and diagnosis
Investigation of gastric cancer includes endoscopy and biopsy. CT scan may be used to identify metastases.
Prognosis
The prognosis of gastric cancer is generally poor as many patients present with advanced disease. Among those with operable disease 5yr survival is about 45%.
Health surveillance
No health surveillance has yet been proven to be beneficial in occupational groups. Screening for gastric cancer in at-risk groups may be appropriate, but further evaluation is necessary.
Medical management and prevention
The treatment of gastric cancer is partial or total gastrectomy. Prevention relies on control of exposure to carcinogens.
Relevant legislation
COSHH Regulations 2002 (as amended).
Renal failure
Acute renal failure
Occupational exposures that can cause acute renal failure (ARF)
Clinical features of ARF
Oliguria or anuria
Nocturia
Ankle oedema
Fluid retention
Impaired appetite
Tremor
Fatigue
Hypertension.
Clinical assessment of renal failure
Urinalysis
Urea, electrolytes, and creatinine
Blood lipids
Full blood count
Renal ultrasound
IVP.
Health surveillance
Health surveillance for nephropathy is only likely to be undertaken in chronic exposure to cadmium. Cadmium workers should wear appropriate protective equipment and have regular biological monitoring of blood and urinary cadmium levels, with retinol binding protein (RBP) if levels are persistently elevated.
Compensation
Kidney toxicity is prescribed (C26(b)) for Industrial Injuries Disablement Benefit in those who are exposed to carbon tetrachloride.
Bladder cancer
Epidemiology
Bladder cancer is the seventh most common cancer in the UK
About 5–10% of bladder cancer in Europe may be due to occupational exposures
Smoking is the major risk factor and may account for up to 80% of cases. However, where smokers are exposed to carcinogens it is not possible to distinguish between occupational and non-occupational causes
Bladder cancer is most common in the elderly and rare under age 40. Therefore, bladder cancer occurring at a young age is a red flag for possible occupational aetiology.
Clinical features
Microscopic haematuria
Frank haematuria
Dysuria
Urinary frequency.
Causal exposures
Polycyclic aromatic hydrocarbons (PAHs)
Aromatic amines:
benzidine
-napthylamine
ortho-toluidine
auramine
magenta.
MbOCA
Arsenic.
Industries at risk
Historically, due to -napthylamine—withdrawn in 1949:
chemical industry (dyestuffs)
rubber industry
Currently:
coke works/coal gas works
printing
metal working
aluminium smelting (Soderberg process)
painting
truck drivers
leather industry
hairdressers.
Individual susceptibility
Family history of bladder cancer.
Clinical assessment and diagnosis
Physical examination including rectal examination
Urinalysis
Intravenous pyelogram (IVP)
Cystoscopy and tumour biopsy
Urine cytology
Disease staging: CT scan, CXR, bone scan.
Prognosis
Five-year survival is ~60% although this is influenced by the presence of multiple tumours, tumour bulk, and tumour stage.
Health surveillance
Workers should remain subject to follow-up after exposure ceases
Once diagnosed, patients with superficial bladder cancer are followed up with regular cystoscopy at 3–6-monthly intervals.
Medical management
Transurethral resection +/– chemotherapy, radiotherapy
Cystectomy for more extensive disease.
Prevention
Improved control of chemical exposures has d incidence of occupational bladder cancer
Most agents associated with bladder cancer are now banned in the UK (e.g. benzidine)
Substitution of carcinogenic agents with less hazardous agents.
Compensation
Primary neoplasm of the epithelial lining of the urinary tract is a prescribed disease (C23) for Industrial Injuries Disablement Benefit in those who are exposed to:
aromatic amines
MbOCA for ≥12mths
orthotoluidine, 4-chloro-2-methylaniline
Coal tar pitch volatiles produced in aluminium smelting involving the Soderberg process for ≥5yrs.
Relevant legislation
Bladder cancer is a reportable condition under RIDDOR 1995 where there has been work with any of the agents listed in Schedule 3.
