Lecture 16 Alcohol and Cancer Bottom Line Alcohol consumption is associated with increased risk of some but not all cancers most notable cancers of the oral cavity and pharynx esophagus larynx breast and liver Alcohol has many potential pathways to lead to cancer Alcohol itself is not a mutagen but associated acetaldehyde may be Moderate alcohol consumption 2 drinks day is associated with a 25 decreased risk of heart disease If you have to drink keep it to 2 for men and 1 for women Mechanism of Action Repeated exposure to alcohol cause tissue damage and cell death in areas of the body with direct alcohol contact In response surviving cells grow and replace destroyed cells Thus the ability to trigger cell proliferation is one mechanism by which alcohol causes cancer Induces cytochrome to activate carcinogens carcinogen binds to DNA alter expression of oncogenes and tumor suppressor genes Relative Risks of Alcohol Consumption and Site Specific Cancers Oral cavity and pharynx 2 drinks per day 1 8 risk 4 drinks per day 2 9 risk and 8 per day 6 Oesophagus 2 drinks per day 1 5 4 drinks per day 2 2 8 per day 4 2 Larnyx 2d drinkers per day 1 2 4 drinks per day 1 4 8 per day 1 9 Liver cancer 2 drinks per day 1 2 4 drinks 1 4 and 8 drinks 1 9 Alcohol and Tobacco act Synergistically Possible expectation additive effect so an individual that is a heavy smoker and heavy drinker would have a cancer risk of 13 fold over a nondrinker smoker Why Tobacco contains potent carcinogens Alcohol stimulates cell division The result of using both Rapid proliferation of genetically damaged cells Men 2X likely than women Leukoplakia white lesions and erythroplakia red lesions Lump thickening in oral soft tissues soreness feeling something caught in throat difficult chewing or swallowing ear pain difficulty moving the jaw or tongue hoarseness numbness of the tongue or other areas of the mouth or swelling of the jaw Detection Diagnosis Visual exam palpation endoscopy MRI CT endoscopy bleeding Treatment Surgery radiation chemo Rehibilitation and plastic surgery Incidence of these cancers are increasing especially in developed countries HPV is suspected culprit Liver Cancer Overall 10 15 5 year survival rate One of the top 10 deadliest cancers in US Screening increased survival rates Main Types Hepatocellular Carcinoma HCC the most frequent liver cancer Variant type patient has both HCC and cholangiocarcinoma Rare Forms of Liver Cancer in depth Mesenchylmal Tissue Sarcoma Hepatoblastoma Primarily developing in children Cholangiocarcinoma Bile duct cancers of the small tubes that carry bile to the intestines Angiosarcoma and Hemangiosarcoma Start in the blood vessels of the liver Grow quickly Often by the time they are found they are too widespread to be removed Most patients do not live more than a year after diagnosis Lymphoma of the liver A rare form of lymphoma that usually have diffuse infiltration to liver It may also form a liver mass in rare occasions Liver Cancer Symptoms Itching Swelling or fluid build up in the abdomen Enlarged veins on the belly that become visible through the skin Worsening of your condition if have chronic hepatitis or cirrhosis An enlarged spleen felt as a mass under the ribs on the left side Mostly asymptomatic until later stages silent killer Fever Weight loss without trying Loss of appetite Nausea or vomiting An enlarged liver felt as a mass under the ribs on the right side Yellowing of the skin and eyes jaundice Pain in the abdomen or near the right shoulder blade Feeling very full after a small meal Hepatitis B Virus and Liver Cancer Chronic HBV infections linked to 80 of world wide liver cancer Infection during infancy results in 90 chance of becoming chronic Chronic HBV infections on the rise in US I Million people Many infected people unaware and can infect others Increase in incidence of liver cancer Interactions Between Alcohol Cirrhosis of Liver Hepatitis B and C and Oral Cancers Alcohol leads to build up acetaldehyde in liver and other parts of the body Acetaldehyde damages liver cells cirrhosis Acetaldehyde is a mutagen cancer HBV and HCV liver cirrhosis HBV and HCV chronic causes changes in DNA cancer Cirrhosis creates hypoproliferation of cells in tissue repair cancer Build up of acetaldehyde in liver leads to build up of ace in mucosa of oral cavities cancer Diagnosis Medical history and physical exam Angiography inserting a flexible catheter into a large vein and injecting a dye Imaging X ray CT MRI enhance vasculature during imaging uncomfortable Laparoscopy inserting flexible camera tube into abdomen bleeding Biopsy bleeding and spread of tumor Staging Liver Cancer TNM T size of tumor N extent to which nearby lymph nodes involved M description of distant metastasis TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 A single tumor any size that hasn t grown in blood vessels T2 Either a single tumor any size that has grown into blood vessel OR more than one tumor where no tumor is larger than 5cm about 2 inches across T3a More than one tumor with at least one tumor larger than 5 cm across T3b At least one tumor any size that has grown into a major branch of large vein of the liver the portal or hepatic vein T4 The tumor any size has grown into a nearby organ other than the gallbladder OR the tumor is growing into the thin layer of tissue covering the liver called the visceral peritoneum NX Cannot be assessed N0 No spreads to nodes N1 Spread to nodes M0 No mets M1 Mets belly lungs bones Staging Once individual T N and M scores have been determined they are combined to generate an overall cancer stage Stage 1 T1 N0 M0 There is a single tumor any size that has not grown into any blood vessels The cancer has not spread to nearby lymph nodes or distant sites Stage 2 T2 N0 M0 Either there is a single any size that has grown into blood vessels OR there are several tumors and all are 5cm 2 inches or less across The cancer has not spread to nearby lymph nodes ore distant sites Stage 3a T3a N0 M0 There is more than one tumor and at least one is larger than 5cm 2 inches across The cancer has not spread to nearby lymph nodes or distant sites Stage 3b T3b N0 M0 At least one tumor is growing into a branch of a major vein of the liver portal vein or hepatic vein The cancer has not spread to nearby lymph nodes or distant sites Stage 3c T4 N0 M0 A tumor is growing into a nearby organ other than the gallbladder OR a tumor has grown into the outer covering of
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