Liver Cancer.
PKGhatak, MD
Liver Cancer is a deadly disease. Cancers of the liver are of two main categories namely, Primary Liver cancer and Metastatic or Secondary liver cancer.
Primary Liver Cancer:
The liver is made up of about 15 thousand individual lobules. Each lobe is a structural and functional unit of the liver. Liver cells, Hepatocytes when turn cancerous called Hepatocellular cancer. The liver has a dual blood supply - portal and systemic circulatory systems and in addition, a bile duct network to drain the bile from the liver. The endothelial cells of the blood vessels and bile duct cells can turn cancerous. Cancers of different cell lines differ from each other in many aspects. In addition, the liver is richly supplied with immune cells and malignant tumors may develop from immune cells also.
A. Hepatocellular cancer.
Hepatocellular cancer is by far the most common cancer of the liver. The annual incidence of hepatocellular cancer in the USA is 35,000. Native Americans have the highest incidence among all the ethnic groups. Older Americans have more cancers than the younger age group. The incidence of hepatocellular cancer in East Asian countries is the highest in the world. A very rare form of cancer is occasionally seen in very your children in the hepatic stem E-MB and MEM-HB cells.
Risk factors.
Hepatitis B and hepatitis C are proven causes of liver cancer. A fungal toxin Aflatoxin is carcinogenic. Alcoholic liver cirrhosis and Non-alcoholic fatty liver disease (NASH) can turn cancerous. Cigarette smoking and alcohol are risk factors. Muscle-building androgenic steroids and oral contraceptive pills are also additional risk factors. Liver cysts and cysts associated with polycystic disease of the kidney are risk factors also. Very rarely, cancerous cysts in the associated use of anabolic steroids and birth control pills are seen
In addition, hereditary metabolic diseases like Hemochromatosis (iron), Wilson disease ( copper), alpha 1 antitrypsin deficiency ( enzyme), porphyria cutaneous tarda, and glycogen storage disease are known to cause Hepatocellular cancer.
Symptoms.
A small size liver cancer does not produce any symptoms. Patient with growing cancer develops loss of weight, loss of appetite, upper abdominal fullness and abdominal pain. At this stage, the diagnosis of liver cancer leads to a better outcome. But most patients come to the doctors when they develop jaundice and dark-colored urine at this stage the disease has progressed too far for a good outcome.
Diagnostic tests.
Alpha fetoprotein in serum is elevated, and Liver function tests show elevated ALT over AST and high bilirubin. Ultrasound is a very useful tool to detect tumors, CT scans and needle biopsies under ultrasound guidance give a definite diagnosis.
Treatment.
In most instances, a complete resolution of liver cancer is not possible because of the advanced stage of cancer at the time of diagnosis. In suitable cases local, or regional resection of the liver is possible. The liver is a remarkable organ in its capacity to grow back to full size if cancer free. In selected cases, a lobectomy or total hepatectomy followed by a liver transplant produces are done. Immunotherapy, chemotherapy and several ablative therapy methods are available.
Prognosis:
In general, this is most disheartening. 5-year survival is less than 20%, and in advanced cases, it is less than 3 %.
Carcinoma of Bile ducts.
The medical term for bile duct cancer is Cholangiocarcinoma (CLC). CLC is less common than hepatocellular carcinoma. However, people who have habits of eating raw fish have an alarmingly high rate of CCL.
The diagram above shows bile ducts inside the liver and also outside. The outside bile duct for this discussion is dealt with into two separate categories namely Hilar and Common bile duct cancers.
CLC (cholangiocarcinoma) is the second most common liver cancer in the world but the incidence in the USA is much less than hepatocellular carcinoma but over all CLC is increasing in all countries including the USA. In the USA, the Hispanic ethnic group has a higher CLC. In the world, Thailand has the highest rate of CCL about 40 in 100,000 people, followed by China, Japan and other East Asian countries, with a clear association with Liver fluke infestation of the biliary system. In the Mekong River basin countries Liver fluke infestation is in between 30 to 70 % of the population and the death rate from CCL is 3% of all deaths.
Risk factor.
Primary sclerosing cholangitis is a precancerous condition, a congenital bile duct disease called Choledochal cyst disease has a high rate of CLC. Ulcerative colitis and Crohn's disease have a higher incidence of CLC. Infestation of the liver fluke is a risk as mentioned above. Both liver cells and the bile duct system developed from the same progenitor cell in the embryonic stage of development. As a result, the non-specific risk factors mentioned under hepatocellular cancer (alcoholic liver cirrhosis, NASH, diabetes, etc.) are also risk factors for CLC.
A. Intrahepatic CLC.
Intrahepatic CLC is the least common among the three CLCs. Initially, CLC is not distinguishable from hepatocellular carcinoma, the diagnosis is made only after a liver biopsy. Patients remain asymptomatic in the early stage. Occasionally diagnosed by chance when ultrasound or abdominal CT scans are done for other reasons. The prognosis at this stage is very good with surgery and chemotherapy. However, the majority of patients seek medical attention because of the development of jaundice. Diagnosis is relatively easy by ultrasound and fine needle biopsy. A standard care protocol in the USA hospitals uses a multidisciplinary approach and provides partial or complete removal of liver and liver transplantations.
B. Hilar CLC.
Hilar CLC is the most common of CLC, accounting for about 70% of CLC. Pathologically these are adenocarcinomas. Because of their location jaundice develop earlier than other liver cancers. The patient seeks medical attention because of worsening jaundice, dark urine and light stool, loss of appetite and weight loss. Laboratory tests confirm obstructive jaundice. CEA and alpha-fetoprotein are positive. Diagnosis requires a fine needle biopsy. Curative surgery is not possible in the majority of cases. Initial therapy is draining bile by inserting a stent in the common bile duct draining into the duodenum done during an ERCP examination, however, transcutaneous bile duct stent can be done also.
C. Common bile duct CLC.
The risk factors are the same as the above group and an additional risk factor is an abnormal opening of the pancreatic ducts.
Abnormal Pancreatic Duct.
Anatomical variations of pancreatic ducts are common. Occasionally one or both pancreatic ducts may join the common bile duct, rather than opening into the ampulla. In this circumstance, chemical inflammation of the duct from pancreatic enzymes leads to fibrosis and stricture, and also carcinoma
Obstructive jaundice is the presenting symptom of common bile duct CLC. In clinical practice, obstructive jaundice is common. The causes of obstructive jaundice are as follows.
Among the benign causes, gallstone and bile duct inflammation are most common, followed by common bile duct stricture, and Mirizzi syndrome. Gallbladder cancer leads the malignant causes followed by cancer of the periampullary region. 12 % of cases are due to cholangiocarcinoma.
Diagnosis and treatment.
Initial diagnostic workup is no different from other types of CLC. Initial treatment is a stent placement during ERCP or can be placed transcutaneously. The definitive treatment is the Whipple procedure or a modified Whipple operation. The prognosis is encouraging with hepatic transplants and immune therapy.
[ See Chronic pancreatitis blog, dated April 9, 2022].
Childhood Liver Cancer, Hepatoblastoma, is seen in children less than 3 years of age. It is more common in premature and underweight newborns. The primary cause of it is unknown. Several inherited conditions are associated with hepatoblastoma. Resection of the liver when performed early produces the best outcome.
************************************************
