Liver Cancer: Anatomy & Physiology

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LIVER CANCER

Liver cancer, also known as hepatic cancer, is a type of cancer that


originates in the liver. It occurs when abnormal cells in the liver grow and
divide uncontrollably, forming a tumor. There are two main types of liver
cancer: hepatocellular carcinoma (HCC) and intrahepatic
cholangiocarcinoma (ICC).
Hepatocellular carcinoma (HCC) is the most common type of liver
cancer, accounting for about 75% of cases. It develops in the main type
of liver cell, called the hepatocyte. Intrahepatic cholangiocarcinoma
(ICC) is a less common type of liver cancer that begins in the bile ducts
that are located within the liver.
There are several types of liver cancer, including:
1. Hepatocellular carcinoma (HCC): This is the most common type of
liver cancer, accounting for about 75% of all cases. It begins in the
main type of liver cells (hepatocytes) and can spread to other parts
of the liver or to other organs.
2. Intrahepatic cholangiocarcinoma (ICC): This cancer begins in the
cells that line the bile ducts inside the liver. It can also spread to
other parts of the liver or to other organs.
3. Hepatoblastoma: This is a rare type of liver cancer that usually
occurs in children under the age of 5. It begins in immature liver
cells and can spread to other parts of the liver or to other organs.
4. Angiosarcoma: This is a rare type of liver cancer that begins in the
cells that line the blood vessels of the liver. It can grow quickly and
spread to other parts of the body.

ANATOMY & PHYSIOLOGY


The liver is a large, wedge-shaped organ located in the upper right side
of the abdomen, just below the diaphragm. It is the largest internal organ
in the body and is responsible for a variety of functions, including
detoxification, metabolism, and storage of nutrients.
The liver is composed of two main lobes, the right and left lobes, along
with caudate and quadrate lobes, which are separated by the falciform
ligament. Within each lobe, the liver is further divided into smaller lobes,
known as lobules.
The liver receives blood from two sources, the hepatic artery and the
portal vein. The hepatic artery delivers oxygenated blood from the heart
to the liver, while the portal vein carries nutrient-rich blood from the
intestines to the liver for processing.
Liver cancer can develop in any part of the liver, but it most commonly
arises in the hepatocytes.

PHYSIOLOGY
The liver is responsible for a variety of important physiological
processes, including detoxification, metabolism, and the synthesis of
proteins and bile. When liver cancer develops, these processes can be
impaired or disrupted, leading to a range of symptoms.
One of the most important physiological changes associated with liver
cancer is impaired liver function. The liver is responsible for detoxifying
the body, removing harmful toxins and waste products from the
bloodstream. In liver cancer, the cancerous cells can interfere with this
process, reducing the liver's ability to detoxify the body effectively. This
can lead to a range of symptoms, including jaundice (yellowing of the
skin and eyes), fatigue, weakness, and weight loss.
Liver cancer can also interfere with the liver's ability to produce and
secrete bile. Bile is a substance that helps digest fats and absorb fat-
soluble vitamins. When the liver is unable to produce enough bile, this
can lead to problems with digestion and malabsorption of nutrients.
Finally, liver cancer can interfere with the liver's ability to synthesize
proteins. The liver produces a number of important proteins, including
albumin, which helps maintain fluid balance in the body, and clotting
factors, which are important for blood coagulation. When liver function is
impaired, the production of these proteins can be reduced, leading to a
range of complications, including edema (swelling due to fluid
accumulation) and bleeding disorders.

EPIDEMOLOGY
Liver cancer is more common in men than women,
More prevalent in individuals over the age of 50.
In addition, certain racial and ethnic groups have a higher incidence of
liver cancer, including Asian Americans and Pacific Islanders, African
Americans, and Hispanics.

RISK FACTORS
The Etiology, or causes, of liver cancer (hepatocellular carcinoma or
HCC) are complex and multifactorial. There are several factors that can
contribute to the development of liver cancer, including:
1. Chronic viral hepatitis: Hepatitis B virus (HBV) and hepatitis C
virus (HCV) are known to cause chronic inflammation of the liver,
which can lead to liver cancer over time.
2. Alcohol consumption: Heavy alcohol consumption over a long
period of time can also cause chronic inflammation of the liver and
increase the risk of liver cancer.
3. Non-alcoholic fatty liver disease (NAFLD): This condition is
characterized by the accumulation of fat in the liver, which can
lead to inflammation and scarring of the liver. NAFLD is associated
with an increased risk of liver cancer, particularly in individuals with
other risk factors such as obesity and diabetes.
4. Exposure to environmental toxins: Exposure to certain
environmental toxins, such as aflatoxin, a type of mold that can
grow on peanuts and corn, can increase the risk of liver cancer.
5. Inherited liver diseases: Certain inherited liver diseases, such as
hemochromatosis and Wilson's disease, can increase the risk of
liver cancer.
6. Metabolic disorders: Metabolic disorders, such as diabetes and
obesity, are also associated with an increased risk of liver cancer.
7. Smoking: Smoking has been shown to increase the risk of liver
cancer, particularly in individuals with other risk factors such as
viral hepatitis

PRECANCEROUS FACTORS
There are several precancerous factors that can increase the risk of
developing liver cancer (hepatocellular carcinoma or HCC). These
factors include:
1. Cirrhosis: Cirrhosis is a condition in which the liver becomes
scarred and hardened due to chronic damage, such as from viral
hepatitis or alcohol abuse. Cirrhosis is the most common precursor
to liver cancer, and individuals with cirrhosis are at a higher risk of
developing HCC.
2. Hepatitis B and C: Chronic infection with hepatitis B virus (HBV) or
hepatitis C virus (HCV) can cause chronic inflammation of the liver,
which can lead to the development of cirrhosis and an increased
risk of liver cancer.
3. Non-alcoholic fatty liver disease (NAFLD): NAFLD is a condition in
which fat accumulates in the liver, leading to inflammation and
scarring of the liver. NAFLD can progress to cirrhosis and increase
the risk of liver cancer.
4. Hemochromatosis: Hemochromatosis is a genetic condition that
causes the body to absorb too much iron from the diet. This can
lead to cirrhosis and an increased risk of liver cancer.
5. Wilson's disease: Wilson's disease is a genetic condition that
causes copper to accumulate in the liver and other organs. This
can lead to cirrhosis and an increased risk of liver cancer.
6. Alpha-1 antitrypsin deficiency: Alpha-1 antitrypsin deficiency is a
genetic condition that can cause liver damage and cirrhosis, which
can increase the risk of liver cancer.
7. Obesity and diabetes: These conditions are associated with an
increased risk of non-alcoholic fatty liver disease, which can lead
to cirrhosis and an increased risk of liver cancer

CLINICAL FEATURES
The clinical features of liver cancer (hepatocellular carcinoma or HCC)
can vary depending on the stage and location of the cancer, as well as
the individual's overall health. Some common clinical features of liver
cancer may include:
Specific symptoms General symptoms:
 Abdominal pain or discomfort  Fatigue or weakness
 Jaundice  Fever or chills
 Unexplained weight loss  Night sweats
 Loss of appetite  Body aches or joint pain
 Nausea or vomiting  Unexplained bruising or
 Swelling in the abdomen or bleeding
legs  Pale or clay-colored stools
 Itchy skin  Dark urine
 Enlarged liver or spleen

1. Abdominal pain: Individuals with liver cancer may experience pain


or discomfort in the upper abdomen, particularly on the right side.
2. Jaundice: Jaundice is a yellowing of the skin and eyes that occurs
when the liver is unable to process bilirubin properly. In individuals
with liver cancer, jaundice may occur due to the cancer blocking
the bile ducts.
3. Fatigue: Fatigue or weakness is a common symptom of liver
cancer, particularly in the later stages of the disease.
4. Loss of appetite and weight loss: Individuals with liver cancer may
experience a loss of appetite and unintentional weight loss due to
the cancer's impact on the body's metabolism.
5. Nausea and vomiting: Nausea and vomiting may occur in
individuals with liver cancer, particularly if the cancer has spread to
other parts of the body.
6. Enlarged liver: In some cases, liver cancer can cause the liver to
become enlarged, which may be felt as a mass in the upper right
abdomen.
7. Ascites: Ascites is a buildup of fluid in the abdomen that can occur
in individuals with advanced liver cancer.
It's important to note that many of these clinical features can also be
caused by other conditions, so a proper diagnosis is essential.
DIAGNOSIS
The diagnosis of liver cancer (hepatocellular carcinoma or HCC) typically
involves several steps, including:
1. Physical exam: A physical exam may be performed to check for
signs of liver cancer, such as an enlarged liver or an abdominal
mass.
2. Blood tests: Blood tests may be used to measure levels of liver
enzymes and to check for markers of viral hepatitis, such as
hepatitis B surface antigen (HBsAg) and hepatitis C antibodies.
3. Imaging tests: Imaging tests, such as ultrasound, CT scan, or MRI,
may be used to look for signs of liver cancer, such as a mass or
tumor in the liver.
4. Biopsy: A biopsy may be performed to confirm the diagnosis of
liver cancer. During a biopsy, a small sample of liver tissue is
removed and examined under a microscope to look for cancer
cells.
5. Staging: If liver cancer is diagnosed, further tests may be done to
determine the extent, or stage, of the cancer. This may involve
additional imaging tests, such as a PET scan, and may also
involve a blood test to measure levels of alpha-fetoprotein (AFP),
which is a marker of liver cancer.

THE BCLC STAGING SYSTEM


The staging of liver cancer (hepatocellular carcinoma or HCC) is based
on the size of the tumor, whether it has spread to nearby lymph nodes or
other organs, and whether there are any signs of distant metastasis. The
most commonly used staging system for liver cancer is the Barcelona
Clinic Liver Cancer (BCLC) system, which takes into account the
individual's overall health status as well as the tumor characteristics. The
BCLC staging system includes the following stages:
Stage 0 (Very Early): There is a single tumor less than 2 cm in size,
with no evidence of vascular invasion or distant metastasis.
Stage A (Early): The tumor is either a single tumor that is larger than 2
cm or multiple tumors, all less than 3 cm in size. There is no evidence of
vascular invasion or distant metastasis.
Stage B (Intermediate): The tumor is either a single tumor larger than 5
cm or multiple tumors larger than 3 cm. There is no evidence of vascular
invasion or distant metastasis.
Stage C (Advanced): The tumor has either invaded blood vessels,
spread to nearby lymph nodes, or both.
Stage D (End-stage): The cancer has spread to other organs or parts of
the body, such as the lungs or bones.
In addition to the BCLC system, other staging systems may also be used
for liver cancer, including the TNM staging system and the Child-Pugh
score. The specific staging system used may depend on the individual's
specific situation and the healthcare professional's preference. Staging
is an important part of determining the appropriate treatment plan for
individuals with liver cancer.

TNM STAGING IN LIVER CANCER


The TNM staging system is used to describe the extent, or stage, of liver
cancer (hepatocellular carcinoma or HCC). The TNM system takes into
account the size of the tumor (T), whether the cancer has spread to
nearby lymph nodes (N), and whether the cancer has metastasized, or
spread, to other parts of the body (M).
Based on the T, N, and M stages, liver cancer is classified into different
stages, ranging from stage I (early stage) to stage IV (advanced stage).
The stage of liver cancer is an important factor in determining the
appropriate treatment approach and predicting the prognosis (outlook)
for the individual with liver cancer.

TREATMENT
The treatment options for liver cancer (hepatocellular carcinoma or HCC)
depend on the stage of the cancer, the size and location of the tumor(s),
the overall health of the individual, and other factors. Treatment options
may include:
1. Surgery: Surgery to remove the tumor(s) is typically the first-line
treatment option for early-stage liver cancer. The type of surgery
used depends on the size and location of the tumor(s). In some
cases, a liver transplant may be recommended.
2. Ablation therapy: Ablation therapy involves using heat or cold to
destroy the cancerous cells. This may be done through techniques
such as radiofrequency ablation (RFA), microwave ablation, or
cryoablation.
3. Radiation therapy: Radiation therapy involves using high-energy
beams of radiation to destroy the cancer cells. This may be done
using external beam radiation therapy or brachytherapy (internal
radiation therapy).
4. Transarterial chemoembolization (TACE): TACE involves
delivering chemotherapy drugs directly to the tumor(s) through the
blood vessels that supply the liver. This may be combined with
blocking the blood vessels to the tumor(s) to cut off their blood
supply.
5. Systemic chemotherapy: Chemotherapy drugs may be given
intravenously (IV) or by mouth to kill cancer cells throughout the
body. This may be used in cases where the cancer has spread
beyond the liver.
6. Immunotherapy: Immunotherapy drugs may be used to stimulate
the immune system to attack the cancer cells.
7. Palliative care: Palliative care is focused on managing the
symptoms and improving the quality of life for individuals with
advanced liver cancer.

FOLLOW UP & PROGNOSIS


The follow-up and prognosis of liver cancer (hepatocellular carcinoma or
HCC) depend on several factors, including the stage of the cancer, the
individual's overall health, the effectiveness of the treatment, and
whether the cancer has spread to other parts of the body.
After treatment, individuals with liver cancer will typically require regular
follow-up appointments with their healthcare team to monitor their
condition and detect any signs of recurrence. Follow-up may include
physical exams, blood tests, imaging studies such as CT scans or MRIs,
and other tests as needed.
For individuals with early-stage liver cancer who undergo successful
treatment, the five-year survival rate is around 70%.
It's important to note that liver cancer can recur even after successful
treatment, so ongoing monitoring and follow-up are essential.
Additionally, individuals with liver cancer are at increased risk of
developing other liver problems, such as cirrhosis, even after successful
treatment.
Maintaining a healthy lifestyle, avoiding alcohol and other liver-damaging
substances, and following a recommended treatment plan can help
improve the long-term outlook for individuals with liver cancer.

REHABILITIATION
Rehabilitation in liver cancer (hepatocellular carcinoma or HCC) aims to
improve the physical, psychological, and social well-being of individuals
with the condition. The type of rehabilitation needed will depend on the
individual's specific situation and the treatment they have received.
Some common rehabilitation strategies for liver cancer may include:
1. Physical therapy: Physical therapy can help individuals with liver
cancer rebuild strength, flexibility, and endurance. It may involve
exercises to improve mobility, balance, and coordination, as well
as activities to reduce pain and improve overall physical function.
2. Nutritional counseling: Proper nutrition is important for individuals
with liver cancer, especially if they have undergone treatment that
affects their ability to digest and absorb nutrients. Nutritional
counseling can help individuals develop healthy eating habits and
ensure that they are getting the nutrients they need to support their
recovery.
3. Emotional support: A diagnosis of liver cancer can be emotionally
challenging, and individuals with the condition may experience
anxiety, depression, and other psychological symptoms.
Counseling or support groups can provide emotional support and
help individuals develop coping strategies.
4. Occupational therapy: Occupational therapy can help individuals
with liver cancer learn new skills and strategies to help them
manage their condition and maintain their independence. This may
include adapting their home environment, learning new work or
daily living skills, and using assistive devices as needed.
5. Complementary therapies: Complementary therapies such as
acupuncture, massage, and meditation may help individuals with
liver cancer manage pain, reduce stress, and improve overall well-
being.
Rehabilitation should be tailored to the individual's specific needs and
may be ongoing throughout their recovery process. A healthcare team
including doctors, nurses, physical therapists, and other healthcare
professionals can work together to develop a comprehensive
rehabilitation plan for individuals with liver cancer.

The Functions of the Liver and Signs You Need to Detox | PatriotDirect
Family Medicine | Natick, MA (patriotdirectfm.com)
Defining new targets in liver cancer (astrazeneca.com)

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