Hepatocellular n.d). Liver cancer is the fifth

 

 

 

 

 

 

 

Hepatocellular
Carcinoma

Andy
Friedt

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Colorado
Christian University

 

Hepatocellular
Carcinoma

             The human body is an
impressive creation and is capable of some extraordinary things; when it is
healthy. Some significant parts of the body are the organs. Organs like: The
brain, heart, kidneys, liver and lungs hold specialized job descriptions. Their
roles function independently but also, work together in a partnership for one
main goal, to keep the body functioning. The liver is an extremely important organ
and it is imperative to keep it healthy in order to prevent damage to the
liver.

The
location of the liver is in the upper-right quadrant of the abdominal area. The
majority of the liver is protected by a portion of the rib cage. It is a dark,
reddish-brown organ that has multiple functions. The main functions of the
liver are to control chemical levels in the blood stream as well as excrete
bile to assist in carrying waste away (University of Rochester, n.d.). It acts as
a storage unit by packing away nutrients from metabolized carbohydrates,
proteins, amino acids, and lipids. The liver also serves as a metabolizer of alcohol
and some medications (University of Rochester, n.d). Liver cancer is the fifth
most common cancer worldwide and if damage to the liver occurs, it will begin
to fail, causing catastrophic diseases like hepatitis and cirrhosis, both of which can lead to liver cancer.

Every year, nearly
700,000 people are diagnosed with liver cancer across the world and males are
up to five times more likely than females to develop the disease (CDC, 2017).
In the United States about 40,710 new cases (29,200 in men and 11,510 in women)
will be diagnosed; of that, 28,920 men and women will die from liver cancers (American
Cancer Society, 2017). That is an disturbing fatality rate of 72%. Among men
and women, the Hispanic population is affected at the highest rates of being
diagnosed with liver cancer (CDC, 2017).

There
are several types of liver cancers but 75% of all
liver cancers are diagnosed as hepatocellular carcinoma (HCC)
(Lippincott, 2016). HCC is a primary malignancy which
arises within the liver. HCC begins at the cellular level; the mutation
starts with the hepatocyte, the liver cells (CDC, 2017).  The cause of HCC is unknown but factors that
increase the risk of primary liver cancer include but are not limited to:
Hepatitis B and C virus infections, cirrhosis, inherited liver diseases,
diabetes, and nonalcoholic fatty liver disease (Medline Plus, 2017). Some signs
and symptoms that display there is trouble with the liver are:  Abdominal pain or tenderness in the
upper-right quadrant, easy bruising or bleeding, ascites, jaundice and
unexplained weight loss (Mayo Clinic, 2017). Since there are so many potential
causes of HCC, it is vital to understand the genetic abnormalities that are associated
with this terrible cancer. 

The
primary affected gene in HCC is the TP53 gene. According to The National
Institute of Health (2015), “the TP53 gene
delivers instructions for making the protein P53 which acts as a tumor
suppressor that regulates cell division.” When this gene becomes damaged with chronic infections like hepatitis B and
C and cirrhosis, this gene begins to produce reactive
oxygen and nitrogen. The process initiates damage to DNA, mutating
cancer-related genes such as TP53 (Hussain et al, 2007). When
looking closer at the genetic mutation of HCC, it is vital to evaluate the
oncogenes that are affected in HCC individuals.

Oncogene
mutations that have been linked with HCC individuals are:  N-RAS, C-FOS and C-MYC. N-RAS is an oncogene that is similar to an on and off
switch that regulates the rate of cell growth and division. When N-RAS works
correctly, it will turn on the cell to activate and attach to a molecule. When
it turns off, the cell will become inactivated and stop transmitting signals to
the nucleus. When N-RAS becomes mutated the regulation process becomes
inoperative. Meaning, the on and off switch is stuck on and cancerous cells will
continue to grow uncontrollably (NIH, 2014). “C-FOS is another oncogene
that creates an overexpression which in turn begins
to increase the proliferation of hepatocytes by stabilizing nuclear Cyclin D1,”
(Zender, 2006).

C-MYC is the third oncogene that is associated with many
types of malignant tumors but specifically, it has a critical responsibility in
the cell’s life span. When there is a mutation with C-MYC there will be a malfunction
and the birth and death of a cell will be off balance; consequentially, apoptosis
stage will be inhibited. If apoptosis becomes obsolete, normal cell death will
not occur and malignant cell growth builds into cancerous tumors (NIH, 2014). Methylation
is a natural adjustment of DNA, and it affects the connection between the two
DNA base pair of cytosine (C) and guanosine (G). C-MYC develops a mutation which
is considered to be hypomethylation and therefore, C-MYC will decrease the
natural connection causing a loss of imprinting core sequence from DNA to RNA,
resulting in an interference with the development of microRNA (Zender, 2006).

MicroRNA’s (miRNAs) play an intricate role
monitoring gene expression. In HCC miRNAs have a specific connection to
miR-222, miR-106a, miR-92, miR-17–5p, miR-20, and miR-18 which might
contribute to HCC tumor development (Braconi et al., 2011). MiR-122 is one of the most abundant miRNAs that is present
in the liver. According to Braconi et al (2011), “miR-122 is present in normal hepatocytes but demonstrations a
decrease in up to 70% of human HCCs.” With the knowledge of genetic mutations
of HCC, it is important to evaluate how this cancer is diagnosed and treated.

Early identification of HCC with aggressive
intervention provides an improved survival for individuals. HCC is diagnosed
using several procedures which include: 
Laboratory testing, imaging and diagnostic procedures. Blood tests that
need to be measured are liver function and complete blood count. Also, a HCC
DNA test may be performed to assess genetic alterations from primary cancers
such as HCC. Imaging procedures will include computed tomography, medical
resonance imaging and ultrasound (Mayo Clinic, 2017). Lastly, a diagnostic
procedure that potentially will be performed is a liver biopsy, in order to remove a sample of liver tissue to send off to
the laboratory for further testing. Once all diagnostic procedures are
completed and HCC is confirmed, treatment options will be discussed with the
individual.

Treatment of HCC will depend on the size as well as the location/involvement
of the cancerous tumor on the liver. The individual’s overall liver function
and health will also be taken into consideration. Treatment options for HCC will
begin with surgery to remove the cancer or liver transplant surgery may need to be an option.
The majority of the liver can actually be removed because it can regrow itself. But, unfortunately, most liver cancers
spread quickly and will consume too much of an individual’s liver. Another
option is radiation therapy with or without
chemotherapy or radiofrequency ablation or cryotherapy. Radiofrequency ablation
or cryotherapy is a procedure that uses extreme heat or cold which is a great
option for individuals that cannot
undergo surgery (Lippincott, 2016).  Adult stem cell transplant may be a new
emerging option for treatment of HCC. A group of surgeons from Germany have
begun trials of injecting blood stem cells into an individual’s liver to grow
more liver cells. This in turn will leave enough of the liver behind after surgery
(Stanford at the Tech, 2008). Lastly, because HCC can cause weight
loss, abdominal pain, appetite loss and nausea, it is vital to evaluate the
diet of the individual. A high-calorie, low-protein diet is most appropriate
because proteins may not be correctly processed
(Lippincott, 2016).

With
the rapid rise in incidence of HCC and little advancement in research, the
prognosis of HCC is unfortunately poor. According to Schlachterman et al (2015)
“Sorafenib was the first approved systemic therapy by
the FDA to demonstrate improved survival in patients with advanced-stage HCC.” Sorafenib is a multi-kinase inhibitor which occludes
cell growth. TACE is another
treatment option for individuals. The main goal of TACE is to increase the
exposure of tumor cells to cytotoxic agents, which then tamponades blood
supply to the lobe of the liver that is being affected by HCC (Schlachterman et al, 2015). It has been studied that treatment
of HCC is shifting from
chemotherapy to a more targeted approach. Also, studies are focusing on
alternative molecular pathways that are associated with biomarkers. “Epigenetic
modifications have also been suggested to drive progression to HCC and include
DNA methyltransferases and miRNAs,” (Eatrides
et al, 2017).

“Or do you not know that
your body is a temple of the Holy Spirit within you, whom you have from God?
You are not your own, for you were bought with a price. So, glorify God in your
body,” 1 Corinthians 6:19-20 ESV
(Bible Gateway, n.d). We must treat our bodies as though they are the structure
of God’s word. We must care for our bodies as though it is invaluable;
maintaining physical, emotional and spiritual well-being. There are steps to
achieving strength within our physical bodies to support our inner spirits such
as:  Eating a clean, healthy diet,
physical activity, stress reduction and keeping our bodies pure and free of
toxins such as tobacco and alcohol. “God make me a hollow vessel and breathe
something through me that would turn people’s eyes to you” – Toby Mac