Prospective Comparison of Hepatic Malignancy Detection Techniques

This report presents a comprehensive analysis of various imaging techniques used in the detection of primary hepatic malignancy, specifically focusing on patients undergoing liver transplants. The study critically evaluates the diagnostic performance of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography (USG) in identifying hepatocellular carcinoma (HCC). The introduction highlights the prevalence and challenges of HCC, emphasizing the importance of early and accurate detection for effective patient management. A detailed literature review explores the principles, advantages, and limitations of each imaging modality, including CT's multi-phasic contrast imaging, PET's use of tracers, MRI's detailed imaging capabilities, and the accessibility of ultrasonography. The methodology section outlines the comparative analysis of these techniques, aiming to determine the most effective and efficient methods for HCC detection. The report also discusses the clinical presentation, diagnostic approaches, and staging examinations associated with HCC, providing a holistic view of the disease and its detection. Finally, the conclusion summarizes the findings, offering insights into the optimal imaging strategies for diagnosing HCC in the context of liver transplantation, and provides a basis for future research in the field. The report is a valuable resource for medical professionals and students alike, providing a detailed overview of the current landscape of HCC detection methods.

Running Head: DETECTION OF PRIMARY HEPATIC MALIGNANCY
Study Developing Detection of Primary Hepatic Malignancy in Liver Transplant Patient:
Prospective Comparison of CT, MR Imaging, Ultrasound and PET
Name of the University:
Name of the Student:
Authors Note:
Table of Content

1Detection of Primary Hepatic Malignancy
s
1.0 Introduction.....................................................................................................................3
1.1 Aims.........................................................................................................................4
1.2 Objectives....................................................................................................................5
2.0 Hypothesis.......................................................................................................................5
3.0 Literature Review............................................................................................................5
3.1 CT................................................................................................................................5
3.2 PET..............................................................................................................................7
3.3 MRI.............................................................................................................................8
3.4 Ultra sonography.........................................................................................................9
4.0 Methodology.................................................................................................................10
Hepatocarcinogenesis......................................................................................................10
Clinical presentation of Hepatocellular carcinoma.........................................................12
Diagnostic Approach.......................................................................................................14
AFP in diagnosis of HCC............................................................................................17
Imaging of the Hepatocellular Carcinoma......................................................................18
Survey examinations.......................................................................................................19
Staging Examinations......................................................................................................20
Characterization of the Hepatic Lesion...........................................................................22
Conclusion...........................................................................................................................23
Summary.............................................................................................................................25

2Detection of Primary Hepatic Malignancy
5.0 References.....................................................................................................................27

3Detection of Primary Hepatic Malignancy
1.0 Introduction
Hepatocellular Carcinoma (HCC) is the most common and prevalent type of liver cancer
that affects majority of patients around the world (Johnson et al. 2015). There are multiple
health conditions due to which patients suffer from this critical health condition such as liver
cirrhosis, due to the critical infection by hepatitis B or hepatitis C (Halazun et al. 2017). The
risk factors of hepatocellular carcinoma are associated with higher consumption of alcohol or
are suffering from critical viral infections. As per Geissler et al. (2018), the cancer cells of
HCC are developed due to the epigenetic alterations which then affects the machinery of the
cellular system and hence, replicates in huge numbers due to which it develops critical heath
conditions. As per Piscaglia et al. (2016), one of the most effective intervention that could
help to prevent the risk of HCC is to conduct orthotic transplantation of liver so that by
removing the carcinogenic liver, another liver could be included in the human body. Further,
it is considered as the most effective treatment process that is implement in patients that are
suffering from HCC. As per Mittal et al. (2016), this process not a new intervention that is
implemented upon patients that suffer from HCC. However, there are cases that indicates that
the rate of infection or other complication arises due to orthotic transplantation in patients
suffering from HCC. Hence, these are the reasons due to which multiple researches are being
conducted so that the rate of survival in patients affected with liver cancer could be
understood. Multiple researches identified that the patients that suffer from critical health
condition such as solitary 5cm or smaller Hepatocellular Carcinoma as well as tumor nodules
less than 3 cm are able to overcome their liver cancer related conditions through proper
transplantation of liver (Sapisochin and Bruix 2017). However, it was also seen that multiple
patients that have already gone through critical conditions associated with their liver
carcinoma are affected with cholangial carcinoma faces poor outcome due to the adverse
conditions as the rate of tumor recurrence becomes higher in those patients. Hence, from

4Detection of Primary Hepatic Malignancy
these critical conditions, it could be understood that to overcome these severe health
complications, proper health screening should be conducted so that they could overcome their
critical health conditions and their eligibility to undergo critical health conditions could be
identified. Further, it should also be conducted to analyze or match the liver profiles of the
donor and the recipient effectively (Mittal et al. 2015).
As per Johnson et al. (2015), it is also important to assess the presence of HCC among
patients so that the accurate diagnosis method of identification of HCC could be identified.
As per the research of Sapisochin and Bruix (2017), it was seen that the there are two kind of
diagnosis method that could be used for the successful diagnosis of the HCC condition
among the patients and as per Zoller and Tilg (2016), CT and MR is considered as the most
effective tools in HCC detection. Hence, the primary aim of this paper was to analyze the
type of detection and identification processes, which is important for the identification and
analysis of the HCC and the type of transplant they need to undergo while suffer from critical
health conditions (Sapisochin and Bruix 2017). The diagnosis processes that this paper would
be assessing is the analysis of magnetic resonance imaging (MRI), computed tomography
scan (CT), Ultrasonography or USG, or positron emission tomography (PET) which could be
considered as the processes that would be used as the process for analysis. Hence, through the
analysis of these imaging technologies or identification process it is estimated that the
successful detection of Hepatocellular Carcinoma (HCC) among the patients of liver
transplant could be identified.
1.1 Aims
The aim of the research is to comparatively study the detection and analysis of the imaging
of the hepatocellular carcinoma exploiting various imaging techniques like positron emission
tomography (PET), computed tomography (CT), ultrasonography (USG), magnetic resonance
imaging (MRI)

5Detection of Primary Hepatic Malignancy
1.2 Objectives
The objective of the research is to analyze and compare the diagnostic performance of the
imaging techniques exploited like Positron emission tomography, ultrasonography, computed
tomography and magnetic resonance imaging. This research exploits the effectiveness of the
imaging techniques in the efficiency to detect the hepatocellular carcinoma among individual
opting for the liver transplant.
2.0 Hypothesis
The hypothesis of this research article is to comparatively analyze the imaging technique
exploited by computed tomography (CT), positron emission tomography (PET), magnetic
resonance imaging (MRI) and ultrasonography. And based on the literature review detect the
most advanced inexpensive mode of detection of the hepatocellular carcinoma.
3.0 Literature Review
3.1 CT
Computed Tomography are special X-ray tests which produces cross-sectional images of
the body exploiting X-rays and a computer. Computed tomography is also referred to as
computerized axial tomography (Kojima et al., 2016). It was established as early as 1974. It
aids to the comfort of the patient since the scan can executed quickly. Exploiting high
resolution of the image formation ensures efficient diagnosis of the disease. Computed
tomography is considered non-invasive, safe as well as effectively tolerated (Yamakawa and
Kojima, 2017). The resolution imaging ensures detailed look at the different body parts. The
design of the scanner rarely makes the patient feel claustrophobic since it is an open donut
shaped scanner.
The patient is exposed to radiation when undergoing CT scan even though it is in the safe
levels. A dye is exploited in the computed tomography as called as a contrast can pose a

6Detection of Primary Hepatic Malignancy
potential risk for the patient as it can cause serious allergic reaction (Kurokawa and Tsubota,
2019). But the contrast aids in distinguishing normal from the abnormal tissues. It also aids in
differentiating blood vessels from lymph nodes.
The evaluation of the CT imaging for patients with suspected hepatocellular carcinoma
should be executed by exploiting hepatic multiphasic contrast imaging. After fast intravenous
infusion of the contrast, imaging is executed at different intervals of time that corresponds to
the enhancement of the phase of contrast (Lee et al., 2015). Triphasic computed tomography
indicates liver imaging performed before contrast, during the arterial and the venous phases.
Hepatocellular carcinoma tumours acquires blood flow predominantly from arteries in the
liver and this has the tendency to enhance in the arterial phase or about 2 to 40 seconds post
contrast infusion (Tang et al., 2017). The hepatic parenchyma surrounding it utilises 75 to
80% of the blood flow through the portal vein and is best observed in the time span of 50 to
90 seconds after infusion of contrast in the portal phase. The enhancement of the arterial
phase can elevate the detection of the hepatocellular carcinoma tumour detection by 10%
(Roberts et al., 2018). In the CT imaging the HCC appears to be heterogeneous in nature that
reflects the intra-tumoural fibrous stranding, necrosis, fatty metamorphosis or calcifications.
Another characteristic exhibited is the occurrence of the satellite nodule in the close
proximity to main lesion. The fibrous structures that encapsulate or is present within the
lesion retains the contrast as well as it enhances readily on the delayed imaging which can be
3 to 10 minutes post infusion (Castilla-Lièvre et al., 2016).
In the literature studies it is described that hepatic lesions can imitate hepatocellular
carcinoma on the CT imaging (Sasikumar et al., 2016). The lesions may include
haemangiomas, regenerating nodules, peliosis and focal fat. The speed of the imaging is
directly proportional to the accuracy of the imaging, this promotes quicker administration of
the contrast media which dramatically impacts the enhancement of the contrast. The

7Detection of Primary Hepatic Malignancy
increased speed as well as the flexibility of the multidetector CT promotes better quality,
thin-section imaging with capabilities of three-dimension (Galle et al., 2018). The computed
tomography arteriography is an invasive as well as effective option to enhance the accuracy
as a result of the greater quantity of the contrast that is administered at a rapid rate. But it
should be noted that this technique is expensive and this acts as a limitation to its use. The
computed tomography arteriography as well as the portography is more frequently used in the
Far East in order to define the liver vasculature prior to surgical interventions (Mulazzani et
al., 2019).
3.2 PET
Positron emission tomography scan is an imaging test that is exploited to detect the
diseases in the body. It exploits the use of dyes that have radioactive tracers. These
radioactive tracers are either swallowed, inhaled or injected into the vein based on the part of
the body that is being examined (Preshlock, Tredwell and Gouverneur, 2016). These tracers
are absorbed by the tissues and organs of the body. These tracers enable doctors to diagnose
any abnormality in the body. The radioactive tracers accumulate in the regions of high
chemical activity and they show up as a bright spot in the scanner. PET scans are mostly
exploited to detect cancer, heart issues and brain disorders including the central nervous
system (Kawai et al., 2017).
In case of the cancer detection since the areas exhibiting carcinogenesis have high
chemical activity they show up as bright spots in the PET scan. PET scans are scanning
techniques that show metabolic changes that occur at the cellular level in an organ or tissue.
This is indeed a vital consideration as the disease usually starts at the cellular level. This is
the reason why PET scan is advantageous over the computed tomography and MRI scanning
techniques (Chalaye et al., 2018).

8Detection of Primary Hepatic Malignancy
PET scan exposes the patient to radioactivity even though it is in the minimal quantity.
The tracer is essentially a glucose molecule that is attached with a radioactive component.
Positron emission tomography plays a prominent role in the Hepatocellular carcinoma
HCC, management. In order to detect the primary tumor, non-FDG PET exploiting [11C]
acetate, [11C]CH or [18F] FCH has a higher sensitivity in comparison to [18F] FDG PET. The
technique of dual-tracer in PET utilizing FDG as well as a non-FDG tracers for the evaluation
of the two in-vivo types of metabolism causes optimization of diagnostic performance. The
several types of hepatocellular carcinoma exhibit differential uptake levels of the tracer
molecules based on the tumor differentiation degree. Presently there has been no literature
studies that can compare the combination of the dual tracers or against technique of
exploiting single tracer with an adjunct imaging of hepatic perfusion. [18F] FDG PET is
comparatively considered as more sensitive in the detection of the extra hepatic metastases
and can be utilized in the evaluation of the high-risk patients, but performing PET for the
purpose of preliminary staging is yet to reach a global agreement. [18F] FDG PET can be
exploited for the pre-treatment prognostication that can include evaluation of the pre-
transplantation which can thus influence the selection of patient. The evidence for the
evaluation of the post-treatment or the detection of the recurrence is comparatively less and it
is also observed in the retrospective studies mostly, with little data that is prospective is
reported in abstracts. The complexity of the hepatocellular carcinoma with respect to the
tumor biology, staging strategies, and the options in treatment warrants the further
prospective research for confirming the role of the positron emission tomography and specific
radiotracers as well as the management course, and also the analysis that is considered cost-
effective to guide the healthcare decisions (Hernandez et al., 2016).

9Detection of Primary Hepatic Malignancy
3.3 MRI
Magnetic resonance imaging exploits the use of a strong magnetic field as well as radio
waves to create a detailed cross-sectional image of the tissues and organs of the body. MR is
considered to be a non-invasive and painless procedure (Wahlstrand et al., 2017). It does not
exploit the usage of potentially harmful ionizing radiation. It is not common that patient who
undergo MRI scan experiences any side effects. But the contrast dye exploited in this
scanning technique can cause nausea, headaches as well as pain or burning at the region
where the dye has been injected. But allergic symptoms are rarely observed in case of MRI
scanning (Tsonton and Thompson, 2016). But some patients may feel claustrophobic while
undergoing MRI scanning.
3.4 Ultra sonography
Ultrasonography is the most common and the frequent imaging modality that is exploited
to analyze and evaluate the parenchymal organs of the abdomen since it is comparatively less
expensive, widely available and non-invasive. The efficacy of the detection of the
hepatocellular carcinoma varies in the individual affected with liver disease with a sensitivity
of 33-96% and the specificity reaches over 90%. There are variety of guidelines that
recommends Ultrasonography as the first-line surveillance modality for the HCC in patients
with high risk. The high- risk patients may include cirrhotic patients as well as the non-
cirrhotic patients with chronic hepatitis B and hepatitis C infection or may have elevated
levels of HBV-DNA levels. Patients with non-cirrhotic family history of hepatocellular
Carcinoma and Non-Alcoholic fatty liver disease should be encouraged to undergo the
routine surveillance. Based on the literature studies it can be inferred that the ultrasonography
has a low rate of sensitivity but comparatively a high rate for specificity. The screening
interval for the hepatocellular carcinoma is approximately 6 months. The recommended
screening interval for HCC is 6 months. In case of the cirrhotic patients, the sub-centimeter

10Detection of Primary Hepatic Malignancy
nodules (< 1 cm) that are detected by the ultrasonography should be followed every 3to 4
months during the initial year followed by every 6 months post the first year (Hernandez et
al., 2016). The nodules that are over 1 cm should be tested for imaging work-ups as well as
biopsy for the characterization of the same. The performance of the US is greatly dependent
on quality of the equipment and the expertise of the operator. US comparatively less sensitive
than the other techniques discussed in this report for the detection of the early-stage of
hepatocellular carcinoma.
4.0 Methodology
Hepatocarcinogenesis
The process of the hepatocellular carcinoma is called as hepatocarcinogenesis and it is the
most common and prevalent cancer that impacts all populations worldwide. Several health
complexities can lead to this chronic health compromised condition. The factors may be
hepatitis b and hepatitis C infections. The risk factor involves excessive consumption of the
alcohol as well as viral infections that are critical can be a risk. It should also be noted that in
most cases this hepatocellular carcinoma can arise silently and progress hence making the
diagnosis challenging at the early stages (Sapisochin and Bruix 2017) (Mittal et al. 2015).
Hepatocarcinogenesis is defined as a complex multistep process that impacts the
molecular, cellular as well as the histologic levels. The liver cells can develop epigenetic
alterations that impacts the system at the cellular level. The chronic inflammation of the liver
can cause repeated cell injury, death and regeneration cycles, this leads to subsequent
epigenetic and genetic in the hepatocytes (Kojima et al., 2016). Considering the molecular
level, the important oncogenes like MYC and the tumour suppressor genes like TP53, E-
cadherin, PTEN, and RASSF1 either undergo mutation or are aberrantly regulated because of
structural genetic alterations and several signalling pathways that are functioning abnormally

11Detection of Primary Hepatic Malignancy
like Ras, epithelial growth factor receptor and insulin-like growth factor receptor 1 signalling.
Post the malignant transformation of the mature liver cells or the intrahepatic stem cells
hepatocellular carcinoma develops at the cellular level. The phenotypically abnormal
precursor lesions in the liver, which includes cirrhotic nodules, high-grade dysplastic nodules
(HGDN) low-grade dysplastic nodules (LGDN), at the histological level dedifferentiate and
evolve to form early and eventually progressed hepatocellular carcinoma. This process can
impact at various rates in several hepatic parts. There are various key alterations that happen
during the process of hepatocarcinogenesis. Firstly, the distinct hemodynamic changes take
place during the multistep process. The blood supply of the nodules diverges with the
malignant transformation: there is a reduction in the number of intra-nodular portal tracts
gradually but there is an increase in the number of unpaired arteries. The hepatic artery
system supplies the hepatocellular carcinoma via the abnormal unpaired arteries. This causes
characteristic enhancement of the pattern of the hepatic arterial phase hyper enhancement and
portal venous phase or the delayed phases wash-out relative to background liver on the
contrast enhanced multiphasic MRI and CT. Additionally, the venous drainage of the nodules
evolves from the hepatic veins to sinusoids as well as the portal veins, that explains why
HCC majorly spreads through the portal venous system than the hepatic veins (Kojima et al.,
2016).
Secondly, the most prominent features morphologically during the hepatocarcinogenesis are
formation of the fibrous tumour capsule which is a smooth, uniform and enhancing rim
formed surrounding most of the nodule or all of the nodule as well as the “nodule-in-nodule”
architecture is also formed which is the formation of smaller nodules with considerably
different imaging features present within the outer larger nodule (Yamakawa and Kojima,
2017). It should be noted that since the cirrhotic nodules, the dysplastic nodules and the early
hepatocellular carcinoma are rarely present with a fibrous capsule, the appearance of the