Biomedical Engineering Reference
In-Depth Information
19
Thermochemical Ablation
19.1 Practical Considerations ........................................................................................................ 343
19.2 Future Directions .................................................................................................................... 350
References ............................................................................................................................................ 350
Erik N. K. Cressman
University of Minnesota
Medical Center
The origins of thermochemical ablation stem from a clinical
problem with many solutions of which none is ideal. The prob-
lem is that to be given a diagnosis of hepatocellular carcinoma
(primary liver cancer, hepatoma, HCC) in many parts of the
world is to be given a death sentence. The question foremost in
the mind of most of these patients is in the absence of a cure,
how long they have left to live. The answer is usually measured
in months. This reflects a combination of factors that include
the insidious yet aggressive nature of the disease, the cost and
relative sensitivities of any available screening programs, the
fact that many people do not know they are at risk and should
be screened, and the limited availability of effective treatments.
Worldwide, HCC is one of the leading causes of cancer death,
and unlike more treatable malignancies, most people with HCC
will die from HCC. Making a bad situation worse is the fact that
the incidence of HCC is increasing.
1-3
Cirrhosis from hepatitis B (HBV) is less common than cirrho-
sis from other forms of hepatitis, but due to the number of people
infected with HBV, it is thought to be the most common cause of
HCC. Vaccination programs for hepatitis B as a long-term solu-
tion are yielding very positive results, but there are already many
developing cases of liver cancer from this single source. There is
as yet no vaccination for hepatitis C (HCV), alcoholic liver dis-
ease is very common, and the incidence of fatty liver disease that
leads to cirrhosis is arguably overtaking all other causes for this
cancer. Etiologies are varied and are changing with the popula-
tion and risk factors. With the rapid pace of advancements in
molecular biology, researchers and clinicians now understand
how diverse their target in fact is. This makes individualized
treatment both critical and extremely challenging from a phar-
macologic point of view. The situation as outlined herein has
thus led to an enormous effort from many different angles for
treatment.
Surgical interventions, such as liver transplantation or par-
tial hepatectomy, can be potentially curative, and transplan-
tation has the added advantage of treating the underlying
cirrhosis. Unfortunately, there are numerous difficulties with
this approach. The large majority of patients are not surgical
candidates at presentation, and regardless of cost, the number of
transplants performed is dwarfed by the demand. Another issue
is that the nature of the disease is such that it will often recur
elsewhere in the liver within a relatively short time.
Chemotherapy would seem to be a reasonable option for
the treatment of liver cancer as it is for so many other forms
of cancer. HCC has proven to be a difficult challenge, however,
with well over 100 clinical trials of various regimens showing
no survival benefit. Indeed, even achieving stable disease or a
partial response has been uncommon. The advent of newer, tar-
geted therapies such as sorafenib has been heralded as a turning
point in the battle as a survival benefit was shown for the first
time.
4, 5
The results must be viewed with some caution, however.
The duration of the benefit was on average slightly less than
three additional months. Furthermore, since the initial trials
were run, there have been many papers published on how toxic-
ity has resulted in a great many patients either lowering the dose
of the drug or stopping it altogether.
6
Since the survival benefit
was observed at the full dose and many patients cannot tolerate
the full dose, it is not clear that the drug provides the anticipated
benefit for a large portion of the population.
With surgery often excluded, and limited benefit from drug
therapies, medicine has turned toward ablative therapies to treat
HCC. The goal in the best cases would be to treat as effectively as
possible while at the same time sparing as much non-tumor tissue
as possible. There is an important semantic issue to make at this
point, which is that in clinical practice it is inaccurate and in fact
dangerously ignorant to refer to tumor versus normal tissue. This
is critical because, as noted before, HCC most commonly occurs
in the setting of cirrhosis. The cirrhotic liver is by no means “nor-
mal,” and this has implications for how aggressive a physician can
be in treating the disease. One must keep in mind that the under-
lying survival curve for decompensated liver disease is an intrin-
sic limiting factor in the maximal benefit that can be attained by
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