Malignant Liver Tumours
Where is the liver located and what is its structure?
With an average weight of 1.5 kg and a capacity of three
litres, the liver is one of the biggest and most important
organs. Three quarters of it are found in the upper abdomen
on the right side, and its form resembles an oblique three-sided
pyramid. On top, it is connected to the diaphragm, and it
thus lowers when a person exhales. The doctor takes advantage
of this if he wants to palpate the lower rim of the liver
and feel its outlines. At the lower part of the liver, the
gall bladder and the lower caval vein are so deeply embedded
in its tissue that there is an asymmetrical external partition
into a small part to the left and a big one to the right.
This external view, however, contrasts strongly with the
very symmetrical inner structure of the liver, which is
subdivided into eight sections as shown by Claude Couinaud.
The internal symmetry results from a regular organisation
of one vein, one artery, and one bile duct in each of the
eight sections. These vessels receive supply from the hepatic
portal located at the bottom of the liver. It is there that
the great supplying vein and artery enter the liver. The
vein carries along oxygen-deficient blood, which is however
rich in protein, from the stomach and the bowel. It is filtered
by the liver and detoxicated in the process. The portal
vein divides into a left and a right branch right after
entering the liver. Both branches go on dividing and form
the portal vascular tree of the liver. The artery supplies
the liver tissue with blood rich in oxygen. It also branches
off various times, thus forming the arterial vascular tree
of the liver. There is a kind of an interdependent steering
mechanism between the two: in case of a very serious disease
of the liver with impairment of the blood supply in one
of the two vessels, the other vessel will compensate it.
After having passed the liver, the blood flows via the third
vascular tree, the big liver veins, into the lower caval
vein and towards the heart. At the same time, the bile produced
in the liver cells is transported from around the hepatic
porta in the opposite direction and partly stored in the
gall bladder or discharged into the duodenum for the digestion
of food. This complex inner structure still takes even highly
qualified surgeons to their limits. This is especially the
case if they try to save a small part of the liver intensively
infiltrated by a tumour, so that the patient receives the
best surgical therapy possible.
Malignant Liver Tumours
How does the liver function?
The liver, serving as a blood filter and being located between
the bowel and the rest of the organism, takes care of the
most various and complex assignments in the metabolism of
the human being. It produces important substances (blood
clotting agents and cholesterol), keeps the equilibrium
of many substances (fat, sugar, hormones, vitamins) and
helps to discharge medicaments, catabolic products, and
toxicants from the body. Besides, it is the biggest gland
and is responsible for the production and delivery of bile,
and it thus plays an important role in the digestion of
fat in the bowel. Consequently, a restriction of the function
of the liver tissue, caused by tumours or inflammations,
results in more or less grave after-effects: the glycometabolism
may be upset (hypoglycaemia), proteins are produced only
insufficiently (disorder of blood coagulation, hydro-abdomen),
and the bile salts and pigments are insufficiently discharged
(itching and yellow colouring of the skin). One of the most
important abilities of the liver is its enormous regenerative
capability. If the liver has to be partly excised and considerable
quantities of liver tissue are removed (maximum 75%), a
compensatory growth of the remaining liver will be observed
after some time. There is an increase of liver cells under
the influence of messenger substances in this process, but
there is also an obvious enlargement of the remaining liver
cells.
The most common malignant liver tumours
In medicine, a fundamental difference is made between primary
and secondary tumours (metastases). The primary malignant
liver tumours form in the liver cells themselves or in cells
of the bile ducts. The secondary tumours or metastases are
scattered cells of a malignant tumour, which developed in
another organ, as for instance the large bowel, the rectum,
or a kidney. Concerning the formation of the most common
tumour of the liver, the hepatocellular carcinoma (HCC),
we only know that several factors play a role in the process:
viruses (hepatitis), hormones, chemicals (solvents, pesticides),
alcohol, and certain habits of nutrition. The HCC may grow
in the liver tissue as a single node, scattered or diffusely.
Much rarer is the carcinoma of the bile duct (CCC), which
develops in the tissue of the bile ducts and whose cause
is not known. Quite often, gall stones are found in patients,
who have this disease. For this reason, there is a discussion
that a chronic irritation caused by these stones and the
consequent inflammation might account for the formation
of this tumour. The appearance of this tumour is characterized
by single tumour nodes which show a high share of connective
tissue, recognizable from its central cicatrisation. Occasionally,
a hybrid form of the two tumours (HCC + CCC) is found in
the liver. Its diagnosis is difficult and requires a careful
preparation and assessment by a pathologist. Compared with
the rarer primary carcinomas of the liver, the secondary
malignant tumours of the liver (metastases) are found much
more frequently. The liver is the organ, where various vagrant
cells of malignant tumours of the rectum, of the large bowel,
and of the kidney accumulate. However, it is not known whether
the liver tissue functions like a sieve and retains metastases.
How do I recognize a malignant liver tumour?
Patients with a hepatocellular carcinoma often do not show
any characteristic symptoms because many pathological changes
of the liver are only found by diagnostic chance. Unfortunately,
the soft liver tissue can easily neutralize pressure, so
that pain due to tension occurs relatively late. In the
case of a bile duct carcinoma, an obstruction of the ducts
may cause a yellow colouring of the skin and thus give a
first indication that there might be a tumour.
Necessary clarifications and diagnostic possibilities
The attending doctor must first find out the exact history
of the disease and then conduct an intensive physical examination:
questions about prior diseases, nutritional habits, previous
operations and blood transfusions (hepatitis?), loss of
weight, and pains are important. During the physical examination,
an approximate assessment of the size and consistency of
the liver is made, the colour of the skin is checked, and
the patient is asked whether there has been any itching.
In addition, the most important blood factors will be determined,
bearing the various functions of the liver in mind: blood
picture, coagulation status, level of blood sugar, total
protein, and tumour markers. The ultrasound is still very
suitable to provide to the doctor a fast orientation of
the disease as it has to be found out whether the tumour
is benign or malignant, whether it comes from the liver
itself, or whether it is a metastasis. Only after this,
it can be decided whether further diagnostic methods like
CT, MRI (with the use of contrast medium), or angiography
should be used. A biopsy will only be made in exceptional
cases because one is afraid of spreading the tumour cells
and of the risk of bleedings. If all the findings result
in the diagnosis of a malignant tumour, the choice of the
best treatment depends on the diagnosis. In case of a surgical
therapy, there are two fundamental questions to be answered
from the surgeon's point of view: Do the age and physical
condition of the patient permit such a great intervention?
To clarify these questions, additional examinations of the
heart (ultrasound) and the lung (functional test) are often
necessary. Then, the surgeon has to ask himself what surgical
conception should be chosen. In this context, the following
questions are important: In what part of the liver is the
tumour located? Is it one node or are there several? Which
part of the vascular tree supplies this part of the liver?
Which bile ducts run here? How much healthy liver tissue
will remain after the removal of the tumour and is it sufficient
to guarantee the survival of the patient? Is it a primary
malignant tumour or is it a metastasis? Before the operation,
an important liver test (GEK, galactose elimination capacity)
has still to be carried out. It is used to answer the question
whether the tumour has left enough functioning tissue in
the liver. A liver operation requires high-tech management
also from the anaesthesiologist. Necessary are a preoperative
examination, availability of packed blood, and information
about the postoperative care at the intensive care unit.
If the physical condition of the patient or the localization
of the tumour speaks against an operation, an interdisciplinary
team of surgeons and oncologists will convene to decide
on the further proceedings, e.g. chemotherapy, frigotherapy,
or radiation therapy.
How can a malignant liver tumour be treated?
Various diseases make the removal of parts of the liver
necessary: benign and malignant liver tumours, metastases,
parasitic infestation of the tissue (fox tapeworm), or tumours
of the gall bladder or the bile ducts. Depending on the
disease, size, extension, and above all, location of the
tumour, differing partial resections are carried out. They
are named after certain sections of the liver: segment resection
(one or more segments) of the right or left part of the
liver, which may be extended within certain limits.
One example: the partial liver resection to the right (hemihepatectomy)
involves the removal of segments V, VI, VII, and VIII. If
it has to be extended, the standard is to remove also segment
IV, located to the left of the gall bladder. The maxim and
objective of the surgeon in this context is to remove "as
much as necessary and as little as possible" of the tissue.
Unfortunately, this is even for specialist not easy due
to the highly complicated anatomy of the liver. In the case
of a malignant tumour, a safe distance must also be kept.
There are various and different methods of partial liver
resection, whose fundamental sequence, however, is similar.
The above mentioned hemihepatectomy (right) may serve as
an example.
When the operation begins, the patient lies on his back,
with his right arm stretched out and his left arm alongside
his body. The incision is made along the right and left
costal arch and may be extended a little in the middle and
to the top, having the appearance of a three-edged star.
After cutting the abdominal wall, the surgeon will first
try to feel the outlines of the liver with his hands and
will palpate it (tumour and tissue assessment), then he
will also check the neighbouring organs. After this, the
liver is partly mobilized by disconnecting certain ligaments
fixing the organ to the abdominal wall or by partly cutting
them. If or if not the preceding diagnosis and the actual
findings are coherent, the surgeon may decide on an intraoperative
ultrasound to perhaps reassess his concept. Basically, there
are now two different options for the removal of liver tissue:
- All important supplying or deferent vessels and the bile ducts are tied up, followed by the actual transection of the liver tissue (finger fracture).
- When the liver tissue has been transacted, the blood supply is controlled and the vessels are tied up.
The procedure may differ, depending on the surgeon and on the given situation. If the surgeon has chosen the first variant, he will first expose the hepatic porta. There, the great arterial and venous vessels and also the bile ducts are located, entering the liver in a thick cord of tissue. Now, the gall bladder and its supplying vessels are exposed as far as the papilla. The gall bladder is then removed for two reasons:
- The surgeon will have a better view of the papilla, which is very important.
- Complications (inflammations) after the operation are avoided, which could occur around the gall bladder.
Now, the lymphatic nodes around the hepatic porta are closely inspected, if necessary removed and examined by a pathologist. The thick cord of tissue of the hepatic porta is tied with a rubber hose, so that the blood supply can be controlled in this place (Pringle manoeuvre). The cord is now carefully exposed, so that finally the artery on the right side, the portal vein, and the bile duct become visible. The vessels are clipped off, pierced and tied up, as is the bile duct. With that, the blood supply to the areas to be excised has been interrupted. Now, the right part of the liver must be further mobilized, so that the deferent vessels at the back can be exposed. Now, the liver tissue is cut, which has already been demarcated after the vessels had been tied up. Different techniques can be used here: application of clips, diathermy, or the clamp technique with piercing. Diffuse bleedings of larger areas from the liver tissue can be stopped by using argon coagulation, smaller ones by using diathermy. Finally, the deferent vein of the liver is removed and sutured. Now, the diseased liver tissue can be totally removed and sent to the pathologist.
The most important task for the surgeon now is a scrupulous suppression of bleedings. Then, the severed areas of tissue are "dried out" with the use of argon coagulation, and the tied off vessels are checked. Special attention is given to the severed bile ducts because a postoperative leakage must be avoided by all means. Only in exceptional cases, a drain is laid into the area. After this, the abdominal wall is closed layer by layer. Depending on the primary disease, for instance in the case of metastases, an additional treatment after surgery could be useful to increase the curative effect: local chemotherapy, thermotherapy, frigotherapy, or laser therapy. Many liver operations follow the above mentioned basic principles. Yet, the surgeon is often forced to choose atypical variants due to the local findings. He has to take special care that the remaining liver tissue is well supplied with venous and arterial blood.
What happens after the treatment?
After every major liver operation, the patient stays for
1 - 2 days at the intensive care unit. Here, an adequate
pain therapy and a balanced infusion therapy are carried
out. The liver data are controlled, and a close monitoring
is maintained to make sure that complications like bleedings
are immediately detected. In the normal ward, the patient
gradually receives adequate food and is slowly induced to
get up and move around. The stitches are removed on the
10th day after the operation. Depending on the disease,
surgeon and oncologist may discuss the possibility of an
additional therapy in the form of an intravenous chemotherapy
and talk about it with the patient. If the tumour has already
advanced, it may be necessary to consult a pain therapist,
who will suggest an individual combination of medicaments
for the patient.
What has to be paid attention to in future everyday life?
All patients with malignant liver tumours are taken care
of by the family doctor, the gastroenterologist, the oncologist,
and the surgeon in a joint follow-up programme. This comprises
laboratory controls to monitor the tumour markers and the
liver values as well as an ultrasound and/or a CT of the
abdomen. Thus, the regeneration of the remaining liver can
be assessed, and new tumours can be detected in good time.
History
Already in Greek mythology, that is to say in the story
of Prometheus, the liver plays an important role: Prometheus,
"the one who thinks ahead", tried to cheat Zeus in favour
of man, and Zeus in turn withdrew the fire from man as a
penalty. But Prometheus stole the fire again to bring it
back to earth. So Zeus had him chained to a rock, where
eagles came to tear his liver to pieces every day, which,
however, renewed itself during the night until Heracles
one day liberated him from his pains. This story hints at
one of the most important qualities of the liver: its capability
for regeneration. For centuries, it had been mainly the
military surgeons who tried to treat open injuries of the
liver. But then, it was the introduction of general anaesthesia
and antisepsis at the end of the 19th century that enabled
Karl Langenbuch to perform the first operation of the liver
in 1888. At the same time, the basic research as to the
regeneration of the liver and the arrest of bleeding (haemostasis)
in the liver was carried out. Between 1899 and 1914, it
was especially the Viennese surgeon and scientist Emerich
Ullmann, who relatively unnoticed promoted the research
of transplantation and who must therefore be called "father
of organ transplantation", if only belatedly. Yet, the foundation
for modern liver surgery was laid in the fifties by the
great Parisian school led by Jacques Hepp. In 1954, his
assistant Claude Couinaud published the standard work on
the anatomy of the liver. He was able to prove the complex
inner structure of eight sections, which are determined
by the liver veins. Also, the immunology of transplantation
had greatly progressed in the meantime. So in 1967, Tom
Starzl was able to carry out the first successful transplantation
of a liver even if the immunosuppressive therapy was still
insufficient. The scientific efforts to develop immunosuppressive
therapies went on until 1972. Then, by chance, a substance
called cyclosporine was found, drawn from a fungus that
grows in the earth. It was able to reliably suppress the
rejection of an organ, and consequently, the rate of survival
of transplanted patients rose dramatically.