Liver

However, this external appearance contrasts strongly with the very symmetrical internal structure of the liver, which has been divided into eight segments (sections) since Claude Couinaud. This internal symmetry results from the regular allocation of one vein, one artery, and one bile duct to each of the eight segments. The large afferent vein, the portal vein and artery, and the hepatic artery enter the liver at the porta hepatis. The vein brings oxygen-poor but protein-rich blood from the intestinal and stomach regions to flow through the “liver filter” and be detoxified durign the process. Immediately after the blood enters, the portal vein divides into left and right branches. Both branches further divide and form the portal vascular tree of the liver. The artery which supplies the liver tissue with oxygenated blood, also divides into several branches and forms the arterial vascular tree of the liver.

After passing through the liver, the blood continues to flow via the third vascular tree (i.e. via the large hepatic veins) into the inferior vena cava and towards the heart. At the same time, the bile produced in the liver cells is transported out of the liver in the opposite direction in the area of the hepatic porta, and partially stored in the gallbladder and excreted via the duodenum for digestion of food. Even until today, this complex internal structure of the liver still pushes highly qualified liver surgeons to their operational limits when they attempt to save a small piece of healthy tissue, in the case of extensive tumor invading the liver, in order to provide the patient with optimal surgical therapy.

Therefore, a functional impairment of the liver tissue, caused by tumors or inflammations, has more or less serious consequences: Sugar metabolism can derail (hypoglycemia), proteins are insufficiently produced (blood clotting disorders, abdominal dropsy), and bile salts/bile pigments are insufficiently removed (itching and yellowing of the skin). One of the most important properties of the liver, however, is its enormous capacity to regenerate: if one has to remove a large amount (up to 75% maximum) of liver tissue as a part of liver resection, one will notice a compensatory enlargement of the remaining liver after a while. Under the influence of messenger substances, there is a proliferation of liver cells on the one hand, but also a significant enlargement of the existing liver cells on the other hand.

The true neoplasms (Latin: tumors) of the liver tissue must be clarified in detail, because both benign and malignant tumors can be found among them. In this patient information, we particularly describe the malignant neoplasms. The benign tumors are described in our patient information “Benign Liver Tumors”.

In medicine, there is a basic distinction between primary and secondary malignant tumors (metastases). Primary malignant liver tumors arise from the liver cell itself or from cells of the bile ducts located in the liver tissue. Secondary tumors, commonly referred as metastases, are scattered cells from a malignant tumor that originated from another organ, such as the colon, rectum, or kidney. Much is known about the development of the most common primary tumor of the liver, hepatocellular carcinoma (Latin: hepatocellular carcinoma, often abbreviated to “HCC”), that several factors are causally involved: viruses (hepatitis), hormones, chemicals (solvents, pesticides), alcohol and other noxae.

HCC can grow in liver tissue both as a single nodule, as well as scattered or diffused. Much rarer case is cholangiocarcinoma (often abbreviated to “CCC”), which arises from the “lining tissue” of the bile ducts, whose cause is still unknown. Gallstones are also often found in affected patients and in this context, a chronic inflammatory stimulus caused by these stones could cause the development of a tumor. The appearance of this tumor in liver is characterized by individual tumor nodules with a high proportion of connective tissue, recognizable by its central scarring. Occasionally, a mixed form of these two tumors (HCC + CCC) is also found in the liver, the difficult diagnosis of which must be made by a pathologist after a careful tissue preparation and evaluation.

Compared with these rare primary carcinomas of the liver, the secondary malignant tumors of the liver, liver metastases (Figs. 2a, 2b, 3a, and 3b), are found much more frequently.

Further, the color of the skin is checked, and itching is asked for. In addition, according to the multiple functions of the liver, the most important blood values will be determined: Blood count, coagulation status, liver values, blood sugar level, total protein and tumor markers. The ultrasound is still an excellent way of providing the physician with a quick orientation regarding the disease, since it is necessary to find out whether the tumor is benign or malignant and whether it originates from the liver itself or is a metastasis, for example. After that, a decision can be made about further diagnostic procedures such as CT, MRI (combined with contrast agent administration), angiography or PET scan (Fig. 5).

A tissue sample will only be taken in exceptional cases, as there is always a risk of tumor cells being carried away and the risk of bleeding. If the diagnosis of a malignant tumor has been made on the basis of all the available findings, different treatment paths must be followed depending on the findings.

This includes the preoperative examination, explanations regarding the creation of arterial and venous accesses, the provision of blood supplies and information regarding postoperative care in the intensive care unit. If the patient’s physical condition or the location of the tumor argues against surgery, an interdisciplinary team of surgeons and oncologists will meet to decide on the next course of action, for example, chemotherapy or locally applied treatments with heat, cold or radio wave irradiation.

Very rare tumors that occur as metastases in the liver can be so-called neuroendocrine tumors, which usually originate from the pancreas and settle in the liver (Fig. 6). They grow like malignant tumors, but often very slowly and somewhat confined to the affected organ. Therefore, combination operations on the liver and pancreas are indicated here. However, after surgery, oncological therapy must also be used.

An example:

Right hepatectomy involves removal of the segments V, VI, VII and VIII on the right side. If it has to be extended, segment IV, which is located further to the left of the gallbladder, is still added as a standard. Removing as much as necessary and as little tissue as possible is the surgeon’s maxim and desire. Unfortunately, due to the highly complicated anatomy of the liver, this is often no small matter, even for the specialist. This also includes a certain safety margin in the case of malignant tumors. As an example of the many different procedures of partial liver resection, the basic procedure of which is similar, the right hemihepatectomy already mentioned above will be described below.

During surgery, the patient lies in the supine position with the right arm extended and the left arm flexed. The skin incision is made along the left and right costal arches and is extended upward a little as needed, centered over the sternum, to create the image of a “Mercedes star” (Fig. 7).

After cutting through the abdominal wall, the surgeon will first use both hands to circumnavigate and palpate the liver (tumor and tissue assessment) and examine the adjacent organs. This is followed by partial mobilization of the liver by loosening or partially severing certain suspension ligaments of the organ to the abdominal wall and diaphragm. Subsequently, an intraoperative examination with ultrasound is performed to determine the exact location of the tumor, to clarify the resection options and to rule out other tumors. Depending on whether or not the preliminary findings match the local findings found, the surgeon will decide to reconsider his approach. Basically, there are now two different technical routes that can be taken to remove liver tissue:

All important supplying and draining vessels including the bile ducts are blocked, after which the actual transection of the liver tissue can be carried out using various methods. Tissue dissection with the finger “finger fracture technique” or with devices that facilitate tissue hemostasis (such as an ultrasound dissector or the Habib Sealer), (Figs. 8a and 8b).

First, the liver tissue is transected while controlling blood flow, then the vessels are tied off.

A tissue sample will only be taken in exceptional cases, as there is always a fear of spreading tumor cells and the risk of bleeding. If the diagnosis of a malignant tumor has been made on the basis of all the available findings, different treatment options must be pursued depending on the findings.

The gallbladder is removed for the following two reasons: the surgeon has a better view of the hepatic portal, which is important for him (Fig. 9), and after the surgery he avoids the occurrence of complications that may arise in the gallbladder area (inflammation). Now the lymph nodes in the area of the hepatic portal are closely inspected, removed and examined by the pathologist. The thick tissue strand of the hepatic portal is looped with a rubber tube so that the blood flow can be controlled at this point during the surgery (Pringle maneuver). The cord is now carefully dissected so that the relevant right-sided artery, portal vein and bile duct are finally exposed.

The surgeon’s most important task now is meticulous hemostasis. The severed tissue areas are “drained” with argon gas coagulation, and any vascular ligations that have occurred are controlled. Particular attention is paid to the severed bile ducts, because here too there must be no leakage under any circumstances postoperatively. Often, a drain will be placed in the surgical area. This is followed by the layer-by-layer closure of the abdominal wall.

Depending on the underlying disease, for example in the case of metastases, a combination treatment for surgery with local chemotherapy or even heat therapy (Fig. 13 Cold (Figs. 15 and 16), and laser therapy may be useful to completely destroy the tumors.

If primary malignant tumors or liver metastases are too large for resection, then various tumor reduction procedures are used today prior to surgery. All procedures attempt to preserve as much healthy liver tissue as possible and to shrink the tumor. For liver metastases from colon cancer, for example, chemotherapy is first carried out in order to shrink the tumors or to destroy smaller metastases that are invisible in the imaging diagnostic methods. If the tissue of the liver remaining after surgery is too small, then by occluding a portal vein branch to the left or right liver portion, the liver portion excluded from the portal vein blood can be reduced, and the opposite portion enlarged. This closure can be achieved by specialists in interventional radiology through a small incision in the groin and by advancing special catheters through the veins into the portal vein.

With the occlusion of a portal venous branch, a so-called hypertrophy (enlargement)-atrophy (reduction) complex is successfully artificially created. This possibility is based on the well-known fact that when liver tissue is lost, the tissue left behind can compensatorily increase in size again to a very large extent. However, in the presence of liver fibrosis or cirrhosis, the remaining liver can no longer enlarge sufficiently.

Intraoperative views of various findings follow (Figs. 18, 19 and 20).

With this legend, among other things, one of the most important properties of the liver is indicated: its ability to regenerate. For centuries, it was primarily the war surgeons who attempted to treat open liver injuries. It was not until the establishment of general anesthesia and antisepsis at the end of the 19th century that Karl Langenbuch was able to perform the first liver surgery in 1888. At the same time, the scientific basis for liver regeneration and hemostasis in the liver were explored during this period. Between 1899 and 1914 there was a scientist, the Viennese surgeon Emerich Ullmann, who advanced transplantation research relatively unnoticed and who in retrospect has to be called the father of organ transplantation. However, the foundation stone for modern liver surgery was laid by the great Parisian school around Jacques Hepp in the 1950s.

In 1954, one of his colleagues, Claude Couinaud, published the standard work on liver anatomy. He described the complex, internal division of the liver into eight segments, which were determined by the location of the hepatic veins and by the location of the bile ducts. In the meantime, transplantation immunology had also made great progress, so that in 1967, despite inadequate immunosuppression, the first successful liver transplantation of a patient by Tom Starzl could be carried out. The scientific struggle for potent immunosuppressants continued until 1972, when a substance (cyclosporine) was obtained by chance from a soil fungus, which was able to reliably suppress the rejection reaction of an organ in the body and then caused the survival rate of transplanted patients to skyrocket.

Only when they exceed nine centimeters in size, effectively causing pain or increasing in size, they have to be treated surgically. Besides these so-called simple cysts, there are also complicated cysts. They are so called because their contents on ultrasound or CT do not show clear fluid as their contents, but subdivisions by septa, hemorrhage, or because their interior shows an indefinable content (Figs. 9a and 9b). Here, the differential diagnosis to other possibly more dangerous liver diseases is important. However, simple cysts are relatively easy to detect with imaging methods.

A specific hereditary disease is cystic liver. In this disease, the liver tissue is diffusely interspersed with many larger and smaller cysts. Cystic livers can grow grotesquely and usually cause mechanical problems with pain and digestive problems for those affected. This disease affects not only the liver but also the kidneys, which are also so heavily riddled with cysts to such an extent that over time there is no longer sufficient kidney function. In the case of pain, mechanical disorders and digestive problems, these cysts can be reduced in size – often laparoscopically – by removing the cyst roofs that are exposed on the surface.

Furthermore, it must be clarified whether there was a tumor condition in the past and whether hormones were taken over several years. Does the patient work as a farmer or in forestry, or have contact with animals for other reasons? For further clarification, laboratory values such as blood count, liver values and tumor markers must be determined in order to confirm the benign nature of the tumor. The clarification of the dog and fox tapeworm also requires a special blood test that looks for antibodies against the larvae in the blood.

As the simplest imaging method in diagnostics, an ultrasound is first carried out for all liver diseases and then decisions are made about other imaging methods such as CT (Fig. 24), MRI or angiography in order to obtain an accurate diagnosis. Very specific for tumors is the PET scan examination (Fig. 25). If the diagnosis indicates that a piece of liver needs to be removed, further special tests are performed to check the functionality of the healthy liver tissue.

Hepatocellular adenoma is considered a precursor of hepatocellular carcinoma and is therefore removed surgically in all cases. Depending on the location of the adenoma within the liver, central or peripheral, the surgeon selects the removal technique that completely removes the tumor and spares the healthy liver tissue, while also posing the lowest risk of surgery for the patient. Surgeries in which parts of the liver have to be removed are subject to an increased risk of bleeding due to the highly complicated blood supply to the liver and are often a major challenge for the surgeon.

If FNH (focal nodular hyperplasia) has been clearly diagnosed, it will not have to be operated on, and here too, patients in particular will be advised against taking hormones for contraception. Especially in this disease, scientists assume that its development is triggered by hormones. Often, however, FNH cannot be diagnosed with such certainty, or it causes discomfort due to its location and size, so that surgical removal has to be carried out anyway.

Regarding the therapy of cysts of both dog and fox tapeworm, there are two principles:

• If somehow possible, they are approached surgically, focusing quite strictly on the criteria of tumor surgery, since no larval material may be carried over.
• All patients are treated with the anthelmintic drug mebendazole.

For dog tapeworm cysts, surgery remains the first choice procedure with the goal of radically removing the parasite. The prerequisite for this is above all a “good” location of the cysts so that the surgeon can peel them out without risk (pericystectomy). If the cysts are diffusely distributed in the liver tissue, the surgeon may need to perform a partial liver resection. The more radical the surgery, the less likely the infection will flare up again.

If the general condition of the patient or an unfavorable distribution of the cysts does not allow surgery, there is another procedure that can be used:

• Laparoscopically, i.e. with the help of keyhole surgery, the cyst is emptied in a controlled manner with a special device and the capsule is ground off, at the same time the vermifuge is administered as a tablet. For the cysts of the fox tapeworm, the same principles apply in principle, except that here the larvae usually spread even more aggressively in the liver. Consequently, radical surgical rehabilitation must be sought here as well, if somehow possible. Therefore, an accompanying medication of up to 24 months, possibly even longer, is necessary.

This means that the patient is cured, but should still receive follow-up care, with ultrasound and possibly CT scans as well as laboratory checks to further monitor the progress. In the case of FNH (Focal Nodular Hyperplasia), patients are also advised to avoid hormone use and undergo regular ultrasound examinations.

The patients with fox or dog tapeworm infection unfortunately have to live with the fact that they have to remain under medical treatment more or less for the rest of their lives. This applies to patients who have undergone surgery as well as those who have received drug therapy. Unfortunately, to date there is no blood test or imaging procedure that proves that the parasites have really been removed 100% from the body despite therapy.

The side effects of the anthelmintic include blood count changes, abnormal liver values, and hair loss. Therefore, close-meshed laboratory examinations to check the active level of mebendazole as well as imaging procedures (CT, MRI) are part of the spectrum of follow-up care.

With this legend, among other things, one of the most important properties of the liver is indicated: its ability to regenerate. For centuries, it was primarily the war surgeons who attempted to treat open liver injuries. It was not until the establishment of general anesthesia and antisepsis at the end of the 19th century that Karl Langenbuch was able to perform the first liver surgery in 1888. At the same time, the scientific basis for liver regeneration and hemostasis in the liver were explored during this period.

Between 1899 and 1914 there was a scientist, the Viennese surgeon Emerich Ullmann, who advanced transplantation research relatively unnoticed and who in retrospect has to be called the father of organ transplantation. However, the foundation stone for modern liver surgery was laid by the great Parisian school around Jacques Hepp in the 1950s. In 1954, one of his colleagues, Claude Couinaud, published the standard work on liver anatomy. He described the complex, internal division of the liver into eight segments, which were determined by the location of the hepatic veins and by the location of the bile ducts.

In the meantime, transplantation immunology had also made great progress, so that in 1967, despite inadequate immunosuppression, the first successful liver transplantation of a patient by Tom Starzl could be carried out. The scientific struggle for potent immunosuppressants continued until 1972, when a substance (cyclosporine) was obtained by chance from a soil fungus, which was able to reliably suppress the rejection reaction of an organ in the body and then caused the survival rate of transplanted patients to skyrocket.

Usually, hepatic hemangioma does not cause any physical symptoms. Only in the case of giant hemangiomas do patients report general, non-specific symptoms such as a feeling of pressure or swelling in the upper abdomen. Sometimes the hemangiomas themselves are palpable, but most often the enlarged liver is palpable through the abdominal wall. In slender individuals, smaller hemangiomas are sufficient for patients to notice.

Symptoms include non-specific upper abdominal pain and a feeling of fullness or discomfort, especially in the upper abdomen. These symptoms can be explained by imagining that the tumor is pressing on the stomach from the liver, for example, and constricting it. In the case of a giant hemangioma, there is a risk of thrombus formation (blood clots) in the tissue of the hemangioma; rupture (rupture) may also rarely occur after an accident involving direct force to the liver. However, spontaneous rupture of hemangiomas is very rare.

The indication for therapy depends on whether there are actual symptoms, or rapid growth, on the part of the hemangioma. It must be carefully clarified whether diffuse upper abdominal pain does not have another cause. Therapy may only be initiated if there are proven problems.

There are several non-surgical options, but they have little prospect of lasting success and their use is controversially discussed:

• Angiography (vascular imaging) and embolization (occlusion) of the arteries supplying the hemangioma. In the case of larger hemangiomas, the hepatic artery that leads to the hemangioma can be ligated or occluded radiologically (through the vessels). Although this therapy should result in decreased blood supply to the hemangioma, it is often unsuccessful because further growth of the hemangioma is possible via collateral arteries. New vessels are formed very quickly.
• Local irradiation of the hemangioma does lead to a temporary reduction in the size of the tumor and can thus reduce the symptoms. However, radiation is not a definitive therapy since a hemangioma can grow again and cause symptoms again.
• The administration of medication (cortisone, interferon α2a) is often discussed, but is not an effective therapy. The long-term side effects and the low efficacy of the drugs actually prohibit such a treatment.

If there is an indication for surgical intervention, two fundamentally different procedures are known:

• The so-called “enucleation”, the peeling out of the hemangioma including the capsule without liver tissue. The normal partial liver resection and thus the removal of the hemangioma and parts of the liver.

  This enucleation (Fig. 6) (synonym peeling) is possible in most cases because there is a normally good boundary between the hemangiomatous tissue and the normal liver tissue. Removal in this boundary layer is often performed with an ultrasound dissector and is possible with virtually no blood loss. Vessels and structures that draw from normal liver tissue to the hemangioma must be found, accurately visualized, and securely ligated.

• Often it is also necessary to stop additional, aberrant vessels far outside of a hemanigoma to prevent major bleeding. It is clear that tissue composed mainly of blood-filled cavities has the potential to bleed profusely. Therefore, it may often be necessary to embolize a hemangioma prior to major surgery, i.e., to occlude the vessels supplying blood to the hemangioma by radiological intervention from the external. This can reduce the great risk of bleeding during the operation.

In the intensive care unit, as well as in the normal ward, adequate pain medication is considered, which is adjusted every day. A moderate physiotherapy supports the healing process and prevents the development of pneumonia. Liver function is checked regularly by taking blood samples.

After 10 to 14 days it is possible to go to rehabilitation to restore the old constitution. Follow-up ultrasound examinations should be performed several times until the second month after the surgery.