Diagnosis and treatment of liver cancer in the Department of Pediatric Oncology at Ichilov Medical Center in Tel Aviv. Liver tumors in children - Alternative methods of cancer treatment Chemotherapy and other methods

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In children, two types of primary liver tumors are distinguished: hepatoblastoma and hepatocellular carcinoma (hepatoma).
Epidemiology. Hepatoblastoma occurs more frequently and exclusively in children under 3 years of age. The ratio of sick boys and girls is 1.5:1. Two age peaks are typical for hepatocellular carcinoma: 4 years and 12-15 years. The ratio of sick boys and girls is 1.3:1.
Birth defects associated with malignant liver tumors are similar to those in patients with Wilms tumor and adrenal tumors. These include congenital hemihypertrophy and widespread hemangiomas. Tumors of the liver and Wilms may occur in the same patient, reflecting identical mechanisms predisposing to their development. Hepatoblastoma and hepatocellular carcinoma occur in siblings.
The frequency of liver carcinoma in combination with cirrhosis is much less in children than in adults. On the other hand, cirrhosis with malnutrition and secondary biliary cirrhosis due to biliary atresia or giant cell hepatitis are associated with an increased risk of primary liver malignancy. In addition, it develops in children with Fanconi anemia treated with androgens. Patients with chronic hereditary tyrosinemia who survive to 2 years of age have an approximately 40% risk of developing liver carcinoma.

Pathology. Hepatoblastoma may consist entirely of epithelial type cells. Sometimes mesenchymal components are mixed with them. There may be structures that are similar in structure to the glands. Individual cells are undifferentiated. In mixed tumors, mesenchymal components or areas of primitive osteoid tissue can be found. Hepatocellular carcinoma consists of highly differentiated large polygonal cells with eosinophilically stained cytoplasm. Cells form structures in the form of beams, surrounded by sinusoidal vessels. With both types of tumors, foci of extracerebral hematopoiesis are found.
Usually the right lobe of the liver is involved in the process. However, in about half of patients, it spreads to both lobes or the tumor is multicentric. The most common site of metastases is the lungs. Characterized by the spread of the tumor along the length in the abdominal cavity. Less often, metastases can be localized in the central nervous system.
Clinical manifestations. Most often, the patient develops a foreign formation in the upper abdominal cavity with an increase in its volume. At the time of diagnosis, pain worries only 15-20% of patients; the frequency of anorexia and weight loss is the same. More rarely, patients complain of vomiting and jaundice. In boys, virilization sometimes occurs due to the production of gonadotropin by the tumor.
Diagnosis. The main problem is to determine the cause of the liver enlargement (primary tumor or other benign or malignant disease). A careful search should be made for another site of localization of the primary tumor, most often neuroblastoma. Enlargement of the liver can cause infantile hemangioendothelioma and cavernous hemangioma, and therefore steps should be taken to identify other hemangiomas. Accumulation diseases can also simulate a liver tumor.
The results of liver function tests usually do not differ from the norm. Approximately 20% of patients may have elevated levels of bilirubin and transaminases. Most patients have elevated serum alpha-fetoprotein levels.
On the radiograph of the abdominal organs, one can see an increase in the liver, in about 30% of patients there are foci of calcification in the tumor. In almost 10% of patients, lung metastases are determined already at the time of diagnosis, so it is necessary to perform computed tomography of the abdominal and chest cavities for the primary identification of the stage of the disease. The practical value of angiography is to detect the source of blood supply to the tumor, which determines the possibility of its excision. Liver regeneration occurs within 4-6 weeks. after him. Around the same time, it is necessary to perform the initial tomography and liver scan. The tumor is relatively radioresistant. Various chemotherapy drugs cause a temporary effect in metastases, but treatment regimens have not been developed.
Forecast. For liver tumors, the prognosis is unfavorable. Overall, the survival rate for hepatoblastoma is 35%, while that for hepatocellular carcinoma is only 13%. Survive only patients who managed to completely excise the tumor. Incomplete excision is always accompanied by local recurrence and ends with the death of the patient.

Pediatric oncology in Israel is a separate, constantly developing and generously funded area of ​​medicine. Thanks to the introduction of modern methods and technologies into practice, the effectiveness of treating liver cancer in children has increased to 70% or more. The principles of pediatric oncology treatment used in the Ichilov Medical Center are the same as for adults, but especially sparing methods are applied to young patients in Israel, which are aimed at a complete cure, speedy recovery and return of the child to a normal life for his age.

Causes of liver cancer in children

To date, reliable causes of liver cancer in children have not been established. It is assumed that a neoplasm in the structures of the liver occurs as a result of abnormal growth and division of immature embryonic cells. The pathological process is triggered by genetic mutations that are inherited from parents to the child.

Symptoms of liver cancer

Normally, the lower border of the liver does not go beyond the edge of the costal arch and is not palpable on palpation. In cancer, the liver is significantly enlarged in size, has an uneven, bumpy surface, and in some cases the neoplasm itself is even palpated.

In the initial stages, the disease proceeds without clear clinical manifestations, only the growing weakness worries the patient. The appearance of abdominal pain, loss of appetite, vomiting, weight loss, persistent fever indicate the progression of the disease.

Icteric syndrome is fixed in 4-5% of patients. In 10% of cases (in boys), very early puberty is observed.

Quite often, tumor ruptures occur with subsequent internal bleeding, accompanied by an appropriate clinic: anemia, pallor of the skin, nausea, vomiting, dizziness, and severe pain in the epigastric region.

Diagnosis of liver cancer in children in Israel

Liver cancer is very often detected only in the later stages due to the asymptomatic course of the disease at the very beginning. To diagnose the disease in Israel, complex laboratory tests and modern instrumental studies are used.

• General and biochemical blood tests;
• Ultrasound procedure;
• CT scan;
• Magnetic resonance imaging;
• radioisotope scanning.

These methods allow doctors to determine the presence, stage, and extent of the disease.

To make an accurate diagnosis, a biopsy is performed - the collection of pathological tissue for subsequent histological analysis.

One of the main diagnostic methods in Israel is a blood test for the content of tumor markers, in particular, alpha protein. Its presence in the blood reliably confirms the presence of liver cancer, since normally a child should not have this protein.

In addition, Israeli doctors carefully study the patient's medical history and hereditary history.

Treatment of liver cancer in children in Israel

In the Ichilov Medical Center, the treatment of liver cancer in children is carried out according to individually compiled programs. When developing a treatment plan, the age and general condition of the patient, the size, location and spread of the cancer, the presence of metastases and possible complications are taken into account.

The main treatment is surgical removal of the tumor . As far as possible, the operation is performed in a minimally invasive way, but sometimes an open intervention (lobectomy) is required. Surgical removal of a cancerous focus along with a part of the liver significantly increases the chances of a small patient to recover. At the same time (during the operation), cancerous tissue is taken for express histological analysis. Focusing on the results obtained, the surgeon-oncologist instantly reacts and decides on further treatment tactics. All medical manipulations are performed under the control of ultrasound and computed tomography.

Often, for successful treatment, the surgical method is supplemented chemotherapy before and/or after surgery. Pharmaceuticals that are given to children have a minimum of side effects, while they have a powerful anti-cancer effect. The dosage is selected strictly individually. During treatment, an alpha protein test is regularly performed, the level of which informs specialists about the effectiveness of the therapy. With inoperable tumors, long-term chemotherapy is indicated, as a result of which the size of the neoplasm decreases several times. Upon completion of the course, an operation is possible.

An alternative treatment for liver cancer in children in Israel is radiofrequency ablation . In terms of effectiveness, this low-traumatic technique is not inferior to surgical treatment and can be performed even in cases of re-emerging cancer (with relapses and metastases). The technology consists in the destruction of a malignant neoplasm with high-frequency currents that enter the affected area through a special sensor. Surrounding healthy tissues remain intact. The procedure does not require immersion of a small patient in a deep narcotic sleep, therefore in Israel it is considered safer and more gentle for the child's body.

Also in Israel, cryotherapy, ablation with ethyl alcohol, exposure to microwave waves, chemoembolization, etc. are very successfully used in the treatment of liver cancer in children. Radiotherapy in pediatric oncology is used very rarely (to avoid possible long-term effects on the child's body).

Specialists in Israel are constantly involved in the development and research of new ways to treat liver cancer in children. Many of the modern and fairly effective techniques are successfully applied in practice today. So, for example, some drugs (Arglabin, Nexavar) interfere with the nutrition of a malignant formation, disrupting the functional activity of the blood supply vessels. As a result, cancer cells die and are rejected. This treatment method in modern medicine is called targeted therapy and is innovative in the treatment of cancer.

Israel is a country where all the advanced achievements of modern pediatric oncology are concentrated, and where doctors successfully apply the opportunities given to them in practice, helping sick children from all over the world to recover from cancer. Thanks to the "superpowers" of Israeli oncologists, many little patients have found hope for salvation and the joy of a long life in good health.

Liver cancer is a disease that manifests itself too late. But there is always a chance for recovery. Don't miss it! You can get a free consultation from a specialist right now: for this, you need to fill out the attached form (all fields!), send a request to the contact center and wait for a call from honey. consultant. The call will go to the phone number specified in the application, so make sure that the numbers entered are correct.

Hepatoblastoma is considered a malignant pathology of infants and young children: the disease mainly develops before 3 years of age, half of the cases occur in the first year of life. This type accounts for 1% of the total number of neoplasms in childhood.

Hepatocarcinoma is a disease of children of all ages. It accounts for 1.5% of cases and is predominantly found in boys.

Causes

The exact cause of the development of tumors has not yet been established. It is assumed that certain factors may contribute to this:

• hereditary burden for neoplasms;
• intrauterine gene mutations;
• intrauterine action of the oncogene;
• developmental defects.

The development of hepatoblastoma in childhood can provoke any other neoplasm (nephroblastoma, intestinal polyposis), hepatitis B, helminthic invasion, hereditary anomalies: hemihypertrophy (asymmetry of the face and body), tyrosinemia (damage to the pancreas, liver, kidneys).

The reason for the appearance of a tumor in a child may be a long-term use by the mother in the past of hormonal oral contraceptives, alcohol and drug abuse.

Symptoms

In the initial period, the tumor does not manifest itself in any way. There are no objective symptoms, the child does not experience discomfort, does not complain. Gradually join the loss of appetite, weight loss, dyspepsia, malaise.

When the tumor grows and enters the progressive or metastatic stage, the symptoms become advanced:

On examination, a protrusion of the abdominal walls is found in the child; on palpation in the right hypochondrium, a painful induration is determined.

With the progression of the tumor process, jaundice joins, the liver increases and reaches a large size, its borders come out of the hypochondrium. Development of ascites (accumulation of fluid in the abdominal cavity) and edema in the lower extremities is possible.

With a rupture of the tumor and bleeding, the symptoms of an acute abdomen: dagger pain in the abdominal cavity, tension in the abdominal muscles, hectic fever.

Kinds

Among oncological neoplasms in children, there are two main types, which we will discuss below.

Hepatoblastoma

Refers to malignant, poorly differentiated tumors of embryonic origin. It develops from stem cell structures even in the prenatal period and is diagnosed in infants and children under 5 years of age, regardless of gender.

Hepatoblastoma is a lobular, nodular formation with areas of necrosis and hemorrhages, without its own capsule, capable of infiltration (germination) into the liver tissues.

According to the histological structure, liver cancer in children is an embryonic liver cells with immature hepatocytes that are incapable of the normal functioning of the organ.

Metastasizes by hematogenous route to bone, lung, brain tissues and into the abdominal cavity.

This type of tumor is also known as hepatocarcinoma or hepatocellular carcinoma.

It has three features:

• high rate of invasion and metastasis;
• multicentricity (not one, but several nodular formations grow into neighboring organs);
• polymorphism (combines blastematous and carcinomatous zones).

According to the histological structure, hepacancinoma is large hepatocytes, with an accumulation of large and rounded nuclei and enlarged mitochondria. According to macroscopic features, hepatoblastoma and hepatoma are no different: large size, no clear demarcation from healthy tissues, with signs of necrotic changes.

stages

A malignant process in liver cells is classified according to the "TNM staging" system, which was developed and introduced by the Association for Cancer Research. In addition to the degree of cancer (I, II, III, IV), the system also describes the number and diameter of neoplasms (T), spread to the nearest organs and lymph nodes (N), the level of metastasis to nearby organs M.

First

At the initial stage of development, the oncological focus is small, its growth is limited to one hepatic lobe or affects no more than 25% of the organ, and does not extend to nearby blood vessels. The work of the liver and bile ducts is not disturbed.

There are no symptoms at this stage. In addition to slight weakness, fatigue, slight soreness in the liver area of ​​​​the child, nothing bothers. At this stage, the tumor can be detected by chance, during examinations for other pathologies.

If a tumor is diagnosed at this stage, the treatment is carried out correctly and in a timely manner, the prognosis for a complete recovery is about 90%.

TNM staging designation: T1 N0 M0.

Second

At this stage, the oncological focus passes into the adjacent hepatic lobe, metastases form in the affected areas. The size of the focus can reach 5 cm. It can be either a single or multiple tumor. The pathological process includes blood vessels. The focus is located only within the organ, the lymph nodes are not affected.

In the second stage, characteristic symptoms appear in children:

• persistent lack of appetite;
• soreness in the abdomen after exercise and after eating;
• dyspepsia in the form of frequent nausea and vomiting;
• prostration;
• weight loss.

On palpation, it can be found that the liver is enlarged, compacted and its borders protrude under the costal arch.

TNM staging designation: T2 N0 M0.

Third

In the third stage, the tumor approaches the falciform ligament, which is located on the convex surface of the liver and borders the diaphragm. The gates of the organ are affected by single metastases.

The third degree of cancer is staged at the subdegree:

1. III A: T3a N0 M0 - one or more focus, diameter does not exceed 50 mm with germination in the blood and lymphatic vessels.
2. III B: T3b N0 M0 - the focus is spread to another organ or there is germination in its venous system.
3. III C:T3 N0 M0 - the malignant process covers nearby organs, lymphatic vessels and nodes.

The symptoms of the third stage are pronounced. In addition to general exhaustion, persistent fever worries, there are signs of acute liver failure with jaundice, swelling of the lower half of the trunk and extremities, and spider veins on the skin.

Fourth

At this period, all organs, the lymphatic and circulatory systems are involved in the oncological process. Liver cancer in children of the IV degree spreads rapidly and uncontrollably.

Symptoms:

• extreme degree of exhaustion;
• bloated belly;
• skin of an earthy-yellow hue, dry, inelastic;
• extreme, severe swelling of the lower half of the body;
• Acute pain in the abdomen or without a clear localization.

The effectiveness and positive dynamics of therapy at this stage of the disease is almost impossible.

TNM staging designation: T (AB) N 1M1.

Diagnostics

If hepatoblastoma and hepatocarcinoma are suspected, general clinical blood and urine tests are indicated with a mandatory study of urobilin, bilirubin and fetoprotein levels.

Further diagnostic procedures are prescribed:

1. To obtain an accurate image of the focus, its structure and size, to assess the condition of the surrounding tissues and blood vessels, an echographic, nuclear magnetic resonance study is prescribed.
2. A slice on a computed tomography study. The procedure gives a detailed picture of the pathological area and removes it from different angles.
3. Biopsy. A small fragment of the organ is taken for further histological examination under a microscope.

If the whole complex of diagnostic procedures and studies has been carried out, the probability of making a correct diagnosis is 100%.

Treatment

Without adequate and timely complex therapy, children with hepatoblastoma and malignant hepatoma are at risk of death.

The only correct and effective vector of therapy is surgical removal (resection) or partial hepatectomy.

According to the indications, a course of chemotherapy may be prescribed before the operation in order to stop and reduce the size of the tumor.

Surgical intervention is performed extensively, with total removal of the lobe, ligation of blood vessels, bile ducts, taking into account possible anomalies of the arteries and veins. Radical surgical excision of the tumor and an adequately selected subsequent course of chemotherapy gives a high degree of survival of small patients. Advanced, inoperable cases in oncology are treated symptomatically and with a course of chemotherapy.

Medical treatment

Medicines are used only for symptomatic and supportive treatment. The list of drugs includes detoxification agents, non-narcotic and narcotic analgesics, drugs to increase hemoglobin levels, hepatoprotectors.

Against the background of the underlying disease, the child is prone to infections, so he is prescribed immunostimulating drugs, vitamin complexes.

If the tumor is diagnosed at a late stage and is considered inoperable, a long course of antibacterial drugs is prescribed in combination with cytostatics.

Chemotherapy

Most malignant children are sensitive to the action of the latest generation of cytostatics, and this gives a good chance of survival. Chemotherapy is prescribed both before and after the operation. The goal of this treatment is to reduce the amount of surgery and destroy the remaining tumor cells in the liver.

The course of treatment is monotherapy or combinations with the use of drugs of the anthracycline group, antimetabolites, antibiotic antitumor agents, taxanes, alkylating agents.

Chemotherapy is indicated for all patients whose lymph nodes are affected. The type of neoplasm and its size do not matter.

Forecast

Whatever the type of tumor and its cause, radical removal gives recovery in 60% of cases. Surgery and a course of chemotherapy at the fourth stage give a prognosis for survival in only 20% of cases. In other words, the probability of a successful outcome largely depends not only on the correctness of the treatment course, but also on the timely diagnosis of tumor formations.

Most often, these tumors are asymptomatic and may be incidentally detected during ultrasound. However, infantile hemangioendothelioma can cause severe symptoms such as abdominal enlargement, hepatomegaly, severe arteriovenous shunting and heart failure, hemodynamic anemia, thrombocytopenia and severe coagulopathy (Casabach-Merritt syndrome), tumor rupture with intra-abdominal bleeding and respiratory distress. Rarely, biliary obstruction with jaundice occurs. Histologically, these tumors are built from strands of normal, albeit immature, hepatocytes separated by vascular spaces lined by a single layer of high endothelium. The size of these vascular spaces determines whether the tumor is classified as a hemangioendothelioma or a cavernous hemangioma. Increased mitotic activity in these tumors, as a rule, is not observed. Hemangioendothelioma may have an alternative histological pattern: more pleomorphic endothelial cells forming papillary structures in places. Such tumors tend to transform into malignant angiosarcoma. Vascular neonatal liver tumors often undergo spontaneous regression.

Mesenchymal hamartoma is a benign tumor of the liver of mesenchymal origin, occurring in fetuses and newborns. In the world literature, there is still no consensus on the nature of mesenchymal hamartoma: is it a tumor or a malformation. Microscopically, the tumor is a multicavitary cyst lined by the endothelium or epithelium of the bile ducts, surrounded by fibrous or myxoid tissue containing the bile ducts and multiple vessels, in particular the branches of the portal vein. There is often a thin fibrous capsule, but there may also be extension into the adjacent compressed or sclerotic hepatic parenchyma. Mesenchymal hamartoma behaves like a benign tumor and rarely recurs after resection, may spontaneously regress or transform into an undifferentiated sarcoma.

Hepatoblastoma is the most common liver tumor in early childhood, but neonatal tumors account for less than 10%. Hepatoblastoma is a malignant tumor of the liver. Histologically, the tumor is represented by malignant epithelial hepatic tissue of varying degrees of differentiation, most often with embryonic or fetal components. Sometimes the tumor contains malignant mesenchymal tissue with immature areas of fibrosis, spindle cells, cartilage-like osteoid.

Such tumors are called mixed hepatoblastomas. The occurrence of hepatoblastoma is associated with genetic anomalies and malformations, namely Wiedemann-Beckwith syndrome, trisomy 18, alcoholic fetopathy, and familial adenomatous polyposis. In newborns, in comparison with older age groups, a rather differentiated fetal component prevails in tumors. Neonatal hepatoblastomas are characterized by earlier systemic metastasis, and due to fetal circulation, the tumor rarely metastasizes to the lungs. In utero, hepatoblastoma can cause polyhydroamnion and stillbirth. A rupture of the tumor during childbirth is possible, which will lead to massive bleeding. Neonatal hepatoblastomas do not produce large amounts of α-fetoprotein, unlike hepatoblastomas in older children.

Liver cancer in children is a disease in which malignant (cancer) cells form in the tissues of the liver.

The liver is one of the largest organs in our body. It consists of four lobes, and is located in the upper right part of the abdominal cavity under the rib. The liver performs many important functions, these include:

Purification of the blood from harmful substances with their subsequent excretion with feces or urine.

Production of bile for the digestion of fats.

Accumulation of glycogen (sugar), which the body uses for energy.

There are two main types of liver cancer in children:

Hepatoblastoma: This is a type of liver cancer that usually does not spread to other organs. This disease usually affects children under 3 years of age.

Malignant hepatoma: This is a type of liver cancer that often spreads to other organs. This disease affects children of all ages.

This article discusses the treatment of primary liver cancer (starting in the liver). Treatment of metastatic liver cancer that originates elsewhere and has spread to the liver is not considered. Primary liver cancer occurs in both adults and children. However, the treatment of children is different from that of adults.

Certain diseases and disorders increase the risk of developing liver cancer in children.

What increases the chance of developing a disease is called a risk factor. Having a risk factor doesn't mean you'll get cancer, but not having a risk factor doesn't mean you won't get cancer. People who believe they are at risk for a disease should discuss this with their doctor. Risk factors for hepatoblastoma include:

Familial adenomatous polyposis (FAP).

Syndrome of visceromegaly, omphalocele and macroglossia.

Very low birth weight.

Risk factors for malignant hepatoma include:

Belonging to the male sex.

Hepatitis B or C. The greatest risk is when the virus is transmitted from mother to child at birth.

Liver damage due to certain diseases, such as biliary cirrhosis or tyrosinosis.

Possible signs of liver cancer in children include swelling or pain in the abdomen.

More often, symptoms appear after the tumor increases in size. The same symptoms can be caused by other diseases. You should consult a doctor if the following symptoms are observed:

Painless swelling in the abdomen.

Swelling or pain in the abdomen.

Weight loss for no apparent reason.

Loss of appetite.

Early puberty in boys.

Nausea and vomiting.

To detect and diagnose liver cancer in children, a liver and blood test is performed.

The following examinations and procedures are used:

Review and history taking. The examination is performed to determine the general state of health, including checking for signs of illness, such as swelling or other signs that seem unusual. The patient is asked about lifestyle, past illnesses and their treatment.

Blood test for tumor markers. The procedure consists in examining a blood sample in order to determine the amount of certain substances released into the blood by organs, tissues and cancer cells of the body. If elevated levels of certain substances are detected in the blood, this is due to the presence of a specific type of cancer. These substances are called tumor markers. Children who have liver cancer may have elevated amounts of a protein known as alpha-fetoprotein (AFP) or a hormone known as the beta subunit of human chorionic genadotropin (beta-hCG) in the blood of children who have liver cancer. Other cancers and some non-cancer diseases, including cirrhosis and hepatitis, can also cause an increase in AFP levels.

Clinical blood test. During this procedure, a blood sample is examined for:

The number of red blood cells, white blood cells and platelets.

The portion of the total blood volume that is made up of red blood cells.

liver tests. The procedure consists in examining a blood sample to determine the amount of certain substances secreted by the liver into the blood. Exceeding the norm can be a sign of liver cancer.

Ultrasound procedure. During this procedure, high-frequency sound waves (ultrasound) bounce off internal tissues and organs, creating an echo. The echo produces an image of tissue called a sonogram. This image can be printed so that you can study it later.

CT slice: This procedure produces a series of detailed images of areas within the body taken from different angles. The images are taken by a computer connected to an x-ray machine. Sometimes the patient is injected into a vein or allowed to swallow a dye so that the organs and tissues can be seen more clearly. This procedure is also called computed tomography, computerized tomography, or axial computed tomography. For liver cancer in children, a CT scan of the chest and abdomen is usually done.

Magnetic resonance imaging (MRI). This procedure is based on the use of a magnetic field, radio waves and a computer to obtain a series of detailed images of the internal organs. This procedure is also called nuclear magnetic resonance imaging (MRI).

Biopsy. This is a collection of cells and tissues that are examined under a microscope for signs of cancer. A tissue sample is obtained during an operation to remove or examine a tumor. A pathologist examines a tissue sample under a microscope to determine the type of liver cancer.

The prognosis (chance for recovery) and the choice of treatment method depends on the following factors:

The stage of the cancer (the size of the tumor, whether the liver is partially or completely affected, whether the cancer has spread to other organs, such as the lungs).

Is it possible to completely remove a cancerous tumor with surgery.

A type of liver cancer (hepatoblastoma or malignant hepatoma).

Is the cancer diagnosed for the first time or is it a recurrence of the disease.

The prognosis may also depend on:

Features of cancer cells (how they look under a microscope).

Does the level of AFP in the blood decrease after the start of chemotherapy.

Liver cancer in children can be cured if the tumor is small and can be completely removed with surgery. Complete removal of the tumor is more often possible in the case of hepatoblastoma than in the case of malignant hepatoma.