Liver cancer

Liver cancer, according to WHO, is among the ten most common malignant tumors in the world.

In Russia, liver cancer is relatively rare and accounts for 3 - 5% of all malignant neoplasms, which roughly corresponds to this indicator for Europe and America. The standardized incidence rate in Russia was 4.9 cases per 100 thousand people. Morbidity tends to decrease. Thus, the decrease in the standardized indicator over 10 years was 14.6%, while in some countries liver cancer occupies a leading position in the structure of oncological diseases. For example, in South-East Asia, its share is 40%, and in the countries of southern Africa - more than 50% in the structure of all cancer.

In Russia, the highest incidence rate was registered in Tobolsk and Vladivostok. The highest incidence of liver cancer was registered in the Republic of Sakha (Yakutia) - 11 cases per 100 thousand people.

The peak incidence falls on the age of 50 - 60 years. Men suffer from this pathology 3 times more often than women.

[1], [2], [3]

Causes of liver cancer

Among the risk factors contributing to the development of a disease such as primary liver cancer, there are four groups:

• factors related to nutrition;
• helminthic invasions;
• infectious disease;
• cirrhosis.

In addition, trauma, biliary tract disease, hemochromatosis, hereditary predisposition may be important.

[4], [5], [6], [7], [8], [9]

Factors related to nutrition

One of the important etiological factors is the kwashiorkor. In the literature, this disease has several names: child pellagra, malignant malnutrition, fatty degeneration. Kwashiorkor is usually observed in children and in early adolescence, if the food ration contains an insufficient number of proteins with a predominance of carbohydrates. There comes fat and protein dystrophy, atrophy of the hepatic tissue, in later stages - necrosis.

Alcoholic drinks with constant use can contribute to the development of the disease.

In recent years, a large number of studies have appeared that indicate the role of aflatoxin in the development of a malignant tumor. Aflatoxin is a metabolite of the ubiquitous saprophytic fungus Aspergellus flavus. Aflatoxin enters the human body with food damaged by the fungus-saprophyte, which produces this toxin. Studies have shown a high content of aflatoxin in dry oysters, soybeans, peanuts, etc.

[10], [11], [12], [13], [14], [15]

Glistular invasion

Most often, the development of a malignant tumor is facilitated by the parasitizing worms Opistorhus felineus, Schistosomiasis, Clonorchis sinensis and others in the human body.

Onistorhoz is distributed in the river basins of the Dnieper, Kama, Volga, Don, Northern Dvina, Pechora, Neva and Siberia - Ob, Irtysh, as well as in the Korean peninsula, Japan and China. Infected with this helminth when used thermally untreated, raw thawed or frozen fish.

Schistosomiasis is observed in Egypt, Equatorial Africa, as well as in Brazil, some places in the PRC, Venezuela, Japan.

Clonorhosis affects, in addition to the hepatobiliary system, and the pancreas. The parasite is distributed in China, the countries of the Korean peninsula, Japan and the Far East.

Of the other helminthic lesions, mention should be made of echinococcosis.

Infectious lesions

The risk of a malignant tumor is increased by such diseases as viral hepatitis, malaria, syphilis.

Symptoms of liver cancer

Numerous variants of the clinical course are summarized in three main forms.

Hepatomegalic, "tumor" form, which is based on nodular, less often - massive cancer. This variant is relatively often recognized in vivo by hepatomegaly and especially by palpable tumor nodes and is accompanied by pain in the hypochondrium, jaundice, rapidly growing nodes deforming the dome of the diaphragm. Splenomegaly, signs of portal hypertension, ascites are rare.

Cirrhotic form with the prevalence of the clinic of cirrhosis, against which the cancer remains unrecognized. By frequency, this form is on the second place and by analogy with cirrhosis is divided into two variants downstream.

The form of chronic perennial cirrhosis with the appearance of clinical symptoms of cancer in the late stage of the disease. The cancer thus has an acute course and is not manifested by hepatomegaly, but rather associated with complications.

The form of acute cirrhosis without a cirrhotic anamnesis is characterized by an acute onset and rapid course of the disease, the presence of edematous-ascitic syndrome, a diminished or slightly enlarged liver, dyspeptic disorders, mild jaundice, fever. All this creates a clinical picture similar to the edematous ascitic variant of epidemic hepatitis or subacute cirrhosis. In these cases, liver cancer can be indicated by symptoms that are not characteristic of cirrhosis in its pure form: persistent pain in the right hypochondrium and thoracic cavity, rapidly increasing cachexia, hemorrhagic character of ascites, deformation of the diaphragm dome, radiologically established lung metastases persistently recurring pleural effusion.

The latent, or masked, form has a number of variants of flow.

• The most acute, perforating, acute hemoperitonsal form, which is more common in cirrhosis-cancer-hepatoma and is caused by a sudden rupture of the cancer node with subsequent hemorrhage into the abdominal cavity with the phenomena of irritation of the peritoneum and anemia.
• Form with the predominance of more rare symptoms:
  • Feverish form, resembling a hepatic abscess;
  • cardiovascular form with edema of the lower limbs, heart failure, portal stasis;
  • cerebral, pulmonary, cardiac and other forms with the prevalence of the corresponding metastases that simulate encephalomyelitis, lung cancer, etc .;
  • mechanical jaundice;
  • endocrine masks.

Stages of liver cancer

Histological classification

1. Hepatocellular carcinoma (hepatocellular carcinoma).
2. Cholangiocarcinoma (cancer of the intrahepatic bile ducts).
3. Cystadenocarcinoma of the bile ducts.
4. Mixed hepatocholangiocellular cancer.
5. Hepatoblastoma.
6. Undifferentiated cancer.

Stages of cancer of the liver by TNM (IUCN, 2003)

This classification is applicable only for primary hepatocellular cancer and cholangiocarcinoma.

• T - primary tumor:
• Tx - insufficient data to estimate the primary tumor;
• T0 - primary tumor is not detected;
• T1 - solitary tumor without vascular invasion;
• T2 - solitary tumor with vascular invasion or multiple tumors less than 5 cm in the largest dimension;
• T3 - multiple tumors more than 5 cm or a tumor involving a large branch of the portal or hepatic vein;
• T4 - a tumor with a direct spread to the adjacent organs (not the gallbladder) or with the perforation of the visceral peritoneum. N - regional metastases
• Nx - insufficient data for assessment of regional lymph nodes;
• N0 - there are no signs of metastatic involvement of regional lymph nodes;
• N1 - there are metastases in the regional lymph nodes. M - distant metastases:
• Mx - insufficient data for the definition of distant metastases;
• M0 - no signs of distant metastases;
• M1 - there are distant metastases.

Grouping by stages:

• Stage I - T1 N0 M0
• Stage II - T2 N0 M0
• Stage III A-T3 N0 M0
• Stage III B - T4 N0 M0
• Stage II 1C - Any T N1 M0
• Stage IV - Any T Any NM

Macroscopic forms

Primary liver cancer is represented by three forms: nodular (nodular), massive, diffuse.

Nodular form

The organ usually contains two or more of the same size tumor nodes, located mainly in the right lobe. Around the main 2 - 3 nodes may be small, on the entire surface, metastatic nodules. Sometimes in the liver, several small, uniformly sized tumor nodes are scattered throughout the body.

Massive form

This form has two options: the first - one large node with metastases on the periphery; the second is a single tumor large node without metastases. The first option is more common. The main node is usually located in the right lobe of the liver or its portal, it has a rounded shape, sometimes with scalloped edges.

Diffuse form

This form is less common than the previous forms and in most cases occurs against a cirrhosis of the liver. Tumors of the same size as the remains of parenchyma preserved in cirrhosis, which presents significant difficulties for diagnosis without microscopic confirmation.

[16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]

Metastasis of liver cancer

The spread of the primary malignant tumor, like other tumors, occurs in two ways: lymphogenically and hematogenously. Conditionally metastases for liver cancer are divided into intra- and extrahepatic. Intrahepatic metastasis is more common. Extrahepatic cancer metastases are predominantly found in the lymph nodes of the gates and lungs. Sometimes there were metastases in the bone. Rarely - in the skin, testicle, penis, spleen.

Diagnosis of liver cancer

Diagnosis presents great difficulties.

Laboratory diagnosis consists in the detection of embryonic protein alpha-fetoprotein in the blood serum.

A positive reaction to alpha-fetoprotein is observed in 70-90% of patients with hepatocellular liver cancer. Of particular importance is the detection of alpha-fetoprotein in the prognosis of the disease - increasing the concentration of alpha-fetoprotein is a poor prognostic sign.

Clinical analysis of the blood of a patient with primary liver cancer is of low specificity: elevated ESR, neutrophilic leukocytosis, rarely - erythrocytosis.

Radioisotope scanning with I-131, Au-198 reveals "cold foci" corresponding to the localization of the tumor. The method is safe, the diagnostic efficiency is 98%.

Ultrasound allows visualization of the tumor focus, enlarged lymph nodes, ascites and metastatic hepatic damage. This method is harmless, does not require special preparation. At the same time focal formations with a diameter greater than 2 cm are found.

Computer tomography is one of the methods of topical diagnosis of neoplasms. The resolving power of this method is the visualization of formations from 5 mm or more. Computed tomography due to its high resolving power allows not only to identify focal lesions, but also to establish its character, to determine intraorganic localization, to obtain information about neighboring organs in which the primary lesion can be located if liver cancer is secondary.

The vascular nature of the tumor can be detected by means of emission computer tomography with the use of labeled erythrocytes.

Magnetic resonance imaging (MRI) is used to diagnose primary liver cancer. This study makes it possible to obtain an image of the organ in various sections, which increases the informative value of the method in determining the localization of the tumor and its intra- and extrahepatic spread.

Selective goals are a special research method, which allows to establish the exact location of the tumor. In the picture, the tumor appears as a hotbed of hypervascularization.

Morphological verification is performed by the method of fine needle puncture biopsy, which is performed under the supervision of ultrasound or laparoscopy. The most important in this regard is laparoscopy with tumor biopsy.

Diagnostic laparotomy is performed in complex diagnostic cases to verify the process and to determine the scope and scope of surgical intervention.

[28], [29], [30], [31]

Treatment of liver cancer

The main method of treating primary liver cancer is surgical. Despite the high regenerative capacity of the organ, the difficulties of resection are due to the need for careful hemostasis due to the rich blood supply of tissues. In this case, the principle of radicalism and ablastics must be observed: resection should be performed within healthy tissues.

To perform a resection at the modern level, a number of technical means are required that allow to determine the functional reserves of the organ, to clarify the prevalence of the tumor process and to reduce the risk of intra- and postoperative complications. Such means include:

• radioisotope study of hepatic function by means of the radiopharmaceutical Brom MESIDA;
• intraoperative ultrasound examination of the organ, allowing to clarify the prevalence of the tumor process and to determine the boundaries of the tumor node, necessary to address the question of the scope of surgical intervention;
• ultrasonic surgical aspirator, which makes it possible to destroy and remove the hepatic parenchyma, without affecting the tubular structures, which leads to a significant decrease in intraoperative blood loss, eliminates the need for the application of hemostatic sutures to the hepatic parenchyma. This decreases the zone of necrosis and ultimately reduces the traumatic nature of the operation;
• water jet scalpel for dissection of the parenchyma;
• Argon coagulator company «Valleylab» (USA), used to stop capillary bleeding from the resected surface of the organ;
• adhesive preparations "Tachokomb" and "Tissukol" to stop capillary bleeding and reduce the risk of formation of bile fistula.

Extensive resections are inappropriate to perform patients with hepatic cirrhosis, gross functional disorders from the kidneys and the heart.

Radiation therapy of primary liver cancer is not used.

Polychemotherapy is used for adjuvant purposes. The independent value in the treatment of primary liver cancer does not have this method.

It is very important to follow a diet for liver cancer.

Treatment of Metastatic Liver Cancer

Secondary liver cancer is observed 60 times more often than primary and is 90% among all malignant tumors.

By localization of metastatic cancer, the liver takes the first place among all organs. Metastasis to the liver occurs on the hepatic artery and portal vein. Most often, the liver metastasizes pancreatic cancer (50% of cases), colorectal cancer (from 20 to 50% of cases), stomach cancer (35% of cases), breast cancer (30%), esophageal cancer (25%).

The clinical picture of secondary liver cancer is due to the symptoms of the primary focus and the degree of lesion metastases of the hepatic parenchyma.

Diagnosis of cancer metastasis in the liver is not very difficult. In this case, use ultrasound, computed tomography, laparoscopy with biopsy.

Treatment is difficult. The presence of hepatic metastases is an indicator of inoculation of the tumor process. If there is a single marginal metastatic focus, it can be surgically removed.

Forecast

The prognosis for liver cancer is unfavorable. According to various data, the five-year survival rate after surgical treatment does not exceed 10-30%.

[32], [33], [34], [35], [36]