Removal of carcinoid at an early stage prognosis. Carcinoid syndrome - what is it, treatment and prognosis. The main treatments are

Heart failure without a significant increase in pressure, severe diarrhea, abdominal pain, red complexion are signs of the growth of a neuroendocrine tumor - carcinoid. The presence of such manifestations in the aggregate in a person makes it possible to suspect the development of a carcinoid syndrome. Neoplasms can be benign or malignant, they affect the small and large intestines, rectum, appendix, lungs, and other organs.

This type of tumor is special. It is able to independently produce hormones and supply them to the circulatory system, which causes the main signs of the pathological process.

A distinctive characteristic that the carcinoid syndrome possesses is a long latent period of development. Such a dangerous situation arises due to the unclear manifestation of symptoms at the onset of the disease, their similarity with the signs of a number of pathologies. Often, an already formed tumor is diagnosed, which has metastases, which significantly worsens the prognosis of the patient's recovery.

Causes of the carcinoid syndrome

Active production of hormones (serotonin, histamine, bradykinin, prostaglandins) by a formed carcinoid tumor provokes the appearance of signs of the syndrome of the same name. The results of the studies do not provide complete information about the causes of the development of the tumor process. A neoplasm can develop from a single altered cell and cause a syndrome. The presence of a carcinoid tumor in a person does not mean that a mandatory development of the syndrome awaits him.

Several common factors can cause the appearance of a tumor, and then the development of signs of carcinoid syndrome:

• the presence of endocrine neoplasia in close relatives;
• constant smoking, drinking alcohol;
• malnutrition;
• the presence of diseases of the stomach and intestines;
• hereditary neurofibromatosis;
• over 50 years of age, male.

Depending on the location of the neoplasm, the most likely causes of the pathological process are noted. They should be considered in more detail.

Carcinoma in the lungs

The main cause of lung cancer, carcinoma, is smoking. An active tobacco lover or people from his close circle who are forced to regularly inhale dangerous carcinogens along with smoke can get sick. Other provoking factors are infection with a viral infection, asbestos and dust particles entering the lungs, and exposure to radioactive radon.

Tumor of the small intestine

The tumor process in the small intestine is associated with several diseases:

• the presence of adenomatous polyps;
• ulcerative colitis (nonspecific);
• Crohn's disease;
• ulcerative processes in the duodenum;
• diverticulitis;
• enteritis;
• pathologies of the gallbladder, causing stagnation of bile and irritation of part of the small intestine.

Rectal carcinoid tumor

Colon carcinoma is caused by hereditary diseases in which gene mutations are observed - Lynch, Petz-Egers and Cowden syndromes, various polyposis. The risk of tumor formation increases in patients with colorectal adenomas, female pathologies - ovarian dysfunction, endometriosis, neoplasms in the mammary glands. Unfavorable environmental factors and malnutrition can provoke a cancerous process.

Colon tumors

The formation of neuroendocrine tumors in the large intestine is associated with the presence of gene mutations, lack of sufficient physical activity and bad habits. The pathological process is provoked by malnutrition, when animal fats, yeast, refined carbohydrates predominate in dishes.

Main features

Carcinoid syndrome is characterized by characteristic symptoms. The patient noticeably changes the condition of the skin. Visible areas - face, neck, shoulders - can suddenly change their color, become pronounced pink, red. After a few minutes, the natural skin tone returns.

The attack can occur several times a day, it is not accompanied by increased sweating, which allows it to be called "dry flush". In different patients, such a symptom can be very short-lived (of the first type), other people begin to look in a special way:

• their face acquires a stable pink tint, during an attack the nose may turn purple (second type);
• prolonged, for several hours or days, an attack of the third type is accompanied by the presence of pronounced wrinkles, tearing and redness of the eyes, there are signs of a decrease in blood pressure and severe diarrhea;
• persisting bright red spots on the neck, hands appear with flushes of the fourth type, pigmentation appears in the form of spots with uneven outlines.

The face of a person with carcinoid syndrome is shown in the photo. The symptom provokes the active production of histamine by the tumor.

With the development of the pathological process, a reaction of the organs of the digestive system is observed. A characteristic manifestation of carcinoid syndrome is diarrhea. It is accompanied by pain, patients describe them as strong, regular contractions. Feces have a special fatty consistency. The clinical picture of the abdominal syndrome is complemented by stable nausea and vomiting.

Changes in the functioning of the cardiovascular system are noticeable, they are associated with the effects of serotonin. The structure of the heart will change, its tissues are replaced by connective ones (the process often affects the right half of the organ), there is a narrowing of the internal ducts of the arteries, which complicates blood circulation. Such transformations are accompanied by symptoms - an increase in blood pressure (slight), heart pain, tachycardia.

An increase in the content of hormones in the blood leads to the appearance of another sign of carcinoid syndrome - bronchospasm. The clinical picture in this case is similar to bronchial asthma. There is an extreme difficulty in breathing, pain, wheezing and whistling in the lungs, lack of air, dizziness.

Research

Diagnosis is necessary to confirm the patient's carcinoid syndrome. The main indicators that the doctor pays attention to are characteristic external manifestations, an increase in the level of serotonin in a blood sample, a change in urine with an increase in the concentration of 5-hydroxyindoleacetic acid in it.

To confirm the development of the syndrome, several laboratory and instrumental research methods are used:

• blood test for the presence of hormones;
• Analysis of urine;
• MRI or CT procedures;
• taking an x-ray;
• ultrasound diagnostics;
• endoscopic and laparoscopic examination of the intestine;
• bronchial research;
• colonoscopy;
• gastroduodenoscopy;
• biopsy of tissues of the stomach, intestines, lung, heart.

An important diagnostic method for confirming the signs of carcinoid syndrome is differential diagnosis. The doctor must exclude the development of other diseases that have similar symptoms.

Modern methods of treatment

The main method of treatment after confirmation of carcinoid syndrome is a surgical operation to remove the tumor. To reduce the rate of development of the oncological process, the spread of metastases in the patient's body, chemotherapy and additional drug treatment are indicated to relieve or mitigate the main manifestations. A good therapeutic effect is seen when using traditional traditional medicine recipes.

Preparations

Medicines are prescribed to patients for the purpose of chemotherapy and symptomatic treatment. In the first case, injections of cytostatic drugs are used to suppress tumor growth, reduce its size, and prevent further spread of cancer cells in the patient's body. The course and treatment program are strictly individual, selected for a particular patient. To improve his general condition are shown:

• serotonin antagonists;
• antihistamines;
• antidiarrheal drugs;
• means for the regulation of hormonal balance.

Surgery

The main stage of treatment is the surgical removal of a carcinoid-type tumor. The surgeon directs additional actions to remove tissues with signs of metastasis, nearby lymph nodes. Patients require manipulation of the hepatic arteries - their ligation. It is used to relieve the patient of debilitating symptoms - diarrhea and regular hot flashes. After the operation, chemotherapy is indicated.

Folk remedies

Herbal medicine can alleviate the manifestations of carcinoid syndrome. Alternative methods of therapy have a goal similar to drug treatment - to reduce symptoms. The antihistamine and antidiarrheal properties of natural remedies are important. In the formulation of herbal infusions and decoctions prescribed by the doctor, there may be nettle, walnut, butterbur, wormwood, oak bark, St. John's wort.

History reference: 1868 - Lanhans first described a carcinoid tumor; 1907 - Oberndofer first used the term "carcinoid"; 1930 - Cassidy described a disease accompanied by watery diarrhea, heart failure, shortness of breath, redness of the skin of the face; 1931 - Scholte was the first to suggest a connection between a tumor of the small intestine and damage to the valves of the valves of the right half of the heart; 1949 - Rapport proposed a structural formula for serotonin; 1952 - Bjork, Aksen, Thorson first described the clinical manifestations of carcinoid syndrome in a boy who suffered from stenosis of the opening of the pulmonary valves, insufficiency of the tricuspid valve and unusual cyanosis; 1954 - Waldenstrem and Pernov discovered hyperserotoninemia in patients with metastatic carcinoid.; 1960 - Harris observed a persistent hypertensive response when serotonin was administered to a human.

Carcinoid syndrome- a disease caused by the circulation of mediators, which is manifested by redness of the skin (90%), diarrhea (75%), noisy breathing (20%), endocardial fibrosis (33%), damage to the valves of the right heart; sometimes there is pleural, peritoneal or retroperitoneal fibrosis.

The development of carcinoid syndrome is due to a hormonally active tumor originating from enterochromaffin (argentaffin) intestinal cells (Kulchitsky cells). At the same time, increasing intestinal disorders are accompanied by hypertensive syndrome (Gogin E.E., 1991).

Until 1953, each case of detection of carcinoid syndrome was considered as casuistic. However, since the description of the clinical picture of the disease, the incidence of carcinoid tumors has increased significantly. However, intravital diagnosis of carcinoid syndrome is quite rare. According to autopsy materials, carcinoids occur in 0.14–0.15% of cases.

Most often, carcinoid tumors are localized in the gastrointestinal tract, less often they occur in the bronchi, gall bladder, pancreas and ovaries. The sizes of tumors, as a rule, are not large and vary from 0.1 to 3 cm. The kacinoid cell is polygonal, has chromatin and a large number of randomly arranged granules. The connective tissue stroma of a carcinoid tumor contains a significant number of mast cells that have the ability to concentrate and possibly produce serotonin.

At the basis of pathogenesis carcinoid syndrome is the production of 5-hydroxytryptamine (serotonin, enteramine) by tumor cells, which causes hyperserotoninemia and an excess of other physiologically active substances. The classic symptoms of carcinoid syndrome with a significant increase in blood pressure develop only when the primary focus or tumor metastases are outside the hepatic barrier. In these cases, the serotonin formed by the tumor cells is not destroyed and enters the general circulation through the hepatic vein, causing various pathological conditions.

The vasoconstrictive action of serotonin was its first property to be known. Most researchers have found a hypertensive reaction when serotonin is administered to a person. However, there is a sufficient number of studies indicating that after giving serotonin, there is a decrease in blood pressure. The nature of the vascular response in response to serotonin is affected by the method of its administration. So, with intravenous administration, an increase in minute volume and blood pressure is observed, and with the introduction of serotonin intraperitoneally, a hypotensive reaction is noted. There is an opinion that the variability of blood pressure responses to serotonin is associated with the ability of the vascular bed to respond differently to this amine.

Close interactions are known to exist between serotonin and other biological amines. For example, it is considered proven that the development of vascular disorders in carcinoid syndrome is due to the interaction of serotonin and catecholamines (Menshikov VV et al., 1972). Cases of combination of carcinoid syndrome with acromegaly and hypercortisolism are described. It is possible that this combination is due to the ability of carcinoid tumor cells to produce GH- and ACTH-like substances.

Under the influence of high concentrations of serotonin fibrosis of the endothelial tissue develops, smooth muscle contraction occurs, which causes narrowing of the arteries. The defeat of the cardiovascular system due to hyperserotoninemia in carcinoid syndrome is reduced to the development of tricuspid valve insufficiency and pulmonary artery stenosis, as well as fibrosis of the endocardium of the right atrium and right ventricle. Narrowing of the arterioles leads to the development of arterial hypertension.

Carcinoid tumors are classified as arising from anterior intestinal tube(bronchi, stomach, duodenum, bile ducts, pancreas), middle part of intestinal tube(jejunum and ileum, appendix, ascending colon) back of intestinal tube(transverse colon, descending, sigmoid and rectum). Sometimes they are also found in the gonads, prostate, kidneys, mammary glands, thymus, or skin.

For the clinical picture Carcinoid syndrome is characterized by the presence of vasomotor disorders of the type of "tides". At the same time, certain areas of the skin become red, sometimes cyanotic, the patient feels heat in these places. In addition to violations of vascular tone and heart damage, there is a pronounced abdominal syndrome, which is manifested by the presence of diarrhea, pain along the intestines. The influence of serotonin on the smooth muscles of the bronchi can lead to a sharp narrowing of the latter and the development of asthmatic attacks. As a rule, the course of the disease is paroxysmal. The duration of the attacks varies considerably - from 30 seconds to 10 minutes, and in some cases the attacks can be repeated several times during the day. Their occurrence is most often provoked in connection with nervous or physical stress, alcohol intake. A number of symptoms, such as cyanosis, telangiectasia, oliguria, and heart damage, persist for a long time and determine the condition of patients in the interictal period.

The most characteristic changes in the blood picture with carcinoid syndrome, there is an acceleration of ESR and leukocytosis, and a direct relationship is determined between changes in the blood and the occurrence of crises. Carcinoids, especially bronchial ones, can secrete ACTH, which causes Cushing's syndrome, a growth hormone-releasing hormone that causes acromegaly.

The diagnosis is confirmed high content of sorotonin in the blood plasma, increased urinary excretion of 5-hydroxyindoleacetic acid, as well as the detection of a tumor of the intestine, liver, lungs during instrumental research methods. Biochemical indicators can be distorted when eating foods containing a large amount of serotonin (bananas, walnuts, citrus fruits, kiwi, pineapples), taking rauwolfia preparations, phenothiazines, salicylates, as well as in pathological conditions complicated by intestinal obstruction, when the excretion of 5-hydroxyindoleacetic acid may increase to 9-25 mg/day.

Immunofluorescent studies confirm the presence of neuropeptides (serotonin, substance P and neurotensin) in carcinoid tumors. Definition carcinoembryonic antigen(CEA) in the diagnosis of carcinoid tumors also has a certain meaning: its level is usually normal or minimal. If the CEA concentration is elevated, another tumor should be suspected.

Complex topical diagnostics carcinoids involves x-ray examination, computed tomography, ultrasound scanning, the use of immunoautoradiographic methods for determining hormones in the blood, selective arterio- and phlebography, scintigraphy with indium-111-octreotide, and morphological examination of the biopsy. The use of the whole complex of modern research methods (fluoroscopy, endoscopy, selective arterio- and phlebography, ultrasound, computed tomography, radionuclide studies, determination of hormones in the blood, immunohistochemical examination of tumor biopsy specimens) provides a correct diagnosis in 76.9% of cases.

Considering the general principles of therapy carcinoid syndrome, it should be noted that the earliest removal of the tumor is advisable. However, it must be remembered that the clinical manifestations of carcinoid syndrome very often occur in cases where there are already functionally active liver metastases. In this case, radical surgical treatment is not feasible. However, mitigation of the carcinoid syndrome clinic can be achieved by excising as many metastases as possible, thus reducing the total amount of serotonin-producing tissue. If surgical intervention is impossible for some reason, X-ray therapy can be used, the effectiveness of which, however, is low due to the resistance of carcinoid tumors to radiation exposure. After radiation therapy, there are no reliable data on the increase in life expectancy.

Among medications, used in the treatment of carcinoid tumors, cyclophosphamide should be distinguished, the effectiveness of which, according to a number of authors, is about 50%. There are also reports that a good therapeutic effect is noted when prescribing serotonin antagonists, of which cyproheptadine and deseryl have found the most widespread use. Cyproheptadine has not only antiserotonin, but also antihistamine action. It is administered intravenously at a dose of 6 to 40 mg. Deseryl is used orally at a dose of 6 to 24 mg and intravenously for 1-2 hours at a dose of 10-20 mg.

Some antidepressants- fluoxetine, sertraline, fluvoxamine, paroxetine can be used for symptomatic therapy.

Histamine H1 and H2 receptor blockers(cimetidine, ranitidine, diphenhydramine / diphenhydramine) are effective in carcinoids that produce mainly histamine. Loperamide (Imodium) is used to treat diarrhea.

Synthetic analogues of somatostatin Octreotide (Sandostatin) and Lanreotide (Somatulin) are widely used to treat carcinoid syndrome. Sandostatin, interacting with somatostatin receptors, inhibits the production of active substances by the tumor. The recommended regimen for the use of sandostatin (octreotide) in the treatment of carcinoid and neuroendocrine syndromes is 150-500 mcg subcutaneously 3 times a day. The drug increases the survival of patients with carcinoid tumors and the presence of metastases, improves the quality of life of patients, facilitating or eliminating hot flashes, intestinal motor dysfunction, diarrhea.

Numerous studies have been conducted on the use of a-interferon in patients with carcinoid tumors. For the treatment of patients, doses of a-interferon 3-9 IU were used subcutaneously 3-7 times a week. The use of higher doses of the drug does not improve treatment rates, but significantly increases the percentage of toxic reactions. In the treatment of a-interferon improvement is observed in 30-75% of cases.

Treatment of arterial hypertension carried out according to general rules. In some cases, treatment should be aimed at combating the complications of carcinoid syndrome, such as cardiovascular insufficiency, gastrointestinal bleeding, etc. It should be noted that the duration of the disease (10 years or more), significant depletion of patients with carcinoid syndrome requires general strengthening therapy.

The occurrence of carcinoid syndrome is determined by several reasons. Of essential importance are: the slow growth of the primary tumor, massive metastasis and the size of metastases. However, the extraportal location of the latter plays a decisive role. All these factors cause hypersecretion of serotonin and other biologically active substances that periodically enter the bloodstream and have a pathological effect on various organs and systems.

The most characteristic group of vasomotor disorders is the so-called "reddening syndrome" (flushing syndrome), described in detail by Waldenstrom and Thorson. First of all, there are periodic "redness" of the face, shoulders, upper body, accompanied by a burning sensation, heat, palpitations, tachycardia, a feeling of weakness, and sometimes profuse sweating. The color of the skin suddenly becomes bright red, and then rather quickly changes to pink and goes to a normal shade. Often, spots of cyanosis (“spotted cyanosis”) remain on the skin against the background of general pallor. Such an attack lasts from 30 seconds to 10 minutes. During the day, the patient has from 5 to 30 such attacks.

Provoking factors for the "reddening syndrome" are: emotional and physical stress, abundant, hot food, alcohol intake, defecation.

Over time, hyperemia of the skin can become permanent, cyanosis progresses, and patients resemble patients with polycythemia (plethoric habitus) in their appearance. Sometimes there are telangiectasias.

Some researchers try to explain the cyanotic phase of an attack of redness by a possible synergistic effect on the vascular system of serotonin and bradykinin, with the simultaneous administration of which to rats, spasm of venules and retrograde blood spasm in the capillaries occurred (Weiner and Altura, 1967).

Bouts of redness in gastric carcinoids begin with bright red patchy erythema with well-defined borders. Apparently, in such patients, in addition to serotonin, significant amounts of histamine and 5-hydroxytryptophan, a precursor of serotonin, periodically enter the bloodstream. The predominant formation of the latter by the tumor tissue is due to a deficiency of decarboxylase, which provides the synthesis of serotonin (Jones et al., 1968).

The carcinoid syndrome that occurs with tumors of the bronchus has specific features, bouts of redness are acute in appearance, often accompanied by fever, lacrimation, runny nose, nausea and vomiting, hypotension and oliguria (Sandler, 1968). Such "carcinoid crises" (Kahil et al., 1964) may be caused by direct rapid entry of humoral agents into the arterial system, bypassing the portal circulation. "Redness Syndrome" is sometimes accompanied by hypertension, as well as diarrhea and asthma attacks.

Diarrhea in some cases is combined with cramping pains in the abdomen, pronounced rumbling. This symptom is due to intestinal hyperperistalsis caused by increased secretion of serotonin, and possibly bradykinin. Both of these agents increase the tone of the smooth muscles of the bronchi, spasm them, which often leads to atypical attacks of bronchial asthma.

In addition to the “reddening syndrome”, with a functioning carcinoid, changes of a different nature can be observed on the skin.

Some patients develop "pellagra-like lesions" associated with endogenous hypovitaminosis PP, caused by a relative lack of tryptophan for the synthesis of nicotinic acid in the intestine. Hyperkeratosis occurs, the skin becomes dry, flaky, grayish-black areas of pigmentation form on the forearms and lower extremities, glossitis is noted.

Along with "pellagra-like lesions", focal hyperpigmentation of a diffuse nature can be observed, due to excessive deposition of serotonin destruction products in the skin. Skin metastases of carcinoid are sometimes painful.

In patients with carcinoid syndrome, insufficiency of the tricuspid valve and stenosis of the orifice of the pulmonary artery are determined in 40-50% of cases (Sjoerdsma, 1956). The pathogenesis of these lesions remains unclear, but most researchers are supporters of the "biochemical theory" of their occurrence. The latter considers damage to the endocardium (mainly proliferative, not inflammatory) in carcinoid syndrome as a result of hypersecretion of serotonin and other biologically active substances that primarily affect the endocardium and contribute to excessive growth of connective tissue.

Serotonin clearly increases the tone of the arterial vessels of the lungs (Page, 1958), which creates an additional load on the right ventricle. The latter hypertrophies early, and then its myogenic dilatation quickly sets in with stagnation in the systemic circulation.

In the origin of edema in carcinoid syndrome, in addition to hemodynamic factors, hypoalbuminemia is involved due to a lack of tryptophan for protein synthesis, as well as a systematic increase in venous pressure in the midst of bouts of "redness". The antidiuretic effect of serotonin also plays a certain role, and in some patients, an increased concentration of antidiuretic hormone.

Patients suffering from carcinoid syndrome for a long time become emaciated, in some cases the weight is maintained.

Sometimes there are severe dizziness, transient visual impairment caused by cerebral hypoxia.

ICD-10 code

Carcinoid (carcinoid syndrome) is a rare potentially malignant hormonally active tumor originating from argentophilic cells. Most often, carcinoid tumors are localized in the gastrointestinal tract, less often they occur in the bronchi, gall bladder, pancreas and ovaries. The size of tumors, as a rule, is not large and varies from 0.1 to 3 cm.

Carcinoid syndrome is a disease caused by the circulation of mediators, which is manifested by reddening of the skin (90%), diarrhea (75%), noisy breathing (20%), endocardial fibrosis (33%), damage to the valves of the right heart; sometimes there is pleural, peritoneal or retroperitoneal fibrosis.

The reasons

The etiology of carcinoid, like other tumors, is still unclear. The origin of many symptoms of the disease is due to the hormonal activity of the tumor. A significant release of serotonin, lysylbradykinin and bradykinin, histamine, prostaglandins by tumor cells has been proven.

The development of carcinoid syndrome is due to a hormonally active tumor originating from enterochromaffin (argentaffin) intestinal cells (Kulchitsky cells). At the same time, hypertensive syndrome accompanies increasing intestinal disorders.

Classification

One of the most appropriate approaches to the classification of carcinoid tumors of the gastrointestinal tract is their division according to embryogenesis into anterior, middle, and posterior. In accordance with this, there are:

• Carcinoid tumors of the anterior part of the digestive tube (bronchi, stomach, duodenum, pancreas); these neoplasms are argentaffin-negative, contain a small amount of serotonin, sometimes secrete 5-hydroxytryptophan and ACTH, are able to metastasize to the bones;
• Carcinoids of the middle part of the digestive tube (lean, ileum, right colon) are argentaffin-positive, contain a lot of serotonin, rarely secrete serotonin or ACTH, rarely metastasize;
• Carcinoid tumors of the posterior part of the digestive tube (transverse colon, descending colon and rectum) are argentaffin-negative, rarely contain serotonin and ACTH, and can metastasize to the bones. Sometimes they are also found in the gonads, prostate, kidneys, mammary glands, thymus, or skin.

Symptoms

Symptoms, the course of carcinoid are made up of local symptoms caused by the tumor itself, and the so-called carcinoid syndrome, due to its hormonal activity. Local manifestations are local soreness; often there are signs resembling acute or chronic appendicitis (with the most frequent localization of the tumor in the appendix) or symptoms of intestinal obstruction, intestinal bleeding (with localization in the small or large intestine), pain during defecation and excretion of scarlet blood with feces (with rectal carcinoid ), weight loss, anemia. Carcinoid syndrome includes peculiar vasomotor reactions, attacks of bronchospasm, hyperperistalsis of the gastrointestinal tract, characteristic skin changes, lesions of the heart and pulmonary artery. In a pronounced form, it is not observed in all patients, more often with tumor metastases to the liver and other organs, especially multiple ones.

Typical symptoms are:

• Hyperemia
• Diarrhea
• Abdominal pain
• Wheezing due to bronchospasm (narrowing of the airways)
• valvular heart disease
• Surgery can cause a complication known as a carcinoid crisis.

Hyperemia is the most common symptom of carcinoid syndrome. In 90% of patients, hyperemia occurs during the disease. Flushing is characterized by redness or discoloration of the face and neck (or upper body), as well as fever. Attacks of flushing usually occur suddenly, spontaneously, they can also be caused by emotional stress, physical stress, or drinking alcohol.

Attacks of hyperemia can last from minutes to several hours. Flushing can be accompanied by a rapid heartbeat, low blood pressure, or dizzy spells if blood pressure drops too low and no blood flows to the brain. Rarely hyperemia is accompanied by high blood pressure. The hormones that are responsible for flushing are not fully recognized.

Diarrhea is the second important symptom of carcinoid syndrome. Approximately 75% of patients with carcinoid syndrome have diarrhea. Diarrhea often occurs along with flushing, but can also occur without it. In carcinoid syndrome, diarrhea is most often due to serotonin.

Heart disease occurs in 50% of patients with carcinoid syndrome. Carcinoid syndrome usually leads to scarring and stiffness of the pulmonary valve on the right side of the heart. Stiffness of these two valves reduces the heart's ability to pump blood from the right ventricle to the lungs and other parts of the body, which can lead to heart failure.

Typical symptoms of heart failure include an enlarged liver (due to the heart's supply of blood in heart failure when it is unable to pump all the blood it receives), swelling of the legs and ankles (dropsy), and swelling of the abdomen due to accumulation of fluid (abdominal dropsy). The cause of damage to the tricuspid and pulmonary valves of the heart in carcinoid syndrome, in most cases, is the intense long-term effect of serotonin on the blood.

A carcinoid attack is a dangerous condition that can occur during surgery. It is characterized by a sudden drop in blood pressure that causes shock, sometimes accompanied by an excessively rapid heart rate, elevated blood glucose levels, and severe bronchospasm.

A carcinoid attack can be fatal. The best way to prevent a carcinoid attack is surgery.

Wheezing occurs in about 10% of patients with carcinoid syndrome. Wheezing is a consequence of bronchospasm (spasm of the airways), which occurs as a result of the release of hormones by a carcinoid tumor.

Abdominal pain is a common symptom in patients with carcinoid syndrome. Pain may occur due to liver metastases, due to the fact that the tumor affects neighboring tissues and organs, or intestinal obstruction.

Diagnostics

The diagnosis is confirmed by a high content of sorotonin in the blood plasma, increased urinary excretion of 5-hydroxyindoleacetic acid, as well as the detection of a tumor of the intestine, liver, and lungs during instrumental research methods. Biochemical indicators can be distorted when eating foods containing a large amount of serotonin (bananas, walnuts, citrus fruits, kiwi, pineapples), taking rauwolfia preparations, phenothiazines, salicylates, as well as in pathological conditions complicated by intestinal obstruction, when the excretion of 5-hydroxyindoleacetic acid may increase to 9–25 mg/day.

Immunofluorescent studies confirm the presence of neuropeptides (serotonin, substance P and neurotensin) in carcinoid tumors. Determination of carcinoembryonic antigen (CEA) in the diagnosis of carcinoid tumors also has a certain meaning: its level is usually normal or minimal. If the CEA concentration is elevated, another tumor should be suspected.

Comprehensive topical diagnosis of carcinoids includes x-ray examination, computed tomography, ultrasound scanning, the use of immunoautoradiographic methods for determining hormones in the blood, selective arterio - and phlebography, scintigraphy with indium-111-octreotide and morphological examination of the biopsy. The use of the whole complex of modern research methods (fluoroscopy, endoscopy, selective arterio- and phlebography, ultrasound, computed tomography, radionuclide studies, determination of hormones in the blood, immunohistochemical examination of tumor biopsy specimens) provides a correct diagnosis in 76.9% of cases.

Treatment

Considering the general principles of therapy for carcinoid syndrome, it should be noted that the earliest removal of the tumor is advisable. However, it must be remembered that the clinical manifestations of carcinoid syndrome very often occur in cases where there are already functionally active liver metastases. In this case, radical surgical treatment is not feasible. However, mitigation of the carcinoid syndrome clinic can be achieved by excising as many metastases as possible, thus reducing the total amount of serotonin-producing tissue. If surgical intervention is not possible for any reason, X-ray therapy can be used, the effectiveness of which, however, is low due to the resistance of carcinoid tumors to radiation exposure. After radiation therapy, there are no reliable data on the increase in life expectancy.

Among the drugs used in the treatment of carcinoid tumors, cyclophosphamide should be singled out, the effectiveness of which, according to a number of authors, is about 50%. There are also reports that a good therapeutic effect is noted when prescribing serotonin antagonists, of which cyproheptadine and deseryl have found the most widespread use. Cyproheptadine has not only antiserotonin, but also antihistamine action. It is administered intravenously at a dose of 6 to 40 mg. Deseryl is used orally at a dose of 6 to 24 mg and intravenously for 1-2 hours at a dose of 10-20 mg.

Some antidepressants - fluoxetine, sertraline, fluvoxamine, paroxetine - can be used for symptomatic therapy.

Histamine H1 and H2 receptor blockers (cimetidine, ranitidine, diphenhydramine/diphenhydramine) are effective in carcinoids producing predominantly histamine. Loperamide (Imodium) is used to treat diarrhea.

Synthetic analogues of somatostatin - octreotide (sandostatin) and lanreotide (somatulin) - are widely used to treat carcinoid syndrome. Sandostatin, interacting with somatostatin receptors, inhibits the production of active substances by the tumor. The recommended regimen for the use of sandostatin (octreotide) in the treatment of carcinoid and neuroendocrine syndromes is 150-500 mcg subcutaneously 3 times a day. The drug increases the survival of patients with carcinoid tumors and the presence of metastases, improves the quality of life of patients, facilitating or eliminating hot flashes, intestinal motor dysfunction, diarrhea.

Conducted numerous studies on the use of a-interferon in patients with carcinoid tumors. For the treatment of patients used doses of a-interferon 3-9 IU subcutaneously 3-7 times a week. The use of higher doses of the drug does not improve treatment rates, but significantly increases the percentage of toxic reactions. In the treatment of a-interferon improvement is observed in 30-75% of cases.

Treatment of arterial hypertension is carried out according to the general rules. In some cases, treatment should be aimed at combating the complications of carcinoid syndrome, such as cardiovascular insufficiency, gastrointestinal bleeding, etc. It should be noted that the duration of the disease (10 years or more), significant depletion of patients with carcinoid syndrome requires general strengthening therapy.

Thus, the main type of treatment for patients with carcinoid and neuroendocrine tumors is the surgical method. Their drug treatment is based on chemotherapy, the use of somatostatin analogues and a-interferons.

Carcinoid syndrome develops in only some patients with carcinoid tumors and is characterized by a peculiar reddening of the skin ("hot flashes"), abdominal cramps, cramps and diarrhea. After a few years, valvular insufficiency of the right heart may develop. The syndrome develops as a result of the action of vasoactive substances secreted by tumor cells (including serotonin, bradykinin, histamine, prostaglandins, polypeptide hormones); the tumor is usually metastatic.

ICD-10 code

E34.0 Carcinoid syndrome

Causes of the carcinoid syndrome

Endocrinologically active tumors from the diffuse peripheral endocrine or paracrine systems produce various amines and polypeptides, the action of which is manifested by certain clinical symptoms and signs that together constitute the carcinoid syndrome.

Carcinoid syndrome is usually the result of endocrinologically active tumors that have developed from neuroendocrine cells (mostly in the ileum) and produce serotonin. Nevertheless, these tumors can develop in other places of the gastrointestinal tract (especially often in the appendix and rectum), pancreas, bronchi, or less often in the gonads. Rarely, some highly malignant neoplasms (eg, small cell lung carcinoma, pancreatic islet cell carcinoma, medullary thyroid carcinoma) are responsible for this syndrome. Carcinoid tumors localized in the intestine usually do not show clinical signs of carcinoid syndrome until liver metastases develop, because tumor metabolic products are rapidly destroyed in the blood and liver by hepatic enzymes, in the portal circulation system (for example, serotonin is destroyed by the hepatic monoamine oxidase).

Symptoms of the carcinoid syndrome

The most common (and often the earliest) symptom of carcinoid syndrome is discomfort associated with the development of characteristic "hot flashes" that appear in typical locations (head and neck), often preceded by emotional stress or heavy consumption of food, hot drinks or alcohol. Striking changes in skin color may appear, ranging from slight pallor or erythema to a purple tint. Gastrointestinal spasms with the development of recurrent diarrheal syndrome are quite common and constitute the main complaints of patients. Malabsorption syndrome may occur. Patients who develop valvular heart disease may have heart murmurs. Some patients may experience asthmatic breathing, decreased libido, and erectile dysfunction; pellagra rarely develops.

Diagnostics of the carcinoid syndrome

Diagnosis of serotonin-secreting carcinomas is carried out on the basis of the presence of a classic clinical symptom complex. The diagnosis is confirmed by detecting an increase in urinary excretion of the product of tumor metabolism - 5-hydroxyindoleacetic acid (5-HIAA). To avoid obtaining a false positive result in a laboratory study, the analysis is carried out under the condition that the patient is excluded from the diet 3 days before the study of serotonin-containing foods (such as bananas, tomatoes, plums, avocados, pineapple, eggplant, walnuts). Some drugs containing guaifenesin, metacarbomol, phenothiazides can also distort the results of the test, so they should be discontinued in advance of the study. On the third day, a 24-hour portion of urine is collected for the test. Normal urinary excretion of 5-HIAA is less than 10 mg/day (250 µmol/day).

Provocative tests with calcium gluconate, catecholamines, pentagastrin or alcohol are used to provoke the occurrence of "hot flashes". These tests can be diagnostically useful when the diagnosis is in doubt, but they must be performed with great care. Appropriate non-invasive modern techniques are used to locate tumors to pinpoint non-functioning carcinomas, although invasive diagnostic intervention, sometimes including laparotomy, may be required. Scanning with radiolabeled 1111-p-pentetreotide somatostatin receptor ligands or using 123-meta-iodobenzylguanedine can detect metastases.

Other conditions that are based on the typical clinical picture of "hot flashes", but which nevertheless may not have any connection with the carcinoid syndrome, should be excluded. In patients who do not have increased urinary excretion of 5-HIAA, disorders involving systemic mast cell activation (eg, systemic mastocytosis with increased urinary histamine metabolites and elevated serum tryptase) and idiopathic anaphylaxis may be the cause of this clinical syndrome. Additional causes of hot flashes include menopausal syndrome and consumption of ethanol-containing foods and medications such as niacin, certain tumors (eg, vipomas, renal cell carcinomas, medullary thyroid carcinomas).

Treatment of carcinoid syndrome

Some symptoms, including hot flushes, are relieved with somatostatin (which inhibits the secretion of most hormones), but without reduction in 5HIAA or gastrin excretion. Numerous clinical studies have shown good results in the treatment of carcinoid syndrome using octreotide, a long-acting analogue of somatostatin. Octreotide is the drug of choice for treating symptoms such as diarrhea and hot flashes. Judging by clinical assessments, the effectiveness of tamoxifen is not always observed; reduces clinical manifestations of the use of leukocyte interferon (IFN).

Hot flashes can also be successfully treated with phenothiazines (eg, prochlorperazine 5 to 10 mg or chlorpromazine 25 to 50 mg orally every 6 hours). Histamine receptor blockers may also be used in therapy. The introduction of phentolamine 5-10 mg intravenously prevented the development of experimentally induced hot flashes. Administration of glucocorticoids (eg, prednisolone 5 mg orally every 6 hours) may be helpful in severe hot flashes due to bronchial carcinoma.

Diarrhea syndrome can be successfully treated with codeine phosphate (15 mg orally every 6 hours), opium tincture (0.6 ml orally every 6 hours), loperamide (4 mg orally as a satiety dose and 2 mg after each bowel movement). up to a maximum of 16 mg per day). Diphenoxylate 5 mg orally every other day or peripheral serotonin antagonists such as cyproheptadine 4 to 8 mg orally every 6 hours or methysergide 1 to 2 mg orally 4 times a day are used.

Niacin and sufficient protein intake are prescribed to prevent the development of pellagra, since dietary tryptophan is a competitive inhibitor of serotonin secreted by the tumor (reduces its effect). Prescribe enzyme inhibitors that prevent the conversion of 5-hydroxytryptophan to serotonin, such as methyldopa (250-500 mg orally every 6 hours) and phenoxybenzamine (10 mg daily).