Carcinoid syndrome - symptoms, diagnosis, treatment. Carcinoid Syndrome - Causes, Signs, Symptoms and Treatment Treatment for Carcinoid Syndrome

• Nausea
• Elevated temperature
• Dizziness
• Abdominal pain
• Vomit
• Heart palpitations
• Diarrhea
• Red spots on the hands
• Redness of the face
• Lachrymation
• Hot flashes
• Swelling of the extremities
• Wheezing in the chest
• Congestion in abdominal cavity liquids
• Redness of the neck
• Swelling of the nose
• Red spots on the neck
• Cyanosis of the skin of the face
• Redness of the nose
• The appearance of deep wrinkles on the face

There is a certain type of neuroendocrine tumors - carcinoids, which release certain hormones into the bloodstream (most often these are serotonin, prostaglandin, histamine, and others). Due to the ingress of these hormones into the bloodstream, a person develops carcinoid syndrome, which is characterized by certain symptoms.

• Causes
• Symptoms
• Diagnostics and treatment

It turns out that the root cause of the development of such a pathological condition is a tumor in any of the organs. In this case, a tumor producing hormones can be located:

• in the appendix;
• in the small or large intestine;
• in the stomach.

As it is already clear from the definition of pathology, the causes of the development of carcinoid syndrome lie in the presence of a neuroendocrine tumor in the patient's body. Fortunately, these tumors grow very slowly, so if pathology is detected at an early stage, it is possible to completely cure or extend a person's life by 10 or more years. Therefore, it is so important to undergo regular examinations and pay attention to any suspicious symptoms that may indicate carcinoid syndrome - a sign of cancer in the body.

The predisposing factors for the development of this pathological condition can be:

• hereditary predisposition (in particular, multiple endocrine neoplasias);
• gender - pathology is more often observed in men;
• excessive consumption of alcohol and smoking;
• certain types of neurofibromatosis;
• history of stomach disease.

Besides, different shapes carcinomas occur in people of different races. Thus, African Americans are more likely to experience stomach tumors, while Europeans have lung carcinomas.

Symptoms

With tumors different localization symptoms of carcinoid syndrome appear with a certain degree of probability. For example, tumors small intestine of all neuroendocrine tumors occur in 10% of cases. In this case, the signs of carcinoid syndrome with such an oncological disease will be as follows:

• diarrhea;
• paroxysmal abdominal pain;
• nausea and vomiting.

Symptoms of carcinoid syndrome

Tumors of the appendix are even less common and often the prognosis for removal of the appendix is ​​favorable in cases where the tumor is small and does not metastasize.

The most common neuroendocrine carcinoma is gastric carcinoma, which is of three types and has a high likelihood of metastasis:

• Type I is a tumor less than 1 cm in size. It is often benign, therefore, the prognosis for the treatment of pathology is favorable;
• Type II - a neoplasm up to 2 cm in size, which rarely degenerates into a malignant tumor;
• Type III is the most common - these are tumors up to 3 cm in size, which are malignant and often invade the surrounding tissues. The prognosis, even with timely diagnosis, is unfavorable. But, if a tumor is detected at an early stage during a preventive examination and treated in a comprehensive manner, then a person can be provided with 10-15 years a fulfilling life, which is already a lot, given the difficult diagnosis.

In other places of localization of neoplasms, carcinoid syndrome develops almost immediately after the appearance of a tumor, therefore, a timely visit to a doctor and treatment of the underlying pathology can save a person's life. If we talk about the symptoms of carcinoid syndrome, then they are typical, but at the same time they are not diagnostically important, since individually they can manifest themselves in many other pathologies of internal organs.

So, the main symptoms of a condition such as carcinoid syndrome are:

with carcinoid syndrome

• diarrhea;
• hyperemia;
• abdominal pain;
• wheezing;
• CVS pathology;
• hot flashes.

In addition, some people may develop a carcinoid crisis - life threatening condition with serious consequences.

Diarrhea occurs in most patients with carcinoid syndrome. It occurs for two reasons - either due to the effects of the hormone serotonin, or due to the location of the tumor in the intestine. Hyperemia in a condition such as carcinoid syndrome is characteristic. A person's face turns red in the cheeks and neck area, the body temperature rises, dizziness appears and the heart rate increases, although blood pressure is within normal limits.

Other symptoms such as abdominal pain, wheezing in the lungs and swelling of the extremities or fluid accumulation in the abdominal cavity (which happens with heart pathologies) are not characteristic - they can occur with any disease, therefore, they are not of diagnostic value. But hot flashes, similar to those that women encounter with menopause, can characterize carcinoid syndrome, since they do not occur with other diseases. Unlike menopausal hot flashes, they are of four types:

• in the first type, redness occurs in the face and neck, which lasts for several minutes;
• in the second, the face acquires a cyanotic hue, which lasts for 5-10 minutes, while the nose swells and becomes purple-red;
• with the third type, the duration of the tide can be from several hours to several days - the condition is characterized by lacrimation, the appearance of deep wrinkles on the face, dilation of the vessels of the face and eyes;
• with the fourth type of hot flashes, red spots appear on the neck and hands of a person irregular shape.

Diagnostics and treatment

Diagnosis of a condition such as carcinoid syndrome is difficult, since all the symptoms of pathology are common, and if there is no characteristic hyperemia of the face or hot flashes, it is difficult to determine the disorder that caused these symptoms, therefore, patients are prescribed comprehensive examination which includes:

• delivery of analyzes for biochemistry;
• immunofluorescence studies;
• instrumental research methods.

The most informative instrumental methods are CT and magnetic resonance imaging, which can detect neoplasms in organs even at an early stage of development, which increases the patient's chances of recovery. But other instrumental methods are also prescribed, which diagnostics has at its disposal: radiography, scintigraphy, endoscopy, phlebo- and arteriography.

Treatment of a pathological condition such as carcinoid syndrome involves treating the underlying cause, that is, the tumor. The method of treatment allows you to determine the diagnosis, since it shows the localization of the tumor, its stage of development and other criteria that are important for developing a treatment plan.

The main methods of treating oncology today are:

• surgical excision of the tumor;
• chemotherapy;
• radiation therapy;
• symptomatic treatment.

The main method is surgical removal of the neoplasm, which can be radical, palliative and minimally invasive. Radical excision involves the removal of the area affected by the tumor, adjacent tissues and lymph nodes, as well as metastases in the body.

Palliative surgery involves the removal of only the primary tumor and the largest metastases. Minimally invasive surgery includes alloying hepatic vein, which makes it possible to get rid of symptoms such as hot flashes and diarrhea. After surgical excision, a complex of chemotherapy drugs is prescribed to destroy metastases in the body and the remnants of the tumor (if any). Complex application surgical techniques and chemotherapy can prolong the life of the patient, and in some cases (when the tumor is detected at an early stage) and completely heal.

As for symptomatic treatment, it is necessary to alleviate the patient's condition. For this purpose, serotonin antagonists, H1 and H2 receptor blockers, antidepressants, alpha-interferon and other drugs are prescribed as indicated.

What to do?

If you think that you have Carcinoid syndrome and the symptoms characteristic of this disease, then doctors can help you: endocrinologist, oncologist.

• Which doctors should you contact if you have Carcinoid Syndrome?

What is Carcinoid Syndrome

Carcinoids- the most common tumors from neuroendocrine cells (APUD-system cells). These cells are derived from the neural crest. They are widespread in the body, contain and secrete some biologically active peptides. Most often, carcinoids develop in the gastrointestinal tract (85%), especially in the small intestine, as well as in the lungs (10%), less often they affect other organs (for example, the ovaries). Intestinal carcinoids rarely (in 10% of cases) manifest clinically. This is due to the rapid destruction of biologically active peptides in the liver. Only with metastases of intestinal carcinoid in the liver do symptoms appear in 40-45% of patients. As for ovarian carcinoids and bronchial carcinoids, they can cause characteristic syndrome in the early stages of the disease.

Carcinoid syndrome- a combination of symptoms that arose due to the secretion of hormones by tumors and their entry into the bloodstream.

Pathogenesis (What Happens?) During Carcinoid Syndrome

Carcinoid tumors can appear where there are enterochromaffin cells, in principle, all over the body. Most carcinoid tumors (65%) develop in the gastrointestinal tract. In most cases, carcinoid tumors develop in the small intestine, appendix, and rectum. Less commonly, carcinoid tumors develop in the stomach and colon; pancreas, gall bladder and the liver are the least susceptible to developing carcinoid tumors (although carcinoid tumors usually metastasize to the liver).

Approximately 25% of carcinoid tumors involve the airways and lungs. The remaining 10% can be found anywhere. In some cases, doctors are unable to locate a carcinoid tumor despite the symptoms of carcinoid syndrome.

Carcinoid tumor of the small intestine

In general, tumors of the small intestine (benign or malignant) are rare, much less common than tumors of the colon or stomach. Small carcinoid tumors of the small intestine may not cause any symptoms, only unexpressed pain in a stomach. For this reason, it is difficult to determine the presence of a carcinoid tumor of the small intestine at an early stage, at least until the patient is operated on. It is possible to detect only a small fraction of carcinoid tumors of the small intestine in the early stages, and this happens unexpectedly on x-rays. Usually, carcinoid tumors of the small intestine are diagnosed in the later stages, when the symptoms of the disease have become evident and usually after the metastases have appeared.

Approximately 10% of carcinoid tumors of the small intestine cause carcinoid syndrome. Usually, the development of carcinoid syndrome means that the tumor is malignant and has reached the liver.

Carcinoid tumors often obstruct the passage of the small intestine when they grow large. Symptoms of small bowel obstruction include paroxysmal abdominal pain, nausea and vomiting, and sometimes diarrhea. Obstruction can be caused by two different mechanisms. The first mechanism is the enlargement of the tumor inside the small intestine. The second mechanism is twisting of the small intestine due to fibrosing mesenteritis, a condition caused by a tumor in which extensive scarring occurs in tissues close to the small intestine. Fibrosing mesenteritis sometimes makes it difficult to pass the arteries that carry blood to the intestine, which can result in the death of a portion of the intestine (necrosis). In this case, the intestines can burst, which is a serious threat to life.

Appendicular carcinoid tumor

Although tumors in the appendix are relatively rare, carcinoid tumors are the most common tumors in the appendix (approximately half of all tumors in the appendix). In fact, carcinoid tumors are found in 0.3% of removed appendices, but most of them do not reach more than 1 cm in size and do not cause any symptoms. In most cases, they are found in appendices removed for reasons unrelated to tumors. Many agencies believe that appendectomy is the most appropriate treatment for such small appendicular carcinoid tumors. Sansa that the tumor will recur after appendectomy is very low. Appendicular carcinoid tumors larger than 2 cm in 30% can be malignant and form local metastases. Thus, carcinoid tumors bigger size should be deleted. A simple appendectomy will not help in this case. Fortunately, carcinoid tumors big size are rare enough. Carcinoid tumors in the appendix, even with local metastases, usually do not cause carcinoid syndrome.

Rectal carcinoid tumors

Rectal carcinoid tumors are often diagnosed incidentally by plastic sigmoidoscopy or colonoscopy. Carcinoid syndrome is rare in rectal carcinoid tumors. The likelihood of metastasis is related to the size of the tumor; 60-80% chance of metastases in tumors larger than 2 cm. In carcinoid tumors smaller than 1 cm 2% chance of metastases. Thus, small rectal carcinoid tumors are usually successfully removed, but larger tumors (> 2 cm) require extensive surgery, which in some cases may even result in partial removal of the rectum.

Gastric (gastric) carcinoid tumors

There are 3 types of gastric (gastric) carcinoid tumors: type I, type II, and type III.

Gastric carcinoid tumors of the first type are usually less than 1 cm in size and are benign. There are complex tumors that have spread throughout the stomach. They usually appear in patients with pernicious anemia or chronic atrophic gastritis (a condition in which the stomach stops producing acid). Lack of acid causes cells in the stomach that produce the hormone gastrin to secrete a large number of gastrin, which enters the bloodstream. (Gastrin is a hormone secreted by the body to enhance the activity of stomach acid. The acid in the stomach blocks the production of gastrin. In pernicious anemia or chronic atrophic gastritis, the lack of acid is the result of an increase in the amount of gastrin). Gastrin also influences the transformation of enterochromaffin cells in the stomach into a malignant carcinoid tumor. Treatment for type 1 carcinoid tumors includes treatments such as taking somatostatin drugs that stop the production of gastrin or surgically removing the part of the stomach that produces gastrin.

The second type of gastric carcinoid tumor is less common. Such tumors grow very slowly and the likelihood of their transformation into a malignant tumor is very small. They appear in patients with a rare genetic disorder such as MEN (multiple endocrine neoplasia) type I. In these patients, tumors develop in other endocrine glands, such as the pineal gland, parathyroid gland, and pancreas.

The third type of gastric carcinoid tumor is tumors larger than 3 cm that are separate (occurring one or more at a time) in a healthy stomach. Tumors of the third type are usually malignant and there is a high probability of their deep penetration into the walls of the stomach and the formation of metastases. Tumors of the third type can cause abdominal pain and bleeding, as well as symptoms due to carcinoid syndrome. Type III gastric carcinoid tumors usually require surgical intervention and removal of the stomach, as well as nearby lymph nodes.

Colon carcinoid tumors

Colon carcinoid tumors usually form on the right side of the colon. Like carcinoid tumors of the small intestine, carcinoid tumors of the colon are often found in advanced stages. Thus, the average tumor size at diagnosis is 5 cm, and metastases are present in 2/3 of patients. Carcinoid syndrome is rare in colon carcinoid tumors.

Symptoms of Carcinoid Syndrome

Symptoms of carcinoid syndrome differ depending on which hormones are secreted by the tumors. These are usually hormones such as serotonin, bradykinin (which promotes pain), histamine, and chromogranin A.

Typical manifestations of carcinoid syndrome:

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

Hyperemia

Flushing 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 parts body), as well as an increase in temperature. Flushing attacks usually occur suddenly, spontaneously, they can be caused by emotional, physical stress or alcohol intake. Flushing attacks can last from a minute to several hours. Flushing may be accompanied by a rapid heartbeat, low blood pressure, or dizziness if arterial pressure drops heavily and blood does not flow to the brain. Rarely, hyperemia is accompanied by high blood pressure. The hormones responsible for flushing are not fully recognized; perhaps these include serotonin, bradykinin, and substance R.

Diarrhea

Diarrhea - second important symptom carcinoid syndrome. Diarrhea occurs in about 75% of patients with carcinoid syndrome. Diarrhea often occurs along with flushing, but can also occur without it. In carcinoid syndrome, diarrhea is most often due to serotonin. Medications that block the action of serotonin, such as ondansetron (Zofran), often relieve diarrhea. Sometimes diarrhea in carcinoid syndrome can result from local impact a tumor that obstructs the passage of the small intestine.

Heart disease

Heart disease occurs in 50% of patients with carcinoid syndrome. Carcinoid syndrome usually leads to fibrotic changes in the pulmonary heart valve. Impaired valve mobility 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 heart failure include: enlarged liver, swelling of the legs, fluid accumulation in the abdomen (ascites). The cause of damage to the tricuspid and pulmonary heart valves in carcinoid syndrome, in most cases, is an intense long-term exposure to serotonin.

Carcinoid crisis

A carcinoid crisis is a dangerous condition that can occur during surgery. A crisis is characterized by a sudden drop in blood pressure, which is the cause of the development of shock. This condition can be accompanied by an excessively rapid heartbeat, high blood glucose, and severe bronchospasm. A carcinoid crisis can lead to lethal outcome... The most the best way Preventing a carcinoid attack is surgery using somatostatin before surgery.

Wheezing

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 from a carcinoid tumor.

Abdominal pain

Abdominal pain is a common symptom in patients with carcinoid syndrome. Pain can occur due to metastases in the liver, due to the fact that the tumor affects adjacent tissues and organs, or due to intestinal obstruction (read about carcinoid tumor of the small intestine below).

Diagnosis of Carcinoid Syndrome

Diagnosis of carcinoid syndrome confirmed by an increase in the daily urine level of the serotonin metabolite - 5-hydroxyindoleacetic acid.

Treatment of Carcinoid Syndrome

Treatment of carcinoid syndrome: radical surgical removal of the tumor. For metastases that cannot be removed, therapy with octreotide, a long-acting analogue of somatostatin, is prescribed.

At frequent attacks use methyldopa preparations (dopegit 0.25-0.5 g 3-4 times a day), opium preparations for diarrhea. It is possible to use prednisolone at a dose of up to 20-30 mg per day.

Carcinoid syndrome is a symptom complex that arose as a result of the release of various hormones by tumors and their entry into the bloodstream. After such an introduction, many readers will decide that they will have a description of another oncological disease: symptoms, signs, methods of treatment, and in the end - a prognosis of the development of events (of course, unfavorable) and a non-binding phrase concerning the need to gather willpower into a fist and believe in a miracle. After all, even those of us who are very far from medicine know perfectly well that a tumor is incurable, and cancer is an inexorable sentence, not subject to appeal.

Dear Readers! If you want to find confirmation of your fears, then you have to upset you: you have come to the wrong address. And the point here is not at all that we strive to give you only positive, encouraging information. Quite the opposite: there are enough resources on the Internet that either claim that cancer (especially, any!) Can be cured perfectly, or gradually prepare the patient for the transition to another world, offering to come to terms with the inevitable and think about something eternal.

We prefer a different approach: to give the most accurate information regarding a particular disease. Yes, a tumor is a special case: formidable symptoms, obvious signs of non-binding duty sympathy in the eyes of a doctor and horror that envelops the patient after the next visit to the oncological dispensary. An exhaustive analysis of such misconceptions requires a separate discussion, especially since the carcinoid syndrome, which we will talk about today, is not, in fact, a malignant neoplasm. This, again, is a complex of symptoms explained by the ingress of hormones into the bloodstream.

The essence of the problem

Carcinoid tumor - special kind malignant neoplasms developing from endocrine and nervous systems... It differs from other types of cancer in that it injects a large amount of certain hormones (serotonin, histamine, bradykinin and prostaglandins) into the bloodstream. Because of this, the patient, in addition to the "usual" cancer signs, there are also some specific symptoms that have nothing to do with the site of tumor localization: hyperemia, diarrhea and stomach cramps, which are called "carcinoid syndrome".

But in order to close the topic of the "incurability" of such tumors once and for all, it should be especially clarified: carcinoids grow and spread very slowly, due to which metastases (the main cause of death in oncology) appear much later than in common types of cancer. Which leads us to a completely obvious conclusion: for early diagnosis and early treatment of a fatal outcome is often avoided. But for this you will have to regularly undergo preventive examinations, refuse bad habits and start taking care of your health. Agree, it is much "easier" for 5-7 years to pretend that nothing is happening, and when the doctor informs you that you have several months of life left, start mourning your own bitter fate. Naturally, the oncologist will be “to blame” for such a development of events, and not the patient himself ...

Possible localization locations

1.Small intestine tumor (10% of cases). It is quite rare, which is "compensated" by the great difficulties with its detection. Long time it may not manifest itself in any way (in exceptional cases, the problem is revealed on X-ray examination). The diagnosis is usually made after the appearance of metastases, involvement of the liver in the pathological process and, as a consequence, a significant deterioration in the prognosis. Obstruction poses the greatest threat to life. small intestine and in individual cases- death of its part (necrosis) or rupture. Typical clinical manifestations are nausea, diarrhea, vomiting, paroxysmal pain in the abdomen and decreased permeability of blood vessels.

2. Appendicular tumor. It is found in less than 1% of cases when the appendix is ​​removed. Such neoplasms rarely reach a significant size (usually no more than 1 cm in diameter) and most often develop without any clinical manifestations. If an appendicular tumor is detected during surgery to remove the appendix, the likelihood of recurrence is extremely low and the patient's prognosis is good. Large neoplasms (at least 2 cm) are malignant in about 30% of cases, but they are relatively rare.

3. Rectal tumor. In this case, carcinoid syndrome develops very rarely, and the likelihood of metastases directly depends on the size of the neoplasm. If the diameter of the tumor is less than 1 cm, this happens in 1-2% of cases, but with larger sizes (from 2 cm or more), the risk increases to 60-80%.

4. Gastric (gastric) tumor. There can be three types, which differ in size, the nature of the neoplasm and the likelihood of developing metastases.

• Type I (size less than 1 cm). Almost always, such a neoplasm is benign, due to which the likelihood of metastases tends to zero. Most often seen in patients with chronic atrophic gastritis or pernicious anemia. With timely diagnosis and timely operation, the prognosis is favorable.
• Type II (from 1 to 2 cm). It is very rare, and the chance of transformation into a malignant form is extremely low. Risk group - patients with MEN (multiple endocrine neoplasia, a rare genetic disorder), and in this case, similar neoplasms are also formed in the pancreas, parathyroid glands or pineal gland.
• III type (more than 3 cm). Almost always, such tumors are malignant, and the risk of invasion of surrounding tissues and organs is extremely high. The prognosis is often unfavorable, and the later the correct diagnosis is made, the worse the outlook.

5. Colon tumor. The usual localization place is Right side end part digestive tract... Most often it is detected too late, when the transverse size of the neoplasm is more than 5 cm, and metastases are observed in two thirds of patients. The prognosis is unfavorable.

Symptoms

Speaking about clinical manifestations, it should be understood that they can be of two types. Carcinoid syndrome has some symptoms, but its root cause - a tumor - others. It often happens that during the initial examination, clinical manifestations "mix", and the doctor begins to treat hyperemia, diarrhea, pain in the heart and abdomen, carcinoid crisis and wheezing, unaware of what caused them. At the same time, the oncological nature of the disease may remain in the shadows, and the patient learns about his true diagnosis much later. Therefore, in this case, an individual approach to each patient is extremely important, and the symptoms themselves (will be discussed below) should be considered in a complex.

1. Hyperemia. It occurs in 90% of patients and is an obvious (but by no means unique) symptom of the syndrome. It is assumed that bradykinin and serotonin are "responsible" for hyperemia, although this issue has not yet been fully clarified. Typical clinical manifestations:

• high temperature;
• redness of the skin of the face and neck;
• heart palpitations against the background of low blood pressure indicators;
• dizziness attacks.

2. Diarrhea. It is observed in 75% of patients diagnosed with carcinoid syndrome. Often (but not always) occurs against the background of hyperemia. The main "culprit" is serotonin, therefore, specific drugs that suppress the action of this hormone (ondansetron, zofran) can alleviate the patient's condition. In rare cases, diarrhea occurs due to a closely located tumor or due to the influence of a metastatic focus.

3. Pathology of the cardiovascular system. Occurs in every second patient. Most often, the pulmonary valve suffers, the violation of the mobility of which significantly reduces the ability of the heart to pump blood from the right ventricle to other organs and systems of the body. Possible clinical manifestations (due to excessive production of serotonin):

• enlargement of the liver;
• swelling of the limbs (most often the legs are affected);
• accumulation of fluid in the abdominal cavity (ascites).

4. Carcinoid crisis. An acute and life-threatening condition that can occur during surgery. Therefore, if a patient with confirmed carcinoid syndrome requires surgery, prior administration of somatostatin is mandatory. The main symptoms of a carcinoid crisis are:

• a sudden and sharp drop in blood pressure;
• life-threatening increase in heart rate;
• increased blood glucose levels;
• the strongest bronchospasm.

5. Wheezing (10% of patients). Are a direct consequence of a spasm of the airways, but on a superficial examination can be explained by problems with the respiratory system.

6. Severe abdominal pain. It is explained either by metastases in the liver, or by sudden intestinal obstruction. In the second case, the patient needs urgent surgery, and the doctor deals with the root cause of the obstruction (carcinoid syndrome and primary tumor) after the immediate danger to life has been eliminated.

7. Tides

The so-called tides deserve special mention. This is a specific symptom that manifests itself as a sudden surging sensation of heat, unmotivated anxiety, increased sweating and redness of the skin. Most women at the age are firsthand familiar with hot flashes, which often appear with the onset of menopause, but when describing carcinoid syndrome, the corresponding Clinical signs look slightly different:

• Type I (erythematous): an attack lasts 1-2 minutes and is limited to the face and neck;
• Type II: the face becomes cyanotic for 5-10 minutes, and the nose becomes red-purple;
• Type III: an attack can last for several hours or days and is expressed in the appearance of deep wrinkles on the forehead, dilatation of the conjunctival vessels, severe lacrimation, diarrhea and attacks of hypotension;
• Type IV: the appearance of irregularly shaped, bright red spots, usually on the arms and around the neck.

Approximate correspondence of the types of hot flashes and the area of ​​tumor localization:

• I and II types: the middle part of the digestive tube, bronchi, pancreas;
• Type III: anterior part of the digestive tube;
• IV type: stomach.

Diagnostics

1. Biochemical studies show:

• high serotonin content in blood plasma;
• increased urinary secretion of 5-hydroxyindoscular acid.

But here it is important to understand that the final results can sometimes be seriously skewed. The main factors affecting their reliability are as follows:

• the use of certain products ( walnuts, kiwi, bananas, citrus fruits, pineapples);
• taking certain pharmacological drugs;
• intestinal obstruction.

2. Immunofluorescence study will reveal:

• the presence of neuropeptides (substance P, serotonin, neurotensin);
• change in the level of CEA (carcinoembryonic antigen).

3. Instrumental research

• scintigraphy ( intravenous administration radioactive isotopes of indium-111 with subsequent visualization on a gamma tomograph);
• endoscopic examination of internal organs by means of a thin probe with a miniature camera at the end (this procedure is often combined with a biopsy);
• selective arterio- and phlebography;
• X-ray examination;
• CT and MRI to confirm the diagnosis.

Unfortunately, carcinoid syndrome is one of those pathologies for which a 100% effective diagnostic method has not yet been developed. Therefore, even a comprehensive examination guarantees the correct diagnosis only in 70% of cases. But what about the characteristic symptoms and clinical manifestations, you ask? Unfortunately, they cannot be called anything unique. They can be useful in the development of treatment tactics, but they are of little help in making a diagnosis and confirming it.

Treatment

A patient diagnosed with carcinoid syndrome may be offered different options therapy:

1. Radical surgery. The main method of treatment with proven efficacy and a high survival rate. The volume and type of intervention is determined by both the localization of the primary tumor and the presence or absence of metastases:

• jejunum and ileum: resection of the affected area, the corresponding area of ​​the mesentery and, possibly, nearby lymph nodes (survival rate: 40 to 100%);
• ileocecal sphincter: right-sided hemicolectomy;
• mesenteric lymph nodes (large carcinoids from 2 cm), colon: hemicolectomy;
• appendix: appendectomy.

2.Palliative surgery. It removes the primary tumor node and the largest metastases. There is no need to talk about a cure in this case, but it is possible to improve the quality of life.

3. Minimally invasive intervention: embolization or doping of the hepatic artery. The procedure gives a high (60 to 100%) chance to get rid of hot flashes and diarrhea.

4. Chemotherapy. It is considered desirable for the generalization of the process, in combination treatment measures after surgical intervention and subject to the presence of some unfavorable factors (heart damage, high excretion of 5-OIAA, impaired liver function).

• the most effective drugs: streptozocin, doxorubicin, 5-fluorouracil, etoposide, dactinomycin, dacarbazine, cisplatin;
• the duration of the remission period is from 4 to 7 months;
• the average efficiency with monotherapy is less than 30%, in the combined mode - up to 40%;
• for some types of tumors (anaplastic neuroendocrine), the effectiveness of chemotherapy increases significantly - up to 65-70%.

5. Radiation therapy... The effectiveness in the treatment of carcinoid syndrome has not yet been proven, although with an integrated approach aimed at maximizing life extension, it should not be abandoned.

6. Symptomatic treatment

• serotonin antagonists: methysergide, cyproheptadine;
• selective serotonin reuptake inhibitors: citalopram, dapoxetine, fluoxetine;
• antidepressants: fluoxetine, fluvoxamine, sertraline, paroxetine;
• H1 and H2 receptor blockers: cimetidine, diphenhydramine, ranitidine;
• synthetic analogs of somatostatin: octreotide, sandostatin, lanreotide;
• alpha interferon (improvement in 30-75% of cases).

Risk factors

Forecast

Taking into account the extremely slow growth of the primary tumor, effective surgical intervention and some improvement in the prognosis with complex chemotherapy, most patients can expect 10-15 years of full life. Early detection of carcinoid syndrome often provides a complete cure, so preventive examinations should not be neglected. Believe me, it's better to spend a few hours a year than regret the missed opportunities later.

John A. Oates, L. Jackson Roberts II (John A. Oates, L. Jackson Roberts II)

In case of carcinoid tumor, accompanied by reddening of the skin of the face, telangiectasia, diarrhea, damage to the heart valves and narrowing of the bronchi, it is assumed that all these manifestations are due to the release from the tumor of one biologically active substance or several. Serotonin was the first of these substances to be discovered. Its overproduction is the most consistent biochemical indicator of carcinoid syndrome. However, this is not the only mediator of symptoms, as carcinoid tumors can produce a variety of indoles and chemically unidentified substances, including vasoactive peptides and histamine. The latter substances can cause flushing of the skin. The extended classification of carcinoid tumors takes into account a wide variety of biologically active substances produced by them, as well as different mechanisms of their production and accumulation. In accordance with this, marked and wide range clinical manifestations of carcinoid syndrome.

Tumors.Carcinoid tumors are slow-growing neoplasms composed of enterochromaffin cells. Metastatic tumors associated with carcinoid syndrome usually arise from small primary tumors of the ileum. This syndrome can also be caused by a neoplastic formation localized in the appendix, in organs originating from the embryonic anterior part of the digestive tract (bronchi, stomach, pancreas and thyroid glands), as well as those developed from ovarian and testicular teratomas.

Carcinoid tumors are extremely prone to metastasis to the liver (and metastases can be extensive) with minimal metastasis to other organs. Extrahepatic metastases include tumors in the bones, mainly represented by osteoblastic elements, as well as in the lungs, pancreas, ovaries, adrenal glands and other organs.

Primary carcinoid tumors are most often localized in the appendix, but they rarely metastasize. The carcinoid can metastasize from the large intestine, but it almost never has hormonal activity.

A common carcinoid tumor of the ileum is histologically characterized by compact clusters of cells of the same size and nuclei of the same type. The histochemical feature of these cells is a positive argentophilic reaction, when silver salts are converted into metallic silver. A positive argentophilic reaction is not required for the diagnosis, however, carcinoid organ tumors that originate from the embryonic anterior part of the digestive tract contain a small number of argentophilic cells. Tumors of these organs are distinguished by a wide range of histological manifestations: for example, in the lungs - from a typical bronchial carcinoid to histological forms indistinguishable from oat cell carcinoma. During electron microscopic examination, electron-dense secretory granules are always found in them.

Clinical manifestations.Unlike most metastatic tumors, carcinoid tumors are characterized by unusually slow growth, and therefore patients survive for 5-10 years after the diagnosis of carcinoid. The hormonal activity of these tumors determines both a wide range of clinical symptoms and a long period of the disease. Death occurs as a result of heart or liver failure, as well as complications associated with tumor growth.

Vasomotor reaction. Most often, the tumor is manifested by skin hyperemia in the form of erythematous redness of the skin of the head and neck (area of ​​blood flow to the face). During vascular reaction skin color can change from red to cyanotic, and then to pronounced pallor. Prolonged bouts of hyperemia may be accompanied by lacrimation and edema of the periorbital region. The systemic effects of these reactions vary. They can be manifested by tachycardia and hypotension, although sometimes blood pressure does not change. Hypertension is rarely recorded, and therefore carcinoid syndrome cannot be considered its cause.

Flushing of the skin can be triggered by emotional factors (excitement and excitement), food intake and alcoholic beverages... In addition, pentagastrin and beta-adrenergic receptor antagonists such as adrenaline may act as a trigger for vasodilation. Since hemodynamic disturbances caused by these pharmacological agents, can be pronounced, they should be prescribed with great care.

Telangiectasia. In carcinoid syndrome, in some patients, as a result of frequent and prolonged attacks of expansion of skin vessels, telangiectasias may appear, first on the face and neck, and then in the area of ​​the zygomatic bone, where they are most pronounced.

Side symptoms gastrointestinal tract... Vasomotor reactions are sometimes accompanied by increased peristalsis, "rumbling" in the abdomen with sudden painful attacks and acute development of diarrhea. However, diarrhea is more often chronic with a secretory component, in severe cases it is accompanied by impaired absorption into the intestine.

Cardiovascular manifestations. A characteristic feature of the carcinoid syndrome is fibroelastosis of the endocardium and valves, predominantly of the right heart, but sometimes small changes are determined in the left. Plaque-like thickening of the endocardium, consisting of smooth muscle cells surrounded by a stroma rich in mucopolysaccharides, collagen and microfibrils, do not penetrate into the inner elastic membrane. Displacement of the valve cusps, tendon chords and papillary muscles leads to dysfunction of the valves of the right heart, which can lead to their regurgitation, stenosis, or both at the same time. The fibrotic process can cause extremely dangerous violations hemodynamics due to insufficiency tricuspid valve and stenosis of the mouth of the pulmonary artery. Large cardiac output with concomitant cardiac dysfunction may result either from the tumor's constant release of vasodilators or from increased blood flow in tumor metastases.

Pulmonary symptoms. The narrowing of the bronchi occurs less often in carcinoid syndrome, it cannot be pronounced, especially during the period of increased vasomotor activity.

General symptoms. In addition to hormonal effects a carcinoid tumor can itself cause an intestinal obstruction or intestinal bleeding. Necrotic changes in a carcinoid tumor localized in the intestine or liver can cause abdominal pain, a general deterioration in the patient's well-being, fever and leukocytosis. With metastasiscarcinoid syndrome is manifested by an increase in the size of the liver. The spread of metastases in the liver can occur before the results of its functional tests change. Sometimes carcinoid syndrome is accompanied by myasthenia gravis.

Hormonal activity of a carcinoid tumor. One of the most persistent characteristics of carcinoid tumors is the activity of tryptophan hydroxylase, which catalyzes the formation of 5-hydroxytryptophan (5-GTP) from tryptophan. Most carcinoid tumors also contain aromatic decarboxylase L -amino acids, which catalyzes the reaction of formation of 5-hydroxytryptamine (serotonin). In carcinoid tumors of the stomach and other organs that develop from the anterior part of the digestive tract of the embryo, the activity of decarboxylase is often reduced, as a result of which they release 5-GTP rather than serotonin. Once released from the tumor, serotonin is inactivated by monoamine oxidase. In addition, it is absorbed by platelets, which also helps to remove free serotonin from the blood. Monoamine oxidase oxidizes serotonin to 5-hydroxyindoleacetate aldehyde, which, in turn, under the influence of aldehyde dehydrogenase, is rapidly converted to 5-hydroxyindoleacetic acid (5-HIAA). This acid is rapidly excreted in the urine, and almost all serotonin circulating in the blood can be measured by the amount of 5-HIAA excreted. Carcinoid tumors differ in their ability to accumulate serotonin, the concentration of which in tumor tissue can range from a few micrograms per gram to 3 mg / g. The concentration of serotonin in the tumor tissue is not related to the intensity of its synthesis, corresponding to the urinary excretion of 5-HIAA. In short, ileal tumors tend to have a greater serotonin accumulation capacity than carcinoids located in other organs, ontogenetically developed from the anterior gastrointestinal tract of the embryo.

In patients with carcinoid syndrome, peptides of the tachykinin class are determined in the tumor and blood. In this syndrome, several peptides belonging to this class have been identified that have a vasodilating effect, including the non-decapeptide substance R. No specific substances of the tachykinin class typical of carcinoid syndrome have yet been found.

Bradykinin, like peptides with a vasodilating effect, is released (but not always) during the period of increased vasomotor activity. In accordance with this, it cannot be considered the main specific substance that determines it in carcinoid syndrome.

Some carcinoid tumors, especially those of the stomach, produce and release large amounts of histamine, which can be detected by an increase in the amount in the urine. The release of histamine from the tumor causes a sudden vasodilation, accompanied by "hot flashes", tachycardia and hypotension.

In a number of cases, carcinoid syndrome is accompanied by hyperadrenocorticism. It is caused by ectopic production of adrenocorticotropic hormone or corticotropin-releasing factor by tumors usually localized not in the ileum, but in other organs (bronchi, pancreas, ovaries and stomach).

In some cases, "multiple endocrine adenomas" accompany carcinoids localized in organs that have developed from the anterior part of the digestive tract of the embryo. These include parathyroid adenomas and pancreatic tumors that cause Zollinger-Ellison syndrome.

Tumors of organs embryogenetically associated with the anterior part of the digestive tract are histologically similar to carcinoid. They can produce very large amounts of gastrin, insulin, calcitonin, glucagon, corticotropin, growth hormone, growth hormone releasing factor, and vasoactive intestinal polypeptides in the absence of the usual clinical manifestations of carcinoid syndrome. These carcinoid tumors appear to have a common embryogenetic origin with tumors responsible for the development of carcinoid syndrome.

Pathophysiology.Serotonin is responsible for the clinical manifestations of carcinoid syndrome associated with increased intestinal motility. In addition, an increase in its level in the blood can lead to the deposition of fibrin in the endocardium.

The secondary effect of excess serotonin production is also manifested in cases where a significant part of the tryptophan supplied with food is metabolized during hydroxylation; moreover, less of it becomes available for the formation of nicotinic acid and proteins. With urinary excretion of 5-HIAA exceeding 200-300 mg / day, the plasma tryptophan level decreases and nicotinamide deficiency is detected.

The mechanism of paroxysmal vasodilation. Despite the fact that paroxysmal vasodilation in patients with histamine-secreting gastric carcinoids may be due to the action of this amine, the mechanism of their occurrence is still not clear enough. Current evidence suggests that serotonin does not mediate these seizures.

The release of substances that cause paroxysmal vasodilation, apparently, can be triggered by catecholamines, since most often these attacks are not spontaneous, but are associated with arousal and other emotional factors. In the experiment, these attacks can be caused by the introduction of isoproterenol in an amount of less than 0.5 μg / day. Pentagastrin in doses of less than 25 mcg also causes severe reddening of the skin, which often occurs with meals. These seizures can be controlled with somatostatin, which most likely inhibits the release of vasodilating substances.

Diagnostics. With the full range of symptoms, carcinoid syndrome is easily recognized. Moreover, the diagnosis can be made even if only one of the symptoms is present. The diagnosis is confirmed by overproduction of 5-hydroxyindoles and increased urinary excretion of 5-HIAA, which normally should not exceed 9 mg / day. In a patient on a diet high in serotonin, biochemical diagnosis of carcinoid may be difficult. So, for example, after taking large quantities walnuts or bananas, which contain significant amounts of serotonin, increase urinary excretion of 5-HIAA. Some medications also interfere with the results of biochemical analyzes of urinary excretion of 5-HIAA and may cause the misdiagnosis of carcinoid syndrome. The excretion of 5-HIAA in the urine is enhanced, for example, with the use of cough syrups containing guaiacolate, as well as some phenothiazines. After excluding the alimentary route of intake of 5-hydroxyindoles, the diagnosis of carcinoid syndrome should be made if more than 25 mg / day is excreted in the urine. With carcinoid syndrome, non-tropical sprue, acute intestinal obstruction, 9-25 mg / day of 5-HIAA can be excreted.

Measurement of the amount of serotonin in the blood or platelets is less important for the diagnosis of carcinoid syndrome compared to the quantitative determination of its main metabolites in the urine. At the same time, the determination of the increased amount of serotonin in the tumor tissue serves as a necessary addition to its study. histological structure to establish its carcinoid nature. Before quantifying serotonin in a suspected carcinoid tumor, a portion of the tumor should always be kept frozen.

The main directions of diagnosis for suspected carcinoid syndrome

1. Quantification of daily urinary excretion of 5-HIAA

2. If increased urinary excretion of 5-HIAA confirms the diagnosis of carcinoid syndrome, an attempt should be made to detect a primary tumor in the testes, ovary, or bronchi.

3. To resolve the issue of the possibility of excision of metastases in the liver, it is necessary: ​​to establish the localization and nature of metastases in the liver using computed tomography, scintillation scanning of the liver, arteriography, ultrasound examination; estimate functional state liver and heart; find extrahepatic metastases (in bones and other tissues)

4. In patients with intractable diarrhea, it is necessary to exclude possible impairment of intestinal absorption processes (malabsorption)

Differential diagnosis... In cases where the patient has paroxysmal vasodilation is not accompanied by an increase in urinary excretion of 5-HIAA, it is necessary to pay attention to other diagnostic signs... It should be borne in mind that some pathological conditions associated with systemic activation of mast cells, including mastocytosis, can also be accompanied by sudden vasomotor seizures, hypotension, and even fainting without an increase in urinary 5-HIAA levels. Sudden "hot flashes" are typical for menopause, they accompany other tumors, which primarily include specific medullary thyroid carcinoma.

Variants of carcinoid syndrome.The origin of the tumor affects the production of its biologically active substances, their accumulation and release. Carcinoid tumors in organs embryogenetically associated with the anterior part of the digestive tract (bronchi, stomach, pancreas) differ significantly from tumors that develop in organs originating from the distal midgut of the embryo. The latter are responsible for the development of the classic carcinoid syndrome, in which the tumor always secretes serotonin with a small amount of 5-hydroxytryptophan (5-GTP) or without it. Typically, a tumor contains a large amount of serotonin, and usually it consists of dense compact clusters of argentophilic cells.

In contrast, carcinoid tumors in organs that develop from the anterior part of the digestive tract of the embryo contain less serotonin and argentophilic cells and can secrete 5-GTP. These tumors appear to be more commonly associated with hyperadrenocorticism and multiple endocrine adenomas.

In addition to these common features characteristic of all carcinoid tumors of this group, carcinoids of the stomach and bronchi differ in specific clinical and biochemical characteristics. For patients with carcinoid tumors of the stomach, unusual "hot flashes" are typical, which usually begin with the appearance on the skin of the face and neck of bright red erythematous spots with sharply delineated sinuous borders, which eventually merge. Most likely, these attacks are provoked by food intake. Carcinoid tumors of the stomach are deficient in the enzyme decarboxylase and secrete 5-GTP. As a rule, they also secrete histamine, and therefore patients often develop peptic ulcer... Diarrhea and cardiac abnormalities are not typical clinical manifestations of carcinoid tumors, abundantly secreting 5-GTP and insufficiently producing serotonin.

In patients with carcinoid tumors of the bronchi, vasomotor attacks are especially prolonged and severe. They are accompanied by edema of the periorbital tissues, excessive tearing and salivation, hypotension, tachycardia, anxiety or anxiety, and tremors. Nausea, vomiting, intractable diarrhea and bronchoconstriction can progress, making the patient's condition extremely severe.

These seizures can be prevented with the help of glucocorticoids, and chlorpromazine allows to stop their main manifestations to some extent.

Treatment.Treatment for carcinoid syndrome is aimed, firstly, at reducing the mass of the tumor by surgery and / or with the help of chemotherapy, and, secondly, at relieving and arresting the symptoms caused by hormones.

After the diagnosis of carcinoid syndrome, u. in some patients, tumors that have developed from testicular or ovarian teratomas, as well as bronchi, are excised. Carcinoid tumors of this localization, due to the release of their secretion directly into the systemic circulation, cause the development of carcinoid syndrome even before the appearance of metastases. If humoral substances are released into the portal circulation system, then they are metabolically neutralized to a large extent by the liver, and therefore these tumors can cause the development of carcinoid syndrome only after the formation of metastases, most often in the liver. Since carcinoid tumors grow relatively slowly, palliative resection of liver metastases in some cases can alleviate the patient's condition. Excision of large isolated metastases in the liver leads to a weakening of the clinical manifestations of the syndrome and a decrease in urinary excretion of 5-HIAA for several years. Sometimes with multiple liver metastases, the liver lobe or the entire liver is resected. This operation is performed only if metastases are localized mainly in the lobe of the liver to be resected. The volume of the operation is determined by the data of ultrasound examination of the liver, computed tomography, as well as examination of the liver surface during laparoscopy or laparotomy.

In patients with diffuse metastases in both lobes of the liver, a decrease in tumor mass and a weakening of clinical symptoms can be achieved with surgical ligation or percutaneous embolization of the hepatic artery. Currently, there is not enough experience yetThis is why it is necessary to further study the effectiveness of this method of treatment and possible postoperative complications.

No universally effective chemotherapy methods have been developed. Palliative action in some cases is exerted by 5-fluorouracil, cyclophosphamide, streptozotocin, doxorubicin and methotrexate, used both individually and in different combinations. The objective response to this chemotherapy is low: the average duration of remission after a course of treatment is usually less than one year, in addition, almost all chemotherapy drugs have a pronounced toxic effect. Only in a very small proportion of patients, treatment with 5-fluorouracil is accompanied by mild toxicity. Initial doses of all chemotherapy drugs should be small if more than 150 mg / day of 5-HIAA is excreted in the urine or if the patient has "hot flashes", since rapid lysis of tumor tissue under the influence of large doses can lead to a massive release of mediator substances and cause a "carcinoid crisis" ... Radiation therapy can be effective at the stage of metastasis, for example, to the bone. Some patients were tried to be treated with tamoxifen and leukocyte interferon.

A certain success can be accompanied by treatment with drugs, the action of which is directed at the humoral mediator substances of the tumor tissue. For example, in gastric carcinoids producing and releasing a significant amount of histamine, its vasodilating effect can be blocked by a combination of H-1 (for example, diphenhydramine) and H-2 (cimetidine or ranitidine) antagonists. With diarrhea, treatment is mostly symptomatic (it is stopped with loperamide). In addition, serotonin antagonists such as cyproheptadine and methysergide can be used for the same purpose, although long-term treatment with methysergide is associated with the risk of developing retroperitoneal fibrosis. To interrupt one of the stages of serotonin synthesis and relieve diarrhea, p-chlorophenylalanine is also used, which inhibits the activity of tryptophan hydroxylase. Another drug - somatostatin - has shown its effectiveness in the massive release of mediator substances by the carcinoid tumor, as well as in the phenomena of "carcinoid crisis", since it sufficiently relieved the vasodilatation attacks, diarrhea and bronchoconstriction developing at the same time. Prevent severe vasomotor seizures using glucocorticoids and relieve the clinical symptoms of carcinoid syndrome using phenothiazines, mainly in patients in whom the tumor is localized in the bronchi or in other organs that have developed fromfront of the digestive tract of the embryo.

Currently, no methods have been developed that contribute to regression or at least partial arrest of the development of endocardial fibrosis in this disease, in connection with which the surgical replacement of the affected fibrosed heart valves is significantly hampered.

When excreted in urine, 5-HIAA in an amount of about 100 mg / day, taking niacin prevents the development of pellagra in the patient.

In hypotension, catecholamines should not be used, since adrenaline, norepinephrine and other adrenergic drugs stimulate the tumor to release vasodilators, which increase and prolong circulatory disorders. If the phenomena of hypotension require correction, then preference should be given to replenishing the volume of fluid or the introduction of methoxamine.

T.P. Harrison. Principles of internal medicine.Translation by Ph.D. A. V. Suchkova, Ph.D. N. N. Zavadenko, Ph.D. D. G. Katkovsky

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Carcinoid syndrome- a symptom complex associated with the growth and hormone production of tumors originating from enterochromaffin cells. Carcinoid is understood as a tumor causing carcinoid syndrome (Table 1).

Table 1

Carcinoid syndrome

Etiology	Tumor from enterochromaffin cells of the gastrointestinal tract, less often bronchi
Pathogenesis	Hypersecretion of serotonin, kinins, histamine, catecholamines, and prostaglandins in combination with invasive tumor growth and metastasis
Epidemiology	The incidence of new cases is 1 in 100,000 per year
Main clinical manifestations	1. Diarrhea, abdominal pain, belching 2. Hot flashes, telangiectasia, cyanosis 3. Bronchospasm, dyspnea, generalized itching 4. Fibrosis of the heart valves 5. Growth and metastasis of the tumor
Diagnostics	1. Excretion of 5-hydroxyindoleacetic acid, serotonin, histamine 2. Topical diagnosis of a tumor
Differential diagnosis	1. Clinical syndromes accompanied by hot flashes (postmenopausal syndrome, liver cirrhosis, idiopathic hot flashes)
	2. Pheochromocytoma 3. Metastases to the liver of a tumor of unknown primary localization
	1. Surgical treatment, chemoembolization and alcohol ablation of liver metastases 2. Antiproliferative and symptomatic therapy: octreotide, α-interferon, polychemotherapy
	5-year survival rate of about 50%

Etiology

According to the histological structure, the set of hormones produced and the degree of malignancy of carcinoid tumors vary significantly depending on the location. Carcinoid tumors are subdivided into those originating from the anterior, middle and posterior sections of the primary embryonic gut (Table 2). Intestinal carcinoid accounts for 90% of all carcinoid tumors. Most often, intestinal carcinoid is localized in the terminal ileum, appendix, rectum.

table 2

Classification of carcinoid tumors

Primary Intestine Division	Localization of the tumor	Produced hormones	Symptoms
Anterointestinal carcinoid	Respiratory tract	5-hydroxytryptophan, hormones of adenohypophysis, neuropeptides	Carcinoid syndrome, Cushing's syndrome
	Stomach, duodenum	Gastrointestinal peptides, serotonin, histamine	Carcinoid syndrome, hypersecretion of hydrochloric acid, diarrhea, diabetes, Cushing's syndrome
Mid-intestinal carcinoid	Small intestine, appendix, right side of the colon	Serotonin, peptides of the tachykinin group	Carcinoid syndrome, hormone-inactive tumors
Posterior intestinal carcinoid	Left Colon, Rectum	Gastrointestinal peptides	Hormone-inactive tumors

Pathogenesis

Most of the symptoms of carcinoid syndrome are due to tumor hypersecretion of substances such as serotonin, kinins, histamine, catecholamines and prostaglandins. The main biochemical marker of carcinoid syndrome is serotonin... Tumors originating from the anterior gut (bronchi, stomach) generally produce 5-hydroxytryptophan rather than serotonin. The main metabolite of biogenic amines is 5-hydroxyindoleacetic acid(5-GIUK). The pathogenesis of individual clinical manifestations of carcinoid syndrome is presented in table. 3.

Table 3

Pathogenesis of individual clinical manifestations of carcinoid syndrome

The detailed symptoms of carcinoid syndrome in intestinal carcinoid correspond to the late stage of the tumor process and metastatic liver damage. The primary tumor, as a rule, is small in size, and the products secreted by it, entering the liver, are completely inactivated. When the liver ceases to cope with massive tumor secretion, its products begin to enter the systemic circulation, and only then the symptoms of carcinoid syndrome appear. In the same way, mechanically, the predominant lesion in intestinal carcinoid of the endocardium of the right heart is explained, where blood from the affected liver enters through the inferior vena cava. The difference between extraintestinal carcinoid and intestinal forms lies in the fact that the products of tumor secretion enter directly into the systemic circulation, and not into the portal system. Thus, in these cases, the symptoms of carcinoid syndrome can develop even in the early stages of the tumor process, when radical surgery is still possible.

Epidemiology

The incidence of new cases of carcinoid tumors is 1 in 100,000 per year. Average age the manifestation of carcinoids of the small intestine is 50-60 years; occurs with the same frequency in men and women.

Clinical manifestations

• Diarrhea, abdominal pain, belching.
• Hot flashes, telangiectasia, cyanosis. Hot flashes can be triggered physical activity, alcohol or products such as cheese, smoked meats, coffee. They can be repeated throughout the day, usually lasting a few minutes, accompanied by heavy sweating... At the same time, patients complain of a feeling of heat, palpitations and tremors. Some may have severe tearing and drooling. Against this background, severe arterial hypotension, difficulty breathing, diarrhea can be observed. The skin of the face and upper half of the body gradually acquires a persistent red-cyanotic hue, telangiectasias appear (Fig. 1). With carcinoid of the stomach and bronchi, hot flashes are bright red spots on the face and upper half of the body with a clear border.
• Bronchospasm (10-15%), dyspnea, generalized itching.
• Fibrosis of the heart valves (2/3 of patients) with the development of right ventricular failure, rarely - mesenteric and retroperitoneal fibrosis (with symptoms of intestinal obstruction and obstruction of the ureters).
• Tumor growth and metastasis (intestinal obstruction, obstructive jaundice etc.).

Rice. 1. Change in the color of the patient's face during hot flashes with carcinoid syndrome

Diagnostics

1. The main marker of carcinoid tumors is the serotonin metabolite - 5-HIAA, determined in daily urine. Determination of serotonin and histamine in the urine is decisive in the diagnosis of bronchial and gastric carcinoid.

2. Topical diagnosis of a tumor. Scintigraphy of somatostatin receptors is highly informative in carcinoid tumors.

Differential diagnosis

1. Clinical syndromes accompanied by hot flashes (postmenopausal syndrome, liver cirrhosis, idiopathic hot flashes).

2. If available in clinical picture a pronounced sympathoadrenal component requires a differential diagnosis with pheochromocytoma.

3. Metastases in the liver of a tumor of unknown primary localization.

Treatment

Surgery may make sense even if distant, especially solitary, slowly growing metastases are detected.

Chemoembolization and alcohol ablation of hepatic metastases.

Antiproliferative and symptomatic therapy: the drug of choice is octreotide. In addition, α-interferon preparations, polychemotherapy (streptozotocin, 5-fluorouracil and adriamycin) are effective.

Forecast

The malignancy of carcinoid tumors varies greatly - the 5-year survival rate is about 50%. Cases of fulminant course have been described, but more often the life expectancy of patients even with a widespread metastatic process is more than 5 years (cases of survival up to 20 years and many cases up to 10 years are described) and can significantly extend against the background of modern antiproliferative therapy. The most favorable prognosis for carcinoid appendix, the worst - with bronchial carcinoid.

Dedov I.I., Melnichenko G.A., Fadeev V.F.