Paraneoplastic syndrome

What do they mean by the term "paraneoplastic syndrome"? Usually this is the combination of symptoms and laboratory indicators of oncopathology, which are not associated with the development of the original tumor and metastasis.

The syndrome is a nonspecific response of the body to the growth of the tumor, as well as the production of cancer cells by bioactive compounds. Paraneoplastic syndrome is characterized by the defeat of the endocrine system, skin, heart and vessels, nerves, muscles, kidneys, digestive system, hematopoiesis - separately or in combination with each other.

[1], [2], [3], [4], [5], [6]

Epidemiology

Paraneoplastic syndrome does not occur in all patients with cancerous tumors: according to statistics, only about 15% of patients are affected.

In approximately one patient out of three, the development of paraneoplastic syndrome is due to a violation of the hormonal balance. In other cases, neurologic, hematologic or rheumatic disorders were detected.

It is believed that signs of paraneoplastic syndrome in patients with cancer can develop during the course of the disease in about 60-65% of cases.

[7], [8], [9], [10], [11], [12], [13]

Causes of the paraneoplastic syndrome

The main cause of the appearance of paraneoplastic syndrome is the active state of the cancerous tumor, as well as the formation of the body's response to this active state.

Cancer cells produce bioactive proteins, enzymes, IG, PG, cytokines, hormonal substances, growth factors that affect the performance of an organ or system. The interaction of healthy tissue and tumor tissue leads to the appearance of immune reactions, which, in turn, stimulates the appearance of autoimmune disorders.

[14], [15], [16]

Risk factors

It is believed that any type of cancer can provoke the development of paraneoplastic syndrome. But most often the syndrome appears with such pathologies:

• with lung cancer;
• with ovarian cancer;
• with breast cancer;
• with testicular cancer;
• with a malignant lesion of the lymphatic system.

[17], [18], [19], [20], [21]

Pathogenesis

Paraneoplastic syndrome can develop in different ways. Malignant neoplasm can lead to disruption of processes in tissues as a result of ectopic isolation of hormone factors. For example, a decrease in the level of calcium in the blood during oncology is due to the ectopic release of PTH-linked proteins, which differ from PTH, but exhibit the same physiological activity. This can explain increased bone resorption. Simultaneously, parathyroid proteins contribute to increased growth of the neoplasm and the initiation of metastasis. This reaction is most common in lung and kidney cancer.

Another variant of the development of paraneoplastic syndrome can be caused by oncoantigens, which cause the body's response in the form of autoantibody production. Modern medicine has data on more than 400 species of such antigens. The clinical role of most antigens, unfortunately, is unknown.

[22], [23], [24], [25], [26], [27], [28], [29], [30], [31]

Symptoms of the paraneoplastic syndrome

The first signs of paraneoplastic syndrome in most cases occur in a short time, sometimes - for several weeks or months. Symptoms can be different, depending on the type of paraneoplastic syndrome, and on which organ is affected.

The syndrome is characterized, in the first place, by myopathy and arthropathy, in conjunction with nonspecific signs of the disease.

Types of Syndrome	Symptoms
Syndrome with dermatomyositis and polymyositis	Increased myasthenia gravis, skin rashes.
Myasthenic syndrome	Myasthenia gravis, omission of the eyelid, diplopia.
Hypertrophic arthropathy	Painful increase in fingers and toes, phenomena of periostitis, pain in the joints.
Paracancreatic polyarthritis	Unsymmetrical arthritis of the joints of the legs.
Amyloidosis syndrome	Weakness in the joints, dermatological purpura, the appearance of subcutaneous nodules, weakness of the heart muscle.
Lupus-like syndrome	Inflammation of the lungs, pericardium, joints, Raynaud's syndrome.
Sympathetic-dystrophic syndrome	Pain in the hands, trophic disorders, fasciitis, an aggressive form of polyarthritis.

• Neurological paraneoplastic syndrome

Neurological (neuromuscular) paraneoplastic syndrome is characterized by damage to the peripheral and central parts of the nervous system.

The syndrome can reveal itself the development of encephalitis, neuroses, dementia. Often, the disease occurs against the background of Guillain-Barre syndrome, which is a kind of peripheral neuropathy, manifested in patients suffering from Hodgkin's lymphoma. It is also possible to develop other types of peripheral neuropathies.

• Paraneoplastic syndrome in lung cancer

In patients with small cell cancer in the lung, paraneoplastic syndrome is usually accompanied by the development of Cushing's syndrome and disorders of water-electrolyte metabolism.

Cushing's syndrome is hypercorticism, provoked by an elevated level of endogenous or exogenous HA in the blood. The pathology is manifested by violations of fat, carbohydrate and protein metabolism, development of immunodeficiency, ecchymosis, myasthenia gravis, disorders of hormonal regulation in the genital area,

• Endocrine paraneoplastic syndromes

Endocrine and metabolic paraneoplastic syndromes are manifested by all kinds of disorders of the hormonal balance and metabolic processes.

With cancer of the thyroid gland may develop hypocalcemia, which is characterized by a latent flow and is characterized by excessive neuromuscular excitability.

• Hematologic paraneoplastic syndromes

Hematologic paraneoplastic syndromes in patients with malignant tumors are most often detected. In most cases, this is a moderate, or weakly expressed normochromic anemia. At the general or common analysis of a blood it is often possible to pay attention to the raised or increased SOS, the raised level of leucocytes with shift of the leukocytic formula to the left.

With b-cell tumors of lymphoid tissues, paraneoplastic syndrome can occur against the background of hemolytic anemia of autoimmune genesis, and in patients with Hodgkin's lymphoma or with melanoma - against agranulocytosis. When blood cancer is observed thrombocytopenia, and with a cancerous lesion of the liver or kidney - erythrocytosis.

Stages

Stages of malignant process

1. Transformative stage (inductive) - the transformation of a healthy cell into a cancerous one.
2. The active stage (the stage of promotion) is the reproduction of degenerated cells.
3. The progressive stage is the period of malignant growth.
4. The final stage is the outcome of the malignant process.

[32], [33], [34], [35], [36], [37], [38], [39], [40], [41]

Complications and consequences

Neoplastic syndrome in itself is a complication of the cancer process, so the only consequence of it can be an unfavorable outcome - the death of the patient due to impaired function of organs and systems. Most often death comes from the inadequacy of cardiac or renal activity.

[42], [43], [44], [45], [46], [47], [48]

Diagnostics of the paraneoplastic syndrome

Patients with suspected paraneoplastic syndrome are primarily assigned laboratory tests:

• general blood test (anemia, accelerated ESR, leukocytosis, etc.);
• general urine analysis;
• analysis of cerebrospinal fluid;

The analysis of blood on tumor markers allows to establish the presence of a tumor in cases when the clinical symptoms of malignant lesions are absent.

Instrumental diagnosis is carried out to determine the localization of the original cancerous tumor. As a rule, use the results of computer and magnetic resonance imaging. In the presence of endocrine pathology, caused by hormone-dependent tumors, scintigraphy can be prescribed.

If there are cancerous neoplasms of the respiratory system or digestive system, biopsy and endoscopy is informative.

[49], [50], [51], [52], [53]

Differential diagnosis

Differential diagnosis is performed with non-paraneoplastic lesions. Sometimes positron-emission tomography is used for differentiation.

[54], [55], [56], [57], [58], [59], [60]

Treatment of the paraneoplastic syndrome

Treatment of paraneoplastic syndrome is, first of all, treatment of the original cancerous tumor. In some cases, additionally prescribed medications that suppress immune processes, which serve as an impetus to the development of paraneoplastic syndrome.

Medications are used as an additional treatment in combination with chemotherapy. Depending on the type of paraneoplastic syndrome, the following groups of drugs may become relevant:

• corticosteroids (prednisolone series);
• immunosuppressive drugs (cyclophosphamide, azathioprine);
• drugs for stimulation of neuromuscular conduction (pyridostigmine, diaminopyridine);
• Remedies for the seizure syndrome (carbamazepine).

	Dosing and Administration	Side effects	Special instructions
Methylprednisolone	Treatment begins with essentially small doses of the drug. Presumably, the dosage can be about 200 mg of the drug per day.	Dryness, atrophy of the skin, osteoporosis, pain in the muscles and joints, dyspepsia, oppression of the production of their own hormones, irritability, vertigo.	Undesirable prolonged treatment with the drug.

	Dosing and Administration	Side effects	Special instructions
Cyclophosphamide	The drug can be taken orally, as well as in the form of injections (the route of administration is determined by the doctor). The amount of the drug per course should be from 8 to 14 g.	Anorexia, toxic hepatitis, impaired consciousness, myelodepression, hemorrhagic cystourethritis, hair loss.	Throughout the course of treatment, blood transfusion is necessary.

	Dosing and Administration	Side effects	Special instructions
Azathioprine	Normally take 1.5-2 mg per kilogram of weight per day, in three divided doses. The duration of therapy is determined individually.	Myelodepression, pancreatitis, hemolytic anemia.	During the treatment it is necessary to regularly monitor the blood picture.

	Dosing and Administration	Side effects	Special instructions
Pyridostigmine	The drug is administered individually. The average amount of the drug per day is 30-60 mg, for three or four doses.	Increased sweating, drooling, tearing, frequent urination, bradycardia, lower blood pressure.	The drug is not prescribed for problems with the respiratory system.

	Dosing and Administration	Side effects	Special instructions
Carbamazepine	Is taken orally, from 100 to 400 mg 1-2 times a day.	Drowsiness, fatigue, depressive conditions, dermatitis, dyspepsia, allergies.	The drug is clinically incompatible with alcohol.

Simultaneously with drug treatment and chemotherapy, it is recommended to take vitamins, which also have an anti-cancer effect to varying degrees:

• Vitamin A is considered an antioxidant and has a reparative effect against cancer cells;
• vitamins of group B are responsible for metabolic processes in the body, and also normalize the function of the central and peripheral nervous system;
• Vitamin C reduces the severity of side effects from chemotherapy, and also protects cells and tissues from the negative effects of free radicals;
• vitamin D restores calcium metabolism, stimulates the processes of cellular differentiation;
• vitamin E has a high antioxidant activity, which allows taking it to prevent the re-development of tumors.

Physiotherapeutic treatment

After consultation of the doctor-oncologist at a paraneoplastic syndrome application of such physiotherapy is supposed:

• Dosed UFD;
• DDT;
• CMT;
• electrosleep;
• muscular electrical stimulation;
• ultrasound;
• electrophoresis;
• hydrotherapy;
• magnetotherapy;
• mineral water.

Contraindicated to apply heat, high-frequency procedures and massage directly on the site of the neoplasm.

Alternative treatment

• In paraneoplastic syndrome, propolis is recommended by mouth, 2 g daily, with food (for breakfast, lunch and dinner). The course of admission is 45 days.
• A good effect is expected from taking propolis in combination with honey. So, it is recommended to take 15 caps. Propolis tincture and 1 tsp. Honey before meals twice a day. The course of therapy is three months. After a month's break, the course can be repeated. Proposed treatment can be long, up to 3 years.
• It is useful to use a mixture based on badger fat: 500 ml of aloe juice, cognac, liquid honey and badger fat are used to prepare the medicine. Take 1 tbsp. L. In the morning, half an hour before lunch and before dinner.
• You can use the following recipe for alternative medicine: chop fresh torn cherry leaves, place 4 tbsp. L. Such leaves in 0.5 liters of boiling milk, boil for 5 minutes, cover with a lid. After 1 hour, filter the infusion and take ½ cup three times a day, for a month. If necessary, the course can be repeated.

Herbal Treatment

• Prepare a mixture of 100 grams of sage, 70 g of yarrow, 70 g of anise seeds, 100 g of a bottle. Three tablespoons of the mixture is placed in a thermos and poured 750 ml of boiling water (overnight). In the morning, the infusion is filtered and drunk 150 ml four times a day for 20-30 minutes before meals.
• Prepare the mixture on the basis of equal parts of the leaves of plantain, sage, ayr, elecampane and licorice. At night steamed in a thermos 2 tbsp. L. Mixture of 0.5 liters of boiling water. In the morning, the infusion is filtered and taken at 100-150 ml 4 times a day, half an hour before a meal.
• Pour 4 tbsp. L. Chamomile color 250 ml of boiling water, insist 20 minutes. Drink daily for 150 ml at least 4-5 times a day.
• Take tincture hemlock three times a day for 2 drops per 1 tbsp. L. Water.

Homeopathy

Homeopathic treatment with paraneoplastic syndrome is prescribed in combination with basic treatment and has several advantages:

• allows to reduce the severity of adverse events from chemotherapy and radiation;
• slows the growth of the growth;
• improves the quality of life and prolongs it;
• prevents metastasis and relapse of the tumor;
• does not have its own side effects.

Homeopathic preparations are prescribed strictly individually, since their dosage directly depends on the stage and severity of the cancer process, on the localization and prescription of the paraneoplastic syndrome.

• Aloe - used in the cancer process in the intestine and rectum.
• Aurum muriatikum - used for cancer of the mucous membranes.
• Barite carbonate - is prescribed for cancerous brain tumors.
• Hekla lava - used to alleviate the condition of patients with cancerous lesions of the bone system.
• Hydrastis - is prescribed for malignant processes in the digestive system.
• Lachesis - is recommended for use in malignant processes in the reproductive system (with cancer of the ovaries, uterus).
• Lilium tigrinum - used in oncopathology of the genital area.

Prevention

The only possible prevention of paraneoplastic syndrome is timely and qualitative treatment of the original cancer process. The earlier treatment is prescribed, the better will be the prognosis of the disease.

[61], [62], [63], [64], [65], [66], [67], [68], [69]

Forecast

Paraneoplastic syndrome can manifest itself in different ways, and affect fundamentally different organs and systems of organs. Therefore, the prognosis may be different and depend on both the degree of neglect of the cancer tumor (its stage) and the variety of paraneoplastic syndrome. For example, the development of DIC syndrome (syndrome of disseminated intravascular coagulation) indicates the onset of irreversible processes in the body, and the development of hypertrophic arthropathy deserves a relatively favorable prognosis.

[70], [71]