“Doctors noted regression of the tumor. This meant that we could do without surgery!”

Tumor disintegration is a natural consequence of too active growth of a cancer node along the periphery or a complication of an excessively high response of a common malignant process to chemotherapy.

Not every patient has to face the severe problem of the disintegration of the cancer process, but with any intensity of clinical manifestations, the condition initiated by the disintegration of the malignant tumor directly threatens life and radically changes the therapeutic strategy.

Tumor decay: what is it?

Disintegration is the destruction of a malignant neoplasm; it would seem that it is precisely disintegration that must be strived for in the process of antitumor therapy. In fact, during chemotherapy, cancer cells are destroyed, only the killing is organic and not massive, but of single cells and small cell colonies - without the death of a large mass of tissue with the release of toxic contents into the blood from decaying cells.

Under the influence of chemotherapy, cancer cells do not decay, but undergo the process of apoptosis—programmed death. The remains of cancer cells are actively utilized by phagocytes and carried away from the maternal formation, and in the place of the dead, normal scar tissue appears, very often not visually detectable.

Regression of a malignant neoplasm in the form of apoptosis occurs slowly; if you observe the neoplasm at intervals of several days, you will notice how along the periphery the cancerous node is replaced by completely normal tissue and shrinks in size.

During decay, the cancerous conglomerate is not replaced by healthy connective tissue cells; dead cell layers form into a focus of necrosis, delimited from the rest of the cancer tumor by a powerful inflammatory shaft. Inside a malignant neoplasm, necrosis is not able to organize itself and be replaced by a scar; it only grows, capturing new areas of the cancer node, thereby destroying the tumor vascular network. From the dead focus, products of cellular decay enter the bloodstream, causing intoxication.

In some malignant diseases of the blood or lymphatic tissue, decay also occurs during chemotherapy, but without the formation of a necrosis zone, while massively dying cancer cells release their contents into the blood, which does not have time to be utilized by phagocytes, “clogs” the kidneys and is carried into the vessels of other organs.

The massive release of cellular substrate causes severe intoxication that can lead to death.

Theory and practice

In behavior, regression is a transition to a previous stage. Particular attention was paid to this phenomenon in the works of Freud, the most famous Austrian psychoanalyst of the last century. He developed an ontogenetic theory, within the framework of which he examines what regression is.

In accordance with psychotherapy, the term should denote the return of the individual to a time when he felt satisfied with the situation. Currently, psychoanalysts prefer to understand regression as an ineffective defense mechanism that is activated when an uncomfortable situation arises. The greatest practical benefit would come from finding a way out of the situation, but in reality, many people only strive to simplify a complex problem, thereby driving themselves into an even more hopeless dead end.

Causes of disintegration of a malignant tumor

The disintegration of a cancerous formation is initiated by only two reasons: the very activity of the cells of the malignant tumor and chemotherapy.

The first cause of spontaneous decay is characteristic of solid neoplasms, that is, cancer, sarcomas, malignant brain tumors and melanoma. The second cause of decay is typical for oncohematological diseases - leukemia and lymphomas; it is extremely rare in oncological processes.

Over time, the central part of a malignant neoplasm of any morphological origin begins to experience difficulties with the delivery of nutrients. This happens because cancer cells multiply faster than the vascular network that “feeds” them is formed. Starving cell layers die, which is manifested by disintegration with the formation of a zone of necrosis, delimited from living tumor tissue, with the gradual formation of a cavity in which slow rotting processes occur.

If the necrotic cavity is close to the skin, it can break out in the form of a disintegrating “ulcer” and the formation of a non-healing ulcer, for example, in the mammary gland. In the lung, an X-ray will reveal a dark “hole” inside a cancerous node with decay with a separately located island piece of necrotic tissue inside – a sequestrum.

The second variant of decay, typical for oncohematological diseases, can be ascertained by the clinical symptoms of severe intoxication with complications - tumor lysis syndrome (TLS) and biochemical blood tests, where the concentration of uric acid, potassium and phosphorus is sharply increased, but calcium is significantly reduced. The specific motivating factor for the development of SOL is an extensive malignant lesion with a very high sensitivity to chemotherapy.

In oncological processes - cancers, sarcomas, melanoma, the reaction to cytostatics is predominantly moderate and not so rapid, therefore SOL is fundamentally possible only in exceptional cases of small-cell, undifferentiated or anaplastic malignant process.

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Official position

You can learn about what it is – regression in simple words – by referring to the works of Sachs and Lish. It was they who examined the phenomenon in particular detail in relation to cancer patients. As we found out during the experimental study, a healthy body has the capabilities and resources to activate the reverse growth of a neoplasm. This is typical not only for the early stages. In Lisch's medical practice, there was a case where a relapse, provoked by weak excision, stopped developing, and then independently developed back.

As can be seen from published works, the regression method when applied to cancer patients can work completely unpredictably. If some part of the tumor is not removed during surgery, the transformed cells may die spontaneously. This was observed both in patients in whom cancer manifested itself in a visible area, and at the stage of only the appearance of the cancer complex in tissue structures.

Symptoms of the collapse of a malignant tumor

The clinical result of the spontaneous disintegration of a cancerous tumor is chronic intoxication, often combined with symptoms of generalized inflammation due to the formation of a purulent focus. Symptoms are varied, but the majority experience progressively increasing weakness, an increase in temperature from low-grade to fever, palpitations and even arrhythmias, changes in consciousness - stupor, loss of appetite and rapid weight loss.

Local manifestations of spontaneous destruction of a cancer tumor are determined by its location:

• breast cancer, melanoma and skin carcinoma, oral tumors - a purulent, profusely secreting open ulcer with rough, undermined edges, often emitting a putrid odor;
• disintegrating lung carcinoma - when a necrotic cavity is perforated into a large bronchus, a paroxysmal cough with purulent sputum occurs, often streaked with blood, and sometimes profuse pulmonary bleeding occurs;
• destruction of neoplasms of the gastrointestinal tract - development of local peritonitis when a cancerous conglomerate perforates into the abdominal cavity, bleeding with black stools and vomiting of coffee grounds;
• disintegrating uterine carcinoma - intense pain in the lower abdomen, difficulty urinating and defecating with the formation of purulent fistulas.

Tumor lysis syndrome in leukemia and lymphoma is a potentially fatal condition leading to:

• first of all, to the deposition of uric acid crystals in the renal tubules with disabling function and acute renal failure;
• additionally damaging the kidneys is rapid acidification of the blood - lactic acidosis;
• a decrease in calcium levels and an increase in phosphates initiates a convulsive syndrome, complemented by neurological manifestations due to the release of cytokines;
• increased potassium negatively affects cardiac activity;
• the release of biologically active substances from cells leads to increased permeability of small blood vessels, which reduces the level of proteins and sodium in the blood, reduces the volume of circulating plasma, clinically manifested by a drop in pressure and worsening kidney damage;
• extensive and profound metabolic disorders in all organ systems resulting in multiple organ failure.

Where is this observed?

Psychotherapists who are forced to work with individuals suffering from neurotic disorders or infantilism know best what regression is. Regression is one of the forms that helps a person cope with emotional overstrain. Experts note that it is quite different from alternative ways of dealing with the problem. Substitution and generalization help maintain the structure of activity, but the phenomenon under consideration changes needs and motivation. All this leads to degradation of personality qualities. The process proceeds very quickly, especially in the absence of outside help.

At the same time, there are cases where the phenomenon has brought benefits to individuals. Thus, within the framework of the cognitive theoretical approach, it is customary to talk about the importance of regression as a technique for accessing simplified schemes that help to understand oneself, the problem, and ways to solve it. Starting from simple understanding, one can achieve personal progress over time.

Treatment of tumor decay

For effective treatment of a disintegrating tumor conglomerate, it is necessary to restore intratumoral nutrition through the rapid formation of a new vascular network, which is completely impossible. Therefore, in case of spontaneous decay, they resort to symptomatic therapy, including palliative surgical - “sanitary” interventions.

Formally, with a decaying tumor, radical surgery is impossible; the disease is often considered inoperable, but chemotherapy and radiation are excluded from the program because they can worsen necrosis. The desperate situation of the patient and the likelihood of massive bleeding from a large vessel eaten away by cancer justifies the performance of a palliative operation, the main goal of which is to remove the source of chronic inflammation and intoxication.

Tumor lysis syndrome is treated with many hours of drip infusions with increased diuresis - urine excretion, binding of uric acid with special medications. At the same time, the functioning of the cardiovascular system is supported, intoxication and inflammation are stopped. When acute renal failure develops, hemodialysis is performed.

Tumor lysis syndrome is difficult to treat, but its symptoms can be prevented or at least reduced. Prevention begins a few days before the course of chemotherapy and continues for at least three days after the end of the cycle. In addition to special drugs that remove uric acid, long-term droppers are prescribed, missing trace elements are introduced, and excess trace elements are removed or bound with other medications.

Prevention of tumor lysis has become the standard of care for hematologic oncology patients, which cannot be said about cancer patients with disintegrating malignant processes, for whom it is very difficult to find a surgeon willing to perform palliative surgery. Intervention for sanitary reasons is refused due to the difficulty of caring for a seriously ill patient after extensive surgery. In our clinic, no one is denied help.

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Modern ideas about the regression of atherosclerosis of the coronary arteries

00:00

Vladimir Trofimovich Ivashkin , academician of the Russian Academy of Medical Sciences, Doctor of Medical Sciences:

– I would like to introduce Professor Marat Vladislavovich Ezhov with pleasure, who will give us a report on “Modern ideas about the regression of atherosclerosis of the coronary arteries.”

Marat Vladislavovich Ezhov , Doctor of Medical Sciences, Professor:

– Thank you very much, dear Vladimir Trofimovich! Dear Colleagues!

I am glad to meet you again. Moreover, since our last meeting, certain changes have occurred in the world of cardiology and in particular in the section that concerns the problem of the reverse development of atherosclerosis. We have received new data. In addition, we have our own unique data that allows us to look into the future with optimism.

Atherosclerosis is a process that begins to develop in the second and third decades of life. Only after negative remodeling of the vessel occurs (narrowing) and the compensatory mechanisms associated with positive remodeling of the vessel or with the Glagov phenomenon are exhausted, do the first symptoms of the disease “angina pectoris” appear.

(Slide show).

Last year, the results of the PROSPECT study were presented. This is a study of the so-called natural history of coronary atherosclerosis. You can see at the top of the slide that we included 700 patients with acute coronary syndrome (ACS). They had changes in one or two main coronary arteries.

After successful stenting, intravascular ultrasound (US) examination of the proximal and middle segments of all three main arteries was performed.

What is important to emphasize.

Why can’t we predict the development of the next ACS, the next exacerbation of the disease?

Each patient may have many, several (more than 3-4) plaques in large segments of the coronary arteries.

01:58

Next aspect.

(Slide show).

You can see on the right side of the slide that the PROSPECT study confirmed the autopsy findings that you see on the left side of the slide. They were published back in 1995.

Most myocardial infarctions occur in changes in the coronary arteries, which have a degree of narrowing not exceeding 50%. You can see that the results of the PROSPECT study, obtained in vivo with intravascular ultrasound, completely repeat the results of pathomorphological studies.

In ACS (you see the data of the so-called virtual histology: red color means necrotic lipid core), fibroatheroma with a thin capsule occurs in every 4th patient. That is, an unstable atheroma.

According to our data, when we performed intravascular ultrasound in 30 patients with stable coronary heart disease and visualized 76 initial or borderline stenoses of the coronary arteries, every 4th plaque also has an unstable phenotype and a greater content of the necrotic zone.

A study that included patients after successful endovascular treatment. The total number of patients is more than 1200. Pay attention to their fate over the five years of observation.

Red ovals and circles indicate coronary events associated with the stented segment. We see that, starting from the second year of observations, the number of these events is small. It does not exceed 2%.

While the red circles, associated with the progression of atherosclerosis of the coronary arteries in all other segments (we remember that the number of plaques there can be three or more), cause a high increase in coronary events over five years of observation.

04:03

(Slide show).

The progression of atherosclerosis, as a rule, in most cases is associated with rupture of the atheroma. This is what an atherosclerotic tear of an atheroma looks like using pathomorphology, intravascular ultrasound and computer graphics.

The histological signs (we have already talked about this earlier) of unstable atheroma are well known.

• Rich lipid core.

• Thin fibrous cap.

• Increased infiltration of inflammatory cells.

As is now well known, based on modern clinical research and a strong evidence base, stabilization and even regression of atherosclerosis can occur if we reduce low-density lipoprotein cholesterol levels below 1.8 mmol/liter. Or we achieve a reduction of this indicator by 50% from the original one.

A necessary condition (as we well understand today) to prevent plaque destabilization is the use of statins in adequate (high) dosages.

The first study we cited frequently here was REVERSAL. It showed that with the help of Atorvastatin at a dose of 80 mg, stabilization of atherosclerotic plaques in the coronary arteries occurs. Data were obtained using intravascular ultrasound.

The left column characterizes standard statin therapy: atherosclerosis in the coronary arteries is progressing.

In the ASTEROID study, Rosuvastatin was prescribed at a dose of 40 mg for two years. This was the first (admittedly uncontrolled) study to show that regression of atherosclerosis in coronary arteries is possible across all sections. The percentage of atheroma volume decreased by approximately 1% in absolute terms. 78% of patients showed signs of regression of atherosclerosis.

05:59

All this led to the launch of the SATURN study about three years ago, where two modern statins in maximum dosages were prescribed in direct comparison to patients with stable coronary heart disease for two years. Atheroma was assessed using intravascular ultrasound.

A large number of Russian centers participated.

(Slide show).

Finally, the results of this study were presented in December. The primary and secondary endpoints are presented on this slide.

If there was no difference in the primary endpoint, the percentage volume of atheroma between the Atorvastatin and Rosuvastatin groups, then in the secondary endpoint, assessed in the total volume of atheroma in cubic mm, Rosuvastatin demonstrated its advantage.

It beat Atorvastatin by about 2 cubic mm. This was probably due to a more pronounced lipid-lowering effect. In addition, on average, high-density lipoprotein cholesterol levels were slightly higher at the end of the studies.

Also a very important aspect for practical healthcare is that during two years of observation, at maximum doses of both statins, the percentage of so-called hard endpoints was extremely low: deaths and non-fatal myocardial infarction. The amount of increase in blood enzyme levels was negligible.

It must be said (and this is noted by all researchers) that this treatment was well tolerated by the patients.

In relation to the situation in our country, we can say that Rosuvastatin in a dose of 40 mg is present in only one form. This is the drug "Mertenil". You see that per month this is quite affordable for our patients.

The original drug is available only in a dose of 20 mg. If we needed to prescribe it even for some period of time (a year or two at a dosage of 40 mg), it would cost 3 times more than the drug “Mertenil”.

08:03

However, each of us understands: despite all our efforts, the so-called best drug therapy is powerless.

Look here please.

A patient who has been under our care for more than 10 years. In 2000, coronary heart disease started with a lower myocardial infarction. In 2004, he underwent stenting of the anterior descending and circumflex arteries. He took dual antiplatelet therapy for a year and a half.

As soon as he stopped it, he unfortunately suffered stent thrombosis in the circumflex artery with the development of anterior myocardial infarction. In 2006, stenting of the circumflex artery was performed again.

Literally 4 months later, he developed new stenoses in the right circumflex coronary artery. There was stenting again. Another 5 years later (very recently), due to the recurrence of angina, he underwent stenting of a new stenosis in the right coronary artery.

However, he does not have obvious risk factors for atherosclerosis: hyperlipidemia, hypertension. We will not talk about heart rhythm disturbances - in this situation this comes as a concomitant diagnosis. In addition, you see that with a disruption of the rhythm (this topic was already raised today), with atrial fibrillation, he also suffered a stroke in 2010.

Why such an aggressive course of coronary heart disease, an aggressive course of atherosclerosis.

Despite all our exhortations, the patient continues to smoke. A very interesting topic, which, unfortunately, goes beyond the scope of today’s possible discussion.

In 1996, he suffered from lymphogranulomatosis with multiple courses of chemotherapy and radiation therapy to the mediastinal area.

He has elevated lipoprotein(a) levels. We already talked about this once. Let me remind you that this is a unique particle, which consists, on the one hand, of low-density lipoproteins, but a long chain is attached to them. This is an apoprotein (a), which has a high degree of structural homology with the plasminogen molecule.

It is believed that the higher the level of lipoprotein (a), the more low-density lipoproteins it carries. Accordingly, the level of LDL cholesterol, which we estimate using the Friedwald formula, in the presence of high values ​​of lipoprotein (a) will be artifactual. It consists, at a minimum, of free LDL cholesterol and that contained in the lipoprotein (a) particle.

10:37

Let me remind you that in 2010 the Expert Consensus of the European Society of Atherosclerosis was published.

It was emphasized that the level of this indicator must be determined:

• all patients with coronary heart disease at a young age;

• patients who, despite constant use of statins, suffer a recurrent coronary event;

• persons at high risk of cardiovascular complications.

Last year, recommendations from the European Society of Cardiology and the European Atherosclerosis Society on the management of dyslipidemia were released.

In them, with class of evidence IIa, it was said that for screening and characterization of dyslipidemia before starting treatment, it is recommended to determine the level of lipoprotein (a) in patients at high risk and with a family history of cardiovascular diseases.

More than two years ago, we began a prospective 18-month study. More than 50 patients were included in it. Half of them received standard statin therapy in doses to maintain ideal low-density lipoprotein cholesterol levels. The other half of the patients received statins and extracorporeal blood purification methods (apheresis), which, first of all, reduced high levels of lipoprotein (a).

At baseline and at the end of the study, patients underwent control coronary angiography and intravascular ultrasound with virtual histology function.

12:08

Of course, the main hypothesis of this study was that specific elimination of the pathogenic factor lipoprotein (a) can lead to regression of atherosclerosis.

Our main task was to prove the atherogenicity or atherothrombogenicity of lipoprotein (a).

Today I can show you the first results of this study using the example of two patients. In particular, a man who suffered a myocardial infarction at the age of 34. The only risk factors he has are smoking and lipoprotein (a) – about 80 mg/dl. It was included in 2009. He underwent lipoprotein(a) apheresis procedures for two years.

You see data from quantitative angiographic analysis of all three great arteries. Black bars are data from 2009. Gray bars are from 2011. A decrease in the degree of stenosis was noted in all main coronary arteries.

(Slide show).

Intravascular ultrasound data of atheroma of the right coronary artery. Left columns – the total volume of atheroma decreased by 12 mm3. Middle columns – the necrosis zone has decreased by 1 mm3. At the same time, you can see from the pictures that the calcium content in the coronary atheroma has increased.

The extreme columns show the ratio of the necrosis zone to the calcification zone. It is believed that the higher this indicator, the worse. This is a sign of atheroma instability. The vulnerability index in this case decreased from 3 to 1.5.

(Slide show).

Another patient who also underwent lipid apheresis procedures for two years. You can see from the picture that the necrosis zone has decreased, but the calcium content has also decreased. At the same time, the total volume of atheroma decreased by almost 2 times. Necrosis zone from 9.4 mm3 to 3.3 mm3. The calcium content has decreased. The vulnerability index has decreased slightly.

14:05

What does our research mean for practice, for practicing doctors?

This is a model for the use of new lipotropic agents that, in addition to statin therapy, may reverse atherosclerosis.

If we look at the drugs that are available today in the arsenal of cardiologists and therapists, how do they affect the main indicators that interest us. Naturally, these are the drugs that we can use in addition to statins.

"Ezetimibe" Additional effect on lipids. The data on the dynamics of atherosclerosis are contradictory. There is no data on the prognosis (with the exception of the SHARP study).

"Fenofibrate" It has a positive effect on lipids. There is practically no effect on the dynamics of atherosclerosis. We know there is no positive data on the prognosis.

A nicotinic acid. Has a positive effect on all lipid fractions, including a reduction in lipoprotein (a) levels by 30%. In combination with statins, it has a positive effect on the dynamics of atherosclerosis of the coronary and carotid arteries.

Also, according to a meta-analysis, a positive effect on prognosis. But last year, the AIM-HIGH trial showed no benefit in patients with low HDL cholesterol.

There is not enough data on Omega3 to discuss today.

What are the prospects? New classes of drugs.

Anacetrapib, an inhibitor of the cholesteryl ester transfer protein. It successfully passed the second phase of clinical trials. It, as you know, significantly increases high-density lipoprotein cholesterol and lowers lipoprotein(a).

Thyroid receptor agonist "Eprotirome". Also has a positive effect on blood lipids.

Antisense therapy, when we influence the messenger RNA for the synthesis of a particular protein.

In particular, Mipomersen. This is a drug that suppresses the synthesis of apoprotein B, the main transport protein of atherogenic lipoproteins.

You see the following drug (abbreviation). It is currently in the preclinical research stage. It is most interesting because it significantly reduces the synthesis of apoprotein (a).

Finally, RVX222. This is a drug that, on the contrary, stimulates the synthesis of apoprotein (A), which is a carrier of high-density lipoproteins.

Unfortunately, the program to study Eprotirome as a promising thyroid receptor agonist drug was closed in February after a successful second phase, where it was prescribed to patients with familial hypercholesterolemia for 12 weeks. With long-term use in dogs, the drug in high and low doses led to the destruction of cartilage tissue, while these effects were absent in the control group.

I would like to conclude that for stabilization and regression of atherosclerosis of the coronary (and not only coronary) arteries it is necessary, first of all:

• modify standard risk factors;

• if we use statins, then they are modern and in high dosages;

• if target levels of low-density lipoprotein cholesterol are not achieved, with high levels of lipoprotein (a), combination therapy and the use of lipid apheresis should be considered.

Thank you for your attention.

Summing up

It’s not for nothing that philologists are proud of the richness of the Russian language. Indeed, one can come across such unique terms, the meaning of which is extremely rich and varied. The considered example of regression is a good proof of the postulate about the diversity and meaningfulness of the Russian language. The word itself came to us from Latin, but was applied to different areas of life and in modern times is widely used by specialists in various fields and ordinary people. The meaning of “reverse movement” has been preserved, while at the same time the scope of application has expanded.

Hormone therapy

Injections or tablets are selected for treatment. The course of treatment is long. Most often, oral contraceptives such as Janine, Yarina, Jess are recommended for use. Treatment is used for the following indications:

• If there is no uterine bleeding;
• Surgical interventions are contraindicated;
• If the fibroid is interstitial or subserous.

Do not use hormonal therapy:

• If a submucosal node is detected;
• There are liver diseases;
• The tumor has grown to a large size;
• There was a suspicion of cancer.

With this treatment, fibroids may become temporarily regressive. As soon as the course ends, it begins to grow again. For this reason, such treatment is most often used to prepare the body for pregnancy, as well as if a woman is approaching menopause.

Lots of meanings!

But not only in psychology, regression is also considered in esoteric teachings. This is typical primarily for those devoted to immersion in past lives. According to experts in this field, the term is usually understood as transvisualization.

To some extent, this phenomenon is similar to lucid dreaming, but at the same time it has specific differences. A person, moving into such a state, completely retains control of his own consciousness, but can get out of it without much effort. Immersion for this state is typically relatively weak. On the one hand, there are no sensations or details inherent in a classic full-fledged sleep, but at the same time a person gets a general idea. You can compare this to peeping through a crack. Many people believe that the degree of perception is determined by the quantity and quality of training.

You can go through regression either on your own, alone, or in a group of interested people gathered in one place and for one purpose. In large cities, such events are regularly organized for those interested. Special sounds are used. A division into levels is accepted, each of which is selected for a specific situation at the discretion of the most responsible and experienced group member or coach.

FUS ablation

New growths are removed using ultrasound therapy. For this purpose, a beam from a magnetic resonance tomograph is used. All fibroid tissues immediately die under the influence of high temperatures, the tumor is, as it were, “burned out.” The procedure takes from 2 to 6 hours. Menstruation after it should remove the remains of dead tissue from the uterus. The organ is then considered completely healthy.

The procedure itself is carried out absolutely without anesthesia, neither general nor even local. After it, there will be no stitches left on the woman’s body, and there will be no blood loss. The operation has minimal complications, their percentage is only 0.5% of all operations performed.

Why is FUS ablation performed? The reasons are as follows:

• It is necessary to preserve the uterus if the tumor is large;
• To prevent clinical manifestations;
• Infertility needs to be cured.