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Molecular genetic foundations and principles of early diagnosis and screening of familial and sporadic variants of colorectal cancer in young patients Text of a scientific article in the specialty - Clinical Medicine

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Colorectal cancer is a malignant tumor of the large intestine. The neoplasm can be localized in the colon, sigmoid or rectum. In terms of prevalence, colorectal cancer ranks second after lung cancer among all localizations of malignant tumors.

For early diagnosis of the disease, oncologists at the Yusupov hospital use all modern diagnostic methods, and conduct colorectal cancer tests. The NADAL test for the hemoglobin-haptoglobin complex (test cassette) is a visual enzyme-linked immunosorbent double rapid test for the qualitative detection of human hemoglobin and the hemoglobin-haptoglobin complex in fecal samples.

Doctors at the Oncology Clinic conduct multidisciplinary treatment of colorectal cancer:

  • Perform radical and palliative surgery,
  • Prescribe the most effective antitumor drugs with a minimal spectrum of side effects,
  • Radiation therapy is carried out using the latest radiotherapeutic units from leading manufacturers.

Medical staff provides professional care for patients after surgery. In the case of stoma formation, hygienic care of the unnatural anus is carried out, patients and their relatives are trained to use the colopriema correctly. Patients in end-stage colorectal cancer receive palliative care.

Types of Colorectal Cancer

According to the development mechanism, hereditary familial non-polyposis, hereditary with familial adenomatosis and sporadic (non-hereditary) colorectal cancer are distinguished. By the nature of growth, the exophytic, endophytic and mixed (saucer-shaped) forms of colon cancer are distinguished, which is characterized by a combination of the two previous forms.

Exophytic colorectal cancer grows mainly in the lumen of the large intestine. It is an easily vulnerable tumor of significant size. Often complicated by bleeding, but rarely overlaps the intestinal lumen. It is localized more often in the right, wider parts of the large intestine.

Endophytic colorectal spreads mainly in the thickness of the intestinal wall. A tumor relatively quickly causes a narrowing of its lumen and a delay in feces. It is located mainly in the left, narrower sections of the large intestine.

According to the histological structure, adenogenic and squamous colon cancer are differentiated. Adenogenic malignant tumor is adenocarcinoma of high, medium or low degree of differentiation. The lower the differentiation, the more aggressive the cancer process. The following histological types of colorectal cancer are particularly aggressive:

  • Cricoid-cell,
  • Small cell undifferentiated,
  • Mucous (mucoideum).

Colorectal cancer hematogenously metastasizes to the liver, lymphogenous to the ovaries, lung and peritoneum.

Single and primary multiple colon carcinomas are distinguished by the number of. The modern classification of colorectal cancer, proposed by the International Cancer Union to determine the stage of cancer, includes the distribution of the tumor process by letters (T - tumor, tumor, N - nodus, node, M - metastasis, metastases).

Oncologists at the Yusupov hospital use the following characteristics of colorectal cancer:

  • Tis (cancer in place - an epithelial neoplasm or tumor with invasion of the mucous membrane,
  • T1 - the neoplasm infiltrates the intestinal wall to the submucosal layer and occupies less than half of its circumference,
  • T2 - a tumor infiltrates the muscle layer and occupies more than half the circumference of the intestine,
  • T3 - the neoplasm infiltrates all layers of the intestinal wall,
  • Tx - the tumor invades the visceral peritoneum or spreads to neighboring tissues and organs.

N0 is characterized by the absence of metastases to regional lymph nodes. N1 indicates the presence of metastases in the lymph nodes of the first order. At stage N2, multiple metastases are detected in the lymph nodes of the first and second order. Nx is indicated when there is not enough data to confirm the presence of regional metastases in the lymph nodes.

Depending on the presence and spread of metastases, the following variants of the course of colorectal cancer are distinguished:

  • M0 - no distant metastases,
  • M1 - there are distant metastases,
  • Mx - not enough data to establish distant metastases.

Colorectal cancer often affects the hepatic and splenic bends of the colon or rectosigmoid angle where fecal retention is observed.

Causes and mechanisms of colorectal cancer

Colorectal cancer occupies a leading position in morbidity and mortality from malignant tumors in Russia. The development of molecular biology has led to a deciphering of the mechanisms of tumor formation and progression. These processes require the accumulation of genetic and epigenetic changes in the tumor cell. It occurs by the accumulation of mutations in genes that control the growth and differentiation of epithelial cells. This leads to their genetic instability.

One of the variants of genetic changes is microsatellite instability in colorectal cancer. It is characterized by a violation of the repair mechanism (a special function of cells, which consists in the ability to repair chemical damage and rupture of unpaired DNA bases). This leads to the fact that mutations in the cell genome accumulate at a faster rate than in the normal state.

With familial adenomatous polyposis, gene mutations occur that damage the DNA of cells with the formation of microsatellites. In patients with hereditary forms of colorectal cancer, the presence of gene defects in various chromosomes has been established. With hereditary forms of the disease, structural changes in the nucleotides were revealed. With sporadic (non-hereditary) colorectal cancer, a hereditary predisposition is the cause of the disease in 18% of patients.

A direct transition of a normal cell to adenocarcinoma is possible. More often this process develops sequentially: first, the differentiation of colonocytes decreases, then benign neoplasms (adenomatous, adenopapillomatous) are formed, then they degenerate into a cancerous tumor.

In the development of colorectal cancer, a certain role is played by exogenous and endogenous factors, including nutritional, functional disorders of the large intestine (chronic constipation). Nutritive risk factors for colorectal cancer include:

  • Eating large amounts of red meat (beef, pork, lamb),
  • Excess dietary fat
  • The predominance of refined foods lacking in fiber,
  • The systematic use of alcohol.

An important risk factor for colorectal cancer is chronic idiopathic inflammatory bowel disease: granulomatous and ulcerative colitis. A certain role is played by dysbiosis of the large intestine of high degrees.

In the presence of adenomatous polyps, their almost inevitable transformation into colorectal cancer occurs. Malignancy occurs at different times during 13-15 years. The cause of sporadic colorectal cancer can be disorders in the cells of the gastrointestinal tract, capable of producing and accumulating biogenic amines and peptide hormones.

Symptoms of Colorectal Cancer

Late diagnosis of colorectal cancer is associated with a significant interval between the onset of the disease and its symptoms. The first signs of colorectal cancer are:

  • Stomach ache,
  • A mixture of blood in the feces
  • Delayed bowel movements.

Even with these symptoms, 50% of patients seek medical help only after 6 months, and 22% after a year. Only 37% of general practitioners make the correct diagnosis during treatment. Oncologists at the Yusupov hospital begin to conduct a comprehensive examination of patients for colorectal cancer in the presence of the following symptoms of the disease:

  • Delays in the evacuation function of the large intestine (chronic constipation),
  • Signs of intestinal bleeding or occult blood in the stool,
  • Tenesmus (false urge to defecate).

Abdominal pain is a late symptom of colorectal cancer in women and men. Pain syndrome develops with the development of a perifocal inflammatory process, intestinal obstruction, or cancer sprouting into neighboring tissues.

A tumor can sometimes be felt through the abdominal integument or with a digital examination of the rectum. Due to hidden or obvious intestinal bleeding, signs of anemia develop:

  • Dizziness,
  • Fast fatiguability,
  • Pallor of the skin,
  • Fragility of nails and hair,
  • Reduced red blood cell count in the peripheral blood,
  • Decreased hemoglobin.

With carcinomatosis and the presence of distant metastases, there is a sharp decrease in body weight, weight loss. With partial intestinal obstruction and severe intoxication, an aversion to food, belching, nausea and vomiting, a feeling of heaviness and overflow, persistent constipation, occasionally followed by diarrhea, flatulence appear. If colorectal cancer affects the sigmoid colon and rectum, an admixture of blood is found in the feces, sometimes mucus and pus. With the act of defecation, patients have a feeling of having a foreign body, incomplete emptying of the rectum.

An objective examination of the late stages of colorectal cancer oncologists reveal pallor of the skin and visible mucous membranes, an increase in the volume of the abdomen. When probing sections of the large intestine, a tumor is determined. If there are metastases to the liver, it increases in size, becomes dense, bumpy. Inguinal lymph nodes increase.

Diagnosis of colorectal cancer

A finger examination of the rectum in the knee-elbow position of the patient in 25% of cases allows probing a tumor in the distal intestine. It has the appearance of a dense formation, which narrows the intestinal lumen. The doctor determines the extent of the lesion, the mobility or immobility of the tumor, the condition of the pelvic lymph nodes and the tissue of the pelvis. He can detect blood on the glove. With progressive bowel stenosis, paroxysmal pain in the abdominal cavity, symptoms of partial obstructive intestinal obstruction appear.

In addition to the clinical examination, oncologists of the Yusupov hospital use various laboratory and instrumental methods in the diagnosis of colorectal cancer. An early diagnosis (in the Tis and T1N0M0 stages) can be established in 2-3% of asymptomatic patients only during random sigmoidoscopy.

Using a test for occult (occult) blood in the feces, colorectal cancer is screened. How to prepare for the study? The patient is recommended to exclude products containing peroxidase (meat, radish, turnips), iron preparations and ascorbic acid from the diet. Feces are collected in a special box for three days.

The second method for screening colorectal cancer is an immunochemical test for occult blood in feces. The study is carried out by the method of hemagglutination with utilized antibodies to the globin of human hemoglobin. The method does not respond to the presence of inhuman peroxidase, which is found in vegetables and fruits, does not require dieting. This simplifies the study.

Other laboratory methods for diagnosing colorectal cancer are also used:

  • Hemoporphyrin test
  • Determining the rate of cell proliferation by studying some nuclear proteins,
  • Determination of fecal calprotectin,
  • Immunological test with determination of cancer-embryonic (oncofetal) antigen (CEA) and tumor marker CA19–9.

In the diagnosis of colorectal cancer, oncologists at the Yusupov hospital use the following instrumental methods.

  • Flexible (on fiber optics) and rigid sigmoidoscopy, which allows to detect a tumor in the lower parts of the large intestine, to establish its location, extent, growth pattern, to make a targeted biopsy for histological examination (instead of the biopsy, you can take smears from the surface of the tumor using a foam swab for cytological examination on a glass slide),
  • Colonofibroscopy - performed once with a time interval of 5 years, combined with targeted biopsy,
  • Virtual colonoscopy - involves computed tomography with analysis of a transformed image resembling that obtained by an optical colonoscope,
  • Transabdominal and endoscopic ultrasonography is a non-invasive method by which the presence of a volumetric formation in the abdominal cavity, metastases in the lymph nodes and liver, the spread of the tumor into the surrounding organs, is detected
  • Computed tomography - allows you to specify the degree of tumor invasion, the presence of metastases in the liver and regional lymph nodes,
  • Irrigoscopy and irrigography - allow you to determine the location and extent of a cancerous lesion, tumor decay, germination in neighboring organs, the presence of complications (fistulas, abscesses, intestinal obstruction, perforation).

For the diagnosis of colorectal cancer, double contrasting and multi-projection x-ray are used.

Colorectal Cancer Treatment

Oncologists and surgeons at the Yusupov Hospital masterly master the technique of performing all the surgical procedures known today that are performed for colorectal cancer. Surgical methods involve radical removal of the primary tumor with the lymphatic system draining it. The essence of the surgical intervention is the resection of the affected segment of the colon (neoplasm, mesentery and tissues or organ involved in the tumor process). Conduct. Careful preoperative preparation is important. The nature of the operation is chosen individually for each patient:

  • Left-sided or right-sided hemicolectomy with transversorectal anastomosis,
  • Subtotal colon resection,
  • Sigmoidectomy with descendorectal anastomosis.

With rectal cancer, abdominal-perineal extirpation is performed, measures are taken to create an artificial locking apparatus from a smooth muscle flap of the wall of the reduced intestine in the area of ​​the perineal colostomy, or an abdominal-anal bowel resection is performed and a colanal anastomosis is formed.

In stages II – III of colorectal cancer, surgical treatment is combined with adjuvant chemotherapy and radiation therapy. They reduce the risk of relapse and the development of tumors of a different location. To suppress tumor growth, 5-fluorouracil is used intravenously, intraarterially and rectally, leucovorin. To reduce their toxic effects, patients are prescribed interferon-a2a. Xeloda, tomudex, eloxatin are used as second-line chemotherapeutic drugs. Chemotherapy is combined with folic acid and immunomodulators.

Targeted therapy is a targeted attack on pathological foci with minimal damage to living tissues and organs that are located next to the neoplasm. Thanks to a special molecular test, doctors determine the type of cell mutation. A specific biological drug is selected for it. It will only “aim” at mutated cells and will not affect healthy ones. This method allows you to stop the development of colorectal cancer. In order to undergo diagnosis and treatment of colorectal cancer with innovative methods, call the Yusupov hospital.

Abstract of a scientific article on clinical medicine, the author of a scientific work is Kaydarov B. K., Afonin G. A., Kaydarova D. R., Dzhansugurova L. B., Music S. V.

The article provides data on the genetic basis for the development of some hereditary and sporadic variants of colorectal cancer. The role of molecular genetic studies in the screening and early diagnosis of tumors in patients with a history of cancer, the possibility of interventional methods in reducing morbidity and mortality in people with a hereditary predisposition to colorectal cancer is considered.

MOLECULAR-GENETIC BACKGROUND AND PRINCIPLES OF EARLY DIAGNOSTICS AND SCREENING OF FAMILY AND SPORADIC COLORECTAL CANCER IN YOUNG PATIENTS

The article deals with the genetic background of developing some hereditary and sporadic types of colorectal cancer. Significance of molecular-genetic investigations in screening and early diagnostics of tumors in patients with oncological burdening anamnesis, possibilities of interventional methods in lowering morb> colorectal cancer have been demonstrated.

The text of the scientific work on the theme "Molecular genetic foundations and principles of early diagnosis and screening of familial and sporadic variants of colorectal cancer in young patients"

MOLECULAR GENETIC BASES AND PRINCIPLES OF EARLY DIAGNOSTICS AND SCREENING OF FAMILY AND SPORADIC OPTIONS OF COLORECTAL CANCER IN YOUNG PATIENTS

Kaydarov B.K.1, Afonin G.A.1, Kaydarova D.R. 5, Dzhansugurova L.B. 2, Music S.V. 3, Lyubchenko L.N. 4, Zhunusova G.S. 2, Ereshenko C.C.1

1 Kazakh National Medical University. S.D. Asfendiyarova, Department of Oncology, Mammology and Radiation Therapy,

Almaty, Kazakhstan. 2 Institute of General Genetics and Cytology, MES RK, Almaty, Kazakhstan. 3 Hospital of modern oncological care, department of endoscopy, Kiev, Ukraine. Russian Cancer Research Center named after NN Blokhina RAMS, Laboratory of Clinical Oncogenetics, Moscow, Russia. 5 Almaty Cancer Center UZ Almaty, Almaty, Kazakhstan.

Summary in the article presents data on the genetic basis for the development of some hereditary and sporadic variants of colorectal cancer. The role of molecular genetic studies in the screening and early diagnosis of tumors in patients with a history of cancer, the possibility of interventional methods in reducing morbidity and mortality in people with a hereditary predisposition to colorectal cancer is considered. Key words colorectal cancer, hereditary tumor syndromes, molecular genetic diagnosis, early diagnosis, screening.

MOLECULAR-GENETIC BACKGROUND AND PRINCIPLES OF EARLY DIAGNOSTICS AND SCREENING OF FAMILY AND SPORADIC COLORECTAL CANCER IN YOUNG PATIENTS

B.K. Kaidarov, G.A. Afonin, D.R. Kaidarova, L.B. Dzhansugurova, L.N., S.V. Mouzyka, L.N. Lyubchenko, G.S. Zhunusova and S.S. Yereshenko. Abstract The article deals with the genetic background of developing some hereditary and sporadic types of colorectal cancer. Significance of molecular-genetic investigations in screening and early diagnostics of tumors in patients with oncological burdening anamnesis, possibilities of interventional methods in lowering morbidity and mortality in persons having hereditary predisposition to colorectal cancer have been demonstrated. Keywords colorectal cancer, hereditary cancer syndromes, molecular-genetic diagnosis, early diagnostics, screening.

ZHASESP1R! M ZHENE GENETIKALYK AURUSHANDYGY BAR ADAMDARDAGY SPORADICALLY ZHENE T ¥ KIM KUALAYTYN KOROREKTALA KATERL! YUKTER CLINICOGENOTYPE! ANALYSIS METHODOLOGY NESHERI

Kaydarov B.K., Afonin G.A., Kaydarova D.R., Dzhansugurova L.B., Music S.V., Lyubchenko L.N., Zhunusova G.S., Ereshenko S.S. Tuish Bul zhumista sporadical jean tukym kualaytin colorectalda katerl! iksikterdsch geneticik negizdy zhaila maglumat bertgen. Oncology tuu kaup bar patient screening screen genete diagnosis of koyudagi molecular genetics molecular pathology magynasy karastyrylgan. Ogan spit aurushandykty zhene elimdikti azaytamy interventionzdyk talaldersch mYmkindikteride talkylangan.

Tyndi sider: colorectalds katerl id ^ tukym kualayn katerl iсiк simndromdary, genetic molecules, diagnosis, diagnosis, screening.

Despite the impressive successes of recent decades in the early diagnosis and treatment of patients with malignant neoplasms, cancer remains one of the most significant threats on a global scale. About 10 million new cases of malignant neoplasms and more than 6.2 million cases of deaths from cancer pathology are registered annually in the world. Among the causes of death on the planet, it occupies one of the leading places, which affects the average life expectancy, its quality, the size of the irreparable loss of the population, and also causes significant economic damage. According to the forecasts of the World

Health organizations, cancer incidence worldwide will increase until 2050 from 10 to 24 million cases, and mortality - from 6 to 16 million cases recorded annually.

Colorectal cancer (ROCK) and rectum (PKK) of the colon is one of the most common malignant tumors. In the structure of oncological morbidity in the world, colorectal cancer currently ranks fourth. More than 1 ml is registered annually in the world. newly identified cases of clorectal cancer (CRC). It is known that the individual risk of developing this disease reaches 5-6%. The annual occurrence of 50 new cases of colon cancer per 100,000 population determines an average 5% population risk of developing the disease over a lifetime. Moreover, the incidence and mortality of colorectal cancer tend to increase. An increase in the incidence rate has been observed in recent years throughout the world, especially in Europe, the USA and the CIS countries. According to the National Cancer Institute (NCI) in the United States in 2010, 102900 cases of colon cancer and 51370 cases of death from colorectal cancer were recorded. In Russia, more than 40 thousand new cases of colon cancer are registered annually. At the same time, the frequency of colon cancer is 11.6 in men and 9.2 in women per 100 thousand of the adult population. The incidence of colorectal cancer, respectively, among men was 11.0 and among women 7.1 per 100 thousand adults. In recent years, Kazakhstan has seen an increase in the incidence of colon and rectal cancer, which reflects global trends and incidence rates for similar types of cancer in the CIS countries. According to the KazNIIOiR in the Republic of Kazakhstan in 2010, 1389 patients with a diagnosis of colorectal cancer (in 2009 - 1224) and 1179 patients with a diagnosis of colorectal cancer (in 2009 - 1140) were diagnosed for the first time in their life. The incidence rate per 100,000 population was 8.5 for colorectal cancer (7.7 in 2009) and 7.2 for colorectal cancer (7.2 in 2009). The rate of increase in incidence in 2010 was 10.7 and 0.9 for ROCK and PPH, respectively. Like other malignant neoplasms, colorectal cancer is a medical and social problem. This is due to a number of objective reasons. The tendency to increase the incidence of CRC and the ever-increasing cost of complex treatment is not enough

satisfactory immediate and long-term results - all this determines the urgency of the problem of the disease. Currently, oncologists are faced mainly with stages III and IV of colon cancer. Moreover, in clinical terms, there are two unequal groups of primary patients. An analysis of the data of the cancer registry of the Almaty Cancer Center (chief doctor - MD Kaydarova D.R.) showed that about 50% of patients with colon cancer in Almaty end up in general surgical hospitals due to complications of the underlying disease, primarily acute colonic obstruction. In surgical departments, such patients are provided with emergency surgical care for health reasons

and not always in the required amount. The patient does not receive specific antitumor treatment in these conditions. On the other hand, oncologists seek to perform more and more extensive volumes of surgical intervention for patients initially arriving at oncological institutions. Modern methods of combined and complex treatment, from year to year, are becoming more complicated and, accordingly, more expensive. Cancer Service Spends Resources on

the above actions, while until recently, due attention has not been paid to solving the problems of screening and early diagnosis of CRC.

In 2011 and 2012 in Kazakhstan, on the initiative of the head of state N.A. Nazarbayev, a number of decisions and state programs that are most important for the development of oncology were adopted. First of all - the State program for the development of health care of the Republic of Kazakhstan “Salamatty ^ aza ^ stan” for 2011-2015, the Program for the development of cancer care in the Republic of Kazakhstan for 2012-2016. The main objectives are to improve the prevention of cancer by introducing national screening programs, increasing the availability of high-tech diagnostic and treatment methods with scientifically based effectiveness and creating a modern system of rehabilitation and palliative care for cancer patients. In 2011, a colorectal cancer screening program was launched and a pilot project for screening for prostate cancer in the East Kazakhstan region was introduced. The currently observed increase in the incidence of colorectal cancer in the world and in Kazakhstan and an increase in the number of patients of a young age category with this pathology (“rejuvenation” of the contingent of patients with CRC) is a motive for revising the traditional risk factors for this disease. Along with traditional risk factors, which include a set of dietary, lifestyle, elderly, and background and precancerous conditions, there has recently been increased interest in genetic risk factors for colorectal cancer (both hereditary and sporadic) 8, 9. By According to various authors, approximately 10% of patients who develop colorectal cancer have an inherited genetic predisposition to this disease. From 3% to 5% of cases of CRC are associated with hereditary non-polypous colorectal cancer (NSCR, Lynch syndrome), in 1% of patients the disease is associated with familial adenomatous polyposis (CAP). About 10% of all cases of RTK are autosomal dominant diseases, i.e. developed in accordance with the laws of Mendel 2,5,6,7. Since the publication of the historical work of Bert Vogelstein in the journal Cell in 1990, and his presentation of a genetic model in which the staging of the molecular pathogenesis of colon cancer was first discovered, a number of important discoveries have been made in the genetics of colorectal cancer, making it clear that oncologists, in fact, they are dealing with several different tumors that arise in one organ. The recognition of the fact that cancer is a disease of the genome made it possible to establish the paradigm of the genetic heterogeneity of tumors developing on the basis of the patient’s unique genotype. This implies the implementation of the carcinogenesis process against the background of an individual profile of mutations and gene activity in interaction with environmental factors. It should be noted that CRC is an ideal model for studying the fundamental aspects of carcinogenesis. The staged morphological transformation is very characteristic of RTK, which, in turn, is due to the staged nature of the accumulation of PTK-associated mutations in oncogenes and suppressor genes. Interesting

A feature of RTK is the existence of fundamentally different variants of molecular pathogenesis.

1. More than 85% of RTKs show the so-called. chromosomal instability, expressed in multiple deletions, amplifications and rearrangements of large sections of chromosomes. A similar state of the genome is characteristic of many tumors.

2. An alternative pathogenesis of RTK involves microsatellite instability. The DNA of such tumors contains a large number of micromutations that violate mono-, di-, and trinucleotide repeats (RER + phenotype), while the structure of the chromosomes remains relatively intact.

3. Excess methylation of the so-called CpG islets. This designation applies to cytosine-guanine pairs arranged sequentially on the same DNA strand. Cytosines preceding guanine show increased sensitivity to methylation. Regulatory (promoter) regions of genes are characterized by the accumulation of a large number of GC pairs. If the latter undergo methylation, then the transcription of the corresponding gene is inhibited.

The translation of the results of basic research on the genetics of colon cancer into practically significant aspects allows a deeper understanding of the etiology and pathogenesis of the disease, and the development of an early diagnosis and optimization system for monitoring, treatment and prevention, taking into account the individual genotype of the patient. This is most relevant for patients in whom the disease arises on the basis of hereditary tumor syndromes, among which two groups of diseases are currently distinguished: familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. It is interesting that, morphologically, it is often not possible to detect any differences between tumors arising as sporadic cancer and neoplasms arising on a known genetic basis. All of them are in the vast majority of cases (about 90%) adenocarcinomas of various degrees of differentiation (mucous, cricoid, undifferentiated carcinomas are also found). However, in relation to the clinical course, genotype-phenotypic correlations, and prognosis of the disease between hereditary and sporadic cancers, there are numerous and significant differences. This applies to such important clinical characteristics of the tumor process as the age of onset of the disease, localization of the process in various parts of the colon, the presence of primary multiple, synchronous and metachronous tumors, the potential for tumor progression and the likelihood of metastasis 11,12,13.

Of great practical interest is the combination of colon tumors with other malignant neoplasms that occur in families with hereditary CRC syndromes. Analysis of the frequency of lesions of various malignant tumors in families of patients with colon cancer showed that it is quite high, in general - 16.2%, the frequency of damage to the same tumor is 2.4%, and stomach cancer - 2.3%. The endometrium is affected with a much lower frequency, and breast cancer is noted in 3.4%. In 9.9% of patients' relatives, single and multiple colon adenomas were noted. The risk of developing malignant tumors in patients with SAP is 18 times higher than the general population risk. On average, cancer in individuals with SAP develops at an earlier age, usually up to 40 years, that is, 20 years earlier than in the general population. Primary multiple malignant neoplasms localized outside the colon may also be observed. NNCRR is also characterized by a combination with other malignant neoplasms: cancer of the body of the uterus, ovaries, stomach, breast, pancreas. Primary frequency

of multiple malignant neoplasms among patients with NNKRR is 17.9% (synchronous tumors - 8.4% and metachronous - 9.5%). At the same time, the risk of developing metachron colorectal cancer increases by 16-19 times compared with the development of primary colon cancer. Often, single and multiple adenomas 11,14 are the substrate for the development of primary multiple colon cancer after removal of the first tumor in patients with NNCRR. The average age of development of RTK on the background of SAP is 30-35 years, which is 30 years earlier than in the general population, in 5% of patients malignancy of polyps occurs by the age of 20. Tumors of other locations (stomach, uterine body, thyroid gland, mammary gland, central nervous system, as well as primary multiple malignant neoplasms) can occur in 75% of patients carrying the pathological genotype (mutant ARS gene, which is the dominant etiological factor in the development of this pathology ) The functional significance of ARS mutations is associated with the key role of this gene in the regulation of cell division of the epithelium of the colon and other tissues.Structural changes in the APC gene are detected in 95% of cases of classical SAP (more than 500 variants). The frequency of terminal mutations is 50-70%. Lynch syndrome is a common hereditary form of RTK with an autosomal dominant type of inheritance, characterized by the development of RTK in several generations, the young (up to 45 years) age of onset of the disease, the predominant lesion of the right-sided colon, the high incidence of synchronous and metachron tumors, as well as the onset of malignant neoplasms of other localizations. Differences in molecular pathogenesis determine the clinical and prognostic factors of NNKRR. Terminal heterozygous mutations of the genes responsible for DNA repair errors (mismatch repair 2 - MMR) - MSH2, MLH1, MSH3, MSH6 (GTBP), PMS1, PMS2 in combination with microsatellite instability are the cause of NNCRR. A tumor usually occurs with a somatic mutation of a wild-type allele that inactivates the MMR system and increases the level of microsatellite instability, which plays a leading role in the initiation and progression of tumor growth 2,10,18. An earlier age of the onset of the disease (about 40-45 and 65 years, respectively), possibly associated with accelerated carcinogenesis, was noted, compared with sporadic RTK. It was shown that the multi-stage process of "adenoma-carcinoma" in patients with a history of oncology and functional genetic disorders proceeds over 23 years, whereas in the general population this process takes an average of 8-10 years. Isolation of various clinical and genotypic variants of SAP and NNCR promotes a differentiated approach to the treatment of each patient, depending on the variant of the disease. During a genetic examination of patients with SAP, it was noted that each clinical variant of the course of the disease corresponds to mutations located at specific sites of the APC gene 16.17. Such a correlation between the genotype and phenotype can serve as a justification for the development of factors for predicting the course of the disease in a particular patient and determine individual therapeutic tactics.

In relation to already ill patients with hereditary forms of RTK, provided that they have molecular genetic confirmation of one or another variant of “family” cancer (setting the so-called “molecular genetic diagnosis”), it is advisable to conduct a special treatment and observation program for these patients. The comprehensive program is multi-level and may include:

1. functionally gentle operations

2. special approaches to dispensary observation (regular examination to determine the dynamics

process and timely recognition of relapses and metastases)

3. a comprehensive rehabilitation program for young patients with CRC (medical, individual, social and labor)

4. genetic counseling.

Considering that patients with hereditary forms of RTK are carriers of mutations that are also found in their practically healthy relatives, special algorithms have been developed for diagnosis, preventive examination, and follow-up observation of patients with a hereditary predisposition to malignant neoplasms. Such programs have been introduced at the national level in the countries of the European Union, Russia and Belarus 12.19. A significant part of these programs relates to screening and early diagnosis of hereditary forms of colon and rectal cancer, as well as medical and genetic counseling for people at high risk for cancer.

Programs typically contain the following permanent components:

1. identification of mutations that determine one or another variant of the development of hereditary forms of colon or rectal cancer (for example, mutations at various sites of the APC gene, MLH1 and MSH2 genes, responsible for almost 90% of cases of Lynch syndrome).

2. special regulations and a set of measures for instrumental examination

3. in the case of molecular genetic verification of the hereditary variant of RTK - carrying out preventive measures or treating patients at the early (subclinical) stages of the tumor process

4. special dispensary observation

5. genetic counseling.

The main goal of such programs is the formation of risk groups and subsequent monitoring of patients related to them.

Primary prophylaxis of hereditary RTK variants is aimed at identifying germline mutations that determine a high risk of cancer. Screening for early diagnosis was shown to reduce the risk of developing RTK by 56% and overall mortality among patients with a history of cancer by 65%. In particular, an annual colonoscopy reveals local tumors of minimal size, which allows minimally invasive surgery without violating the principles of oncological radicalism, which also leads to a decrease in mortality. For patients with a pathological genotype, a follow-up observation is recommended, including a colonoscopy, starting from 25-30 years of age and a consultation of a proctologist. For women, the examination should be supplemented with intravaginal ultrasound of the pelvic organs, mammography, analysis of the level of the CA-125 marker, consultation of a mammologist and gynecologist in order to identify tumors of the female reproductive system. Total or subtotal colectomy followed by observation of the rectal condition is recommended for patients with hereditary non-polypous colorectal cancer, in whom, during the course of observation, CRC or progressive adenoma was detected. The motive for this decision is the high incidence of metachronous cancer (25–40%) in patients who underwent segmental colectomy. For women who already have children, preventive hysterectomy and bilateral salpingo-ovariectomy are appropriate measures. If family members have cases of cancer of the urinary and genital organs, it is necessary to conduct an annual analysis and cytological examination and ultrasound of the urinary organs from the age of 30-35 years. Of preventive operations in patients with SAP use

partial colectomy; in patients with Lynch syndrome, sub-total colectomy and bilateral

salpingo-ovariectomy after the end of the childbearing period. The 5-year survival rate in patients with NNKRR after performing preventive operations is 98%.

Secondary tumor prophylaxis is a program that is implemented through screening of relatives of patients and active medical examination of people with a high risk of cancer. So far, this is the only approach for the organization and functioning of the genetic prevention system for hereditary forms of cancer. One of the methods for the early diagnosis of SAP and NNCR is the creation of a register of families with patients with RTK. The information on the patient’s relatives contained in the register allows them to be actively involved in the examination until the development of clinical manifestations of adenomatosis or cancer. This approach, in turn, significantly reduces the number of patients with colon cancer developing at the time of diagnosis from 70 to 3-5%, and also allows you to identify risk groups, which facilitates the early diagnosis of the disease 16,20. The functioning of the register is advisable only in combination with molecular genetic studies, i.e. genetic screening that allows

to differentiate sick and healthy people among relatives in the same family. Patients identified based on the results of genetic screening should be included in the monitoring system, and healthy relatives should be removed from further monitoring.

We believe that genetic testing should be performed for all relatives of patients or family members with a hereditary history, subject to their voluntary informed consent to this procedure. The work on identifying carriers of the pathological genotype (mutations), and accordingly on the formation of risk groups and its stratification, taking into account the age and individual genotype of the patient, includes the following steps:

1. accumulation of clinical observations of already ill patients with hereditary forms of CRC and genetic verification of the nature of the process.

2. collection of anamnestic data (questionnaire) by the method of single registration of probands - patients, as well as their relatives, who are at risk, actively called for examination. Particular attention is paid to the clinical picture of the course of the disease in a particular family: the nature of the inheritance of adenomatosis or Lynch syndrome on the maternal or paternal side, the time of first complaints, the nature of the first diagnosis and the analysis of the reasons for its discrepancy with the true diagnosis, the time of development of colon cancer.

3. Verification and correction of the genealogical data obtained as a result of a survey of probands is carried out by inviting relatives for examination, including genetic testing, regardless of the presence or absence of clinical manifestations of the disease.

4. Instrumental examination includes: sigmoidoscopy, colonoscopy with examination of all parts of the colon in order to identify signs of malignancy. Previously, colonoscopy was recommended to be supplemented with irrigoscopy in order to visualize and document the distribution of polyps in the colon and to establish signs of their malignancy. However, the conducted studies demonstrate a low sensitivity of irrigoscopy with respect to adenomas, especially with a size of less than 1 cm. It is advisable to document the process during a colonoscopy by video archiving, which should become the standard of practice.

5. The methodology of genetic research is as follows: based on the data of the register that served

The basis for the recruitment of patients for genetic research is the selection of family members who undergo genetic testing for mutations that determine the risk of developing SAP or NNKRR. When a syndromic pathology is confirmed, the total genetic risk for a given individual is calculated during medical and genetic counseling with subsequent recommendations for preventive

events and timing of follow-up.

Even today, the current level of molecular genetic diagnosis allows you to fundamentally change the tactics of screening and diagnostic measures. This became possible with the introduction into practice of medicine of the concept of a human genetic passport - an individual database of DNA sequences reflecting the unique genetic characteristics of each person, his predisposition or resistance to certain hereditary or multifactorial diseases. Therefore, for the purposes of early diagnosis and screening with an oncologically burdened history, today there is no need to calculate the probabilistic risks of tumors in the relatives of patients (clinical genealogy method). Determination of a specific mutation in a specific DNA sequence of a patient can effectively identify individuals predisposed to malignant neoplasms and conduct early (preclinical) diagnostics followed by appropriate preventive measures. Despite the fact that the introduction of genetic screening into practice increases the absolute number of patients and potentially sick individuals, adequate early diagnosis and treatment in the early stages of the disease have great social and economic efficiency. Preventive and screening measures will reduce the burden on the health budget due to minimally invasive medical and preventive procedures, as well as by reducing the cost of expensive and long-term antitumor and symptomatic treatment of patients with advanced forms of tumors, maintaining the health and ability of patients to return to a full life , social activity and work.

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12. Chirivella I., Rosello S., Insa A. Hereditary cancer syndromes: the role of prevention and screening. // ESMO Handbook of cancer prevention. Edited by D. Schrijvers, H.-J. Senn, H. Mellstedt, B. Zakotnik. Informa, 2008.

13. Jarvinen H., Aarnio M., Mustonen H., et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary non-polyposis colorectal cancer. // Gastroenterology. 2000. - vol. 118. - p. 829-834.

14. Sijmons R.H. Hereditary cancer syndromes: common principles and the role of prevention and screening. // ESMO Handbook of cancer prevention. Edited by D. Schrijvers, H.-J. Senn, H. Mellstedt, B. Zakotnik. Informa, 2008.

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What is colorectal cancer?

"Colorectal cancer" is a collective concept for cancer (tumor) of various sections of the colon (colon) and rectum. Among the many oncological diseases, this pathology remains the least illuminated and most covered by the myths and fears of patients, but, nevertheless, modern opportunities for early diagnosis give reason to consider CRC on

95% preventable cancer.

Colorectal Cancer Prevalence

Statistics from developed countries of the world indicate a steady growth of newly diagnosed cases of colon and rectal cancer compared with malignant tumors of any other localization except lung cancer. In the world as a whole, the incidence is not the same: the highest incidence rates in Australia and New Zealand, Europe and North America, and the lowest in Africa and Central and South Asia. Such geographical differences, most likely, are determined by the degree of influence of risk factors for CRC - dietary features, bad habits, environmental factors against the background of genetically determined susceptibility to the development of this type of cancer.

In Russia, colorectal cancer occupies one of the leading positions. Among men with malignant neoplasms, CRC is in third place after lung and stomach cancer, and in women, respectively, after breast and skin cancer. An alarming fact is the high mortality rate in the 1st year of life after diagnosis, due to the fact that when patients first go to the doctor, advanced forms of cancer (stage III-IV) already have more than 70% of patients with colon cancer and more than 60% of patients with rectal cancer, with about 40% of patients undergoing surgical treatment.

In the United States, approximately 140,000 new cases of illness and approximately 50,000 deaths due to CRC are reported annually. Surprisingly, it is in the United States that there is a slow but constant tendency toward a decrease in the incidence of CRC, and survival rates in CRC are among the highest in the world. Reporting from the National Cancer Institute of the United States shows that 61% of patients with this diagnosis overcame five-year survival.

In the United States and many other Western countries, improved results were achieved, in particular, by the timely detection and removal of colon polyps, the diagnosis of early stage CRC and more effective treatment. Unfortunately, in many countries with limited resources and a different health infrastructure, especially in Central and South America and Eastern Europe, mortality from CRC continues to increase.

Colorectal Cancer Risk Factors

Colorectal cancer most often develops as a degeneration of adenomatous (glandular) polyps.

Despite the fact that a hereditary predisposition significantly increases the risk of developing CRC, most cases are sporadic (in other words, unpredictable, episodic), and not family: approximately 80-95% of cases are sporadic versus 5-20% having a hereditary cause. But among all other types of cancer in humans, CRC is most associated with family morbidity. Studies of the molecular mechanisms of colorectal cancer development have revealed a number of genetic disorders, most of which are inherited in an autosomal dominant manner and significantly increase the risk of cancer. Familial adenomatous polyposis and Lynch's syndrome (hereditary non-polyposis colorectal cancer) are the most common of family cancers with genetic defects, together they account for only about 5% of cases of colorectal cancer.

Among the other most well-known predisposing factors, inflammatory bowel diseases (ulcerative colitis, Crohn's disease) should be noted - the risk of cancer increases with the duration of the course of these diseases. The total incidence of colorectal cancer begins to increase approximately 8–10 years after the onset of inflammatory bowel disease and rises to 15–20% after 30 years. The main risk factors are the duration of the disease, the prevalence of the lesion, young age and the presence of complications.

Age is a significant risk factor: colorectal cancer is rare up to 40 years, but the incidence of colorectal cancer increases in each subsequent decade and reaches a maximum of 60-75 years.

There are factors that increase the risk of colorectal cancer. It has been established that populations of people in which the incidence of colorectal cancer is high consume foods that are low in fiber, but with a high content of animal protein, fat and refined carbohydrates. Obesity increases by about 1.5 times the risk of colorectal cancer, and more so in men. Excessive alcohol consumption and smoking are also among the factors that increase the sporadic incidence of polyposis of the colon and colorectal cancer, and significantly increase the risk of cancer in patients with hereditary diseases of the large intestine (for example, with Lynch syndrome).

What is colorectal cancer screening?

These are methods for actively identifying individuals with risk factors for developing CRC or with asymptomatic CRC, based on the use of special diagnostic methods. Screening for colorectal cancer can significantly reduce the likelihood of developing it, as it allows you to identify precancerous bowel disease or cancer at an early stage and provide timely medical treatment.

First of all, screening is required for people who have cases of colon or rectal cancer, adenomas, and inflammatory bowel diseases among first-line relatives (children, parents, brothers and sisters). The presence of such a diagnosis in a relative increases the risk by about 2 times compared with the population as a whole.

The recommendations of a number of colorectal cancer research communities (American College of Gastroenterology, Multisociety Task Force on Colorectal Cancer from the American Cancer Society, American College of Radiology) provide guidance on the timing of the first colonoscopy in the following patients:

earlier, up to 40 years old, in patients with close relatives with intestinal adenoma diagnosed before the age of 60,

10-15 years earlier than the “youngest” CRC in the family was identified, and / or this diagnosis was established at 60 years of age or younger.

The timing of screening studies can be changed if the patient has additional risk factors for CRC: radiation exposure of the abdominal cavity at an early age for cancer, a diagnosis of acromegaly (in which development of colon adenomatosis is possible), kidney transplantation (as the reason for long-term immunosuppressive therapy).

CRC screening and diagnosis

In the presence of the complaints described above, as well as in patients belonging to the high-risk group for the disease of CRC, an examination is carried out. The most informative and generally accepted method of early diagnosis is colonoscopy - an endoscopic (intraluminal) examination of the mucous membrane of the rectum, colon and part of the small intestine (for about 2 m). All pathological altered tissues and polyps will either be completely removed during colonoscopy, or pieces will be taken from them and sent for histological examination. If the education is on a broad basis or cannot be safely removed during a colonoscopy, the doctor will consider surgery.

Once cancer is diagnosed, patients need to have a CT scan of the abdomen and chest in order to detect metastatic lesions, as well as laboratory tests to assess the severity of anemia.

In 70% of patients with colorectal cancer, there is an increase in the level of cancer-embryonic serum antigen (CEA) and oncomarker CA19.9. Further monitoring of CEA and CA19.9 may be useful for the early diagnosis of tumor recurrence. According to indications, other markers of colorectal cancer are also being investigated.

The main screening study in patients older than 50 years with an average degree of risk is colonoscopy. In the presence of polyps or other pathology in the colon and rectum, the regularity of studies can increase to annual or every 3-10 years. Assessing the risk of colorectal cancer in patients with intestinal diseases, the doctor decides on the frequency of studies individually for each patient.

Only such an active position of doctors regarding the early diagnosis of polyps and the prevention of colorectal tumors has led to a slowdown in the incidence of colorectal cancer in the United States.

What types of colorectal cancer are there?

Colorectal cancer (CRC) includes several types. The first and most common is colon cancer (colon adenocarcinoma). The second most common is colorectal cancer (rectal adenocarcinoma). And the third type is cancer of the anal canal, as a rule it is squamous.

Other colorectal malignancies are much less common: gastrointestinal stromal tumor, neuroendocrine cancer or carcinoid - a more benign version of the neuroendocrine tumor. And very rarely there are melanomas of the rectum and anal canal.

What is the incidence of colorectal cancer?

If we take all types of cancer that are attributed to CRC, then in third place in the world. But in developed countries, the percentage of patients with CRC is slightly larger. Most likely, this is due to increased life expectancy and nutritional characteristics.

It is believed that if more meat products and less plant foods are consumed in a population, then the likelihood of colorectal cancer increases.

What types of CRC are more common among women, and which are among men?

It is reliably known that women suffer from any type of CRC more often. This is usually attributed to the fact that women live longer, and colorectal cancer, like most other types of cancer, is a disease of the elderly. It used to be that anal cancer was also more common in women. In 1975, in the United States per 100 thousand people, less than 1% of women and about 0.7% of men were sick. And by 2007, this level increased by 1.7 and 3 times, respectively.

The cause of this type of cancer has been reliably established - it is caused by the human papillomavirus (HPV) and is transmitted between partners practicing the anal type of sexual intercourse. Therefore, now many gay men are suffering from cancer of the anal canal, but, of course, women are also at risk.

If mass vaccination against oncogenic HPV strains is carried out, the current situation could be improved. Moreover, this works not only with the above disease, but also for other types of squamous cell carcinoma: cervical cancer and some types of head and neck tumors.

How can you understand that you have an increased risk of colorectal cancer? At what age should preventive examinations be started?

It is very important to remember that 10% of cases of CRC are hereditary forms.

In the USA, where screening is most developed, it is customary to distinguish between groups of medium, high and high risk.

Medium risk group - this is the majority of us: healthy people who do not have close relatives who would have had CRC, stomach cancer, uterine cancer or breast cancer. They lack hereditary syndromes and chronic inflammatory bowel diseases, namely ulcerative colitis or irritable bowel syndrome. In this group, screening examinations should be carried out from the age of 55.

High risk group - these are patients in whom blood relatives (parents or grandparents) were ill with the above types of cancer. Such people have an increased risk of malignant neoplasms, including CRC. Representatives of this group should start examinations earlier, in the United States they advise doing this from the age of 45.

And finally, there is a high-risk group. It includes patients with proven hereditary syndromes: diffuse familial polyposis, Peitz-Jägers syndrome, or Lynch syndrome. Such people are characterized by the early occurrence of polyps in the intestine and then the development of a malignant tumor from them. Also included here are patients who have been suffering from ulcerative colitis or Crohn’s disease for more than 10 years.

This group needs to start the screening program much earlier. For example, the presence of relatives with diffuse family polyposis shifts this boundary by as early as 20 years. And with Lynch's syndrome, a patient in 100% of cases will develop colorectal cancer if he survives. If an intestinal tumor is found in such people, then the entire colon and rectum are removed, realizing that sooner or later they will develop cancer in the remaining part.

The first stage of screening for all risk groups is an immunochemical analysis of feces for occult blood. A test can be quantitative and qualitative, but it is better to choose a quantitative one, it’s more accurate. If the test shows the presence of blood in the feces, then fibrocolonoscopy should be performed to see the entire colon and rectum.

What screening programs are currently in operation in Russia?

Unfortunately, in Russia there are no screening programs at all if we are talking about population screening. We have only some elements. For example, a program for screening for breast cancer was conducted in St. Petersburg several years ago. Women were examined, mammograms performed, mammologists' rooms were specially equipped, etc.

But such programs should be funded separately, and we are all trying to include in the clinical examination program, not completely understanding that clinical examination and oncological screening are two different things.

In total, three tumor localizations are known in the world for which population screening has been proven effective: CRC, breast cancer, and cervical cancer. All other issues related to screening, such as lung cancer or prostate cancer, are still being studied, there is no obvious evidence of effectiveness today. And the introduction of a screening program for CRC in the United States helped reduce mortality by about 10%, this is the life of 13.5 thousand people annually.

But what is very important for population screening is good coverage of population groups. If it is less than 50%, then the cost of screening exceeds the benefit. Such programs should involve not only oncologists, epidemiologists and other doctors, but also the media, media personnel and society as a whole. This is a large integrated work, which is currently not in Russia.

What preventive measures will help reduce the risk of CRC?

Of course, the first thing you can do is quit smoking. You should also try to consume more fiber and less processed red meat. If there are problems with the functioning of the intestine (irritable bowel syndrome, stool disorders) - this must be treated. And finally, you need to understand that if you are fifty years old, then you need to just pass the feces for occult blood and make a colonoscopy.

Any complaints: a change in stool, the presence of blood - should be an occasion for visiting a doctor. You can’t give up on such circumstances, thinking that you simply have hemorrhoids. You need to contact a specialist who will prescribe the correct examination and treatment. For any competent proctologist, the presence of blood in the stool is an occasion to prescribe fibrocolonoscopy.

What points should I look for when a colonoscopy is prescribed?

As with any other invasive manipulation, the more often the doctor performs it, the more experience he has in this. Fairly commonplace truth, but you need to contact the institution with a good flow of patients. Secondly, you need to go where the procedure will be done on high-quality equipment. And, preferably, where you will provide pain relief.

Unfortunately, we have a problem with the lack of quality control for colonoscopy. Although quite objective criteria for its implementation exist. These problems are taken very seriously in the West. Hypothetically, you can do a colonoscopy for all people, for example, in the city of St. Petersburg.

Spend a lot of money on it. But if you do it all and poorly, then the value of such a procedure is lost. If the doctor misses 15% of the polyps in 15% of patients, then the value of this screening will be zero. That is why abroad there are clear objective criteria for assessing the quality of the performed procedure. And we don’t have them yet.

And what are these quality criteria?

The most understandable for non-specialists - a colonoscopy should not last less than 15 minutes. If the doctor says that he put the colonoscope very quickly, immediately examined the entire intestine and he was well done, then this is not so.

So he looked inattentively. And polyps are small, for example, a half-centimeter-centimeter. If the doctor missed these polyps, and the next time a person was going to have a colonoscopy, say, after 10 years, then during this time cancer can develop from the polyp.

By the way, the quality criteria of surgical intervention in CRC is also an important issue. After all, what is an oncological operation? This is an operation whose quality we cannot determine today, tomorrow or the day after tomorrow. Unlike any hemorrhoids, a patient with cancer often has no complaints. He lay down on the table and felt good, got up and feels the same.

But how this operation is performed, we do not know. We can determine this only after a year, when a person arrives, makes a CT scan and everything will really be fine there, without signs of a relapse of the disease. But if he comes, and these signs will be, then it is too late to say something to the doctor. Time is already lost.

Today, for CRC, there are quite clear quality criteria. They were invented by oncological surgeons in developed countries. This is the so-called drug-oriented surgery. Based on the characteristics of the removed drug, one day after the operation, it can be said whether it was performed qualitatively or not.

But according to these criteria in Russia, no one evaluates surgeons. We are now trying to rectify the situation, creating a cancer registry. Already covered several institutions in St. Petersburg and other cities of Russia, which will participate in assessing the quality of operations.This is very important, since a qualitatively performed operation with CRC gives an increase in survival of 10%.

Does a colonoscopy biopsy need to be performed?

Modern colonoscopic technique makes it possible to distinguish an ordinary benign polyp from something more serious. But you need to understand that any polyp more than half a centimeter should be removed. Small ones can be removed on an outpatient basis, right during the procedure. But for large polyps or polyps with suspected malignant growth, you need to perform a biopsy. And if it is large, but benign, then they remove it in a hospital - usually it takes no more than two days.

And if we get a malignant result when studying a biopsy, then we need to undergo a full examination, determine the clinical stage of the disease. And depending on the stage, treatment tactics are already being determined: starting from endoscopic removal during a colonoscopy and ending with the application of all treatment methods.

Please tell us more about the treatment methods.

Ideally, we should find oncological diseases, in particular colorectal cancer, at such stages that a little intervention is enough. If all patients were diagnosed with CRC in the first stage, then we could restrict ourselves to endoscopic intervention during colonoscopy. And that would be great. And moreover, this would be the final method of treatment, which would lead to recovery in most patients in 99% of cases. But, unfortunately, we are far from this.

There are patients with larger tumors, but still quite operable. In these cases, only surgery is sufficient, which will also lead to the complete cure of most patients. Nothing more will be required than observation by an oncologist.

When the patient falls into the hands of oncologists already in the third stage, he needs to use several treatment methods. Fundamentally, in oncology there are three of them: surgical treatment, drug (chemotherapeutic) treatment, and radiation exposure to the tumor.

If we are talking about colorectal cancer, then in the third stage, the patient must necessarily receive all three components. Moreover, treatment should be started, as a rule, with chemoradiotherapy, and then surgery. In this case, we increase relapse-free survival by 10-15%, when compared with only surgical treatment.

If we talk about colon cancer, then, as a rule, it is not exposed to radiation exposure. It is very difficult to irradiate a tumor that is located in the abdominal cavity. The patient breathes, moves, the intestines peristalsis and non-target organs can be exposed to radiation. In the third stage of this type of CRC, chemotherapy is definitely used, but as a preventive treatment after surgery. It allows you to increase the survival of such patients by about 5-10%, which is undoubtedly important.

Since the third stage requires combined and complex treatment, this should not be dealt with by a general hospital. In addition, it is very important that the decision on treatment tactics is made by a consilium consisting of an oncologist surgeon, chemotherapist and radiologist. This is spelled out in our order of the Ministry of Health “On the approval of the Procedure for the provision of medical care to the population on the profile of oncology”.

And finally, the saddest group of patients who turn to oncologists for 4 stages of the disease with metastases to distant organs. In order not to induce pessimism at all, we can say that over the past 20 years quite significant breakthroughs in the treatment of such patients have been achieved.

Firstly, it turned out that single metastases to distant organs are very “accommodating” in the treatment of CRC. We know that in about 70% of cases, CRC metastases to the liver. Secondarily, to the lung. Now there are different ways to influence liver metastases.

In addition to conventional chemotherapy and surgical treatment, there are also methods of minimally invasive treatment, which boil down to blocking one or more blood vessels of the liver with an embolizate containing a chemotherapy drug. In addition, minimally invasive instruments include methods of local exposure to liver metastases: cryoablation, microwave ablation, and radiofrequency ablation of metastatic foci.

All of the above allows you to use, combine and choose the most effective approaches in a particular case. This allows you to fight for such patients for a long time and significantly extend their life.

Secondly, there are new targeted drugs that give a very good effect. Against the background of these drugs, when performing surgery on the liver, some patients received a significant 30-40% increase in survival. This is a big breakthrough.

The above once again proves that patients with CRC should be treated in hospitals, where all groups of specialists work. In addition to just a surgeon who can remove the tumor, you need competent chemotherapists and radiologists, specialists in surgical treatment of the liver, etc. If the patient can get all this in one hospital, he has a chance to live much longer.

In Russia there are such places. For example, in St. Petersburg there are at least three such institutions: “St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncology)”, “NRC Oncology named after N.N. Petrova ”and“ City Clinical Oncology Dispensary ”. And in Moscow, one can distinguish “Moscow City Oncology Hospital No. 62”, “NRC Oncology named after N.N. Blokhin "," MNII them. P.A. Herzen ”and“ State Scientific Center of Coloproctology ”.

No need to be afraid of the name. Patients often think that if the word oncology is written, then everything is bad with them, we will not be treated there. Well, no! The word "oncological" means that the clinic has everything you need to treat this complex group of diseases.

Please tell us more about the effect of cancer localization on survival.

There is evidence that when the primary tumor is located in the left half of the colon (that is, in the descending colon, sigmoid and rectum), survival is significantly higher than with cancer localization in the right half (cecum or ascending colon). But so far this question is under study, and alternative points of view are already appearing.

As a rule, tumors on the left side of the colon are diagnosed earlier. This is due to the fact that, firstly, in the left half of the colon, the tumor often causes stenosis - because of it, defecation disorders and blood in the stool occur, therefore, patients go to the doctor earlier. Secondly, when a colonoscopic examination is performed, sometimes they cannot pass a colonoscope beyond a certain place. The left half is easier to reach, far from all endoscopists reach the cecum and carefully examine the right half.

And so far no one has taken this into account in research. It is believed that this is not connected with the biology of the tumor, but only with such factors. I now refer to our most famous oncogenetics, Professor Imyanitov Evgeny Naumovich. He believes that there are no global genetic differences between the right and left half of the tumor.

What advice could you give patients?

First: you should not be afraid of examinations.

Second: if you have a confirmed diagnosis of CRC, be sure to contact a specialized institution! Often the patient chooses a doctor on the advice: they say he has "good hands." But if we are guided by this principle, then we will never know the real quality of the operation, we will only see a seam. The surgeon, as a rule, is not aware of the patient’s further fate; they come to the oncologist with relapse.

Therefore, it is important that the patient selects a place of treatment that specializes in his disease. If there is a branch in the city where five hundred colorectal cancers are operated on per year, then you need to go there. And not to the clinic, where this intervention is done twenty times a year, but every time they say that with "good hands."

In developed countries, if a department performs less than fifty operations per year related to CRC, then it will be reprofiled. In St. Petersburg there is a perfect scatter in this regard. Patients turn to different institutions and are not operated in specialized centers. And the point is not that there are bad doctors, it's just not their job. Just as if I start to operate on hernias. Yes, I can do it, but that’s not my task. And we all, who are not lazy, grab on to operate on cancer.

And then the Minister of Health comes and is surprised that in St. Petersburg there are poor oncological statistics. And this is all due to the fact that in St. Petersburg they often do not follow the procedure for providing assistance to cancer patients. In our country, about half of the patients are not operated in specialized institutions today. And oncologists are responsible for the results.

We have been struggling with this for a long time and will continue to do so in order to consolidate this simple truth: cancer patients should be treated by oncologists. It is very important.

And the third point, people know little about their rights. In our city, a patient who has been diagnosed with cancer has the right to do all the examinations that are necessary to determine tactics, for free and within one institution.

What is happening to such patients today? They are diagnosed and started to drive: in one place - to have a CT scan, in another - to perform an MRI for a fee, and then they only take for surgery to a non-core institution. And then it turns out that he needs to do chemotherapy. And it is also desirable, before prescribing medications, to conduct immunohistochemical and molecular genetic counseling for more precise treatment. And all this is paid.

Such a mess is happening now in St. Petersburg all the time. Patients should know that they can come and get the entire amount of research in one place, for free, in order to determine the tactics of treatment. And do not be afraid that in a government agency it will take a long time.

To date, there is an order from the health committee that states that the patient should be examined within ten working days. Any doctor from the clinic, if he suspected a diagnosis of CRC, can refer a person to us. The patient calmly calls and signs up for a consultation the next day.

This is what you need to do in case of detection of colorectal cancer, but, unfortunately, few people know about it.

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