Introduction. Stomach cancer remains one of the most common malignancies with an unfavorable prognosis. It is the 5-th most frequent cancer and the 3rd leading cause of cancer death worldwide and in Russia as well. Combined modality treatment including radical surgery and perioperative / adjuvant therapy is the current therapeutic strategy for locally advanced gastric cancer. New approaches to combined modality treatment including neoadjuvant chemoradiotherapy for locally advanced gastric cancer were developed at A. Tsyb Medical Radiological Research Center (Obninsk, Russia) and tested in a phase 2 randomized clinical trial. The results obtained showed the safety and high efficiency of the method.

To objectify the results, a multicenter randomized trial was initiated in 2016. the main objective of the study was to assess the immediate efficacy and safety of neoadjuvant chemoradiotherapy using pathological response criteria and to evaluate the frequency/severity of toxic reactions and postoperative complications. Additional objectives of the study were to assess the accuracy of preoperative staging of gastric cancer; tumor regression grade of the primary tumor and regional lymph node metastases according to CT findings; treatment outcomes according to the criteria of frequency and time to recurrence/metastasis; 1-, 2 -, and 3-year survival rates.

Material and methods. The study included 70 patients with equal distribution between the treatment groups. There were more males than women; the median age was 62 years. The main criterion for inclusion of patients into the study was morphologically confirmed gastric cancer of сT2–4N1–3, сT3–4N0–3; сМ0, IIA-IIIC stages. Patients of the first (investigated) group were treated with neoadjuvant chemoradiotherapy (total dose of 46 Gy in 23 fractions and chemotherapy with capecitabine and oxaliplatin) followed by surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) and 4 cycles of adjuvant chemotherapy. Patients of the second (control) group underwent surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) followed by 6 cycles of adjuvant chemotherapy. 

Results. The tumor was localized in the middle and lower thirds of the stomach in most cases. There were mostly low-grade adenocarcinomas (47 patients). None of the patients showed the presence of distant metastases; 2B and 3 clinical tumor stages were mostly observed. The comparison of clinical and pathomorphological stages in the control (surgical) group showed that a comprehensive examination, including CT and laparoscopy, allowed the correct assessment of the tumor stage and formation of the control group according to the main inclusion criteria in more than 90 % of patients. Comparison of patients between the study and control groups showed that they were well balanced on the main prognostically important factors. The differences between all parameters were not statistically significant (p>0.05).

The purpose of the study was to evaluate a combined approach to surgical treatment of patients with morbid obesity.

Material and methods. Between January 2017 and December 2018, 26 women with stage I endometrial cancer underwent laparoscopic gysterectomy in combination with panniculectomy.

Results. No episodes of intraoperative hemodynamic instability, significant hypoxemia or hypercapnia were reported. The average blood loss was 236.4 ± 114.8 ml; surgery time: 264.2 ± 57.3 min; mass of the removed flap: 10.52 ± 6.5 kg; length of hospital stay: 11.2 ± 3.7 days. There was no delay in the start of adjuvant radiation therapy.

Conclusion. Surgical treatment of endometrial cancer patients with morbid obesity presents significant technical challenges. The choice of surgical access in such cases may depend not on the stage and prevalence of the tumor, but on the constitutional characteristics of the patients. Sometimes surgeons can refuse to perform surgery for such patients and offer them an alternative treatment. Classical laparotomic access is associated with the maximum risk of perioperative complications. Laparoscopic techniques have technical limitations associated, for example, with the length of trocars and surgical instruments. Robotic surgery is considered generally safe, but due to its low availability, it is limited only to large clinical centers. The combined approach to surgical treatment of endometrial cancer patients with morbid obesity is the most effective surgical modality for these patients.

The purpose of the study was to analyze immediate outcomes of pulmonary artery reconstruction for lung cancer in terms of safety, functional feasibility and quality of life.

Material and methods. From 2009 to 2016, the study included 183 patients with non-small cell lung cancer (156 men and 27 women, median age: 58.4 ± 12.3 years). Angioplasty lobectomy was performed in 92 cases and pneumonectomy in 91 cases.

Results. There were no intraoperative complications. Postoperative complications were observed in 23 (25 %) cases after angioplasty lobectomy and in 36 (39.6 %) cases after pneumonectomy. Three (3.3 %) patients died after angioplasty lobectomy and 7 (7.7 %) after pneumonectomy. When comparing the parameters of the external respiration function after surgery, it was found that after angioplastic lobectomy, FEV1 decreased by 0.69 (27 %) liters 1 year after surgery, VC decreased by 1.17 (32.9 %) liters, and FLC reduced by 0,64 (20.5 %) liters. After removal of the lung, reduction in these parameters was, respectively, 1.02 (42 %); 1.53 (43.8 %); 1.24 (40.3 %) liters. The main SF36 questionnaire parameters were higher in the group of angioplasty lobectomy than in the group of pneumonectomy.

Conclusion. Pulmonary artery reconstruction for lung cancer is safe, with low morbidity and mortality. This technique is an effective alternative to pulmonectomy in lung cancer surgery. 

Background. Tumors demonstrating the phenomenon of microsatellite instability (MSI) represent a special category of colorectal cancer (CRC). Such neoplasms account for up to 20 % of CRC and are characterized by specific molecular and clinical manifestations, including high immunogenicity and sensitivity to immunotherapy. MSI phenotype occurs in two different groups of patients: young individuals with Lynch syndrome and patients older than 70 years with non-hereditary CRC. We assume that the development of sporadic MSI-positive tumors in elderly patients may be associated with age-dependent decrease in immune defense.

The aim of the study was to investigate clinical and morphological characteristics in elderly patients with MSI-positive colorectal cancer.

Material and methods. MSI status and mutations in the BRAF gene were tested in a group of 384 CRC patients older than 65 years by PCR-based techniques. A comparative analysis of clinico-pathological features was further conducted in the groups of 23 MSI-positive and 34 MSI-negative CRC cases.

Results. MSI-positive phenotype was associated with the proximal tumor location, low degree of differentiation and the presence of the mucinous component in the tumor (p<0.0001, p=0.005, and p=0.0001, respectively). Patients with MSI-positive CRC containing BRAF mutations showed a significant prevalence of RhD-negative erythrocyte phenotype (53.3 % vs 11.8 %, p=0.004). In patients with MSI-positive carcinomas, the increased frequency of preoperative leukocytosis (p=0.009) and lymphopenia (p=0.014) was observed.

Conclusion. The increased occurrence of Rh-negative erythrocyte phenotype and white blood formula changes in elderly patients with MSI-positive CRC may indicate the role of immune system disorders in the development of microsatellite-unstable carcinomas.

The purpose of the study was to analyze treatment outcomes in prostate cancer patients, who received external radiotherapy combined with high dose rate (HDR) 198Ir brachytherapy boost of 10 Gy in 2 fractions or 15 Gy in 1 fraction.

Material and methods. Between July 2012 and June 2017, 98 patients with prostate cancer received radiation therapy at N.N. Petrov National Medical Research Center of Oncology (St-Petersburg, Russia). Intensitymodulated radiation therapy (IMRT) at a total dose of 46–50 Gy was delivered to the prostate, seminal vesicles and regional lymph outflow areas (RTOG, 2009). The patients were then divided into 2 groups. Group I patients (81 patients, 82.7 %) received HDR brachytherpy boost of 10 Gy in 2 fractions, Group II patients (17 patients, 17.3 %) received HDR brachytherpy boost of 15 Gy in 1 fraction. Inclusion criteria were: high or extremely high risk of relapse according to NCCN (2010), no evidence of distant metastases and no evidence of pronounced urinary tract disorders (residual urine volume less than 50 ml, IPSS less than 17 points, maximum urination rate ≥10 ml / sec). Assessment of radiation-induced complications (toxicity) was carried out in accordance with generally accepted RTOG / EORTC (1995) criteria and taking into account the terminological recommendations of CTCAE v 4.0 (2009).

Results. The median follow-up time was 39.2 [30.7; 48.7] (20.3–69.8) months in Group I and 37.0 [30.9; 47.9] (23.7–50.7) months in Group II. The 3-year disease-free survival rate in the study groups regardless of the boost was 77.1 % (75.9 % in Group I and 77.8 % in group II, p=0.7). The 3-year disease-free survival rates in patients with high and extremely high risk regardless of the radiotherapy regimen were 88.6 % and 70.8 %, respectively (р=0.04). Genitourinary early radiation toxicity and rectal intestinal early radiation toxicity of grade 3 were observed in 13.5% and 12.3 % of Group I patients and in 17.6 and 5.9 % of Group II patients. The most significant late complications were the formation of urethral stricture (1 patient of group I) and postradiation rectal stenosis (1 patient of group II). Evaluation of the level of erectile function in both groups showed a significant decrease in satisfaction with the quality of sexual life, which, apparently, can be explained not only by radiation damage to the structures responsible for hemodynamics of the penis, but also by castration syndrome due to prolonged hormonal deprivation in the vast majority of patients.

Conclusion. The combination of external beam radiation therapy with HDR brachytherapy boost is an effective method of radical treatment of prostate cancer patients with high and extremely high risk of recurrence.

Purpose: to compare immediate, short-term and long-term treatment outcomes after radical prostatectomy and robotic radiosurgery in patients with localized prostate cancer.

Material and methods. The study included 2 groups of patients. Group I patients (n=80) underwent radical surgery (nerve-sparing prostatectomy). Group II patients (n=102) underwent KiberKnife stereotactic robotic radiotherapy.

Results. Immediate treatment outcomes after both radical prostatectomy and robotic radiosurgery did not demonstrate increased number of postoperative complications and severe radiation-induced injuries. The PSA level decreased and reached a nadir PSA level immediately after radical prostatectomy. After stereotactic radiation therapy, the PSA level decreased gradually every three months, reaching a nadir within a year. In the group of patients receiving CyberKnife treatment, changes in the prostate volume affected the quality of urination, which was confirmed by the assessment of the volume of residual urine. When comparing the quality of urination in treatment groups using the IPSS scale, the values were comparable. No differences in the 1-year disease-free survival rates between groups were found. However, 60 months later, disease free survival rate was higher by 8.2 % in patients treated with radiosurgery than in patients who underwent radical prostatectomy (p<0.005). No differences in the 1-year cancer-specific survival rates between the groups were found. In patients, who underwent radiosurgery, the 5-year cancer-specific survival rate was 96.3 % (3.7 % higher than that observed in patients, who underwent radical surgery, p<0.005).

Conclusion. High 5-year survival rates in patients with localized prostate cancer indicate that both radical prostatectomy and KiberKnife stereotactic robotic radiosurgery are safe and effective treatment options.

A prospective randomized controlled clinical study included 80 women aged 54.9 ± 8 years, who underwent radical surgery for breast cancer and had late postmastectomy lymphedema (II–IV degree). No evidence of erysipelas was observed for the last 3 months.

Material and methods.The severity of lymphedema and treatment outcomes were assessed using water plethysmography in relative units (in %). Changes in the subcutaneous adipose tissue thickness were measured by ultrasound. To assess the severity of liposuction complications, the Clavien–Dindo classification was used. Three homogeneous groups of patients were treated. In Group 1 (n=30), conservative methods (intermittent pneumatic compression of the arm, electrostimulation of skeletal muscles, magnetic therapy, massage, therapeutic exercises, compression bandaging) were performed in the preoperative period; in group 2 (n=30) – in the late postoperative period of liposuction; in group 3 (n=20) liposuction was followed by compression bandaging.

Results. The average volume excess in the edematous upper extremity significantly decreased, being 84.2 ± 10.0 % in group1 patients, 87.8 ± 9.3 % in group 2 and 72.2 ± 9.6 % in group 3 (p<0.001). The regression rate of grade 2 lymphedema was 94.8 ± 1.2 % in group 1 patients, 96.1 ± 0.7 % in group 2 patients and 82.1 ± 2.5 % in group 3 patients. The regression rate of grades 3 lymphedema  was 81.7 ± 2.2 % in group 1, 86.9 ± 2.2% in group 2 and 65.2 ± 0.8 % in group 3. The regression rate of grades 4 lymphedema was 71.0 ± 2.8% in group 1, 73.4 ± 2.2% in group 2 and 62.6 ± 4.2% in group 3 (p<0.001). Early complications of grade 1 liposuction occurred in 5% patients. Favorable immediate treatment outcome (reduction in lymphedema by 50100 % and reduction in the thickness of subcutaneous fat by 50 %) was noted in 100% of patients of groups 1 and 2 and in 90 % patients of group 3. A good long-term result (after 12–18 months) was observed in 93.3 % of group 1 patients, in 100 % of group 2 patients and in 55 % of group 3 patients.

Conclusions. The results obtained show that the elimination of excess adipose component without improving the drainage function of the lymphatic system does not lead to good long-term treatment outcomes for late lymphedema.

The purpose of the study was a comparative assessment of long-term toxic effects of cytotoxic drugs (anthracycline antibiotics, topoisomerase activity inhibitors, platinum and taxane complex compounds) on male reproductive function.

Material and methods. 2.5-month-old male Wistar rats were used in the experiment. The following cytotoxic drugs were administered to animals in the maximum tolerated dose: Vepesid (etoposide, Teva, Israel), Irinotecan (Campto, Rhone-Poulens, Great Britain), Carboplatin (kemokarb, Dabur India Ltd., India), Paclitaxel (mitotax, Dr. Reddy`s, India), Platidiam (Lachema, Czech Republic), Pharmorubicin (Farmitalia, Carlo Erba). The reproductive status was assessed 90 and 180 days after administration of cytotoxic drugs. The fertilizing ability, productivity of spermatogenesis and the viability of a fertilized egg were evaluated. To determine the sensitivity of different types of spermatogonia to the drugs, we studied the dynamics of the number of their cell populations 2, 5, 10, 15, 30, 90 and 180 days after starting the experiment.

Results. In long-term follow-up following administration of farmorubicin and paclitaxel to male rats, a complete (pharmacorubicin) or partial (paclitaxel) decrease in the fertilizing ability due to oligospermia was detected. The decrease in spermatogenesis productivity
was reversible. In rats treated with topoisomerase activity inhibitors, the fertilizing ability was preserved, however spermatogenic failure was also seen, as judged by the total sperm number. In the long term after the administration of platinum complexes, no decline in the reproductive function was observed, and the spermatogenesis productivity corresponded to the control values. The severity of toxic effects on gonads was determined by the sensitivity of different types of spermatogonia to the action of drugs. Pharmorubicin and paclitaxel exerted a pronounced toxic effect on stem spermatogonial cells. Paclitaxel and carboplatin induced dominant lethal mutations in spermatogonia, but the likelihood of gametes bearing genetic damage incompatible with life decreased over time.  

Local synthesis and metabolism of sex hormones allow the skin to regulate autonomously both nociceptive reactions and proliferative processes in various pathologies.

The purpose of the study was to reveal the influence of chronic neurogenic pain on the balance of sex hormones in the skin, tumor and perifocal area in male mice in the dynamics of В16/F10 melanoma growth.

Material and methods. The study included С57ВL/6 male mice. Animals were divided into the main group – animals with В16/F10 melanoma transplanted after the development of chronic neurogenic pain (n=25), comparison group (n=27) – animals with standard tumor transplantation, controls – males with chronic neurogenic pain (n=8), and intact mice (n=8). Levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4) (CUSABIO, China), estrogen receptors – ERα, ERβ (Сloud-Clone Corp. USA, China), progesterone (RP4) and androgens (RA) (CUSABIO, China) were determined in 10 % homogenates of skin, tumor and perifocal tissues 1, 2 and 3 weeks after В16/F10 melanoma transplantation using standard ELISA test systems adapted for experimental animals.

Results. Chronic neurogenic pain causes an imbalance of sex steroids with marked hyperestrogenism. The imbalance is achieved by increased content of estradiol and receptors of estrogen, increased concentration of progesterone with inhibition of its receptor apparatus, as well as reduced levels of testosterone with increased concentration of androgen receptors. Melanoma in animals with chronic neurogenic pain grows and develops in a target organ with an altered steroid balance, which leads to changes in the tumor characteristics. Chronic neurogenic pain and B16/F10 melanoma has a unidirectional effect on the local hormonal status of the skin.

In 2016 3158 patients with colorectal cancer (CRC) were registered in the Republic of Kazakhstan, out of them, 1,484 patients died. Colorectal and colon cancers are the 8th and the 5th leading causes of mortality, respectively. One of the most significant events in the molecular pathogenesis of CRC is an activating mutation in the KRAS oncogene. Recently, studies of the KRAS gene mutation and analysis of its relation with the clinical course of CRC have been carried out in different countries. The effect of gender and age on the KRAS gene status in CRC remains a subject for discussion.

The purpose of this study was to study the relationship between the KRAS gene status and gender, age and race in colorectal cancer patients residing in the Republic of Kazakhstan.

Material and methods. Data on 332 patients with CRC for the period from 2010 to 2014 were studied. KRAS test was performed using BioLink kits to detect mutations in 12 and 13 codons of 2 exon using allele-specific PCR method.

Results. In our study, the frequency of KRAS gene mutations in CRC patients residing in the Republic of Kazakhstan was 44.9 %. The frequency of mutations in the studied codons among women and men was the same. When analyzing the mutation frequency of the KRAS gene, it was revealed that among both sexes the G12D mutation was more often observed. The least common mutations were G12C, G12S, which occurred in both sexes (up to 5 % of cases). The analysis of the dependence of the mutation on the race of the patients revealed some predominance of the wild type in the Asian group – 94 (51.4 %), while Europeans were more often detected with the KRAS mutation – in 81 (54.4 %) patients. Mutation of the KRAS gene was more frequently observed in the group of older patients.

Background. Standard imaging techniques, including chest x-ray, ultrasonography, magnetic resonance imaging and computed tomography have some limitations in terms of their ability to detect distant metastases.

The purpose of the study was to search for additional diagnostic techniques for breast cancer detection.

Material and methods. Results of 18F-FDG PET/scans were retrospectively analyzed in 50 breast cancer patients.

Results. Traditional imaging techniques showed suspicion for distant metastases in 29 patients. Of them, metastatic disease was histologically confirmed in 16 patients. Sensitivity and specificity of traditional imaging techniques were 80 % and 67.5 %, respectively. Distant metastases were not detected by 18F-FDG PET/CT in 29 patients, however in one of these patients, both CT and cytological examination performed during the follow-up period revealed pleural metastases. 18F-FDG PET/CT detected distant metastases in 21 patients. Of these patients, two had no evidence of metastases confirmed by biopsy and other diagnostic imaging methods as well as during follow-up period. The sensitivity and specificity of 18F-FDG PET/CT in detection of distant metastases were 95 % and 93.3 %, respectively.

Conclusion. Sensitivity of 18F-FDG PET/CT in the detection of breast cancer distant metastasis was significantly higher than that of the traditional imaging techniques.

The purpose of the study was to comparatively analyze surgical outcomes in patients with histologically proven rectal cancer.

Material and methods. From 1999 to 2012, 174 patients with histologically proven rectal cancer underwent abdominal-anal resection of the rectum with bringing down the sigmoid colon into the anal canal and sphincter-preserving low intra-abdominal resection of the rectum with coloanal anastomosis.

Results. Two groups of patients were studied: the main group (sphincter-preserving low intra-abdominal rectal resection) and the control group (abdominal-anal resection of the rectum). The 5-year survival rates and quality of life of the patients (Wexner scale) were compared. Improvement in fecal retention function was observed in both groups a year after surgery. However, 17 patients in the control group (25 %) had unsatisfactory function of the closure apparatus (11–20 points on the Wexner scale), sharply limiting their social activity and requiring the use of anal tampons. Fecal incontinence was observed in 95% of the control group patients 1 year after surgery. A significant improvement in the quality of life associated with adequate sphincter function was found in the main group of patients. In 40 out of 88 patients who had survived 1 year (45 %), no significant violations of the closure function were revealed. The remaining patients had symptoms of fecal incontinence or inability to control bowel movements for a long time (less than 10 points on the Wexner scale).

Conclusion. The use of low anterior rectal resection with coloanal anastomosis in the surgical treatment of cancer, significantly improves the patient’s quality of life without compromising the radicality and safety of treatment.

Background. Air-leak after lung resection is a common complication occurring in 30–50 % of patients immediately after surgery. The prolonged air-leak (PAL) is a serious problem if it lasts more than 5 days after lung surgery with the reported incidence of 15 %. Despite the progress in thoracic surgery including energy-based vessel-sealing devices and digital drainage systems, there is no universal agreement on the optimal treatment of patients with prolonged air-leaks.

The aim of the study: to improve postoperative outcomes in patients with PAL by optimization of postoperative treatment algorithm.

Material and methods. Treatment outcomes were analyzed in 194 patients, who underwent lobectomy for non-small cell lung cancer in 2017–2018. results. The prolonged air-leak was detected in 19 (9.8 %) patients after. The average time interval between surgery and development of this complication was 3.4 days. There was no mortality in our series. The median postoperative hospital stay was 8.7 days in patients with non-complicated postoperative period and 14.8 days in patients with PAL. Based on our own experience and practice we have developed and implemented an algorithm of the management of patients with PAL.

Conclusion. The treatment of patients with PAL should be based on multidisciplinary approach providing safety of the patients after major lung resection. Each case with PAL should be discussed individually to achieve better results.

The purpose of the study was to analyze the world experience in the objective assessment of the functional state of the bronchopulmonary system in lung cancer patients with chronic obstructive pulmonary disease (COPD) using modern diagnostic tools and techniques as well as correction of ventilation disorders in the perioperative period using long-acting inhaled bronchodilators.

Material and methods. A literature search was conducted using the Medline, Elibrary etc. databases. Out of 112 publications concerning the study of the incidence of lung cancer and COPD, external respiration function and rehabilitation of patients, 37 were included in this review.

Results. COPD was shown to be the major cause of postoperative non-surgical complications and the main predictor of perioperative mortality in lung cancer patients. Modern techniques for studying the function of external respiration, such as bodyplethysmography, spirography, high-resolution computed tomography, ventilation and perfusion lung scintigraphy, were highlighted. It was shown that preoperative correction of obstructive syndrome and postoperative pulmonary rehabilitation, including drug therapy with long-acting bronchodilators in combination with smoking cessation, eradication of foci of chronic infection and respiratory gymnastics were necessary to detect functional respiratory disorders in lung cancer patients with COPD.

Conclusion. To date, there are no standards clinical practice guidelines for diagnostic testing and the correction of ventilation disorders in lung cancer patients with COPD in the pre- and postoperative periods. Therefore, further studies aimed at developing a diagnostic algorithm to improve the accuracy of detecting bronchial obstructive syndrome, especially in the early stages of COPD, as well as compensation for respiratory disorders using modern bronchodilator therapy are needed.

Purpose of the study: to analyze available data on the combination of radiation therapy with antiangiogenic drugs in the treatment of patients with brain metastases.

Material and methods. The search for relevant sources was carried out using Medline, Cochrane Library, Elibrary, PubMed databases concerning publications describing the role of radiation therapy in the treatment of patients with brain metastases. results. To date, there are various options for the combination of radiation therapy with antiangiogenic drugs.

The results obtained indicate that radiotherapy combined with antiangiogenic drugs is more efficient in the treatment of patients with brain metastases than radiotherapy used alone. Conclusion. Treatment of patients with brain metastases remains extremely challenging and requires a multidisciplinary team approach.

In 2017, esophageal cancer was detected in 7126 patients, including 1962 patients with cervical esophageal cancer. Metastases in regional lymph nodes were detected in 60–70 % of cases. the 5-year survival rate was 25–50 %. Currently, the benefits of minimally invasive surgeries for cancer have been proven, but these surgeries have restricted indications leiomyosarcoma is a rare malignant tumor of smooth muscle, accounting for about 0.3 % of the malignant tumors of the esophagus.

Case presentation. in our first clinical case, we have shown the feasibility of performing surgical resection of cervical esophageal carcinoma with larynx preservation. We have described a rare postoperative complication bending of the graft. the complication was resolved and good voice, protective and swallowing functions were achieved. in the second case, the tumor initially spread to the pear-shaped sinus and beyond the cricoid area, which was a contraindication for the organ-preserving surgery.

Conclusion. the extent of surgery should always be planned taking into account the extension of the primary tumor. in our practice, we prefer to use visceral (intestinal) transplants for patients with circular pharyngeal defects, thus allowing radical surgery to be performed and esophageal motility to be restored. this technique helps patients recover faster after surgery.

Background. the presence of functionally significant intron mutations in the TP53 gene was demonstrated in experiments in vitro and on samples of patients with some variants of non-Hodgkin’s lymphomas. to date, the studies of TP53 in tumor tissue of patients with diffuse large B-cell lymphoma (dlBCl) have been focused on the mutations in 5–8 exons of the gene. For these reasons, further studies of the spectrum of changes in the intron sequences of the TP53 gene and the determination of their functional effect in dlBCl are required.

Description. We present two case reports that are of interest as the cases for detection of functionally significant intron TP53 mutations in dlBCl tissue, first published in the Russian scientific literature. the first clinical case of dlBCl was clinically characterized by extranodal tumor at the onset of the disease, severe symptoms of tumor intoxication, high paraclinical tumor activity, and early hemoblastosis recurrence. the second case of dlBCl was characterized by initially massive tumor lesion, rapidly progressive course of the disease, severe symptoms of tumor intoxication, high paraclinical tumor activity and poor response to therapy with subsequent generalization of lymphoma.

Conclusion. Mutations in the TP53 gene are the driver of the tumor process, serve not only as a marker of aggressive tumor progression, but also as an independent predictor of reduced sensitivity to treatment. the presented clinical cases show that an in-depth analysis of the results of the TP53 sequencing in tumors and functional assessment of all detected changes, including changes in the introns of the gene and involving in silico analysis techniques, are necessary.  

Although many currently known molecular targets are characterized by organ specificity, they can be found in various types of tumors. Molecular diagnostic techniques can be used to help select patients who are most likely to benefit from target therapy.

Case presentation. We describe the case of a 38-year-old patient with advanced gastric cancer with peritoneal dissemination. On december 11, 2014, the patient underwent palliative subtotal gastrectomy followed by 18 cycles of chemotherapy (xelOx) and radiotherapy. On February 2, 2017, percutaneous transhepatic cholangiostomy of the left lobe bile duct was performed. in May 2017, the stent was inserted into the common bile duct due to bile duct stenosis. three months later, disease progression (multiple liver metastases) occurred, and chemotherapy with paclitaxel was given in a weekly schedule. therapy with crizotinib was administered 3 months after determining the alK mutation. the duration of treatment was 8 months with satisfactory tolerability.

Conclusion. target therapy with krizotinib seems to be an effective treatment for alK-positive tumors.