MEDICAL SCIENCES
Abstract.
Morphological response of the tumor was investigated after sonodynamic chemotherapy during distal gamma-therapy (DGT) in patients with cancer of the oral cavity. Sixty-one patients were divided into two groups: group 1 (n=31) received DGT and local ultrasound treatment (0,88 MHz±0,33% and I=1,0Вm/cm2) with 5 mg of platidiam and group 2 (n=30) received only DGT. Biopsies were investigated by standard morphological and immunohistochemical analysis after achieving total dose of radiation 40 Gy. In the main group the mass of stroma increased 1,9 times after starting of treatment and 1,6 times in comparison with the control group, mitotic activity of the cells decreased 3,9 and 1,9 times respectively, and index of parenchymal damage was 2,4 times higher in the main group than in the control. There was fibrosis and focuses of cells with “cells – shadows” with dystrophic changes of the nucleus and cytoplasma.
There was a high index of Ki-67 proliferating activity (60-75%) and high apoptotic index (50-65%) of all cell layers. The rate of Ki-67 and gene p53 decreased 1,3 and 1,5 times respectively after treatment. In specimens of the main group basal layer cells expressed Ki-67 and p53 in 10-15% of area and didn’t differ from normal values. The rate of KI-67 and expression of p53 gene decreased 7.1 and 6.5 after treatment. Sonodynamic chemotherapy contributes to the suppression of the biological aggressiveness of the tumor, provides a much more pronounced antitumor effect compared to the effect of ionizing radiation alone.
Oncogenic impact of transformative viruses on the risk of cancer is well known. Today there are no studies focused on the effect of widespread, often persisting infections, such as herpes simplex virus (HSV), cytomegalovirus (CMV) and chlamydial infections on the level of hormones in the reproductive organs and their role in the pathogenesis of endometrial cancer. The aim of this study is to evaluate the effect of infectious agents in the substantive and concomitant conditions on the local hormone production in tissue of uterus and ovaries in patients with cancer of the body of uterus in menopausal age.In the tumor, in perifocal zone and in unaltered ovaries in patients with cancer of the body of uterus ELISA and PCR method determines the presence of herpes simplex virus types 1 and 2, cytomegalovirus and chlamydial infection. Depending on the level of infection in the tissues the local level of saturation of sex hormones, sex hormone binding globulin, prolactin were evaluated in samples of endometrium and ovaries. The presence of infectious agents have a modifying effect on local hormone production, increasing the intensity of disorders resulting in an imbalance of steroids, estrogen metabolites disturbance ratio and strengthening prolactinemia not only in tumor tissue but also in unchanged ovaries in patients with cancer of the body of uterus.
Cerebrospinal fluid (CSF) studied in 52 patients operated for malignant gliomas (T2-3NxMo) to study the acute-phase 2-macroglobulin (2M) and 1-proteinase inhibitor (-1PI) after two types of local intraoperative chemotherapy (LICT-1 and LICT-2). 2M and determined to -1PI before LICT (background) as well as on the 7th day after 1 and 2 months of post-operative period (p/o) using standard ELISA tests. Liquor of 9 patients with no inflammatory or malignant process in the brain served as control. Gender and age differences in the cerebrospinal fluid have not been established. After each method of treatment there were different response in patients after LICT, so patients were separated into groups with unfavorable and favorable postoperative period. On POD 7 after LICT-1 and LICT-2 ingroups with an unfavorable postoperative period 2M in both types of treatment was significantly lower than in both groups with a favorable postoperative period. -1PI on POD 7 after LICT-1 and2 inthe groups with negative dynamics was significantly higher than in the groups with positive dynamics and in samples before LICT and in control group. Two months after LICT-1 in18.5% of 27 patients had continued growth of the tumor with a fatal outcome, the remaining survivors the activity of 2M remained high. Two months after LICT-2 2M in samples of liquor decreased relative to the previous period and the samples before LICT (p <0.01 inall cases), while it remained significantly higher to control samples; there were no deaths registered during this period. After 2 months -1PI in the cerebrospinal fluid of patients with negative dynamics after LICT-1 remained higher than in control samples by 38.8%, and after LICT-2 it was lower by 24.1%. In both groups with positive dynamics α-1PI matched conditional normal value in the control group. Persisting of a high inhibitory capacity of liquor or its reduction below the conventional standards demonstrates local inflammation, or the possibility of continued tumor growth and can serve as a predictor for the early detection of the severity of the patient's condition in p/o period. LICT-2 was more successful because all the patients survived, neurological deficit wasn’t observed.
DOMESTIC RESEARCH IN FUNDAMENTAL AND CLINICAL ONCOLOGY
Hyperdiagnosis of lung cancer in recent years is of concern because of the emergence of new screening methods that detect small nodules, which clinical significance is unknown. The incidence of lung cancer ranged from 0.4% to 2.7% according to the results of screening studies, depending on the size of the population surveyed. The large number of false-positive diagnoses is unsolved problem yet. At the initial stage of the examination in the groups with high risk the number of false diagnoses is in the range of 10-20%, but can reach 50%, with positive predictive values of 2.8% to 11.6%. It is found that pathological nodules less than5 mmare unlikely malignant, and nodules from 5 to10 mmin diameter are undefined, 25-40% of which contain calcifications. Management of patients with such nodules, as a rule, is to perform repeated CT scans over time and if the growth of nodules is detected then fine-needle aspiration biopsy or surgical resection must be performed. Videothoracoscopy with biopsy provides a high efficiency in differential diagnosis of single tumors located in the cortical and subcortical regions of the lung or near the interlobar fissure. Presented here results indicate that the current VTS in peripheral tumors and metastatic lesions of the lung is the only minimally invasive method to verify the process with 100% accuracy.
The role of neoadjuvant chemotherapy in NSCLC still remains unclear. It may be useful in the treatment of resectable NSCLC like in other solid tumors. Only prospective studies will answer this question. Determination of optimal candidates for comparative studies of preoperative and postoperative chemotherapy in practice is a challenge. The best approach for patients with I and II stages of NSCLC is to provide combined treatment including surgery and adjuvant chemotherapy, and for patients with borderline resectable tumors with stages IIB, IIIA, but with minimal or without involvement of mediastinal lymph nodes is to provide neoadjuvant chemotherapy. For today, traditional ways of improving chemotherapy of NSCLC are exhausted, however, in connection with the development of recombinant cytokines (available for Phase I clinical trials), it opened real possibilities for clinical research on the development and evaluation of methods of neoadjuvant chemoimmunotherapy of NSCLC.
A comparative evaluation of different methods of neoadjuvant chemotherapy in 67 patients with locally advanced cervical cancer (T1b2-2bN0-1M0 stages) in age from 25 to 48 years was done. Main group included patients, received neoadjuvant chemotherapy in combination with plasmapheresis and non-specific immunotherapy at the first stage of the treatment. The control group included patients who underwent standard neoadjuvant chemotherapy. In both groups the same cytostatics were used. It was established that using of neoadjuvant chemotherapy combined with plasmapheresis and immunotherapy helps to achieve pronounced clinical effect, improve disease-free survival, reduce the frequency and severity of complications of specific treatment and delay the relapse and metastasizing of the disease.
Introduction: Features of angiogenesis in regional lymph node (RLN) in patients with gastric cancer are not well understood. The aim of our study is to give morphological characteristics and clinical evaluation of different types of vessels in the tissue of RLN in patients with gastric cancer.
Materials and methods: Specimens of RLN without metastases in 32 patients with gastric cancer were investigated. Sections were stained with hematoxylin and eosin and immunohistochemistry (IHC) with CD34 antibodies was performed.
Results: It was found that the density of cells expressing CD34 in lymphocytes of LN is correlated with the ПМС in the cortical layer of LN (r = 0.483, p = 0.005), with cell density in LN (r = 0.550, p = 0.01) and with the number of lymphocytes in gastric mucosa (r = 0.576, p = 0.001). The density of cells expressing CD34 in lymphocytes in LN was higher in gastric mucosa with multiple lymphocytes (7.21 + 2.91 and 13,47 + 6.45 respectively in gastric mucosa with single and multiple lymphocytes, p = 0.006). Tin tissues of RLN identified 3 types of vessels having different morphology and clinical significance: capillaries with usual structure, dilated capillaries and atypical vessels. ПМС in cortex layer of LN correlated with the stage of gastric cancer (r = -0,410, p = 0.01) and the number of metastases in RLN (r = -0,440, p = 0.01).
ПМС was lower in cases of locally advanced gastric cancer (28.4 + 4.91, 32.5 + 13.32 and 23.79 + 6.193 in microvessels on УЕП, at the stage of T1-2N0M0, T3N0M0 and T2-4N1-2M0, respectively, p1 -3 = 0.02) and in multiple metastases in the RLN (29.8 + 8.51, 25.2 + 5.82 and 22.7 + 6.63 respectively in microvessels on УЕП in the absence of single and multiple metastases, p1 - 3 = 0.001). The presence of multiple atypical vessels was also correlated with the stage of gastric cancer (r = 0,390, p = 0.04) and with 3-year disease-free survival (r = 0,630, p = 0.002). For early stages of gastric cancer it was characterized the absence of abnormal blood vessels in paracortical layer. Whereas in locally advanced gastric cancer atypical vessels were often detected. When there are multiple atypical vessels into a tissue of LN, a decrease of 3-year relapse-free survival from 87% to 42.9% was established (p = 0.03). While when the sinuses in the LN were preserved it was associated with its increase (83.8% and 57.1% for the presence and the absence of sinuses in RLN respectively, p = 0.04).
Conclusion: these data suggest a close relationship between lymphoproliferative processes in the lymph nodes and in the gastric mucosa with each other and with the processes of angiogenesis. The origin of the abnormal vessels requires further research.
In the experimental intraperitoneal chemotherapy with cyclophosphamide for sarcoma 45 and peritumoral administration of the factors inhibiting the Krebs cycle (diphenhydramine and ATP) histological, ultrastructural and immunocytometric indicators characterizing the development of the involutive processes of the tumor and its regression were studied. Modeling of metabolic microenvironment on the background of systemic neoadjuvant chemotherapy in patients with the stages T3-4N0-3M0 breast cancer led to an increase in antitumor effect. Assessment of tumor response was correlated with cytochemical indicators of the status of the key enzymes of the Krebs cycle (SDH, -GPDH) in lymphocytes of peritumoral area.
From 2004 to 2014 forty-six patients with sarcomas of the musculoskeletal system with metastatic lesions in the lungs were operated in MRRC. In 22 patients with a primary bone sarcoma metastases were detected in 27% cases, and in 29% of 24 patients with soft tissue sarcomas metastases were identified at the time of diagnosis. Twenty women and twenty-six men aged 16 to 72 years (mean age was 39 years) were operated. In most cases metastases were located subpleurally. Solitary metastases were observed in 8 patients (17%), single in 11 (24%) and multiple in 27 (68%) and 18 patients of them had bilateral disease. In all cases, chemotherapy was conducted at the first stage of treatment, according to histology of the tumor. In cases of large metastases or close location to the root of the lung (27 patients) preoperative distal radiotherapy was conducted in hyperfraction regimen with a daily dividing of the dose (2 times a day with an interval of 4 h every other day with single dose of 3 Gy and the total dose of 30 Gy that was isoefficiency to 42 Gy), after that the removal of pulmonary metastases was performed. A total of 73 surgical interventions performed in 46 patients. Most often precision resection of the lung using a neodymium YAG surgical laser MY 40 (wavelength 1318 nm) was performed. One patient underwent pneumonectomy. Videothoracoscopy was used in 6 cases. From 1 to 103 metastases were excised during one intervention. Pneumonia with abscesses were diagnosed in 3 patients, persistent pneumothorax in 5 patients, all complications were treated conservatively. There was no postoperative mortality. Fourteen patients underwent 2 procedures, two patients – 3 procedures, two patients – 4 procedures and one patient had 6 procedures. Follow-up ranged from 3 to 126 months. Twenty-six patients died due to progression of the disease. 3-year and 5-year survival was 46% and 41% respectively. Median survival was 32 months. Thus, the combined treatment of generalized forms of sarcomas of the musculoskeletal system can achieve long-term remission and significantly prolong life. Surgical resection should be applied in patients with solitary and with multiple metastases in the lungs and should be combined with systemic treatment (PCT) and, if indicated, with additional local treatment (distant radiotherapy) of metastases. Precision resection is adequate and well-tolerated method of surgical treatment of metastases in the lungs and does not correlate with severe postoperative complications.
Transrectal high-intensity focused ultrasound (HIFU) is a new, non-invasive local treatment of prostate cancer with 17 years of clinical experience, during which about 32,000 patients underwent this treatment worldwide, including2700 intheMunichclinic Harlaching, and1000 inSamaraOncologyCenter. This article shows the current status of HIFU as a noninvasive local therapy for radical or palliative approach in patients with various stages of prostate cancer, and how HIFU fits into long-term conception of the coherent multimodal treatment. This article reflects the experience of 17 years of clinical practice in two centers and results of 3700 treated patients.
Aim: To investigate argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins) in proliferating cells in connection with clinical and morphological parameters and survival in patients with adenocarcinoma of the lung.
Materials and methods: Specimens of 94 operated patients with lung adenocarcinoma were investigated using double staining for antigen Ki-67 (Clone MIB-1, DAKO) by immunohistochemistry and Ag-NOR proteins staining with silver nitrate.
Results: In the tumor tissue Ag-NOR proteins in the MIB-1 positive cells correlated with clinical and morphological parameters on TNM-system: T-index, the tumor size, N-index, disease stage and differentiation. Survival of patients with a small area of Ag-NOR proteins in the MIB-1 positive cells was better than in patients with large area. The area of Ag-NOR proteins in the MIB-1 positive cells – is an independent prognostic factor in patients with adenocarcinoma of the lung.
Conclusion: The area of Ag-NOR proteins in the MIB-1 positive cells correlated with clinical and morphological parameters of the TNM-system and survival in patients with adenocarcinoma of the lung.Introduction: Application of ipilimumab (IPI) in the treatment of patients with disseminated melanoma, first demonstrated an increase in survival that was an important event in cancer immunotherapy. We present the results of treatment of patients within the framework of enhanced access to the drug (SA184-EAP).
Materials and methods: from September 2012 to August 2014 71 patients with metastatic melanoma, with signs of tumor progression, received earlier from 1 to 6 lines of drug therapy were enrolled in protocol of treatment in Petrov Oncology Institute. Median age of patients was 51 years (range from 21 to 76 years). In 39 (60%) of patients IV stage was diagnosed, 25% of patients had metastases to the brain, 28% - had liver metastases, 19% - had bone metastases. All patients received IPI 3 mg/kg once every 3 weeks for total 4 administration.
Results: A total there were 229 administrations of IPI in 71 patients (average number of administrations was 3.2). Thirty-nine patients (59%) had 4 administrations and 21 patients (35%) had 1-2 administrations. Most of the patients had at least one adverse event (AE) associated with the treatment. In 15 patients (21%) there were no adverse events. Three patients died due to adverse events possibly related to treatment: 1 – had kidney failure, 1 - had pulmonary embolism, 1 - had cerebral edema and the progression of cancer. Grade 3-4 adverse events were observed in 10 (14.1%) patients: grade 3 rash - in 3 (4.2%) patients, grade 3 diarrhea - in 2 (2.8%) patients, grade 3 fatigue - in 2 (2 8%) patients, grade 3 dyspnea - in 1 (1.4%) patients, grade 4 of ALT and AST increasing - in 1 (1.4%) patient, grade 3 hypokalemia - in 1 (1.5%) patient. Efficacy of treatment was assessed in 54 patients, complete regression was detected in 3 (6%) patients, partial - in 6 (11%) patients. An objective response to treatment was observed in 28% of patients, the stabilization of process in 6 (11%) patients. Median follow-up was 144 days. The median time to progression was 81 days (95%; CI 73-105). The median overall survival was 411 days (95%; CI - 303-519).
Conclusion: Treatment with IPI satisfactorily tolerated by most patients and has significant clinical efficacy as the second and subsequent lines of drug therapy in patients with disseminated melanoma.
MULTIDISCIPLINNARY APPROACH IN ENDOMETRIAL CANCER TREATMENT
Surgical treatment is the "gold standard" in the treatment of patients with rectal cancer. The aim of surgical treatment is to minimize the rate of local recurrence, the occurrence of which depends largely on the quality of procedures.
Relationship between the tumor and own fascia of the rectum is the cornerstone in the choice of treatment strategy. Even using modern surgical techniques, most tumors of the rectum below the peritoneum should be treated using preoperative radiotherapy. Preoperative radiation can reduce the incidence of local recurrence and to create conditions for increasing the number of sphincter-preserving operations. The degree of tumor regression after chemoradiation is directly correlated with survival and local recurrence. Tumor regression creates prerequisites for decrease of postoperative complications and mortality related to the implementation of extensive radical surgery in patients with a tumor of the rectum. The use of standardized systems for the assessment of tumor regression can provide valuable information for centers specializing in the treatment of patients with such pathology. MRI of the pelvic organs is a very effective tool in the initial evaluation of the degree local and regional spreading of colorectal cancer including relationship to the mesorectal fascia. Difficulties in predicting of complete pathologic regression of the tumor by MRI are associated primarily with the problem of differential diagnosis between tumor and post-radiation changes in the rectal wall and surrounding tissues. A multidisciplinary approach provides the accuracy of staging and facilitates the development of an optimal treatment strategy in patients with rectal cancer.
Most patients with endometrial cancer (EC) have stage I disease, the treatment of choice is a total hysterectomy with bilateral salpingo-oophorectomy with or without pelvic lymphadenectomy. Concerning adjuvant radiotherapy for early endometrial cancer is unclear and determined by the risk of recurrence. In accordance with the depth of invasion of the myometrium, histological type and degree of differentiation stage I endometrial cancer is classified into low, intermediate and high risk of lymph node and distant metastasizing. Randomized studies have shown significant improvement in local control after radiation of pelvis and/or intracavitary radiation of the vagina without improving overall survival among patients of high and intermediate risk. At the same time the most controversy associated with the using of adjuvant radiation therapy in intermediate risk EC due to the heterogeneity of the group, which required selection of a subgroup of high intermediate risk, taking into account additional factors: lymphovascular invasion and age. In a subgroup of high-intermediate risk loco-regional effect of adjuvant radiotherapy was more significant. Taking into account the heterogeneity of patients with early EC, the complexity of the assessment of prognosis in case of not provided regional lymphadenectomy and the risk of late radiation complications attempts to optimize the indications, the volume and method of adjuvant radiation therapy in accordance with the risk factors.
The article is devoted to one of the most controversial issues of modern oncogynecology - interventions in the regional lymph nodes for cancer of the uterus. The arguments of supporters and opponents of this approach were reviewed.
ONCOGYNECOLOGY
Indications for treatment of ovarian cancer with taxane derivatives requires individualization, and this is necessary to have a reliable marker allowing to determine the rationality of the using of cytostatics. One of the progressive trends in this issue may be related to the immunohistochemical identification in removed tumors of transducing-like protein TLE3, which is a transcriptional repressor that is involved in the differentiation of epithelial cells and carcinogenesis. In the present study retrospectively analyzed 100 patients and prospectively 73 patients with serous ovarian cancer treated in MCCOC from 2007 to2014. In the first stage of treatment all patients underwent debulking surgery followed by adjuvant chemotherapy with platinum and taxanes or cyclophosphamide. Providing of immunohistochemical investigation of removed tumor tissue was carried out with a standard peroxidase-antiperoxidase method. Statistically significant influence of expression of TLE3 on disease-free survival (log-rank = 0.023). Five-year disease-free survival in the group with positive expression of TLE3 was 1.2 times higher than in the group with negative expression of TLE3 (0.490; 95% confidence interval [0.287, 0.837] and 0.261; 95% confidence interval [0.179, 0.380], respectively). An objective response in patients with TLE3-positive tumors was obtained in 93.8%. There were no benefits of taxanes using compared with cyclophosphamide in group of patients with negative expression TLE3. Thus, it is advisable to evaluate the expression of TLE3 to identify groups of patients that are sensitive to chemotherapy with taxanes.
ONCOUROLOGY
The study included 323 patients (the first group - 150 patients with suspected bladder cancer, the second - 173 patients with bladder cancer after treatment). All patients underwent cytological investigation of washings of bladder using conventional method and liquid cytology. This study presents comparative characteristics of these methods and shows considerable effectiveness of the method of liquid cytology in the diagnosis of bladder cancer and its local recurrence.
LUNG CANCER
PROSTATE CANCER
The aim of this study is to assess relative risk of prostate cancer (PC) and other tumors in families of patients with multiple primary malignancies (MPM) and the syndrome of hereditary nonpolyposis colorectal cancer (HNPCC). The study is based on data from the cancer register of families that includes information on 560 patients with MPM, 126 families with HNPCC and their first-degree relatives. Incidence of these diseases in population served as the control.
Among 560 probands with PPN 217 (38.7%) were male and 343 (61.3%) – female. Only 12 (2.1%) male patients had tumor in the prostate. In these patients 24 tumors were identified. Two patients had synchronous tumors, other ten patients had metachronous. Eight patients with prostate cancer had tumors of other organs: 5 – in rectum, 2 – in colon and 1 – in bladder. As a second tumor prostate cancer was diagnosed in 4 patients, three of them had rectal cancer and one – colon cancer. Only 2 (0.3%) patients had prostate cancer as a primary tumor. Clinical and genealogical information achieved from 543 patients with MPM, including in 206 male probands. Among 3637 first-degree relatives of probands with MPM prostate cancer was diagnosed in 2 (0.11±2.3%) patients that was 1.7 times higher than in population (0.063±0.0019%). The relative risk of prostate cancer for relatives of patients from families with HNPCC syndrome was 0.8 ± 6.3% that was 12/7 times higher than in the control group (p <0.05). The estimation of the relative risk in families of male probands was perfprmed. Among 1460 male relatives with MPM only 1 (0.14%) case of prostate cancer was diagnosed (son of proband). Among 42 families of male probands with HNPCC syndrome, prostate cancer was detected in 2 (1.3%) brothers that exceeds population risk 20.6 times. Although the molecular mechanisms and pathogenesis of prostate cancer in such families is unknown, its association with a HNPCC-syndrome and possibly MPM-syndrome is obvious.
Higher relative risk of developing prostate cancer for male relatives of probands with MPM and HNPCC syndrome presupposes inherited genetically determined predisposition to disease development. Further molecular and genetic studies are needed to determine the genetic basis of predisposition to prostate cancer in these families.
BREAST CANCER
Aim. The aim of this article is to present review of current trends in organ-sparing treatment of breast cancer. Summary of own 15-year experience of organ-sparing breast cancer surgery and its analysis in the light of global trends.
Materials and methods. The analysis of results of radical treatment of 429 patients with invasive breast cancer T1-2N0-3M0 during period 1999-2013 is presented. From 1999 to 2007 quadrantectomy was performed. Since 2007 we stopped to excise fascia, and the boundaries of removed tissues around the tumor was limited by 0.5-1.0 cm. The skin over the tumor was excised only if there was suspicion of its possible tumor involvement. After removal of the specimen its margins were marked and express histological examination was performed. In case of positive margin re-resection of this margin was performed, and in case of repeatedly positive margin mastectomy was performed. Axillary lymph node dissection was performed in all patients with tumors diameter 1.0 cm or more. Until 2007 third level of lymph node dissection was performed. Since 2007, the volume of the procedure was determined depending on the level of attached lymph nodes, which was established by preoperative ultrasound or examination of axillary tissue during surgery. In cases of N0-tumors D1-lymph node dissection was performed, in cases of N1-tumors – D2 and in cases of N2-tumors – D3. Postoperative radiotherapy was used in all patients, except some patients older than 70 years with pT1N0-tumors and favorable morphological characteristics of the tumor.
Results. In January 2014 415 patients from 429 were observed. A relapse in saved breast occurred in 18 (4.3%) patients. In 6 (33.3%) cases it was combined with distant metastases. Noteworthy is that all patients with relapse received adjuvant radiotherapy and in 16 (88.9%) cases quadrantectomy was made. Patients with recurrent disease and with absence of distant metastases underwent mastectomy. In January 2014 they were all alive with the time of follow-up ranged from 30 to 162 months. Overall 5-year survival (Kaplan-Meier) was 92,3 ± 1,8% and 10-year survival was 84,2 ± 2,5%.
Conclusion. Organ-sparing treatment with careful selection of patients should be the method of choice. A retreat from the visible borders of the tumor 0.5 cm is sufficient. The main goal of breast preserving is to achieve a good cosmetic result, so if this is not feasible - conserving surgery is meaningless.
METASTATIC BREAST CANCER
Brain metastases of breast cancer are severe complication of oncological process. Despite the spreading of the process, many patients receive treatment and live for years in contrast to patients with cerebral metastases of other cancers (lung cancer, melanoma, renal cell carcinoma). At different stages of metastatic disease in these patients may be offered different types of treatment: chemotherapy, hormonal therapy, targeted therapy, radiotherapy, radiosurgery, surgical treatment. However, there are no standards that define the indications for surgical treatment of cerebral metastases of breast cancer. This article describes the surgical techniques and defines indications and contraindications for surgical treatment.
The Blokhin RCRC the effectiveness of various schemes of drug therapy in breast cancer patients with brain metastases was evaluated.
When using the schemes with anthracyclines (CAF, AC) among 26 patients objective response in the brain (full and partial regression) was registered in 16 (62%) patients (previously untreated patients). Median survival was 12 months. In the group of patients received monotherapy (30 patients), capecitabine was administered at a dose of 2000 mg/m2/day per os the 1 to 14 days every 3 weeks. Partial effect in the brain was registered in 9 patients (30%). Median survival was 15.1 months. In the combination therapy group (capecitabine + radiotherapy) among 30 patients overall effect in the brain was registered in 4 patients (13%), partial response - 18 (60%). Median survival was 22 months. The effectiveness of chemotherapy scheme gemcitabine and cisplatin in 30 breast cancer patients with metastases in the brain, previously treated with I-III line of chemotherapy and radiation therapy in the area of the brain was evaluated. In 4 cases (13.3%) complete regression of metastases in the brain was achieved. In 12 patients (40.0%) a partial regression of metastases in the brain was achieved. Median survival was 10 months. Twenty-three breast cancer patients with overexpression of Her2/neu, and with metastatic brain lesions received capecitabine + lapatinib. Complete response in the brain was achieved in 2 cases (8.7%), partial regression - in 9 cases (39.1%) and stabilization of the disease - in 10 cases (43.5%). Median overall survival was 16 months. Nine patients with breast cancer with overexpression of Her2/neu, and with metastatic brain lesions received therapy with capecitabine + trastuzumab. In 2 cases (22.2%) complete regression of metastases in the brain was achieved, in 4 cases (44.4%) - partial response, in 2 cases (22.2%) - stabilization. The median overall survival was 15.5 months.
Thus, the results of this study have shown high efficiency of drug therapy in the treatment of breast cancer patients with metastases in the brain.
EPIDEMIOLOGY AND PREVENTION OF BREAST CANCER
Epidemiology of breast cancer (BC) is the most studied, not only because of the high incidence of this tumor, but also of the significant aesthetic and social importance of this organ for women [2,5]. The incidence of breast cancer holds a leading place for more than 20 years in the structure of cancer pathology in women in the Russian Federation and in the Altai region [5,8]. There are no trends in decreasing of morbidity: in 2002 in the Russian Federation this parameter was 38.89 per 100 thousand (%ooo, standardized parameter), in 2012 - 46.17%ooo (increase during past 10 years - 19.94%) [5]. There is the same trend in the Altai region: the growth of "rough" parameter of the incidence of breast cancer in the period 2004-2012 was 28.2%, the standardized parameter - 46.76%ooo in 2012 [5]. Breast cancer - one of the 3 malignant neoplasms (MN) which is designed for mammography screening, which significantly reduces the mortality from this MN in women aged 50-69 years [2,7,9,15]. Today, multiple risk factors are studied and identified enabling the development of oncological risk group, which aims is the prevention and early diagnosis of breast cancer [1,3,6,12,19,23]. It is proved that up to 10% of malignant breast tumors are genetically determined and, perhaps, the most of molecular genetic studies in oncology are focused on breast cancer problems [10,13,14,16,17,24]. At the same time, despite the many advances in the prevention and diagnosis of this disease, the high levels of mortality are stably maintained. Mortality from breast cancer in the Altai region in 2013 was 28.1%ooo (in the Russian Federation in 2012 - 29.8%ooo) [5]. Thus, the problem of prevention of malignant tumors of the breast is not yet resolved and remains extremely relevant.
LOCALIZED RECTAL CANCER
Relevance. Endoscopic electroexcision through the colonoscope, transanal removal of tumors, as well as their transabdominal removal are used For the treatment of benign and malignant tumors of the rectum. These methods have both advantages and indications, as the limitations and drawbacks. Priorities of the modern oncology to develop organ-preserving methods of treatment have led to development of transanal endoscopic surgery method. Full visual control and microsurgical technique allow to achieve precise en-bloc removal of tumors with adequate lateral margins, with the possibility of excision of the entire thickness of the bowel wall.
Aim. To evaluate the results of transanal endoscopic removal of rectal tumors.
Materials and methods: The study included 46 patients operated by transanal endoscopic surgery for adenoma and early rectal cancer. Tumors were located at a distance of 3 to 13 cm from the dentate line, their size ranged from 1.2 to 5 cm, 85% of tumors had a wide base. Rectum polyps (65%) were removed with entire wall of the rectum, polyps with signs of malignancy and early rectal cancer (35%) were removed with the mesorectal tissue. Final pathological examination revealed adenocarcinoma in situ in 15% of patients with adenomas.
Results: Postoperative complications occurred in 3 patients (6.5%). Two patients had a febrile temperature reaction. One patient had an intestinal bleeding, that was stopped by conservative measures. Follow-up of these patients ranges from 3 months to 2 years. In follow-up period rectal tumor recurrence was detected in 2 patients (4.3%) during 10-14 months after surgery. Transanal endosurgical intervention didn’t have any significant impact on the function of the rectum.
Conclusion. Described capabilities allow to recommend this method for widespread introduction into surgical practice. Based on these results we can conclude that transanal endoscopic removal of tumors may become the treatment of choice in patients with early cancer of the rectum.
At stage II and III colon cancer (cT3/PT 4 or cN +), in most cases, the standard approach in the treatment strategy is a combination of surgery and preoperative chemoradiotherapy. This approach allows to reduce significantly the frequency of relapses and, according some studies, it leads to improvement in overall survival. However 10 years after surgery from 30% patients with stage IIc to 70% patients with stage IIIc die from disease progression. This progression of the disease in the majority cases manifests with distant metastasis, which dictates the need of improving of systemic therapy. Adjuvant chemotherapy is the main method of preventing distant metastasis at the early stages of the disease. However, for today the data on the effectiveness of post-operative treatment of rectal cancer after preoperative chemoradiotherapy remains controversial. This literature review is devoted to the analysis of the results of studies evaluating the effectiveness of adjuvant chemotherapy in patients with rectal cancer after preoperative treatment for stage II disease.
RADIOTHERAPY
The development of chemotherapy led to significant advances in cancer treatment, but its efficacy in treatment of brain metastases is insufficient. Fractionated whole brain irradiation has been the standard treatment for brain metastases, but provides limited local control and as a result, poor clinical results. Radiosurgery using "Gamma Knife" and "Cyber Knife" significantly changed the results of treatment of patients with metastatic brain lesions, which allowed to formulate new standards in the therapy of this group of patients. This review summarizes the current literature data on radiosurgical treatment of metastatic brain lesions with an emphasis on survival and quality of life, tumor response and potential combinations of treatments.
MODERN ENDOSCOPIC DIAGNOSTICS AND TREATMENT OF THE RESPIRATORY AND GASTROINTESTINAL TRACT TUMORS
The results of many years of work on the identification of patients with hiatal hernia and Barrett’s esophagus, their examination and treatment are presented in this study. The technique to prevent the development of esophageal adenocarcinoma in the background of Barrett's esophagus and improve the quality of life of patients was developed.
PROBLEMS IN DIAGNOSTICS AND TREATMENT OF HEAD AND NECK TUMORS
Treatment and rehabilitation of patients with cancer of the larynx is a complex issue, as the majority of patients (60-70%) are diagnosed at the III and IV stages of the disease. The main type of surgery is a laryngectomy which leads to organ dysfunction and disability. It is known that in cases of locally advanced laryngeal tumors resection may be performed. However, after these operations from 22 to 57% of patients couldn’t be rehabilitated due to the difficulty in creating of sufficient lumen of the larynx, development of chondroperihondritis, growth of granulation tissue, fibrosis formation and stenosis of the larynx (Bukhman L.A., 1982; Bityutskij P.T., 1990; Park H.Y., 2009; SoYeonLimatal, 2012).
SUPPORTING CARE IN ONCOLOGY
Introduction: The frequency of venous thromboembolic complications (VTEC) in cancer patients increased by 10% during chemotherapy. The combination of systemic hypercoagulation and hypofibrinolysis are the most dangerous risk factors of VTEC.
Aim of this study was to evaluate the parameters of thromboelastography (hypercoagulation and hypofibrinolisis) to assess the impact of the use of low molecular weight heparin.
Methods: We studied 78 cancer patients (women - 47, average age - 56 years) before chemotherapy with a high risk of VTEC according to Khorana scale (≥3 points). Blood tests were taken before and 3-4 hours after injection of LMWH (dalteparin sodium 5000 IU per day). The following parameters of thromboelastography were studied (TEG 5000, USA): R - the start of the reaction (our modification, RF patent №2015515, normal values = 660-970), fibrinolysis (our modification, RF patent №2358657, normal values = 60-120%). To evaluate the complex interaction of these two parameters, we decided to introduce a point scoring: 1 point when the parameter R was less than 500 seconds and 1 point when fibrinolysis was lower 40%. In case of reduction of these parameters above the a/n values we began therapy with LMWH.
Results: Before the use of LMWH 38% of cancer patients had moderate/expressed hypercoagulation (mean score = 0.5), and 80% - moderate/expressed inhibition of fibrinolysis (average score = 0.95); total score was 1.45. Therefore, inhibition of fibrinolysis is a leading risk factor for VTEC in cancer patients. At the peak of the action of LMWH total score decreased by 64% (p <0.01). In 10% of patients with total score = 1.0, we increased dose up to 5000 IU LMWH x 2 times per day. As a result, the control of tromboelastography parameters showed a reduction of total score by 14% of the initial value. Thus, additional drug correction of the hemostatic system and fibrinolysis reduced total score by 78% of the initial value.
Conclusion: Hypofibrinolysis is a major risk factor of VTEC development. Combined evaluation of hypercoagulation and hypofibrinolysis allows a better assessment of the risk of VTEC in cancer patients. The proposed parameters of thromboelastography are the most appropriate for the evaluation of LMWH antithrombotic effect.
PALLIATIVE CARE
In 2012, the State program of development of health care in the Russian Federation included a program of palliative care (PC), the result of the implementation of which should be a creation of a full infrastructure in the regions to provide PC to patients requiring active symptomatic treatment and psychosocial support in the later stages of incurable progressive disease. The aim of this study was to investigate the volume and location of inpatient medical care to patients who died from malignant neoplasms during the last year of life to determine their needs in the PC on the actual use of health services. Patients who died from cancer at home, in the last year of life received inpatient care at different levels of the health system (69.5 admissions per 100 patients per year), mostly in the MO Ministry of Healthcare (79.77 of all hospitalizations (CI 78, 9% -80.6%)), and 20,23 ± 3,0% in the regional oncologic center. Two hundred and twenty beds, which are used today to provide medical care for cancer patients during the last year of life, can be regarded as the minimum volume requirements in the palliative care for cancer patients, including a specialized hospitals (33.54 beds) at the existing levels of morbidity and mortality from cancer in the region, as well as the functioning and effectiveness of the health care system, primarily of outpatient care. The number of beds used by cancer patients for palliative care during the last year of life, made up 80.12% of the total number of beds for palliative care, calculated according to the standard recommended by the State Program of Health of the Russian Federation until 2020. We must bear in mind that in accordance with the standard of palliative care 80% of the number deployed beds should be used for cancer patients, and only 20% - for patients with other nosological forms of diseases. This underscores the relevance of developing and using practical criteria for the selection of patients with chronic progressive disease, and non-cancer diseases to provide specialized palliative care.
PREVENTION AND TREATMENT OF INFECTIONS IN ONCOLOGY
Urinary tract infections become a source of multiresistant microorganisms in the hospital due to underestimation of its incidence and importance, especially in the presence of urinary catheters. Particular problems are fluoroquinolone-resistant gram-negative urinary tract pathogens, as well as Enterobacteriaceae producing extended spectrum beta-lactamases. Understanding of modern trends in development of microbial resistance and the rational use of antibiotics will help oncologists to provide qualified care to patients who develop urinary tract infections.
The problem of bloodstream infections associated with intravascular devices, is currently still relevant. The increase in demand of installation of intravascular catheter is caused by requirements for therapeutic, prophylactic, diagnostic and other procedures. Minimising the risk of potentially life-threatening infections, including bloodstream infections related to intravascular devices, as well as reduce the incidence of nosocomial infections should be considered as a priority in a comprehensive work to improve the quality of medical care.
PREVENTION AND TREATMENT OF THROMBOEMBOLIC COMPLICATIONS IN ONCOLOGY
Patients with malignant neoplasms are characterized by a high risk of thrombotic complications, which could complicate antitumor treatment and worsen the survival rate. Changes in the hemostatic system, caused by both the tumor and the treatment methods have the main role in the pathogenesis of thrombotic complications in cancer patients. Low molecular weight heparins are the basis for specific prevention of thromboembolic complications in cancer patients. The use of low molecular weight heparins before and after surgery and chemotherapy reduces the activation of intravascular coagulation, reduces the incidence of venous thrombosis and prevent fatal pulmonary embolism, which enhances the antitumor treatment and improves the quality of life in cancer patients.
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