Vol 22, No 4 (2017)

Articles

NEW IMMUNOLOGICAL CHECKPOINTS FOR CANCER IMMUNOTHERAPY

Chapoval A.I., Podlesnykh S.V., Kolosova E.A., Shcherbakov D.N.

Abstract

Members of B7-CD28 family ligands and receptors play the important role in the co-stimulation and inhibition of the T-cell mediated immune response. Blocking of the B7 family molecules inhibiting the immune response (also called immunological checkpoints), CTLA4 and PD-1 / PD-L1 promoted to important therapeutic achievements in cancer immunotherapy and improved survival of cancer patient. The recent discovery of new B7 family molecules (such as B7-H3 [CD276], B7-H4 [B7S1 / B7x / Vtcn1], B7-H5 [VISTA / PD-1H / GI24], B7-H6 and B7-H7 [HHLA2]) has expanded therapeutic possibilities for the management of cancer patients. In this article, we discuss the clinical application of known blockers of immunological checkpoints and the prospects for the use of newly discovered molecules.
Russian Journal of Oncology. 2017;22(4):175-179
pages 175-179 views

AN APPROACH OF THE INTRAOPERATIVE RESTORATION OF THE ANTERIOR WALL OF THE MAXILLARY SINUS FOR PRECANCEROUS DISEASES

Artamonova A.V., Samsonova O.A., Lazarev A.F., Glikenfreid G.M., Matviyenko K.N., Zorkina Y.N., Glotov S.S.

Abstract

Osseous defects in the anterior wall of maxillary sinuses, which might appear as a result of maxillary sinusotomy, cause the retraction of soft tissues into the sinus with a follow-up adhesion to the posterior wall. This results in the obliteration of the sinus with scar tissue, formation of synechia, the obliteration of anastomosis and an increase in disease recurrences rate. We propose a new method of the plastic closure of the defect of the anterior wall of the maxillary sinus to restore the continuity of osseous walls of sinuses, which can be used in ORL clinics, oncological centers or dental clinics. For the first time a fragment made from polyether-polytetrafluorethylene threads was used. This implant has all necessary properties: it is durable, flexible and elastic; it is light and bioinert, it has no negative impact on the body; it is easily treated and is available for the use. We determined exact indications for the plastic closure of the defect of the anterior wall of the maxillary sinus. Using of the implant and the placing it on the muscle-periosteal graft protects it from the contact with the mucous lining of the maxillary sinus. The fixation of this implant not only to the underlying soft tissues but also to the overlying ones, creates a good frame, whereas preliminary sinus sanitation by ultrasound cavitation and layer-by-layer low-frequency ultrasonication of stitches allows slash risks of infecting the plastic material and surrounding soft tissues and, as a result, to reduce the number of recurrences of the disease in patients.
Russian Journal of Oncology. 2017;22(4):180-183
pages 180-183 views

THE EVALUATION OF THE EFFECTIVENESS OF LOCAL APPLICATION OF OZONE THERAPY FOLLOWING CRYOTHERAPY OF LESIONS OF VERRUCOUS LEUKOPLAKIA OF THE ORAL MUCOUS MEMBRANE

Tokmakova S.I., Bondarenko O.V., Shilova J.N.

Abstract

There are presented results of the study morphological and clinical changes of the oral mucosal membrane. In the experiment on laboratory animals the use of ozone therapy following the destruction of the mucous membrane of the mouth was proved to appear earlier with the more complete epithelization of the defect, compared to the treatment implemented according to the traditional scheme. There was performed a clinical examination of 32 patients with verrucous leukoplakia of the oral mucosal membrane, the treatment of which was carried out according to the traditional scheme (cryotherapy and topical anti-inflammatory treatment - group comparison) and with the use of the ozonized solution of olive oil with a known peroxide during the postoperative period (control group). To assess the effectiveness of the proposed method of the management of the postoperative wound there was used a point scoring system of clinical signs at stages of the postoperative period. There was revealed a more earlier onset of the complete epithelization in cases of the application of the local ozone therapy in comparison with traditional local treatment.
Russian Journal of Oncology. 2017;22(4):184-187
pages 184-187 views

MOLECULAR TYPES IN THE PROGNOSIS OF PAPILLARY THYROID CANCER BASED ON THE ANALYSIS OF THE STATUS OF BRAF V600E, INDEX AND KI-67 EXPRESSION

Ivanov A.A., Avdalyan A.M., Gerval'd V.J., Lushnikova E.L., Zorkina Y.N., Kruglova N.M., Lazarev A.F.

Abstract

The aim of our research was to determine the possibilities to stratify patients with papillary thyroid cancer (PTC) on the group’s forecast, depending on the status of the mutation BRAF v600e and Ki-67 expression. The study included 89 PTC patients with the known prognosis for the period of 2005-2015. They were treated in the Altai regional oncology center and underwent surgery for PTC over the period of 2005-2013. Mutation p. Val600Glu (V600E) BRAF gene was determined with the use of allele-specific real-time PCR kit «Real-time-PCR-BRAF-V600E («BioLink»)». Immunohistochemical examination was performed with antibodies Ki-67 (clone MIB1, «DAKO») on stainer «Ventana XT» according to standard protocols. We revealed BRAF V600E not to be an independent predictor. Different variants of PTC, depending on the level of expression of Ki-67 in combination with a mutation of BRAF V600E was allowed to identify 3 groups of molecular types of PTC: a lack of mutation and a low Ki-67 (type I), with mutation and a low Ki-67 (type II) and with the presence and/or absence of a mutation and high level Ki-67 (type III). I molecular type PTC is the most favorable from the point of view of survival: 100% of patients live 10 years. Molecular type II is characterized by an intermediate prognosis: 76% of patients lived out up to 10 years. Molecular type III is characterized by the poor prognosis: only 36.8 percent of cases lived up to 10 years. In multivariate analysis of survival in PTC patients the independent prognostic factor happened to be the molecular type of tumor. In this case χ2 = 35 at p ≤ 0.000005.
Russian Journal of Oncology. 2017;22(4):188-193
pages 188-193 views

PROGNOSTIC SIGNIFICANCE OF REARRANGEMENTS OF EML4-ALK IN PATIENTS WITH STAGE TI-II ADENOCARCINOMA IN THE RELATIONSHIP WITH SOME CLINICAL AND MORPHOLOGICAL PARAMETERS

Avdalyan A.M., Panasyan A.U., Ivanov A.A., Samuilenkova O.V., Bakharev S.Y., Bliznyuk A.S., Lazarev A.F.

Abstract

The purpose of the study: determination of ALK gene status (mutation) in patients with stage TI-II adenocarcinoma in the relationship with survival, stage, size, metastases in bronchopulmonary lymph nodes and the amplification of Her2/Neu. Materials. 98 stage I-II adenocarcinoma patients. Cases with a mutation in ALK account for 20 (4.8% without randomization). There was used the immunohistochemical method and in situ hybridization. Results. The survival rate of adenocarcinoma patients with metastases in the lymph nodes was lower than in cases without metastases: 8.3 ± 7.8% and 40.9 ± 13% respectively. None of patients with a mutation ALK lived up to 9 years in contrast to the cases without mutations (37.4 ± 12.6%). In the presence of amplification of the Her2 gene survival rate in adenocarcinoma patients was lower if compared to cases without amplification (p = 0.02). Correlation between ALK mutation and amplification of Her2 with increased N is not revealed. Thus, an independent criterion of the prognosis for cases with of stage I-II lung adenocarcinoma is the N index (χ2 = 9.6, p = 0.001). The rate of mutation of ALK was lower, but had the second largest impact on the prognosis (χ2 = 7.7, p = 0.005).
Russian Journal of Oncology. 2017;22(4):194-197
pages 194-197 views

MANAGEMENT OF SEVERE PERIOPERATIVE BLEEDING IN PATIENTS DURING EXTENSIVE LIVER RESECTIONS FOR COLORECTAL METASTASES

Mamontov K.G., Khays S.L., Varnavskiy E.V., Mamontov A.K., Lazarev A.F.

Abstract

Aim of the study. To estimate an influence of the Cavitron ultrasonic surgical aspirator (CUSA) on intraoperative blood loss. Material and methods. An analysis of 185 cases of extensive liver resections in patients for colorectal liver metastases has been performed. All patients were assigned to CUSA group (n = 56) or clamp crashing group (n = 129). Patients from the first group received regional FOLFOX6 or FOLFOX6 + bevacizumab chemotherapy. Preoperative chemotherapy did not performed for second group of patients. Results. Liver transection with CUSA did not lead to the decline in intraoperative blood loss (p = 0.35). Conclusion. Median intraoperative blood loss was 1065 and 1180 ml respectively. Method for liver transection did not lead to the decline in intraoperative blood loss (p = 0.35). Intraoperative blood loss increases from standard to extensive liver resection (p = 0.0007). Resection of contralateral blood lobe metastases did not lead to statistically significant increase in blood loss as compared with standard mode of the operation (p = 0.005).
Russian Journal of Oncology. 2017;22(4):198-202
pages 198-202 views

ASSOCIATION OF THE FOLATE METABOLISM GENES WITH THE RISK FOR LUNG, PROSTATE, BREAST AND UTERINE CANCER

Shilova A.N., Shkoda O.S., Lomivorotov V.V., Shilova J.N.

Abstract

We examined 324 patients with various oncological diseases (157 patients with prostate cancer, 54 - with lung cancer, 47 - with uterine cancer, 42 - with cervical cancer and 24 patients - with breast cancer) and 391 relatively healthy donors. We investigated the frequency of key polymorphisms of folate metabolism genes (MTHFR: 677 C>T (Ala222Val); MTHFR: 1298 A>C (Glu429Ala); MTR: 2756 A>G (Asp919Glu); MTRR: 66 A>G (Ile22Met)). Analysis revealed no differences in the frequency of all examined gene polymorphisms and alleles between patients with oncological diseases and relatively healthy donors. All investigated genotypes and alleles of key folate cycle genes were not associated with the risk for the development of oncological diseases.
Russian Journal of Oncology. 2017;22(4):203-208
pages 203-208 views

INTERRELATION OF THE EXPRESSION OF PROTEINS ALK, HER2 AND AMPLIFICATION OF THE GENE OF HER2 WITH THE PROLIFERATIVE ACTIVITY AND SURVIVAL IN PATIENTS WITH STAGE I-II LUNG ADENOCARCINOMA

Panas’yan A.U., Kobyakov D.S., Avdalyan A.M., Ivanov A.A., Lushnikova E.L., Bakarev M.A., Lazarev A.F.

Abstract

To investigate protein content of ALK, Her2 and gene of Her2, CEP17 in interrelation with proliferative activity and survival in I-II stages lung adenocarcinoma cases. There were investigated 82 surgery samples taken from I-II stage lung adenocarcinoma patients. With the use of immunohistochemical method ALK protein (clone D5F3, Ventana), Her2 protein (clone 4B5, Ventana), topoizomerase IIα (clone JS5B4, Ventana), Ki-67 (clone MIB-1, Dako) were determined, Her2 gene was investigated with the use of the SISH method (Ventana) also. The positive expression of ALK is detected in 4(5%) cases, Her2 - in 16(20%) cases and amplification of Her2 gene - in 7(9%) cases. In lung adenocarcinoma with positive expression of ALK protein and amplification of Her2 gene low proliferative activity was noted (on labeling index Ki-67 and topoizomerase IIα). The survival of lung adenocarcinoma patients was less in cases of a positive expression of ALK protein in comparison with patients with the negative expression (difference is not reliable). Statistically significant low survival rates of patients is found in cases with amplification of Her2 gene. According to data mono- and multifactor regression analysis the amplification of Her2 gene has been interrelated with the poor forecast. Mutation of ALK gene and amplification of Her2 gene are interrelated with the proliferative activity and survival rate of lung adenocarcinoma patients.
Russian Journal of Oncology. 2017;22(4):209-213
pages 209-213 views

MOLECULAR GENETIC TESTING IN DIAGNOSTICS OF LUNG CANCER AND OVARIAN CARCINOMA WITH THE USAGE OF CYTOLOGICAL SPECIMENS

Grigoruk O.G., Pupkova E.I., Bazulina L.M., Lazarev A.F.

Abstract

This article presents results of the introduction in practical oncology of molecular genetic investigations performed with the use of tumor DNA cells taken from the cytological specimens. There was investigated the molecular genetic characteristics of cytological specimens from 126 patients. In 80 cases with the proved diagnosis of pulmonary adenocarcinoma (n = 80) EGFR gene mutations were noted in 11.7% cases. KRAS, BRAF and BRCA1/2 gene mutations were determined in 46 women suffering from serous ovarian carcinoma. KRAS gene mutations in cells of ovarian low-grade serous carcinoma were determined in 62.5% of patients, BRAF- in 12.5% cases. BRCA1 gene mutations have been determined in 14.3% cases from the ovarian high-grade serous carcinoma group. In conditions of the presence of the sufficient amount of tumor cells the cytological material is the fully-featured material for molecular genetic investigations. The investigation both of EGFR gene mutations in pulmonary adenocarcinoma cases and KRAS, BRAF, BRCA1/2 gene mutations with serous ovarian carcinoma are mandatory in the appointment of targeted therapy.
Russian Journal of Oncology. 2017;22(4):214-218
pages 214-218 views

EXPERIENCE IN IMPLEMENTATION OF THE PROJECT «POLYCLINIC WITHOUT QUEUES» IN THE TOMSK REGIONAL ONCOLOGY CENTER

Kudyakov L.A., Pikalova L.V., Ryabova L.M., Shtogrina Y.I., Ananina O.A., Lazarev A.F., Zhuikova L.D.

Abstract

The problem of queues in polyclinics and hospitals is a deterrent to ensuring access to oncological care. In order to optimize anti-cancer control there were shortened timelines both for the diagnosis and the beginning of the specific treatment. Since 2012, in the Tomsk Regional Oncology Center a new concept of the polyclinic organization on the profile of «oncology» was formed. The key aspects of this concept were: 1) standardization of the medical staff work; 2) the rules for the routing of patients with the execution of the first medical appointment booking for visiting doctor through the registry, for the second visit - by an oncologist and with the differentiation of the streams of patients for medical care in the framework of MHI and medical services on a fee basis; 3) intensification of the provision with outpatient specialized care with the staff reinforcement: the regime of the polyclinic is organized in two shifts and 6 days a week, the number of doctors and nurses is increased by 60.8%, the number of medical registrars - by 7 times. To coordinate their work, the position of the senior medical registrator was introduced; 4) modernization of all workplaces of doctors, nurses, medical registrars with the provision of modern medical equipment, communications and information support; 5) logistics of the registry: the division of its zone into a «front office» - were the office-medical registrator communicates with patients only as «face-to-face» and «call center» - with a dialogue by phone. 6) quality control of the clinic work with evaluation of video and audio recordings of interaction between registrars and patients, visitors questioning. 7) the reform of the oncological consultation on an ongoing basis regulations; 8) increasing the comfort of waiting for patients with the organization of comfortable seats, coolers with glasses, air conditioners, corporate identity and logo. The result of the implemented activities was a reduction in the start of specialized treatment by 68.3%, increased coverage of antitumor therapy by 16.4%, including among rural residents. This contributed to the improvement of the situation in a number of indices: the increase in the share of early forms of malignant neoplasms, active detectability by 21.6% and 164.7%, respectively, a decrease in one-year mortality rate, neglect by 25.2% and 8.6%, respectively. Population satisfaction with the provision of cancer care increased.
Russian Journal of Oncology. 2017;22(4):219-223
pages 219-223 views

THE FACTOR OF IONIZING RADIATION AND THYROID CANCER IN WOMEN IN THE ALTAI KRAI

Lazarev A.F., Shoikhet Y.N., Pisareva L.F., Petrova V.D., Terekhova S.A.

Abstract

The purpose of the study was to study the dynamics of the incidence of thyroid cancer in the female population of the Altai Territory during the period of 1992-2016. Studies were performed with the use of data of the patient register of thyroid cancer, including information on 3026 women, with the use of methods of modern medical statistics. Intensive and standardized indices were calculated for the female population, resided near to traces of nuclear explosions executed at the Semipalatinsk test site, in the zone of the most significant radiation doses (the Main group). As a comparison, incidence rates of the remaining population of the Altai Territory (the Comparison group) and average values for the region were used. The article presents results of a descriptive epidemiological study of the incidence of thyroid cancer in the Altai Territory over 25 years (1992-2016). The results of the probabilistic association of the incidence of thyroid cancer with the ionizing radiation factor due to nuclear tests at the Semipalatinsk test site were obtained. The dynamics of the incidence of thyroid cancer by the data for five-years periods (averaged data): 1992-1996; 1997-2001; 2002-2006; 2007-2011 and 2012-2016 was studied in various territories of the Altai Territory: both on the traces of nuclear explosions - the main group, and in the rest territory (the comparison group), indices of average values for the regions. There were revealed the dynamics of the incidence of thyroid cancer in tens of years after nuclear tests in the population living in the zone with the most significant doses of radiation and its gradual decrease, due to rehabilitation measures. New approaches to the formation of high cancer risk groups for thyroid cancer in the Altai Territory are substantiated.
Russian Journal of Oncology. 2017;22(4):224-228
pages 224-228 views

THE STATE OF THE MEDICAL CARE FOR LUNG CANCER PATIENTS IN THE ALTAI REGION

Cherdantseva T.M., Ageev A.G., Fedoskina A.V., Sekerinska E.L., Popov V.A., Lazarev A.F.

Abstract

The relevance of the study of lung cancer is associated with a high incidence and mortality rate. The article is devoted to the study of indices of the prevalence rate of the lung cancer in the Altai Territory for the period of from 2014 to 2016. An increase in the prevalence rate of lung cancer has been established to be of 61.4% (2016) per 100 00 population (both genders), the increase in the «rough index» accounted for 7.4%. With the bearing in mind the age-gender characteristics, statistical analysis showed the highest level of the prevalence rate of cancer of the trachea, bronchus and lung to be observed in males, that amounts of 19.3% among malignant tumors detected in 2016 in the Altai Territory. The greatest increase in the incidence rate of lung cancer is observed in both males and females in the age group of 60-69 years. In stage I-II lung cancer patients there is noted the gain of the specific weight and the decline in the mortality rate to 40.3 per 100 000 population of the Altai Krai.
Russian Journal of Oncology. 2017;22(4):229-232
pages 229-232 views

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