RESULTS OF THE INNOVATIVE SCENTIFIC RESEARCHES PERFORMED IN P. HERTSEN MOSCOW ONCOLOGY RESEARCH CENTER, BRANCH OF THE FSBI NMRRC OF THE MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION
V. V. Starinsky, L. M. Alexandrova, E. N. Vyazmina,
Concern and special attention to oncology is one of the characteristic features of health care of all developed countries which is caused by a steady tendency of growth in oncology incidence.
In the Russian Federation in 2011 522,410 new cases of the malignant neoplasms (MNP) were revealed, women made 54.0%, men – 46.0%. The absolute number of the diseased for the last decade increased by 15.8%. Unfortunately, almost 60% of the incident population are revealed at the III-IV stage. It leads to the considerable invalidism of patients because of lower treatment effectiveness. According to the Ministry of Labor of Russia and to calculation of Rosstat in 2011 185 thousand patients were recognized for the first time as disabled for an oncology disease (22% of the total number of disabled people), and this index grows year by year. In this regard the development of new medical technologies of diagnostics, treatments and rehabilitations of the oncology patients based on the modern achievements of medical science and technology is extremely important.
One of the major activity of P. Hertsen Moscow Oncology Research Center is the innovative activity that, as a result, brings new ideas, new or improved techniques. In recent years in P. Hertsen Moscow Oncology Research Center the number of research papers performed at the level of the inventions has considerably increased, i.e. these papers meet patentability conditions: novelty, degree of inventiveness, industrial applicability.
Along from 2007 to 2013 82 applications for inventions and 4 applications for a utility model were prepared and submitted for consideration to Federal State Budgetary Institution Federal Institute of the Production Property of Federal Service for Intellectual Property, Patents and Trademarks. 88 invention patents were granted. More than 70% of applications fall into the category of new and improved malignant neoplasms treatment methods, and 22% - into diagnostic methods category.
One of the priority development orientations of clinical oncology is the development of photodynamic therapy techniques (PDT) and fluorescent diagnostics of malignant tumors, photosensitizers of new generation. In Russia P. Hertsen Moscow Oncology Research Center is the leader in developing this sphere. Now huge activity is under way in the fields of implementation of new developments into practical health care of various territories of the country, and in the field of improvement of treatment of tumors of various location. A series of new PDT technologies was developed and covered by patents, including: a method of treatment of the surface bladder cancer (patent No. 2346657), a method of intraoperative photodynamic therapy in cases of tumorous pleura damage (patent No. 2391907), a method of conservative treatment and prophylaxis of virus recurrence - the associated precancer and early cancer of uterus neck (patent No. 2494616), a method of treatment of the surface bladder cancer (patent No. 2346657), the device and the method for delivery of an intertissual laser hyperthermic and photodynamic therapy (patent No. 2424009). Development of this sphere allows accurately estimate the area of tumorous damage as a result of detection of the latent cancer forms, carrying out the organ-preserving functional sparing treatment of patients, including functionally inoperable ones, facilitating improvement of their life quality.
Research associates of the institute take an active part in development of photosensitizers of the new generation and methods of their use. Research is mainly conducted jointly with Federal State Unitary Enterprise SSC Research Institute of Organic Intermediates and Colorants (the CEO, the Corresponding member of RAS G. N. Vorozhtsov). A bunch of patents concerning methods of suppression of tumors growth (patents No. No. 2339414, 2383370, 2376999), "Composition for fluorescent diagnostics" patent No. 2379026) were among such developments. The patent No. 2339414 dated 27.11.2008 for the invention "Method of tumor growth suppression", whose essential features are intravenous administration of nanoparticles of phthalocyanines with the subsequent radiation of a tumor by laser impulses with a wavelength in the field of intensive absorption of nanoparticles was included into the Russian register of 100 best inventions of year.
In the recent decade the tendency of growth in number of throat cancer cases of mainly male population of the country has been noted. At the same time the considerable proportion of patients’ neoplasms are reveled in late stages when the process is considered inoperable, or the surgical intervention may lead to substantial anatomic-functional defects of the adjacent organs and tissues. At a stage of surgical treatment of patients with the recurrent locally-spread tumors of throat and laryngopharynx, affecting trachea, the method of restrosternal tracheostome formation in cases of location of the trachea resected edge in anterior mediastinum (patent No. 2312626) is used. The tracheostome ring is created as a result of a partial resection of the presternum and formation of a bridge-like fasciocutaneous flap on a chest wall. The technology allows executing surgical treatment of patients previously considered inoperable, avoiding possible complications during operation, ensuring in the early postoperative period 3-year and 5-year survival, creating conditions for improvement of quality of life of this complex category of patients.
After a laryngectomy for cancer the major stage is restitution of the patient’s voice function. In recent years restitution of voice function after larynx amputation using voice prosthesis was widely adopted. In these cases the design of a tracheostome is of huge importance for performing respiration and a phonation functions in the postoperative period, and creation of a non-cannule tracheostome of the stable, adequate size (0.5 - 2 cm) is the most important task. The method of restitution of voice function after a laryngectomy including trachea-gullet shunting with the use of endoprosthesis and formation of a non-cannule tracheostome (patent No. 2302824) has been developed and introduced into clinical practice. The method allows creating the wide stable tracheostome, providing unassisted respiration and is suitable for restitution of voice function among patients with amputated larynx by means of using voice prosthesis that makes the use of a tracheotomic tube unnecessary and improves quality of life.
The present stage of clinical oncology development is characterized by development of new methods of organ-preserving and functionally sparing treatment. The method of primary organ-preserving treatment of invasive uterus neck cancer, including a radical trachelectomy with abdominal access with preservation of uterus and its ascending arterial and venous blood vessels (patent No. 234859) has been developed in the Institute. Such an operative treatment allows preserving genital function, and is an adequate alternative to expanded hysterectomy in reproductive age patients.
An important sphere of innovative activity of P. Hertsen Moscow Oncology Research Center is the development of new materials for bone defects restoration, its experimental approbation and introduction of treatment methods in clinic. Together with A. A. Baykov Institute of Metallurgy and Materials Science of RAS the following composites were created and covered by patents of the Russian Federation: material for bone defects restoration in reconstructive plastic surgeries (patent No. 2333010) representing the particles of a carbonate-substituted hydroxyapatite, made in the form of porous spherical granules. Material has the following properties: high adhesion to cells, a combination of properties of osteoconductivity and osteoinductance, similarity of chemical and phase composition of the implanted material to composition of the replaced tissue, adjustability of speed of dissolution during its replacement with a bone tissue, a possibility of three-dimensional uniform filling of the bone defect repeating its shape. Material can be sated with autologous mesenchymal stem cells. The method of bone defect restoration in reconstructive plastic surgeries with the use of this material is legally protected (patent No. 2375007). P. Hertsen Moscow Oncology Research Center and A. A. Baykov Institute of Metallurgy and Materials Science of RAS have also co-developed a porous synthetic coral for reconstruction of bone defects and a method for its production (patent No. 2368354) and porous composites on the basis of chitosan for filling of bone defects (patent No. 2376019).
The bioengineering product (the patent for the useful model No. 86455) intended for bone defect restoration is among original promising composites. The bioengineering product represents the coral fragment, created in accordance with the shape and size of the defect replaced, containing the autologous multipotent mesenchymal stromal cells immobilized on a coral surface. The method of bone defect restoration using this product has been successfully tested on the test models.
Along with development of new methods of surgical treatment of malignant tumors, much attention is paid to the methods of prophylaxis and prediction of postoperative complications. In particular, methods of intraoperative prophylaxis of a postoperative lymphorrhea are protected by a network of patents and applications for issue of the invention patents: "Method of lymphorrhea prophylaxis after a radical mastectomy" (patent No. 2334485), "Method of intraoperative prophylaxis of lymphorrhea in radical mastectomy" (patent No. 2410034). Use of the developed preventive technologies in clinical practice allows reducing the volume and duration of lymphorrhea, preventing formation of lymphocele in axillary area, early wound complications, avoiding development of the expressed cicatricial changes, postmastectomy hypostasis of the top extremity, and also reducing terms of social and labor rehabilitation of patients.
For prophylaxis and correction of a critical bradycardia and other cardiac rhythm and conduction disorders among oncology patients with a serious cardiovascular illness, the method of prophylaxis of intra-and postoperative complications, including methods of temporary electrocardiostimulation – intra-gullet electrostimulation of auricles or endocardiac electrocardiostimulation (patent No. 232670) and a method of assessment of risk of development of the perioperational cardiovascular complications in extracardiac surgical interventions (patent No. 2410017) have been developed. Technologies allow reducing operational and anesthesiology risk by optimization of preoperative diagnostics, premedication and differentiated intra-and postoperative use of non-drug – electrocardiostimulation, methods of prophylaxis and elimination of dangerous cardiac rhythm and conduction disorders in case of inefficient work of medication. The developed algorithm of managing this serious category of patients allows reducing perioperational cardiovascular complications by 2.3 times, including a 5 time reduction of myocardial infarction, and reducing lethality by 10 times.
Methods of prophylaxis and treatment of entheropathy, that develops on grounds of multiagent chemotherapy (patent No. 2405546), and treatment of a postoperative pain syndrome in cases of extensive thoracoabdominal operations (patent No. 2382646) were developed.
In scientific work of the institute much attention is paid to a problem of MNP diagnostics. Methods of differential diagnostics of pathological volume neoplasms in the root of a mesentery and/or in a big epiploon (patent No. 2344762), predictions of tumorous diseases of a mammary gland (patent No. 2390025), formation of a risk group on mammary gland tumorous pathology (patent No. 2386968) have been developed. Assessment of probability of existence of mammary gland tumorous diseases is carried out with application of a high performance solution chromatographic test of urine by identification and the quantitative determination of content of nucleosides and forecast function estimation The last two inventions were created as a result of scientific cooperation with the personnel of MCRC "Intermedbiofizkhim", chemical faculty of MSU, A. A. Harkevich Information Transmission Research Institute of RAS.
For the purpose of increase in accuracy of tumor cells detection, in delicacy and taking measurements, the method of cytologic diagnosis of cancer by coherent phase microscopy has been developed (patent No. 2306868). During research of the unstained, not activated living cells intensity and spectral characteristics of fluctuations of phase thickness of cells nuclei are determined in the automatic mode and, when finding the studied parameters in the frequency range from 0.8 to 20.0 Hz, the presence of cancer cells is diagnosed. For this research the domestic hardware and software for blood cells morphometry KMKK-01 Granat-hemo, produced by N. E. Bauman Public Educational Institution of Higher Professional Training MSTU», is used.
The list of the developments of P. Hertsen Moscow Oncology Research Center, executed at the level of inventions, includes the works devoted to a methodology of determination of an algorithm of managing the patient cases, for example, a method of prediction of postoperative complications among oncology patients (patent No. 2384297).
The method, that involves the sonographic research with the use of three-dimensional reconstruction of area of tumorous affection (patent No. 2305494), was developed for assessment of effectiveness of conservative antineoplastic therapy. The research determines the tumor volume, bulk volume of the feeding blood vessels and coefficient of its vascularization before treatment. The technology allows increasing accuracy of presurgical diagnostics, planning the volume of a surgical intervention, including organ-preserving and reconstructive plastic surgeries and estimating effectiveness of a specific conservative therapy. Increase in vascularization of a tumor after treatment indicates progressing of a tumorous process. With the use of computer technologies the method of assessment of extent of vascularization of tumorous tissue (patent No. 2366951) has been developed. The methodology of a morphological research includes the use of a new method of the quantitative assessment of vascularization for determinination of biological properties of malignant neoplasms. The method allows determining one of indexes of metastatic potential of epithelial tumors and taking into account this index for the purpose of target therapy which helps optimization of tactics of patient treatment.
Now the institute gives its support to 47 patents. 33 patents served as grounds for new medical technologies of diagnostics and treatment of oncology pathology development, the permit for the clinical use of which was issued by Federal Service for Supervision in Healthcare and Social Development.
The innovative activity of P. Hertsen Moscow Oncology Research Center is performed in close cooperation with many institutions of science, that are leading branch centers such as: Federal State Unitary Enterprise SRC Research Institute of Organic Intermediates and Colorants, Public Educational Institution of Higher Professional Training MIREA, A. A. Baykov Institute of Metallurgy and Materials Science of RAS, Lomonosov Moscow State University, A. A. Harkevich Information Transmission Research Institute of RAS, FRCC of Otolaryngology FMBA, Federal State Institution, SU of "Scientific Research Institute of Neurosurgery of academician N. N. Burdenko of the Russian Academy of Medical Science". Collateral scientific research of diversified specialists in the problem of diagnostics and treatment of malignant neoplasms allows creation of the new hi-tech methods of medical care of patients.