[ENDOCYTOSCOPY--NOVEL ENDOSCOPIC DIAGNOSTICS APPROACH: PRINCIPLES AND PROCEDURE].

Endocytoscopy is one of the most novel endoscopic diagnostic procedures, providing optical magnification up to 1150 times of gastrointestinal and respiratory tract mucosa. Such approach allows real-time tissue and cellular structure visualization. Endocytoscopy, along with confocal laser endomicroscopy, can be considered as "optical biopsy" in vivo. Of course, endocytoscopy currently is experimental diagnostic method, all available endocytoscopes are prototypes. According to published data, endocytoscopy can be used in precancerous conditions and early intramucosal cancer diagnostics in esophagus, stomach, colon and bronchial tree. Different types of endocytoscopes are used for examinations: some of them are baby-scopes, with fixed magnification 570-1150 times, introduced into accessory channel of the therapeutic parent-endoscope, others--are integrated type, providing scalable magnification from 80 to 380 times. As for traditional pathology ex vivo, for endocytoscopy mucosal cell nuclei stain is needed. For vital staining during endocytoscopy methylene blue, toluidine blue and crystal violet in different concentrations are more often used. In cases of squamous-cell dysplasia or cancer, it is recommended to use 1% methylene blue solution, whereas in intestinal type metaplasia, dysplastic changes and cancer (Barrett's esophagus, P. Correa precancerous cascade, colon adenomas), 1% toluidine blue is preferred. With endocytoscopy, after vital staining, we can visualize and estimate mucosa tissue and cell characteristics: papillae, crypt and gland shapes and sizes, their integrity (tissue markers); cell nuclei size and shape, polarity and nuclear dye intensity (cell markers).

[ENDOCYTOSCOPY--NEW TYPE OF ENDOSCOPIC EXAMINATION OF LOWER GASTROINTESTINAL AND RESPIRATORY TRACT].

Majority of published data describing endocytoscopic examination of upper gastrointestinal tract mucosa, but in recent publications, it is reported, that endocytoscopy is suitable for small bowel, colon, respiratory tract and even peritoneum "optical biopsy". In number of articles possibilities of celiac sprue diagnostics with endocytoscopy is discussed, but small-bowel endocytoscopy is limited, due to absence of endocytoscopes, compatible with enteroscopes. More widely endocytoscopy is used in colon, mostly in lateral-spreading adenomas diagnostics. Prof. S-E. Kudo developed endocytoscopic classification of colonic mucosa changes, used for differential diagnostics and lesion mapping, describing hyperplasia, adenomas with different grades of intraepithelial neoplasia, non-invasive and invasive cancer. Some authors reported about good possibilities of endocytoscopy in inflammatory bowel disease diagnostics. Most of data, related to respiratory tract endocytoscopic examination, focused on precancerous conditions and early pharyngeal and lung cancer, and the preliminary results are promising, but, unfortunately, for now, endocytoscopy in bronchial tree is limited, due to lack of thin endocytoscopes. According to some article data, it is possible to use endocytoscopy not only in gastrointestinal and respiratory tract, but also in optical confirmation of peritoneal tumor dissemination in gastric and ovarian cancer patients, and--in bladder mucosa examination.

[PRECONDITIONING AT THE STAGES OF INVASIVE AND REHABILITATIVE TREATMENT OF PATIENTS WITH CORONARY HEART DISEASE].

The comprehensive analysis of efficiency of different variants of preconditioning is currently of special importance since the realization of the potential of endogenous protective effects extends possibilities for anti-ischemic protection of myocardium at different stages of CHD. Today, the main principles of preconditioning are purposefully applied to the development of therapeutic strategies for the treatment of CHD. The most widely used in the clinical practice are local and distant preconditioning modalities as well as preconditioning by physical exercises whose well-known protective effects are used in cardiosurgery and routine clinical practice. Elaboration of rehabilitative and preventive programs taking account of vaso- and cardioprotective effects of preconditioning may significantly increase the effectiveness of the rehabilitative treatment of CHD patients with poor organic coronary and myocardial reserve.

[THE FIRST CLINICAL EXPERIENCE IN THE CELIAC PLEXUS BLOCKADE UNDER ENDOSCOPIC ULTRASOUND NAVIGATION IN PATIENTS WITH PANCREATIC CANCER].

OBJECTIVE: Implementation into clinical practice and getting our own data of the effectiveness of EUS-CPN in chronic pain syndrome associated with pancreatic cancer in the palliative treatment. MATERIALS AND METHODS: In the period from October 2014 to May 2015 in P.A. Herzen Moscow Research Oncological Institute--filial FGBI "NMIRC" gained the first clinical experience in the celiac plexus blockade under endoscopic ultrasound navigation in 10 patients with pain associated with pancreatic cancer. The study group included 6 women and 4 men aged 54-83 years. In 2 of 10 cases out celiac ganglia were located and injections made in side them. In eight cases, the blockade was performed after injection into the tissue surrounding the celiac trunk. In most cases, we used standard FNA-needle with diameter 22G. Blockade performed by a combination of local anesthetic (3-4 ml of 0.5% bupivacaine) and 14-20 ml of 96% ethanol. RESULTS: There were no complications after EUS-BCS. 9 of 10 patients (90%) had a significant (2-4 points on a visual analogue scale) reduction of pain after 1-3 days after the procedure. These patients had a significant reduction in the frequency and dosage of analgesics. Four patients required repeat of anesthesia after 2 months--the same with a marked positive effect. One patient, in spite of the double execution of EUS-CPN did not note reduction in pain intensity. CONCLUSION: EUS-CPN procedure is highly effective, very simple and safe. It provides a high quality of life and of social adaptation oncology patients. It should be more widely used in clinical practice.

[Confocal laser endomicroscopy principles and performing algorithm in gastric mucosa examination].

Accuracy of endoscopic examination in early gastric cancer and precancerous conditions diagnostics for many years depended only on quality of biopsy. That's why, risk of overlooking gastric focal carcinoma, particularly-- multiple, was relatively high. Last couple of years new endoscopic method--confocal laser endomicroscopy (CLE) was released for commercial use. This approach provides real-time information about morphology of gastric mucosa during endoscopic examination. CLE is a variation of confocal microscopy--morphologic technique, providing examination of thick specimens or live tissue. CLE system is a single-channel fluorescence microscope, used in endoscopy, where confocal probe incorporated into endoscope or mounted into accessory channel. For proper results of CLE intravenous administration of fluorescence agent is needed. In our study in P.A. Herzen Moscow Cancer Research Institute we have used 10% fluorescein sodium, due to acriflavine use is prohibited in Russian Federation. In 157 patients with suspected early gastric cancer mean time of CLE was 24 ± 3.5 min. In all cases descriptive images were acquired. Mean amount of endomicrosocpic images in one patient was as high as 162 ± 8.3.

[Early gastric cancer and precancerous conditions diagnostics with confocal laser endomicroscopy].

AIM: To develop endomicroscopic criteria of early gastric cancer and precancerous conditions METHODS: 157 suspected for early gastric cancer patients were included in our study. In all cases complex endoscopic examination (narrow-band imaging NBI-HD endoscopy, endosonography (EUS) and endoscope-based confocal laser endomicroscopy (CLE) with precise biopsy) was performed. CLE images compared to pathology data. RESULTS: Precise criteria of intestinal metaplasia in CLE was presence of oval gray goblet cells in epithelium. Gastric adenoma with moderate dysplasia appeared on CLE images as glandular structures in mucosa surface layers. The signs of high-grade dysplastic changes in adenoma were appearing of different shape and size cells with lost polarity. Well-differentiated carcinoma featured destruction of some glands and forming dark cell clusters. Revealed criteria of poor-differentiated carcinoma was total disintegration of glandular structures. Overall accuracy of CLE in early gastric cancer and precancerous conditions diagnostics reached 95,6% (P < 0.001). Selected accuracy in different condition was: 100% in intestinal metaplasia identifying, 86.1%--in adenoma with moderate dysplasia, 96.2% in high-grade dysplasia and cancer in situ, and 100%--in poor-differentiated gastric carcinoma types). CONCLUSION: As the result of our study we have developed precise endomicroscopic criteria of intestinal metaplasia in stomach, gastric adenoma with moderate and high-grade dysplasia and early gastric cancer--as well-differentiated, as poor-differentiated.

[Endoscopic stenting of malignant stenosis in the cervical esophagus].

OBJECTIVE: to define the optimal approach for self-expanding metal stents (SEMS) installing in the cervical esophagus in cases of malignant stenosis and to select the optimal types of stents for this tumor location. MATERIALS: From 2004 to 2013 in P.A. Herzen Moscow Cancer Research Institute in 24 patients with cervical esophagus tumor stenosis endoscopic stenting was performed. 70% of installed stents were Choo Cervical (M.I. Tech, Korea), 13%--unspecialized Choo and Hanaro stents (M.I. Tech, Korea), and 17%--Gianturco-Z stents (Wilson-Cook, Ireland). Main contraindication for cervical esophagus stenting was location of the tumor margin less than 1 cm from the upper esophageal sphincter. In 21% of cases, endoscopic stenting was performed under combined fluoro- and endoscopic guidance, in 79%-- using only endoscopic approach. RESULTS: Technical success of stent placement was achieved in all patients; SEMS was installed at the previously defined level. The accuracy of stenting was not depended from the type of guidance procedure. The most intensive pain was observed in cases with "not specialized" stents with diameter of 18, 20 or 22 mm. Average pain level in such patients was 4.54 points (VAS). In the subgroup with "cervical" stents average pain intensity was not exceed 3 points. Chronic pain syndrome lasts lifelong in 17% of patients. CONCLUSION: The procedure of SEMS positioning under endoscopic guidance with individual selection of stent type allows restoring oral nutrition in patients with severe tumor stenosis of the cervical esophagus.

[Adaptation to hypoxia and ischemic preconditioning: from basic research to clinical practice].

Experimental and clinical studies of the last ten years gave evidence of successful application of the protective effect of hypoxia in clinical practice. The view of hypoxia as an exclusively injurious factor has undergone significant changes. A promising approach to solving the problem of heart adaptation to ischemic injury is the use of cellular mechanisms realized through myocardial ischemic preconditioning (IP). Modern understanding of the mechanisms of IP protective effect takes into consideration the processes underlying the development of adaptation to hypoxia related to the changes in intracellular metabolism and accompanied by a stronger activation of the systems responsible for adaptation. All this provides a real opportunity for studying intracellular functional and metabolic mechanisms of adaptation to hypoxia and ischemia, formation of adaptive syndromes in clinical practice, development and implementation of new evidence-based medical technologies for diagnostics, prevention, and rehabilitative treatment of heart pathology.

[Cardioprotective capabilities of drug meldonium in secondary prevention after percutaneous coronary intervention in patients with documented myocardial ischemia].

The purpose of research ­ analysis of capabilities in cytoprotective drug mеldonium, in complex in the cardioprotective effect of secondary prevention after percutaneous coronary intervention (PCI). Patients with stable coronary heart disease (n=35 ) aged ≤65 years with incomplete revascularization at 6 months after PCI and positive exercise test (SFI) were randomized 1:1 to groups controlled physical training (CPT) with intensity 80% and a duration of 2 weeks (10 SFI): group 1 (n=17; 53,9±6,2 years) and group 2 (n=18; 56,1±4,8 years). Patients in Group 1, in addition to SFI mеldonium administered at a dose of 1000 mg/ml intravenously. In the 1st group on the background mеldonium adjunctive therapy showed a significant increase in the duration from 15±2 to 32±7 min for the 10th CPT (p<0.05). Index of maximum oxygen consumption after 10 intense CPT increased to 20.8±1.06 ml/kg/min compared to baseline (18.6±1.1 ml/kg/min, p<0.05) and the control group (18.5±1.5 ml/kg/min, p<0.05). Use of meldonium was also associated with decrease of maximum ST-segment depression (from -0.18±0.1 to 0.10±0.2 mV), increases of exercise duration (from 364±22 to 556±29 s) threshold heart rate (from 118±12 to 132±5 bpm), decrease of time of ST segment recovery to baseline (from 385±32 to 242±22 s, p<0.05). Final level of free fatty acids in the meldonium group was significantly lower than that in the control group (0.248±0.047 vs. 0.265±0.031 mg/dl). Inclusion of meldonium in complex treatment after PCI potentiates cardioprotective effect of intensive CPT as evidenced by the positive dynamics of ECG and biochemical markers of myocardial ischemia.

[Approaches potentiating cardioprotective effect of ambulatory physical training in patients with ischemic heart disease and multivessel coronary artery involvement after coronary stenting].

Cardiorehabilitation of patients with multivessel coronary lesions is an obligatory component of ambulatory stage of care. With the aim of potentiating cardioprotective and antiischemic impact of rehabilitative preventive measures in 36 patients with ischemic heart disease (IHD) and multivessel coronary artery involvement who had undergone percutaneous coronary intervention we studied cardioprotective and antiischemic effect of long-term (24 weeks) administration of 70 mg/day trimetazidine in combination with moderate intensity physical training with the use of distance surveillance by a physician. The chosen therapeutic approach in patients with residual ischemia after incomplete anatomical revascularization provided early persistent formation of cardioprotective and antiischemic effect proven by increase of tolerance to physical exercise, improvement of diastolic function, and positive dynamics of both ECG parameters and biochemical markers of myocardial ischemia.

[Clinico-economic aspects of physical rehabilitation of patients with coronary heart disease after endovascular interventions].

Physical rehabilitation is an important component of cardiorehabilitation and secondary prophylaxis programs for patients with coronary heart disease (CHD) especially after endovascular interventions. Of special importance among a variety of rehabilitative technologies under current conditions of financial crisis are those ensuring high-quality and cost-effective medical aid The clinico-economic analysis of the programs of long-term physical training is presented with reference to their application for rehabilitation of patients with CHD after endovascular intervention. The use of this approach on an individual basis is believed to promote the introduction of physical training methods into clinical practice, rational planning of secondary prophylaxis programs and reduction of financial burden on public health services.

[Possibilities of improvement of prognosis in patients with type 2 diabetes mellitus after coronary interventions].

We present results of investigation of fenofibrate in patients with ischemic heart disease and type 2 diabetes mellitus after myocardial revascularization at various terms of its administration. We have shown its efficacy in correction of diabetic dyslipidemia, positive influence on clinical status and long term result of coronary intervention. We have established that early (first 7 days) prescription of fenofibrate - Tricor to patients with ischemic heart disease and type 2 diabetes mellitus after myocardial revascularization lowers number of diagnostic coronary angiograms and repeat percutaneous coronary interventions by 11% during first year of follow-up.

[Rehabilitative and prophylactic measures including physical training for the correction of risk factors in patients presenting with ischemic heart disease following percutaneous coronary interventions].

The authors report the results of analysis of effectiveness of active rehabilitative and prophylactic measures undertaken at the outpatient treatment stage including long-term controlled physical training of moderate intensity in patients presenting with coronary heart disease following percutaneous coronary interventions. The emphasis was laid on the possibility to prevent traditional risk factors of cardiovascular diseases. It was shown that the proposed approach allows a few risk factors (dyslipidemia, hypodynamia, arterial hypertension, smoking, and obesity) to be simultaneously corrected.

[Novel approaches to assessment of rehabilitative-preventive quality measures in patients with ischemic heart disease].

Cardiorehabilitation and secondary prevention in patients with ischemic heart disease (IHD) are at present actively introduced in practical health care. However problems of standardization of methods of cardiorehabilitation and secondary prevention remain unsolved and criteria of efficacy of conducted measures in patients with IHD have not been elaborated. On the basis of analysis of clinical status, physical working capacity, blood pressure dynamics, lipid spectrum, smoking, body mass index, and quality of life of patients we have created a set of clinical indicators of efficacy of rehabilitative-preventive aid which will allow to present all components of efficacy at the level of conduction of clinically proven measures.