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Madiyorov Bakhtiyor Tashpulatovich, National Cancer Research Center, Ministry of Health of the Republic of Uzbekistan, Tashkent
E-mail: baxa_bum@mail.ru Krotov Nikolay Fedorovich, Federal State management "Institute of Oncology named N. N. Petrov",
the Ministry of Health of Russia E-mail: info@ronc.uz Rasulov Abdugaffar Elmanovich, National Cancer Research Center, Ministry of Health of the Republic of Uzbekistan, Tashkent
E-mail: info@ronc.uz
The comparative analysis of surgical treatment of mediastinal tumors in children oncology
Abstract: The analysis of the surgical treatment of the mediastinal tumors has been performed in 41 patients. In 23 cases there are carried out diagnostic and medical thoracoscopies, the standard approaches (thoracotomy, sternotomy) in 18 patients. The main parameters for comparison included duration of the operative intervention, staying of children in the department of rehabilitation of the hospital, duration of the use of anesthetic agents, terms of the pleural cavity drainage, bed-days after intervention, where there was revealed reliable improvement of results. Keywords: thoracoscopy, mediastinal tumors, oncopediatrics.
The surgical method remains to be extremely important in the structure of the current multimodal strategy for treatment of children with tumor pathology of the mediastinal organs. Actually the majority ofpatients with solid tumor cannot be treated without surgical stage [2, 199-203; 8; 14, 12-15; 15, 1243-1750].
The surgery in children oncology has changed significantly due to the progress in the chemo- and radiotherapy over the last years. The character of surgery changes owing to coming of all modern surgical technologies including endosurgery, microsurgery and organ transplantation to the oncopediatrics. The safety and adequacy of the oncological intervention depends to a large extent on the appropriate choice of the surgical approach. The critical moments at the choice of the approach seem to be such moments as tumor size, morphology and tumor response to the ambient structures [4, 562-576; 5; 6, 37-38; 8, 1725-1728; 12; 13-19; 14, 12-15].
The role of the current thoracoscopic techniques in mediastinal tumors and cysts is not a subject to doubt. The standard surgical approaches at removal of the tumors and cyst of the mediastinum preents by mediastinoskopy, thoracotomy, sternotomy. All the open (standard) approaches are characterized by great traumaticity of the operation, heavy postoperative development and prolonged restoration period. At the present stage of development of medicine the children's surgery is difficult for presenting without endoscopic operations. The surgeons efforts to the reduction of traumaticity of operations resulted in wide use of minimally invasive interventions in the childlren's surgery. The main advantages of the thoracoscopic operations include reduction of the postoperative pain; absence of requirement in narcotic analgetics; shortening of bed-days, excellent cosmetic outcome; possibility of the repeated interventions in recurrence of disease, as well as after the open operations. The thoracoscopic operations at mediastinal tumors have a number of advantages in comparison with traditional operations and combine minimal traumaticity and radical necessity [1, 335-343; 3, 2893-2909; 7, 1086-1090; 9, 725-727; 10, 304-305; 15, 1243-1750].
At the large masses in the chest, in particular tumors of anterior and posterior mediastinum, top of the thoracic aperture, standard
surgical approaches — thoracotomy, sternotomy have not lost their importance [2, 199-203; 4, 562-576; 13, 252; 14, 12-15].
On the basis of experience of a combination of endosurgery and open surgery in the adults at the esophageal cancer, thymus gland tumors, pulmonary neoplasms, neurogenic tumors of the posterior mediastinum, there are data of the combined use of endosurgery and open surgery during one operation, at the "complex" localizations of the tumor, such as posterior mediastinum with involvement of the peritoneal space, zone of aperture of the chest involving to the neck and anterior mdiastinum with distribution into both hemitho-rax [5, 138-148; 12, 13-19].
On the basis of the literature data, analysis of the work performed, the purpose of our research was to study the results of surgical treatment of children with mediastinal tumors removal by thoracoscopic and standard access.
Material and methods
During the period from 2000 to 2014, there were treated 114 patients with mediastinal tumors. Of them the boys were 70 (61.41 %), girls — 44 (38.59 %). The age fluctuated from 1 year till 19 years, the average age was 8.89 ± 2.34 years. Terms of the admission to the hospital were from 1 months to 3 months — 9 patients, to 6 months — 12 patients, more than 6 months — in 13 patients.
From 114 patients 41 (35.9 %) underwent operative interventions. 23 (67.64 %) patient were performed thoracocopic operations: on the right — in 15 (65.3 %), at the left — 8 (34.7 %). In 7 (20.5 %) cases diagnostic thoracoscopy was ended by biopsy taken from the tumor. For comparative analysis there was formed control group of 18 children with mediastinal tumors, operated by open method: tumor removal by thoracotomy access in 12 patients, by sternotomy— in 5 patients, neck approach in one case
Variants of the cysts location: in 5 cases — paratracheally, in one — parabronchially.
Distribution of the patients the histological structure was as follows: thymus gland tumors in 8 cases (3 malignant thymoma, 5 benign thymoma), lymphoma — 4, intrathoracic goiter — 1 case, mesenchyma — 5, (fibrolypoma, desmoid by type offibromatosis),
mature teratoma — 7, bronchial cysts — 7, benign neurogenic-tumors, tubervulous lymphadenitis in 2 children. Thoracoscopic operations were performed in patients with bronchogenic cysts, one extragonadal germinogenic tumor of mediastinum (mature teratoma) in 3, nevrinoma of the posterior mediastinum in 4, and fobrolipoma in 2 patients.
At extended and extended - combined interventions there were additionally used resected following structures: decortication and pleurectomy in one case, rib resected with spinal islands in two cases, and in one cases during involvement of the malignant thymoma into the lung the pulmonectoniain the lung was performed.
Multispiral computed tomography (MSCT) and magneto-resonance tomography (MRT) have the most informativity in the diagnosis of the mediastinal tumors. For more precise visualization, differentiation of the tissues and anatomic interrelations with the thoracic organs and blood vessels in 19 (56.8 %) patients were performed investigation with contrast intensification of the mediastinal vessels. The investigation also included ultrasound examination with duplex scanning of the mediastinal organs, functional methods of investigations, clinical blood analysis, biochemical blood analysis. Fibroezophagogastroduadenos-copy (FEGDS) was carried out in 3 (8.9 %) children with features of dysphagia; bronchoscopy—in 14 (41.2 %). In 22 (54.5 %) of children were studied the level of tumor markers, such as neurospecific enolase, alpha-fetoprotein, ferritin. At suggestion ofthe extragonadal germino-geic tumor of the mediastinum there was included ultrasound investigation of the testicles, as well as measurement of the level of serum markers — a-fetoprotein (AFP), ^-chorionic gonadotropin (^CG) and lactatdehydrogenase (LD G). The increase of the levels ofmarkers was not noted in the operated patients.
The quantitative variables were described by the following statistical data: by number of the patients, average arithmetic meaning, standard deviation from average arithmetic meaning, the 25 4 and 75 th percentiles, median. The qualitative variables were presented by absolute (numbers) and relative frequencies (percents). The distinctions were considered statistically significant at a level of mistake p < 0.05. The calculations were performed on the personal computer with use of the application Microsoft Excel and package ofthe statistical analysis of the data Statistica 5.1 for Windows ("Stat Inc.", USA).
We present an example of thoracoscopic removal of the bronchogenic cyst of the superior mediastinum: The patient of13 years of age. At preventive examination at the place of residence there was diagnosed tumor of the anterior-superior mediastinum on the right side. By the data of radiodiagnosis in the paratracheal area on the right, at a level VTh1-VTh3 there was noted mass of sizes 4.2 x 3.0 x 5.0 cm. with contours well defined. The neoplasms is parietal to the lateral trachea wall and thoracic vertebra bodies. The signs of invasion into the mediastinal vessels were not revealed. The bronchoscopy showed constriction of the lower third of tracheal wall on the right side of the trachea wall mucosa, the picture of catarrhal endopronchitis. There was performed thoracoscopic removal of the cystic tumor of the anterior-superior mediastinum. Histological conclusion: bronchogenic cyst.
The technique of the thoracoscopic operations:
The patients was in lateral position. Into the pleural cavity there were administered 3-4 trochars. After introduction of the 1-st trochar the insufflation of CO2 began into the pleural cavity under pressure 6-8 mm. Hg. Then there were entered the rest 2 trochars of diameter 5 mm. for endoscopic instruments.
The arrangement of the trochars:
- In VII intercostal in the middle auxillary line for telescope introduction;
In V or VI intercostals in the anterior auxillary line for instruments;
- In VI intercostals in the posterior auxillary line for instruments and aspirator.
If necessary the 4 th trochar is located in the VII intercostals in the posterior auxillary line. At the first stage of the thoracoscopic removal there was made revision of the pleural cavity and lung. There was studied diaphragm, anterior and posterior surfaces of the lung and presence of adhesions, cysts or bulla. At presence of adhesions in the pleural cavity the division of the adhesions was performed with use of monopolar coagulation and scissors that provided careful examination of the lung surface for specification of the localization, character and size of mass. Before opening of the cyst membrane the hydropreparation was performed with the consequence coagulation of its surface. Then the cyst was open with monopolar coagulator. The contents of cyst was evacuated with help of electroaspirator and the cyst membranes were dissected. After evacuation of the cyst contents its membranes stuck together that created additional free volume of the pleural cavity. Then there was performed dissection of the membranes of the cysts with use of bi- and monopolar coagulation. Postoperative period was without events. The patient was discharged on the 6 th day after operation. The time of operation was 90 min. Blood loss — 50 ml. The term of observation was 24 months — remission.
There is presented the sample of the removal of mesenchial tumor of the lower mediastinum.
The patient of the age 15 years She addressed with the complaints on a pain and presence of swelling on the posterior surface of the right half of the chest. The pains in the chest disturbed within one year. 2 months prior to admission to the stationary the roentgenological examination showed tumor of the middle mediastinum. At the MSCT there was revealed structural mass in the right hemiothorax and paravertebral area with well-defined contours of sized 135 x 134 x 167 mm., density +28+35 un. H. This neoplasm, evidently, located outside from the parietal abdominal leaf, moves diaphragm and liver forward, invades into the soft tissues of the back, XI and XII ribs and VTh11, VTh12 on the right. At MRI: the large mass of the paravertebral area on the right invades into the lumen of the cerebrospinal canal — its lumen of the right side is considerably narrowed. The neoplasm borders on a spinal cord, which is shifted to the left — its contours is differentiated, however on some scans they are some poorly defined. In the preoperative period under the control of USG there was performed tranthoracic sliced biopsy. Histology: desmoid tumor. Together with meuro-surgeons there was performed operation of lateroposterior thoracotomy. The removal of the desmoid tumor of the posterior lower mediasnum on the right with resection of IX, X and XI ribs and spinal processes VTh 11, VTh 12, without opening of dural suc. At revision the signs of invasion into the cerebrospinal canal were not revealed. Postoperative period proceeded smoothly. The patient was discharged on 16 day after operation. The time of operation accounted for 220 mines. Blood los was 550 ml. In the postoperative period there was received the course of the chemo-radio-therapy. The time of observation was 6 years — remission.
Results and discussion
In a course of all performed thoracoscopic interventions there were no dangerous complications. At standard interventions the complications were not registered too. The conversion have been performed in 1 (2.9 %) child at the initial stages of development of a technique in our clinic. The adhesive process in the pleural cavity has become a reason of conversion in one case.
The basic parameters of comparison were: duration of opera- of the pleural cavities, bed-days after interventions. The parameters tive intervention, duration of stay of children in the department of of comparison between two groups of the patients are summareanimation, duration of analgetics application, terms of drainage rized in table 1.
Table 1. - Parameters of comparison between open and thoracoscopic operations
Indicator Thoracoscopic surgeries (n = 23) Standard operations (n = 18) P
n M ± 8 n M ± 8
Operation period, min. 23 80 ± 20 18 110 ± 25 < 0.05
Duration of reanimation, days 16 1.1 ± 0.6 18 1.9 ± 0.9 < 0.05
Duration of anaesthetization, days 23 2 ± 0.6 18 4 ± 1.6 < 0.05
Duration of drainage of the pleural cavity, days 23 2.5 ± 0.8 18 4 ± 1.4 < 0.05
Duration of postoperative hospitalization, days 23 18 ± 2.2 18 28 ± 8.5 < 0.05
Analyzing the received results it has been established, that the duration of operations in the main group was from 30 up to 90 mines (on the average 80 ± 20 mines), in control — from 80 up to 240 mines (on the average 110 ± 25). Thus, the average duration of operations in the main group was reliably lower, than in control (p < 0.05). First of all it is explained by reduction of time of access to an operational field, decrease of time spent on he-mostasis, absence of necessity in closure of thoracotomy wound. At standard thoracotomy, sternotomy the operational access required from 20 up to 40 mines, at thoracoscopy — 3-5 mines. In connection with development of the postoperative period without events in the main group only 50 % of children were in the department of reanimation and intensive therapy, whereas in control group all patients after thoracotomy were transferred in the department of reanimation, that was related to the necessity of realization of the prolonged artificial lung ventilation. At the analysis of the received results there was established reliable reduction of duration of the patients staying in the department of reanimation after thoracoscopic operations in comparison with a similar parameter at standard: 1.1 ± 0.6 and 1.9 ± 0.9 days, respectively (p < 0.05).
In the patients, operated by an open way, the application of narcotic and not narcotic analgetic preparations has appeared to be longer. In the main group its duration accounted for 2 ± 0.6 days, in control — 4 ± 1.6days. The average duration of the period of analgetics application in the main group was significantly lower, than in control (p < 0.05). In group with thoracoscopy, beginning from the first day the pains had moderate and weak character, stopping by application of not narcotic analgetics, and after removal of drainage tubes they were very weak or were absent. At the patients in
control group the pain syndrome had fluctuated character and in the first 3 days was defined, mainly by severe and very severe pains requiering prescription of the narcotic analgetics.
Duration of the pleural cavity drainage in the main group was from 1 to 3 days (on the average 2.5 ± 0.8 days), and in the control group — from 2 to 6 days (on the average 4 ± 1.4 days). Thus, the period of drainage of the pleural cavity was, reliably, lower in the group of endoscopy (p < 0.05). The period of the postoperative staying of the patients in the hospital in the group of thoracoscopy accounted for from 3 to 27 days (on the average 18 ± 2.2 days), in the group of open operations — from 5 to 42 days (on the average 28 ± 8.5 days), the difference was statistically reliable (p < 0.05). Term of supervision of the patients, operated with use of thoracoscopy, was from 2 months till 8 years. Term of supervision after standard approaches was from one year till 9 years.
The results were estimated on the basis of general clinical methods of examination, roentgenological investigation, CT. The good functional and excellent cosmetic results have been achieved in all the patients.
Conclusions
The thoracoscopic operations at the modern stage seem to be complex methods of the surgical treatment requiring the special training combined with learning from the endosurgical technique as well as mastering of skills of the traditional oncosurgery. On the basis of small experience in surgical treatment of tumors and tumor-like mediastinal masses it is possible to conclude, that thoracoscopic interventions differ by radical necessity in a combination with minimal traumaticity that allowed shortening of the patients staying in the hospital, lowering of the economic expenses for treatment.
References:
1. Altay C., Erdogan N., Karasu S. et al. CT and MRI findings of developmental abnormalities and ectopia varieties of the thyroid gland// Diagn. Interv. Radiol. - 2012. - Vol. 18, no 4. - P. 335-343. - doi: 10.4261/1305-3825.DIR.4913-11.2. Epub 2012, Feb 13.
2. Davidescu M., Mota§ N., Bluoss C. et al. Neurogenic tumors of the posterior mediastinum//Chirurgia (Bucur). - 2011. - Vol. 106, no 2. - P. 199-203.
3. Duwe B. V., Sterman D. H., Musani A. I. Tumors of the mediastinum//Chest. - 2005. - Vol. 128, no 4. - P. 2893-2909.
4. Ettinger D. S., Riely G. J., Akerley W. et al. Thymomas and thymic carcinomas: Clinical practice guidelines in oncology//J. Natl. Compr. Canc. Netw. - 2013. - Vol. 11, no 5. - P. 562-576.
5. Gonzalez M., Ris H. B., Krueger T.,Jayet P. Y. Management of anterior mediastinal masses in adults//Rev. Mal. Respir. - 2012. - Vol. 29, no 2. - P. 138-148. - doi: 10.1016/j.rmr.2011.11.015. Epub 2012 Jan 11.
6. Grishin H., Butenko F., Vashakmadze L., Lukin V. Minimally invasive surgery in the treatment of malignancies. Modern trends// Endoscopic surgery. - 2005. - Vol. 1. - P. 37-38.
7. Hoerbelt R., Keunecke L., Grimm H. et al. The value of a noninvasive diagnostic approach to mediastinal masses//Ann. Thorac. Surg. - 2003. - Vol. 75, no 4. - P. 1086-1090.
8. Lacreuse I., Valla J., de Lagausie P. Thoracoscopic resection of neurogenic tumors in children// J. Pediatr. Surg. - 2007. - Vol. 42, no. 10. - P. 1725-1728.
9. Lisowska A., Knapp M., Sobkowicz B. et al. Pathological mass in media mediastinum - diagnostic difficulties//Kardiol. Pol. - 2011. -Vol. 69, no 7. - P. 725-727.
10. Michels G., Drebber U., Pfister R. Thymoma - an important differential diagnosis of mediastinal tumours//Acta Clin. Belg. - 2012. -Vol. 67, no 4. - P. 304-305.
11. Pishchik V. G., Yablonsky P. K. Algorithms of differential diagnosis in mediastinal neoplasms//Vestnik Sankt-Pb. univ. - 2008. - Vol. 11, no 2. - P. 111-118.
12. Polyakov V. G., Ryabov A. B., Kim E. F., Lebedev V. I. Surgical Methodology for Tumors of Thoraco-abdominal Localization in Children//State of the Art and the Experience of the Clinic. Onkopediatriya. - 2014. - Vol. 1. - P. 13-19.
13. Razumovskiy A., Mitupov Z. Endosurgical operations in thoracic surgery in children. - Moscow: Geotar-Media, 2010. - P. 252.
14. Ryabov A. B., Volobuev A. V., Kazantsev A. P., Kerimov A. P., Rubansky M. A., Rybakov D. V., Polyakov V. G. Combined use of open and videohirurgii in onkopediatrics//Surgical Practice. - 2011. - Vol. 1. - P. 12-15.
15. Sundararajan L., Parikh D. Evolving experience with video-assisted thoracic surgery in congenital cystic lung lesions in a British pediatric center//J. Pediatr. Surg. - 2007. - Vol. 42, no 7. - P. 1243-1750.
Mamatkulov Ibrokhim Homidovish, Research Institute of Epidemiology, Microbiology and Infectious Diseases, doctor of medical sciences, professor
E-mail: bibinor@list.ru Kosimov Odiljon Shodiyevish, Research Institute of Epidemiology, Microbiology and Infectious Diseases, candidate of Medical Science E-mail: Saodat.us@mail.ru Ignatov Peter Evgenyevich, President Company of «IGN», E-mail: ignatovpeter@gmail.com Fedorov Andrey Ivanovich, Director Company of «<NICI», E-mail: nici@mail.ru
Protective and preventive efficiency of «Imnamak» in brucellosis
Abstract: Preclinical study of safety of application of domestic immunostimulating forage preparation "Imnamak" was carried out. Its immunologic, protective and preventive activity for neutralization of the first stage of epidemiological process was investigated. "Clearance test" with experimental anmials infected with brucellosis demonstrated protective efficiency of the preparation. Epidemiologic efficiency of «Imnamak» for neutralization of the source of the infection, i. e. "sanitation" of hyperendemic foci of brucellosis induced by Brucella melitensis was proved.
Keywords: brucellosis, "Imnamak", immunostimulation, protection, prevention.
Prevention of brucellosis includes a set ofveterinary-sanitation, economical and medical-sanitation measures, the ultimate aim is the elimination of infection among animals and termination of diseases among the population. Taking into consideration that brucellosis is zoonotic infection, on the basis for epidemic safety are prevention measures of infections among animals and hotbeds elimination of epizootic diseases when they occur [2; 8].
Our study investigated the protective efficacy of the drug "Imnamak", which is a balanced blend of natural active biological substances (immunofor, fodder salt and etc.), the effect of which is aimed at activation immune system of farm animals organism.
The drug "Imnamak" is used for small cattle (SC) in order to prevent brucellosis. It is recommended that one course per year in the parturition period. One dose of the drug "Imnamak" three grams a day (daily dose of the need for fodder salt small ruminants) within 30 days, two months before parturition company among the sheep. If brucellosis drug used for the first time since the pathogenesis features ofbrucellosis infection include immunological mechanisms that are targeted by the drug "Imnamak" [1; 3].
The aim of the study was to evaluate the protective activity of the drug "Imnamak" in the experiment and evaluation of its effectiveness in preventive hyperendemic hearth ofbrucellosis goat - sheep species.
Materials and methods
The experimental materials were white mice and guinea pigs, respectively 30 and 40 animals. We consider the comparative group of the control and experimental animals. In determination the effectiveness of the drug were used indicators "clearance-test", and white mice and experimental infection of guinea pigs.
To assess the effectiveness of preventive parturition during the campaign over two years was treated drug "Imnamak" 183 thousand heads SC in the "H". In the first year of treatment it was covered only public livestock, while in the second year — both public and agricultural livestock small cattle held by individual owners.
There was a retrospective epidemiological analysis and the analysis of own research results about epidemic situation of brucellosis for 1998-2002 years. Serological screening for brucellosis among the population was conducted by classical serological testing by Heddelson, Wright reactions and passive hemagglutination.
Statistical processing of the results was carried out on the computer IBM PC using the Excel program.
The results of research and its discussion. To study the protective activity of the drug "Imnamak" performed experimental infection of laboratory animals. In "clearance-test" as used experimental model of white mice treated by immunostimulant "Imnamak".
