2007, vol XV, # 3
2007, vol 15, # 3, page 295
V.I. Sipitiy, Y.O. Babalan, V.V. Vorobjov, I.I. Kalinovskay
Neuroradiodiagnosis of posttraumatic frontoorbital skull defects
Objective: To determine the efficacy of neuroradiodiagnosis techniques in posttraumatic frontoorbital skull defects.
Material and Methods: The study involved 32 cases of posttraumatic frontoorbital skull defects who were treated at neurosurgery department of Kharkiv Regional Clinical Hospital in 1997-2007. All 32 patients (100 %) were performed x-ray skull investigation, staged CT in bone and softtissue modes and in 12 (44.4 %) cases spiral (3D) computed tomography with three-dimensional reconstruction.
Results: Radiography of the skull bones and orbits did not aid in adequate visualization of defects in upper orbital wall going out the superciliary arch in 2 cases (14 %) of 14. The whole volume of the defect in the orbit roof larger than the superciliary arch could not be determined in 4 cases (28 %) of 14. The use of 2D staged CT of the brain and orbits allowed accurate diagnosis of the defects in the upper wall of the orbit in all 28 cases (87.5 %), when the defect was limited to the anterior 1/3 of the orbit roof. In large defects occupying more than 1/3 of the orbit roof, the area of the defect and its outlines were inaccurate in 2 of 4 cases (50 %). Spiral CT of the brain and orbits in all 12 cases (44.4 %) allowed accurate visualization of deformity of the parabasal areas of the skull, upper wall of the orbit with determining the full volume of the area of the defect in the orbit roof.
Conclusion: Radiological investigation of the skull is the first step in diagnosis of frontoorbital defects of skull bones allowing significant diagnosis of the area and shape of the bone defect of the frontal squama and the superciliary arch. The use of staged 2D computed tomography expands the capabilities of visualization of bone changes in the frontoorbital area not going out of the limits of the 1/3 of the orbit roof. High informativity and sensitivity of the method make spiral computed tomography the method of choice in investigation of the patients with large frontoorbital defects of the skull bones involving more than 1/3 of the orbit roof.
Key words: frontoorbital bone defects, informativity, craniography, computed tomography three-dimensional reconstruction.
2007, vol 15, # 3, page 300
Complex treatment of high-grade brain gliomas
Objective: To improve the efficacy of multimodality treatment of high grade brain gliomas using hyperfractionated radiotherapy against a background of chemotherapy with Temodal (Temozolomide) and radiomodifying with Xeloda (Capecitabine).
Material and Methods: The results of traditional and hyperfractionated radiotherapy of 295 patients with high-grade brain gliomas (glioblastoma - 169 patients, anaplastic astrocytoma - 126 patients) were analyzed. The traditional irradiation was delivered at a dose of 2 Gy up to summary dose of 60 Gy. At hyperfractionated irradiation was delivered at a dose of 1.5 Gy twice a day up to summary dose of 70.4-76.8 Gy. 76 patient were administered a radiomodifying medication Xeloda orally (1000 mg two times a day) and 14 patient were administered chemotherapy with Temodal (75 mg/m 2 during the whole course of radiotherapy).
Results: Administration of postoperative hyperfractionated radiotherapy with time-space optimization of the dose allowed to increase medium survival of the patients with glioblastomas up to 36.8±4.1 months and patients with anaplastic astrocytomas up to 40.1±5.4 months. Administration of radio-modifying medication Xeloda and chemotherapy with Temodal increased the survival by 6 and more months in similar groups of the patients.
Conclusion: Postoperative hyperfractionated radiotherapy with time-space dose optimization against a background of chemotherapy with Temodal (Temozolomide) and radiomodifi-cations by Xeloda (Capecitabine) increases two and more times medium survival of the patients with high grade brain gliomas.
Key words: high grade brain gliomas, multimodality treatment, traditional and hyperfractionated radiotherapy, Temodal (Temozolomide), Xeloda (Capecitabine). S. P. Grigoriev Institute of Medical Radiology
2007, vol 15, # 3, page 304
Chemoradiation therapy efficacy in patients with local cervical cancer
Objective: To analyze the efficacy of the original chronomodulation chemoradiation for local cervical cancer (CC) comparing it with the results of the standard treatment protocol and Hydrea administration as a radiomodifier.
Material and Methods: The study involved 176 patients with stage IIb-IIIa-b CC. All patients received combined therapy according to the radical protocol. Group 1 comprised 75 patients with CC who were administered chronomodulated chemoradiation with 5-fluorouracil according to the original protocol. Group 2 consisted of 52 patients who were treated using chemotherapy with Hydrea (1.5 g per day). Group 3 (49 patients) was treated using the traditional method of treatment. The treatment efficacy was assessed using immediate results.
Results: Relapse-free and general survival in group 2 did not differ from those ones in the controls (group 3) and differed from group 1 where 5-FU and non-traditional technique was used. Relapse-free 2-year survival in this group was higher by 35.1 and 28.0% when compared with the other groups. In stage III local CC the incidence of relapses in groups 1 and 2 (administration of radiomodifiers 5-FU and Hydrea) was 2.3 and 5.3 times lower than in group 3 (traditional treatment). The use of the original protocol reduced the number of long-term metastases 6.3 times when compared with Hydrea use and 4.5 times when compared with the traditional treatment.
Conclusion: The findings of the research suggest reasonability of the original protocol of non-traditional irradiation and the use of 5-FU in chronomodulated mode in patients with local CC, which promotes better immediate results, especially in IIIa-b stage on the account of increase of relapse-free and general survival and reduction of the number of relapses and long-term metastases.
Key words: cervical cancer, chemoradiation, radiomodifiers, 5-fluorouracil.
2007, vol 15, # 3, page 310
T.P. Yakimova, O.A. Mihanovskiy, O.V. Slobodynuk
Peculiarities of endometrium cancer pathomorphisms after pre-operative radiation therapy
Objective: To determine the role of surgery and radiotherapy in treatment of different clinical morphological variants of endometrial cancer at low total focal doses of radiation therapy.
Material and Methods: Clinical morphological peculiarities of the tumors from 20 patients with uterine body cancer (T1a-2N0M0) aged 55-76 were investigated.
Preoperative radiotherapy was delivered using РОКУС - М unit in traditional fractionation 2 Gy to the area of the small pelvis and regional metastases (total focal dose of 20 Gy). The uterus with the adnexa were removed surgically. From days 10-14 of the postoperative period RT was continued up to focal dose of 40-46 Gy. Morphology of the removed tissue was done using the original protocol to determine the tumor histology, degree of differentiation, depth of invasion as well as the degree of radiation damage.
Results: Main histological form of endometrial cancer was moderately differentiated adenocarcinoma (60.0%). Poorly differentiated glandular cancer was revealed in 15.0% of cases, highly differentiated in 5.0%. Radiation damage of the tumor was moderate, 1.58 ± 0.06 conventional units using 4-point system. The volume of the residual tumor was 39.5%, its irradiation damage was registered in 8 persons (40%). Dystrophic changes in the tumor cells were revealed in 95.0% of cases (19 persons). Low mitotic index (5.4 ± 0.3%o) and medium level of pathological mitoses were revealed against a background of inconsiderable radiation lesion, which suggests inhibition of proliferative properties of the tumor due to RT.
Conclusion: Gamma therapy to endometrial cancer at a dose of 20 Gy produces a weak radiation damage of the tumor, the regression is low both at tissue and cellular levels. Post-operative RT at a focal dose of 20 Gy inhibits proliferative properties of the tumor, which suggests about low mitotic index and high level of pathological mitoses.
Key words: uterine body cancer, preoperative radiation therapy, pathomorphism.
2007, vol 15, # 3, page 315
O.I. Solodannikova, N.P. Atamanuk, V.P. Levchenko, N.K. Rodionova, V.M. Shevel, S.S. Makeev, G.G. Sukach
Results of pre-clinical investigation of 99m Tc-pertechnetate produced in Ukraine
Objective: To perform experimental investigation of pharmacokinetics and pharmacodynamics of 99m Tc-pertechnetate produced in Ukraine with the purpose to determine the possibility to use it in clinical conditions.
Material and Methods: The experimental study of pharmacokinetics, acute toxicity as well as the influence on the peripheral blood count, pyrogenicity of 99m Tc-pertechnetate produced by RADIOFARM Ltd (Institute of Nuclear Research of Academy of Science of Ukraine) was performed on rats, mice and rabbits.
Results: 99m Tc-pertechnetate was excreted from the rat organism with an effective half-excretion period of 10.5 hours, which corresponded to radiation load on the organism (absorbed dose) of 0.035 cGy. The radiopharmaceutical distribution in the organism was uneven. Its maximum amount was observed in the thyroid gland and stomach. These organs may be considered to be critical. Minimum 99m Tc-pertechnetate amount was found in the brain. The radiopharmaceutical did not cause any considerable changes in the peripheral blood of the rats at intravenous administration of 5.7 MBq/kg. This dose did not cause acute toxicity. The experimental data suggests that 99m Tc-pertechnetate administration did not cause local irritation and did not possess any pyrogenic effect at this dose.
Conclusion: Our investigation of 99m Tc-pertechnetate produced by Institute of Nuclear Research of Academy of Science of Ukraine suggests that administration of 5.7 MBq/kg (400 MBq per a standard human body) does not affect the organism of experimental animals.
Key words: pharmacokinetics, pharmacodynamics, 99m Tc-pertechnetate.
2007, vol 15, # 3, page 326
L.I. Simonova, Y.V. Malukin, V.Z. Gertman, L.V. Bilogurova, Y.Y. Mikulinskiy, J.E. Vikman, O.I. Paskevich
Experimental assessment of the possibility to identify the bone marrow stem cells using modern biocompatible tracers
Objective: To work out new methods of labeling bone marrow stem cells (BMSC) using a diagnostic radionuclide Tc-99m as well as a new luminescent stain H-510/C2 and assess the possibility to identify the transplanted labeled BMSC in the organism of experimental animals.
Material and Methods: In vitro investigation was performed on rat BMSC. In vivo investigation was performed on white mongrel male rats weighing 180-200 g. The efficacy of binding the radionuclide tracer when using 3 RP of Tc-99m with various levels of activity (100, 200, 300 MBq/ml) was investigated in BMSC culture (2 mln cells in 1 ml). 0.5 ml of BMSC suspension labeled with 100 MBq of Tc-99m sodium pyrophosphate was injected to the tail vein of intact rats. Scans were obtained using gamma-camera 3, 5, 24 hours after the injection. To label BMSC with luminescent technique the dye solution was introduced to the cell culture (1mln/ml), 0.1 ml per 1 ml of the suspension. 0.5 ml of labeled BMSC suspension was injected after partial hepatectomy. 7 and 14 days after the procedure native histological specimens of the liver and bone marrow were made with cryotome. Identification of the labeled cells was done using luminescent microscopy with Olympus-IX-71.
Results: New methods of labeling BMSC with Tc-99m and new luminescent label (H-510/C2) were suggested. Intravenous administration to intact animals of BMSC with the radionuclide tracer demonstrated the possibility of their vital identification within 24 hours to reveal the initial direction of donor cell migration in early terms after he transplantation. Intravenous injection of BMSC with luminescent label to the rats after partial hepatotomy on the specimens of native liver and bone marrow showed the possibility of long-term monitoring of the dynamics and homing of donor cells in the conditions of inner organs regeneration.
Conclusion: Effective methods of BMSC labeling using Tc-99m and a new luminescent nano-label - H-510/C2 were worked out. Radionuclide BMSC labeling can be used in vital identification of donor stem cells in early terms after transplantation. Luminescent technique of BMSC labeling using a new stable dye can be used for long-term observation of the transplanted stem cell homing in the organism.
Key words: stem cells, bone marrow, rats, transplantation, Tc-99m pyrophosphate, hepatectomy, liver, luminescence.
2007, vol 15, # 3, page 332
L.I. Simonova, V.Z. Gertman, L.V. Bilogurova, A.M. Kurov
Experimental investigation of stem cell transplantation efficacy at various exposure doses
Objective: To study the efficacy of bone marrow stem cell transplantation to the rats exposed to various doses of x-rays.
Material and Methods: The study involved mature male Wistar rats weighing 180-200 g exposed to x-rays at a dose of 3.5, 5.0 и 6.5 Gy. 0.5 ml of bone marrow stem cell suspension (1.0 mln cells per 1 ml) was introduced to the tail vein 24 hours after the exposure. Survival, mean life span, the state of peripheral blood, for 30 days after the exposure were used as efficacy criteria.
Results: Bone marrow stem cell transplantation efficacy depended on the exposure dose. Only a tendency to survival increase was observed at a minimal lethal dose (3.5 Gy) (10 %, P > 0,05), but the amount of leucocyte in the peripheral blood increased considerably and the leucocyte count restored. At exposure to semilethal dose (5.0 Gy) bone marrow stem cell transplantation significantly increased survival of the exposed animals (by 20 % , P < 0.05) as well as considerably influenced hemopoiesis, controlled anemia and leucopenia, restored leucocyte count. The dose of 6.5 Gy and bone marrow stem cell transplantation showed the tendency to increased survival and some improvement of hemopoiesis.
Conclusion: Bone marrow stem cell transplantation increased survival of the experimental animals at all doses but the highest and significant increase of survival (by 20%) was observed at exposure to semilethal dose (5.0 Gy). Bone marrow stem cell transplantation also considerably improved hemopoiesis in the exposed animals, controlled anemia and leucopenia and restored leucocyte count. The most pronounced effects were noted at a dose of 5.0 Gy. The obtained findings of positive influence of bone marrow stem cell transplantation prove the possibility to use this method in radiation-induces myelosuppressions.
Key words: stem cells, bone marrow, rats, transplantation, x-rays, survival, hemopoiesis.
2007, vol 15, # 3, page 339
N.A. Mitriaeva, N.O. Babenko, T.S. Bakay, V.P. Starenkiy, N.E. Uzlenkova, S.M. Pushkar
Influence of ionizing radiation and etoposide on ceramide pathway of apoptosis activation in Guerin's carcinoma
Objective: To study the influence of x-rays, etoposide and their simultaneous action on the metabolism of ceramide in Guerin's carcinoma.
Material and Methods The experimental model consisted of rats weighing 160-180 g with subcutaneously inoculated Guerin's carcinoma. Local x-ray irradiation was delivered in fractions (5 Gy per fraction) with 24-hour intervals up to total dose of 10 Gy using RUM-17 unit. Etoposide was administered intraperitoneally at a dose of 5 mg/kg 24 hours before the exposure. Tissue homogenate was used for lipid extraction according to Folch. Ceramide, sphingosine, glucosyl-ceramide and sphingomyelin were separated with chromatography in a thin layer of silicagel Sorbfil ( Russia ). Ceramide, sphingosine, glucosyl-ceramide and sphingomyelin standards were used to identify the lipids (Sigma). Protein was isolated according to Lowry. [ 14 C]-palmitate as radioactive precursor of lipid synthesis was used (2.07 GBq/mmol; Amersham, YE Healthcare , UK ). Radioactivity of the samples was measured using P-counter. The statistical analysis was done using Student's t-test.
Results: It was established that etoposide increased de novo sphingolipid synthesis which contributed to accumulation of ceramide (tumor cell apoptosis inducer). Increase of ceramide level in tumor cells led to synthesis of other sphingolipids: glucosyl-ceramide and sphingomyelin, which may be precursors of lipids taking part in cell proliferation. Simultaneous action of etoposide and radiation on tumor of experimental rats led to accumulation of sphingosine (product of ceramide degradation), which produced apoptosis and pressed down synthesis of glucosyl-ceramide (proliferative lipid).
Conclusions: The results of investigation showed that etoposide is a powerful inducer of sphingolipid metabolism in Guerin's carcinoma. Simultaneous action of etoposide and radiation increases sphingosine amount (proliferative sphingolipid).
Key words: Guerin's carcinoma, ceramide, sphingomyelin, sphingosine, glucosyl-ceramide, etoposide, x-ray exposure.
2007, vol 15, # 3, page 344
O.P. Lukashova, O.A. Mihanovskiy
Morphofunctional state of Guerin's carcinoma after fractionated x-ray irradiation and simultaneous action of cryo- and radiation factors
Objective: To study the pathomorphism of Guerin's carcinoma cell at exposure to ionizing radiation and to use irradiation with preliminary cryodestruction of the tumor to reveal the most effective variants of cryoradiation therapy.
Material and Methods: The investigation involved white Wistar rats with inoculated Guerin's carcinoma. Local fractionated irradiation of the tumor at a dose of 5, 10, 15, 20, 25, 30, 35 and 40 Gy was performed using RUM-17 unit under standard conditions. Cryodestruction was performed using cryogenic unit AKG-01 at -70°C for 10 min. The material for investigation of the tumor was prepared using standard techniques for electron microscopy. The number of mitoses and cells with granules was calculated using a light microscope. Statistical assessment was done using Statistica v. 6.0 for IBM.
Results: Regularities of radiation effect on structural functional state of Guerin's carcinoma, their mitotic activity as well as the influence of partial tumor cryodestruction before the exposure were established.
Conclusion: Guerin's carcinoma is a rather radioresistant tumor. The tumor irradiation results in considerable differentiation of Guerin's cells with prevalence of highly specific forms at high summary doses. Mitotic activity of the tumor is stimulated by lower dose f radiation and inhibited by higher ones. The appearance of undifferentiated forms with accompanying growth of mitotic activity at a dose of 40 Gy can suggest appearance of a clone of radioresistant cells. Partial cryodestruction 24 hours before the irradiation does not change the tendencies of the tumor cells to differentiation under the influence of radiation exposure but considerably reduces the tumor proliferation. Cryodestruction 48 hours before the irradiation does not prevent radiation-induced differentiation of the cells in Guerin's carcinoma but increases the processes of division in the tumor and appearance of undifferentiated radioresistant cells, which are unfavorable signs. For cryodestruction of cancer it is reasonable to observe 24-hour interval between cryo- and radiation therapy.
Key words: Guerin's carcinoma, irradiation, cryodestruction, ultrastructure.
2007, vol 15, # 3, page 352
O.P. Lukashova, N.A. Mitriaeva, S.M. Pushkar
Ultrastructure of Guerin ' s carcinoma cells after chemotherapy and local tumor irradiation
Objective: To study ultrastructural pathomorphism of Guerin's carcinoma cells after administration of cisplatin and Taxotere at local fractionated irradiation of the tumor.
Material and Methods: Standard electron microscopy was used to investigate Guerin's carcinoma cell ultrastructure after single administration of cisplatin (CP) at a dose of 6 ug/kg and Taxotere (TT) at a dose of 8 ug/kg followed by local fractionated standard x-ray irradiation at a total dose of 10 Gy.
Results: It was established that administration of CP resulted in pronounced disorders in Guerin's carcinoma cell ultra-structure and did not influence the number of mitoses in the tumor. Main effect of TT was significant reduction of mitotic activity in the tumor against a background of inconsiderable changes in the cell ultrastructure. Administration of CP followed by irradiation changed little in the structural functional state of Guerin's carcinoma cells while Taxotere administration prior to irradiation caused necroses of the tumor tissue and significant reduction of the number of mitoses in the survived cells.
Conclusion: Cisplatin causes pronounced ultrastructure pathomorphism in Guerin's carcinoma cells not influencing the processes of division in the tumor. TT inhibits cell division in the tumor tissue without visible changes in the cell ultra-structure. CP does not possess radiosensitizing properties as to Guerin's carcinoma. TT is an active radiosensitizer considerably potentiating the effect of irradiation on Guerin's carcinoma. Various radiomodifying effects of CP and TT can be associated with their influence on division processes.
Key words: ultrastructure, Guerin's carcinoma, irradiation, cisplatin, Taxotere.
We are proud to announce the annual scientific conference of young scientists with the international participation, dedicated to the Day of Science in Ukraine. The conference will be held on 20th of May, 2016 and hosted by L.T. Malaya National Therapy Institute, NAMS of Ukraine together with Grigoriev Institute for medical Radiology, NAMS of Ukraine. The leading topic of conference is prophylaxis of the non-infectious disease in different branched of medicine.
Since 1993 the Institute became the founder and publisher of "Ukrainian Journal of Radiology”: