Surgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

SURGICAL TREATMENT RESULTS IN PATIENTS WITH PELVIC BONE TUMORS IN CASES OF PREOPERATIVE 3D MODELING USE. / REZUL'TATY KhIRURGIChNOGO LIKUVANNIa U KhVORYKh Z PUKhLYNAMY TAZOVOÏ KISTKY ZA VYKORYSTANNIa PEREDOPERATsIY̆NOGO 3D-MODELIuVANNIa.

The use of computer and magnetic-resonance therapy permits high accuracy visualization of tumor lesion zone in patients with pelvic bone tumors. More precise results concerning lesion zones before surgical intervention have been obtained in cases of 3D modeling use. OBJECTIVE: improvement of surgical treatment results due to determination of the optimal level for pelvic bone resection. MATERIALS AND METHODS: Cohort study was realized using 3D modeling based on computer tomography data applying the software packet RadiAnt DICOM Viewer with 3D Volume Rendering and the software packet «SolidWorks¼. Two patient groups were investigated: 1) 13 patients without preliminary preoperative 3D modeling (control group) and 2) 14 patients with modeling (main group). In both groups relapse-free survival and age-dependent survival were evaluated. RESULTS AND DISCUSSION: Tumor relapses were found in 6 patients (46.15 %) of control group and in 5 patients (33.33 %) of the main group. No statistically significant difference between groups concerning relapse-free survival results was detected. In both groups, medians of relapse-free survival were not obtained, two-year long relapse-free survival reaching (53.8 ± 13.8) % and (66.7 ± 12.2) % in control and main groups, respectively. Analyzing the cor- relation between patients age and results obtained the authors demonstrated the two-year relapse-free survival to reach (47.4 ± 11.5) % and (88.9 ± 10.5) % in patients aged above 40 and below 40, respectively (p = 0,06). CONCLUSION: Because of small sample sizes in both groups, the use of 3D modeling does not demonstrate any signif- icant difference regarding two-year relapse-free survival. However, there is a tendency for further progress. The search of approaches for improvement of the treatment results for pelvic bone tumor patients remains among the most important study problem in current orthopedics for tumor patients.

[Status of the antioxidant protective system of rat liver exposed to carbon tetrachloride]. / Sostoianie antiokislitel'noi zashchitnoi sistemy pecheni krys pri vozdeistvii chetyrekhkhloristogo ugleroda.

The dynamics of enzyme activity of antioxidative protective system of the liver and the content of restored glutathione have been studied in rats poisoned by CCl4 injection. During the first hours followed the injection against the background of maximum accumulation of dienic conjugates and decrease of the restored glutathione level no significant changes in the enzyme activity of the antioxidative protective liver system were observed. At the same time 48 hours later the superoxide dismutase and catalase activity decreased by 38% and 36%, respectively, with relative stability of glutathione-dependent enzymes and a two-fold increase of the restored glutathione level. It is shown that a fall of activity of the cytoplasmic antioxidative liver enzymes is not a result of the immediate inactivating effect of free-radical reactions initiated by CCl4, but is, evidently, caused by the covalent binding of its radical metabolites with corresponding macromolecules.

[The mechanism of the antioxidant action of D-penicillamine]. / Mekhanizm antioksidantnogo deistviia D-penitsillamina.

The mechanism of the antioxidative effect of D-penicillamine was studied under the conditions of NADPH- and CCl4-dependent lipid peroxidation in microsomes of rat liver and adrenalin autooxidation reaction. The antioxidative action of the drug was shown to be due to both its chelating properties and direct anti-radical influence. The chelating effect was more pronounced and depended on the concentration of ferric ions in the medium.

[The role of covalent binding and lipid peroxidation in liver damage by carbon tetrachloride]. / Rol' kovalentnogo sviazyvaniia i perekisnogo okisleniia lipidov v povrezhdenii pecheni chetyrekhkhloristym uglerodom.

4-[N-sodium-N-(5-ethyl-1,3,4-thiadiazol-2-yl)]- sulphanylamido-5-methoxy-1,2-benzoquinone selectively inhibiting lipid peroxidation (LPO) was used to study the hepatotoxic effect of carbon tetrachloride in vivo. It was found that inactivation of the liver microsomal oxidation system during the first few hours after CCl4 injection is due to covalent binding rather than LPO.

[Effect of o-benzoquinone derivatives on free radical processes, induced in rat liver microsomes by carbon tetrachloride]. / Vliianie proizvodnykh o-benzokhinona na svobodnoradikal'nye protsessy, initiiruemye v mikrosomakh pecheni krys chetyrekhkhloristym uglerodom.

The effect of o-benzoquinones on free radical reactions stimulated in rat liver microsomes was studied by using 14C-labeled CCl4. It was found that o-benzoquinones decrease the amount of 14C from CCl4 covalently bound to proteins and lipids. This effect may be due to both decontamination of free radical products of CCl4 metabolism and to inhibition of their synthesis by a shunt via the NADPH-dependent electron transport chain of microsomes. There is evidence that under conditions of ClC4 poisoning the protective effect of o-benzoquinones correlates with their ability to inhibit the covalent binding. It is concluded that covalent binding plays the key role in CCl4 hepatotoxicity.

[Use of a heptane-isopropanol system for extraction of primary lipid peroxidation products]. / Ispol'zovanie sistemy geptan-izopropanol dlia ékstraktsii pervichnykh produktov perekisnogo okisleniia lipidov.

Products of different lipids oxidation were studied for the peculiarities of their distribution in the extracting system heptane--isopropanol widely used in spectrophotometric determination of primary products of peroxide oxidation of lipids. It is shown that hydroperoxides of phospholipids and their reduction products almost completely transfer to the alcohol phase while hydroperoxides of triacetin and cholesterol esters are 70-85% extracted by heptane. Thus, it is necessary to analyze the alcohol phase when using the systems heptane-isopropanol to determine the content of primary products of lipid peroxide oxidation in those tissues, where phospholipids are the basic oxidation substrates.

[Antioxidative activity of antiarthritic preparations]. / Antiokislitel'naia aktivnost' protivoartritnykh preparatov.

Antioxidative activity of acetyl salicylic acid, indometacin, ibuprophen, orthophen, delagil, D-penicillamine and levamysol was studied under conditions of NADPH- and CCl4-dependent lipid peroxidation both in rat liver microsomes and in adrenaline autioxidation. All the drugs studied exhibited only slight antioxidative activity being dissolved in mater, and especially towards lipid peroxidation, as compared with quercitrol and ionol; their activity was noted at concentrations exceeding distinctly the therapeutic doses. At the same time, D-penicillamine inhibited lipid peroxidation not only by means of free radicals neutralization but also via binding of iron ions. This property of the drug may be responsible for its effects, to some extent, in treatment of joint inflammations.

[A simple and sensitive method of determination of superoxide dismutase activity based on the reaction of quercetin oxidation]. / Prostoi i chuvstvitel'nyi metod opredeleniia aktivnosti superoksid- dismutazy, osnovannyi na reaktsii okisleniia kvertsetina.

An indirect method for determination of superoxide dismutase (SOD) activity, based on inhibition of quercetin autooxidation, was developed. The optimal conditions of reaction ensuring high sensitivity of measurement (I50 = 1.5 ng/ml) were selected. NaN3, catalase and physiological concentrations of ascorbic acid did not interfere with the SOD estimation in blood and tissue homogenates.

[Antioxidative activity of flavonoids in various systems of lipid peroxidation]. / Antiokislitel'naia aktivnost' flavonoidov v razlichnykh sistemakh perekisnogo okisleniia lipidov.

The antioxidant action of flavonols in different systems of lipid peroxidation (LPO) was studied. Quercetin and rutin were found to inhibit NADPH and CCl4-dependent LPO in rat liver microsomes, however, in the case of CCl4-dependent LPO, rutin had a very poor antioxidant effect. Study of flavonols oxidation by products of the cytochrome c catalyzed destruction of linoleic acid hydroperoxide demonstrated that the differences in the antioxidant offects of quercetin and rutin can be due to their different capability to terminate free radical chain reactions. The antioxidant effect of rutin was shown to be largely due to the chelating properties of this compound.

[Photodynamic effect of chlorine e6 on erythrocyte membranes]. / Fotodinamicheskoe deistvie khlorina e6 na membrany éritrotsitov.

Photodestruction of erythrocyte membranes sensitized by water soluble chlorophyll derivative chlorine e6 (Chl e6) was studied. It has been determined that light irradiation of erythrocyte ghosts with wave length lambda-660 nm in the presence of Chl e6 caused in protein and lipid components of the membrane deep destructive changes which were expressed in cross-linking of the membrane polypeptides and accumulating in the membrane products of peroxidation of unsaturated fatty acids residues, in phospholipids mainly. It has been shown that these processes were realized only in the presence of molecular oxygen and consequently possess pure photodynamic character.

[Antioxidative effect of o-benzoquinone derivatives during CCl4-induced lipid peroxidation in the rat liver]. / Antiokislitel'noe deistvie proizvodnykh o-benzokhinona v usloviiakh CCl4-indutsiruemogo perekisnogo okisleniia lipidov v pecheni krys.

It was found that o-benzoquinones (oBQ) inhibit the CCl4-dependent lipid peroxidation (LPO) in rat liver microsomes in vitro. The experimental data suggest that the antioxidant effect of oBQ is not due to the ability of these substances to shunt the NADPH-dependent electron transport pathways. More likely, oBQ inhibit LPO due to the ability of their reduced forms to scavenge the free radicals which induce LPO. Based on the experimental data, it was concluded that the increasing absorption of liver lipids at 230-236 nm after administration of CCl4 is due to the accumulation of reduced hydroperoxides. This process was shown to be inhibited by oBQ.

[Determination of lipid peroxidation products using thiobarbituric acid in anaerobic states]. / Opredelenie produktov perekisnogo okisleniia lipidov s pomoshch'iu tiobarbiturovoi kisloty v anaérobnykh usloviiakh.

Products of lipid peroxidation were estimated in aerobic and anaerobic conditions using thiobarbituric acid (TBA) test. The main amount of malonic dialdehyde estimated in tissue homogenate in presence of oxygen was found to develop during the analytical procedure as a result of lipid peroxidation. At the same time, content of lipid peroxidation primary products did not correlate with amount of malonic dialdehyde in the sample studied. This suggests that TBA analysis may be carried out only under anaerobic conditions.

[Inhibition of microsomal oxidation by o-benzoquinone derivatives]. / Ingibirovanie mikrosomal'nogo okisleniia proizvodnymi o-benzokhinona.

It was found that o-benzoquinone derivatives inhibit the hydroxylation of aniline without any appreciable influence on the spectral changes which are due to cytochrome P-450 binding to the substrate. A comparative kinetic study of inhibition of aniline hydroxylation and NADPH-dependent reduction of o-benzoquinones in liver microsomes revealed that the inhibition is due to the ability of these compounds to shunt microsomal electron transport pathways.

[Stability of lipid oxidation products in the rat liver and pathways of their utilization]. / Ustoichivost' produktov okisleniia lipidov v pecheni krys i puti ikh utilizatsii.

The ability of liver homogenates to utilize various lipid peroxidation products was studied. Conjugated dienes and TBA-reactive products of unsaturated fatty acid phospholipids and triglycerides were found to be more stable that the corresponding lipid hydroperoxides. It was shown that decomposition of lipid hydroperoxides in liver homogenates is due to their reduction to corresponding oxycompounds without activation of free radical reactions. The ability of lipid hydroperoxides to be reduced in liver homogenates is determined by their chemical structure and decreases in the following order: polyunsaturated fatty acids--phospholipids--triglycerides--cholesterol esters.

[Effect of lipid peroxidation on the Mg-ATPase activity of the brain and liver]. / Vliianie perekisnogo okisleniia lipidov na aktivnost' Mg-ATFazy mozga i pecheni.

Effect of ascorbate-dependent lipid peroxidation on activity of Mg2+-ATPase was studied in rat brain and liver tissues. Lipid peroxidation was shown to inactivate Mg2+-ATPase in the fraction of "heavy" brain microsomes. The rate of inactivation was directly related to the amount of the primary products of lipid peroxidation, accumulating in membrane lipids. At the same time, more intensive lipid peroxidation, as evidenced by content of diene conjugates and malonic dialdehyde, did not affect the liver Mg2+-ATPase.