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Objective: To evaluate postoperative outcomes in patients with chest wall metastases., Material and Methods: We analyzed 40 patients who underwent surgery for chest wall metastatic lesions. Fourteen (35%) patients had sternal lesion, 26 (65%) ones - rib metastases. We used implants for chest wall defect closure in 15 (37.5%) patients. Chest wall repair with autologous tissues was performed in 19 (47.5%) patients., Results: Median survival was 17 months. Most patients ( n =30, 75%) showed improvement in the quality of life according to Karnofsky and EGOG scale after surgery. Continued tumor growth occurred in 4 (10%) patients within 8-16 months after surgery. There were 2 patients who suffered from tumor recurrence accompanied by other metastatic foci (progression). Complications were diagnosed in 5 (12.5%) patients. Tactical errors were identified in 4 (10%) patients and they were associated with progression of cancer in the form of new metastatic foci within 6 months after surgery., Conclusion: Active surgical approach for bone metastases in patients with favorable cancer-related prognosis can improve quality of life and survival at least in case of solitary lesions. New program for treatment strategy selection based on prognosis of life expectancy and algorithms of surgical treatment will reduce the risk of erroneous management and increase its effectiveness.

Results of ELISA investigation of the pretreatment sPD-1 and sPD-L1 content in blood serum of 133 bone neoplasms patients aged 6-70 years and 57 practically healthy control persons aged 12-70 years are described. In 14 patients the neoplasms were of a benign character, in 16 - borderline giant-cell bone tumor was diagnosed, and in 103 - malignant bone lesions including 39 osteosarcomas and 42 chondrosarcomas were revealed. The sPD-1 receptor concentrations in blood serum did not differ between control healthy persons and primary bone tumor patients, while serum sPD-L1 level in bone tumor patients was statistically significantly increased (p<0.0000001). By means of ROC curve construction a cut-off sPD-L1 level of 16.5 pg/ml was found that imposed 75,9% sensitivity and 75,4% specificity in relation to healthy control. However, the frequency of sPD-L1 levels exceeding 16.5 pg/ml was approximately similar in benign, borderline and malignant bone tumor patients. Analysis of the pattern of sPD-1 and sPD-L1 circulation in the peripheral blood of patients with the most prevalent malignant bone tumors - osteosarcoma and chondrosarcoma - demonstrated that in both sarcoma types sPD-L1 level was significantly higher than in control, but in patients with chondrogenic tumors the soluble ligand sPD-L1 dominates in the circulation, while in those with osteogenic tumors - sPD-1 receptor prevails. In particular, sPD-1 level is statistically significantly higher in patients with typical osteosarcoma than in those with typical chondrosarcoma (p=0.002437), and sPD-L1/sPD-1 concentration ratio in chondrosarcoma is highly significantly more than 2-fold higher than in osteosarcoma (0.81 and 0.35 respectively; p=0.000284). The sensitivity of sPD-L1 ≥16.5 pg/ml test in typical osteosarcoma patients' group comprised only 70.2%, and in those with typical chondrosarcoma - 84.6%. Serum sPD-1 and sPD-L1 concentrations in osteosarcoma and chondrosarcoma patients were not associated with the indices of tumor advancement, its histological grade, localization in the osseous system, and type of affected bone. Thus, it can be concluded that the ratio between circulating soluble forms of the receptor and the ligand of PD-1/PD-L signaling pathway differs between patients with chondrogenic and those with osteogenic tumors, sPD-L1 being diagnostically valuable mostly for chondrogenic bone neoplasms., Competing Interests: The authors declare no conflict of interest.

The levels of sPD-1 and sPD-L1 were analyzed in blood serum of 132 patients (age 14-70 years) with primary bone tumors: osteosarcoma (N=39), chondrosarcoma (N=42), Ewing sarcoma (N=9), chordoma (N=12), giant-cell bone tumor (GCBT) (N=16), benign neoplasms (N=14) and in and practically healthy subjects (age 19-58 years; N=27). sPD-L1 levels in all studied bone neoplasms were significantly higher than in the control. Serum sPD-1 level in GCBT patients was significantly higher than in the control, benign neoplasms, chondrosarcoma, and chordoma patients, but did not differ from osteosarcoma group. sPD-1 concentration in Ewing sarcoma was significantly higher than in chordoma and chondrosarcoma, but did not differ from the control. sPD-1 level in chondrosarcoma patients was also lower than in osteosarcoma, Ewing sarcoma, and in the control. Both sPD-1 and sPD-L1 concentrations were not significantly associated with the type of affected bone, process localization, disease stage, tumor histological grade, patients' age and sex. These results suggest the possibility of using these biological markers for preliminary assessment of the character of the process in the bone.

Background: A giant congenital melanocytic nevus (GCMN) is found in 0.1% of live-born infants. If present, the lesion has a chance of about 6% to develop into malignant melanoma. Both children and adults can be affected by malignant melanoma arising in a giant congenital nevus. Up to 95% of GCMNs harbor NRAS mutations, and mutations in the BRAF, MC1R, TP53, and GNAQ genes have also been described. The individualization of therapy is required, but diagnostic and prognostic criteria remain controversial., Case Presentations: We report two cases: 1) melanoma arising in a giant congenital nevus during the first month of life complicated with neurocutaneous melanosis (NCM), and 2) melanoma arising in a giant congenital nevus during the first 6 months of life. Pathology, immunohistochemistry, and genetic analyses of tumor tissue were performed. The first case revealed only a non-pathogenic P72R polymorphism of the TP53 gene in the homozygote condition. For the second case, a Q61K mutation was detected in the NRAS gene., Conclusion: Malignant melanoma associated with GCMN is rare and therefore poorly understood. Outcomes have been linked to the stage at diagnosis, but no additional pathological prognostic factors have been identified. The most frequent genetic event in giant CMNs is NRAS mutations, which was discovered in one of our cases. To accumulate evidence to improve disease prognosis and outcomes, children with congenital melanocytic nevus should be included in a systemic follow-up study from birth.

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation., Objective: To analyze the literature and present a clinical case of a patient with Li-Fraumeni syndrome and multiple anaplastic oligodendrogliomas of the brain., Clinical Case: A 42-year-old male patient presented with complaints of headaches, word finding difficulty, memory loss, right hemianopsia, and generalized convulsive attacks. For 10 years, he underwent multiple interventions and chemotherapy courses for colon adenocarcinoma and recurrent B-cell lymphoma. MRI revealed multiple space-occupying lesions of the cerebraln hemispheres, which were located in the left temporo-occipital and right frontal regions., Results: The patient underwent resection of multiple space-occupying lesions of the left temporo-occipital and right frontal regions. The postoperative period proceeded without complications. The histological diagnosis was WHO grade III anaplastic oligodendroglioma. The patient and one of his sons were detected with a R248W missense mutation in the TP53 gene. The patient underwent six courses of temozolomide chemotherapy. At a follow-up examination 20 months after surgery and chemotherapy, the patient's condition was satisfactory; he returned to work. Control MRI of the brain revealed no signs of continued tumor growth., Conclusion: An analysis of the literature and the clinical case indicate the success of multiple surgical interventions and chemotherapy courses performed for a long time in the patient with Li-Fraumeni syndrome manifested by colon adenocarcinoma, recurrent B-cell lymphoma, and multiple anaplastic oligodendroglioma of the brain. The patient had a good quality of life and returned to professional activity.

Purpose: To investigate beneficial advantages of the ultrasonic method of bone cement removing in, compare with mechanical as well as to qualitatively improve the technology of bone cement removing in revision arthroplasty., Material and Methods: The study included 55 patients with benign, primary and metastatic malignant tumors. From March 2014 to January 2016 there were performed 56 revisions. In 36 cases revisions were made using ultrasound system <>. The quality of stem fixation was evaluated radiologically., Results: Mean follow-up after surgery was 11.5 months. One patient had second revision after mechanical extraction of bone cement due to aseptic loosening. In the group of patients after ultrasonic extraction of the cement mantle deterioration of the cement fixation was not revealed. The average time.of surgery using ultrasonical and mechanical technology of bone cement removal was 154.5 and 158.1 min. in replacement of one stem, 200 and 182 min. in replacement of two stems respectively. The average blood loss was 427 and 430 ml. in a time of one stem revision, 445 and 525 ml in a time of two stem revision after using ultrasound and mechanical technol- ogy respectively. In one stem revision with using ultrasound extractor was achieved the reduction in blood loss at 10% and in two stem revision at 16%. There were no any complications in using ultrasonic extractor., Conclusion: The use of ultrasonic technology in the re- vision arthroplasty can improve the quality of cement fixa- tion, reduce the amount of bleeding and severity of surgical treatment regardless of the surgery time, improve economic efficiency. Further enhancement of the ultrasonic method for cement mantle extraction has a potential to improve its effectiveness.

Among the wide array of human neoplasms, primary tumors of bone are relatively uncommon and sundry group of solid tumors traditionally categorized according to their presumed mesenchymal differentiation. A locally aggressive or malignant group of cartilaginous matrix-producing neoplasms with diverse morphological features and clinical behavior require additional ancillary studies for prompt diagnosis and appropriate surgical treatment. They are histologically, behaviorally and genetically diverse, their pathogenesis is poorly understood Moreover treatment options are limited with surgical resection continuing to provide the only possibility of cure in many cases. However, there has been tremendous progress in the last decade in understanding the molecular pathogenesis of sarcoma, which may ultimately lead to more effective therapy and prognostification for these rare malignancies (1. Atypical cartilaginous tumor/grade1chondrosarcomas behave as locally aggressive lesions, and only metastasize in exceptional cases. Only a small percentage of the IDH1mutations can be identified using the specific IDHIRI32H antibody Histologic grade is the most important predictor of local recurrence and metastasis in chondrosarcoma , commonly patents die from locally recurrent tumor ofpelvis or scull, that is difficult to manage surgically Association between ratio of matrix metalloproteinaise- 1 and tissue inhibitor ofmetalloproteinase- 1, expression of metalloproteinase-1, -2 and-9, Col-IV, Cox-2, Bcl-2, Bax in context with histological and clinical data could play a significant role in determining prognosis in patients with borderline cartilaginous tumors. The mandatory application of multidisciplinary care in management of atypical cartilaginous tumor/grade 1 chondrosarcomas with integration of histologic, molecular, radiographic and clinical data is difficult to overestimate.

Bone neoplasms - are a rare group of diseases, which ethiology and pathogenesis are not fully understood. We have studied 6 single nucleotide polymorphisms rs792/(GHI), rs7956547(IGFI), rs3761243(GNRH2), rs11737764(FGF2), rs6599400(FGFR3), and rs1690916(MDM2) associations with bone tumors. In our work we've detected significant associations with some single nucleotide polymorphisms: IGFl.rs7956547, GNRH2.rs3761243 and FGFR3.rs6599400 in patients with malignant and borderline bone tumors.

Association study of 6 candidate single-nucleotide polymorphisms (rs7921, rs7956547, rs3761243, rs11737764, rs6599400, rs1690916) was carried out in a group of patients with bone tumors of different histological structure (n=68) and control group of normal subjects (n=96). Significant associations of rs6599400 and rs1690916 polymorphisms with disease risk were detected (odds ratio 2.15 [1.06-4.24] and 0.39 [0.19-0.78], respectively). These polymorphisms were located in untranslated genome regions: polymorphism rs6599400 in the 5' region of fibroblast growth factor-3 receptor gene (FGFR3), rs1690916 in the 3' region of mouse MDM2 p53-binding protein homolog (MDM2). These data indicated a possible role of hereditary genetic factors in the formation of predisposition to bone sarcomas and confirmed previous findings according to which these genes should be regarded among the most probable factors involved in tumor development, including tumors of the bone and cartilage tissues.

Our investigation involved 27 patients with osteosarcoma and 2--malignant fibrous histiocytoma of long tubular bones treated at the Center's Clinics (2001-2008). Two regimes were used for relapsed tumor: ifosamide up to 5-10 g/m2 (median 7.5) + carboplatin 300-750 mg/m2 (median 350) + etoposide 300-500 mg/m2 (median 450) (ICE), or doxorubicin 50-80 mg/m2 (median 60) (ICA). Surgical treatment used atypical resection of the lung or precision excision of metastasis. Median post-relapse follow-up was 18 months. When ICE was used, partial effect was reported in 3 (17.6%), stabilization--10 (58.8%), and tumor progression--4 (23.5%); ICA: partial effect--3 (25%), stabilization--6 (50%), tumor progression--3 (25%). Metastases were removed after a course of chemotherapy in 16 cases. Overall 3- and 5-year survival was 51.6 +/- 11% and 34.4 +/- 16%, respectively. Relatively more aggressive was the course of the disease in cases of early relapse (< or = 12 months), combination of local recurrence and distant metastasis and those who had not survived until a second surgical remission. Hence, timely combination therapy of relapsed high-grade osteosarcoma may secure relatively long remission in 35-40.3%.

Serum levels of endostatin, placental growth factor (PlGF), and fibroblast growth factors-1 and -2 (FGF-1 and FGF-2) were measured in 58 patients with primary osteosarcomas before therapy and in 21 healthy subjects. The incidence of serum FGF-1 in bone tumors was 2.5 times higher than in healthy individuals (p=0.004); significant levels of FGF-2, PlGF, and endostatin were detected in all examined subjects. The mean serum level of endostatin in healthy individuals was significantly lower than in the total group of patients with bone tumors (p=0.005). The level of FGF-1 in osteosarcomas was significantly higher than in chondrosarcomas (p<0.05). No appreciable differences in FGF-2 levels were detected in patients with tumors of different histological structure. The mean serum content of PlGF was virtually the same in healthy individuals and patients with bone tumors. A significant relationship between serum PlGF level and maximum tumor size (p=0.008) was detected in osteosarcoma. No relationships between the levels of FGF-1, FGF-2, PlGF, and endostatin were detected in healthy subjects and patients with primary tumors of the bones. Differences in 3-year overall survival values of patients with bone sarcomas with different initial serum levels of FGF-1 and endostatin were detected.

The paper reports a review and analysis of the literature on preparation of hemopoietic stem cells (HSC) for allogeneic and autologic transplantation to adult patients with malignant neoplasms. Original data on the collection of HSC from different sources are presented along with prognostic factors for preparing sufficient amounts of HSC. The cells were obtained from a total of 122 subjects (298 procedures). It is shown that the choice of a HSC source and mobilization procedure on an individual basis ensures relatively safe HSC transplantation to all the patients for whom this operation is the treatment of choice.

The Department of Musculoskeletal System Tumors was formed in November 1989 within Research Institute of Pediatric Oncology and Hematology of N. N. Blokhin Russian Oncological Scientific Center of Russian Academy of Medical Sciences. Treatment is carried out with the newest achievements in oncopediatrics applied; priority is given to limb-sparing techniques. The total 5-year survival rate of patients with Ewing's sarcoma is 65.6%, the total 2-year survival rate of patients with soft tissue sarcomas is 62.2%, and the total 2-year survival rate of children with osteosarcoma is 76%. Study of complications and side-effects of chemotherapy, as well as the development of methods of their prevention and correction, present a separate direction in the department's activity. In 1999, the team of the institution's researchers was awarded Russian Federation State Prize for outstanding scientific achievements in the work Development and Clinical Application of Combined Methods of Treatment of Osteogenic Sarcoma. In 2003 and 2004, leading researcher N. M. Ivanova was awarded the institution's diplomas as a part of Biotech prize for the development of new methods of treatment of malignant tumors in children.

Data from 44 patients (23 males, 21 females) with a median age of 39 (range 13-80) years who underwent total hip arthroplasty for proximal femoral tumours (1994-2004) were analysed. The histological diagnoses included 14 metastases, six osteosarcomas, six chondrosarcomas, four Ewing's sarcomas, four giant cell tumours, three malignant fibrous histiocytomas, two parosteal and two periosteal osteosarcomas, and one each primary neuroectodermal tumour, myeloid disease, and aneurysmal bone cyst. Twenty-one patients (48%) had pathological fractures. The cause of the pathological fracture was metastasis in 12 patients (57%). Twenty-eight patients (64%) had soft tissue invasion. Complications observed in 17 patients (37%) were local recurrence in two, postoperative haematoma in two, dislocation of prosthesis in five, deep infection in six, and one patient died of myocardial infarction in the early postoperative period. During our midterm survival analysis, functional results were excellent in 25% of patients, good in 57%, fair in 12%, and poor in 6%.

A case of clinical application of endoscopy in the course of surgery for sacral resection is discussed. Video-assisted frontal approach was used to ligate internal ileac vessels and to detach the fore end of tumor. Subsequently, the sacrum was removed via back access. Unlike standard methods using trans- or extraperitoneal frontal approach, our procedure involved less trauma and was followed by a shorter rehabilitation period.

Data on radio- and thermoradiotherapy of 83 patients with extra-abdominal desmoid tumors are discussed. In a group of 57 patients followed up for 10 years or less, the relapse-free survival rates, in thermoradiotherapy-treated cases, were significantly higher (74.4% and 28.6%) than in those receiving radiotherapy (9.3% and 57.1%). Monitoring tumor temperature during local hyperthermia is a factor of relapse-free survival of vital importance.

Choice of procedure of treatment of defects of reconstructive surgery for locally advanced tumors is discussed. Part 1 deals with use of autovenous vessels and synthetic prosthetics for management of chief artery defects, while Part 2--with bone, soft tissue and skin defects as well as combination defects. Experience with application of free grafts and flaps in microvascular anastomosis is evaluated and relevant recommendations are given.

The paper considers data of the long-term studies of androgen metabolism, baseline serum levels of reproductive steroid hormones and their receptors in the tumor, in the blood concentrations of sex steroid-binding globulin and pituitary hormones, the expression of epidermal growth factor, its receptors and ligands, soluble Fas-antigen, vascular endothelial growth factor, angiogenin, and the content of calmodulin, cAMP in the osteosarcoma in 300 patients aged 14 to 56 years, which were made at the N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. Analyzing the findings identified some lines in the study of new pathogenetic treatments for osteosarcoma, aimed at regulating androgen metabolism, correcting the cyclooxygenase pathway of arachidonic acid, the expression of receptors of epidermal growth factor and its ligands, the processes of neoangiogenesis in the tumor. A role of the above parameters in the pathogenesis of osteosarcoma is discussed.

The Russian Cancer Research Center has experience in diagnosing and treating more than 800 patients with osteosarcoma who have been treated at the Clinic of General Oncology since 1952. Survival rates were no more than 10% before the 1970s when the only treatment was surgical. The use of adjuvant chemotherapy after radical surgery has increased survival up to 45-60%. In 1982 to 1986, a protocol involving intraarterial chemotherapy with adriamycin, 90 mg/m2, radiation therapy in a dose of 40 Gy, preserving surgery, and adjuvant chemotherapy was used to improve local and regional guidance. Survival was 55-60%. The high incidence of purulent complications prompted us to do away with radiation therapy. A protocol of neoadjuvant therapy that implies preoperative intraarterial monotherapy with cisplatin, 120-150 mg/m2, adriamycin, 90 mg/m2 or large-dose methotrexate (8-10 g/m2) was implemented in 1986 to 1998. The best results were achieved only in patients with complete tumor necrosis, among whom survival being over 70%. Preserving surgery following ineffective chemotherapy caused a high incidence of local relapses (30%). The second line of chemotherapy did not greatly improve prognosis when a histological response was slight. Complete tumor necrosis was noted only 10% of more than 150 patients so survival in the whole group was 40%. In 1998, a new protocol was initiated to improve immediate and late outcomes. Preoperatively, 3-4 sessions with adriamycin, 90 mg/m2 and cisplatin, 120 mg/m2, are performed. Postoperatively, 3 or 4 sessions of chemotherapy with the same drugs are made if there is a marked therapeutical pathomorphism. If a response is weak, 6 sessions with ethoposide, 100 mg/m2 and iphosphamide, 1.8 g/m2 during 1-5 days are given. This study has covered just 30 patients. The rate of a full histological responses has increased by 4 times. In every second patient, an amputable tumor could be made a resectable one. The proportion of candidates for preserving surgery has increased up to 90%. Intensified chemotherapy increased the incidence of severe adverse effects, primarily degrees 3-4 hematological toxicity reaching 40%. At the turn of centuries, osteosarcoma is a highly promising curable disease. The survivals of 65-70% and satisfactory functional results can be achieved only at highly specialized centers.

The paper provides data of comparative assessment of activity of the key enzymes in metabolism of androgens in various morphological variants of sarcomas and benign bone tumors in 46 patients within the age range from 15 to 61, which were under treatment in the ORC named after N. N. Blokhin, RAMS, from 1996 to 1997. On the basis on publications and our own research results we can suggest that malignant human bone tumors of various histogenesis are subject to metabolic processes of testosterone (T), the principal androgen regulator in the bone tissue, as well as formation in bones of 5 alpha-dihydrotestosterone (DHT). One cannot exclude a possibility that metabolism of androgen in bone tissues is directed towards formation of other androgens (in addition to DHT), which may participate in the bone tissue regulation, for instance, 3 alpha- and 3 beta-diols; specific activity of the latter has recently been intensively scrutinized. One can expect that further research shall disclose the clinical significance of metabolism of androgens and of individual androgens in human bone formations.

The content of selenium in the serum and bones was compared in persons having no neoplasms and in patients with malignant and benign bone tumors. The mean level of selenium in the healthy femoral bone was 81 micrograms/kg, with more predominant accumulation in the epiphysis than in the metaphysis and diaphysis and with higher concentrations in the periosteum than in the cambial layer. The normal mean bone/serum selenium ratio was 0.74. This index varied 0.8 to 5.1 in patients with benign tumors and 2.3 to 10.0 in those with malignant tumors. Benign tumors were characterized by significant multiple variations of tumor selenium levels depending on the type of an abnormality with maximally observed values in giant-cell tumor. In patients with various osteosarcomas, the mean selenium content was decreased to 71% in the serum and increased up to 300% in the tumor. The examination of the impact of the type of non-adjuvant therapy on serum selenium levels in patients with bone tumors indicated a negative selenium effect in the application of radiation therapy and a positive selenium effect in the transfusion of bone marrow suspension and in the use of platidium or SAR-regimen therapy.

The authors have investigated the blood supply of the hip joint in aseptic necrosis following a bloodless reduction of a congenital dislocation of the hip with the help of serial angiography in 6 patients aged 3.5 to 8 years. The angiographic examination has allowed us to determine a reduction in the vascular field on the side affected by hip joint dysplasia as compared with the values on the conventionally normal side. The experimental investigation of the vessels by means of introduction of a radiopaque mixture has demonstrated that in case of a non-physiological position of the lower extremities (Lorenz I) a compression of the blood supplying vessels of the hip joints takes place.

The hip joints in 10 children were investigated with computerized tomography (CT). The method permitted the determination of the geometry of hip joints. It was used for a study of the pathogenesis of aseptic necrosis at early stages of its development in children with congenital dysplasia of the hip joint at early stages of disease. CT made it possible to establish anteversion of the cotyloid cavity, its degree, the shape and structure of the anterior and posterior wall of the cotyloid cavity, and a shift of the proximal hip end anteriorly in combination with the above changes in the whole hip joint.