[Surgical treatment of patients with chest wall metastases]. / Khirurgicheskoe lechenie patsientov s metastaticheskim porazheniem grudnoi stenki.

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.

Comparative analysis of the levels of soluble forms of receptor and ligand of the immunity control point PD-1/PD-L1 in the blood serum of patients with typical bone osteosarcoma and chondrosarcoma.

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.

Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors.

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.

[Li-Fraumeni syndrome in a patient with multiple anaplastic oligodendrogliomas of the brain (a case report and literature review)]. / Sindrom Li-Fraumeni u patsienta so mnozhestvennymi anaplasticheskimi oligodendrogliomami golovnogo mozga (klinicheskoe nabliudenie i obzor literatury).

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.

[Clinical results of the use of ultrasonic bone cement extractor in revision arthroplasty in oncology].

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.

Associations of single nucleotide polymorphisms with malignant and borderline bone tumors.

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.

Expression of molecular markers in low-grade chondrosarcomas and cartilaginous tumors with uncertain differentiation.

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.

Association of FGFR3 and MDM2 gene nucleotide polymorphisms with 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.

[Treatment of relapsed osteosarcoma. Role of chemotherapy using ifosamide and carboplatin].

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%.

Endostatin, placental growth factor, and fibroblast growth factors-1 and -2 in the sera of patients with primary osteosarcomas.

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.

[Preparation of hemopoietic stem cells for transplantation to adult patients with malignant neoplasms].

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.

[Innovation approaches to treatment of children with malignant tumors of the musculoskeletal system].

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.

Total hip replacement for proximal femoral tumours: our midterm results.

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%.

[Comparison of methods of reconstructive vascular and microvascular surgery used in management of tumors].

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.

[Thermoradiotherapy as a component of desmoid tumor management: 10-year experience].

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.

[Use of endoscopy for sacral resection: a clinical case].

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.

[Osteosarcoma: biochemical and endocrinological studies as a basis for its pathogenetic treatments]. / Biokhimicheskie i éndokrinologicheskie issledovaniia pri osteosarkome -- osnova patogeneticheskikh metodov lecheniia opukholi.

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.