Clinical Consequences of Unreconstructed Pelvic Defect Caused by Osteosarcoma with Subsequent Progressive Scoliosis in a Pediatric Patient-Case Report.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The standard and most effective treatment is wide resection of the tumor combined with neoadjuvant chemotherapy. Adolescent idiopathic scoliosis (AIS) is a genetically determined three-dimensional spinal deformity, which occurs in teenage patients and is mostly progressive. The basic management strategy is surgical treatment when the curve exceeds 50 degrees. However, the indications are different in oncologic patients. The aim of this study was to describe a case of adolescent scoliosis with osteosarcoma of the pelvis. The authors conducted a scoping review using PubMed and Embase to analyze the state of knowledge. The presented paper is the first report of pelvis osteosarcoma coexisting with adolescent idiopathic scoliosis. Treatment for this complex case finished with very good results, with no recurrence observed during the nine-year follow-up.

Osteoprotegerin Gene as a Biomarker in the Development of Osteoporosis in Postmenopausal Women.

Osteoporosis is a multifactorial and polygenic disease caused by an imbalance between osteoclastogenesis and osteoblastogenesis, leading to a decrease in bone mineral density and the occurrence of disorders in the microarchitecture and metabolism of bone tissue. In postmenopausal women, there is a significant decrease in the production of estrogens, which play a key role in maintaining proper bone mineral density. Estrogens have an inhibitory effect on the development and activity of osteoclasts by reducing the synthesis of pro-resorption cytokines and stimulating the expression of osteoprotegerin (OPG). Osteoprotegerin is a cytokine that prevents bone loss by inhibiting the process of osteoclastogenesis, reducing bone resorption. The aim of our study was to determine the influence of the rs3102735 (-163A>G), rs3134070 (-245T>G), rs207361 (-950T>C), rs7844539 (6890A>C), and rs2073618 (1181G>C) polymorphisms of the OPG gene on the risk of osteoporosis and osteopenia in postmenopausal Polish women. The study included 802 unrelated women (osteoporosis: n = 317, osteopenia: n = 110, controls: n = 375) at postmenopausal age (54.7 ± 8.6 years). Genetic analysis was performed using real-time PCR. BMD values as well as clinical and bone parameters with the tested polymorphisms were analyzed among the study population. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, for the OPG rs207361 polymorphism, we observed a statistically significant association with the risk of osteoporosis, suggesting that the OPG rs207361 variant may be one of the genetic markers associated with the pathogenesis of osteoporosis.

Analysis of the Polymorphisms and Expression Levels of the BCL2, BAX and c-MYC Genes in Patients with Ovarian Cancer.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

The influence of ESR1 polymorphisms on selected hormonal, metabolic and mineral balance markers in women with hyperandrogenism.

Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance in normal estrogen and androgen levels in the blood. Androgens influence bone mineral density, body mass composition, muscle mass, mental state, and the regulation of sexual function.. The aim of the study was to assess the effect of estrogen receptor α gene (ESR1) polymorphisms on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group included 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, sRANKL (soluble receptor activator of nuclear factor-kB ligand), osteoprotegerin and 25-OH vitamin D total levels. An analysis of ESR1 gene polymorphisms was performed using the real-time PCR method. A relationship was demonstrated between the concentration of free estradiol (FEI) and the concentration of 17-OH-progesterone, and the ESR1 gene polymorphisms: rs3020314 (p = 0.031, p = 0.026 respectively) and rs1884051 (p = 0.033, p = 0.026 respectively). In conclusion, the ESR gene polymorphisms may be associated with hormonal disturbances in the concentration of estrogens and androgens, in hyperandrogenism in young women which may indirectly affect bone mineral density. However, no statistically significant relationships between the studied polymorphisms and the selected parameters of mineral metabolism have been demonstrated..

The Role of Forkhead Box O in Pathogenesis and Therapy of Diabetes Mellitus.

Type 2 diabetes is a disease that causes numerous complications disrupting the functioning of the entire body. Therefore, new treatments for the disease are being sought. Studies in recent years have shown that forkhead box O (FOXO) proteins may be a promising target for diabetes therapy. FOXO proteins are transcription factors involved in numerous physiological processes and in various pathological conditions, including cardiovascular diseases and diabetes. Their roles include regulating the cell cycle, DNA repair, influencing apoptosis, glucose metabolism, autophagy processes and ageing. FOXO1 is an important regulator of pancreatic beta-cell function affecting pancreatic beta cells under conditions of insulin resistance. FOXO1 also protects beta cells from damage resulting from oxidative stress associated with glucose and lipid overload. FOXO has been shown to affect a number of processes involved in the development of diabetes and its complications. FOXO regulates pancreatic ß-cell function during metabolic stress and also plays an important role in regulating wound healing. Therefore, the pharmacological regulation of FOXO proteins is a promising approach to developing treatments for many diseases, including diabetes mellitus. In this review, we describe the role of FOXO proteins in the pathogenesis of diabetes and the role of the modulation of FOXO function in the therapy of this disease.

Rhabdomyosarcoma of the Cervix in a Post-Menopausal Woman-An Unparalleled Phenomenon.

Rhabdomyosarcoma of the cervix is a soft tissue sarcoma that usually occurs in young women. It is very rare in adulthood. We discuss symptoms, the process of diagnosis of rhabdomyosarcoma embryonale of the cervix in a 61-year-old women and differences in treatment dependent on patient's age. A 61-year-old woman with symptoms such as palpable mass in the external cervical opening and post-menopausal hemorrhaging was admitted to the oncology ward where excision of the polyp was performed. Embryonal rhabdomyosarcoma (ERMS) was diagnosed by histopathological examination of obtained tissues. The diagnosis was complemented by chest computed tomography and pelvis magnetic resonance imaging to exclude metastases. A Wertheim-Meigs operation and excision of the ovaries, the fallopian tubes and the surrounding tissue was performed in the course of treatment. In the patient's follow-up of 25 months to date, there have been no signs of recurrence or symptoms connected to ERMS. Based on the therapeutic outcome, the decision to limit the treatment to a surgical resection was adequate for a post-menopausal patient. Because of the rarity of ERMS in the post-menopausal age, we think that the patient should be carefully followed up to further examine this issue and develop diagnostic and treatment guidelines.

Preliminary Results of Highly Injectable Bi-Phasic Bone Substitute (CERAMENT) in the Treatment of Benign Bone Tumors and Tumor-like Lesions.

BACKGROUND: CERAMENT™|BONE VOID FILLER is an injectable and moldable ceramic bone substitute material intended for bone voids. The material consists of hydroxyapatite and calcium sulfate hemihydrate. The aim of this study is to present the first long-term results following open curettage of benign bone tumors and tumor-like lesions and void filling with this novel injectable and synthetic bone graft. METHODS: Thirty three patients were enrolled into the study between June 2013 and October 2014 .Totally, we treated 24 women and 9 men with a median age of 47 years (range: 22-74). All patients suffered from primary musculoskeletal system disorders (enchondroma 63,6%, giant cell tumor 18%, aneurysmal bone cyst 9%, fibrous dysplasia 9%, Gaucher disease 3%). We performed curettage of pathological lesions, then the bone substitute was administered by means of needle to the void. RESULTS: The average follow-up was 13 months (range: 2-13 months, median 10 months). No metastasis or recurrence had been detected. We received significant clinical improvement relating to VAS, MSTS, and oncological results. CONCLUSIONS: The results of our study report that CERAMENT can be successfully used as a bone substitute in patients with various bone diseases, as well as benign bone tumors. CERAMENT can provide an effective and long-term solution for reconstructive procedures following curettage of bone tumors and tumor like lesions.

From ophthalmologist to dentist via radiology.

BACKGROUND: The aim of this paper was to analyze the causes of orbital cellulitis in connection with covert dental changes as well as to establish the role of radiological procedures in the final diagnosis and further treatment of such cases. MATERIAL/METHODS: Thirty-two patients, aged 25-56, 22 women and 10 men were diagnosed and treated between January 2007 and April 2011 at the Pomeranian Medical University in Szczecin. The patients were examined in the infirmary of the ophthalmological department due to unilateral blepharo-oedema, abrupt pain and vision disturbances; in 5 cases, body temperature increased up to 37.8°C was observed. Next, the patients underwent conventional X-ray examinations of the orbit to exclude any foreign bodies in the eyeball, as well as pantomographies to evaluate the dental status. Visible periapical or periodontal changes in dentition were analyzed with intraoral X-rays with the use of DIGORA System 2.1. Changes found in 3 patients on pantomograms and connected with iatrogenic procedures were further evaluated with CT (64 lines and 128 layers) in frontal, sagittal and axial projections. Orbital disorders were also diagnosed by an ophthalmologist and radiologist with Doppler ultrasound (US) examinations. A linear transducer of 7.5-10 MHz to observe the morphology and vascularity of the eyeball was applied. RESULTS: IATROGENIC TREATMENT WAS THE CAUSE OF SINUSITIS AND CELLULITIS IN THREE CASES: incorrectly implanted dental implant in one case, root of the 3(rd) molar pushed into the sinus in the second case, and communication between the maxillary alveolar process and the sinus after extraction in case of the third patient. Asymptomatic periapical osteolysis, periodontal disease or dead teeth were found in all cases. Diagnosis of orbital cellulitis of dental origin was determined on the basis of clinical, radiographic and ultrasound findings. Ophthalmologic and dental treatment was applied simultaneously. CONCLUSIONS: Co-operation between ophthalmologists, radiologists and dentists is necessary during the treatment of such orbital diseases.

[Clinical and radiological evaluation of malignant metaplasia of benign primary bone tumors on the material of University Orthopaedic Department of Szczecin between 2002-2007]. / Ocena kliniczna i radiologiczna metaplazji zlosliwej pierwotnych lagodnych nowotworów kosci oraz zmian pseudonowotworowych w materiale Kliniki Ortopedii PAM w Szczecinie w latach 2002-2007.

The study presents clinical and diagnostic problems in patients with malignant bone metaplasia. Material is composed of 13 patients treated surgically between april 2002 and august 2007. In three cases tumors were localised in tibia, in 5 patients around distal femur, in 2 in pelvis, in 2 in humerus and in 1 in lumbar spine. None of the patients has had recurrence by february 2006 r, 12 patients have been free of the disease so far. However, one individual diagnosed with giant cell tumor metaplasia to osteosarcoma did not accept proposed therapy. The authors have particularly emphasized thorough clinical and radiological evaluation and the need of team work before surgical procedure.

Polymorphism in the P-glycoprotein drug transporter MDR1 gene in renal transplant patients treated with cyclosporin A in a Polish population.

P-glycoprotein (P-gp), the product of MDR1 gene, is a protein which mediates transmembrane transport of a great number of xenobiotics including cyclosporin A used as an immunosuppressive drug in patients with allogenic kidney grafts. The P-gp activity and expression is dependent on the MDR1 gene polymorphism in position C3435T of exon 26. In this study, C3435T polymorphism was analyzed in 116 patients with allogenic kidney graft treated with cyclosporin Aand 144 randomly selected healthy individuals. The prevalence of MDR1 gene genotypes 3435CC, 3435CT, 3435TT were also compared in patients after allogenic kidney graft with both acute and chronic graft rejection (48 patients with acute and 76 with chronic graft rejection) and control groups (respectively 139 and 112). The results of the study demonstrated that the allelic frequency and MDR1 genotype distribution were similar in all evaluated groups. It was revealed that MDR1 gene polymorphism was not a predisposing factor for terminal kidney failure leading to renal transplantation. Moreover, evaluation of C3435T polymorphism of MDR1 gene will probably not be useful for characterization of groups of patients at increased risk of acute and chronic kidney graft rejection.

Peripheral blood lymphocytes P-glycoprotein (P-gp, gp-170) expression in allogenic kidney transplant patients.

AIM AND METHODS: P-glycoprotein (gp-170, P-gp) is a transmembrane transporter involved in drug, for example cyclosporine A, efflux from the cells thus limiting their intracellular concentration. Expression of the transporter on the surface of immune competent cells may be associated with poor prognosis in kidney transplant patients. The aim of the present study was to evaluate P-gp expression on the surface of CD4(+), CD8(+), CD19(+) and CD56(+) cells in kidney transplant patients treated with cyclosporine A as a main immunosuppressant, using flow cytometry. RESULTS: It was found that P-gp expression in kidney transplant patients with acute rejection did not differ significantly from transplanted patients without rejection studied in the same period after transplantation, as well as from the healthy controls. Administration of 3-day course of 1,000 mg/24 h methylprednisolone did not affect the expression of P-gp in the studied cells, except for significant elevation in CD56(+) cells, which disappeared at 2 weeks after cessation of steroid administration. CONCLUSION: Based on the results from the present study it can be concluded that P-gp expression is not a prognostic factor of acute kidney graft rejection.

MDR1 gene polymorphism in allogeenic kidney transplant patients with tremor.

P-glycoprotein (P-gp), an ATP-dependent efflux pump, is a membrane protein encoded by MDR1 gene, which demonstrates functional polymorphism. It is present in endothelial cells of the blood-brain barrier. P-gp pays a role in transmembrane transport of various xenobiotics, thus limiting their accumulation in the central nervous system. Cyclosporine A which is used as an immunosuppressive drug in patients with allogenic kidney grafts is a substrate for P-gp. Cyclosporine A may cause neurotoxic adverse effects, among them tremor. It was assumed that polymorphism of MDR1 gene which is associated with change in P-gp activity plays a role in induction of tremor in some patients with allogenic kidney graft treated with cyclosporine A. A total of 118 unrelated postransplant kidney patients were enrolled into the study. The tremor group included 23 cases and 95 randomly selected posttransplant individuals with no signs of tremor served as controls. No statistically significant correlation between MDR1 gene polymorphism C3435T and tremor was found. The tremor group and the control group were characterized by similar distribution of MDR1 genotypes, i.e. 3435CC, 3435CT, 3435TT.