Seudoartrosis atrófica: Efecto de la aplicación de ondas de choque extracorpóreas en un modelo experimental en tibia de conejos / Atrophic pseudoartrosis. Effect of extracorporeal shock waves application in an experimental model in tibia of rabbits

Introducción: Los efectos de las ondas de choque extracorpóreas se han investigado en osteoblastos humanos, focos fracturarios, seudoartrosis y células periósticas. Los mejores resultados del tratamiento de la seudoartrosis con ondas de choque extracorpóreas se han documentado para seudoartrosis hipertróficas. El objetivo de este estudio fue investigar el efecto de la terapia con ondas de choque extracorpóreas sobre un foco de seudoartrosis "atrófica" generado en tibia de conejo. Métodos: Se establecieron tres grupos: A, fracturados sometidos a ondas de choque extracorpóreas; B ("control"), fracturados no sometidos a ondas de choque y C, no fracturados (pierna derecha). Se trataron 37 conejos (cuniculus NV) blancos y esqueléticamente maduros de Nueva Zelanda. Se practicó la cauterización del periostio con electrobisturí bipolar en una extensión de 20 mm, en ambos muñones óseos (proximal y distal). Luego se aplicaron ondas de choque extracorpóreas en una sola sesión. Se realizaron tinciones con hematoxilina-eosina. Se efectuó el análisis biomecánico con un método de carga a "3 puntos". Se estudiaron la carga máxima aplicada y el módulo de elasticidad para cada grupo. Resultados: El estudio histológico permitió registrar signos de consolidación -callo fracturario perióstico y endostal- considerablemente mayores en las tibias de los animales del grupo A (tratado con ondas de choque extracorpóreas) que en las del grupo B "control". Conclusión: En un modelo experimental original de seudoartrosis atrófica generada por electrocauterización en tibia de conejos, se registraron cambios significativos radiográficos e histológicos luego de la intervención del foco mediante ondas de choque extracorpóreas. Nivel de Evidencia: II

Introduction: The effects of extracorporeal shock wave therapy (ESWT) have been investigated in human osteoblasts, fracture foci, nonunion and periosteum cells. The best results of nonunion treatment with ESWT have been documented for hypertrophic type. The objective of this study was to investigate the effects of ESWT in an atrophic nonunion focus generated in a rabbit tibia model. Methods: Three groups were included: A, fractures receiving ESWT; B ("control"), fractures not receiving ESWT, and C, no fractures (right leg). A total of 37 New Zealand white and skeletally mature rabbits (cuniculus NV) were treated. Periosteum was cauterized using bipolar electrocautery at 20 mm in both bone stumps (proximal and distal). Then ESWT was applied in one session. Staining with hematoxylin-eosin was used. A biomechanical analysis with a 3-point loading system was performed. Maximum load and elastic modulus were evaluated in each group. Results: Histological study evidenced signs of union (periosteal and endosteal fracture callus) which were considerably larger in tibias of Group A (treated with ESWT) as compared to the control group (Group B). Conclusion: In an experimental model of atrophic pseudarthrosis caused by electrocautery in tibias of rabbits, significant radiographic and histological changes were observed after focus intervention with the application of ESWT. Level of Evidence: II

Undifferentiated Pleomorphic Sarcoma and the Importance of Considering the Oncogenic and Immune-Suppressant Role of the Human T-Cell Lymphotropic Virus Type 1: A Case Report.

INTRODUCTION: Soft-tissue sarcomas account for 0.7% of all malignant tumors, with an incidence rate of 3 per 100,000 persons/year. The undifferentiated pleomorphic sarcoma (UPS) with giant cells, a high grade tumor of soft tissue, is very unusual, especially in young adults before the age of 40. Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus, classified as group 1 human carcinogens by The International Agency for Research on Cancer, that causes an aggressive malignancy known as adult T-cell lymphoma/leukemia and a progressive chronic inflammatory neurological disease named HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 causes accumulation of genetic mutations in the host genome that could contribute to cellular transformation, one of the oncogenic features of HTLV-1. CASE REPORT: We describe a case of a young woman with UPS who suffered from HAM/TSP with 3 years of evolution. In 2013, the patient started with neurological symptoms: weakness in the legs and bladder dysfunction. One year later, the patient developed a mild paraparesis in both extremities, anti-HTLV-1 antibodies were detected in plasma and in cerebrospinal fluid, and HAM/TSP was confirmed. In November 2015, a benign ganglion cyst was first suspected without intervention and by March 2016 a sarcoma was diagnosed. Three weeks after surgical resection, the tumor aroused in deep tissue and behaved aggressively, implicating a curative wide resection of the fibula, joint reconstruction, and soft-tissue graft. Histopathological examination confirmed UPS with giant cells. CONCLUDING REMARKS: The unapparent subclinical immunodeficiency state due to HTLV-1 infection deserves to be considered in order to carefully monitor the possibility of developing any type of cancer. Besides, reaching an accurate and timely diagnosis of UPS can be challenging due to the difficulty in diagnosis/classification and delayed consultation. In this particular case, considering the high grade of UPS and the progressive invalidating myelopathy caused by HTLV-1, treatment should be carefully evaluated to positively impact on the patient's life expectancy.

IDH Mutation Analysis in Ewing Sarcoma Family Tumors.

BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis. METHODS: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. RESULTS: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. CONCLUSIONS: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

Juvenile Paget's disease with heterozygous duplication within TNFRSF11A encoding RANK.

Mendelian disorders of RANKL/OPG/RANK signaling feature the extremes of aberrant osteoclastogenesis and cause either osteopetrosis or rapid turnover skeletal disease. The patients with autosomal dominant accelerated bone remodeling have familial expansile osteolysis, early-onset Paget's disease of bone, expansile skeletal hyperphosphatasia, or panostotic expansile bone disease due to heterozygous 18-, 27-, 15-, and 12-bp insertional duplications, respectively, within exon 1 of TNFRSF11A that encodes the signal peptide of RANK. Juvenile Paget's disease (JPD), an autosomal recessive disorder, manifests extremely fast skeletal remodeling, and is usually caused by loss-of-function mutations within TNFRSF11B that encodes OPG. These disorders are ultra-rare. A 13-year-old Bolivian girl was referred at age 3years. One femur was congenitally short and curved. Then, both bowed. Deafness at age 2years involved missing ossicles and eroded cochleas. Teeth often had absorbed roots, broke, and were lost. Radiographs had revealed acquired tubular bone widening, cortical thickening, and coarse trabeculation. Biochemical markers indicated rapid skeletal turnover. Histopathology showed accelerated remodeling with abundant osteoclasts. JPD was diagnosed. Immobilization from a femur fracture caused severe hypercalcemia that responded rapidly to pamidronate treatment followed by bone turnover marker and radiographic improvement. No TNFRSF11B mutation was found. Instead, a unique heterozygous 15-bp insertional tandem duplication (87dup15) within exon 1 of TNFRSF11A predicted the same pentapeptide extension of RANK that causes expansile skeletal hyperphosphatasia (84dup15). Single nucleotide polymorphisms in TNFRSF11A and TNFRSF11B possibly impacted her phenotype. Our findings: i) reveal that JPD can be associated with an activating mutation within TNFRSF11A, ii) expand the range and overlap of phenotypes among the Mendelian disorders of RANK activation, and iii) call for mutation analysis to improve diagnosis, prognostication, recurrence risk assessment, and perhaps treatment selection among the monogenic disorders of RANKL/OPG/RANK activation.

Osteosarcoma of the jaw: an analysis of a series of 74 cases.

AIMS: To analyse a series of cases of osteosarcoma of the jaw. METHODS AND RESULTS: The study included 74 cases of osteosarcoma of the jaw. Their clinical, radiographic and histopathological features were analysed, and their frequency with respect to aggressive and malignant pathologies of the jaw was determined. Survival was assessed in 17 cases with available follow-up. Osteosarcoma of the jaw accounted for 10% of primary malignant and aggressive tumours of the jaw, and for 8% of all malignant lesions of the jaw, including metastatic and lymphoproliferative tumours. The mean age was 43 ± 18 years. Radiographic features varied greatly and were non-specific, with a predominance of mixed images. The dominant histological pattern was osteoblastic (48.4%), followed by chondroblastic (37.1%). The survival rate at 5 years was 68%. Females and patients with a predominantly chondroblastic pattern had lower survival rates. CONCLUSIONS: Osteosarcoma of the jaw was the most frequent primary malignant tumour of the jaw. Female gender and a predominantly chondroblastic pattern may be associated with a worse prognosis.

Technical aspects of core needle biopsy and fine needle aspiration in the diagnosis of bone lesions.

OBJECTIVE: Percutaneous needle biopsy is an effective and safe technique for obtaining diagnostic material from bone lesions. STUDY DESIGN: We describe the technical details of fine needle aspiration and core needle biopsy performed in our laboratory of orthopedic pathology. RESULTS: With these procedures, we obtained accurate diagnosis in 83% of 7,375 cases, sent by different orthopedic centers in our country, over a period of 21 years (1986-2007). CONCLUSION: We describe the percutaneous needle procedure (fine needle aspiration, core needle biopsy), the handling of the materials in detail, the different cytological techniques, as well as the advantages of the procedures and how to avoid its disadvantages. We believe that accurate diagnosis with bone needle biopsy mainly depends on the training of the surgical cytologist and the pathologist, who must integrate all the knowledge on the clinical data, image diagnosis, histological procedures and the experience in the histopathological interpretation of bone lesions.

Expression of heat shock proteins in osteosarcomas.

AIMS: Heat shock proteins (HSPs) protect cells against stress-associated injuries and are overexpressed in several malignant tumours. We investigated the potential roles of HSP27, HSP60, and HSP70 in conventional and low grade central osteosarcoma. METHODS: Expressions of HSP27, HSP60, and HSP70 were analysed using immunohistochemistry on tissue sections from 52 cases of conventional osteosarcoma and 21 cases of low grade central osteosarcoma. We evaluated the expression of each protein and examined its relationship with clinicopathological parameters. RESULTS: We found significantly different expressions of HSP27 and HSP70 between conventional and low grade central osteosarcoma [34.6% versus 4.8% (p = 0.008), 88.5% versus 14.3% (p < 0.001)]. However, HSP60 was highly expressed in both kinds of osteosarcoma (92.3% versus 85.7%). In conventional osteosarcoma, a higher expression of HSP27 was significantly related to distant metastasis (p = 0.034) and histological subtype [osteoblastic versus non-osteoblastic (p = 0.041)]. The expressions of HSP60 and HSP70 were not significantly related to any tested clinicopathological parameter. CONCLUSIONS: HSP27 and HSP70 may be used as differential markers to distinguish conventional and low grade central osteosarcoma. HSP27 may be used as a possible prognostic marker in conventional osteosarcoma cases.

Evaluation of nucleolar organizer regions in maxillary osteosarcoma.

Maxillary osteosarcomas are a relatively frequent malignant tumor of the oral cavity. Similarly to other skeletal osteosarcomas, they exhibit different cellular differentiation patterns, i.e. chondroblastic, osteoblastic, or fibroblastic. Although their histological features resemble those of osteosarcomas of the long bones, their pattern of evolution usually differs. Morphometric variations in silver stained Nucleolar Organizer Regions (AgNOR) have proved of value to study the biology of several tumors. However, information on the analysis of AgNOR in maxillary tumors is scarce. The aim of the present study was to analyze the variations of different morphological parameters related to AgNOR in a series of 32 cases of maxillary osteosarcoma. In each case we analyzed 100 nuclei corresponding to the prevalent cellular differentiation type, selecting the most aggressive area. We employed software previously developed at our laboratory that yields information on different AgNOR-related parameters. The results were compared with those previously reported in a study on 12 cases of osteosarcoma of long bones. Six cases of oral mucosa squamous cell carcinoma were also included for comparative purposes. Single AgNOR volume proved to be the most discriminatory and informative parameter. The value of single AgNOR volume was considerably lower in mandible osteosarcomas than in osteosarcomas of the upper maxilla (p=0.02). The values were significantly lower in maxillary osteosarcomas than in long bone osteosarcomas and in oral carcinomas. This finding would suggest a slower rate of cell activity in maxillary osteosarcomas, associated in turn to its known lower degree of aggressiveness. The present results suggest that the analysis of AgNOR is a valuable and easily applicable marker to determine the degree of malignancy and biology of maxillary osteosarcomas.

Malignant fibrous histiocytoma associated with coxofemoral arthrodesis.

The discovery of biomaterials led to their use in the manufacture of implants for biomedical applications. In vivo, no metal or alloy is completely inert. The potential toxicity of some of the metals most frequently employed in the manufacture of orthopedic implants has been reported. Their carcinogenic potential has been evaluated in experimental animal models. However, few reports have discussed the potential development of malignant tumors associated with prosthetic structures in humans. The present study documents a case of intraosseous sarcoma that developed in the vicinity of a metallic prosthesis 43 months after a coxofemoral arthrodesis with metallic pins and screws. With this report the authors seek to contribute to the understanding of the potential toxicity and risks of using metallic implants. Since metallic implants employed in the rehabilitation of osteo-muscular-articular disorders usually remain in the organism for long periods of time, the need to monitor the metallic structures and the adjacent tissues is extremely relevant.

Reparacion tendinosa con la utilizacion de plasma rico en plaquetas. Estudio experimental en conejos / Achilles tendon repair using platelet rich plasma. An experimental study in rabbits

Introducción: Si bien se conoce bastante la actividad de los factores de crecimiento, sobre todo del factor de crecimiento derivado de las plaquetas in vitro, la información de su actividad en modelos experimentales in vivo es limitada. El objetivo del presente trabajo es crear un modelo para estimar la eficacia del plasma rico en plaquetas en la cicatrización del tendón de Aquiles de conejo. Materiales y métodos: Se utilizaron 12 conejos de raza neozelandesa esqueléticamente maduros. Se realizó un abordaje posterior sobre la zona medial del tendón de Aquiles y sección quirúrgica a 1 cm de su inserción distal. Del lado izquierdo se efectuó la sección quirúrgica del tendón y sutura terminoterminal, y del lado derecho, sección del tendón, sutura terminoterminal y colocación de plasma rico en plaquetas. Resultados: No se observaron diferencias significativas entre ambos grupos en la evaluación macroscópica, con resonancia magnética, histológica y de tensión con Instron 4487. Conclusiones: Estos datos experimentales no apoyarían la utilización del plasma rico en plaquetas en las lesiones tendinosas de los seres humanos.

Reparacion tendinosa con la utilizacion de plasma rico en plaquetas. Estudio experimental en conejos / Achilles tendon repair using platelet rich plasma. An experimental study in rabbits

Introducción: Si bien se conoce bastante la actividad de los factores de crecimiento, sobre todo del factor de crecimiento derivado de las plaquetas in vitro, la información de su actividad en modelos experimentales in vivo es limitada. El objetivo del presente trabajo es crear un modelo para estimar la eficacia del plasma rico en plaquetas en la cicatrización del tendón de Aquiles de conejo. Materiales y métodos: Se utilizaron 12 conejos de raza neozelandesa esqueléticamente maduros. Se realizó un abordaje posterior sobre la zona medial del tendón de Aquiles y sección quirúrgica a 1 cm de su inserción distal. Del lado izquierdo se efectuó la sección quirúrgica del tendón y sutura terminoterminal, y del lado derecho, sección del tendón, sutura terminoterminal y colocación de plasma rico en plaquetas. Resultados: No se observaron diferencias significativas entre ambos grupos en la evaluación macroscópica, con resonancia magnética, histológica y de tensión con Instron 4487. Conclusiones: Estos datos experimentales no apoyarían la utilización del plasma rico en plaquetas en las lesiones tendinosas de los seres humanos

Reparacion tendinosa con la utilizacion de plasma rico en plaquetas. Estudio experimental en conejos / Achilles tendon repair using platelet rich plasma. An experimental study in rabbits

Introducción: Si bien se conoce bastante la actividad de los factores de crecimiento, sobre todo del factor de crecimiento derivado de las plaquetas in vitro, la información de su actividad en modelos experimentales in vivo es limitada. El objetivo del presente trabajo es crear un modelo para estimar la eficacia del plasma rico en plaquetas en la cicatrización del tendón de Aquiles de conejo. Materiales y métodos: Se utilizaron 12 conejos de raza neozelandesa esqueléticamente maduros. Se realizó un abordaje posterior sobre la zona medial del tendón de Aquiles y sección quirúrgica a 1 cm de su inserción distal. Del lado izquierdo se efectuó la sección quirúrgica del tendón y sutura terminoterminal, y del lado derecho, sección del tendón, sutura terminoterminal y colocación de plasma rico en plaquetas. Resultados: No se observaron diferencias significativas entre ambos grupos en la evaluación macroscópica, con resonancia magnética, histológica y de tensión con Instron 4487. Conclusiones: Estos datos experimentales no apoyarían la utilización del plasma rico en plaquetas en las lesiones tendinosas de los seres humanos.(AU)