Management of Apatinib-Related Adverse Events in Patients With Advanced Osteosarcoma From Four Prospective Trials: Chinese Sarcoma Study Group Experience.

Four prospective trials have reported apatinib-related efficacy in osteosarcoma, with a high response rate of 43.2%. Currently, Adverse Events (AEs) have increasingly gained attention, as treatment with multiple tyrosine kinase inhibitors (TKIs) is potentially lifelong. For this reason, a consensus meeting of the Chinese Sarcoma Study Group (CSSG), which is a multidisciplinary panel composed of pediatric, medical and surgical oncologists specializing in sarcoma, nurse specialists, oncological senior pharmacists and gastroenterologists, was held to develop comprehensive guidelines on AEs emerging due to apatinib treatment to better assist in the prevention, management, and understanding of AE development. We summarized all AEs that arose in ≥10% of the participants as well as rare AEs that required extra caution to prevent that were observed in these four published prospective trials and arranged these AEs into 14 disorder systems according to CTCAE 5.0. In this review, we discuss strategies for the management of AEs in patients with advanced osteosarcoma, with the aim of maximizing treatment benefits and minimizing the need for apatinib treatment discontinuation. We also focus on providing recommendations for the prophylaxis and treatment of advanced osteosarcoma using apatinib to achieve optimal outcomes.

[The effect of repeated bonding of octyl-a-cyanoacrylate adhesive on human tibia cortical bone].

During clinical operation, the repeated bonding of octyl-a-cyanoacrylate adhesive is necessary for satisfactory reduction and fixation. This is because the repeated bonding will change the morphologic characteristics of the bone surface in biomechanical study. The influence of repeated bonding of octyl-a-cyanoacrylate on fresh human tibia cortical bone was assessed in this experiment. First, we made the transverse fracture model on the anterior part of cortical bone of fresh human tibia shaft. After 24 hours of bonding, the tensile strength, shear strength and angular strength were tested; then we made the bonding for the second time and third time, tested the tensile strength, shear strength and angular strength respectively, and observed the change of tensile strength, shear strength and angular strength. We found the shear strength of the primary bonding being greater than that of the second bonding and the third bonding (P<0.05). The shear strength of the second bonding and the third bonding showed no statistically significant difference. The tensile strength, elastic modulus, rigidity coefficient and moment of area inertia exhibited no statistically difference between the first, second and third bonding. The repeated bonding of octyl-a-cyanoacrylate adhesive will change the morphologic characteristics of the bone surface, this will decrease the shear strength during the experiment. When the shear strength test is to be repeated, the residue of the adhesive on the surface of the bone bonded area should be removed. During clinical application, bonding should be performed only once in the area for resisting the shear strength.

Octyl-a-cyanoacrylate adhesive in the treatment of tibial transverse fracture in rabbits.

OBJECTIVE: To observe the effect of octyl-a-cyanoacrylate upon bone healing and its degradation in vitro after middle tibial transverse fracture in rabbitsì and to establish treatment of higher efficacy with the application of octyl-a-cyanoacrylate. METHODS: Middle tibial transverse fracture model of New Zealand rabbits was established. In the experimental group, internal fixation with 2 mm Kirschner wires was performed and the broken ends were fixed with octyl-a-cyanoacrylate. In the control group, only internal fixation with 2 mm Kirschner wires was conducted. Animals were killed at preset time intervals of 2, 4, 6, 8, 10 and 12 weeks postoperatively and samples were harvested. RESULTS: Two weeks after operation, clear fracture lines were observed in both the experimental and the control groups. Fibrous soft tissue connection was noted between the broken ends and there was soft tissue adhesion around the fracture site. There was no callus formation and the broken ends were surrounded by adhesive soft tissues. Obvious external callus formation was confirmed at 8 weeks after operation in both groups with partial disappearance of fracture lines. Ten and twelve weeks after the operation, fracture lines disappeared completely and there was obvious external callus formation and bone union. In the fourth week, fibrous cells and chondrocytes were found to grow into the colloid and surround it at the 6th week. The adhesive material was degraded and gradually absorbed at the 8th week. Chondrification was observed. CONCLUSIONS: Two weeks after fixation for tibial fracture in rabbits, octyl-a-cyanoacrylate begins in vivo degradation. Chondrocytes and fibrocytes gradually grow into the degradation area and surround the adhesive material, which broke into pieces at 8 weeks. Complete degradation and disappearance of the adhesive material is present between 10 and 12 weeks. No barrier effect hampering fracture healing is noted.

Observation and establishment of an animal model of tractive spinal cord injury in rats.

OBJECTIVE: To establish an animal model of tractive spinal cord injury in rats in order to investigate its pathophysiological changes and clinical significance. METHODS: T(12)-L(3) spines were tracted longitudinally with a special spinal retractor that was put on the proccessus transverses of T(12)-L(3) vertebrae of the rat after exposing T(13)-L(2) spinal cord via dual laminectomy. At the same tine, the spinal cord function was monitored by cortical somatosensory evoked potential (CSEP). Rats were randomly divided into four groups according to the amplitude of CSEP P(1)-N(1) wave, the amount of the decreasing P(1)-N(1) wave was 30% (the 30% group), 50% (the 50% group) and 70% (the 70% group), respectively. After traction, the changes of the neural behavioral function in rats were observed and the morphological structure of the spinal cord was analyzed quantitatively with image analysis system of computer. RESULTS: With traction of spine, compared with the control group, the 30% group had no marked difference in combined behavioral score (CBS), neuron count, section area of neuron and Nissl body density, but the 50% and 70% groups had marked difference (P<0.01). Light microscope showed that the neuron volume was slightly small and the Nissl body was reduced lightly in the 30% group; the neuron space was enlarged and the neuron was degenerative, reductive, and dissolved, and the spinal cord structure was destroyed in the 50% and 70% groups. CONCLUSIONS: The animal model of tractive spinal cord injury in rats is a reproducible, graded and clinic mimic. The model in this article provides a valuable assistance in further understanding etiopathology and screening effective measures of therapy and prophylaxis of the injury.

[Biomechanical study of medical hard tissue adhesive bonding butterfly fracture fragment in middle part of fresh human tibia].

A medical hard tissue adhesive, octyl-a-cyanoacrylate, was tested in 6 fresh human tibiae. A 90 degrees butter-fly fracture fragment was made in the middle part of tibia by bandsaw. The compressive stress, torsional stress and angular deflection were assessed before and after osteoectomy respectively. After adhesive bonding, the compressive stress, torsional stress and angular deflection were tested again. The butterfly fracture fagment decreased the bending strength, torsion strength, yielding strength of tibia bone. In torsion test, the torque of tibia before osteoectomy is greater than bonded tibia, the bonded tibia is greater than that of the unbonded tibia. In compression test, before adhesive bonding broken, the compressive curve slope of tibia before osteoectomy is greater than that of bonded tibia, the bonded tibia is greater than that of the unbonded tibia. In angular deflection test before adhesive bonding of broken,the curve slope of tibia before osteoectomy is not different from that of bonded tibia (P>0.05), the slope the bonded tibia is greater than the slope of unbonded tibia(P<0.05). The elastic modulus, rigidity coefficient and moment of area inertia show no statistical difference between the bonded tibia and intact tibia. The used of medical hard tissue adhesive to bond the fracture fragment could improve the bending strength, torsion strength, yielding strength of tibia bone. In operation, it can reduce the soft tissue injury when the fracture fragment is being fixed, and this will benefit bone healing.