Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The application of neoadjuvant chemotherapy has improved the 5-year survival rate of osteosarcoma patients, and limb-preserving treatment has become the mainstream of surgical treatment. Children and adolescents are in the growth and development period, and traditional limb-preserving treatment is bound to bring about limb inequality. Limb preservation surgery with preservation of epiphysis can preserve the patient’s growth plate and effectively prevent postoperative limb inequality, but only if the epiphysis is not invaded and the tumor can be completely removed; extendable prosthesis can solve the problem of limb inequality after limb preservation in children; bone graft with vascular tip provides the basis for early healing of bone defects after resection of osteosarcoma segments; for children with epiphysis close to closure, the application of allogeneic bone graft can also be considered Tumor-based artificial joints can also be used for limb-preserving treatment in older children.
At present, the limb preservation treatment of osteosarcoma in children and adolescents is still faced with such and such problems. The limb preservation surgery that can extend the prosthesis and preserve the epiphysis is currently expensive and technically complicated, and for adolescent patients whose epiphysis is expected to close soon, traditional prosthesis, free fibula with vascular tip, and allograft bone graft can also be used as options.
Osteosarcoma is a malignant tumor of bone origin that occurs in children and adolescents and is the second cause of cancer-related death in children and adolescents, often with fatal pulmonary metastases, and these patients have a low survival rate despite surgery, chemotherapy, or/and radiation therapy. Typical osteosarcoma accounts for 0.2% of all tumors, with an annual incidence of less than 3% per million population, and is the most common primary malignant bone tumor of childhood and adolescence. patient survival.
In bone tumor centers, surgery combined with preoperative and postoperative chemotherapy can cure 60% to 70% of patients with osteosarcoma, with a surgical limb preservation rate of more than 90% and good limb function after limb preservation surgery; statistics found that 78% of patients had satisfactory limb function after limb preservation surgery [7 ,8], and limb preservation therapy for osteosarcoma has become the mainstream of treatment. In skeletally immature patients, preserving the epiphysis of the long bones is difficult due to extensive damage to the long bones, and the resulting osteosarcoma resection leads to limb inequality and gait abnormalities [9], which affects normal walking and causes a series of complications such as pelvic tilt, scoliosis, and joint damage due to abnormal stress. it is controversial whether to perform limb-preserving treatment for pediatric malignant bone tumors. according to Grimer, limb-preserving surgery can make The main surgical challenge is limb reconstruction after tumor resection.
Children and adolescents are growing and the growth of the periprosthetic epiphysis accounts for 70% of the developmental length of the lower extremity. Removal of the lower femur or upper tibial epiphyseal plate before the growth spurt (14-16 years for males and 12-14 years for females) results in a loss of approximately 10-16 mm of growth per year. face long term failure and revision. Currently, epiphysis-preserving limb preservation and lengthenable prosthesis have received clinical attention and become a hot spot for research. The suitability of limb preservation depends on the extent of tumor invasion, stage, and response to neoadjuvant chemotherapy.
1.Limb preservation with epiphysis preservation
Epiphysis preservation surgery is to preserve the growth plate of the limb under the premise of complete removal of tumor and reduction of postoperative recurrence rate, so as to avoid unequal limb length caused by tumor removal and minimize the impact on limb length.
San-Julian et al. classified the invasion of bone tumors in children’s epiphysis into 3 types: type I for tumor adjacent to epiphyseal plate and tumor edge >2 cm from epiphyseal plate; type II for tumor distance <2 cm or adjacent to epiphyseal plate; type III for partial contact between epiphyseal plate and tumor and distance >2 cm from subchondral bone of joint end; this type refers to cases with large epiphyseal volume. Type I is the absolute indication for epiphysis-preserving limb-preserving surgery, and types II and III are relative indications; previously, it was thought that the epiphyseal plate had a barrier effect on tumor invasion, but after the study of osteosarcoma MRI, it was found that the tumor could cross the epiphyseal plate and invade the epiphysis or even the joint, and Jesus-Garcia et al. found through a study of 25 cases (14 males and 11 females) of children aged 4 to 17 years with epiphyseal plate unclosed osteosarcoma that Radiological examination only showed that the tumor infiltrated the epiphyseal plate in 11 cases, and histological examination showed that the tumor passed through the epiphyseal plate in 21 cases, which proved that the epiphyseal plate is not a barrier to prevent the growth of tumor, and emphasized that caution should be exercised in preserving the epiphyseal plate during limb preservation surgery.
2. Extendable prosthesis
Primary bone tumors in children require complete resection of the tumor and joint reconstruction, and in order to keep the tumor under control, it often leads to growth plate damage, which results in limb inequality, and extendable prosthesis is an option for limb preservation technique [19].Saravanan et al [20] concluded that it is feasible to apply extendable prosthesis for limb preservation treatment to repair primary bone tumors in children.
Although some authors reported good short-term results with the application of extendable prostheses for the treatment of bone tumors in children, the incidence of complications increases with time. Gitelis et al. reported that of 18 patients with SEER (Stanmore extensible endoprosthetic replacement) series prostheses, 7 required revision surgery. Among them, two had fractures at the extension site of the prosthesis, one had a fracture of the distal femur, two had fractures at the stem of the prosthesis, one had aseptic loosening, and one had deep infection.
Pediatric and adolescent patients who underwent reconstruction with a proximal femoral extendable prosthesis can develop hip dislocation due to acetabular dysplasia, causing pain and limited motion, and this subluxation cannot be corrected by acetabular osteotomy and can only be replaced with an acetabular replacement after skeletal maturity.Futani et al [32] concluded that in skeletally immature children with malignant bone tumors at the end of the femur artificial prosthesis and biologic reconstruction provided a limb preservation as good functional outcome, despite the problems of high revision with limb lengthening. The main complications of lengthenable prostheses are infection, postoperative arterial embolism, prosthesis fracture, aseptic loosening, lengthening failure, subsidence, and damage to internal components. Prosthesis replacement, despite its more complications and the need for multiple surgeries, is more acceptable mentally and cosmetically to the child and family, and the quality of life of the child is better.
3.Bone graft with vascular tip
Modern repair and reconstruction techniques can avoid most osteoarticular tumor amputations, and free fibula with vascularization is used to repair long bone defects as the first choice in limb preservation surgery, Chen et al [34] used free fibula with vascularization to reconstruct complex long bone defects after tumor resection, with low infection rate, high bone healing rate and good function compared with traditional allograft, Gebert et al used fibula graft with vascularization as a biologic reconstruction to repair a large segmental bone defect with 31% hypertrophy of the fibula, and the main complications were fracture, pseudarthrosis, delayed healing of the incision, and transient nerve injury, with acceptable complication and reoperation rates.
Innocenti et al. reported that a fibular graft with a vascularized tip including the epiphysis and epiphysis could replace a bone defect of the proximal humerus or distal radius in pediatric patients, allowing continued growth of the grafted epiphysis.Noguchi et al [37] applied a free fibular graft with a vascularized tip combined with autologous bone baroreflexion to reconstruct a bone defect after osteosarcoma resection, based on the principle that the inactivated bone provided mechanical strength and the fibular bone with a vascularized tip provided healing. The main complications are fracture, infection, pseudarthrosis, and bone resorption.
4. Allogeneic bone grafting
Allogeneic frozen bone is used to repair bone defects after amputation of the tumor segment and to reconstruct joint function, which can provide normal morphology of the articular surface and allow reattachment of muscles, tendons, and ligaments, and more importantly, the allogeneic bone structure becomes a matrix for autologous bone to grow into, and through improvements in soft tissue coverage and internal fixation, joint complications can be controlled at an acceptable level, and the selection of precisely sized allogeneic bone to reconstruct Joint force lines can avoid eventual joint replacement and can achieve good long-term clinical results, but the activation of the replacement process after transplantation is slow, and it is difficult to achieve complete replacement of large segments of allograft cortical bone.
The joint surface can be degenerated and resorbed after surgery, the articular cartilage is lifeless and cannot be regenerated, the strength of the bone and the healing with natural bone are limited, while the allograft bone joints are mostly adult bones, which are difficult to match with children’s joints, and there are postoperative complications such as infection, non-healing, and fracture, and the incidence of infection after reconstruction with allograft bone graft in patients with osteosarcoma has been reported in the literature to be 10%-15% [39], while structural allograft There is a risk of microfracture of structural allograft bone, which can cause large structural collapse if the patient is significantly weight-bearing. The main problem facing allograft bone grafting in pediatric and adolescent patients is still bilateral limb length inequality, and allograft bone grafting can also be chosen to reconstruct limb function for patients whose epiphysis is close to the age of closure and the expected future limb length difference is less than 3 cm, and limb inequality can be corrected by wearing orthopedic shoes.
5.Tumor type artificial prosthesis
Tumor-type artificial prosthesis is used for reconstruction of osteoarthritic defects, and the customized phased prosthesis has a standardized component system, so that the operator can choose the right size component according to the specific situation without having to be concerned about the extent of bone tumor resection, and the prosthesis can be divided into distal femur type and proximal tibia type, which has the advantages of good stability and early weight-bearing after surgery; Sharma et al. used a cemented rotating type with microporous surface for 77 cases Sharma et al. followed up the clinical outcomes of 77 cases of bone defects after distal femoral tumor resection reconstructed with cemented rotary hinge-type prosthesis with microporous surface. The average follow-up time was 52 months and the longest follow-up time was 157 months, and the 5-year utilization rate of the artificial joint was 84% and the 10-year utilization rate was 79%.
Flint et al. reported 44 patients with proximal tibial malunion replaced with a surface porous prosthesis with a mean follow-up of 60 months and no case of aseptic loosening of the prosthesis; Chao et al [42] followed 43 patients with extracortical bone bridge technique with a mean follow-up of 9.7 years and only one case of aseptic loosening of the prosthesis without osteolysis. Tumor-based prosthesis became the main choice of limb preservation treatment for patients with osteosarcoma of the limb, and for adolescent patients with osteosarcoma whose epiphyses are close to the age of epiphyseal closure, artificial prosthesis can also be chosen to reconstruct limb function.
Modern orthopaedic oncology surgery aims at ideal tumor resection as well as preservation of limb function and prolonged survival, and modern reconstructive techniques can avoid amputation in most patients with osteomyosarcoma. The development of limb preservation technology that can extend prosthesis and preserve epiphysis provides new hope for limb preservation in children and adolescents. The choice of limb preservation method should be carefully selected according to the specific situation of each patient, and children and adolescents are different from adults. Otherwise, it will bring endless troubles to children’s future life and put doctors in a dilemma.
It should also be clear that currently extendable prostheses are expensive, postoperative complications are essentially the same as those of joint replacement after general tumor resection, complex internal components increase the likelihood of internal component failure, and revision surgery is even more expensive. It is also important to emphasize the importance of chemotherapy in the treatment of osteosarcoma, and that modern chemotherapy regimens can enable patients with highly limbic osteosarcoma to preserve their limbs while prolonging their survival. Patients with osteosarcoma often develop fatal lung metastases, and survival rates remain low despite surgery, chemotherapy, and/or radiation therapy, so it is necessary to explore new effective treatments as well as other therapies. New drugs as well as molecularly targeted therapies are being investigated, and it is believed that with the advancement of techniques and technology, the survival of patients with osteosarcoma will be improved and the rapid development of limb preservation therapy for children and adolescents will be promoted.