In the past 30 years due to the use of neoadjuvant chemotherapy and adjuvant chemotherapy, the survival rate of patients with osteosarcoma has dramatically improved. 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; statistics found that 78% of patients had satisfactory limb function after limb preservation surgery. The purpose of treatment has shifted from saving the patient’s life to limb preservation treatment and preserving the function of the limb, and limb preservation treatment for osteosarcoma has become the mainstream of treatment.
1. Indications and contraindications for limb preservation.
The indications for limb preservation in osteosarcoma are.
①The patient’s epiphyseal growth and development has basically matured, and the age is preferably >15 years old.
②Enneking surgical stage IIA, for stage IIB patients, if the response to chemotherapy is good, it can also be considered appropriately;
③No major vascular nerve involvement, pathological fracture, local infection and diffuse skin infiltration;
④Able to remove the tumor completely outside the tumor;
⑤ It is expected that the function of the preserved limb is better than that of the prosthesis;
(6) The local recurrence rate of limb preservation surgery will not be higher than amputation, and the expected survival rate will not be lower than amputation;
(7) The patient and family members have the desire to preserve the limb.
Currently, limb-preserving surgery has become the main choice of surgical treatment for osteosarcoma of the limb. With the continuous improvement and development of treatment methods, the scope of limb preservation surgery is expanding. Traditionally, it is believed that Enneking surgical stage IIA is the best indication for limb preservation surgery, but in fact, most clinical patients are in stage IIB. If they are sensitive to preoperative chemotherapy, the local boundary of the tumor becomes clear and the tumor shrinks significantly after chemotherapy, limb preservation therapy is also feasible.
2.Limb preservation methods
2.1 Tumor segment inactivation and reimplantation
Suk et al [5] put the resected tumor bone into saline at 65oC for 30 min and reconstructed the affected limb with bone cement and metal prosthesis after inactivation, and the result was that 2 cases of inactivated bone fracture occurred among 12 cases, only 1 case of bone discomfort occurred, and there was no local recurrence. Soaked the tumor bone in saline at 60oC for 30 min and inactivated the bone fracture in 3 out of 25 patients and bone resorption in 2 cases without local recurrence.
Inactivated tumor segments have been replaced by tumor-based prosthetic joints, which have been developed subsequently, because of the problems in wound healing, incision infection, bone graft healing, bone fracture, arthritis, bone resorption, and joint function.
2.2 Homogeneous composite prosthesis
Allogeneic frozen bone is used to repair bone defects after tumor segment amputation and reconstruct joint function, but the activation of the replacement process after transplantation is slow, and it is difficult to achieve complete replacement of large segments of allogeneic cortical bone, and postoperative joint surface degeneration and resorption can occur, and the strength of the bone and healing with natural bone is limited, so some scholars advocate the use of allogeneic composite prosthesis replacement, which usually consists of the distal end of the donor femur or The donor proximal tibia is usually cemented together with a rod-like stem of the artificial prosthesis, and the entire composite prosthesis is stabilized mainly by the medullary stem. In accordance with the biomechanical requirements of the artificial prosthesis, the ratio of the length of the weight-bearing stem inserted into the medullary cavity to the axial length of the allograft bone should be 0.8 to 1.0.
The advantages of homogeneous bone composite prosthesis are that the homogeneous bone has the ability to heal with the host bone, thus reducing the rotational stress at the connection with the prosthesis, and the allogeneous bone can provide good tissue attachment, which is conducive to knee joint stability. Disadvantages include: potential fracture of the homogeneous bone, infection, infectious disease infection, bone discontinuity, deformed healing, and resorption.
2.3 Artificial Prosthesis
Tumor-based artificial prosthesis is used to reconstruct osteoarthritic defects, custom staged prosthesis has a standardized component system, 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, this prosthesis can be divided into distal femur type and proximal tibia type, containing polyethylene tibial platform, extensor device attachment point and other designs, this prosthesis has the advantages of good stability, early postoperative weight bearing; in In the follow-up study of survival, Zeegen et al [9] found in 141 patients with this type of prosthesis that 88% did not require revision at 3 years and 76% at 5 years, and that local tumor recurrence, infection, and loosening were independent risk factors for prosthesis failure.
Malo et al [10] conducted a comparative study between non-cemented fixed hinge prosthesis and cemented rotary hinge prosthesis, where the tumor site was distal femur. 31 patients were implanted with non-cemented fixed hinge prosthesis and 25 patients were implanted with cemented rotary hinge prosthesis with an average follow-up of 34.4 months. The postoperative function was much higher in the cemented rotary hinged prosthesis group than in the non-cemented fixed hinged prosthesis group.
The hinged prosthesis was first used in the limb preservation treatment of malignant bone tumors around the knee joint because of its firm restrictive design, which does not require soft tissue to provide stabilization, but the hinged prosthesis is a completely restrictive prosthesis with limited freedom of movement, high interface stress, and collective susceptibility to complications such as aseptic loosening and fracture, and was replaced by the rotating hinged prosthesis, which has an axial rotation function that reduces motion limitation, while improving the mechanical effect of the extensor device, reducing the stress at the bone-cement-collective interface, reducing the generation of wear particles, and decreasing the rate of aseptic loosening, significantly improving the survival rate and knee function scores.
In terms of survival follow-up studies, Springer et al [11] reported 69 patients treated with a rotating hinge-type prosthesis (75.2 months follow-up), of whom 23 (33%) had at least one complication and 9 knees underwent a second surgery, with the most common complication being deep infection (14.5%), followed by knee extension dysfunction (13%), prosthetic dysfunction (10%), and despite the complications, patient satisfaction rates were generally high (81% more or very satisfied).
Brickees et al [12] followed 110 patients with this prosthesis in a multicenter combined study, showing a 5-year survival rate of 93% and a 10-year survival rate of 88%, with no significant difference in survival rates compared to those of conventional total knee replacement prostheses, in which mechanical factors caused a higher incidence of complications, all of which could be resolved by further surgery. Local recurrence of tumor after surgery often requires amputation, Jeys et al [13] followed up 1261 patients after prosthetic replacement, and 71 of the 112 patients who eventually underwent amputation were because of local recurrence and received amputation 31 months after surgery, and the risk of amputation decreased with time, and was still 10% 5 years after prosthetic replacement surgery.
2.4 Microwave inactivation
Fan et al. pioneered the insertional microwave antenna array-induced high-temperature in situ inactivation therapy for limb malignant bone tumors for limb preservation treatment.Fan et al. performed insertional microwave antenna array-induced high-temperature in situ inactivation therapy for 176 patients with limb malignant bone tumors, and chemotherapy was administered before and after surgery, with a mean follow-up of 49 (24-96) months after surgery and an overall survival rate of 73.9%, which showed that the method can be used as one of the limb preservation methods for malignant tumors of the limbs.
2.5 Bone graft with vascular tip
Chen et al. used free fibula with vascularization to reconstruct a complex long bone defect after tumor resection, with low infection rate, high bone healing rate and good function 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, and the complications and reoperation rate is acceptable.
3.Limb preservation in children.
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 [17], which affects normal walking and causes a series of complications such as pelvic tilt, scoliosis, and joint damage due to abnormal stress, etc. It is controversial whether to perform limb-preserving treatment for pediatric malignant bone tumors.Grimer believes that limb-preserving surgery can enable 85% of pediatric osteosarcoma patients have limb preservation, and the major surgical challenge is post-tumor resection reconstruction. Limb preservation therapy in children is a major challenge in the treatment of bone tumors with limb preservation, and addressing limb inequality after limb preservation surgery has been a hot topic in recent years.
Kumta et al [20] followed up 43 children aged 4 months to 13 years for an average of 6 years, and 81% of them were suitable for limb preservation, and the suitability of limb preservation depended on the extent of tumor invasion, stage, and response to neoadjuvant chemotherapy. In the management of the epiphysis, limb preservation surgery with preservation of the epiphysis has also been carried out. Manfrini et al. concluded that limb preservation with preservation of the epiphysis is feasible if preoperative MR examination does not reveal invasion of the epiphysis, and such patients account for about 10-15% of pediatric osteosarcoma, while Jesus-Garcia et al. found through 25 cases (14 males and 11 females) of children aged 4 to 17 years with epiphyseal plate unclosed osteosarcoma that The study found that radiological examination showed tumor infiltration of the epiphyseal plate in only 11 cases and histological examination showed that the tumor crossed the epiphyseal plate in 21 cases, proving that the epiphyseal plate is not a barrier to prevent tumor growth and emphasizing that caution should be exercised in preserving the epiphyseal plate during limb-preserving surgery.
Tsuchiya et al. concluded that the key to successful epiphyseal preservation surgery is that the length of the limb lesion is within 15 cm and that at least 0.5 cm thick epiphysis is preserved after tumor resection. Complications of epiphysis preservation surgery are mainly infection, graft resorption, fracture and loosening of internal fixation. Among the 20 patients treated by Tsuchiya et al, there were two cases of infection, three cases of graft displacement, one case of common peroneal nerve palsy and one case of graft fracture. The key to the success of epiphysis preservation surgery is to correctly determine the extent of tumor resection and reasonably select the bone defect reconstruction.
In Lewis, according to the characteristics of children’s limb growth, the placement of an adjustable-length prosthesis to repair bone defects after resection of malignant bone tumors in children can prevent the occurrence of unequal limb length in the future.
The indications for lengthenable prosthesis are osteosarcoma or other malignant bone tumors without distant metastases, expected bradykinesia >2 cm, and children aged 5 to 15 years (too young for complications), who can undergo tumor resection prosthesis replacement in one stage. The lengthenable prosthesis is broadly divided into invasive lengthenable prosthesis and non-invasive lengthenable prosthesis, the former requires multiple surgeries to lengthen the prosthesis, the latter such as phenix prosthesis, whose main components include titanium prosthetic stem, composite tube structure, compression spring three parts, the lengthening mechanism of the prosthesis is under the action of the external magnetic field, release the compression spring, relying on its potential energy reserve will be prosthetic stem from the composite tube, so that the prosthesis The length of extension depends on the compliance of soft tissues and the pressure stored in the spring inside the prosthesis, and to avoid nerve and vascular damage, the length of each extension should be less than 2 cm.
Gitelis et al. reported an average follow-up of 24.8 months for 14 patients, with 58 lengthenings of the prosthesis, an average of 8.5 mm per lengthening, and an average lengthening of 38 mm per patient, reaching an average of 83.5% after surgery according to the International Symposiun On Limb Salvage ISOLS0 functional scoring system, with only one lengthening failure and three cases reaching maximum lengthening after lengthening treatment. Neel et al [26] performed a 21.5-month follow-up of 15 children undergoing phenix limb-preserving reconstruction after osteosarcoma resection with a total of 60 lengthenings, averaging 8.5 mm per lengthening, and achieved 90% knee function according to the postoperative bone tumor scoring system.
It has been reported that 25% of lengthenable prostheses require revision after 5 years, with the main reasons for revision being infection, tumor recurrence, prosthetic function failure, and aseptic loosening. In addition, it has been reported that secondary growth plate disruption can occur after limb preservation with extendable prostheses. In the case of the distal femur, for example, prosthesis placement may cause proximal tibial growth plate damage, which in turn has a growth imbalance leading to limb angulation and eventual loosening of the prosthesis.
Futani et al. concluded that in skeletally immature children with malignant bone tumors at the end of the femur artificial prosthesis and biologic reconstruction provided a good functional outcome as limb preservation, despite the problems of high revision with limb lengthening. The main complications of lengthenable prosthesis are infection, postoperative arterial embolism, prosthesis fracture, aseptic loosening, lengthening failure, sinking, and damage to internal components.
5.Postoperative functional evaluation
Osteosarcoma limb preservation treatment is the requirement to preserve the length and function of the postoperative limb, and the establishment of postoperative limb function criteria is an important basis for evaluating limb function, which is widely used in the Musculoskeletal Tumor Society scoring system (MSTS) and the Toronto Extremity Salvage Scores TESS.
The first version of the MSTS in 1987 had 7 assessment factors (pain, mobility, joint stability, strength, deformity, general mobility, and emotional acceptance of surgery), each of which was scored out of 5, and was also classified into 4 grades of excellent, good, moderate, and poor according to certain regulations. 1993, the second version of the MSTS added factors from the patient’s perspective, and the functional assessment criteria in this version were based on the analysis of The whole body factors (pain, functional activity and psychological acceptance) as well as local factors of the upper or lower extremity were established. each of the 6 local factors was divided into 6 grades of 0, 1, 2, 3, 4 and 5 points based on well established scoring criteria.
The TESS is a system for investigating limb function and focuses on self-care and mobility in daily life. There are 30 items in this scoring system, such as the limitation of daily activities, self-care ability, etc. Patients choose the items they think are relevant to complete according to their own judgment, and each item is scored into 6 levels such as 0, 1, 2, 3, 4, 5, etc. Finally, the scores are converted into a percentage system, and higher scores indicate better function.
Limb preservation therapy for osteosarcoma of the limb is based on neoadjuvant chemotherapy and adjuvant chemotherapy, chemotherapy improves the tumor-free survival of patients, and limb preservation therapy improves the quality of life of patients, limb preservation therapy has made great development, but it is not complete, there are such and such problems, and limb preservation in children faces more challenges, I believe that with the improvement of understanding and technology this problem will have a better It is believed that with the improvement of awareness and technology, there will be better solutions for this problem.