The traditional treatment of malignant bone tumors is mainly amputation or joint dissection, and the high disability rate is the characteristic of malignant bone tumor treatment. With the continuous progress of malignant bone tumor treatment and the development of related disciplines, especially the clinical application of adjuvant chemotherapy and neoadjuvant chemotherapy, various limb-preserving surgeries have gradually replaced traditional amputation or joint dissection, however, due to the high surgical technology required for limb-preserving surgery of bone tumor, it is often caused by improper operation or unreasonable surgical design, resulting in tumor recurrence, incision non-healing or secondary infection, tumor prosthesis loosening or sinking and other complications. Therefore, the high complication rate and failure rate of limb preservation surgery is one of the difficulties of limb preservation surgery for malignant bone tumors; in addition, osteosarcoma occurs in adolescents and children, and the epiphysis and epiphyseal plate required for bone growth must be removed in the usual limb preservation surgery, resulting in unequal limb length after surgery. How to preserve the epiphysis of pediatric patients and ensure the continued growth of the limb after surgery without violating the principles of tumor treatment has become a difficult issue in the treatment of pediatric malignant bone tumors. Therefore, the current treatment concept of malignant bone tumors is to expand the indications for limb preservation surgery, to preserve healthy tissues as much as possible to reconstruct limb functions, to reduce the recurrence and metastasis rates of tumors after surgery, to reduce the occurrence of postoperative complications, and to achieve the treatment purpose of prolonging life and preserving limbs with better functions. Since 1994, our hospital has performed various limb preservation surgeries on 217 patients with malignant bone tumors. The corresponding clinical research has been conducted for the problems existing in the treatment of limb preservation in malignant bone tumors in China, and satisfactory treatment results have been achieved. The results are as follows: Yu Xiuchun, Department of Orthopedic Surgery, General Hospital of Jinan Military Region
General information
Since 1991, 217 patients with malignant bone tumors have undergone various limb-preserving surgeries in our hospital. There were 113 male cases and 104 female cases. The average age of the patients was 26.4 years old, ranging from 5 to 89 years old. All diagnoses were histologically confirmed, including 104 cases of osteosarcoma, 26 cases of Ewing’s sarcoma, 25 cases of chondrosarcoma, 14 cases of malignant fibrous histiocytoma, 8 cases of fibrosarcoma of bone, 40 cases of giant cell tumor of bone (grade II-III), and 45 cases of combined pathological fracture.
Surgical methods and number of cases
There were 107 cases of lumpectomy for artificial joint replacement (1 case of artificial total femur replacement), 65 cases of lumpectomy for inactivation and reimplantation (6 cases of inactivation and reimplantation with preservation of epiphysis), 32 cases of extended tumor resection for autologous bone grafting (9 cases of ipsilateral clavicle reversal for humerus), and 13 cases of extended tumor resection alone.
Follow-up method and number of cases
All patients in this group were followed up by outpatient follow-up. Hematological examinations, imaging examinations of the chest and surgical site, and evaluation of limb functions were routinely performed during the follow-up visits, and corresponding treatment or rehabilitation recommendations were made according to the patients’ examination results. Patients are generally required to be reviewed monthly within six months after surgery, every three months after six months, every six months after two years, and annually after five years.
Results
The group lost 41 cases, 176 cases (including 90 cases of osteosarcoma, 40 cases of giant cell tumor of bone, 23 cases of chondrosarcoma, 14 cases of Ewing’s sarcoma, 5 cases of malignant fibrous histiocytoma, and 4 cases of fibrosarcoma of bone) were followed up for six months to 12 years. 16 cases had delayed healing of the incision during the follow-up period, 1 case gave up treatment, and 15 cases were repaired by advancing the flap and muscle flap transfer, respectively, 9 of which The incision was healed in 9 cases, 5 cases were amputated due to recurrent incisional oozing and infection, and 1 case was due to rejection after allograft bone grafting, and the incision was healed after removal of allograft bone. There were 19 cases of recurrence, with a recurrence rate of 10.8%; 6 cases had enlarged resection of recurrent tumors and 1 case had amputation due to recurrence 4 years after reoperation; 13 cases had amputation due to unconditional limb preservation. There was one case of amputation due to joint dislocation caused by limb spasm, which made it difficult to keep the limb. Therefore, the success rate of limb preservation surgery in this group was 88.6%. In addition to recurrence and non-healing incision, there were 2 cases of nerve injury, 4 cases of bone fracture of graft or inactivated bone, 2 cases of prosthesis loosening, 1 case of prosthesis fracture, and 3 cases of joint dislocation (including patients with amputation due to spasm), so the complication rate of this group was 26.7%; 49 cases of lung metastasis, 1 case each of adrenal, soft tissue, and sacral metastasis occurred during the follow-up period, and 41 cases of death (including During the follow-up period, there were 49 cases of pulmonary metastasis, 1 case each of adrenal, soft tissue and sacral metastasis, 41 cases of death (25 cases of osteosarcoma, 2 cases of giant cell tumor of bone, 2 cases of chondrosarcoma, 8 cases of Ewing’s sarcoma, 2 cases of malignant fibrous histiocytoma and 2 cases of fibrosarcoma of bone), 11 cases of survival with tumor (all patients with osteosarcoma, the longest being 11 years), and the remaining 124 cases without abnormality. The overall survival rate of this group was 71.0%, and the overall tumor-free survival rate was 70.4%; the 2-year survival rate of osteosarcoma was 80.22%, and the 5-year survival rate was 63.79%. Limb function evaluation (excluding patients who died): excellent 38 cases, good 59 cases, acceptable 20 cases, poor 18 cases. The excellent limb function rate was 71.87%, and the satisfactory limb function rate was 86.67%.
Discussion
I. Neoadjuvant chemotherapy and limb-preserving treatment of osteosarcoma
Osteosarcoma is a kind of primary bone tumor with extremely high malignancy. In order to improve its survival rate, foreign scholars have made a lot of work and achieved great achievements. Neoadjuvant chemotherapy, which has been carried out since the early 1970s, has increased the five-year survival rate of osteosarcoma from 15%-20% in the past to about 80% [4], and on this premise, limb-preserving therapy has replaced amputation as the main treatment method. A very important principle in neoadjuvant chemotherapy is the emphasis on increasing the number and duration of preoperative chemotherapy, which is usually six or more times. Adequate preoperative chemotherapy can eliminate micro metastases as soon as possible and effectively and improve the survival rate; chemotherapy can make tumor necrosis and primary lesions shrink, providing safer margins for limb preservation surgery; it can also preserve the soft tissues of the limbs and facilitate the improvement of limb function after surgery. The effect of preoperative chemotherapy can be evaluated by the calculation of postoperative TCNR and guide postoperative chemotherapy.
Many foreign literatures have demonstrated the important value of preoperative chemotherapy in improving the success rate of limb preservation for osteosarcoma. In China, there are few reports on preoperative chemotherapy, and its clinical application is not popular and standardized, and there are few chemotherapy regimens supported by clinical data and data. In this regard, based on the review of foreign literature and domestic recommended regimens [4], we applied the MMIA regimen consisting of HDMTX, ADR, and IFO to the preoperative chemotherapy of osteosarcoma, which strictly followed the principles of neoadjuvant chemotherapy and dose intensity, increased the dose of ADR, and raised IFO to preoperative application. Through clinical application, MMIA is considered an effective and feasible chemotherapy regimen that can expand the indication for limb preservation in osteosarcoma without increasing postoperative complications. In our clinical application, we found that pain was relieved to different degrees after chemotherapy, and after the end of preoperative chemotherapy, 87.5% of the pain disappeared without nocturnal pain and the mass was significantly reduced; AKP and LDH showed a significant trend of decrease after chemotherapy. The imaging examination showed that the tumor boundary was clear, osteosclerosis and calcification increased, and soft tissue swelling disappeared after chemotherapy; the TCNR of postoperative specimens was calculated, and it was found that the TCNR of grade IV-III accounted for 68.8%; all patients had complications such as digestive system, hematological system, hair loss, etc., but they could be relieved after symptomatic treatment, and no one discontinued chemotherapy due to serious complications; preoperative Preoperative chemotherapy did not affect postoperative incisional healing; preoperative chemotherapy can expand the indications for limb preservation surgery and improve the success rate of limb preservation surgery: six pediatric patients in the chemotherapy group had significant tumor shrinkage after preoperative chemotherapy, and the epiphysis was not invaded, so we completed inactivated reimplantation with preserved epiphysis under the premise of effective preoperative chemotherapy, and the current follow-up is up to 48 months, with ideal recovery of joint function; in addition, one case of iliac bone osteosarcoma was treated with iliac bone tumor resection after chemotherapy. The tumor was found to be very limited with clear borders, and the pelvic ring was reconstructed with fibula after complete resection of the tumor, which has been followed up for 30 months without any abnormality. The recurrence rate of the preoperative chemotherapy group was found to be significantly lower than that of the non-preoperative chemotherapy group at follow-up (p<0.05). Therefore, we believe that preoperative chemotherapy is of great importance for osteosarcoma planned for limb-preserving treatment.
II. Osteosarcoma invading the epiphysis and preservation of the epiphysis for limb preservation
It has long been believed that the epiphyseal plate is a natural barrier to prevent osteosarcoma invasion, but recent studies have proven this view to be wrong, and it has also been found that in about 10-30% of patients diagnosed with osteosarcoma, the epiphyseal plate is not invaded [2][3][4], especially the application of MR in orthopedic clinics has provided a reliable and non-invasive examination method to clarify whether osteosarcoma invades the epiphysis through the epiphyseal plate. San Julian [3] et al. analyzed 65 cases of osteosarcoma of the epiphysis less than 16 years of age and found that MR had an accuracy of 90.3% and a sensitivity of 100% in diagnosing whether osteosarcoma invaded the epiphysis. Norton’s study demonstrated the accuracy of MR to be 100%[2] .
Epiphysis-preserving limb-sparing surgery is a new approach for the treatment of osteosarcoma in children, which aims to reduce the occurrence of surgical complications, avoid bilateral postoperative limb inequality, and improve limb function in postoperative patients without increasing the local recurrence rate [3] [7]. At present, most scholars believe that it is crucial to strictly grasp the indications for surgery, otherwise it will lead to the development of disastrous consequences [1]. The indications for preserving the epiphysis for limb preservation are generally considered to be [3] [4] [5]: ① the tumor must be located in the epiphysis of the stem bone and the epiphyseal plate has not yet closed. (ii) It must be clear before surgery that the osteosarcoma has not crossed the epiphyseal plate and invaded the epiphysis. (iii) The procedure must be performed strictly following the treatment principles of neoadjuvant chemotherapy and under the protection of effective high-dose chemotherapy. In six patients with osteosarcoma, we applied two courses of preoperative chemotherapy with MMIA. After chemotherapy, the pain disappeared, the local masses shrank significantly, AKP and LDH decreased significantly to normal levels, and radiographs and MR showed clear tumor margins, significant sclerosis and ossification, intact epiphyseal plates, and no epiphyseal erosion, and the operation with preservation of the epiphysis was performed with no recurrence in 12-48 months of follow-up. Therefore, it is important to emphasize the importance of effective preoperative chemotherapy in this procedure.
One is the preoperative lengthening of the epiphysis to create a wide band of new bone between the tumor and the epiphysis, as described by Caradell [5], followed by a limb-sparing procedure after chemotherapy, in which the tumor and new bone are removed while the epiphysis is preserved, and the bone defect is repaired with allograft bone when the cut edge is histologically confirmed to be free of tumor cells. The other method is the one introduced by Manfrini [4], in which the tumor is removed and the epiphysis is preserved by applying fluoroscopic techniques to prove the absence of tumor cells at the resection site, and the defect is repaired with allograft bone or autologous bone, and the epiphysis is fixed to the allograft bone with screws.Tsuchiya [7] et al. combined the above methods in the clinical treatment process by first removing the tumor, temporarily shortening the limb, and then lengthening the limb. . Based on the application of alcohol to inactivate the tumor segment bone to repair the tumor bone defect, we applied this method to preserve the epiphysis in limb preservation surgery, and therefore named the procedure as inactivated reimplantation with preservation of the epiphysis. To ensure complete removal of the tumor during the procedure, a C-arm X-ray machine was used to determine the site of osteotomy while strictly following the indications for the procedure, and the absence of tumor cells at the cut edge was confirmed by postoperative pathological histology. Compared with other methods, this procedure has the advantages of easy operation, good match between inactivated bone and bone at the replantation site, no rejection reaction, fast bone healing, and low price, etc. Through clinical application, it is considered a feasible treatment method.
Manfrini [4] et al. found that a 5-mm-thick epiphysis could continue to grow until skeletal maturity after long-term observation of six cases of proximal tibial osteosarcoma; the patients’ height increased by 22 cm on average during the follow-up period, and the affected limb was 2.2 cm shorter on average compared with the healthy side （The sagittal and transverse diameters of the proximal tibial epiphysis were increased, but slightly smaller than the healthy side; the morphology of the distal femur was slightly larger than the healthy side; the function of the affected knee was restored to 95% of normal, and there was no joint instability or anterior cruciate ligament There was no instability or laxity of the ACL. In addition, he found that the screws used to fix the epiphysis did not affect the growth of the epiphysis. We have also used screws to fix the epiphysis to the inactivated bone during surgery, and recent observations have shown that the screws do not affect the function of the limb, and that care should be taken to screw the screws into the epiphysis during surgery or to cut the articular cartilage a little before screwing the screws to allow screwing.
Through the clinical treatment of pediatric osteosarcoma patients, recent follow-up and review of the literature, we believe that inactivated reimplantation with preservation of the epiphysis under the protection of effective high-dose chemotherapy is a feasible method for the treatment of pediatric osteosarcoma, which preserves the main structures of the joint and the epiphysis, thus laying the foundation for improving joint function and solving the problem of postoperative limb equinus, and the long-term efficacy needs further increase in the number of cases and observation.
Medial gastrocnemius muscle flap and incision healing problem
The surgical treatment of malignant bone tumors in the 1980s has undergone a fundamental transformation, especially the continuous development of neoadjuvant chemotherapy, which makes limb preservation treatment possible. Due to the increasing application of prosthesis and allogeneic bone graft in limb preservation surgery for malignant bone tumors, the soft tissue coverage technique has been put forward with higher requirements. Postoperative incision healing is an important factor affecting the overall treatment of malignant bone tumors, because both postoperative radiotherapy and chemotherapy must be based on the premise of good incision healing. In the past, large soft tissue defects often required multiple surgeries to heal, and there was also the possibility of incisional dehiscence or infection. With the development of microsurgery, healthy tissue can be covered by transferring or rotating or applying free tissue to the tissue defect. A tipped muscle or myocutaneous flap can not only achieve the purpose of covering the defect, but also improve local blood circulation, which has clinical significance for postoperative radiotherapy and chemotherapy in patients with malignant bone tumor conserving surgery.
Winberg [3] performed muscle flap transplantation in 26 patients after resection of giant malignant tumors around the knee joint, and all the flaps survived with excellent limb function during the follow-up period of 3-7 years, which proved that the transplantation of tipped muscle flap and myocutaneous flap is of great value to improve the success rate of limb preservation for malignant bone tumors. We [4] analyzed 30 patients with complications of limb preservation surgery for malignant bone tumors and found that 7 patients had incisional healing problems and 6 cases occurred in the upper tibia, which were related to the relative weakness of soft tissues and the lack of blood flow in this area, so it is necessary to perform medial gastrocnemius head transposition at the same time when performing limb preservation surgery for malignant bone tumors in the upper tibia to cover the prosthesis and improve local blood flow.
Jeon [5] and Malawer [6] reported the application of gastrocnemius medial head transfer to cover soft tissue defects after limb-sparing surgery for malignant bone tumors of the upper tibia and simultaneous repair of knee extension devices, which was found to significantly reduce wound complications, increase knee stability with patellar ligament biologic connection, improve joint function, and receive good therapeutic results, and concluded that medial gastrocnemius head transfer in one stage has operational Simple, less complications, suitable muscle belly size, improved local tumor control, and the function of the donor area is not affected, especially for those who use chemotherapy after artificial joint replacement is more suitable. In our hospital, we have performed anterior transposition of the medial head of the gastrocnemius muscle in one phase along with limb preservation surgery for 20 cases of malignant bone tumors of the upper tibia since 1996, and found that except for one case of postoperative skin necrosis of the anterior tibia, which was healed by free skin grafting after debridement, the incisions of the remaining 19 cases healed in one phase after surgery. Therefore, we believe that medial gastrocnemius head advancement should be an important part of limb preservation surgery for malignant bone tumors of the upper tibia, which provides a soft tissue condition with good blood flow for subsequent treatment such as skin grafting even if the skin has problems after surgery.
IV. Ipsilateral clavicle reversal to repair tumor bone defect of proximal humerus
The proximal humerus is an important component of the shoulder joint, and is also a common and favored site for bone tumors. There are many methods to repair bone defects after resection of tumor segment, and it is difficult to evaluate one method as the best choice. However, there are many complications and problems during clinical treatment [2], especially the function of the shoulder joint.
In 1992, Winkelmann et al [1] were the first to report the application of the ipsilateral clavicle to repair a tumorous bone defect of the proximal humerus. in 1996, Wozniak et al [3] applied this method to treat three cases of bone tumors of the proximal humerus (two osteosarcomas and one Ewing sarcoma), and the length of the resected proximal humerus was 12-14 cm. with a follow-up of 10 months -Ozaki et al [4] reported a case of osteosarcoma of the proximal humerus treated with a combination of a turned clavicle and a tipped fibula, with intraoperative preservation of the soft tissue and periosteum around the clavicle, and good bone healing at 3 months postoperatively, with a functional shoulder score of 26 points. Yan Shigui et al [5] applied this method to treat 11 patients (6 with free clavicle graft and 5 with periosteal clavicle graft), among which 3 cases fixed the clavicle at the scaphoid gland. It was found that the bone joints healed in all 11 cases, with a mean healing time of 11.2 weeks for the free clavicle and 7.1 weeks for the clavicle with periosteum, and one postoperative fracture of the clavicle with periosteum. The function of the shoulder joint was poor after surgery, and the function of the hand, forearm and elbow joints was basically normal. We applied ipsilateral free clavicle to repair 6 cases of tumorigenic superior humeral defects, and all patients completed the operation successfully with an operative time of 2~3 hours and intraoperative blood transfusion of 400 ml~800 ml. 5 patients were followed up for 6~40 months. 1 case died and 1 patient with giant cell tumor of bone had a fracture of the overturned clavicle caused by an accidental fall 8 months after surgery, and the bone healed after 4 months of external fixation. The other three cases showed good bone healing between the grafted clavicle and the humerus, and two cases showed clavicle thickening. At follow-up, all patients maintained good function of the elbow, wrist, and hand joints. The shoulder joint maintained some forward flexion and posterior extension function with limited abduction function. Therefore, we believe that this method is a feasible procedure for repairing tumorigenic bone defects of the proximal humerus. The procedure reduces the number of surgical operations and can be performed in the same enlarged field, especially in patients with unclosed epiphysis who cannot repair the proximal humeral bone defect by other methods; in addition, the ipsilateral clavicle graft does not increase the financial burden of the patient, which is one of the reasons why patients are willing to accept this procedure. In the process of clinical application, we also found that the turned clavicle can make the shoulder joint slightly abducted naturally, avoiding the close contact between the upper limb and the chest wall after surgery. Some scholars have found that the clavicle can be dislocated by periosteal peeling and the periosteal canal can be left after the clavicle is displaced, and a slender clavicle can be regenerated after a few days.
Reversal of the clavicle fracture is the most common complication of this procedure and has been reported in all cases seen in the literature. It has been suggested that preservation of the clavicle periosteum may be effective in preventing fractures while improving bone healing rates. However, the periosteum was preserved in all the patients with clavicle fractures reported by Ozaki and Yan Shigui et al. Our experience is that increasing the amount of bone graft and prolonging the duration of external fixation at the turned clavicle and humeral stump can promote bone healing and prevent fractures.
V. The value of cortical external bone bridge in oncological prosthesis replacement
In recent years, there has been a fundamental change in the surgical treatment of malignant bone tumors, so that limb preservation surgery has become the main development direction of surgical treatment of malignant bone tumors, and amputation is relatively rare. In particular, with the close cooperation of basic research and bioengineering, it is possible for clinicians to preserve the function of the limb while maximizing the resection of the tumor. Clinical findings have demonstrated that although there are many ways to repair tumorigenic bone defects, tumorigenic prosthesis replacement is the most desirable option as far as function is concerned. It has been suggested that tumorigenic prostheses can produce wear debris that can lead to loosening of the prosthesis and subsequent surgical failure. Therefore, the prevention of prosthesis loosening due to wear debris from tumorigenic prostheses is a current clinical research priority [1]. For this reason, we have applied the method of extracortical bone bridging to prevent postoperative loosening of tumorigenic prostheses since 1997.
To avoid loosening of the prosthesis, a variety of methods can be used to form an extracortical bridge between the bone and the prosthesis to transfer the stress between the bone and prosthetic contact and to protect the bone cement from the debris generated by joint wear. In an experiment on dogs, Virolainen [5] et al. wrapped autologous bone around the femur in contact with the prosthesis and used no bone implant as a control; it was found that the biomechanical indexes on the experimental side were significantly higher than those on the control side, and he concluded that without bone implant, only a small amount of bone bridge was formed between the prosthesis and the bone. He concluded that without bone grafting, only a small amount of bone bridge was formed between the prosthesis and the bone, while bone grafting could obtain the ideal extra-cortical bone bridge, which obviously increased the stability of the prosthesis. Another way to prevent the occurrence of aseptic loosening of the prosthesis is to use a prosthesis covered with some biologic or nonbiologic material. The earliest application was hydroxyapatite covered prosthesis, which has a similar crystal structure to bone and can be used as a biologically compatible scaffold to allow new bone to grow in and form a new bone to prosthesis bond. They measured the length of new bone formation and the width of the permeable radiolucency between the newly formed bone and the inserted rod, and the average follow-up was 14 months after surgery. In 21 of 27 cases with distal femoral prosthesis, new bone grew in; in cases with more than 2 years of follow-up, imaging showed bone remodeling and trabecular formation between the hydroxyapatite grooves; bone remodeling indicates that the new bone formed was bonded to the surface of the prosthesis and both were subjected to simultaneous stress [11].
Since 1997, we have applied a tumor-type prosthesis with aluminum oxide sprayed on the stalk and intramedullary pin surface by a special process, and experiments have demonstrated that the aluminum oxide coated prosthesis is tightly bonded to the bone and that bone tissue can grow into the micro-pores on the surface of the coating, indicating that this type of prosthesis has an induced bone formation effect [6]. At the same time, the normal bone excised during surgery was constructed into bone strips and tied at the prosthesis and the osteotomy end to facilitate the formation of extra-cortical bone bridges and prevent the prosthesis from loosening. In addition, we found that the formation of the bone bridge was mainly concentrated on the posterior side and both sides of the bone, which may be related to the stress of the limb, therefore, the intraoperative laying of the Therefore, the bone strips should be placed on the posterior and lateral sides of the bone as much as possible. The analysis did not reveal that the formation of extra-cortical bone bridges would affect the function of the affected limb after surgery. The rate of prosthesis loosening in this group was only 5.7%, one case occurred 7 years after surgery, this patient was a giant cell tumor of the lower femur, obvious extra-cortical bone bridge formation was seen after surgery, 6 years after surgery, the limb was found to be shortened, and the X-ray showed a gap between the bone bridge and the prosthesis; 7 years after surgery, a large amount of metal abrasions were found around the prosthesis during revision surgery; the other case was related to repeated oozing of the incision and no extra-cortical bone bridge formation The other case was related to repeated oozing of the incision and the formation of a non-cortical extracortical bone bridge. Therefore, the use of surface coated aluminum oxide prosthesis and intraoperative formation of extra-cortical bone bridges using bone strips are important to prevent postoperative loosening of the prosthesis. It should be noted that the intraoperative binding of the bone strips should be done before the prosthesis is attached. Because this method is simple, easy to master, does not increase surgical trauma, and has reliable clinical results, it has some clinical application value.