Epiphysis preserving limb surgery is a new method proposed in the late 1990s for the treatment of malignant bone tumors in children, aiming to improve the limb function of postoperative children and avoid bilateral limb inequality after surgery without increasing the local recurrence rate. Since January 1999, we have proposed inactivated reimplantation with preservation of the epiphysis based on the experience of alcohol inactivation reimplantation surgery for osteosarcoma in China, and applied it in clinical practice, and achieved satisfactory recent efficacy [1]. However, what is the long-term effect? Whether the original design of the operation is really achieved and what long-term complications exist in the operation are matters of concern. Therefore, we analyzed the clinical data of 5 patients during 5-10 years of follow-up and reviewed the literature to elaborate on these issues. Yu Xiuchun, Department of Orthopedics, Jinan Military General Hospital
Clinical data
I. Case selection criteria and general information: 1. Children with histological confirmation of osteosarcoma by puncture biopsy in our hospital. 2. MR examination before and after chemotherapy confirmed that the osteosarcoma had not penetrated the epiphyseal plate and invaded the epiphysis, i.e., osteosarcoma and epiphyseal MR typing type I and II [2]. 3. distant metastases were ruled out by chest radiograph and CT scan before treatment. 4. 2 courses of chemotherapy were administered before surgery by receiving MMIA or DIA chemotherapy regimen, and surgery was performed 2 weeks later. All children were operated by the authors and were followed up regularly for more than 5 years. A total of 5 patients treated in our hospital from January 1999 to January 2009 met the above criteria.
There was one male and four female cases in this group. The ages ranged from 6 to 14 years, with a mean of 9.2 years. All lesions were located in the distal femur. The duration of the disease was as short as 1 month and as long as 6 months. The MR typing before chemotherapy: 3 cases of type I (Figure 1) and 2 cases of type II (Figure 2). 1 of the 3 cases of type I was combined with pathological fracture. All children in this group were administered according to the chemotherapy plan, and the surgical procedure was an inactivated reimplantation with preservation of the epiphysis, which was performed as previously reported in the literature [1]. The details of the patients are shown in Table 1.
II. Follow-up time and content: All children received regular follow-up. They were reviewed monthly within 6 months after surgery, every 3 months within 2 years, every 6 months after 2-5 years, and annually after 5 years. The periodic examinations mainly excluded local recurrence and metastasis of the tumor, measured the changes of the lower limb length and the mobility of the knee joint, evaluated the limb function of the patients with reference to the MSTS score standard [3], and performed dynamic imaging observation of the healing between the inactivated bone and the amputated end and the epiphysis of the bone, and the condition of the bone quality.
Results
Five patients were followed up for a minimum of 60 months and a maximum of 126 months, with a mean of 82 months. There was no recurrence, metastasis or death during the follow-up period. The function of the affected knee (evaluated at the time of final follow-up) was flexion ≥110º in 3 cases, 90º in 1 case, and 70º in 1 case. The length of both lower limbs was equal in 1 case, and the shortening of the affected limb was <2 cm in 3 cases and 8 cm in 1 case. The details of the patients are shown in Table 1. 5 patients were finally followed up, except for case 5 who showed obvious abnormal limb function with a functional score of 13, and the remaining 4 patients had a functional limb score of 27-30 with an average of 28.8, as shown in Table 2.
Table 1 Details of the five cases of distal femoral osteosarcoma with preserved epiphysis inactivation and reimplantation
No. Gender Age MR subtype Pathological fracture Follow-up time (months) Limb length comparison Flexion Knee Recurrence Metastasis Death Other
1 Female 9 I No 126 Short 2cm 110 None None None Inactivated bone fracture
2 Female 14 II no 89 Isometric 135 none none none none
3 Female 6 II no 66 short 2cm 90 none none none none
4 Male 9 I No 60 Short 1cm 135 None None None None Inactivated bone fracture
5 Female 8 I Yes 69 Short 8cm 70 None None None None Inactivated bone fracture
Table 2 List of postoperative limb function evaluation in 5 patients
No. Pain Function Mental tolerance Support Walking Gait Total score
1 None Slightly restricted Like None Not restricted Slightly limping 28
2 No No restriction Like No No restriction Normal 30
3 No Slight limitation Like No No limitation Slight limp 27
4 No No limitation Like No No limitation Normal 30
5 None Partial loss of use Satisfactory Double abduction Restricted Severe abnormality 13
Imaging observations: In addition to the previously reported changes in healing of inactivated bone and host bone, the most recent follow-up imaging data revealed varying degrees of bone atrophy in the femur of the affected limb compared to the healthy side. four cases had normal knee gaps (Figure 3), and one case (patient in case 5) had a narrowed joint gap (Figure 4).
Complications: In this group of patients, except for case 3, who did not undergo reoperation, the remaining four cases were reoperated for various reasons. In case 1, the patient underwent internal fixation with an incisional repositioning implant for an inactivated bone fracture at 26 months postoperatively, and the bone was found to be healing well at 6 months postoperatively and is now 100 months postoperative (Figures 5 and 6). In case 4, the patient underwent internal fixation with an incisional repositioning implant 18 months after surgery for an inactivated bone fracture and is now 42 months postoperative again, walking normally, with 1 cm of shortening of the affected limb compared to the healthy side and knee flexion to 135º (Figures 7 and 8). Case 5 patient had an autologous fibula combined with allograft bone graft to repair the bone defect due to inactivated bone fracture 1 year postoperatively, and now 20 months postoperatively the allograft bone resorption occurred and the autologous bone graft was performed again, now 36 months postoperatively with good bone healing (Figure 4), but there was significant limb shortening and knee flexion up to 70º. Case 2 patient underwent arthroscopic release and quadriceps plication 3 years after surgery because of difficulty in meeting daily life with knee flexion to 70º. After postoperative exercise, the knee has now returned to normal range of motion with equal length of both lower extremities 53 months after reoperation (Figure 3,9).
DISCUSSION
Epiphysis-preserving limb-sparing surgery is a new approach to the treatment of osteosarcoma in children, with the aim of reducing the incidence of surgical complications, avoiding postoperative bilateral limb inequality, and improving limb function in postoperative patients without increasing the local recurrence rate. Several surgical approaches have been reported in the literature, including the preoperative lengthening of the epiphysis by Canadell [4] to form a wide band of new bone between the tumor and the epiphysis, followed by limb-sparing surgery at the end of 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 pathological histology confirms the absence of tumor cells at the cut edge. intraoperatively applied fluoroscopic technique to prove the absence of tumor cells present at the resection site, removed the tumor, preserved the epiphysis, and repaired the defect with allograft bone or autologous bone, and fixed the epiphysis to the allograft bone with screws.Tsuchiya [6] 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. Wang Zhen [7] reported tumor resection allograft bone grafting with preservation of the epiphysis in pediatric patients with bone tumors. We have applied epiphysis-preserving inactivated reimplantation to clinical practice since 1999 and reported the recent clinical efficacy of this method and the related matters that should be noted during clinical application, respectively [8].
Complications of epiphysis-preserving surgery reported in the literature are mainly infection, graft resorption, fracture, and loosening of internal fixation.Canadell et al [4] treated 20 cases with 2 infections, 3 graft displacements, 1 common peroneal nerve palsy, and 1 graft fracture.Tsuchiya et al [6] had 4 skin infections, 7 deep infections, 3 fractures, 5 common peroneal nerve palsy, and 7 cases of delayed bone healing in their patients. Of the 13 cases reported by Muscolo et al [9], 11 received final follow-up, 7 had complications, 3 had graft bone fractures, 2 had non-healing epiphyses, and 1 had deep infection and soft tissue recurrence. Among the patients with a mean follow-up of 37.6 months (12-72) reported by Wang Zhen [7], four cases had five complications, mainly bone nonunion, fracture and nerve injury. The shortest follow-up was 5 years and the longest was 11 years in our group of 5 patients, and the long-term complications were mainly fractures and limitation of flexion of the affected knee. Three patients in our group had fractures of the inactivated bone 1-2 years after surgery, and two fracture sites occurred at the junction of the inactivated bone and the host bone, suggesting that we should enhance bone grafting at this site to promote bone healing during future surgical procedures. The other case occurred at the inactivated bone, which was related to the improper selection of the patient. The patient had an osteosarcoma out of the distal femoral epiphysis, MR type I, but it was combined with a fracture. However, due to multiple surgeries and long-term braking of the limb, the lack of movement stimulated the development of the epiphysis and epiphyseal plate, the affected limb was significantly shortened (8 cm shorter than the healthy side) and the knee flexion was limited. The lessons learned from this case suggest that we can perform epiphyseal preservation surgery in patients with MR type I fractures, but that allograft bone grafting with preservation of the epiphysis should be chosen, and that intramedullary fixation is the preferred method of internal fixation.
Through long-term follow-up of the five cases in our group, we found that except for cases 2 and 4, the bone quality of the other three patients was significantly thinner than that of the healthy side, which was related to the bone quality base at the time of surgery, in addition to the surgical operation, disuse atrophy of the affected limb by braking and self-protection. Therefore, we believe that when choosing epiphysis-preserving inactivation and reimplantation surgery, in addition to the basic indications [4], we should also pay attention to the bone quality development of the affected limb , and the nature and invasive range of the tumor, etc. The best indications should be that the patient has strong bone, that the bone is significantly sclerotic after chemotherapy, and that the extent of the lesion should not exceed 1/2 of the diameter of the affected bone.
Knee stiffness is a common complication of distal femoral surgery and an important factor affecting the outcome of surgery in this area. In our case 2, 3 years after the surgery, the patient underwent arthroscopic release and quadriceps kyphoplasty because the knee joint was flexed to 70º and it was difficult to meet the daily life, and some fibrous adhesions were seen in the knee joint under the arthroscope, but the meniscus, femoral condyle and tibial plateau had good articular cartilage. The knee joint could be flexed to normal range. CPM exercises were given immediately after the drainage was removed 2 days after surgery, and the knee has now returned to normal range of motion with equal length of both lower extremities 53 months after reoperation (Figure 7,8). Therefore, we believe that arthroscopic soft tissue release and quadriceps plication can be chosen to further improve the surgical outcome in this type of post-operative patients with knee stiffness or limited motion due to intra- and extra-articular soft tissue reasons, provided the presence of tumor factors is excluded.
One of the objectives of applying epiphysis-preserving surgery is to avoid postoperative limb length discrepancies. manfrini [5] et al. found, during the follow-up period of six cases, that the affected limb was on average 2.2 cm (0.5-3.3 cm) shorter compared to the healthy side without surgical correction; the function of the affected knee could be restored to 95% of normal without joint instability or anterior cruciate ligament laxity. In our recent follow-up of 11 patients, we found 6 cases with knee flexion ≥90º, 4 cases with 60º-90º, and 1 case with <60º, with no signs of joint instability. The lower limb length was equal in 4 cases, and the shortened limb was <2 cm in 5 cases and 2 to 3 cm in 2 cases, and all children walked without orthopedic shoes. The rate of excellent limb function in patients reported by Wang Zhen [7] was 82.8%, with an average limb shortening of 3.2 cm (2-6 cm). All patients had good joint stability, no dislocations or knee valgus deformities, and no osteoarthritis occurred during the follow-up period. Among the five patients in this group, except for case 5 due to the choice of surgical procedure (limb function score of 13), the remaining four cases had one patient with equal limb length and three patients with 1-2 cm limb shortening at 60-126 months of follow-up, with good joint stability and slight limp in walking and an average limb function score of 28.8. The inactivation and reimplantation of the epiphysis can achieve satisfactory long-term clinical results.
Through the long-term follow-up of the five patients in this group, we believe that inactivated reimplantation with preservation of the epiphysis is a feasible surgical method. Under the premise of strictly following the indications for surgery, careful analysis of the bone quality of the affected bone and the extent of lesion invasion, intraoperative attention to the bone implantation at the site of connection between the inactivated bone and the host bone, and active treatment measures in case of complications will be conducive to obtaining satisfactory clinical results. Restriction of joint movement and fracture of the inactivated bone are the most common long-term complications of this procedure. Although most patients have varying degrees of limb shortening, this does not affect the long-term clinical outcome of the procedure.