Nine of the nineteen patients who had a lengthening procedure and six of those who did not were treated with a shoe lift. The Musculoskeletal Tumor Society functional scores were available for sixteen patients before the limb-lengthening procedure. Importantly, the mean functional score increased significantly to 81% ± 11% (range, 60% to 100%) after limb-lengthening from 65% ± 21% (range, 23% to 100%) before the lengthening (p = 0.0016). Regression analysis showed a significant negative correlation between functional score and a limb-length discrepancy of ≥2 cm (r = 0.53 and p = 0.0091) (Fig. 4).
Five early complications occurred in four patients, and twenty-eight late complications occurred in twenty-two patients. In summary, one patient had three complications, seven patients had two complications, and sixteen patients had one complication each, while the remaining nine patients had no complications. Early complications included skin necrosis, infection, vessel occlusion, and peroneal nerve palsy, and late complications included superficial and deep infection, implant breakage, aseptic loosening, fracture, nonunion, and dislocation. Details of the complications are shown in Table I. In the endoprosthetic reconstruction group, the most frequent complication was deep infection (six patients) followed by aseptic loosening (five patients), and implant breakage and dislocation (two patients each). In the biological reconstruction group, the most frequent complications were implant breakage and nonunion (three patients each), followed by superficial infection, deep infection, and fracture (two patients each).
A tendency toward higher functional scores was noted in the patients who did not have complications (mean score, 77% ± 27%) compared with those who did (mean score, 70% ± 13%); however, the difference did not reach significance (p = 0.3596).
The cumulative event-free rate with regard to complications related to surgery was calculated for the total series of patients. Complications had occurred in 55% (95% confidence interval, 38% to 71%) of the patients at five years, and the rate increased to 74% (95% confidence interval, 57% to 90%) at ten years. Furthermore, the cumulative event-free rate in the two surgical groups was determined (Fig. 5). At five years, complications had occurred in 45% (95% confidence interval, 25% to 66%) of the patients in the endoprosthetic reconstruction group and in 73% (95% confidence interval, 46% to 99%) of those who had biological reconstruction (p = 0.0472). At ten years, the complication rate had increased to 69% (95% confidence interval, 47% to 91%) of the patients in the endoprosthetic reconstruction group and to 86% (95% confidence interval, 63% to 109%) of those in the biological reconstruction group (p = 0.0836).
Survival of Reconstruction Modes
With regard to the management of the complications, revision operations were necessary in thirteen patients, and one of them eventually underwent amputation. In addition, four other amputations were performed. The details of the revisions and amputations for these patients are shown in the Appendix and are summarized in relation to complications in Table I. A total of seventeen patients (52%) needed additional surgery because of complications of the initial surgery.
The survival rate of the reconstructions in the two surgical groups was estimated (Fig. 6). The survival rate was 77% (95% confidence interval, 60% to 95%) at five years and 51% (95% confidence interval, 29% to 73%) at ten years for the endoprosthetic reconstructions and 46% (95% confidence interval, 16% to 75%) at both five and ten years for the biological reconstructions. Interestingly, during the first six years, a tendency toward better survival was noted for the endoprosthetic reconstructions, but it did not reach significance (p = 0.0646) and did not persist during longer follow-up. The total success rate for limb salvage was 85%, with a success rate of 91% for the endoprosthetic reconstructions and 73% for the biological reconstructions.
Chemotherapy has dramatically changed the cure rate of malignant bone tumors5,19. Since the introduction of effective neoadjuvant chemotherapy in the 1980s, >80% of patients with osteosarcoma of the extremity have been considered candidates for limb-salvage surgery20. Previous studies have found no difference in the long-term survival rate between patients treated with amputation and those treated with limb-salvage of the distal end of the femur1,2. In the present study, the ten-year cumulative survival rate was 82%. This finding is comparable with that in the study by Schindler et al.8, who reported an overall survival rate of 78% in children after limb-salvage surgery of the femur. Local recurrence was not observed in any patient in our series. This finding was similar to that in the study by Schiller et al.19, who performed limb salvage of the distal end of the femur in five children who were less than fourteen years old, and to that described by Wilkins and Miller21 in a study of thirty-one patients who were less than nineteen years old.
We studied forty children who were eleven years of age or less at the time of diagnosis. The purpose of selecting patients of this age was to evaluate the effect of growth for at least two years, as skeletal maturity is expected by the age of sixteen years in boys and fourteen years in girls9,10. The children were selected to undergo limb salvage with one of two major procedures, either endoprosthetic or biological reconstruction. Furthermore, they had a relatively long duration of follow-up of six to twenty years. All patients had reached skeletal maturity at the time of the last follow-up. To our knowledge, this is the largest report of the long-term results of limb salvage for the treatment of sarcomas of the distal end of the femur in skeletally immature children.
Kenan and Lewis reported that limb-lengthening was necessary in twenty-one patients who were twelve years old or less at the time of limb-salvage surgery11. A limb-length discrepancy of ≥2 cm has been considered substantial enough to require corrective surgery17. Therapeutic options range widely from no treatment or the use of a shoe lift to contralateral surgical shortening or a limb-lengthening procedure14,22,23. In the present study, limb-lengthening procedures were performed in nineteen (58%) of the thirty-three surviving patients. Only one patient had a discrepancy of <2 cm, five patients needed amputation, and the eight other patients refused to undergo any lengthening procedure (six of them used a shoe lift). Lengthening was achieved mainly with two procedures, distraction osteogenesis and endoprosthetic expansion. In nearly half of these patients (nine of the nineteen patients), an additional shoe lift was necessary, as a considerable discrepancy remained. Importantly, we found that the functional score was significantly higher following limb-lengthening. In addition, at the time of the final follow-up, we found that, as the limb-length discrepancy decreased, the functional score increased (see Fig. 4). Even if this relationship were significant, the functional score is clearly not only dependent on limb-length discrepancy, as other factors that have not been explored further in this study may contribute. However, we believe that limb-length discrepancy is a rather important factor relating to a poor functional outcome, and our findings support the concept that lengthening procedures are required to obtain better function in these young patients.
The final functional scores in the endoprosthetic and biological reconstructions were 74% and 68%, respectively, despite the frequent necessity for additional operations, such as limb-lengthening procedures and revisions. Function in the endoprosthetic group was comparable with that described in the study by Schindler et al., in which the mean Musculoskeletal Tumor Society functional score was 77% in twelve children with Stanmore custom-made extendable distal femoral prostheses8. Wilkins and Miller21 found mean functional scores of 73% in twenty-six patients with primary limb-preservation surgery with reoperations and 79% in ten patients without reoperations. With regard to the different categories of the Musculoskeletal Tumor Society functional scoring system, pain received the highest score, which indicated that the patients experienced little pain, whereas emotional acceptance and the ability to walk received the lowest scores.
Deep infection was the most common complication, occurring in eight (24%) of the thirty-three patients in our study. In the previous literature, the rate of deep infection in the femur has ranged from 4% (one of twenty-four patients) in the study by Cool et al.24 to two of five patients in the study by Schiller et al.19. Comparable results have been reported by other investigators8,25,26. Among the patients who had endoprosthetic reconstruction in our study, six had a deep infection. Débridement and irrigation without removal of the endoprosthesis was performed in two patients; staged reimplantation, in two patients27; removal of the endoprosthesis followed by arthrodesis28, in one patient; and amputation8, in one patient. Two of the patients in the biological reconstruction group had a deep infection. One was treated with débridement alone, and the other required amputation.
In the present study, five (23%) of twenty-two patients with endoprosthetic replacement experienced aseptic loosening. Aseptic loosening has been reported as a major problem, accounting for a complication rate of 13% (three of twenty-four patients) in the series by Cool et al.24 and up to six of twelve patients in the study by Schindler et al.8. Our results are comparable with those in several other reports19,24,29. Unwin and Walker30 found that sixteen (15%) of 105 patients managed with a Stanmore custom-made extendable endoprosthesis of the distal end of the femur had to have a revision because of aseptic loosening. This rate is similar to that in our study, in which revision surgery was required in three (14%) of twenty-two patients.
Implant breakage was found in 15% (five) of our thirty-three patients. In the endoprosthetic reconstruction group, two patients fell accidentally; one had breakage of the femoral stem and the other had breakage of the femoral ceramic component. Those types of prostheses are no longer used. In the biological reconstruction group, three of four patients who had reconstruction with a Küntscher nail had breakage. Breakage of the nail after arthrodesis occurred in twenty (24%) of eighty-four patients in the series by Donati et al.31 and in four of thirty-nine patients in the series by Weiner et al.32.
In the present study, revision surgery other than limb-lengthening was necessary in seventeen (52%) of thirty-three patients; five of them eventually needed amputation. In previous studies, revision rates have ranged from a minimum of 21% (five of twenty-four patients in the series by Cool et al.24) to 100% (all twelve patients in the study by Schindler et al.8). Comparable results have been reported by other investigators19,24,26,30,33. After long-term follow-up in our series of patients, the survival rates for endoprosthetic and biological reconstructions were similar. The survival rate for endoprosthetic reconstruction was 77% at five years and 51% at ten years, whereas the survival rate for biological reconstruction was 46% at both five and ten years. Unwin and Walker reported that 105 patients with distal femoral extendable prostheses had a probability of survival of 80% at four years30. However, long-term results were not reported in that study. Our long-term results are comparable with those reported in studies that included all age-groups, such as that by Kawai et al., who found a survival rate for endoprosthetic reconstruction of 67% at five years and 48% at ten years in thirty-two patients33.
There are few studies on the survival rate of biological reconstructions. In a report on eighty-four patients who had knee arthrodesis with use of a temporary spacer, Donati et al.31 found that the overall rate of implant survival was only 5% at twelve years, which was low compared with our findings. It should be noted that the rate of mechanical complications, such as implant breakage, bending, and migration, in that study was very high (39%; thirty-three patients). Those complications occurred soon after the initial surgery. Also, wound complications occurred in twenty-six patients. Alman et al.26 reported on eight young patients with a tumor of the femur who were managed with knee arthrodesis or an intercalary reconstruction of the femur; all except one had failure of the reconstruction and needed a revision.
The use of arthrodesis has decreased after the introduction of expandable endoprostheses26. However, an arthrodesis may still be considered in patients with a large tumor when an extensive resection of bone or soft tissue, such as complete resection of the quadriceps muscle, is expected; when there is a lack of bone source; or when there is a poor prognosis for the patient31. Furthermore, tumor resection with preservation of the epiphysis followed by reconstruction with distraction osteogenesis is the only current technique that has the advantage of preserving the natural joint, and thus it might be considered for patients with a tumor of <15 cm in length and with at least 0.5 cm of the epiphysis remaining after removal of the tumor14.
The rate of amputation in our study (five patients; 15%) is comparable with that in previous reports8,26. In our series, the causes leading to the amputations varied. In the previous literature, the major causes of amputation were infection or local recurrence8,30,31. In order to improve the success rate of limb-salvage surgery, every effort should be made to avoid these two complications.
One limitation of this study is the relatively small number of patients in each of the surgical reconstruction groups, and therefore any firm conclusion about differences across the groups should be made with caution. The study design represents another limitation, since this was a multicenter retrospective study and no randomization protocol for the implementation of surgical procedures was followed. Thus, tumor-related factors; the preferences of the institution, the surgeon, or the patient; or other unexplored factors might have biased the decision with regard to the type of surgery performed.
We concluded that, even if additional revision and limb-lengthening procedures are required, endoprosthetic or biological reconstructions provide good functional outcome in skeletally immature children with a malignant bone tumor of the distal end of the femur. However, the patients and their families must be carefully selected with an emphasis on motivation and acceptance, since rather frequent and substantial treatment during follow-up is inevitably required. In the future, improvements in the surgical techniques and equipment are needed to diminish the number of complications related to the initial limb-salvage surgery.
A table presenting demographic data on the patients in the study is available with the electronic versions of this article, on our web site at jbjs.org (go to the article citation and click on “Supplementary Material”) and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM). ▪
A commentary is available with the electronic versions of this article, on our web site () and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).
NOTE: The authors thank their colleagues in the Japanese Musculoskeletal Oncology Group for their participation in the present study: H. Yoshida, MD, Nihon University; K. Yonemura, MD, Kumamoto University; K. Isu, MD, National Sapporo Hospital; K. Yokoyama, MD, National Kokura Hospital; N. Araki, MD, Osaka University; T. Goto, MD, The University of Tokyo; A. Kawai, MD, National Cancer Center Hospital; T. Ozaki, MD, Okayama University; S. Tatezaki, MD, Chiba Cancer Center Hospital; T. Hotta, MD, Niigata University; T. Tajino, MD, Fukushima Medical University; S. Nasuno, MD, Kitasato University; E. Chousa, MD, Miyazaki Medical College; H. Kakizaki, MD, National Hirosaki Hospital; K. Shinjo, MD, Nagoya National Hospital; N. Ueda, MD, Osaka Medical College; Y.H. Lee, MD, Tokai University; H. Watanabe, MD, Gunma University; H. Murata, MD, Kyoto Prefectural University of Medicine; K. Ihara, MD, Yamaguchi University; T. Nakagawa, MD, Kansai Medical University; H. Isaki, MD, National Defense Medical College; T. Nishikori, MD, Shimane Medical University; T. Takagi, MD, Juntendo University; A. Imakiire, MD, Tokyo Medical University; H. Tsuchiya, MD, Kanazawa University; Y. Aoki, MD, Osaka National Hospital; T. Nagai, MD, Saitama Medical School; H. Kuroda, MD, Tokyo Medical and Dental University; and M. Hatori, MD, Tohoku University.
In support of their research for or preparation of this manuscript, one of the authors (H.F.) received grants or outside funding from the Fund for Cancer Research from Hyogo Prefecture Health Promotion Association. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Department of Orthopaedic Surgery, Hyogo College of Medicine, Hyogo, Japan
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