Oncologic Approaches to Pediatric Limb Preservation Abstract Preservation of limb function in the pediatric oncology patient is uniquely challenging. Treatment must be strictly prioritized in terms of the patient’s life, the limb, its function, length equalization, and cosmetic appearance. At the same time, social, socioeconomic, and cultural factors must be understood and respected to achieve the most advantageous outcome for both the patient and family. Given these considerations, as well as the relative rarity of many oncologic diagnoses and the myriad of presentation scenarios, drafting generalized treatment recommendations is difficult. Instead, orthopaedic intervention in the care of children and young adults with oncologic conditions must be individualized, with the broad goal being optimization of limb function rather than rigid advocacy of limb salvage. M usculoskeletal malignancies are relatively rare, accounting for approximately 10% of newly di- agnosed cancers in children, adoles- cents, and adults. 1 Historically, pedi- atric patients with a limb sarcoma had a dismal prognosis. Surgery largely was limited to ablative proce- dures, and medical care most often was palliative and supportive. Over the past three decades, advances in chemotherapy, radiation therapy , ra- diologic imaging, and surgery have resulted in substantial improve- ments in survival and functional outcome. Chemotherapy in particu- lar is credited with increasing 5-year survival from historic rates of 10% to 20% to the current range of 60% to 70%. 1 Although patients with metastatic musculoskeletal tumors continue to have a poor prognosis (10% to 30% have 5-year, disease- free survival 1 ), aggressive therapy should still be rendered, especially to those with isolated or limited me- tastases that are amenable to resec- tion. As overall survival has improved, methods for preserving limb func- tion have increasingly become im- portant. Modern bone-banking tech- niques and advances in implant design have allowed a high percent- age of children to undergo limb sal- vage procedures at specialized cen- ters. Early enthusiasm for allograft transplantation and endoprosthetic replacements has been tempered by complications that have become ev- ident with long-term follow-up. 2-7 The search for safe, effective, dura- ble, and versatile reconstructive op- tions continues; at the same time, interest in modified or specialized amputation options remains strong. Initial Evaluation Patient care in orthopaedic oncology begins with a careful history and physical examination before proceed- ing to laborator y and radiologic eval- uation. Information obtained by the history may help to direct attention toward non-neoplastic processes, Jason S. Weisstein, MD, MPH, Robert E. Goldsby, MD, and Richard J. O’Donnell, MD Dr. Weisstein is Partner, Tucson Orthopaedic Institute, Center for Orthopaedic Oncology, Tucson, AZ. Dr. Goldsby is Assistant Professor of Clinical Pediatrics, Department of Pediatrics, University of California, San Francisco, CA. Dr. O’Donnell is Associate Professor of Clinical Orthopaedic Surgery, University of California, San Francisco. Dr. Weisstein or the department with which he is affiliated has received research or institutional support from a commercial source or sources. Neither Dr. Goldsby nor the department with which he is affiliated has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article. Dr. O’Donnell or the department with which he is affiliated has received research or institutional support from a commercial source or sources. Reprint requests: Dr. O’Donnell, UCSF Comprehensive Cancer Center, University of California at San Francisco, 1600 Divisadero Street, San Francisco, CA 94115-1939. J Am Acad Orthop Surg 2005;13:544- 554 Copyright 2005 by the American Academy of Orthopaedic Surgeons. 544 Journal of the American Academy of Orthopaedic Surgeons such as infection, vascular malforma- tions, or myositis ossificans. In the preponderance of cases of malig- nancy, however, the elicited history is that of a mass that is less painful than might be expected. Most mus- culoskeletal tumors arise sporadical- ly; in some cases, however, there can be an association with rare heritable conditions, such as exists between osteosarcoma and retinoblastoma or between osteosarcoma and Li- Fraumeni syndrome. Physical examination supplies ad- ditional useful data. For instance, café-au-lait spots may signal fibrous dysplasia or neurofibromatosis. Evaluation of the presence and size of a mass, warmth, erythema, ten- derness, range of motion, gait, and neurovascular status are important but may not considerably narrow the differential diagnosis. Laboratory and Radiologic Evaluation Laboratory studies can be helpful but are often overlooked on initial screening. Of particular relevance are the complete blood count, eryth- rocyte sedimentation rate, and C-reactive protein test. Alkaline phosphatase and lactic dehydrogena- se levels may be elevated in some cases of sarcoma. The important aspect of the workup of a child with a potential oncologic condition is plain radiog- raphy. Diagnosis must not be de- layed for matters of convenience, in- surance issues, or poor radiographic technique. Good-quality radiographs in two planes often are the best clue to the final diagnosis. They frequent- ly prompt early referral to an ortho- paedic oncalogy specialist, who can determine the need for timely addi- tional imaging, such as technetium Tc-99m, computed tomography, magnetic resonance imaging, and positron emission tomography. A timely and thorough initial evalua- tion is crucial to enhance the chanc- es for preserving the life and limb of the pediatric oncology patient. Biopsy The most critical issue with re- spect to the initial management of children with bone and soft-tissue neoplasms is that of obtaining biop- sy material in an appropriate man- ner. Improperly performed biopsies can delay the initiation of therapy, lead to incorrect treatment, hinder attempts at limb salvage, and in- crease the chance for local recur- rence. 8 It is estimated that the risk of diagnostic errors and complications increases 4- to 12-fold when tissue biopsy is incorrectly performed. 8 Biopsy procedures should be done through a longitudinal approach that minimizes length and avoids the risk of bleeding and sepsis. The inci- sion should be placed in such a way that it can be completely excised during the definitive resection pro- cedure. A multidisciplinary team should be available, including a skilled musculoskeletal pathologist to interpret the frozen section, a pe- diatric medical oncologist to per- form bone marrow studies, and a general surgeon to place the central venous line. Considerable experience has been gained in adults with soft-tissue neo- plasms from interpretation of mini- mally invasive fine-needle and core biopsies. The mass can be widely sampled, and complications, such as extensive contamination of the sur- rounding tissues, are minimized. Such approaches, often using ultra- sound or computed tomography– guided technology, can be effectively used in the pediatric population. In many centers, however, biopsies—es- pecially in children younger than 16 years—typically are performed in an open fashion with a general anes- thetic for the following reasons. (1) Most pediatric malignancies arise in bone rather than in soft tissue and thus are less amenable to reliable per- cutaneous biopsy. (2) Pediatric pa- tients and their families often are un- derstandably reluctant to undergo office-based biopsy procedures using sedation and a local anesthetic. (3) Cooperative pediatric oncology groups often require that sufficient tissue (fresh, snap-frozen, and fixed) be submitted by express mail for cen- tral pathologic review and an array of biologic studies. (4) Depending on the results of frozen-section analysis, the child can immediately undergo a pri- mary tumor resection procedure or adjunctive procedures, such as a bone-marrow aspirate or central venous-line insertion. Given all of these considerations, pediatric pa- tients with lesions suspected of being high-grade malignancies should be referred to an orthopaedic oncology center before biopsy. Treatment: General Considerations Once the diagnosis is established in terms of histologic type and grade, the disease must be staged to deter- mine whether metastatic disease is present. In some centers, the staging is performed before the biopsy if pri- mary tumor resection is planned im- mediately associated with the biop- sy. Important tests to r ule out occult malignancy and metastatic disease include a computed tomography scan of the chest, abdomen, and pel- vis, a technetium Tc-99m total body bone scan, and, increasingly, a positron emission tomography scan. 9 The timing of local control varies according to diagnosis and stage of disease. Most protocols use chemo- therapy before definitive surgery. This formulation offers several ad- vantages. Any documented meta- static or suspected micrometastatic disease can be treated immediately. In addition, time is made available to discuss options for local control. Also, surgical resection may be eas- ier in tumors that respond to chemo- therapy. Finally, histologic analysis of tumor necrosis in response to che- motherapy can guide future inter- ventions. Many factors affect the recom- mendations made by the treating Jason S. Weisstein, MD, MPH, et al Volume 13, Number 8, December 2005 545 physicians, including (1) patient age, (2) histologic diagnosis, (3) tumor grade, (4) disease stage, (5) anatomic location, (6) expected response to neoadjuvant treatment, (7) family socioeconomic and cultural factors, and (8) potential philosophical and technical biases and capabilities of the multidisciplinary team itself. Successful strategies may vary wide- ly, even among patients who present in similar fashion. For instance, sur- gical management of a 5-year-old with distal femoral osteosarcoma will differ greatly from that of a 12- year-old with the same tumor and location. Similarly, management of a 14-year-old patient with hemipelvic Ewing’s sarcoma and bone metastas- es will differ substantially from that of a patient without metastases. Although discussions of function- al pediatric limb preservation can be categorized according to any of the previously noted factors, it is easiest to highlight types of surgical inter- vention first, with issues such as age and tumor location referenced in a subordinate manner. Amputation Versus Limb Salvage Many relative contraindications to limb salvage procedures are gener- ally accepted (Table 1). Although no absolute contraindications to limb salvage exist, the most difficult ob- stacles to overcome are major neuro- logic involvement by the tumor and very young skeletal age (approxi- mately younger than 8 years). The latter consideration is of paramount relevance to lower extremity cases, in which multiple surgeries span- ning several years would be neces- sary to minimize limb-length in- equalities. The risks inherent in repeated procedures include system- ic complications, need for blood transfusion, infection, neurovascular injury, and mechanical difficulties (eg, inability to expand a prosthesis); some of these complications ulti- mately could lead to amputation. Conversely, the fact that chemother- apy slows skeletal growth and delays maturation, potentially adding to the relative contraindication of sur- gery at a very young skeletal age, should neither preclude a careful limb salvage effort nor be expected to complicate the ultimate outcome in terms of limb-length equalization. These issues must be carefully re- viewed with the patient and family before undertaking a limb salvage e f- fort. Nonetheless, very young skele- tal age should not necessarily ex- clude efforts to save the limb, provided the family is cognizant of these considerations. Relative contraindications to limb salvage with the most immedi- ate postoperative implications in- clude infection that exists at the time of definitive surgery or that de- velops in response to inadequate wound coverage. Flap coverage should be included as part of the in- dex procedure whenever necessary. Although many wound problems that occur in cases of limb-sparing surgery ultimately can be success- fully treated with local measures (with chemotherapy continuing un- interrupted), any additional major surgical procedures could delay po- tentially life-preser ving chemother- apy. The sequelae of tumor bed con- tamination, positive surgical mar- gins, or pathologic fracture often will manifest in a delayed fashion as in- creased risk of local recurrence. Al- though both local recurrence and metastatic disease are thought to be markers of biologic aggressiveness, no proof exists that local recurrence directly causes metastasis. Thus, the surgeon should not allow anticipat- ed close surgical margins to prohib- it a vigorous approach to limb sal- vage. Should local recurrence occur, oncologic control almost always can be established with amputation. However, such secondary proce- dures occasionally are at a higher level, with a more adverse function- al outcome, than would have been the case had amputation been pro- posed as the initial procedure. As a treatment plan is being for- mulated, it is important for the pa- tient and family to understand re- search that compares patients who have had amputation with patients who have undergone limb salvage. Most of these studies have been done in populations with a distal femoral tumor. 10-13 It is generally thought that no statistically signifi- cant difference in terms of overall survival or local control exists when amputation and limb salvage proce- dures are compared. According to available outcome measures, func- tion of these patient populations is similar; the same can be said in terms of acceptance of the surgical result and psychological end points. 14 It is reasonable to suggest that limb salvage patients often will have what many consider to be a cosmetically superior result, al- though at the expense of durability and endurance in certain physical and recreational tasks. Limb salvage Table 1 Relative Contraindications to Limb Salvage Factors most likely to preclude attempting limb salvage Major neurovascular involvement Very immature skeletal age Factors most likely to delay reinstituting chemotherapy Infection preceding definitive resection Difficulties with postoperative wound healing Factors most likely to be associated with local recurrence Tumor-bed contamination (eg, biopsy complications) Positive surgical margins Pathologic fracture Oncologic Approaches to Pediatric Limb Preservation 546 Journal of the American Academy of Orthopaedic Surgeons patients require, on average, more surgical interventions than do pa- tients who have had amputations. Finally, families should know that financial considerations play no role in recommendations regarding am- putation over limb salvage because the lifetime expense of external prostheses is estimated to be far greater, on average, than that associ- ated with implants. 15 Amputation Surgery Choice of Amputation Level Whether the tumor involves the upper or lower extremity , the ampu- tation level essentially is chosen at the most distal level that will guar- antee local control of the tumor. A longer residual limb will serve to en- hance ease of prosthetic fitting, and hence, function. For any of the reasons noted in Table 1, ablative surgery may be rec- ommended to achieve local control. In most cases, amputations are nec- essary to treat effectively massive extracompartmental tumors that in- volve neurovascular structures. The most common indication for pediat- ric amputation involves high-grade proximal tibial or fibular tumors (Figure 1). Provided that negative surgical margins and adequate soft- tissue coverage can be obtained, a knee disarticulation procedure is recommended because it will pre- serve the distal femoral physis in skeletally immature individuals and provide an end-bearing residual limb. When necessary, a standard su- pracondylar above-knee amputation provides satisfactory function and somewhat easier prosthetic fitting compared with the through-the- knee procedure. Immediate Postoperative Prostheses When a lower extremity amputa- tion is performed, consideration should be given to the use of an im- mediate postoperative prosthesis. Although this technique has fallen out of favor for patients with periph- eral vascular disease because of con- cerns regarding wound healing, the technique is safe for pediatric pa- tients, including those receiving chemotherapy. In addition to allow- ing partial weight bearing on the first postoperative day, an immedi- ate postoperative prosthesis enhanc- es wound healing and decreases the interval to definitive prosthetic fit- ting (Figure 1, C ). The technique also provides a tremendous psycho- logical benefit for patients and their families. 16-18 Specialized Amputation Another common scenario in which amputation often becomes necessary is t he very young pediatric patient with a distal femoral sarco- ma. Although it typically affects ad- olescents, osteosarcoma also can oc- cur in children during the first Figure 1 A, Anteroposterior radiograph of a 12-year-old girl with a massive proximal fibular osteosarcoma. B, Axial T2-weighted magnetic resonance image demonstrating neurovascular involvement by the tumor. C, Following knee disarticulation amputation of the lower limb, an immediate postoperative prosthesis was applied in the operating room to enhance rehabilitation. Jason S. Weisstein, MD, MPH, et al Volume 13, Number 8, December 2005 547 decade. For children younger than 8 years, the number o f subsequent sur- gical treatments necessary to achieve limb-length equalization of- ten serves to preclude an otherwise technically feasible limb-sparing op- eration. Because standard above-knee am- putations in this setting would re- sult in a particularly short residual limb, specialized amputation proce- dures have been developed to pro- vide increased length and better function to the residual limb. The most widely used approach is rota- tionplasty, in which the distal por- tion of the patient’s extremity is transposed to the residual proximal limb via femoral-tibial osteosynthe- sis. In the process, the distal tibia is rotated 180° about the longitudinal axis, with the ankle serving as a new knee joint. The foot is left intact, es- sentially serving as a below-knee amputation segment, providing ad- ditional biomechanical advantage. Results in selected populations of ro- tationplasty have been extremely encouraging. 19 In some areas of the United States, however, there is less experience with the technique, less cultural acceptance of the cosmetic appearance of the residual limb, and less familiarity with prosthetic fit- ting. Another alternative for distal fe- mur tumors in young patients is the tibial turn-up plasty. 20-22 In this sur- gical procedure, the proximal por- tion of the tibia is preserved togeth- er with its vascular pedicle, and femoral-tibial plating is accom- plished after the tibia has been rotat- ed 180° in the coronal plane. The re- sulting limb has the cosmetic appearance of an above-knee ampu- tation while maintaining the capa- bility of longitudinal growth from the preserved proximal tibial phy- seal plate (Figure 2). Limb Salvage No Surgery Surgery often is not required or advisable in several pediatric onco- logic conditions. This is true for the many benign tumors and tumor-like conditions, such as fibrous dysplasia, and for high-grade tumors that are not resectable because of location or disease stage. For instance, a posteri- or iliac osteosarcoma that also in- volves more than half of the sacrum or the lower lumbar spine would not be treated surgically, although the condition is not particularly respon- sive to radiation therapy. Conversely, for many of the small, round, blue-cell lesions (in- cluding Ewing’s sarcoma, rhabdo- myosarcoma, and lymphoma), radia- tion therapy is particularly helpful in achieving local control. In many cases, chemotherapy and radiation therapy are recommended to the ex- clusion of surgery. With pelvic Ew- ing’s sarcoma, for instance, contro- versy remains as to whether surgery adds to either local control or overall survival. 23-25 The consensus among tumor surgeons is that surgery may be important for extremity Ewing’s sarcoma, but this also remains to be proved in a definitive fashion. 26 Indi- cations that generally are more ac- cepted for surgery in round-cell le- sions include pathologic fracture at the time of presentation and the fre- quent need to avoid or mitigate the side effects of radiation therapy, in- cluding growth arrest, deformity, joint stiffness, secondary malignan- cy; and osteonecrosis with subse- quent fracture. Resection Only When pediatric malignancies oc- cur in expendable bones, including selected portions of the ulna, scapu- la, sacrum, pelvis, and fibula (Figure 3), local control can take the form of resection without reconstruction. Pediatric soft-tissue sarcomas are ex- ceedingly rare. Nonetheless, when synovial sarcomas, malignant fi- brous histiocytomas, and similar Figure 2 Anteroposterior preoperative (A) and postoperative (B) radiographs of a 5-year-old girl with a distal femoral osteosarcoma treated with a segmental tumor resection and tibial turn-up plasty. The proximal tibia was rotated 180° and plated to the residual femur. Osteosynthesis readily occurred. The proximal tibial physeal plate remained open for longitudinal growth. Oncologic Approaches to Pediatric Limb Preservation 548 Journal of the American Academy of Orthopaedic Surgeons lesions do occur, surgery can be limited to resection without re- construction. Intraoperative radia- tion therapy or brachytherapy tech- niques sometimes are used to limit the morbidity to physeal plates, joints, and soft tissues. The relative- ly uncommon extraosseous variants of osteosarcoma and Ewing’s sarco- ma also can be treated in this man- ner (Figure 4). Medical management of pediatric soft-tissue sarcomas is less standardized than that of bone malignancies, but chemotherapy is commonly offered to these patients as well, particularly in cases of rhab- domyosarcoma. Resection and Reconstruction Autografts and Bone Graft Substi- tutes Indications for the use of au- tograft in pediatric orthopaedic onco- logic cases are limited. The amount of bone available for use often is quite small, especially in younger pa- tients. In addition, harvesting au- tograft involves another incision and can be fairly morbid, with an overall complication rate of up to 30%. 27 Cancellous cadaveric allograft offers an alternative for small, benign cys- tic defects, but parents understand- ably are concerned regarding the po- tential, albeit rather rare, for infectious complications. 28 For these reasons, bone graft substitutes, such as coralline hydroxyapatite, calcium sulfate, and demineralized bone ma- trix, have demonstrated great utility for filling pediatric oncologic de- fects 29 (Figure 5). Perhaps one of the best applica- tions of autograft bone in pediatric cases is that of a vascularized fibular transplant. This technique is best suited for intercalary long bone defects (eg, the tibia) with allograft supplementation, or for proximal humeral osteoarticular reconstruc- tion. 30 The vascularized fibula pro- vides a graft that not only heals at the osteosynthesis site but also has Figure 3 A, Anteroposterior preoperative radiograph demonstrating a proximal fibular osteosarcoma in a 7-year-old girl. B, Axial T2- weighted magnetic resonance image further delineating the sarcoma. C, In this expendable bone, resection without reconstruction was chosen. Figure 4 Axial T2-weighted magnetic resonance image of a 10-year-old boy with a massive proximal medial thigh extraosseous Ewing’s sarcoma. Local control was established with radical en bloc resection and intraoperative external-beam radiation therapy. Jason S. Weisstein, MD, MPH, et al Volume 13, Number 8, December 2005 549 the capacity for potential longitudi- nal growth and remodeling from the proximal physeal plate (Figure 6). Osteoarticular Allografts Prior to the development of modern pros- thetic implants, allograft bone pro- vided the basis for reconstruction of the massive defects often encoun- tered in limb tumor surgery. Throughout the 1970s and 1980s, advances in tissue banking occurred, allowing osteoarticular and interca- lary grafts to become available es- sentially on a custom-made, size- matched basis. Cadaveric specimens are procured in a sterile manner, and low-dose radiation at times is added to limit the possibility of bacterial contamination. Although osteolysis sometimes occurs, immunologic rejection is not a major factor, and immunosuppressive agents are not necessary. Disease transmission, principally hepatitis and AIDS, re- mains an extremely low but finite risk, despite increasingly sophisti- cated testing of allograft donors. 28 Massive allograft usage offers sur- geons and families the attractiveness of a biologic solution to difficult re- constructive problems. Nonetheless, although glycerol and specialized freezing techniques are employed to preserve articular cartilage, studies have shown that few chondrocytes actually survive the preservation process. The cadaveric bone itself is incorporated only to a modest degree at osteosynthesis sites and below t he periosteal sleeve, making the al- lograft at best a biomechanical sup- port scaffold. 31 Because they have been in use for decades, allografts have been the subject of many long-term follow-up reports. In general, results have been favorable; however, depending on the site studied, up to 50% of pa- tients can expect at least one major complication, divided on an approx- imately equal basis between frac- ture, bacterial infection, and non- union. 2 In some series, serious allograft infections have been noted to occur nearly twice as often as en- doprosthetic infections (11% versus 6%, respectively). 32 Patients and par- Figure 5 A, Anteroposterior radiograph of a 12-year-old boy with a large ulnar aneurysmal bone cyst, recurrent after packing with allograft. The lesion was successfully treated with curettage, burring, and packing with coralline hydroxyapatite. B, Incorporation of the hydroxyapatite is demonstrated on the 2-year follow-up radiograph. Figure 6 Anteroposterior radiograph (A) and axial T2-weighted magnetic resonance image (B) of a 14-year-old boy with a proximal humeral osteosarcoma. C, Postoperative anteroposterior radiograph demonstrating resection and reconstruction with vascularized fibula autograft. Oncologic Approaches to Pediatric Limb Preservation 550 Journal of the American Academy of Orthopaedic Surgeons ents thus should be advised regard- ing the likelihood of complications and revision surgery. Alloprosthetic Composites Major challenges encountered with os- teoarticular allografts are those of soft-tissue reconstruction and artic- ular congruity. At the knee, restora- tion of cruciate and collateral liga- ment function is problematic. At the hip, duplication of the precise three- dimensional fit between the native femoral head and acetabulum is dif- ficult. The same difficulties, in terms of restoration of function and articular congruency, exist to a less- er extent at the glenohumeral joint. For these reasons, alloprosthetic reconstruction has gained favor for select indications, particularly in cases of failed allografts. For exam- ple, a constrained total knee implant can be combined with a distal femo- ral allograft, or a bipolar hemiarthro- plasty prosthesis can be combined with a proximal femoral graft. Sim- ilarly, cemented proximal humeral alloprostheses allow reconstruction of the joint and rotator cuff mecha- nism while minimizing traditional allograft complications, including nonunion and fracture. 33 Intercalary A llografts Perhaps the most predictably successful indica- tion for the use of large allografts is that of intercalary defects, for which joint stability and congruity are not issues. The most common applica- tion is that of long bone Ewing’s sar- coma, which is sometimes limited to a diaphyseal location. 34 In some cases, both Ewing’s sarcoma and os- teosarcomas extend to the metaphy- sis yet do not involve the growth plate. In these patients, careful resec- tion with intercalar y allograft recon- struction can result in preservation of both the epiphyseal structures (ar- ticular cartilage, ligamentous struc- tures, and menisci) and the physeal plate. Intramedullary fixation through the center of the physis can allow normal three-dimensional growth of the bone (Figure 7). Provid- ed that a local recurrence does not supervene because of the anticipated close surgical margins, the function- al outcome of this joint-sparing ap- proach makes intercalary allograft a compelling choice in very select cir- cumstances. 35 Incorporation can be enhanced by placement of a vascu- larized fibula inside the allograft. Corticocancellous Allografts When nonsegmental bone resection is undertaken, reconstruction is readily accomplished with cortico- cancellous allografts. This often is possible with parosteal and peri- osteal variants of osteosarcoma, which most commonly affect the posterior femoral metaphyseal- diaphyseal junction and midanterior tibial diaphysis, respectively. 36 Be- cause of the broad cancellous sur face area, healing generally is enhanced compared with massive cortical al- lografts. When titanium alloys (no ferrous magnetic effect) are used for internal fixation, magnetic reso- nance imaging surveillance for local recurrence remains an option (Figure 8). Conventional Endoprostheses Megaprosthetic technology has evolved considerably over the past 50 years. Initially, devices were lim- ited in both sophistication and sup- ply. The fact that surgery had to be delayed until custom-made prosthe- ses could be fabricated actually had a fundamental, albeit unintended, effect on protocols for treating os- teosarcoma. These protocols were altered to include preoperative che- motherapy, which later proved to be a superior approach. Presently, al- though some major centers continue to rely on custom-made endopros- theses, many cases can be complet- ed with modular, segmental, off-the- shelf implants. Initial problems with these de- vices included prosthetic fracture and dislocation. Design changes, in- Figure 7 A, Coronal T2-weighted magnetic resonance image of the distal femurs of a 10- year-old boy with a distal femoral osteosarcoma of the left leg that extended to within 1 cm of the physeal plate. B, Postoperative anterioroposterior radiograph demonstrating epiphyseal preservation and intramedullary fixation with healing at the proximal femur allograft osteosynthesis sites (arrow). Jason S. Weisstein, MD, MPH, et al Volume 13, Number 8, December 2005 551 cluding the use of curved stems and rotating-hinge total knee replace- ments, helped to overcome these difficulties. Currently, longevity of conventional prostheses is limited by prosthetic loosening secondary to stress-shielding of large stems as well as to particle-induced osteoly- sis. As with allografts, deep infec- tion remains a formidable complica- tion. Failure of standard endoprosthe- ses, whether cemented or cement- less, varies with anatomic location. In general, proximal humeral and proximal femoral implants fare best, whereas distal femoral and proximal tibial sites perform less well. 3-6 A re- cent report of cemented stems showed prosthetic survival rates at 15 years ranging from 79% for the proximal humerus to 14% for the proximal tibia; distal femoral im- plants had a 31% failure rate from a ll events. 7 As is true for allograft com- plications, such patients will need to undergo revision surgery, some more than once; ultimately, some might require an amputation. New Approaches in Endoprosthe- ses In younger pediatric patients (those with approximately 2 or more years remaining until skeletal matu- rity), limb-length equalization be- comes important whenever recon- structive options are considered. This is especially true for distal fem- oral tumors because this physis accounts for such a high degree of longitudinal growth. A definite ad- vantage of amputation procedures is the avoidance of this problem; as mentioned, the Van Nes procedures have the additional advantage of re- sidual limb growth from the rotated physis. Children reconstructed with allografts potentially would need to undergo ipsilateral lengthening or contralateral shortening procedures, including epiphysiodesis. With endoprostheses, the capaci- ty exists for expansion as a means to achieve limb-length equality. It is known that the distal femoral and proximal tibial physes provide longi- tudinal growth despite central pene- tration of a prosthetic stem; thus, the number of mechanical lengthen- ings is fewer than might otherwise have been anticipated. 37 Nonethe- less, a variety of novel engineering solutions has been developed to en- able prosthetic expansion over time. 38,39 Almost all of these tech- niques involve open or, at best, per- cutaneous procedures to achieve ex- pansion. To minimize the possibility of neurapraxia, repeated lengthen- ings of 1 to 2 cm are required. To achieve increased length in a noninvasive manner, a promising implant was created that uses an ex- ternal electromagnetic field to re- lease the energy stored in a spring 40 (Figure 9). The Repiphysis expand- able implant (Wright Medical Tech- nology, Arlington, TN) enables chil- dren to have their replacement bone grow without undergoing traumatic surgeries. This implant was recently reported to have allowed an average of 8.5 mm of lengthening per proce- dure, for a total average lengthening of 38 mm in 18 pediatric patients with sarcoma about the knee. 41 Al- though eight revisions were required for stem fracture or loosening, the opportunity of minimizing the num- ber of open procedures required to achieve limb-length equality is ap- pealing to patients and families. Another new product uses a spring-loaded design for prosthetic anchoring to eliminate the loosening complications of stemmed implants. Compliant prestress fixation (Com- Figure 8 A, Anteroposterior radiograph of an 18-year-old man demonstrating proximal tibial low-grade parosteal osteosarcoma (arrows). B, Axial computed tomography scan confirming the presence of the sarcoma of the proximal medial tibia. C, Three-year postoperative lateral radiograph demonstrating a completely healed reconstruction, accomplished with size-matched corticocancellous allograft, plate, and screws. Oncologic Approaches to Pediatric Limb Preservation 552 Journal of the American Academy of Orthopaedic Surgeons PreSs System; Biomet, Warsaw, IN) makes use of a stacked series of Belleville washers compressed with- in the prosthetic taper to achieve im- mediate rigid fixation and, thus, en- doprosthetic stability, without a stem 42 (Figure 10). Ongoing compli- ant forces foster bone hypertrophy and ingrowth that seem to provide long-term stability while sealing the medullary canal from particulate de- bris. This technology has proved to be fully versatile, especially in terms of the variety of anatomic locations, including short metaphyseal- diaphyseal segments, which are made amenable to salvage. In addi- tion, when necessary, revisions are entirely straightforward because the device spares the amount of addi- tional bone that must be resected. Initial results are encouraging, espe- cially for pediatric patients who are expected to place high demands for prolonged periods on any prosthetic implant. 43 Summary Many elements can affect successful outcome in pediatric orthopaedic oncologic care, including patient age, diagnosis, anatomic location, stage of disease, and socioeconomic factors. Thus, treatment algorithms cannot easily be devised. Consider- able controversy regarding manage- ment of these diverse neoplasms continues among or thopaedic oncol- ogists, and limb salvage rates are un- derstandably institution-dependent. A proper management strategy can be devised only after careful deliber- ation by all members of the treat- ment team as well as the patient and family. In these discussions, priori- tizing the goals of a multidisci- plinary program is essential. These goals, in order, are (1) life, (2) limb, (3) limb function, (4) leg-length equalization, and (5) cosmetic ap- pearance. When all else is equal in terms of overall survival and local control, proper emphasis should be placed on preservation of limb func- tion, including the possibility of am- putation. Because of the complex na- ture of the decision-making process and the risky nature of the surgery, referral of pediatric patients with a malignent neoplasm to oncologic centers is strongly recommended. References Evidence-based Medicine: Rougraff et al (reference 11) is a level III retro- spective cohort study. Hillmann et al (reference 19) is a level III retro- spective randomized study. 1. Arndt CA, Crist WM: Common mus- culoskeletal tumors of childhood and adolescence. NEnglJMed1999;341: 342-352. 2. Mankin HJ, Springfield DS, Gebhardt MC, Tomford WW: Current status of allografting for bone tumors. Orthopedics 1992;15:1147-1154. 3. Malawer MM, Chou LB: Prosthetic survival and clinical results with use of large-segment replacements in the treatment of high-grade bone sarco- mas. J Bone Joint Surg Am 1995;77: 1154-1165. 4. Unwin PS, Cannon SR, Grimer RJ, Kemp HB, Sneath RS, Walker PS: Aseptic loosening in cemented cus- tom-made prosthetic replacements for bone tumours of the lower limb. J Bone Joint Surg Br 1996;78:5-13. 5. Kawai A, Muschler GF, Lane JM, Otis JC, Healey JH: Prosthetic knee re- placement after resection of a malig- nant tumor of the distal part of the fe- mur. J Bone Joint Surg Am 1998;80: 636-647. 6. Ward WG, Yang R-S, Eckardt JJ: En- doprosthetic bone reconstruction following malignant tumor resection in skeletally immature patients. Orthop Clin North Am 1996;27:493- 502. 7. Yasko AW, Lin PP, Weber KL: Survi- vorship of segmental prosthetic ar- throplasty for limb salvage following bone sarcoma resections. Sarcoma 2001;5:61-62. 8. Mankin HJ, Mankin CJ, Simon MA: Figure 9 Postoperative anteroposterior radio- graph of a 9-year-old boy after resec- tion of a distal femoral osteosarcoma and reconstruction with the Repiphysis expandable implant (Wright Medical Technology). Figure 10 Anteroposterior (A) and lateral (B) 5-year postoperative radiographs of a 13-year-old boy with proximal tibial osteosarcoma who underwent resection and reconstruction with a ComPreSs System implant (Biomet). Stable osteointegration is evident. Jason S. Weisstein, MD, MPH, et al Volume 13, Number 8, December 2005 553