Wide en bloc extra-articular excision of the elbow for sarcoma with complex reconstruction.

We describe a consecutive series of five patients with bone or soft-tissue sarcomas of the elbow and intra-articular extension treated by complex soft tissue, allograft bone and prosthetic joint replacement after wide extra-articular en bloc excision. All had a pedicled myocutaneous latissimus dorsi rotation flap for soft-tissue cover and reconstruction of the triceps. Wide negative surgical margins were obtained in all five patients. No local wound complications or infections were seen. There were no local recurrences at a mean follow-up of 60 months (20 to 105). The functional results were excellent in four patients and good in one. Longer term follow-up is necessary to confirm the durability of the elbow reconstruction.

Acetabular development after bipolar hemiarthroplasty for osteosarcoma in children.

A retrospective analysis was performed of eight patients with an open triradiate cartilage, who underwent resection for osteosarcoma and reconstruction of the proximal femur with a hemiarthroplasty, in order to identify changes of acetabular development. An analysis of the centre-edge angle, teardrop-to-medial prosthesis distance, superior joint space, teardrop-to-superior prosthesis distance, degree of lateral translation, and arthritic changes, was performed on serial radiographs. The median age at the time of the initial surgery was 11 years (5 to 14). All patients developed progressive superior and lateral migration of the prosthetic femoral head. Following hemiarthroplasty in the immature acetabulum, the normal deepening and enlargement of the acetabulum is arrested. The degree of superior and lateral migration of the prosthetic head depends on the age at diagnosis and the length of follow-up.

Resection of the sciatic, peroneal, or tibial nerves: assessment of functional status.

BACKGROUND: Lower-extremity tumors are often treated by amputation rather than limb-sparing excision that sacrifices the sciatic nerve or a branch. This study assessed the functional outcome of major nerve sacrifice during limb-sparing resections for lower-extremity soft tissue sarcoma. METHODS: Patients who underwent division of the sciatic, tibial, or peroneal nerve(s) during limb-sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven surviving patients evaluated their pre- and postoperative functional status by self-administered questionnaire (six sciatic, two tibial, and three peroneal nerve divisions). RESULTS: Eighteen patients (10 male, 8 female; 14-84 years old) had nine primary and nine locally recurrent tumors. Tumors were high (16) or low grade (two). Five patients died of disease and two died of other causes. Median overall survival was 50 months. One of 11 reported increased pain. Eight had new phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All patients used an ankle brace to walk after a sciatic (four) or peroneal (one) division. Walking ability and distance after surgery was unchanged (nine), improved (one), and worsened (one). Standing improved in 7 of 11 patients. Proprioception in the affected extremity was retained in six. The median postoperative leg functional score was 8 (1 = worst; 10 = best). No patient developed foot ulcers. One patient underwent amputation for recurrence. All patients preferred their status over having an amputation. CONCLUSIONS: Objectively and subjectively, division of the major lower-extremity nerves causes acceptable functional deficits in most patients. Resection of affected sciatic nerve (branches) during limb-sparing tumor surgery is an excellent alternative to amputation.

Lack of correlation of functional scintigraphy with (99m)technetium-methoxyisobutylisonitrile with histological necrosis following induction chemotherapy or measures of P-glycoprotein expression in high-grade osteosarcoma.

In osteosarcoma, some studies have suggested P-glycoprotein expression is a prognostic factor. The clearance of (99m)technetium hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been used in some tumor systems as an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored the correlation between (99m)Tc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma. The primary tumors of 20 patients with high-grade osteosarcoma were imaged at diagnosis with (99m)Tc-MIBI, and the uptake ratios and biological half-lives were calculated. P-Glycoprotein expression in the tumor tissue was determined immunohistochemically and by measuring mRNA expression of the multidrug resistance-1 gene. The histological necrosis following induction chemotherapy was assessed by the Huvos grading system. The biological half-life of (99m)Tc-MIBI ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent of necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio showed no correlation with histological necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio did not correlate with either measure of P-glycoprotein expression. The results of this pilot study indicate that (99m)Tc-MIBI imaging is not an effective predictor of histological necrosis following induction chemotherapy in high-grade osteosarcoma. (99m)Tc-MIBI imaging did not correlate with measures of P-glycoprotein expression in the tumor tissue.

Amputation for recurrent soft tissue sarcoma of the extremity: indications and outcome.

BACKGROUND: Limb salvage after primary site failure of extremity soft tissue sarcoma is a challenging problem. Amputation may be the most effective treatment option in selected patients with local recurrence. We compared the outcome of patients treated with amputation versus limb-sparing surgery (LSS) for locally recurrent extremity sarcoma. METHODS: From 1982 to 2000, 1178 patients with localized primary extremity sarcoma underwent LSS. Of these, 204 (17%) developed local recurrence. Eighteen (9%) required major amputation and the remainder underwent LSS, of which 34 were selected for matched-pair analysis according to established prognostic variables. Rates of recurrence or death were estimated by the Kaplan-Meier method. Following adjustment for prognostic variables, a Mantel-Haenszel test was used to compare the outcome between the two treatment groups. RESULTS: Patients in each group were well matched. All patients had high-grade tumors deep to the fascia. Median time to local recurrence was similar for both groups. Median follow-up was 95 months. Amputation was associated with a significant improvement in local control of disease (94% vs. 74%; P = .04). We observed no difference in disease-free (P = .48), disease-specific (P = .74), or overall survival (P = .93) between the two groups. Median postrecurrence survival was 20 months and 5-year OS was 36% for the entire study group. CONCLUSIONS: Limb-sparing treatment achieves local control in the majority of recurrent extremity sarcomas for which amputation is infrequently indicated. Amputation improves local disease control but not survival under these circumstances.

Biomechanical evaluation of the origin of the long head of the biceps tendon.

PURPOSE: Lesions of the superior glenoid labrum extending anterior and posterior (SLAP) have recently been recognized as important sources of shoulder pain and dysfunction. Among the 4 described types of SLAP lesions, the type II SLAP involves detachment of the superior labrum from the bony glenoid and destabilization of the origin of the long head of the biceps tendon (LHBT). The purpose of this cadaveric biomechanical study was to evaluate the relative contribution regarding linear stiffness and displacement under load of the 2 origins of the LHBT: the superior glenoid labrum and the supraglenoid tubercle (the biceps anchor). TYPE OF STUDY: Cadaveric biomechanical study. METHODS: Seven pairs of fresh-frozen cadaveric shoulders were dissected free of all soft tissue except for the glenoid labrum and LHBT. Tension from 0 to 55 N was applied to the LHBT while keeping the tendon perpendicular to the face of the glenoid. Each specimen was tested for linear stiffness and biceps tendon displacement in the intact state, after releasing 1 of the LHBT origins, and after releasing the remaining origin. RESULTS: The average stiffness of the LHBT origin was 103 N/mm. Sectioning the anchor alone resulted in a 52% reduction in linear stiffness, whereas only detaching the superior glenoid labrum from the 10 o'clock to the 2 o'clock position resulted in a 15% reduction in linear stiffness. Maximum displacement of the biceps tendon origin in the intact state at the 55 N load averaged 0.99 mm. With a minimum load applied, displacement changed less than 1 mm unless both origins were released. CONCLUSIONS: The results indicate that the biceps anchor is the primary restraint of the LHBT and that the superior labrum is a secondary restraint in regard to linear stiffness. However, disruption of both restraints is required to produce the laxity typically seen in a type II SLAP lesion.

Interstitial fluid pressure and blood flow in canine osteosarcoma and other tumors.

This study aims to characterize interstitial fluid pressure and blood flow in naturally occurring appendicular bone tumors in dogs because high pressure may influence the response of tumors to chemotherapy and radiation therapy. Eighteen client-owned dogs with naturally occurring appendicular bone tumors were included in this study. At the time of surgical biopsy, interstitial fluid pressure and blood flow were measured using wick-in-needle probes and laser Doppler flowmetry, respectively, within the soft tissue and bony components of the lesions and in normal muscle. Interstitial fluid pressure within the bony and soft tissue components of the tumors was significantly higher than interstitial fluid pressure in normal muscle. Blood flow in the bony component of the tumors was significantly lower than blood flow in normal muscle. There was no significant difference between blood flow in the soft tissue component of the tumors compared with that in normal muscle. Appendicular bone tumors in dogs have significantly higher interstitial fluid pressure and lower blood flow than do adjacent, unaffected soft tissues. The higher interstitial fluid pressure and lower blood flow may reduce tissue oxygenation and impede drug delivery. The effects of increased interstitial fluid pressure and decreased blood flow should be considered in the formulation of treatment strategies for the clinical management of appendicular bone tumors.

The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25.

Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identified non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBX-like domain that shows significant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocation-associated sarcomas. Oncogene (2001) 20, 48 - 57.

Human epidermal growth factor receptor 2 as a prognostic indicator in osteogenic sarcoma.

Prognostic biologic factors that can be assessed at the time of diagnosis for patients with osteogenic sarcoma have not been identified. The current study was designed to evaluate the prognostic significance of the human epidermal growth factor receptor 2 as it relates to histologic response to preoperative chemotherapy and event-free survival. A retrospective immunohistochemical study was performed on material from patients who were newly diagnosed with osteogenic sarcoma who were treated according to the T12 protocol from the authors' institution between 1986 to 1993. Staining for HER2/erbB-2 was accomplished using standard monoclonal antibodies and methods. At the time of initial biopsy, 42.6% of the samples showed HER2/erbB-2 overexpression. Higher levels of expression were observed in samples from patients with clinically detectable metastases at initial presentation and at relapse. Expression of HER2/erbB-2 correlated with inferior event-free survival in patients with nonmetastatic disease (47% versus 79% at 5 years). In addition, HER2/erbB-2 expression was associated with significantly less tumor necrosis after preoperative chemotherapy as determined by the Huvos grading system. These data suggest that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator and clinical trials using antibodies that target this receptor should be considered for the treatment of patients with osteogenic sarcoma.

Intralesional resection of primary and metastatic sarcoma involving the spine: outcome analysis of 59 patients.

OBJECTIVE: Surgery plays an important role in achieving local tumor control and cure for primary and metastatic tumors of the spine. As has been established with regard to sarcomas at extraspinal sites, these goals may best be achieved by en bloc resection with negative histological margins. Unfortunately, sarcomas of the spine often present with tumor patterns that are amenable only to intralesional resection, if neurological preservation is a priority. This study is a retrospective analysis of the long-term outcomes of patients who had operations for sarcomas of the spine using modern surgical approaches, intralesional resections, and spinal instrumentation. METHODS: Between 1985 and 1997, 59 patients had spinal operations for sarcoma involving the extrasacral spine. Data regarding tumor histology, grade, surgical indications, patterns of spinal tumor involvement, and neurological and functional outcomes were reviewed at presentation and at tumor recurrence. RESULTS: Thirty-five patients underwent a single operation, and 24 patients required reoperation for locally recurrent tumors. At presentation, only nine patients (15%) had tumors that were amenable to marginal or wide resections. Functional outcomes after initial spinal surgery and after operations performed at first tumor recurrence showed that 95% of patients had maintained or regained ambulation. Intradural extension of tumor was seen in 5 of 12 patients who had three or more operations for locally recurrent disease. The median survival from first spine operation was 18 months, and the median event-free interval between the first and second spine operations was 13 months. CONCLUSION: Surgery for sarcoma of the spine is useful for maintaining or improving neurological and functional outcomes, but local tumor recurrences are common. Because of the anatomy of the tumor at presentation and concern for neurological preservation, few patients are candidates for marginal or wide resections.

Cartilage tumors: evaluation and treatment.

The proper treatment of cartilaginous tumors is dependent on the clinicopathologic and radiologic findings. Enchondroma is a benign tumor that is usually asymptomatic and thus should be treated nonoperatively. Symptomatic enchondromas are often treated by intralesional excision. Intramedullary low-grade chondrosarcoma is a malignant tumor that is usually painful. The treatment of low-grade chondrosarcoma may range from intralesional excision with or without adjuvant therapy to wide excision. Although intralesional excisions have a higher bone and joint preservation rate than wide excisions, they may be associated with a higher local recurrence rate. Intermediate- and high-grade chondrosarcomas are treated with wide excisions. The treatment of these cartilaginous lesions should involve a multidisciplinary team including a musculoskeletal surgeon, a radiologist, and a pathologist.

Single-stage posterolateral transpedicle approach for spondylectomy, epidural decompression, and circumferential fusion of spinal metastases.

STUDY DESIGN: Retrospective review of prospectively maintained institutional spine database. OBJECTIVES: To assess the pain, neurologic, and functional outcome of patients with metastatic spinal cord compression using a posterolateral transpedicular approach with circumferential fusion. SUMMARY OF BACKGROUND DATA: Patients with spinal metastases often have patterns of disease requiring both an anterior and posterior surgical decompression and spinal fusion. For patients whose concurrent illness or previous surgery makes an anterior approach difficult, a posterior transpedicular approach was used to resect the involved vertebral bodies, posterior elements, and epidural tumor. This approach provides exposure sufficient to decompress and instrument the anterior and posterior columns. METHODS: During the past 15 months, 25 patients were operated on using a posterolateral transpedicular approach. The primary indications for surgery were back pain (15 patients) and neurologic progression (10 patients). All patients had vertebral body disease, and 21 patients had high-grade spinal cord compression from epidural disease as assessed by magnetic resonance imaging. Seven patients underwent preoperative embolization for vascular tumors. In each patient, the anterior column was reconstructed with polymethyl methacrylate and Steinmann pins and the posterior column with long segmental fixation. RESULTS: All patients achieved immediate stability. Pain relief was significant in all 23 patients who had had moderate or severe pain. Neurologic symptoms were stable or improved in 23 patients. One patient with an acutely evolving myelopathy was immediately worse after surgery, and one patient had a delayed neurologic worsening, progressing to paraplegia. CONCLUSIONS: The posterolateral transpedicular approach provides a wide surgical exposure to decompress and instrument the anterior and posterior spine. This technique avoids the morbidity associated with anterior approaches and provides immediate stability. Vascular tumors may be removed safely after embolization. Patients can be mobilized early after surgery.

Gait characteristics of patients after proximal femoral replacement for malignant bone tumour.

We analysed the gait characteristics of 15 patients with prosthetic reconstruction of the proximal femur after resection of a malignant bone tumour using stride analysis and measurement of oxygen consumption. Compared with normal volunteers their gait was slower, with less cadence and reduced stride length. The mean net energy cost of free walking was 141% of normal. The degree of asymmetry of the single-limb support time correlated with the free-walking velocity and the net energy cost. If they used a single cane the subjects walked with less cadence, longer stride length, and prolonged single-limb support times. The net energy cost of walking and asymmetry of the single-limb support time had a negative correlation with the strength of the hip abductor muscles. Their walking performance was better than that of six subjects who had hip disarticulation.

Prognostic impact of P53 status in Ewing sarcoma.

BACKGROUND: Disease stage at the time of diagnosis and response to therapy are the main prognostic factors for patients with Ewing sarcoma or peripheral neuroectodermal tumor (ES/PNET). The primary genetic alteration in ES/PNET, the fusion of the EWS gene with FLI1 or ERG, is diagnostically highly specific for these tumors, and molecular variation in the structure of the EWS-FLI1 fusion gene also is of prognostic significance. In contrast, secondary genetic alterations, such as P53 alterations, are relatively uncommon in ES/PNET, and their prognostic impact has not been extensively studied. METHODS: Prechemotherapy, paraffin embedded, nondecalcified, primary tumor material in a well-characterized series of 55 patients with ES/PNET with defined EWS-FLI1 fusion transcripts (32 patients with type 1 and 23 patients with other types) was studied retrospectively by immunohistochemical techniques for cell cycle regulators and proliferative markers, such as P53, P21(WAF1), and Ki-67, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique for apoptosis. Nuclear P53 expression in > 20% of tumor cells was scored as aberrant overexpression. Histologic response to neoadjuvant chemotherapy was assessed. RESULTS: Aberrant P53 expression (in > 20% of tumor cells) was present in 6 patients (11%) but showed no statistically significant correlation with disease stage, tumor size, proliferation rate (Ki-67), apoptotic rate (TUNEL), or EWS-FLI1 fusion type. By univariate analysis, the P53 > 20% group showed a significantly poorer overall survival among patients with localized disease (n = 43 patients) (P = 0.001) and in the entire study group (P = 0.01). In multivariate Cox analyses of overall survival, P53 > 20% was the strongest negative factor among prognostic factors available at the time of diagnosis (P = 0.001; relative risk [RR] = 9) and when chemotherapy response was included in the analysis (P53 > 20%: P = 0.01; RR = 10). CONCLUSIONS: P53 alteration appears to define a small clinical subset of patients with ES/PNET with a markedly poor outcome. The current observations warrant a systematic prospective study with comprehensive P53 mutation analysis. [See related article on pages 793-9, this issue.]

Prognostic impact of INK4A deletion in Ewing sarcoma.

BACKGROUND: The primary genetic alteration in > 95% of Ewing sarcomas (ES) is a specific fusion of EWS with FLI1 or ERG. Secondary genetic alterations possibly involved in progression of ES are not well understood. A recent study found loss of the negative cell cycle regulator gene INK4A in 8 of 27 ES samples (30%). To confirm these findings and evaluate their prognostic significance, the authors studied INK4A deletion in 41 ES samples from 39 patients. METHODS: Using Southern blot analysis with an INK4A p16 cDNA probe, the intensity of the INK4A bands in ES DNA samples was normalized to that of a control probe and compared with nondeleted control DNA; > 50% signal reduction was scored as evidence of deletion. All ES tumor DNA samples previously were confirmed to have EWS rearrangements on the same Southern blots, using a cDNA probe spanning the EWS breakpoint region. RESULTS: Tumors from 7 patients (18%) showed INK4A deletion independent of disease stage (localized or metastatic) or sample source (primary tumor or metastasis). INK4A was a strong negative factor for disease specific survival in univariate analysis (P = 0.001) and in multivariate analysis including stage (relative risk = 6; P = 0.001). CONCLUSIONS: INK4A deletions appear to be the most frequent secondary molecular genetic alteration found to date in ES. Their possible clinical usefulness in identifying a subset of ES patients with poor prognosis merits systematic prospective analysis. [See related article on pages 783-92.]

"Artificial lymphatic system": a new approach to reduce interstitial hypertension and increase blood flow, pH and pO2 in solid tumors.

A mechanical drainage system, the "artificial lymphatic system" (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN probe and IFP profile data were analyzed using numerical simulation and distributed mathematical models, respectively. The model parameter, P(E), reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration. The simulation demonstrated that spatial averaging inherent in WIN measurements reduced the calculated magnitude of the model parameter changes. IFP was significantly lower (p<0.05), especially in regions surrounding the drain, and BFR was significantly higher (p<0.05) following 25 and 45 min of aspiration, respectively; pH and pO2 profiles increased following aspiration. The experimental and mathematical findings suggest that ALS aspiration may be a viable way of reducing IFP and increasing BFR, pO2, and pH and should enhance solid tumor chemo and radiation therapy.

Enhancing the uptake of chemotherapeutic drugs into tumors using an "artificial lymphatic system".

This paper presents findings from uptake studies to evaluate the ability of an "artificial lymphatic system" (ALS) to enhance large and small molecular weight drug transport into solid tumors and the therapeutic effect of the additional drug on their growth. These studies also served to test the effectiveness of an implantable multidrain ALS. Walker 256, Neuroblastoma, and Sarcoma dual-tumor models were used to evaluate the effect of ALS aspiration on the uptake of 3F8 monoclonal antibody, and doxorubicin. A tumor shrinkage experiment using Walker 256 dual tumors was used to evaluate the efficacy of an implantable ALS with cyclophosphamide chemotherapy. Drug uptake significantly increased in all aspirated tumors; 3F8 uptake was enhanced 37.4% in the Walker and 93.1% in the Neuroblastoma tumor lines (p<0.05). Doxorubicin uptake increased 23.2% in Sarcoma tumor (p<0.05). The shrinkage study demonstrated that one-drain aspirated tumors shrank 90% faster (p<0.01) than control tumors, while three-drain aspirated tumors shrank 123% faster than control tumors (p<0.01).

MDR1 gene expression and outcome in osteosarcoma: a prospective, multicenter study.

PURPOSE: Increased expression of the multidrug resistance gene (MDR1) has been implicated in osteosarcoma prognosis. This study represents the first prospective assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma. PATIENTS AND METHODS: A series of patients with high-grade, nonmetastatic extremity osteosarcoma were enrolled from six tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 30 months). All patients were treated with (neo)adjuvant chemotherapy and surgery. Tumors from 123 patients were analyzed for MDR1 mRNA expression. The association of the level of MDR1 expression with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Using the highest MDR1 value for each patient, a dose-response relationship was not identified between the level of MDR1 expression and systemic relapse (relative risk, 1.15; P =.44). Analyses based on biopsy or resection values alone gave similar results (P =.11 and.41, respectively, log rank test). In multivariate analysis, large tumor size (> 9 cm) was the only significant independent predictor of systemic outcome (relative risk, 2.8; P =.002). CONCLUSION: We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma. It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease.

Complications of bone metastases: surgical management.

BACKGROUND: Patients with metastatic disease to the bone present a management challenge. Of the complications encountered in these patients, the predominant types that require surgical intervention are pathologic or impending fractures and neurologic compromise secondary to cord compression from spinal metastases. A multimodality approach is helpful in caring for these patients, and addressing complications related to bony metastatic disease with timely and appropriate intervention is an important step in optimizing care and quality of life. METHODS: This article incorporates information from multiple sources and presents recent reviews of the experience at the Memorial Sloan-Kettering Cancer Center with acetabular reconstruction for metastatic lesions, and with the use of the posterolateral transpedicular approach to address metastatic disease in the spine. RESULTS: Of 55 patients who underwent reconstruction of the acetabulum for metastatic disease, although there was a 25% incidence of local disease progression, there was only a 9% incidence of late fixation failure. Of the 41 who were evaluable at 3 months, 83% continued to experience significant pain relief, and 50% of nonambulatory patients regained walking ability secondary to the procedure. Of the patients with more than 2 years of follow-up, 86% maintained pain relief and 71% maintained their ability to ambulate and function in their community. The preliminary series of 25 patients managed with a posterolateral transpedicular approach to address metastatic disease in the spine showed excellent tumor control, pain relief, and neurologic preservation with the technique. Particular benefit was obtained for patients with extensive epidural disease in which an anterior approach was contraindicated. CONCLUSIONS: Although a multimodality approach to the treatment of patients with metastatic disease to bone combining appropriate surgical intervention with systemic therapy and radiation can entail a major operative procedure, the overall benefits to a patient's quality of life outweigh the risks in most cases. Clinician awareness of the various therapeutic options and their indications, and aggressive advocacy of quality of life for these patients, can improve the care delivered to people with metastatic disease.

Monoclonality of multifocal myxoid liposarcoma: confirmation by analysis of TLS-CHOP or EWS-CHOP rearrangements.

Multifocal presentation, defined as the presence of tumor at two or more anatomically separate sites, before the manifestation of disease in sites where sarcomas usually metastasize (e.g., lungs) occurs in about 1% of extremity soft tissue sarcomas (STSs). Debate still persists whether multifocal STSs represent an unusual pattern of metastasis or multiple separate primary tumors. Among STSs with multifocal presentation, myxoid liposarcoma is the predominant histological type. This subtype of liposarcoma contains the specific t(12;16) chromosomal translocation, which results in rearrangement of the TLS and CHOP genes that is clone specific at the DNA level. We, therefore, sought to address the question of clonality by molecular analysis in six patients who presented with either synchronous or metachronous multifocal myxoid liposarcoma. In all six cases, adequate frozen tumor was available for DNA extraction from at least two distinct anatomical sites. Southern blot analysis using CHOP, TLS, and EWS cDNA probes was performed on genomic DNA. Five cases contained a TLS-CHOP rearrangement, and one case had the variant EWS-CHOP fusion (seen in <5% of cases). The size of the rearranged CHOP fragment differed among the six patients, as expected, but was identical in all anatomically separate tumor samples from each patient. Likewise, the sizes of the rearranged bands observed with either the TLS or EWS probes supported the monoclonality of all cases. Our results confirm the monoclonal origin of multifocal myxoid liposarcoma, establishing the metastatic nature of distant soft tissue lesions in these cases. It remains unclear whether this unusual pattern of metastasis represents an intrinsic property of this subset of myxoid liposarcoma or merely a rare chance occurrence. The clinical outcomes observed in this small series suggest that the prognosis of multifocal myxoid liposarcoma is poor, regardless of its often bland or "low-grade" histological appearance.