Biomedical subjects

John H Healey

Publications and source records attributed to John H Healey.

At least 37 records · Page 2Linked to original sources

PubMed2005

Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.

PURPOSE: EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. PATIENTS AND METHODS: We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively. RESULTS: Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases. CONCLUSION: Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.

Adolescent↗

PubMed2005

Cell proliferation of cultured human cancer cells are affected by the elevated tumor pressures that exist in vivo.

Elevated interstitial fluid pressure (IFP) is observed in most solid tumors. However, the study of the cellular processes of tumors and the development of chemotherapy are routinely studied using in vitro culture systems at atmospheric pressure. Using a new pressurized cell culture system, we investigated the influence of hydrostatic pressure on population dynamics of three primary osteosarcoma (HOS, U2OS, SaOS2) and two metastatic tumor cell lines (MCF7 breast, H1299 lung) that invade bone. Values of IFP in normal human bone and muscle, and in osteosarcoma tumors obtained during their surgical biopsy established the hydrostatic pressure range for the in vitro cell studies. The IFP values were obtained from a retrospective review of patient records. IFP from confirmed osteosarcoma was 35.9+/- 16.2 mmHg. Tumor IFP was significantly higher than muscle IFP (p < 0.001) and bone IFP (p < 0.003). The in vitro study measured the cell-line proliferation using hydrostatic pressures of 0, 20, 50 and 100 mmHg. The findings suggest that hydrostatic pressure either increases or decreases tumor proliferation rates depending on cell type. Furthermore, cell death was not associated with apoptosis.

Cell Death↗

PubMed2005

De novo osteogenic sarcoma in patients older than forty: benefit of multimodality therapy.

UNLABELLED: The treatment of primary osteogenic sarcoma is well established in younger patients; however, controversy surrounds the treatment of this disease in the older population. To confirm multimodality therapy results in longer survival than surgery alone, 58 patients older than 40 years with primary osteogenic sarcoma were assessed retrospectively for the benefits of multimodality treatment versus surgery alone. We then asked whether specific patient and tumor characteristics and treatment modalities affected the rates of survival. Finally, we questioned whether pulmonary metastatectomy increased survival. The 5-year and 10-year overall survival for the group was 58% and 44%, respectively. Multimodality therapy increased survival compared with surgery alone in patients with high-grade disease. On multivariate analysis, considerable prognostic factors for improved overall survival for the entire group were age younger than 60 years, volume less than 100 cm, normal alkaline phosphatase, localized disease, negative surgical margins, and absence of recurrence. Pulmonary metastatectomy improved survival in selected patients. LEVEL OF EVIDENCE: Therapeutic study, Level III-1 (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

PubMed2005

Advances that are changing the diagnosis and treatment of malignant bone tumors.

PURPOSE OF REVIEW: Several neoplastic conditions may affect bone. These include primary bone tumors as well as metastatic disease from distant primary sites. Often, these entities produce symptoms that may be difficult to distinguish from those of various rheumatologic entities. The purpose of this review is to discuss recent developments in orthopedic oncology, with special attention given to advances that are changing the diagnosis and treatment of bone sarcomas and carcinomas metastatic to bone. RECENT FINDINGS: Much effort in the field of musculoskeletal oncology has been dedicated to the elucidation of the molecular mechanisms underlying bone sarcomas, especially in the case of osteogenic sarcoma and Ewing family tumor. Telomere maintenance mechanisms are emerging as potential targets for anticancer therapy. The most exciting advances have been in the development of novel treatments for cancers affecting bone. The anticancer effects of bisphosphonates, cyclooxygenase-2 inhibitors, and statins may expand their indications to the treatment of primary bone tumors. Finally, new expandable implants have been developed for the treatment of bone tumors in growing children. These devices may help solve some of the problems encountered with reconstruction of the growing skeleton. SUMMARY: Recent discoveries in the molecular mechanisms of bone sarcomas may help to elucidate the pathogenesis of these rare diseases. This, combined with the recent findings of the anticancer effects of bisphosphonates, cyclooxygenase-2 inhibitors, and statins, may lead to the development of novel treatments for sarcomas of bone and of carcinomas metastatic to bone.

Antineoplastic Agents↗

PubMed2004

Ankle instability after vascularized fibular harvest for tumor reconstruction.

BACKGROUND: The vascularized fibular graft is an important tool in the reconstruction of defects caused by resections of orthopedic tumors. Children often undergo this form of reconstruction, but there is little information about the complications after vascularized fibular graft harvest in this age group. METHODS: We present a series of 32 patients who underwent this procedure to reconstruct an extremity in our institution. There were 12 children and 20 adults. RESULTS: The residual distal fibula was significantly longer in adults as compared with children (P < .048). Among children, 3 of 11 undergoing the procedure developed ankle instability, in distinction to adults, none of whom developed this complication (P < .041). This reflects a disruption of normal ankle function that develops in skeletally immature patients with a short residual fibula but not in patients with a longer residual fibula (P < .008). When the sum of patient age in years and residual fibula length in centimeters was less than 16, 3 of 6 patients developed deformity, in contrast to no deformity developing in the remaining 23 when the sum was >16 (P < .004). Adults were more likely to develop pain than instability. CONCLUSIONS: Our series suggests that children with an age-length sum <16 should be considered for prophylactic tibiofibular synostosis creation.

Adolescent↗

PubMed2004

Biomechanical analysis of anterior poly-methyl-methacrylate reconstruction following total spondylectomy for metastatic disease.

STUDY DESIGN: Three reconstruction options were evaluated biomechanically following total spondylectomy using human cadaveric spine specimens. OBJECTIVES.: To evaluate and compare the stability of combined anterior and posterior fixation incorporating poly-methyl-methacrylate with alternative accepted reconstruction techniques. SUMMARY OF BACKGROUND DATA: Total spondylectomy represents the most radical option for decompression in metastatic spinal cord compression. Poly-methyl-methacrylate is considered a useful adjunct in spinal column stabilization and arthrodesis; however, there is little published biomechanical data to support its use in this setting. METHODS: Ten fresh-frozen human cadaveric spines (T9-L3) were used. After intact analysis, a total spondylectomy was performed at T12. Three potential reconstruction techniques were tested for their ability to restore stiffness to the specimen: 1) multilevel posterior pedicle screw instrumentation from T10-L2; 2) anterior instrumentation (ATL Z plate II) and rib graft at T11-L1 with multilevel posterior pedicle screw instrumentation from T10-L2; and 3) anterior cement (Simplex P) and pins construct (T12) with multilevel posterior pedicle screw instrumentation from T10-L2. Each of the three potential reconstruction techniques was tested on each specimen in random order using nondestructive testing under load control. RESULTS: Only combined stabilization techniques (e.g., anterior instrumentation and rib graft with multilevel posterior pedicle screw instrumentation and anterior cement-and-pins construct with multilevel posterior pedicle screw instrumentation) restored stiffness to a level equivalent to or higher than that of the intact spine in all loading modes (P < 0.05). Anterior cement-and-pins construct with multilevel posterior pedicle screw instrumentation provided more stability to the specimen than anterior instrumentation and rib graft with multilevel posterior pedicle screw instrumentation in compression and flexion testing (P < 0.05). Posterior instrumentation alone did not restore stiffness to the intact level in compression and flexion testing (P < 0.005). CONCLUSIONS: Combined anterior and posterior reconstruction using a cement construct provides equal to or more stability than the intact spine in all testing modes. Posterior stabilization alone is an inferior method of reconstruction following total spondylectomy. Poly-methyl-methacrylate has the advantage over traditional anterior reconstruction techniques in that it can be inserted using a posterior approach.

Aged↗

PubMed2004

Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway.

Osteosarcoma (OS) is a primary malignancy of bone with a tendency to metastasize early. Despite intensive chemotherapy and surgical resection, approximately 30% of patients still develop distant metastasis. Our previous work using clinical OS samples suggested that expression of the Wnt receptor LRP5 might be associated with tumor metastasis. In the present study, we used a Dickkopf (Dkk) family member and a dominant-negative LRP5 receptor construct to modulate Wnt signaling in OS cells. Saos-2 cells, which ectopically express Dkk-3, do not undergo apoptosis and exhibit enhanced resistance to serum starvation and chemotherapy-induced cytotoxicity. Transfection of Dkk-3 and dominant-negative LRP5 into Saos-2 cells significantly reduces invasion capacity and cell motility. This blockade is associated with changes in cell morphology consistent with a less invasive phenotype. In addition, Dkk-3 and dominant-negative LRP5 also induce changes in beta-catenin localization consistent with an increase in cell-cell adhesion. Taken together, these results support a possible role for Wnt signaling in the pathobiology and progression of human OS.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Divergent patterns of telomere maintenance mechanisms among human sarcomas: sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas.

Two types of telomere maintenance mechanisms (TMMs) have been described in human tumors: telomerase activation and alternative lengthening of telomeres (ALT). Although the vast majority of epithelial tumors rely on telomerase activation, many mesenchymal tumors rely on ALT for telomere maintenance, but within this tumor group, the TMMs used by translocation-associated sarcomas have not been systematically studied. We studied telomere lengths and telomerase expression and activity in 30 uncultured tumor samples and in 10 cell lines of Ewing's sarcoma, a prototypical translocation-associated sarcoma, and compared the data to an identical analysis of 60 osteosarcomas, the most common type of sarcoma lacking a specific translocation. Telomerase activity was demonstrated in 21 Ewing's sarcoma tumor samples (70%) and in 9 of 10 Ewing's sarcoma cell lines. Evidence of ALT, indicated by the presence of long and heterogeneous telomeres, was observed only in the cell line without telomerase activity and in none of the 30 Ewing's sarcoma tumor samples. The 9 Ewing's sarcoma patients whose tumors lacked detectable telomerase activity did not differ significantly from the remaining patients in age, stage, EWSR1-FLI1 fusion type, prevalence of TP53 point mutations, or overall survival. The low prevalence of ALT in Ewing's sarcoma contrasted sharply with our data on TMMs in 60 osteosarcomas, which showed ALT in 38 of 60 cases (P<0.0001). The present study, together with emerging published data on other sarcoma types, suggests that a predominance of telomerase activation in the absence of ALT may characterize sarcomas with specific chromosomal translocations (such as Ewing's sarcoma), whereas a high prevalence of ALT appears typical of sarcomas with nonspecific complex karyotypes (such as osteosarcoma).

Actins↗

PubMed2004

Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma.

The Wingless-type (Wnt) family of proteins and its coreceptor LRP5 have recently been implicated in human skeletal development. Wnt pathway modulates cell fate and cell proliferation during embryonic development and carcinogenesis through activation of receptor-mediated signaling. Osteosarcoma (OS) is a bone-forming tumor of mesenchymal origin whose growth control has been linked to autocrine or paracrine stimulation by several growth factor families. We examined 4 OS cell lines for WNT1, WNT4, WNT5A, WNT7A, WNT11, FZD1-10 and LRP5 expression by reverse transcription polymerase chain reaction (RT-PCR). In addition, RT-PCR for LRP5 expression was performed in 44 OS patient samples and the findings were correlated with clinical data. Expression profiling of Wnts and their receptors revealed the presence of several isoforms in OS cell lines. Overall, 22/44 (50%) of OS patient samples showed evidence of LRP5 expression. Presence of LRP5 correlated significantly with tumor metastasis (p = 0.005) and the chondroblastic subtype of OS (p = 0.045). In addition, patients whose tumors were positive for LRP5 showed a trend toward decreased event-free survival (p = 0.066). No significant association was found between LRP5 expression and age, gender, site of disease, site of metastasis or degree of chemotherapy-induced tumor necrosis. Sequencing of exon 3 of LRP5 in 10 OS patient-derived cell cultures showed no activating mutation of LRP5. These results showed that expression of LRP5 is a common event in OS and strongly suggest a role for LRP and Wnt signaling in the pathobiology and progression of this disease.

Adolescent↗

PubMed2004

The patterns of relapse in osteosarcoma: the Memorial Sloan-Kettering experience.

BACKGROUND: With the introduction of intensive high-dose chemotherapy for the treatment of osteosarcoma, changes in the pattern of metastases observed at relapse have been reported. To further investigate this hypothesis, the relapse patterns among groups receiving chemotherapy regimens of variable intensity at Memorial Sloan-Kettering Cancer Center were analyzed. PROCEDURE: All patients treated with the protocols T4, T5, T7, T10, and T12 were included. Patients were divided into two groups, one including those patients treated with less intense therapy (T4, T5, and T7) and the other, those treated with current regimens (T10 and T12). RESULTS: Of the 25 patients who relapsed on the earlier protocols, 76% relapsed to the lungs, 8% had local recurrences, and 16% distant metastases to the bone. The median time to first relapse was 12 months. Of the 69 patients who relapsed on the T10 and T12 protocols, 75% relapsed in the lungs, 9% had local recurrences, and 16% distant bone metastases. The median time to first relapse was 17 months. There was no statistically significant difference in the timing of relapse between the two groups studied, although a longer median time to relapse was observed for patients treated on the later protocols. The range of time to relapse was also wider in the later protocols. CONCLUSIONS: These data do not support the hypothesis that patterns of relapse are changing with alterations in osteosarcoma treatment. This limited single institutional experience can be explored further in the context of a multi-institutional effort.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

VEGF expression in osteosarcoma correlates with vascular permeability by dynamic MRI.

Dynamic enhanced magnetic resonance imaging has been used to assess tumor angiogenesis in osteosarcoma. Vascular endothelial growth factor has been shown to correlate with pulmonary metastasis and a poor prognosis in osteosarcoma. The purpose of this investigation was to determine whether vascular endothelial growth factor expression in osteosarcoma correlates with vascular permeability detected by dynamic enhanced magnetic resonance imaging and to explore the role of dynamic enhanced magnetic resonance imaging as a noninvasive means of assessing tumor angiogenic activity. Fifty-five osteosarcoma patients with osteosarcoma enrolled in a treatment protocol that included dynamic enhanced magnetic resonance imaging. In 15 patients, tumor tissues were available for vascular endothelial growth factor immunohistochemical studies. A two-compartment model used the exchange rate constants (kep) between the plasma and tumor compartments to quantify vascular permeability during dynamic magnetic resonance imaging studies. Immunohistochemical staining for vascular endothelial growth factor was graded according to the intensity and number of positively stained cells. Vascular endothelial growth factor-positive tumors showed higher mean vascular permeability when compared with vascular endothelial growth factor-negative tumors. Vascular permeability also correlated with increasing vascular endothelial growth factor expression. The preliminary results in this study show an association between vascular endothelial growth factor and dynamic MR signal enhancement in osteosarcoma. Dynamic enhanced magnetic resonance imaging should be investigated as a means to prognosticate osteosarcoma patients with osteosarcoma according to their tumor angiogenic activity.

Adolescent↗

PubMed2004

Percutaneous CT-guided biopsy of osseous lesion of the spine in patients with known or suspected malignancy.

BACKGROUND AND PURPOSE: CT-guided spinal biopsy (CTGSB) is considered a safe and accurate procedure. Our goal was to determine the accuracy of a CTGSB of osseous spinal lesions in patients with known or suspected underlying malignancy in reference to major variables such as the radiographic appearance of the biopsied lesion and its location within the spinal column. METHODS: We retrospectively reviewed results of 410 consecutive percutaneous CTGSB procedures of osseous spinal lesions. Biopsy was determined to be adequate if diagnostic tissue was obtained (n = 401) or unsatisfactory (n = 9) if only blood without cellular elements was present on final pathologic-cytologic examination. RESULTS: The level of spinal biopsy was cervical in nine patients (2%), thoracic in 123 (31%), lumbar in 164 (42%), and sacral in 96 (25%). The overall diagnostic accuracy of CTGSB was 89%, with a false-negative rate of 11%. Biopsy of lytic lesions yielded an accurate diagnosis in 93% (220 of 236). Despite technical challenges inherent to biopsy of sclerotic lesions, diagnostic accuracy was 76% (63 of 83), although more importantly, 24% (20 of 83) of the results in sclerotic lesions were falsely negative. CONCLUSION: CTGSB of osseous spinal lesions is an important tool in the workup of patients with known or suspected underlying neoplastic disease. However, a negative result must be confirmed with either close follow-up or, preferably, open biopsy, especially in cases of sclerotic lesions for which diagnostic accuracy is decreased and the false-negative rate is high.

Adolescent↗

PubMed2003

Long-term event-free survival after intensive chemotherapy for Ewing's family of tumors in children and young adults.

PURPOSE: To improve the long-term event-free survival of patients with Ewing's family of tumors (EFTs) using high-dose, short-term chemotherapy. PATIENTS AND METHODS: P6 was a prospective study of previously untreated patients with newly diagnosed EFTs. Patients received seven cycles of chemotherapy. Cycles 1, 2, 3, and 6 consisted of cyclophosphamide 2,100 mg/m2/d on days 1 and 2, and a 72-hour continuous infusion of doxorubicin 75 mg/m2 and vincristine 2 mg/m2 starting day 1. Cycles 4, 5, and 7 consisted of 5 consecutive days of ifosfamide 1,800 mg/m2/d and etoposide 100 mg/m2/d. RESULTS: Sixty-eight patients were enrolled from 1991 to 2001 (median age, 18.7 years; range, 3.7 to 39.9 years). At diagnosis, 44 patients had local-regional disease, and 24 had distant metastases. The 4-year event-free survival (EFS) rate for patients with local-regional disease is 82%; overall survival (OS) is 89%. The 4-year EFS rate for patients with distant metastases is 12%; the OS rate is 17.8%. All events occurred within 51 months of diagnosis. Four patients with distant metastases had progressive disease during therapy, and no patient with local-regional disease experienced disease progression during therapy. CONCLUSION: Sustained EFS and OS can be achieved with intensive chemotherapy in children and young adults with local-regional EFTs. This therapy is relatively ineffective in the treatment of metastatic EFTs.

Adolescent↗

PubMed2003

Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma.

BACKGROUND: Recurrent osteosarcoma is a drug-resistant disease with a dismal prognosis. The objective of this Phase II study was to evaluate the activity of ecteinascidin 743 (ET-743) as a salvage therapy in these patients. METHODS: Patients with recurrent osteosarcoma who had received standard chemotherapeutic agents were eligible. ET-743 was administered at a dose of 1500 microg/m(2) as a 24-hour infusion every 3 weeks. Pharmacokinetic studies were performed during the first cycle. RESULTS: Twenty-five patients were enrolled, 23 of whom were assessable for response (median age of 18 years; range, 12-67 years). The median number of previous chemotherapeutic agents was five (range, three to eight previous agents). Sixty-one cycles were administered (median number of cycles per patient was 2; range, 1-9 cycles per patient). Three patients (12%) achieved minor responses (49% 36% and 25%, respectively). Fifteen patients (60%) developed a transient elevation of hepatic transaminases (Grade 3 or 4 [according to the National Cancer Institute Common Toxicity Criteria]), which was not cumulative. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 12 patients (48%) and 6 patients (24%), respectively. The mean area under the curve (AUC) in 4 patients experiencing Grade 4 toxicity (76.4 +/- 29.3 ng x hr/mL) was significantly greater (P = 0.034) than that in those for whom the most severe toxicity was Grade 3 (39.5 +/- 17.2 ng x hr/mL [n = 12]) or Grade 1-2 (52.6 +/- 15.6 ng x hr/mL [n = 5]). There were no other significant correlations found between pharmacokinetic variables and patient characteristics, toxicity, or therapeutic response. CONCLUSIONS: ET-743 was found to be well tolerated in heavily pretreated osteosarcoma patients but had limited antitumor activity as a single agent. The combination of ET-743 with cisplatin or doxorubicin should be considered.

Adolescent↗

PubMed2003

Absence of a telomere maintenance mechanism as a favorable prognostic factor in patients with osteosarcoma.

There are two telomere maintenance mechanisms (TMMs) in human tumors, telomerase activation (TA) and, more rarely, the process termed alternative lengthening of telomeres (ALT). Unlike most carcinomas, sarcomas, including osteosarcomas (OS), have been reported to display TA and ALT in more balanced proportions and, thus, present an opportunity to examine the impact of different TMMs on clinical tumor behavior. We studied OS samples from 62 patients for molecular evidence of TA and ALT. Kaplan-Meier analysis demonstrated that the absence of both TA and ALT (in 18%) was more strongly associated with improved survival (P = 0.05) than were stage (P = 0.16) or chemotherapy response (P = 0.18) in this group of patients with OS. Subsets of OS cases with either TA or ALT did not differ significantly from each other in clinical outcome. There were no significant associations of presence, absence, or type of TMM with patient age, stage, or chemotherapy response. Thus, the absence of a detectable TMM may identify a favorable clinical subset of OS patients. Our study also suggests that the likelihood of detecting correlations between TMMs and clinical outcome in studies of certain other tumor types might be improved if, in addition to TA, ALT is included in future analyses. Finally, we note that OS cases with a TA-/ALT+ phenotype seem to be as clinically aggressive as TA+ cases in terms of stage and clinical outcome.

Adult↗

PubMed2003

Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.

PURPOSE: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. RESULTS: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.

Adolescent↗

PubMed2003

Epiphyseal osteoblastoma of tibia with xanthomatous stromal reaction.

Osteoblastoma occurring in long bones has a distinctive predilection for the metaphysis and the diaphysis. Epiphyseal location is rare. Although variation in histologic patterns is a well-known feature of this tumor, xanthomatous stromal reaction has not yet been described. We report a case of a 34-year-old man who developed an osteoblastoma primarily located in the epiphysis of his left tibia with extension into the metaphysis. The striking histologic features included a prominent xanthoma-like stroma consisting of foamy histiocytes in addition to focal areas with classical configuration of an osteoblastoma. The significance of this finding is discussed.

Adult↗

PubMed2003

Salvage reconstruction for lateral ankle instability using a tendon allograft.

Lateral ligamentous instability may result after an inversion injury to the ankle. Although it generally responds well to nonsurgical treatment, recurrent cases may warrant surgical intervention. There is extensive literature detailing various procedures designed to restore lateral ankle stability. We describe a case in which a patient had a distal fibulectomy for multiple symptomatic osteochondromas, with reconstruction of the lateral ligament complex using peroneus brevis tendon. The patient subsequently disrupted this surgical construct with a severe inversion injury and had recurrent lateral ankle instability. The lateral ligament complex then was reconstructed using a tibiotalar bone-tendon allograft directed to counteract inversion forces. Fourteen years after the procedure, the patient remains satisfied with a painless, stable ankle. The described technique provides a salvage reconstruction of the lateral ligament complex using allograft tissue, in the unique setting of an absent fibula and deficient peroneus brevis tendon.

Adult↗