Background: Skeletal metastases from renal cell carcinoma are highly destructive vascular lesions. They pose unique surgical challenges due to the risk of life-threatening hemorrhage and resistance to other treatments. The goal of this retrospective study was to evaluate factors that may affect survival after surgical treatment of metastases of renal cell carcinoma. Methods: We performed a retrospective review of a series of 295 consecutive patients who had been treated for metastatic renal cell carcinoma at one institution between 1974 and 2004. There were 226 men and sixty-nine women. A total of 368 metastases of renal cell tumors to the extremities and pelvis were treated. The surgical procedures included curettage with cementing and/or internal fixation (214 tumors), en bloc resection (117), closed nailing (twenty-seven), amputation (four), and other measures (six). Overall survival was calculated with Kaplan-Meier analysis. The log-rank test was used to evaluate the effect of different variables on overall survival. Results: The overall patient survival rates at one and five years were 47% and 11%, respectively. The metastatic pattern had a significant effect on the survival rate (p < 0.0001): patients with a solitary bone metastasis had the most favorable overall survival rate. Patients with multiple bone-only metastases had a better survival rate than patients with pulmonary metastases (p = 0.009). A clear-cell histological subtype was also associated with better survival (p < 0.0001). The tumor grade did not predict survival (p = 0.17). Fifteen patients (5%) died within four weeks after surgery. The causes included acute pulmonary failure (seven patients), multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia (one). There were no deaths attributable to intraoperative hemorrhage. Discussion: Survival beyond twelve months is possible for a substantial proportion of patients with metastatic renal cell carcinoma. Patients with a clear-cell histological subtype, bone-only metastases, and a solitary metastasis have superior survival rates. The presence of pulmonary metastases does not predict early death in a reliable manner, and some patients may survive for years with pulmonary and systemic disease. The data are important for surgeons to consider when choosing treatment for these patients. For example, local control of disease and implant stability are important issues for patients with a potential for a long duration of survival. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

BACKGROUND: Giant cell tumors of the bone can behave as aggressive and sometimes lethal tumors. In the sacrum, the tumor can be extremely difficult to manage. Standard treatments, including surgery and radiation, are associated with significant complications and recurrence rates. The goal of this study is to evaluate the long‐term outcome of selective arterial embolization as an alternative treatment modality.METHODS: From 1975 to 2001, 18 patients were treated with selective intraarterial embolization. The embolization method was a combination of Gelfoam particles and coils for peripheral and central occlusions, respectively. The number of embolizations was based on clinical symptoms, radiographic response, and the vascularity of the tumor. Nine patients received intraarterial cisplatin as part of their treatment. The median follow‐up was 105 months.RESULTS: Of 18 patients, 14 responded favorably to embolization with improvement in pain and neurologic symptoms. Computed tomographic and magnetic resonance imaging scans showed reossification and stabilization of tumor size. Arteriograms showed diminished vascularity. With long‐term follow‐up, three patients developed late disease recurrences within the sacrum. Kaplan–Meier analysis showed that the risk of local recurrence is 31% at 10 years and 43% at 15 and 20 years. The long‐term outcome was not affected by intraarterial cisplatin. There was one death that occurred 1 day after embolization.CONCLUSIONS: Most patients demonstrate an objective early radiographic response to embolization. Long‐term follow‐up shows that the response is durable in approximately one half of the patients. Given the potential morbidity of other treatments, embolization should be included in the armamentarium of treatment for this difficult disease. Embolization may be used alone or in conjunction with other therapy. Long‐term follow‐up is recommended for all patients because late disease recurrence or sarcomatous change can occur. Cancer 2002;95:1317–25. © 2002 American Cancer Society.DOI 10.1002/cncr.10803

Chondroblastoma is an aggressive tumor of bone with the capacity for recurrence and metastasis. We sought to determine the prognostic factors that affect survival and local recurrence with particular emphasis on surgical technique and the anatomic constraints of the open physis. It was hypothesized that an open growth plate would impact the local recurrence rate negatively and be a primary determinant of treatment outcome. We retrospectively reviewed 82 consecutive patients treated at one institution. Intralesional treatment with meticulous curettage and bone graft resulted in local control in the majority of patients. Four local recurrences developed between 5 and 51 months. An open growth plate was not found to correlate with local recurrence. In most cases, the open physis did not considerably impact surgical technique. Although the median age of the patients was 16 years, the majority of patients had a closed or closing physis. Few patients had substantial growth remaining. A physeal-sparing operation was done in six patients, and no local recurrences were observed in this group. The factors that seemed to affect local recurrence included inadequate surgery and biologic aggressiveness of the tumor. Inadequate surgery was likely to be the cause of local recurrence in patients who presented after previous treatment elsewhere. Three patients who developed local recurrence manifested increased biologic aggressiveness of disease. These patients subsequently developed metastatic disease and malignant transformation of disease. All three patients died from their disease. Pelvic tumors tend to be biologically more aggressive and more apt to recur locally and metastasize to distant locations. Level of Evidence: Therapeutic Study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Mice bearing germ line mutations of p53 develop sarcomas at a significant rate. Since they are susceptible to a variety of other malignancies, they are not ideally suited to the study of sarcomas. To test the possibility that targeted mutation of tumor suppressor genes in early mesenchymal cells would induce formation of sarcomas, the Prx1-cre transgenic mouse was crossed to mice-bearing floxed alleles of p53 and Rb. Mice with homozygous deletion of p53 (Prx1-cre p53 ^lox/lox ) developed sarcomas in the extremities at a mean time of 50 weeks. Osteosarcomas (OS) were the most common type of sarcoma (61%) followed by poorly differentiated soft tissue sarcomas (PDSTS) (32%). Homozygous deletion of p53 produced sarcomas significantly more rapidly than heterozygous deletion, which resulted in sarcoma formation after a mean of 96 weeks. Mice with homozygous Rb mutation (Prx1-cre Rb ^lox/lox ) developed normally and had no ostensible defects in the limbs. In contrast to p53, targeted deletion of Rb did not produce sarcomas in the limbs. However, simultaneous deletion of Rb and p53 accelerated the time to sarcoma formation, and a greater percentage of PDSTS were found. Deletion of p53 in committed osteoblasts by the Col1a1-cre transgenic mouse bearing an osteoblast-specific enhancer resulted in a high percentage of OS. These findings suggest that deletion of p53 in mesenchymal cells that give rise to osteoblasts is a powerful initiator of OS. Deletion of Rb does not initiate sarcoma formation in mice, but it accelerates formation of both soft tissue sarcomas and OS.

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of theEWS-FLI1fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore,EWS-FLI1by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further.

BACKGROUND: Soft tissue sarcomas of the hand and foot present unique management challenges. The purpose of the current study study was to determine oncologic outcome, particularly with respect to factors affecting local recurrence, distant recurrence, and disease‐specific survival.METHODS: A retrospective study was performed on 115 patients with soft tissue sarcomas of the hand or foot who were evaluated, treated, and followed at the authors' institution between 1980 and 1998. The medical records and radiographs were reviewed. Kaplan–Meier analysis was used to assess patient survival.RESULTS: Most patients (95%) were referred after previous surgery. The majority of tumors (75%) were T1 lesions (less than 5 cm), and most tumors (81%) were high grade. Patients who were treated by definitive, wide re‐excision (n = 43) had a 10 year local recurrence‐free survival of 88%, which was significantly better than the corresponding rate of 58% for patients who did not have re‐excision (n = 40, P = 0.05). Radiation improved local control in patients who did not undergo re‐excision (n = 17, P = 0.02). However, radiation did not improve local control in patients who had definitive re‐excision with negative margins (n = 13, P = 0.51). The disease‐specific survival at 5 and 10 years was 76% and 65%, respectively, for patients who presented with localized disease. Disease‐specific patient survival was significantly worse for patients who had regional or distant metastasis. Radical amputation as initial surgical treatment did not decrease the likelihood of regional metastasis and did not improve disease‐specific patient survival. The presence of distant metastasis at presentation was an independent predictor of local recurrence.CONCLUSION: Limb sparing treatment is possible in many patients with soft tissue sarcomas of the hand and foot. Re‐excision to achieve microscopically negative surgical margins is an effective method of achieving a high rate of local control in appropriately selected patients who present after unplanned excision of the primary tumor. There does not appear to be a survival benefit to immediate radical amputation, which should be reserved for cases where surgical excision or re‐excision with adequate margins cannot be performed without sacrifice of functionally significant neurovascular or osseous structures. Cancer 2002;95:852–61. © 2002 American Cancer Society.DOI 10.1002/cncr.10750