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Biomedical subjects

F R Eilber

Publications and source records attributed to F R Eilber.

At least 19 recordsLinked to original sources
PubMed1996

Novel synthetic analogs of sialyl Lewis X can inhibit angiogenesis in vitro and in vivo.

Selectins have been shown to play an important role in angiogenesis. We have set out to synthesize multiple analogs of the selectin ligand sialyl Lewis X. We show here that analogs of sialyl Lewis X at concentrations of 50 micrograms/ml or greater significantly inhibited angiogenesis in in vitro assays of endothelial cell migration and proliferation (p < 0.05). These analogs also exerted significant inhibitory effects in in vivo angiogenesis assays using the chick chorioallantoic membrane at doses of 2 mg/chick or greater (p < 0.05). In contrast, the related carbohydrate Lewis X did not inhibit angiogenesis in both in vitro and in vivo assays. These data indicate that angiogenesis can be inhibited specifically by synthetic analogs of sialyl Lewis X. These analogs may potentially be useful in the treatment of angiogenesis-related diseases.

Animals↗
PubMed1995

Surgical indications for Ewing's sarcoma of the pelvis.

BACKGROUND: Despite advances in adjuvant therapy, Ewing's sarcoma of the pelvis remains an anatomic site with a poor prognosis. This study evaluate the role of surgery in the management of patients with pelvic Ewing's sarcoma who also received conventional radiation therapy and chemotherapy. METHODS: From May 1978 to February 1994, 19 patients with Stage IIB Ewing's sarcoma of the pelvis were treated at the UCLA Medical Center (Los Angeles, CA). There were eight lesions of the ilium, two of the sacrum, and nine involving two adjoining regions of pelvis. All patients received conventional medical management. The 19 patients were divided into two groups according to treatment modality. A group of 12 patients (Group A) had surgical resection, and their results were compared with those of another group of 7 patients (Group B) who did not have surgery. RESULTS: The 5-year cumulative survival (Kaplan-Meier method) was 39% for all patients, 51% for Group A, and 18% for Group B. The 3-year cumulative survival was 59% for all patients, 72% for Group A, and 36% for Group B. Although the survival rate of Group A seemed better than that of Group B, the difference was not statistically significant (P = 0.093, log rank method). This study also suggested that, regardless of treatment modality, the outcome of patients with lesions involving two adjoining pelvic bones was poorer than that of those with a single lesion. In Group A, the 3-year cumulative survival rate for patients with single bone lesions (n = 8) was 86% and for patients with lesions involving two adjoining pelvic bones (n = 4) was 50% (P = 0.045, log rank method). Furthermore, the statistical analysis of the combined data of the single pelvic bone lesions in UCLA and that of Mayo Clinic series (n = 16 for surgery group and n = 15 for nonsurgery group) confirmed the better results for the surgical patients, which was consistent with the results from the Mayo Clinic with an even greater significance (P < 0.002). CONCLUSION: This study demonstrates that surgery plus chemotherapy and radiation therapy is helpful for treating patients with pelvic Ewing's sarcoma so long as the tumor is limited to a single pelvic bone.

Adolescent↗
PubMed1995

High grade soft tissue sarcoma of the flexor fossae. Size rather than compartmental status determine prognosis.

BACKGROUND: High grade soft tissue sarcoma arising in the popliteal space, axilla, and antecubital fossae (flexor fossae tumors) have by convention been classified as extracompartmental tumors by the accepted staging and grading criteria of the Musculoskeletal Tumor Society (MSTS). Advances in neoadjuvant chemotherapy and radiation therapy have made surgical resection more feasible. The hypothesis to be tested is that compartmental status may not be of prognostic significance if the tumor is adjusted for size, histologic grade, and distant metastasis after undergoing adjuvant chemotherapy and radiation. METHODS: From June 1976 to December 1992, 22 patients with high grade soft tissue sarcomas of the flexor fossae (Group A) were treated at UCLA Medical Center. The histologic subtypes were liposarcoma (five), synovial cell sarcoma (eight), malignant fibrous histiocytoma (four), leiomyosarcoma (two), angiosarcoma (two), and rhabdomyosarcoma (one). The popliteal fossa was the location in 11, the axilla in 10, and the antecubital fossa in 1. Wide resection was attempted in all patients after preoperative chemotherapy and radiation therapy. Amputation was performed in 5 patients because of repeated or extensive recurrent tumor. A group of 77 patients (Group B) with high grade soft tissue sarcoma located within an extremity compartment were chosen to test the hypothesis that survival of patients with tumors in the flexor fossae is equal to that of patients with intracompartmental tumors of similar size and grade if both are given adjuvant therapy. This group was chosen so that histologic subtype, size, sex, and location would be similar in the two groups. The authors selected thigh and calf tumors for comparison with popliteal fossa tumors and periscapular, deltoid, and arm tumors for comparison with axilla and antecubital fossae tumors. All of these patients had similar treatment and follow-up protocols. The median follow-up of survivors in Group A was 104 months and for patients in Group B was 79 months. RESULTS: The 5-year cumulative survival rate (Kaplan-Meier method) of patients in Group A was 76%, and 67% for those in Group B. The difference was not significant. Three patients in Group A (14%) and 17 (22%) in Group B had local tumor recurrence. Eight patients in Group A (36%) and 27 (35%) in Group B had lung metastases. Age, sex, histologic subtype, and surgical margins did not affect survival outcomes, lung metastasis, and local recurrence. However, patients with larger tumors (maximum dimension > or = 8 cm or cross-sectional area > or = 40 cm2) had significantly poorer survival, more metastases, and local recurrences. CONCLUSION: Flexor fossae sarcomas do not have a poorer prognosis than extremity intracompartmental tumors when adjusted for size, distant metastasis, and histologic grade when they are treated with adjuvant radiation therapy, chemotherapy, and surgery.

Adolescent↗
PubMed1994

Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases.

PURPOSE: This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis. PATIENTS AND METHODS: We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected. RESULTS: The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P < .001) and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P < .003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (> or = 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P < .001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P < .048), four or fewer recurrent pulmonary nodules (P < .047), unilateral pulmonary metastases (P < .037), or longer intervals between primary tumor resection and metastases (P < .082). CONCLUSION: Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.

Adolescent↗
PubMed1994

Thoracotomy in the management of metastatic soft-tissue sarcomas in adults.

The multidisciplinary management of metastatic soft-tissue sarcomas in adults is capable of salvaging approximately half of the afflicted patients. This management includes preoperative chemotherapy for three months, thoracic surgery, continued chemotherapy, and the use of intrapleural mitoxantrone for once-present malignant pleural effusions or suspected pleural seeding of tumor. Thus, there is a definite role for the inclusion of thoracic surgery in the management of patients with soft-tissue sarcomas in whom pulmonary metastases develop.

Adolescent↗
PubMed1994

The role of thoracic surgery in the management of metastatic osteogenic sarcoma.

Fifty percent of patients with osteogenic sarcoma who develop pulmonary metastases are salvageable with continued effective chemotherapy and thoracotomies, as long as good local control is achieved in the primary tumor. In patients presenting with simultaneous primary tumor and pulmonary metastatic disease, the cure rate is potentially as high as it is in those patients who present with primary tumor alone. However, in the latter patients, curative surgery must be done to obtain permanent local control for the primary tumor, and thoracotomy must be performed to remove residual disease to ensure against recurrent disease.

Adolescent↗
PubMed1993

Expandable endoprosthetic reconstruction of the skeletally immature after malignant bone tumor resection.

The mainstay of local control of primary bone malignancies in the skeletally immature has been amputation or, in selected cases, rotationplasty. The development of expandable endoprostheses has permitted an alternative approach for local control in the growing child. Between January 1985 and December 1987, 12 skeletally immature patients with primary malignant bone tumors were treated with extremity reconstruction with cemented custom-expandable endoprostheses after wide resection of their lesions. All patients were observed until death (four) or revision (two) with a minimum two-year follow-up period for the survivors (average, 3.1 years). Seven patients have undergone a total of 11 expansions and one patient was lengthened with a revision-expandable prosthesis. Four patients have not needed expansion. Eight patients have had a total of ten complications. Seven of the ten complications (70%) were prosthesis related and associated with failure of the expansion mechanism. The Musculoskeletal Tumor Society (MSTS) overall rating was good to excellent in seven patients (58%), fair in three (25%), and poor in two (17%). In five distal femoral arthroplasties and one total femoral arthroplasty where the tibial bearing component was cemented through the physis, tibial and epiphyseal growth was observed to be normal and equal to the nonoperative side. This suggests that partial central epiphyseal and physeal ablation does not cause physeal arrest. Although the high rate of expansion mechanism failure necessitates redesign, preliminary results suggest that expandable endoprostheses do offer an alternative to amputation and rotationplasty as a means of local control and extremity reconstruction in children with primary malignant bone tumors.

Adolescent↗
PubMed1992

Surgical treatment and chemotherapy for pulmonary metastases from osteosarcoma.

Between 1971 and 1991, 247 patients with stage I osteosarcoma were treated at UCLA. Patients were treated in four sequential groups, with group 1 receiving surgery alone, and groups 2 through 4 receiving various adjuvant chemotherapeutic regimens. The incidence of lung metastases in these patients decreased from 92% (group 1) to 31% (group 4), while the proportion of patients undergoing pulmonary resection increased (17% vs 82%). Overall 5-year survival rate among patients with pulmonary metastases increased from 0 in group 1 to 41% (actuarial) in group 4. No clinical factor correlated significantly with outcome using univariate analysis, although there was a trend toward prolonged survival in those with longer disease-free intervals. Adjuvant chemotherapy and resection of pulmonary metastases have transformed a uniformly fatal condition into one with a reasonable expectation of long-term survival.

Adolescent↗
PubMed1991

Reirradiation for extremity soft tissue sarcomas. Local control and complications.

The treatment for patients who have locally recurrent soft tissue sarcoma of the extremity after surgery and radiation therapy is primarily amputation. A second course of radiation and local excision is usually not considered because of two major concerns: radiation complications and inability to achieve local disease control. This study examines the clinical course of 32 patients who received a second course of radiation for soft tissue sarcoma. Four groups of patients were defined by the sequence of radiation (preoperative and postoperative) and surgery. Despite high cumulative doses of radiation, complications requiring amputation were rare. Local tumor control was achieved with a second course of preoperative radiation and wide local excision in 15 of 18 (84%). However, local excision and a second course of postoperative radiation resulted in eight of 14 (57%) local failure and cannot be recommended as a comparable therapy to amputation.

Adult↗
PubMed1991

Endoprosthetic replacement for stage IIB osteosarcoma.

Over an eight-year period, 100 patients with IIB osteosarcoma have been managed. Eighty-one were treated with limb-salvage procedures, 78 of which involved reconstruction utilizing endoprostheses. Only 19 patients received amputation as the primary treatment for local control. Since 1984, all patients received preoperative and post-operative adjuvant chemotherapy. Those patients who received chemotherapy had a statistically significant improvement in five-year survival over those who did not (57% and 32%, respectively, p = 0.014). The functional results were good overall, with excellent results seen in distal femoral reconstruction. Twenty-eight of the 78 patients treated with endoprosthetic reconstruction experienced 30 complications (36%). Mechanical failure was the most common complication (10%) but was generally correctable. The local recurrence rate was 5% and the infection rate was 3%. Local complications were manageable. A statistical analysis revealed that the relative risk of patient death was 2.5 times higher than prosthesis failure for the 78 patients with endoprosthetic reconstruction. The intermediate-term results, with a median follow-up period of 43 months, remains encouraging.

Adolescent↗
PubMed1991

Endoprosthetic reconstruction after bone tumor resections of the proximal tibia.

The advent of successful adjuvant chemotherapy and radiation therapy protocols for primary malignant tumors and the development of custom-designed metallic endoprostheses has now made possible a successful limb salvage procedure for malignancies of the proximal tibia. Use of the transposed medial gastrocnemius flap, as proposed by Dr. Jean Duboussett of Paris, has been critical to the soft-tissue reconstruction that routinely permits an excellent active and passive range of motion for these patients. This article describes the operative techniques and technical considerations necessary for a successful proximal tibial endoprosthesis reconstruction.

Bone Neoplasms↗
PubMed1991

Soft tissue sarcomas of the extremity and retroperitoneum: advances in management.

The treatment of soft tissue sarcomas continues to pose significant challenges. The past decade has seen a dramatic increase in multimodality therapy for these tumors, with a resultant decrease in the number of amputations performed for extremity lesions. Even with combined modality treatment, however, the prognosis remains grim for most patients with retroperitoneal sarcomas, in which delay in diagnosis and tumor proximity to vital structures hinder the chances for cure. Improved protocols for the treatment of retroperitoneal sarcomas must be developed if we are to match the successes achieved with extremity tumors. As efforts to decrease local recurrence of extremity sarcomas have been largely successful, a new challenge to decrease the frequency of systemic metastases has emerged. Although aggressive surgical approaches to recurrent and metastatic sarcomas can result in long-term survival in some cases, better treatments are needed for those patients whose resections fail or those who are not candidates for resection. Combined modality treatments and new modalities, such as adoptive immunotherapy, need to be carefully evaluated in this group of patients. Enormous strides have been made in the treatment of osteogenic sarcomas and some pediatric soft tissue sarcomas. Additional research into basic tumor biology, as well as major intergroup studies of therapy, will be necessary if we are to duplicate those achievements in the more refractory adult soft tissue sarcomas.

Combined Modality Therapy↗
PubMed1990

Progress in the recognition and treatment of soft tissue sarcomas.

Over the past 10 years there has been significant progress made in the recognition and treatment of soft tissue sarcomas. With the advent of CAT scans and MRI, preoperative delineation of soft tissue tumors has become readily available. The diagnostic use of these modalities in patients presenting with an ill-defined asymptomatic mass has been extremely helpful in terms of screening patients to decide whether or not a biopsy is indicated. These techniques have also provided a much clearer delineation of the anatomic extent of the primary tumor, which has been of great assistance both in radiation therapy treatment calculations as well as in preoperative surgical planning. The recognition that tumor grade is the dominant prognostic variable has resulted in the more common use of a grading system, and a more uniform reporting and stratification of end results. Recent studies with immunohistochemical staining have proven of value in determining the histogenesis of many tumors that in the past were difficult to classify accurately. Most recently the use of flow cytometry suggests that this will also be a valuable adjunct in determining tumor grade and thereby prognosis. The most recent investigations of molecular biologic evaluation of genetic DNA and RNA sequences, as well as of oncogenes are extremely interesting from a diagnostic standpoint and in demonstrating the potential of molecular biologic evaluation for understanding the origin of these tumors. Multimodality therapy with surgery, radiation, chemotherapy, or all three has resulted in a marked improvement in local tumor control for patients with soft tissue sarcomas. The combination of modalities has allowed smaller surgical excisions of the tumor and thereby preservation of the extremity and much of its function. There are currently several different methods of multimodality therapy used including neoadjuvant therapy and postoperative therapy, both of which have been proven efficacious. Chemotherapy is now playing an increased role in clinical investigation and treatment. The availability of Adriamycin, DTIC, cisplatin, and most recently ifosfamide has added several chemotherapeutic agents for use by the clinician. Combination chemotherapy and radiation is of value in the neoadjuvant setting, and several studies are now underway to determine whether postoperative adjuvant chemotherapy is of similar value in reducing systemic spread of disease. Finally, surgical resection of pulmonary metastases has been proven of value in 20% to 25% of patients who subsequently develop metastatic disease. As a result of these advances in several different treatment disciplines, the overall survival rate and quality of life of patients with soft tissue sarcoma have improved markedly over the past 10 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Limb salvage therapy for soft tissue sarcomas of the foot.

From 1974 to 1988, 20 patients with soft tissue sarcomas of the foot underwent attempted limb preservation at UCLA. Eighteen patients had localized tumor and two had metastases. Sixteen patients had previously untreated tumors and four patients had experienced 2-4 local recurrences before definitive management. Eleven patients had grade 3 sarcomas and nine had grade 2 sarcomas. Fourteen patients had an excisional biopsy and six had an incisional biopsy. At the time of definitive local treatment, nine patients had palpable tumor ranging from 2-10 cm (median 5 cm). Sixteen patients received sequential preoperative chemotherapy and irradiation followed by attempted conservative resection. Four patients underwent immediate conservative resection followed by postoperative irradiation. Preoperative chemotherapy was administered over 3 days intraarterially, intravenously or by a combination of routes. Fifteen patients received 60-90 mg doxorubicin and one received 120 mg doxorubicin plus 220 mg cisplatinum. Preoperative irradiation was delivered in 350 cGy fractions to total doses of 3500 cGy (one patient), 2800 cGy (8) or 1750 cGy (7). Postoperative irradiation doses were 4140-6480 delivered in 180-200 cGy fractions. Fifteen of 16 preoperatively treated patients had limb salvage surgery. Four of these 15 had positive histopathologic margins and none received postoperative irradiation. One patient required a primary amputation due to gross involvement of the os calcis. Three of four patients undergoing immediate conservative excision had positive margins and one had gross residual disease. Five patients received chemotherapy following local treatment: 3 adjuvantly and 2 for metastatic disease. Follow-up for salvage patients ranged from 6 to 99 months (median 36). Local control was achieved in 17 of 19 (90%). Two patients recurred in-field at 24 and 30 months. Fourteen of 15 preoperatively treated and salvaged patients maintained local control. Three of four managed with excision and postoperative irradiation were controlled. The actuarial local control at 3 years was 83%. One patient recurred in the inguinal lymph nodes and three patients died of metastatic disease. The actuarial survival and relapse-free survival at 3 years were 83% and 63%. Eleven patients developed acute complications and four had late complications. Of 14 patients surviving with local control, function was good or excellent in 86%. No patient has required an amputation for complications or a dysfunctional foot. Limb salvage therapy for a selected patient with a soft tissue sarcoma of the foot can reasonably be expected to result in a high probability of local control and useful function without compromising survival.

Adolescent↗
PubMed1989

Patterns of recurrence after resection of osteosarcoma of the extremity. Strategies for treatment of metastases.

We studied recurrence patterns in 255 patients with high-grade osteosarcoma of the extremity and the efficacy of the treatment of these recurrences. One hundred seven patients developed metastatic disease: 77 had isolated pulmonary metastases, 17 had simultaneous metastases to lung and elsewhere, and 13 had metastases to other sites. Of the 77 patients with metastases confined to the lung, 51 (66%) underwent thoracotomy for resection of the metastases, and 13 (17%) are long-term disease-free survivors. Patients with simultaneous metastases to lung and other sites, and patients with metastases to sites other than lung, have a poor prognosis with only one long-term disease-free survivor in these groups. Thoracotomy has a limited role in the treatment of metastatic disease. Improvements in aggressive, systemic chemotherapy are essential for improving the prognosis in these patients.

Adolescent↗
PubMed1989

Preoperative intra-arterial chemotherapy.

The major factors affecting prognosis of patients with soft tissue sarcomas are local control, size of the primary tumor, and the grade of the tumor. The only factor that can be influenced following appropriate diagnostic procedures is local control. Surgery alone, even radical surgery or amputation, is insufficient to control large, poorly differentiated tumors in many cases. Preoperative therapy has been shown to be a highly effective method for local disease control. Intra-arterial therapy appears to have several advantages in the treatment of extremity sarcomas. (1) Intra-arterial therapy results in at least a sixfold increase in the concentration of drug in the blood perfusing the tumor. If combined with proximal occlusion of blood flow (balloon occlusion or tourniquet occlusion), the concentration of drug being delivered to the tumor may increase by 30-fold [32]. This high local concentration of chemotherapy is achieved in most cases without the high systemic toxicity that would be required by intravenous therapy. (2) Chemotherapy infusion prior to surgery allows administration of cytotoxic therapy through an undisturbed blood supply. This allows for an improved effect of therapy at the tumor margin, which is the area at risk for seeding the wound at the time of extirpative surgery. This may facilitate limb salvage in patients with bulky tumors. (3) Responses to this preoperative therapy allows an in vivo evaluation of the efficacy of the drug against the individual tumor. This may aid in determining efficacy of using the drug for postoperative adjuvant therapy. (4) Preoperative therapy allows treatment of the tumor while awaiting construction of custom prostheses, especially in patients with osteosarcomas of the extremities.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗