Estrogen affects the cellular metabolism of the anterior cruciate ligament. A potential explanation for female athletic injury.

Investigations from this laboratory have established the presence of estrogen receptors in the human anterior cruciate ligament. This study further investigates the effects of 17 beta-estradiol on the cellular proliferation and collagen synthesis of fibroblasts derived from the rabbit anterior cruciate ligament. Fibroblast proliferation and collagen synthesis in response to near log concentrations of 17 beta-estradiol (at 0.0029, 0.025, 0.25, 2.5, and 25 ng/ml) were assessed by measuring [3H]thymidine and [14C]hydroxyproline incorporation, respectively. Collagen synthesis was significantly reduced with increasing local estradiol concentration (P < 0.001). Declining collagen synthesis was first noted at a 17 beta-estradiol concentration of 0.025 ng/ml. Within normal physiologic levels of estrogen (0.025 to 0.25 ng/ml), collagen synthesis was reduced by more than 40% of control, and at pharmacologic levels of 2.5 and 25 ng/ml, by more than 50% of control. A significant reduction of fibroblast proliferation was also observed with increasing estradiol concentrations (P = 0.023). Clinically, alterations in anterior cruciate ligament cellular metabolism caused by estrogen fluctuations may change the composition of the ligament, rendering it more susceptible to injury.

Morphology and matrix composition during early tendon to bone healing.

This study outlines the early morphologic phenomenon of tendon to bone healing in the rabbit model. Twelve skeletally mature, male New Zealand White rabbits received transplantation of the hallucis longus tendon into a 2-mm calcaneal bone tunnel. The morphologic characteristics of the healing tendon to bone interface were evaluated at 1, 2, 4, and 6 weeks after surgery by the use of conventional histology and immunohistochemical localization of collagen Types I, II, and III. Histologic analysis illustrated progressive maturation and reorganization of the tendon to bone interface with subsequent development of tissue collagen fiber continuity between the tendon and bone. Initially, diffuse immunolocalization of all three collagen types was observed within the scar tissue filling the space between the tendon and bone. During a 6-week period, reorganization of the scar tissue into an interface occurred, similar to an indirect insertion. Although a definitive fibrocartilage region did not form, Type II collagen was localized at the remodeling insertion site throughout the first 6 weeks of repair. In addition, Type III collagen fibers, resembling Sharpey's fibers, were noted to span this interface. The characterization of the insertion between tendon and bone is important to the understanding of healing in commonly used orthopaedic grafting procedures, such as anterior cruciate ligament reconstructions.

Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament.

To identify estrogen and progesterone target cells in the human anterior cruciate ligament immunohistochemical localization of both estrogen and progesterone receptors was performed in 17 specimens of human anterior cruciate ligament. All ligament specimens were obtained at surgery. Thirteen specimens were from women, and four were from men: the average age was 57 years (range, 18-78 years). Eleven specimens (from nine women and two men) came from total knee replacements for osteoarthritis of the knee: three (from two women and one man), from reconstructions of the anterior cruciate ligament: two (both from women), from medial meniscectomies; and one (from a man), from an amputation secondary to chondrosarcoma of the pelvis. An immunoperoxidase method using monoclonal antibodies to the estrogen and progesterone receptors was employed to identify estrogen and progesterone target cells in the anterior cruciate ligament. Staining of both receptors was demonstrable in 14 specimens and in the remaining three specimens less than 15% of the cells were stained. Both estrogen and progesterone receptors were localized to synoviocytes in the synovial lining, fibroblasts in the anterior cruciate ligament stroma and cells in the blood vessel walls of the ligament. This demonstration of receptors for estrogen and progesterone in the cells of anterior cruciate ligament suggests that female sex hormones may have an effect on its structure and composition.

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.

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.

Collagen in tendon, ligament, and bone healing. A current review.

Cells that produce a particular type of collagen under normal physiologic circumstances can be induced by certain local triggers to change the amount and type of collagen synthesized. This has become most apparent during bone, tendon, and ligament healing, where cells that once produced the collagen of normal intact tissue are induced to synthesize different types of collagen at the repair site of injured tissue. For example, Type III collagen, not a major component of the extracellular matrix in normal tendons, is believed to be of great advantage during the healing process because of its ability to form rapid crosslinks and precariously stabilize the repair site. Although much is known about the gross histologic changes occurring during tissue healing, little is known about the specific role of the individual collagen types or what influences their development. This review addresses the role of collagen in normal and healing bone, tendon, and ligament. Much experimental effort is needed to uncover the distribution and function of the collagen types within connective tissue elements and the effect of growth factors on the phenotype of collagen produced in these tissue, with the ultimate goal of developing clinical manipulations that take advantage of the unique properties of each type of collagen.