Roby C. Thompson

Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits.

Large doses of cortisone were given to growing and adult rabbits over a five-month period to produce avascular necrosis of the femoral head. The cortisone caused an increase in the serum cholesterol, fatty metamorphosis of the liver, and fat emboli visible in sections of the femur and humerus. These emboli partially obliterated the microcirculation of the subchondral vessels of both femoral and humeral heads. The average diameter of the marrow fat cells also increased more than ten micrometers. This increase in cell volume might be significant because in the closed chamber of the femoral head it could increase tissue pressure, diminish perfusion, and be the mechanism for avascular necrosis induced by cortisone.

Osteoarthrotic changes after acute transarticular load. An animal model.

The canine patellofemoral joint was subjected to a standardized transarticular load of 2170 newtons for two milliseconds, and the gross and histological changes were examined at two, twelve, and twenty-four weeks after injury. Initially, the load creates fractures in the zone of calcified cartilage, with minimum damage to the articular cartilage surface. Surface fissures were visible in all patellae only after staining with India ink. Histologically, these surface clefts extended into the transitional or superficial radial zone, and they did not communicate with the subchondral bone except in two patellae. However, there were reproducible clefts in the region of the subchondral bone and the zone of calcified cartilage in all patellae. Six months after loading, there was a loss of safranin-O staining above the deep clefts, and there was new-bone formation in the subchondral region and fibrillation of the cartilaginous surface. Thus, the initial changes had progressed to osteoarthrotic-like conditions at six months. In this animal model, the joint is not invaded and the changes that result from loading are reproducible. The injury to the joint creates superficial disruption of the cartilage and subchondral changes that lead to arthritic-like degeneration of the cartilage within six months.

Lumbosacral chordoma. Prognostic factors and treatment.

STUDY DESIGN Retrospective analysis. OBJECTIVES To analyze the prognostic factors in patients with chordomas, the success of various treatments, the diagnostic value of open versus needle biopsy, the neurologic impairment after sacral nerve resection, and the clinical presentation and site of origin. SUMMARY OF BACKGROUND DATA Staging of chordomas has not been of much value, compared with other bone tumors, because for chordomas, grade is similar, metastasis is infrequent at presentation, and the prognostic significance of size is uncertain. METHODS A review of patients with chordoma from 1965 through 1996 found 23 cases (mean age of patients, 55 years). The mean follow-up was 84 months. Mean tumor size was 81 mm (range, 35-135 mm), location was lumbar (n = 6), S1 (n = 4), S2 (n = 3), S3 (n = 7), S4 (n = 2), and S5 (n = 1). RESULTS No tumors were found in the higher sacrum (S1-S2) alone, without involvement of the lower sacrum. Survival analysis at 5 years showed overall survival (OS) 86%, continuous disease-free survival (CDFS) 58%, and local recurrence-free survival (LRFS) 60%. The location of tumor, defined by highest level of involvement (lumbar vs. sacrum) was of prognostic significance for OS (P = 0.01; log-rank test), CDFS (P = 0.036), but not for LRFS (P = 0.189). Results of multivariate regression showed that location was significant for OS (P = 0.007), CDFS (P = 0.008), and LRFS (P = 0.001). For patients with positive margins (n = 16), initial radiation correlated with longer CDFS (P = 0.002; Mantel-Cox) and LRFS (P = 0.005, Mantel-Cox), but was not significant for OS (P = 0.41). For patients who received no radiation, a positive margin correlated with a shorter CDFS (P = 0.04), a trend to shorter LRFS (P = 0.08), but no difference in OS. Therefore, both a tumor-free margin and initial radiation correlated with a longer survival. No patients had urinary or bowel dysfunction when both S3 nerves were preserved. If one S3 nerve was preserved, 1 of 3 patients had partial urinary incontinence and 2 of 3 patients required bowel medications. If both S3 nerves were resected, all patients required intermittent urinary catheterization and bowel medications. If both S2 nerves were resected, there was complete urinary and bowel incontinence. CONCLUSIONS The highest level of tumor involvement was prognostically significant for OS, CDFS, and LRFS. Radiation was of value when complete excision was not achieved. Bilateral S3 nerve preservation is necessary to ensure retention of normal urinary and bowel function.

The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis.

The zone of calcified cartilage (ZCC) forms an important interface between cartilage and bone for transmitting force, attaching cartilage to bone, and limiting diffusion from bone to the deeper layers of cartilage. The height of the ZCC is a relatively constant percent of articular cartilage and the height is maintained by a balance between progression of the tidemark into the unmineralized cartilage and changing into bone by vascular invasion and bony remodeling. During its formation, the cells that form the ZCC have properties similar to the cells of the growth plate. In the adult, the ZCC becomes quiescent but not inactive. The ZCC may be reactivated in osteoarthritis and may progressively calcify the unmineralized cartilage. This might contribute to cartilage thinning which would increase the concentration of forces across the uncalcified cartilage leading to more damage.

Soft tissue sarcomas: Preoperative versus postoperative radiotherapy

External beam radiation may be given either before or after excision of a primary soft tissue sarcoma. This study was undertaken to determine whether or not the timing of radiotherapy was associated with any difference in either local control, survival, or incidence of complications. The files of 112 patients with a primary, nonmetastatic, extremity soft tissue sarcoma, treated with limb salvage surgery and irradiation were evaluated. Data regarding tumor stage, grade, site, surgical margin, dosage and timing of radiotherapy, treatment complications, disease relapse, and relapse‐free survival (RFS) were analyzed. Kaplan‐Meier lifetable analysis was used to determine survival estimates. There was no significant difference in the 5‐year RFS between patients receiving radiotherapy (RT) preoperatively versus postoperatively; 56 ± 15% and 67 ± 12% (P = 0.12, Mantel‐Cox), respectively. There was no significant difference in the overall survival between patients receiving RT preoperatively versus postoperatively; 75 ± 15% and 79 ± 11% (P = 0.94), respectively. Actuarial local control at 5 years for preoperative versus postoperative RT patients was not statistically different; 83 ± 12% versus 91 ± 8% (P = 0.41), respectively. Wound complications were more frequent in preoperative RT patients (31%) compared to postoperative RT patients (8%) (P = 0.0014, chi‐square). Preoperative irradiation was not associated with any benefit in terms of relapse‐free survival, overall survival or actuarial local control in this series. A higher incidence of major wound complications was found among patients treated with preoperative irradiation. We recommend that patients with a resectable extremity soft tissue sarcoma be treated with postoperative irradiation, reserving preoperative irradiation for those situations in which either the tumor is initially thought to be unresectable or the original tumor boundaries are obscured.

Pathologic fracture in osteosarcoma : prognostic importance and treatment implications.

Background: The presence of a pathologic fracture in an osteosarcoma has been considered a poor prognostic factor and an indication for immediate amputation. The purpose of the present study was to determine, in the current era of neoadjuvant chemotherapy, whether a pathologic fracture in an osteosarcoma has prognostic importance and whether limb salvage can be safely performed in such patients without compromising clinical outcome. Methods: In a cooperative effort of the Musculoskeletal Tumor Society, members from eight institutions provided retrospective data on fifty-two patients with osteosarcoma who had a pathologic fracture and on fifty-five patients with osteosarcoma who had not had a pathologic fracture and had been followed for at least two years or until disease recurrence, metastasis, or death. The two groups were matched for patient age and tumor location. Outcomes examined were survival and local recurrence. A subgroup analysis was performed to assess differences in outcome within the group with the pathologic fracture. Results: The five-year estimated survival rates were 55% for the group with a pathologic fracture and 77% for the group without a fracture (p = 0.02). The rate of survival without a local recurrence at five years was 75% for the group with a fracture and 96% for the group without a fracture (p = 0.007). In the group with a fracture, seven (23%) of the thirty patients managed with limb salvage and four (18%) of the twenty-two managed with an amputation had a local recurrence (p = 0.75). Eleven (37%) of the thirty patients with a fracture who were managed with limb salvage and ten (45%) of the twenty-two patients with a fracture who were managed with an amputation died of the disease (p = 0.50). Five patients underwent open reduction and internal fixation followed by limb-salvage surgery. Two of them had a local recurrence and died at an average of eight months postoperatively. The remaining three patients were alive at an average of 6.1 years postoperatively. Local disease control and the survival of these patients were not significantly different from those for the thirty-three patients who were treated with nonoperative immobilization of the fracture followed by limb-salvage surgery. Conclusions: Patients with osteosarcoma who present with a pathologic fracture or sustain one during preoperative chemotherapy have an increased risk of local recurrence and a decreased rate of survival compared with patients who have not sustained a pathologic fracture. The performance of a limb-salvage procedure in carefully selected patients with a pathologic fracture does not significantly increase the risk of local recurrence or death. Factors predictive of improved outcome, such as the response to chemotherapy and union of the fracture, should be taken into account when limb salvage is being considered.

Fractures in large-segment allografts.

Sixteen of thirty-five large-segment allografts that had been implanted after resection for neoplastic conditions, and had been followed for a minimum of thirty-six months, were found to have fractured at a mean of twenty-six months after the implantation. Thirteen of the fractures were treated operatively, and we found a lack of vascularization and soft-tissue attachments to the graft at the fracture site. For seven fractured grafts, there were radiographic and clinical signs of union with the host bone. Eight of the sixteen grafts that had fractured were salvaged with one or more autogenous bone grafts, and two healed spontaneously. Thus, twenty-nine of the thirty-five grafting procedures were considered to have been successful in that the initial objective--provision of a functional segment for skeletal replacement--had been achieved. Multivariate analysis revealed a significant correlation for fracture in patients who were receiving chemotherapy when internal fixation of the graft had included devices that penetrated the cortices of the graft (p < 0.05).

Fractures associated with neuropathic arthropathy in adults who have juvenile-onset diabetes

Eighteen patients, twenty-five to fifty-two years old, who had juvenile-onset diabetes, had neuropathic arthropathy and fractures at the ankle or tarsus, most of which were bilateral. After a minimum follow-up of one year, four patients could not walk and fourteen were dependent on orthoses. In nine patients, the lesions produced fixed skeletal deformities that caused severe malum perforans, which in three patients was so severe that a below-the-knee amputation had to be done. In patients who had bilateral lesions, when the extremity that was initially involved was prevented from bearing weight, involvement of the contralateral limb became evident after an average of 4.5 months, compared with an average of twelve months in the patients who were allowed weight-bearing on the extremity that was initially involved. Our current treatment protocol is non-weight-bearing immobilization of the involved extremity, and we recommend prophylactic immobilization of the contralateral extremity with a protective cast or orthosis. All of the patients who had this treatment regimen could walk; in contrast, of the eleven patients who were not so treated, four could not walk.

Cell death after cartilage impact occurs around matrix cracks.

The damage from rapid high energy impacts to cartilage may contribute to the development of osteoarthritis (OA). Understanding how and when cells are damaged during and after the impact may provide insight into how these lesions progress. Mature bovine articular cartilage on the intact patella was impacted with a flat impacter to 53 MPa in 250 ms. Cell viability was determined by culturing the cartilage with nitroblue tetrazolium for 18 h or for 4 days in medium containing 5% serum before labeling (5‐day sample) and compared to adjacent, non‐impacted tissue as viable cells per area. There was a decrease in viable cell density only in specimens with macroscopic cracks and the loss was localized primarily near matrix cracks, which were in the upper 25% of the tissue. This was confirmed using confocal microscopy with a fluorescent live/dead assay, using 5′‐chloromethylfluorescein diacetate and propidium iodide. Cell viability in the impacted regions distant from visible cracks was no different than the non‐impacted control. At 5 days, viable cell density decreased in the surface layer in both the control and impacted tissue, but there was no additional impact‐related change. In summary, cell death after the impaction of cartilage on bone occurred around impact induced cracks, but not in impacted areas without cracks. If true in vivo, early stabilization of the damaged area may prevent late sequelae that lead to OA.

Entrapment neuropathy of the inferior branch of the suprascapular nerve by ganglia.

In a 37-year-old man, bilateral infraspinatus muscle weakness was associated with compression of the suprascapular nerve. The compression occurred at the spinoscapular angle by bilateral development of ganglia. The lesion was confirmed by electromyography. Surgical approaches to the area are described along with a review of the literature on different diagnosis. Complete recovery of neurologic function was documented.