Dale B. Glasser

Survival, prognosis, and therapeutic response in osteogenic sarcoma. The memorial hospital experience

Two hundred seventy‐nine consecutive patients with Stage II osteogenic sarcoma of the appendicular skeleton treated between 1976 and 1986 were studied to identify predictors of long‐term survival. Survival was 77% and 73% at 5 and 10 years, respectively, with continuously disease‐free survival being 70% and 69%. On univariate analysis, the most significant predictors of survival were the location of the primary lesion, local control of the tumor, and the degree of necrosis in the primary tumor after intravenous neoadjuvant chemotherapy (histologic response). On initial multivariate analysis, similarly, only location and histologic response to chemotherapy predicted disease‐free outcome. After statistical control for local recurrence, only histologic response to chemotherapy was retained as an independent predictor, suggesting that in this data set, the location of primary lesion exerted its effect only secondarily through its association with the ability to provide local control. The risk of local recurrence was almost fivefold higher in tumors of the femur than in tumors of other locations (relative risk, 4.6) and, within the femur, was more than threefold higher in the proximal femur than in the distal femur (relative risk, 3.4). None of the other primary tumor or patient characteristics studied yielded independent predictive significance for survival. The rate of failure was almost fivefold as high in those with an incomplete response to chemotherapy compared with those with a complete response to chemotherapy (relative risk, 4.9; 95% confidence interval, 2.2 to 11). Even in those patients with minimal or no necrosis in the primary tumor, ultimately 62% and 54% were disease‐free at 5 and 10 years, respectively.

Prosthetic and extremity survivorship after limb salvage for sarcoma. How long do the reconstructions last

Ninety-three consecutive prosthetic reconstructions performed for limb salvage after the resection of sarcomas of the lower extremity were reviewed to determine how long the reconstructions lasted, how successful they were in avoiding amputation in the long term, how significant a problem was aseptic loosening, and what was the associated patient survival. Reconstruction was of the proximal femur in 16, distal femur in 61 and proximal tibia in 16 patients. Minimum follow-up time was 24 months, with a median of 66 months and mean of 80 months. If any event leading to the removal of the prosthesis is considered a reason for failure, the event-free prosthetic survival at five years for the proximal femur was 88%, distal femur 59%, and proximal tibia 54%. Limb survival at five years was significantly better, with the proximal femur at 88%, distal femur at 88%, and proximal tibia at 78% intact. Aseptic loosening survival was better than the event free prosthetic survival, which demonstrates the influence of factors such as sepsis (hematogenous) or wound necrosis that lead to prosthetic removal. Aseptic loosening survivorship of the proximal femur at five years was 100%; distal femur, 78%; and the proximal tibia, 73%. At five years, patient survival was low for the proximal femur (62%) and distal femur (75%) but notably better for the proximal tibia (93%). Prosthetic, extremity, and patient survival differed depending on the site. Wound necrosis was a significant cause of prosthetic removal and loss of limb early in this series, but the more aggressive use of soft tissue procedures has improved this.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of cell surface antigen HBA71 (p30/32MIC2), neuron-specific enolase, and vimentin in the immunohistochemical analysis of Ewing's sarcoma of bone.

The HBA71 antigen is an M, 30,000/32,000 cell surfaceglycoprotein (p30/32MIC2), encoded by the pseudoautosomal MIC2 gene on chromosomes X and Y, that is expressed in Ewings sarcomas. Immunohistochemicalstudies demonstrate a striking specificity for HBA71 among neoplasms of diverse histologic types. In the present study, 43 cases of Ewings sarcoma of bone weretested for HBA71 expression and six additional immuno-histochemical markers regularly used in the differential diagnosis of small round-cell tumors of childhood and ad-olescence (neuron-specific enolase, vimentin, leukocytecommon antigen, cytokeratins, muscle-specific actin, desmin). The study design included (a) random selection of Ewings sarcoma cases from the files of Memorial Hos-pital beginning in 1968, (b) blind review of the original histopathologic diagnoses of ES, -(c) side-by-side immu-nohistochemical study of recut histologic specimens, and (d) statistical analysis of immunohistochemical findings in view of clinical outcome. Of the seven antigens studied, only HBA71, neuron-specific enolase and vimentin were expressed in a significant proportion of cases. Forty-one of the 43 cases were HBA71+ (95% sensitivity); of these, 21 were neuron-specific enolase+, 29 were vimentin+,and 15 were both neuron-specific enolase+ and vimen-tin+. One tumor lacked all antigens, and one was vimentin + only. Comparison of tumor tissues in five patients obtained before and after cytostatic chemotherapy showed no change in HBA71 expression or in the otherantigens tested. Product-limit survival analysis (median disease-free survival was 27.3 months for the study co-hort) revealed no significance of neuron-specific enolaseor vimentin marker status. These results raise doubts about the usefulness of neuron-specific enolase and vi-mentin immunohistochemistry to distinguish Ewings sar-coma from other small round-cell tumors of childhoodand adolescence or as prognostic indicators in Ewingssarcoma. The positive identification of Ewings sarcomaof bone now becomes a reality using HBA71 immunohis-tochemistry, either as a sole method or in combination with chromosomal breakpoint analysis. This may result inachieving uniform diagnostic criteria for evaluating the biologic, therapeutic, and prognostic aspects of Ewings sarcoma and related neoplasms.

The effect of chemotherapy on growth in the skeletally immature individual

One hundred twenty-two children with nonmetastatic osteogenic or Ewings sarcoma were studied to assess the effect of multiagent adjuvant chemotherapy on skeletal growth and final stature. No deviations from the height distributions of a normal population were noted at diagnosis. There was a marked retardation of linear growth during the year of intensive chemotherapy. Only 15% of the patients grew at the expected rate during that year. The distribution of nutritional status scores was significantly different at the end of the first year than at baseline. The distribution of ultimate height scores was significantly different than the baseline distribution. The overall final distribution was also significantly different from the normal population expectation. Any absolute difference in height, however, is likely to be small. The subgroups that were observed to full adult stature showed mean heights of 162 cm for girls and 176 cm for boys.

Human Immunodeficiency Virus Infection: Complications and Outcome of Orthopaedic Surgery

&NA; Orthopaedic surgeons practicing in areas with a high prevalence of human immunodeficiency virus (HIV) infection may expect that up to 7% of their patients who undergo emergent procedures and 1% to 3% of those who undergo elective surgery will be HIV‐positive. Although basic science studies have demonstrated impairment of defenses to routine orthopaedic pathogens as well as to opportunistic organisms, clinical studies have shown that this impairment has not resulted in an increased incidence of postoperative infections or failure of wound healing in the asymptomatic HIV‐positive patient. Even for the symptomatic patient, current medical management appears adequate to reduce the risk of early postoperative infection. The HIV‐positive patient with a prosthetic implant may be at increased risk for late hematogenous implant infection as host defenses diminish. Regular medical attention, prophylactic antibiotic therapy before dental work and invasive procedures, and early evaluation and treatment of possible infections are especially important in this setting. Decisions regarding elective surgery should be made on a risk‐benefit basis. Because the risk of surgical complications increases with progression of the disease, guidelines for elective surgery should include an assessment of the HIVpositive patients immune status, including the CD4 lymphocyte count, history of opportunistic infection, serum albumin level, the presence of skin anergy, and the state of nutrition and general health.

Stage IIB Osteogenic Sarcoma

Two hundred seventy-one consecutive patients treated from 1976 through 1986 were reviewed to estimate long-term survival. Disease-free survival for the entire cohort was 77% at five years and 74% at ten years. Humeral lesions had the best probability of survival (84% at ten years), followed by tibial lesions (81%) and femoral lesions (67%). Histologic response to preoperative chemotherapy was the strongest predictor of outcome. Those with little response had a survival estimate of 54% at ten years as compared to 68% for partial responders and approximately 90% for complete responders. Local recurrence was seen in 6.6% and was associated with an adverse effect on survival. Only two of the 18 patients with local recurrence have been rendered long-term disease-free survivors.

Lactase dehydrogenase as a tumor marker for recurrent disease in Ewing's sarcoma

The serum lactase dehydrogenase (LDH) of 56 patients with Ewings sarcoma was examined to determine the use of LDH as a tumor marker. The initial LDH level was used to determine its ability to predict survival. The follow‐up LDH level also was examined, as an indicator of recurrent disease. The initial LDH level was found to have no prognostic value. Both patients with elevated and normal LDH levels had the same survival rate. The LDH level at recurrence was significantly higher, however, than the follow‐up LDH level of those without recurrence (P < 0.001). The LDH level was most sensitive as a tumor marker for recurrent disease in those patients with multiple sites of tumor involvement at the time of recurrence.

Transmission of Human Immunodeficiency Virus Infection in the Surgical Setting.

&NA; The emergence of the human immunodeficiency virus (HIV) has highlighted the need for orthopaedic surgeons to understand the epidemiology of percutaneous injuries and other blood exposures in the surgical setting. The American Academy of Orthopaedic Surgeons and the Centers for Disease Control and Prevention have worked to increase understanding and prevent transmission of blood‐borne viral diseases in orthopaedic surgery. This article addresses the risk of HIV transmission in the surgical setting, with a focus on surveillance efforts to monitor the extent of occupational HIV infection, specific risk factors, and postexposure management. Health‐care worker‐to‐patient transmission and patient‐to‐patient transmission are also addressed.