Biomedical subjects
Publications and source records attributed to J C Ivins.
A 48-year-old woman with an extensive pituitary adenoma developed atlanto-occipital instability secondary to erosion of the base of the skull by the tumor. The pathophysiology, diagnosis and surgical treatment are described.
Limb-saving resection has become a valid alternative to amputation in carefully selected patients with bone tumors. As interest grows in this technique, efforts continue to improve our methods of bone and joint reconstruction to restore a functional extremity. Previously there was little interest in this form of treatment despite a limb-saving potential, because of inadequate methods of skeletal reconstruction. The purpose of this paper is to review these previous methods and to outline our present approach to the problem.
To determine whether immediate or delayed lymphadenectomy is more beneficial than none in cases of localized (stage I) melanoma, we undertook in 1972 a prospective randomized study. Patients with midline trunk lesions were excluded as well as patients with lesions situated directly over the node-bearing area. In addition, because of the low risk of metastasis, the protocol was changed to exclude level 2 lesions. Of the 173 patients studied, 63 were randomized to no lymphadenectomy, 56 to delayed (3 months) lymphadenectomy, and 54 to immediate lymphadenectomy. None of these regimens differed significantly from the others in its effect on length of survival or interval to metastasis. And of the 110 patients who underwent elective lymphadenectomy, 103 were without nodal involvement. Our preliminary conclusion is that elective node dissection is not beneficial in management of melanoma. However, disease progression was advanced significantly by age of the patient (greater than 60 years) and by invasiveness (level 4 or 5) and thickness (greater than 1.5 mm) of the melanoma.
After nodal metastasis from malignant melanoma, approximately 80% of patients die from disseminated disease. To clarify the role of radiation therapy (XRT) following node dissection. 56 patients with biopsy-proven nodal metastasis participated in a randomized, prospective clinical trial which compares radiation therapy to the regional lymph node area following lymphadenectomy (27 patients) with lymphadenectomy alone (29 patients). Interesting differences in the survival curves (p = 0.09) and in the disease-free interval curves (p = 0.08) for the two treatment groups proved to be attributable to imbalances in the age and nodal distributions in the treatment groups. Covariate analysis identified age and sex as the factors having the most significant (p less than 0.04) effect on survival and identified the number of positive nodes as the covariate having the most significant (p less than 0.02) effect on disease-free interval. Treatment did not have a significant effect upon survival or disease-free interval.
Osteogenic sarcoma continues to present a tremendous therapeutic challenge. Until recently, treatment has continued at a relatively unsophisticated level. Although amputation, usually at a cross-bone level with a safe margin above the lesion, continues to be the treatment of choice, increased interest is being demonstrated in radical en bloc limb-saving resections. Modern joint implants are proving effective in restoring the osseous integrity and joint function after the resection.
Survival of patients with primary osteosarcoma who received traditional surgical management has been very poor. Several studies have reported the percentage of patients alive 3 years after first treatment to be between 20 and 25%. In a study of such patients first treated at the Mayo Clinic between Jan. 1, 1963, and July 1, 1974, the survival noted in the first few years was typical of that of other reports, about 25%. However, by 1972 through mid-1974, the 3-year survival had become 50%. This improvement was not the result of adjuvant treatment or any basic change in type of patient treated, yet it is similar to that reported in connection with some of the new adjuvant therapies used in trials depending on historical controls. Our results cast doubt on findings made in the absence of concurrent, randomly selected controls.
A randomized study compared the effects of combination chemotherapy (high-dose methotrexate, adriamycin, and vincristine) with immunotherapy in the form of transfer factor in the adjuvant treatment of patients with nonmetastatic osteogenic sarcoma after apparent complete surgical ablation of the primary tumor. Thirty-two patients were evaluated. Of 22 patients who received chemotherapy, three died of drug-related complications and six were alive without disease recurrence between 260 and 673 days after operation. Ten patients in the transfer factor group converted their markers, and of these, five were alive without recurrence 420--753 days after operation. Neither treatment program was considered superior with respect to disease-free survival.
Several measurements indicate that cellular and humoral immunity is depressed in patients with sarcoma; but whether such observations reflect diminished numbers of lymphocytes and their subpopulations is not known. We determined the numbers of peripheral leukocytes, lymphocytes, rosette-forming thymus-dependent cells (T cells), and nonthymus-dependent SmIg-bearing cells in 134 patients with various mesenchymal sarcoma and in 47 normal controls. In all of these determinations, patients and controls gave similar values. Furthermore, values for patients with or without tumor, with or without metastasis, and with bone or soft-tissue sarcomas were similar. All 134 patients were studied prospectively, and the 84 who remained free of disease after 6 months had virtually identical values to the 50 who showed disease progression.
Four patients with extra-articular synovial chondromatosis and one patient with combined intra-articular and extra-articular involvement are described. In all five patients the lesion was anomalously located (knee, shoulder, hip, and ankle). The lesion usually occurs in the hands and feet. Accurate diagnosis is important, because if the synovial origin of the cartilaginous proliferations is ignored, the evidence of cellular activity may lead to an erroneous diagnosis of chondrosarcoma. All five patients had a benign clinical course.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A clinicopathologic study of 79 patients with parosteal osteogenic sarcoma revealed that more females than males were affected and that most of the patients were in the second to the fourth decades of life. Sixty-eight percent of the patients had involvement of the posterior aspect of the lower femoral shaft. The roentgenogram characteristically showed a large, dense lobulated mass attached by a broad base to the underlying bone but with no involvement of bone itself. Microscopically, the tumor presented as well-formed bands of osteoid within a hypocellular spindle cell stroma. Seven of the lesions had foci of high-grade osteogenic sarcoma within an otherwise typical parosteal osteogenic sarcoma. Six of the 79 lesions showed involvement of the medullary cavity at surgery. Thirty-one patients had excision as their initial treatment; four of the 31 required nv further therapy. Ten patients had resection initially; three of the ten had recurrence. Only four of 27 patients who underwent amputation initially developed pulmonary metastasis. The presence of histologically "active" tumor and medullary involvement seemed to affect the prognosis adversely. Our data indicate that complete radical removal of the tumor is the treatment of choice, with resection when feasible and amputation when necessary.
Fifty-three patients with histologically confirmed osteogenic sarcoma of bone and no clinical evidence of pulmonary metastases were divided into two equivalent groups: one received elective pulmonary irradiation of 1500 rads administered to both lung fields, and the other acted as a control group. There were no significant differences in either survival probabilities or the interval between treatment and the development of pulmonary metastases. Therefore, elective whole lung irradiation so administered was not found to be of value as a prophylactic measure in the treatment of osteogenic sarcoma. There were no recognized untoward reactions to the pulmonary irradiation.
Forty-seven patients with mesenchymal sarcoma seen at the Mayo Clinic were tested for humoral and cellular immunologic responsiveness by means of a humoral cytotoxicity test, skin tests for delayed-type hypersensitivity, and lymphocyte transformation with concanavalin A, phytohemagglutinin, and pokeweed. Prospective follow-up of the clinical and laboratory results revealed that patients with low humoral cytotoxic indices, anergic skin test responses, or low lymphocyte transformation responsiveness tended to have the worst short-term clinical outlook.
In a Mayo Clinic prospective study of metastasis from osteogenic sarcoma, so-called prophylactic whole-lung irradiation (a 1,500-rad tumor dose to the whole of both lungs, in divided doses, with oxygen and actinomycin) proved ineffective. 14 patients underwnet an operation for metastatic pulmonary disease. The earlier the excision of a metastatic lesion, the greater the chance of an effective cure. Preoperative irradiation of the bone tumor had no positive effect. The primary lesion should also be excised as soon as possible. Surgical removal of a tumor should be followed by immunotherapy or chemotherapy or both. The rate of reliably "cured" cases could be improved by extensive studies of immunologic reaction before and after surgical intervention.
Twenty-six patients with classic osteosarcoma were randomized to receive either transfer factor or combination chemotherapy. Eight of 14 patients who received transfer factor converted their skin test markers, evidence of activity of the transfer factor. Of these eight patients, all are alive; four are free of disease. Of the 18 patients who received combination chemotherapy, 14 are alive, 12 of whom are free of disease. The immunologic test procedures performed sequentially reveal that transfer factor appears to enhance cell-mediated immunity, but it is evident that in this study, a control (saline) arm in the protocol could not be included. It is of interest that the chemotherapy regimen used does not appear to suppress such activity permanently. The individual test results, however, are not very helpful for predicting response to treatment. The small numbers of patients and the short duration of this study, combined with the exclusion of parosteal osteogenic sarcomas and jaw tumors, do not permit a meaningful comparison with other published studies.
A retrospective analysis of thirty patients who underwent pulmonary resection for metastatic osteosarcoma over a twenty-eight-year period revealed that most were young males with previous amputations for primary lesions of the lower extremity. In each, one to four thoracotomies had been performed, for a total of fifty-two chest operations with resection of 124 pulmonary metastatic lesions. At last follow-up, eleven of the thirty patients were alive and free of disease. At five years 28 per cent had survived: three of them were alive at more than nine years, and one was alive at nearly twenty years. Adverse survival factors identified were short tumor-free interval and multicentricity of pulmonary metastases. Long-term survival was associated with a tumor-free interval of more than two years and one to four thoracotomies at which few foci were present. As a group, patients selected for lung resection had significantly longer suvival than did patients whose pulmonary metastasis was untreated.
The clinical courses of 60 patients with hemangiopericytoma of the somatic soft tissues are summarized in this retrospective study. The tumors were subjected to a comparative histologic review and classified as benign (12 lesions), borderline malignant (16 lesions), and malignant (32 lesions). Tumors with 1 mitotic figure per 10 high-power field and moderate cellular anaplasia or 1 mitotic figure per 20 high-power fields and moderate cellular anaplasia may be expected to follow a malignant clinical course. Six of the 16 tumors with these microscopic features (borederline lesions) metastasized (37.5%), and 6 exhibited local recurrences after excision. Of the 32 malignant tumors, 25 (78%) metastasized. Twenty-three patients with malignant tumors were followed for more than 5 years or until death from tumor, and only one patient was alive and free of disease. Fifteen of the 23 patients experienced one of more local recurrences. None of the benign tumors metastasized. Surgical ablation of hemangiopericytioma is, in our experience, the only satisfactory method of treatment. Amputation of an extremity need be done only when the location of the lesion precludes a wide local excision. Local recurrent tumor was experienced by 22 patients after an inadequate local excision. Long-term follow-up is recommended because metastasis became apparent in 11% of patients with malignant tumors and 7% with borderline tumors after 5 "disease-free" years.