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Serial antibody dependent cellular cytotoxicity (ADCC) effector cell function estimates and renal biopsies were obtained from 74 recipients to determine the ADCC modifications induced by azathioprine/steroid therapy and the histological character of rejection associated with the modifications. Recipients with suppressed ADCC did not experience rejection episodes while recipients with non-suppressed ADCC suffered graft failure following steroid-resistant rejection. The majority of recipients experienced reversible rejection episodes which were preceded by increased ADCC activity in the five day period preceding the commencement of high-dose steroid anti-rejection therapy. It was concluded that ADCC was active in the rejection process, and that in vitro ADCC measurement provided a means of monitoring the modifications induced by azathioprine/steroid therapy which promote a post-graft term free of rejection episodes.

The rosette inhibition test has been used to detect an early pregnancy factor (EPF) in the serum of ewes. EPF was shown to be to be present within 72 h of mating and was still detectable after one month of gestation and in some cases after four months' gestation. The detection of EPF could be of value in the diagnosis of pregnancy in the ewe during the first month of gestation.

Isograft studies were performed in the murine model of cardiac transplantation to investigate the morphologic effects of operative ischemia. Primarily vascularized CBA mouse hearts were grafted heterotopically into the recipient CBA mouse's abdomen with standard microsurgical techniques. After ischemia times of 30 and 60 minutes, histologic examination showed minimal myocardial damage, with necrosis or scarring occupying less than 5% of the cross-sectional area of hearts bisected from apex to base after grafts had been removed on the seventh day after transplantation. Maximal ischemic damage was seen at 7 days after transplantation after 120 minutes of ischemia, with more than 30% myocardial necrosis or scarring of myocardial tissue. Isografts performed with ischemia times of less than 60 minutes were followed for more than 100 days. All hearts showed a fine, generalized, perimyocytic fibrosis, which was maximal at 28 days after transplantation and did not progress thereafter. These results will serve as important control measures for future studies in this model because ischemic damage must be considered in examining histologic samples from long-surviving cardiac allografts maintained in immunosuppressed recipients.

This paper discusses the use made of the antigenic specificity of malignant tumours in the diagnosis and subsequent management of a patient with secondary malignant disease who had previously been treated for both carcinoma of the breast and malignant melanoma. A comparatively simple, rapid test (leucocyte adherence inhibition) was used to determine the patient's antitumour immunoreactivity. Cell-mediated immunity against both types of tumour was detected, but this was accompanied by serum-blocking factor corresponding to melanoma only, which indicated that the secondary malignant disease was melanoma.

Thoracic duct lymph was drained for 28 days from a patient with disseminated malignant melanoma. Lymphocytes were separated from the lymph by centrifugation, and returned to the patient daily. Biochemical and hematologic parameters were monitored in blood and lymph, and were maintained at satisfactory levels throughout the period. Cell-mediated immunity and specific blocking activity directed against melanoma antigens were examined by the leukocyte adherence inhibition test. Blocking factors in drained lymph fell to undetectable levels after 6 days' thoracic duct drainage, whereas it took 9 days for serum blocking factors to fall to similar levels. Peripheral blood leukocytes demonstrated cell-mediated immunity against melanoma antigens before and throughout the period of drainage, except for the immediate postoperative period. Within 24 hours of closure of the thoracic duct fistula, serum blocking activity had returned, and 17 days later the patient died.

Between September, 1969, and December, 1978, 290 patients received 325 cadaveric renal allografts; 11 others transplanted elsewhere were also observed. Cancers developed in 28 patients (9.3%); 26 of these (93%) had skin cancers. The incidence of skin cancer increased by 5% annually after the first year of graft function, to a cumulative 44% in those surviving 9 years with functioning grafts. This represents an incidence of 4,356/100,000 person years of post-transplant risk--20.6 times the annual incidence of skin cancer in the general population of Southern Queensland. Half of the patients had multiple tumors when the first skin cancer was diagnosed, after a mean latent interval of 34 months. A total of 138 skin cancers occurred in 26 patients (average, 5.3 per patient), with a maximum of 19 in one individual. The ratio of basal to squamous cell carcinoma was reversed from 4:1, in the general population, to 1:1.7. Conventional surgical excision gave satisfactory results, with the one local recurrence being controlled by reexcision. Two patients (7%) died of melanoma and metastatic squamous cell carcinoma, respectively, whereas two of the other four patients who died from cancer had coincidental skin cancer. The two skin cancer deaths represent only 2% of all deaths in allograft recipients. These results suggest that the problem of skin cancer in these patients can be controlled and thus is not a significant contraindication to the continued clinical use of cadaveric renal transplantation.

The leukocyte adherence inhibition test was used to monitor tumor-specific cell-mediated immunity in 15 patients who had a variety of malignant tumors and were undergoing chemotherapy alone or in combination with immunotherapy by Corynebacterium parvum. A rapid and prolonged loss of cell-mediated immunity in blood leukocytes was observed after treatment in all but one of the patients studied. Abolition of reactivity was due to the lack of production of the soluble lymphokine-like factor affecting leukocyte adherence to glass. A new phenomenon of adherence stimulation by antigen, also mediated by a soluble factor, was observed after treatment in some patients. A drop in titer or total abrogation of serum blocking factors occurred in six of six patients tested following chemotherapy or immunotherapy. The lowered levels of blocking activity persisted during treatment and, with the possible exception of one patient, were not correlated with clinical benefit.

Studies using the rosette inhibition test have demonstrated a depression of lymphocyte activity in pregnant mice which occurs as early as 6 hr after fertilization and persists until just before delivery. This depression of lymphocyte activity is induced by two serum factors, the relative contributions of which vary with the time of gestation. The first, a high molecular weight early pregnancy factor, appears within hours of fertilization and then slowly declines in activity as gestation proceeds. The second, a lower molecular weight substance which cross-reacts with antiserum to human chorionic gonadotrophin, appears after the formation of the trophoblast at 4--5 days and persists until parturition.

Nonspecific immunotherapy with monthly intramuscular (IM) injections of Corynebacterium parvum has been investigated in patients with disseminated melanoma. Forty-nine patients were randomized to receive either imidazole carboxamide (DTIC) alone or DTIC plus C parvum. A 24% overall objective response rate was observed, with no significant difference between the response rate or survival of the two treatment groups. Immunologic studies revealed no significant difference between the two groups. One patient undergoing chemoimmunotherapy demonstrated profound pancytopenia which responded to cessation of therapy, but toxic reactions were otherwise minimal. No advantage was obtained by adding IM injected C parvum to standard chemotherapy in the treatment of disseminated melanoma.

Surgical oncology is now a defined discipline, and the training requirements require precise definition. The training period requires exposure to and understanding of tumour biology, tumour pathology and the role of surgery, together with that of the related disciplines of medical and radiation oncology. Training can be provided at three levels. The first occurs during the period of training for surgery in general for those with an interest in but not essential role in the delivery of tumour surgery. The second should be provided during subspecialty or regional specialty training where the treatment of tumours forms a major portion of the activities of that discipline. Finally, there should be a period of formal experience and training in an accredited unit for those who intend to specialize definitively in the treatment of malignant disease.

Evidence suggests that blood transfusions depress immunologic reactivity; as some tumors are influenced by the immune status of their host, it is possible that transfusions could promote tumor growth by impairing host immunity. The influence of blood transfusion on the growth of a transplantable B16 melanoma was examined in nude (athymic) CBA mice and immunocompetent C57 BL/6J mice. Recipients were given infusions of saline solution or syngeneic or H-2-incompatible allogeneic blood transfusions on two occasions 3 days apart. Infusions were begun 10 days before inoculation of a single cell suspension of B16 melanoma. Growth was determined by measurements of primary tumor volume and tumor weight after excision. There was no statistically significant difference in tumor size or weight between the three recipient groups of athymic mice. However, immunocompetent mice given H-2-incompatible allogeneic blood had higher rates of tumor engraftment--saline solution recipients versus allogeneic recipients: chi 2 = 13.2, df = 1, p less than 0.001; syngeneic recipients versus allogeneic recipients: chi 2 = 2.97, df = 1, p greater than 0.05. In the allogeneic group significantly larger and heavier tumors developed than in mice given syngeneic blood or saline solution. The study indicates that H-2-incompatible allogeneic blood transfusions can influence the growth of a transplantable murine tumor by a mechanism that involves a cell-mediated immune response.