Robert C. Burton

OBJECTIVES: To measure the incidence of treated non-melanoma skin cancer (NMSC) in Australia in 2002 and investigate trends since 1985 by histological type, sex, age group, latitude and skin type. DESIGN: Face-to-face survey between 1 January and 31 December 2002 using stratified sampling of households to identify people treated for skin cancer in the previous 12 months. Self-reported diagnoses were confirmed with treatment providers. Data from similar surveys conducted in 1985, 1990 and 1995 were used to assess trends. SETTING: Whole of Australia (population 19.6 million). PARTICIPANTS: Of 57 215 people interviewed, 4098 said they had been treated for skin cancer in the past year and 3198 gave permission for their diagnoses to be confirmed with their doctor. RESULTS: 817 people were confirmed as having at least one skin cancer treated in the past year. The age-standardised rate per 100 000 population for NMSC was 1170, for basal cell carcinoma (BCC) 884, and for squamous cell carcinoma (SCC) 387. The estimated number of NMSC cases in Australia for 2002 was 374 000. Cumulative risks to age 70 years of having at least one NMSC were 70% for men and 58% for women. Rates of BCC and SCC have increased since 1985, and the increases greatest for people aged 60 years and older; rates for those younger than 60 years have stabilised. CONCLUSIONS: The incidence of treated NMSC in Australia in 2002 was more than five times the incidence of all other cancers combined. Although the overall NMSC rates have risen since 1985, the stabilisation of rates for people younger than 60 years who were exposed to skin cancer prevention programs in their youth highlights the importance of maintaining and strengthening these programs.

Using monoclonal antibodies and flow cytometry, wer serially monitored lymphocyte subpopulations in renal-allograft recipients treated with either conventional immunosuppression or a monoclonal antibody. In 29 patients given conventional suppression, highly significant correlations between changes in T-cell subsets and rejection were noted. Normal or elevated ratios of OKT4 (helper/inducer) to OKT8 (suppressor/cytotoxic) cells were associated with rejection unless the donor was HLA identical or the total number of T cells was extremely low. In patients with low ratios, rejection seldom occurred. Two patients treated with OKT3 monoclonal antibody for acute rejection had rapid disappearance of OKT3-reactive cells from the peripheral blood and prompt reversal of rejection. The use of monoclonal antibodies allows the precise determination of changes in T-cell subsets and promises the development of therapeutic protocols that can be designed to manipulate selected lymphocyte populations.

Effector lymphoid cells that inhibit hematogenous tumor metastasis in normal unimmunized mice were studied. Mice pretreated with cyclophosphamide (Cy) exhibited a diminished ability to destroy circulating tumor cells, which, in turn, caused an increased incidence of experimental pulmonary metastasis. Adoptive transfer of spleen cells from unimmunized syngeneic donors abrogated the Cy-induced enhancement of metastasis formation. The effector cell active in these adoptive transfer experiments was sensitive to treatment with specific anti-NK-1.2 antibodies and complement. This treatment was shown by in vitro tests to deplete or inactivate NK cells selectively. These findings provide direct evidence that NK cells play a significant role in the inhibition of hematogenous tumor metastases in vivo.

Eight cadaver donor renal allograft recipients, who had received azathioprine and prednisone from the day of transplantation, were treated with OKT3 monoclonal antibody (reactive with all mature peripheral blood T cells) at the time of diagnosis of acute rejection. In all cases, loss of essentially all detectable peripheral blood OKT3-reactive cells was noted within minutes after the initial 1- to 5-mg i.v. infusion. Chills and fever invariably occurred following the first or second infusion of monoclonal antibody, but were not noted during the subsequent, 10- to 20-day course of therapy, suggesting rapid cell lysis as the etiology of this toxicity. The established rejection episode was reversed in all cases within 2 to 7 days without addition of any therapy other than OKT3 antibody and despite continued lowering of the steroid dosages. During the subsequent 3- to 12-month follow-up period, further rejection episodes occurred in five of these patients, two of these were irreversible with conventional therapy so that six of the eight allografts continue with excellent renal function. These preliminary observations suggest that homogeneity, limited dosage requirements, and ease of in vitro monitoring of dosage effects should markedly simplify the use of monoclonal antibody to T cell populations in human allograft recipients. This second generation of antilymphocyte preparations offers the potential for not only increased effectiveness but also the possibility of manipulating specific T cell subsets.