This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration. Tumor responses can be evidenced in melanoma and sarcoma. Furthermore, combination of rTNF alpha, rIFN-gamma, and melphalan seems to achieve high efficacy with minimal toxicity, even after failure of prior therapy with melphalan alone.

TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.

Twenty-seven patients treated with high-dose rTNF alpha, IFN gamma and melphalan by isolated limb perfusion were histologically documented. There were 20 cases of melanoma-in-transit metastases and 7 cases of high-grade soft-tissue sarcoma. Biopsies were taken before IFN gamma, after IFN gamma, before TNF alpha and between 2 hr and 60 days after the TNF alpha perfusion. Immunohistochemistry was performed for adhesion molecules ICAM-I, ELAM-I (E selectin), VCAM-I and PECAM. During the first hours after beginning perfusion, the endothelial cells of the tumour capillaries appeared swollen. Significant tumour necrosis was already observed 3 hours after the perfusion in melanoma cases. The overall predominant feature was coagulative necrosis associated or not with haemorrhagic necrosis. TNF alpha induced increased expression of ELAM-I and VCAM-I adhesion molecules on intratumoral endothelial cells. The activated tumour vessels were progressively destroyed. Significant intravascular recruitment of polymorphonuclear cells (PMNs) was observed 3 hr after starting TNF alpha; it was followed by diapedesis and tumour colonization 3 days later. T lymphocytes and macrophages were detected during the first 7 days and B lymphocytes during the second week. Melanoma in transit metastases treated with alkylating agent alone did not show significant necrosis and did not express high levels of adhesion molecules (ELAM-I, VCAM-I) nor infiltration by PMN.

Probiotics have been proposed for a number of urogenital infectious conditions. In this study, we examine a possible effect on human papillomavirus (HPV)-related precancerous lesions in cervical cytology. We conducted a prospective controlled pilot study, in which 54 women with an HPV+low-grade squamous intraepithelial lesion diagnosis in their PAP smear were followed for 6 months. The intervention group consumed a daily probiotic drink during the study period; the control group received no treatment, according to common care policy. Outcome measures were the control PAP smear and HPV status after 6 months. Probiotic users had a twice as high chance of clearance of cytological abnormalities (60 vs. 31%, P=0.05). HPV was cleared in 19% of control patients versus 29% of probiotic users (P=0.41). This exploratory pilot study suggests that the probiotic studied promotes the clearance of HPV-related cytological abnormalities. If confirmed, this would represent an entirely new option to manage cervical cancer precursors.

Melanoma in children is rare. Nevertheless, it is imperative th at clinicians be aware th a t melanoma does occur in childhood. Y et th ere is very little information available on the clinicopathologic variations, and the prognostic parameters of mela noma in children. This report presents the results of a multicenter study of 102 lesions originally diagnosed as cutaneous melanoma, conducted among 5 Western European countries and collected during the period 1961-1994. Criteria for inclusion in the study included: ( I ) diagnosis of cutaneous melanoma; (2) age up to 16 years at diagnosis; and (3) availability of representative microscopic slides. On the basis of the histologic review only, 60 lesions were confirmed as melanoma, and 42 lesions initially diagnosed as mela noma were reclassified as nevi; 31 of the latter contained a predominance of spindle cells. The only significant parameter associated w ith the development of metastases or fatal outcome was thickness of more than 2.00 mm. The 5-year survival rate observed in this study was 84%. Based on these findings we conclude th at considerable over-diagnosis of melanomas in children occurs. In order, therefore, to give consistent epidemiological data on melanomas in children and to improve proper recognition of their diagnostic features, both by clinicians and by pathologists, we propose to set up a central registry of melanomas in children in Europe, under the auspices of the European Organization for Research and Treatm ent of Cancer.