Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options.

Between 1979 and 1996 303 men with stage I testicular germ cell tumours (120 seminoma and 183 non-seminomatous germ cell tumours (NSGCT)) were enrolled onto a programme of surveillance. In our institutions the frequency of computed tomography (CT) scans is reduced compared with other centres. For all 303 men, the median follow-up is 5.1 years (range: 0.1-21.7 years) and there have only been 3 deaths (1 from disease, 1 from neutropenic sepsis and 1 from secondary leukaemia). 52/183 (28%) patients with NSGCT and 18/120 (15%) patients with seminoma have relapsed. The relapse-free survival at 5 years is 82% for seminoma and 69% for NSGCT (Logrank P=0.004). All men who relapsed, except 1 man with NSGCT, were in the International Germ Cell Cancer Collaborative Group good or intermediate prognosis group at relapse. Half of the seminoma relapses presented with symptoms and 31% of the NSGCT relapses. The remaining relapses were detected serologically or radiologically by the surveillance programme. 5 men (2%) on surveillance, 3 with initial diagnosis of seminoma and 2 with NSGCT, have developed second contralateral testis tumours (all stage I seminomas). In a well motivated centre a policy of surveillance for stage I testicular germ cell tumours (both NSGCT and seminoma) is associated with a low mortality rate (3/303, 1%) and may have the advantage of sparing overtreatment with potentially toxic therapies in this group of young men.

A molecular cytogenetic approach to studying platinum resistance.

The technique of comparative genomic hybridisation (CGH) has until recently been used to screen for common genomic abnormalities in fresh tumour material; it has identified previously unrecognised regions of amplification associated with poor prognosis subtypes of breast cancer and lymphoma. Our group has applied this technique to resistant cell lines and their sensitive counterparts in order to define chromosomal abnormalities associated with acquired drug resistance. We have demonstrated the applicability of this technique to the study of drug resistance using cell lines with known mechanisms of resistance. The ability to detect novel genomic alterations in cell lines with novel mechanisms of resistance was also demonstrated. We subsequently examined the CGH profiles of seven different cell lines made resistant to three platinum analogues and showed the most consistent abnormalities to involve over-representation of regions 4q and 6q. More recently, we have applied the CGH technique to a series of testicular germ cell tumours (TGCTs) collected as formalin-fixed paraffin-embedded biopsy specimens from patients, both pre- and post-therapy using a platinum-based regimen (POMB/ACE). Previous reports have shown over-representation of X, 7q, 8q and 12p and loss of 13q to occur in 25% of primary TGCTs. Over-representation of 12p was confirmed in the majority of these biopsy samples; deletion of 13q was noted in the initial biopsies of several patients. We also demonstrated alterations of 4p, 4q, 5q and 6q in this series of patients. Newly acquired deletions of 2q and 18q and amplifications of 8q were frequently observed in post-chemotherapy samples from resistant tumours. The CGH studies on these patients with TGCT will not only enable us to correlate our observations on clinical material with those from long-term cell lines, but should also identify sites of key genes involved in clinical platinum resistance.

Storage iron depletion in male blood donors: its significance for iron status in women.

Among 24 male blood donors without anaemia who had been giving a mean of 2.2 donations per year involving a mean blood loss of about 900 ml a year, 10 (41%) were found to be depleted of storage iron. This is somewhat higher but similar to the previously recorded findings in healthy women without anaemia. The results may well support a policy of limiting blood donation to twice a year in men and to once a year in women. Both men and women blood donors require medicinal iron after each donation. It is considered that storage iron depletion in non-anaemic women is not in the main related to pathological levels of menstrual loss but rather to inadequate dietary iron. Food iron in present-day diets should be supplemented.

Iron chelation in haematomas at fracture sites.

Previous work suggested that during the catabolism of haemoglobin a physico-chemical form of iron was released which was more readily chelatable by desferrioxamine than normal storage forms, as ferritin-haemosiderin. Desferrioxamine chelation was therefore investigated in five patients with major fractures in which haemoglobin catabolism is greatly enhanced by the red cell destruction which proceeds in the associated haematoma. Considerable increases in the amounts of iron mobilized by desferrioxamine were observed from the second day after injury. In severe interstitial haemorrhage, these values tended to increase until 10 to 20 days, and sometimes were as high as chelation values seen in haemochromatosis. These results are considered to support the hypothesis that a highly chelatable form of iron is found at some stage during haemoglobin catabolism.

Differential ferrioxamine test in idiopathic haemochromatosis and transfusional haemosiderosis.

The differential ferrioxamine test measures the amount of body iron as ferrioxamine (Fv) chelated by a standard dose of desferrioxamine.Five patients with untreated, uncomplicated idiopathic haemochromatosis and one with transfusion haemosiderosis gave Fv in the range 1,948 to 2,462 mug./kg. (normal 110 to 500). One case of transfusion haemochromatosis with haemolytic anaemia and renal failure gave an Fv value of 8,019 mug./kg. Four patients with idiopathic haemochromatosis after therapeutic venesection gave Fv values of 212 to 885 mug./kg. One relative with a value for Fv of 776 mug./kg. was shown to have early cirrhosis by liver biopsy. Serial Fv measurement after venesection in this patient provided a preliminary assessment of the relationship between Fv values and available iron stores up to about 2,000 mg. iron. This relationship applies only when red cell survival is normal. Approximate figures for the range of available storage iron in 31 healthy men are deduced, namely, 200 mg. to 1,000 mg. (3 to 14 mg./kg.). The test should prove useful in the diagnosis of iron overload, in the screening of relatives for early haemochromatosis, and in the management of iron storage diseases.