1282

chromosomes. Chromosome 12 is thus a focus of particularinterest in the molecular biology of this tumour. However,though KRAS2, a known oncogene, is located at 12p 12.1 noconsistent evidence of its mutation or amplification has beenfound. It is not clear whether loss of the long arm or theburden of extra copies of genes on the short arm is

important. There is no uniform loss of heterozygosity ofpolymorphic markers on 12q, which proves that theformation of the isochromosome occurs after

aneuploidisation.There are few consistent findings about molecular lesions

in testicular cancer. However, a study on a highlypolymorphic region close to Ha-Ras 1 on chromosome 1 lpshows that the incidence of rare alleles is significantly higherin patients with testicular cancer than in controls, whichsuggests that there could be a susceptibility gene nearby.

Environmental factors are another area of interest in the

pathogenesis of testicular cancer. In a large case-controlledstudy from Oxford, delayed puberty was found to beprotective, whereas a sedentary lifestyle carried a moderateincrease in relative risk. Testicular atrophy may be acommon theme in many environmental and inherited riskfactors. 32% of patients presenting with testicular cancerhave atrophy of the other testis and 75 % may have reducedsperm counts. The finding of gonadotropin receptors onCIS and seminoma but not on normal testis suggests that

pituitary trophic drive (which would be high in patients withtesticular atrophy) influences the development of malignantdisease.

Since CIS is found in the contralateral testis in 57% of all

patients with testicular cancer, it has been suggested that allpatients should undergo biopsy of the apparently unaffectedtestis, which should be irradiated if positive for CIS. Thoseopposing this policy point out that these young patients willbe rendered irreversibly sterile before they have hadfamilies, whereas, with careful follow-up, the cure rate fromsecond tumours approaches 100%. It was generally agreedthat patients should be fully informed of the availability oftesticular biopsy and irradiation and helped to make theirown decision.

This workshop established CIS as the indisputableprecursor of seminoma and NSGCT. This conclusion

exposes the weaknesses of the WHO classification, whichnow needs urgent reconsideration.

Michael Leahy

Noticeboard

PTCA vs CABG

Percutaneous transluminal coronary angioplasty (PTCA) wasintroduced in 1977. For 1991, the numbers done per 100 000population were estimated to be between 9 and 24 for Spain, theUK, Sweden, and Japan, between 40 and 60 for Switzerland,France, Canada, West Germany, the Netherlands, and Belgium,and 123 for the United States. The procedure accounts for 20-50%of coronary revascularisation procedures. To what extent has therapid uptake of the procedure been accompanied by a thoroughassessment of its value? A report by the Swedish Council ofTechnology Assessment in Health Carel cites a survey that showedthat 250 original research studies of varying degrees of

methodological rigour were published between 1980 and 1990 onefficacy, complications, costs, utilisation, and indications, but only13 were of randomised controlled trials and none of these was adirect comparison of PTCA with coronary artery bypass grafting(CABG).

Several prospective randomised clinical trials oomparing PTCAwith CABG are underway, but as the report points out, "fewtechnologies stand unchanged for the convenience of assessment". ’.

PTCA will change with refinement of equipment and operatingtechnique, and it may increasingly be complemented by laserablation, atherectomy, the use of stents, or other procedures. CABGwill also change, with use of different graft types, for instance. So toowill the medical management of coronary insufficiency, with thedevelopment of genetic engineering and modifications in drugdosage and delivery. And patient selection criteria are alreadywidening as operator experience increases and results improve.Thus by the time long-term data are available they may be outdated.However, comparisons too early on in the development of atechnique, before sufficient operator experience has been obtainedand before the most suitable types of patients have been identified,could result in an unfavourable assessment.

For the time-being, though, what information is there aboutcost-effectiveness of PTCA as a substitute for CABG? According tothe report, of the few studies that address the costs of either or boththe procedures, most are flawed. The limited data available suggestthat costs ofPTCAare roughly 33-50% ofCABGatthetimeoftheoperation, 50-60% after a year, 67% after two years, and more than80% after 5 years. But, warns the report, it is premature to concludethat PTCA is a cost-effective substitute for CABG; fuller

accounting of the costs of surgical standby and indirect costs mayclose the cost gap between the two procedures, especially formultivessel disease. The report also points out that in practicePTCA is not used as a direct substitute for CABG; in many casespatients offered PTCA are those who are judged to be unsuitable forCABG, so PTCA may be increasing the aggregate costs of coronaryrevascularisation procedures.

1. Goodman C. The role of percutaneous transluminal coronary angioplasty in coronaryrevascularisation; evidence, assessment, and policy. Stockholm: SBU (SwedishCouncil on Technology Assessment in Health Care. 1992. Pp 118. ISBN92-87890-16-X.

Vaccines quality control deficient

Turning from encouraging reports of progress in pursuit ofeventual single-shot--even oral-immunisation against the mainchildhood killers, the consultative group of the CVI (Children’sVaccine Initiative), meeting earlier this week, confronted the crucialissue of substandard production. Dr David Magrath, head ofWHO’s biologicals unit, said that confidential reports would soonbe forthcoming from the CVI quality-evaluation and assessmentteams on Brazil, China, Egypt, Indonesia, Mexico, Vietnam,Bangladesh, India, Iran, Pakistan, and Thailand. There was noalternative to independent international control in establishing thecredibility of local vaccine production.Dr Donald Henderson, formerly in charge of WHO’s successful

smallpox eradication programme and now associate director forLife Sciences, Office of Science and Technology Policy, in

Washington, took the example of diphtheria/pertussis/tetanusvaccine, 70% of which is produced in developing countries withoutadequate quality control. He estimated that no more than 10% ofthis output would meet accepted standards. Some of it was sodeficient in antigens as to be little more than water. This had beenthe situation in the early phase of smallpox eradication, he pointedout. WHO had therefore concentrated on improving quality.Regular publication of lists of laboratories achieving internationalnorms helped in motivating governments to raise standards. InHenderson’s view, the WHO biologicals unit should be given moreresources for universal monitoring. I

Underlining that globally about 50% of all vaccines "are not ofassured quality", Dr 1. Arita, vice-chairman of Japan’s Agency forCooperation in International Health, made the point, as did otherspeakers, that this did not mean that developing countries wereunable to produce satisfactory vaccines. India was cited as anexample of what had been achieved. Globally, over 80% of theworld’s children are being protected against poliomyelitis andmeasles, tuberculosis, diphtheria, pertussis, and tetanus-

compared with 5% some 12 years or so ago. Much progress is beingmade towards thermostable-up to 45°C for at least 7 days-oralpoliovaccine.