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particular, failure to deal with large perforators atthe time of high ligation or stripping commonlyleads, in the long run, to the " bottle leg " picturewith superficial venous hypertension in the lower calfand progressive secondary skin changes. Two ques-tions that need answers are: how much of the longsaphenous vein should be removed; and, when thereare incompetent perforators, does a careful dissectionfor perforators give better results than postoperativesclerotherapy ? Clinical trials are necessary to

determine the relative merits of stripping the fulllength of the long saphenous vein, stripping its thighportion only, or no stripping at all. While it may be

possible to control all varicosities below knee level(including perforators) by sclerotherapy-providedthat the saphenofemoral incompetence has been dealtwith-the respective merits of ligation and injectionin this situation have not been properly compared.

Pending clinical trials, varicosities associated withsaphenofemoral or saphenopopliteal incompetenceshould probably be dealt with surgically, the operationbeing followed, if necessary, by sclerotherapy. Wherethe problem is either incompetent perforators aloneor superficial varicosities without obvious incompe-tence between deep and superficial systems, sclero-therapy may be the primary treatment of choice.Such a policy should mean that patients rarely needto be admitted to hospital for treatment of theirvaricose veins.

Rauwolfia and Breast CancerALMOST a year ago three articles appeared together

in The Lancet asserting that an elderly but still

popular group of antihypertensive drugs, the rauwolfiaderivatives (which include reserpine), were associated,possibly causally, with breast cancer and perhapsother cancers as well. 1-3 The Lancet 4 and theBritish Medical Journal suggested that the use

of these drugs should be restricted, whereas theScientific Council on Hypertension of the Inter-national Society of Cardiology stated 6 that, untildefinitive conclusions were possible, there should beno general change or disruption of therapy in patientswith high blood-pressure. All were agreed that moreevidence was required. Further sources of data havenow been tapped and a new series of papers presentsthe opportunity for a further summing-up. If thefirst series is the case for the prosecution, the secondis the case for the defence. Final judgment may haveto await more evidence, but- a conviction nowseems unlikely.1. Boston Collaborative Drug Surveillance Programme. Lancet,

1974, ii, 669.2. Armstrong, B., Stevens, N., Doll, R. ibid. p. 672.3. Heinonen, O. P., Shapiro, S., Tuominen, L., Turunen, M. I. ibid.

p. 675.4. ibid. p. 701.5. British Medical Journal, 1974, iv, 121.6. Scientific Council on Hypertension of the International Society of

Cardiology. Lancet, 1974, ii, 895.

The initial suggestion that there was an associationbetween rauwolfia therapy and breast cancer 1 arosefrom a study of drug therapy immediately preceding25 000 hospital admissions in Boston in 1972.

Among 150 newly diagnosed breast-cancer cases

11 (7-3%) had been on rauwolfia therapy comparedwith 26 (2.2%) of 1200 female medical and surgicaladmissions matched for age and hospital. The differ-ence was large, but the design of the study precludedany assessment of statistical significance. A verylarge number of associations between drug use anddiseases was being looked at without prior hypotheses.The small number of remarkable associations pickedout because they seemed unlikely to have occurredby chance had to be tested on other sources of dataelsewhere. The first two sources reported on werecancer records in Bristol and surgical clinic recordsat the University of Helsinki.The Bristol study 2 compared 708 newly diagnosed

patients with breast cancer registered in 1971-73with 1430 female controls with other neoplasms,matched for age and year of registration. Search of

hospital records and inquiry of general practitionersrevealed only 10 (1-4%) breast-cancer patients and 11(0-76%) controls on rauwolfia derivatives. This resultwas not statistically significant, but, by transferringsome cancers, which the Boston group also suspectedof an association with rauwolfia, from the controlsto the cases, a bigger estimate of relative risk wasobtained. As in the Boston study, the ability tochoose extreme findings for presentation lowers theirstatistical significance by an unknown amount.

In Helsinki 3 438 breast-cancer cases admitted for

mastectomy in 1960-72 were compared with 438women admitted for other elective surgery, matchedfor age and year of admission. 53 cases (12-1%) and31 controls (7.1%) were recorded as being on reser-pine. The difference was highly significant.The first paper of the second series reports a

study based in an affluent retirement community nearLos Angeles. Since 1971, 99 new cancers of thebreast had been discovered; and the controls were396 females in the community, matched for age andyear of entry. 20% of controls had had rauwolfia,and a risk ratio of 1-2 was obtained for breast cancer.However, similar risk ratios were obtained for hyper-tension, for any hypertensive drug, for use of any ofseveral groups of drugs, and for attendance at theclinic.The two investigations reported in this week’s

Lancet complete the second series. The Mayo Clinicteam compared two well-documented groups of

patients from a defined community-450 breast-cancer patients diagnosed after 1954 and 475 womenwith cholelithiasis matched for age and diagnosedbetween 1955 and 1970. More cholelithiasis patientshad been hypertensive and more had been on rau-

7. Mack, T. M., Henderson, B. E., Gerkins, V. R., Arthur, M.,Baptista, J., Pike, M. C. New Engl. J. Med. 1975, 292, 1366.

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wolfia (8-0% versus 6-4%), but rauwolfia usage wasidentical among hypertensive cases and controls

(16-8% and 16-9%). The final study comes from amental hospital in the State of New York whererauwolfia usage was high over the years for psycho-tropic as well as hypotensive purposes. 32 out of 55breast-cancer patients and 31 out of 55 controlsmatched for age, year of admission, psychiatricdiagnosis, race, and religion had a history of reserpinetherapy. Although several differences are shownbetween cases and controls in a formidable series of

analyses of drug usage over 21 years, these differencesare not consistent. More breast-cancer cases were

hypertensive.No doubt these three investigations will be dis-

cussed as fiercely as the previous three,8-18 but is aninterim conclusion possible ? We think so. The lackof a consistent, specific association makes a causalrelation less likely than it seemed last September.The association is least convincing in groups inwhich the drug is used most frequently. Can we

explain away the earlier findings ? The Los Angelesgroup have had a good try, by invoking the con-founding factor of socio-economic status. They pointout that the risk of developing most cancers and ofbeing admitted to hospital with many complaints isgreater in those of low socio-economic status.

However, this is not true of breast cancer and some ofthe other cancers suspected by the Boston group,which seem to be commoner in those of highersocio-economic status. If medication for mild

hypertension in women, and the repeated follow-upvisits it entails, were also correlated with highersocio-economic status, then a misleading associationwould appear. Another hypothesis might be sugges-ted by the Bristol finding that control cancer patientswere more commonly on antidepressants.2 2 If theseantedated their malignant disease it would suggestthat potential breast-cancer victims were less likelyto be depressives, and therefore more likely, to bethought suitable for starting or continuing treatmentwith rauwolfia. What lessons does this episode havefor the future ? Firstly, it is a mistake to think ofdrugs entirely in terms of organ systems-like patients,they cross the boundaries between specialties.Secondly, drugs used long-term and preventivelyhave to be much safer than those used temporarily torelieve established disease. Finally, when suspicionfalls on a drug of proven value, caution is right, butrejection should await hard evidence.

8. Immich, H. Lancet, 1974, ii, 774.9. Saxén, E. ibid. p. 833.

10. Peto, R. ibid.11. Mann, R. D., Troetel, W. M., Nadelmann, J. ibid. p. 966.12. Siegel, C., Laska, E. ibid.13. Magnus, K. ibid. p. 1080.14. Venezian, E. C. ibid. p. 1266.15. Boston Collaborative Drug Surveillance Programme Research

Group. ibid. p. 1315.16. Heinonen, O. P., Shapiro, S. ibid. p. 1316.17. Laurain, A. R. ibid. p. 1317.18. Garfinkel, L., Hammond, E. C. ibid. p. 1381.

THE STATE OF FOOD AND AGRICULTURE, 1974THE annual report of F.A.O.l emphasises again how

dependent farmers are on the weather. After largeharvests in 1967-70, there have been four lean years,1972 being especially poor. In 1974 cereal productionagain declined-notably in North America. It isestimated that the world stocks of cereals carried overinto mid-1975 are below 100 million tons, less thanhalf the amount in 1970. This is only 11% of worldproduction, compared with an estimate of 17-18%needed for world food security. Whereas Canadaand the U.S.A. had in 1970/71 just over 40 milliontons of wheat in stock, they now have only about 12.Exports of wheat from North America have variedfrom 21 to 51 million tons a year. Should 1975harvests be bad again in many parts of the world, thedeficiencies could not be made good, as formerly, byimports from North America on the scale that hasbeen necessary in the past few years.The report contains a major review of population,

food supply, and agricultural development. Data are

presented for nine regions-North America, WesternEurope, Eastern Europe and U.S.S.R., and Oceania(the developed countries) and Africa, Far East, NearEast, Latin America, and Asian centrally plannedeconomies (the developing countries). In the de-

veloped countries over the period 1962-72, populationand food production have been increasing at estimatedannual rates of 1-0 and 2-7%, respectively. In the

developing countries the figures are 2’4 and 27%,respectively, and agriculture is thus barely keepingpace with the growth of population. The terms

developed and developing are U.N. double-talk. Inthe " developed " regions, the signs of developingagriculture are evident in the corpulence of theinhabitants and in the large amounts of food waste inthe garbage cans, estimated to be the equivalent of2 MJ (480 kcal) per head per day in some wealthydistricts. By contrast, the thin inhabitants of most" developing " regions see little sign of an increasein their food supply. It would be more honest andaccurate to label the two groups of regions rich andpoor-there is much to be said for four-letter words.The report does not discuss the reliability of data

presented ’in the numerous tables and charts. Thecensus and figures for agricultural production are

probably reliable in the rich regions, but for. the poorregions the figures can often be little better thanintelligent guesses. However, they make commonsense. Travellers in countries in the poor regionswould, for the most part, agree that there appears tohave been little change recently in the food supply orin the state of nutrition of the people, either in therural areas or in the greatly increased populations inlarge towns. Malnutrition remains widespread.A section of the report relates the supply of energy

and protein in the food to F.A.O. statements ofrequirements. In the poor regions supply falls belowthe need by 25%. On this figure, supported bynumerous family dietary surveys showing that intakeof energy and protein is closely correlated with

income, it is concluded that some 460 million people1. Food and Agriculture Organization of the United Nations. The

State of Food and Agriculture 1974. 1975. Rome: FAO. Pp.196+12. Obtainable from H.M. Stationery Office.