651

Dr. R. DuLBECCO (Pasadena) described plaque for-mation in tissue-cultures in which virus had grown.Strains differed in the types of plaque shown, a,11dmutants with individual plaques and other olha,rac-teristics had been segregated. The typing of strainsfrom Scandinavia was reported by Dr. T. WES8LEN

{Stockholm) and Dr. HERDIS vON MAGNUS (Copenhagen) ;more than 99% of strains in Scandinavia were type I.

Dr. V. MONACI (Milan) described the isolation of all threetypes in Italy. Dr. A. P. GOFFE (London) spoke of thequantitative relationship between virus and anti-serum,which varied in cultures of different types. Dr. J. T.SYVERTON (Minnesota) had used a stable strain of humanepithelial cells from an epidermoid carcinoma of thecervix for many types of laboratory studies of polio-myelitis. Dr. G. C. BROWN (Ann Arbor), by using specificmetabolic inhibitors and amino-acid analogues, had beenable to find certain growth factors essential for theformation of poliomyelitis virus in tissue culture.

Dr. W. KLONE (Hamburg) showed a series of beautifulphase-contrast photomicrographs of tissue-culture cells

undergoing cytopathogenic degeneration ; lie believedthat the process differed with the different types of virus.Purified preparations of virus were demonstrated underthe electron microscope and televised to the mainauditorium by Dr. R. ViLMAM (California). Virus

particles were spherical with a mean diameter of 28 ni[jL.The Prospects

Dr. J. H. S. GEAR (Johannesburg) and Dr. A. M. T.PAYNE (W.H.O., Geneva) both referred to the factthat the danger of poliomyelitis to civilised populationsincreased with better hygiene and sanitary provisions.It was to deal with this danger that such conferenceswere called.

Dr. J. R. PAUL (New Haven), summarising the con-ference, said that the outlook for the future withoutvaccine would have been increasingly bleak ; but nowit was hopeful. There was evidence that the presentvaccine was safe and antigenic, and better vaccines mightfollow. If the presence of antibody protected an

individual against poliomyelitis, then control was in

sight. ZD

.

CLINICAL PATHOLOGYAND GEOGRAPHICAL PATHOLOGY

WASHINGTON: SEPT. 5-11

FROM CORRESPONDENTS

THREE conferences in one were held in Washingtonearlier this month, when the 3rd International Congressof Clinical Pathology, the 5th International Congressof Geographical Pathology, and the International

Meeting of the Association of Medical Museums gatheredunder the chairmanship of Dr. ROBERT A. MooRE

(Pittsburg). The scientific sessions were well-proportionedand the selection of papers was sufficiently varied tointerest all tastes, though there were relatively few paperson hsematology because the International Society of

Haematology was meeting in Paris during the sameweek. A joint session of the three organisations enabledparticular emphasis to be laid on the geographicaland racial differences in disease and on the pathologyoi the diseases of undernutrition, which tend to be

neglected in countries where the standard of livingis comparatively high. Moreover, pathologists from themore highly organised parts of the world were shownsomething of the isolation in which many of their col-leagues from India, Africa, and elsewhere work.There were 24 scientific sessions, and some of the

papers are summarised below.

Incidence of Malignant DiseaseH. F. DORN (Washington) described a two-year survey

conducted by the National institute of Cancer in 10 metro-

politan areas of the United States with a total population ofnearly 15 million. The study was confined to 46,390 newlydiagnosed cases of cancer in residents in these areas. The inci-dence-rate was found to 1:HB the same for both white males andfemales but for the non-white population the rate for femaleswas 16% greater than that for males. Males, it seems, startedlife with a slightly greater risk of developing cancer, butafter puberty the incidence-rate for females increased so thatby the age of 20 the incidence of cancer was approximatelythe same for each sex, while at 35 twice as many females asmales were found to have a malignant tumour. The incidence-rate for females fell appreciably after the menopause and, byage 60 in the white population and 70 in the non-whitepopulation, morbidity for cancer was greater for men than forwomen and continued so for the rest of life. Most forms ofcancer were commoner among males than among females,except for cancer of the genital organs and breast.

Excluding these forms of cancer, the risk of malignancywas 60% greater in males than females, but not until age 50did the incidence of all forms of cancer among males exceedthe incidence of cancer of’ the reproductive system amongfemales. The incidence of cancer of the large intestine, biliarypassages. and thyroid was higher in females than in males.The incidence of skin cancer was 46 greater in males thanfemales when the exposed areas were considered separately,but for the covered parts of the skin it was the same in bothsexes. Carcinoma of the bronchus and lung was found to beover four times as common in males as in females but incarcinoma of the larynx over twelve times as many maleswere affected as females.

Negroes were found to have a low incidence of skin cancerand a high incidence of genital cancer. The racial differencein the incidence of skin cancer was greatest for the exposedareas ; in fact, the risk of skin cancer in these parts is fifteentimes as great in whites as in the coloured population. Cancerof the prostate and penis is more common in the coloured

population but cancer of the testis has a higher incidence inwhite men. Cervical cancer is twice as common amongNegroes as among white women ; moreover, the incidence isnoted at an earlier age. The incidence of cancer of the ovaryon the other hand is 50% greater among white than amongcoloured females. Other sites for which the incidence of cancerare greater among Negroes are salivary glands, oesophagus,stomach, and pancreas. Among the white males the risk ofdeveloping skin cancer is about four and a half times greaterfor a white male living in the south than it is for one in thenorth. Cancer of the lip is also less frequent among whitepersons living in the north, suggesting that ultravioletradiation may be a cause.

Malnutrition and Cancer

J. N. P. DAVIES (Uganda) discussed the way in whichnutritional deficiencies may influence the siting of cancer.Although frank vitamin deficiency was rarely seen even inthe more primitive African communities, malnutrition wascommon, for in the dry seasons the daily caloric intake oftenfell below 1000, and the diet was poor in protein and fat. InEast Africa only about 10% of the population was- over theage of 45 and this fact must profoundly alter cancer statistics.Contrary to general opinion, underfed Africans may show ahigher incidence of cancer than Europeans. The high incidenceof primary liver cancer may well be connected with thedisturbance of liver function in chronic malnutrition, and theconsequences of a disordered liver may affect the generalmetabolism of the oestrogenic hormones. Gynsecomastia,testicular atrophy, and other feminising changes in the malewere common, and so were carcinoma of the male breast,lymphosarcoma, and Kaposi’s disease.

Geographical Distribution of CancerC. OBERLING (Paris) wondered to what extent experimental

evidence was able to explain the geographical distribution ofdifferent forms of cancer. He believed experimentation stillhad an important part to play in the study of geographicalpathology. It was now known, for instance, that it is not theparasite Cysticercus jasciolaris which is the cause of thetumour associated with the disease, but a thermolabile sub-stance, possibly of a virus-like nature, carried by the parasite.A similar substance may operate in the causation of bilharziancancer, for this complication of the parasitic infestation wascommon in Egypt (it has been reported in one hospital ascomprising 43% of all cancer) ; but it was rare in South Africaand Morocco where bilharziasis was prevalent.

652

Research on amino-cancer of the liver in rats had revealedthe importance of nutritional deficiencies in the formation ofliver tumours. It was becoming abundantly clear that whereverhepatic cancer is endemic, subjects can be found whose dietis notoriously deficient in essential food factors. Breton, ina careful review of the experiments of Copeland and Salmon,noted that it was the absence of both choline and vitamin B2which was essential, in the absence of a carcinogenetic sub-stance, for provoking hepatic tumours in rats. It was import-ant, however, to remember that in this form of cancer toothere may be other factors. If malnutrition were the solecause of a hepatic cancar, then it should be seen more fre-quently in certain countries where undernourishment wassevere. Moreover, spontaneous hepatoma would be expectedin rats which sometimes cannot avoid malnutrition ; McCoywas unable to find such a tumour in a study of 100,000 rats.It was possible that undernutrition renders the hepatic paren-chyma particularly sensitive to the action of poisonous sub-stances ; as an example of this, it had been pointed out thatcarbon tetrachloride is widely used without the slightest harmin the treatment of ringworm, but that its administration wasassociated with so many cases of severe hepatitis in Indonesiathat it had to be given up.

Professor Oberling referred to the high frequency of gastriccarcinoma in Denmark where it is twice as high as in theUnited States in the case of men and three times in the caseof women : in Denmark the diet is rich in fats. In Icelandthis disease amounts to 43% of all cancer in that country :this, in the opinion of Dungal, may be due to the largeconsumption of heated fats. Carcinoma of the stomach inIndonesia was common in the Chinese population and rare inthe Javanese ; both communities live largely on rice but theChinese use pork fat in their cooking whereas the Javaneseuse vegetable fats.PAUL E. STEINER (Chicago) dealt with the problem of the

world distribution of cancer and the setiologieal significanceof racial studies. There was little doubt that the best incidencedata, measuring risk to cancer, now available came from smallcountries having well-developed health services and a criticalcancer registry. Already, however, some of the geographicaldifferences point to environmental factors, but morphologyin cancer is independent of aetiological agent, race, and

geography". Dr. Steiner believed, however, that we requiredmuch more information on comparative pathology. Did thedomestic dog and the cat, which share man’s atmosphericpollution and overcooked food, have more lung and gastriccancer than their wild relatives, the wolf and tiger

Comparison of StatisticsH. HAMPERL (Bonn) discussed certain fallacies which must

be avoided in the comparison of various collections of’cancerstatistics. The definition of malignancy as applied to tumoursstill gave rise to difficulty. We knew some qualities to befound only in malignant tumours but not in all of them, andsome qualities to be found in all malignant tumours, but notonly in them. This meant that the clinical course and notthe gross and histological findings decided eventually whethera type of tumour was considered malignant or not. Statistics

may or may not include as malignant such tumours as

carcinoids, basal-cell carcinomas, myxomas, and so on.

Professor Hamperl reported that carcinoma-in-situ had beenfound in 3% of 500 unselected pregnant women, whereasthe incidence of cancer of the cervix at this age was only0-1%. He concluded that carcinoma-in-situ found in pregnantwomen could possibly be identical with the lesion we usuallycall carcinoma. In fact the follow-up of these cases showedthat the lesion sometimes persisted without further growthand sometimes even disappeared completely.

Inherited Susceptibility to CancerMADGE T. Th1ACKLIN (Columbus) said that animal experi-

mentation and observation on human patients had shownthat there was no inheritance of cancer in general but rather ofcancer of specific sites, and probably at definite ages. She

reported a series of 300 cases of proved breast cancer, fromthe University of Ohio Clinic. It was evident that the

daughters and sisters of women with breast cancer ran a

decidedly greater risk of having breast cancer, the incidencein the former being 4-5 and in the latter 3 times the normal.Similar studies on patients with gastric and intestinal cancershowed that there was a significantly greater amount ofcancer in sons and daughters in the same organ affected inthe parent. The increase of cancer in the same organ as the

sibs was not so striking, for there wore many instances inwhich one sib had rectal and the other gastric cancer. Theevidence to date was that there are genetic factors for gastriccancer and for intestinal cancer in man, and that these appearto be site specific.

Antimitotic AgentsN. B. FRUJDMAN (Los Angeles) presented the results of

studies of the effect of various agents on the dynamics ofmitosis. The intermitotic interval appeared to have a numberof phases, and antimitotic agents might prolong or completelyinhibit these stages. Sometimes these agents interfered withcellular differentiation. Dr. Friedman’s studies were madeon the jejunum of the rat where, it was believed, mitosisoccurs every thirty-six hours and is completed in about

thirty minutes.

C.S.F. Changes in Cerebral TumourW. H. McMENE1B1EY and J. N. CuMTNGS (London) believed

that a study of the cells and protein patterns of the cerebro-spinal fluid in cases of cerebral tumour was of value in

diagnosis : the cells sometimes gave the correct diagnosisstraight away, especially in carcinoma of the central nervoussystem. Malignant cells could sometimes be found in fluidswith cell-counts within the normal range. The finding ofrelative increased amounts of p-globulin in the fluid in casesof histologically malignant disease of the brain warrantedfurther attention.

HistoplasmosisC. H. BIXFORD (Washington), reporting 22 cases of histo-

plasmosis, drew attent,ion to the wide variations in thehistological reactions and to the prominence of central necrosis.The non-caseating lesions were readily confused with thoseseen in sarcoidosis. Histoplasma capsulaturn was not alwaysseen in haematoxylin and eosin preparations but may be readilyidentified when the section is stained with periodic-acid-Schiff reagent. A recent review of 35 cases of so-called’’ tuberculoma," in which the diagnosis had not been con-firmed by demonstrating the organisms, proved on furtherexamination to contain Histoplevmw capslllatum in 19 instances.Vegetative endocarditis was present in 3 of the 22 cases.

Fungus DiseasesL. ZDB1ERIAX (Washington) said that several fungus

diseases, once considered rare and invariably fatal, were nowthought to be common subclinical infections ; and they,mayappear as a lethal complication of other diseases which mayhave responded to primary treatment. Six such cases were

presented. He believed that ecological disturbances, often

brought about by antibiotics, cortisone, or corticotrophin,were operative in most cases of disseminated aspergillus andcandida infection.

Industrial Lung CancerTwo new series of cases of industrial lung cancer were

described by GEORGIANA BoNsrR (Leeds). In a series dealingwith this type of cancer in asbestos textile workers, one

important observation was that exposed females were also

susceptible. The other series concerned a similar type Gfcancer in iron-ore miners, the material being collected fromthe post-mortem records of Faulds of Carlisle. In 192 post-mortem examinations of iron-ore miners, 17 lung cancers werefound-a significantly greater incidence than the 44 lungcancers occurring in 2378 post mortems in males over 20 yearsof’ age in Cumberland during the same period. This reportseems to clinch the already suspected association betweensiderosilicosis and lung cancer. Many of these tumours inasbestos workers and in iron-ore miners were peripheral,spreading sometimes, but not, always, to the hilum via thelymphatics.

Carcinoma of the Liver

J. HIGCfN’-0-N (Johannesburg) referred to the relation ofliver cancer to cirrhosis, malaria, syphilis, and parasiticdiseases. There was, he said, no precise meaning to1. cirrhosis " so that geographical comparisons were difficultto make. It, seemed clear, however, that primary liver cancerwas often associated with cirrhosis, more so in males thanfemales, and that the liver-cell type was more commonlyassociated with cirrhosis than the hepatic-cell type. InAfrica and Asia. whore primary liver carcinoma was common,the proportion of’ cirrhotic livers that become cancerous

appeared much higher than elsewhere. In Dr. Becker’slaboratory in Johannesburg it had been found that 5-2% of

653

Europeans with cirrhosis developed cancer, in contrast to

32% of Bantus.C. BERMAN (Maraisburg, Transvaal) pointed out that

information was badly needed on the relative frequency ofprimary liver cancer from a number of localities wherenutritional syndromes resembling kwashiorkor were common.It would also be interesting to know the prevalence of livercancer in places where kwashiorkor was said not to occur,despite the fact that it was common in adjoining districts.It seemed clear, however, that a poor diet alone was insutHC’ientto induce liver cancer.

.Pertussis

J. UKGAR (Greenford, Middlesex) said that there was noevidence that Haemophilu8 pertu8sis existed naturally in anyother than the typical virulent form, although artificiallyproduced forms were well known in the laboratory. H. para-pertussis had its own characteristic biological and antigenicproperties. A Laboratory InfectionW. McD. HAMMON, G. E. SATHElt (Pittsburg). and Wi-;BB

HAYMAKER (Washington) described an instance of fatal

laboratory infection with the virus of Russian spring-summerencephalitis. This was believed to have been the result ofaccidental inhalation of a dried powder of infected mousebrain. The patient, and another worker in the same roomwho was not apparently ill, both developed antibodies.

Breast CancerH. GRADY (Washington) reported the results of a

questionnaire instigated by the International Society of

Geographic Pathology. It was found that the death-rate frombreast cancer was lowest in Japan (3-2 per 100.000) and highestin the English-speaking countries, with the exception ofIreland. The figure for Canada was 19-3, Xew Zealand 1!)’O,England and Wales 18-7, and U.S.A. 18’.’). The incidenceseemed to be higher in urban than in rural communities, whilethere seemed to be general agreement that the unmarriedwere more prone to the disease than the married. Severalobservers were impressed with the frequency with whichmastopathia chronica cystif’a was mentioned as a likelyprecursor of malignancy. Colonel Grady reported considerableconfusion in the replies received on the histology of cancerof the breast, and he thought that statistics were unlikely tobe of value till there was more uniformity in the method ofreporting sections. He recornmended pathologists to adhereto the classification published 1->y 1<’. W’. Stewart.PERCY STOCKS (Colwyn Bay) said that not enough attention

had been paid to the question of the social status of patientswith breast cancer. It might he that the associations withfertility arose indirectly from some socio-economic factorwhich affected breast cancer frequency and fertility in oppositeways. High fertility appeared to have a protective effect

provided that marriage had not been too long delayed. In

England there were opposite gradients for breast and cervixcancer among the social classes, and these were still presentafter correction for class differences in the proportion thatwere infertile. Dr. Stocks drew attention to the strikingly lowincidence of breast cancer in Japan and said that a good dealof research was still needed to explain this fact. It was

easy to speak of a racial peculiarity, but the low incidence ofthis disease in Japan might well he due to some environmentalfactor, such as the continuance of’ breast-feeding for a longerperiod of time than in the West.

J. CLEMMESEN (Copenhagen), discussing the relation betweenmammary and uterine cancer, said that the frequency ofcarcinoma of the cervix may depend upon sexual activity, forit did not strictly follow the birth-rate, and Ilojel had shownthat the disease was particularly common in prostitutes. Theleft breast was more commonly involved than the right incarcinoma, and also in chronic inastitis, and in gynsecomastia,in starving men, suggesting a difference in reactions whichwas influenced by hereditary factors.

A. T. H. MARSDEN (Kuala Lumpur) drew attention to thefrequency of cancer of the male breast in Malaya and in certainother parts of the Orient. He recommended that all malecases of breast cancer be examined for evidence of liverdisease and hyperoestrogonism. A failure by the liver toinactivate’ oestrogens normally could follow malnutrition orcirrhosis; but malnutrition had not been noted in associationwith cancer of the male breast.

Renal Diseases ’

C. P. STEWART (Edinburgh) discussed the renal clearance ofcreatinine in relation to inulin, both substances being given by

steady infusion after a priming dose. He suggested that thetechnically easier method of estimating

"

glomerular filtration-rate

"

by means of the endogenous creatinine clearancesmight well be substituted for measurements of inulin clearance.

G. WALLMNtus (Uppsala) referred to the way in whichdextran clearance could be used as a measure of glomerularpermeability. The permeability of the glomerular membranewas found to be relatively fixed under normal conditions. In

proteinuria, larger dextran molecules were to be found in theurine, indicating an increase in the dimension of the pores ofthe membrane.

C. L. PIRANI and his associates (Chicago) described the valueof percutaneous renal biopsy in the diagnosis of certain diseasesof the kidney, as first practised by Alwall. Changes werefound in 10 out of 14 cases of lupus erythematosus, andinformation of value had been obtained in 22 cases of nephrosi3.The technique was especially useful in assessing the need forlumbar sympathectomy.

Demyelinating DiseasesJ. T. Cu-NTtxcs (London) described the chemical changes in

the brain in 5 cases of multiple sclerosis ; in these cases hehad noted a loss of phospholipin and total cholesterol, butwith the presence of cholesterol esters, which were normallyabsent. Often the abnormality was detectable in areas whichwere histologically normal.DOROTHY S. HfssjjLL (London) drew attention to the

histological resemblance between acute haemorrhagic leuko-encephalitis and postvaccinal and postexanthematousencephalomyelitis, there being, in effect, a gradation from thehaemorrhagic to the non-haemorrhagic forms. There was

increasing evidence, both clinical and experimental, for thetheory that the changes in the brain in these conditionsresulted from tissue sensitisation. Cavanagh’s (1953) case of apatient who developed hypersensitivity during treatment withstreptomycin and p-aminosalicylic acid was of a similar kind.

J. FREUND and M. M. LiPTON (New York) reported experi-ments in which allergic encephalomyelitis had been induced inguineapigs after a single intracutaneous injection of 0-08 ml.of’ an emulsion containing rabbit spinal cord in paraffin oil,together with killed tubercle bacilli : they found that excisionof the site of injection as early as 3 hours afterwards decreasedbut did not prevent the chances of encephalomyelitis.

N. P. GOLDSTEIN (Bethesda) and associates reported thatthey had failed to verify previous reports that a non-lipidsubstance was capable of inducing allergic encephalomyelitisin experimental animals : they had come to the conclusion thatthere were at least two " antigens " present-one soluble inchloroform and the other soluble in a chloroform-methanolmixture.

Carcinoma of the Uterus

E. W. GAULT (Vellore, Madras) discussed the geographicaldistribution of cervical and fundal carcinoma. An analysisof 1145 biopsy-confirmed cases studied at Vellore suggestedthat the great frequency of cervical carcinoma was the resultof early marriage and multiple pregnancies, which resulted inconstantly recurring instability of the cervical epithelium.The presence of cervicitis might accentuate this instability,as also might dietary deficiency with its attendant liver diseaseand thiamine lack. The absence of circumcision and of penilehygiene in a large section of the community provided a possiblecarcinogen in smegma.

F. GAGNON (Quebec) said that no case of cancer of thecervix had been noted among 222 cancer cases in FrenchCanadian nuns over a 25-year period, whereas carcinoma ofthe cervix accounted for 16% of all forms of cancer inCanadian women in general.A. T. HERTIG (Boston, Mass.), in a review of the pathological

anatomy of cancer of the uterus, drew attention to the factthat the inguinal lymph-nodes were involved in 30% of casesof carcinoma of the endometrium, as against 7% of cervicalcarcinoma. He believed that, if a radical hysterectomy wasundertaken for endometrial carcinoma, the inguinal glandsshould be removed.

Chemotherapy of TuberculosisROBERT KNOX (London) reported recent work on the

laboratory control of chemotherapy in pulmonary tuberculosis.Microscopy had often been found to be positive when culturehad failed. Direct testing of bacilli against drugs on solidmedia was now used in all cases with heavily film-positivesputa ; indirect testing was reserved for those cases whichwere scantily positive or negative.