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THE EFFECTS OF RADIUM AND X RAYSUPON NORMAL AND CANCEROUS

TISSUES.

THE admirable memorandum on cancer issued forthe guidance of local authorities from the Ministryof Health in August last,l is to be supplemented, asoccasion permits, by additional memoranda. Theeffects of radium and X rays upon normal andcancerous tissues is the subject dealt with in thefirst2 of these supplemental monographs by Prof. W. S.Lazarus-Barlow.

Early Investigations and Conclusions.In discussing early investigations and conclusions,

he points out that from the empirical employmentof X rays and radium, shortly after their discovery,in the treatment of cancer, the following facts emerged.It became clear that? all varieties of cancer were

not equally amenable to irradiation ; also that X rayswere not an entity, but that the rays were ofdifferent wave-lengths. Similarities between the raysfrom radium and X rays were noted immediately ;differences were detected at a later date. At thepresent time each agent of radiation has its own moreor less well-defined region of applicability, whilesometimes a combination of the two is more effectivethan either used singly. It became clear that theaction of radiations upon a group of cancer cellsregarded as a new growth was not identical withthat upon cancer regarded as a disease. Even thoughthe duration of the disease were unmodified by treat-ment with X rays or radium, there was ample evidencethat by their use the lot of the patient was oftenrendered more endurable. It became clear thatwhatever the degree of amenability of a growth toirradiation in the first instance, it became less respon-sive to irradiation on subsequent occasions. Lastly,it became clear that research was necessary upon theresponse of animal cells of all kinds to the varietiesof radiation represented by soft, medium, and hardX rays, and alpha, beta, and gamma radiationsfrom radium. More or less synchronously someattention was given to the biological properties ofultra-violet light, which consists of rays whosewave-length is greater than that of the softest X rays,and to the radiations from mesothorium, whichcompare with the rays of radium.The casual nature of much of the pioneer work on

the therapeutic use of radiations, together with theabsence of fundamental data or precautions, muchimpaired its value. Later observations of the bio-logical action of radiations are more systematic.Prof. Lazarus-Barlow divides these into investiga-tions into their effects upon (1) normal cells andtissues; (2) cells of new growths, whether malignant(cancer) or non-malignant; and (3) cancer as a disease,where the radiations act on cancer cells intermingledwith non-cancerous cells in an individual abnormalbecause the subject of disease. Owing to the lacunaein our knowledge, it is impossible to consider X raysand radium rays separately, but there is reason tobelieve that much that is true for gamma rays ofradium is also true for hard X rays, and that to somedegree the same obtains for beta rays and soft X rays.

The Effects of Radiations upon Normal Cellsand Tissues.

The nucleus, or cytoplasm, or both, may becomedropsical or show isolated clear spaces (vacuoles)after exposure to irradiation ; the rod-like chromo-somes become irregular in shape, or granular, anddivide irregularly; the framework of the nucleus,instead of showing an even arrangement, becomescollected into irregular heaps ; the material formedby secreting cells is altered in quality or quantity ;and the cytoplasm may undergo degenerative changes,

1 THE LANCET, 1923, ii., 479.2 Circular 476. H.M. Stationery Office. 1d.

chiefly mucoid. These are early changes. A day ortwo later, if the irradiation has been severe, dying anddead cells and fragments of nuclei or cells are seen,or a structureless mass of material may be the solerepresentative of the former living cells. If theirradiation has not been too severe, signs of recoverybecome manifest, and there is evidence that thedamaged cells are being removed.Changes such as those described, when occurring

over a large area, lead to profound disintegration oftissue. This action must be remembered whendeeply-seated abdominal new growths are treated bylarge doses of highly penetrating (hard) X rays.Before the great radio-sensibility of the intestine wasrecognised, cases occurred in which the medicalpractitioner, in his endeavour to irradiate sufficientlya cancer of the womb, damaged the intestine tosuch an extent as to be dangerous, and in a few casesfatal, to the patient. At the present time this dangeris well recognised and guarded against.

It has been shown that cells and tissues manifestgreat differences in the degree to which they areaffected by rays. The radio-sensibility of the lympho-cyte of the blood and lymphatic glands is so greatthat an intense destruction occurs within an hour aftera slight exposure of the animal to gamma rays ; cellsof the pancreas and thyroid, on the other hand, appearto be unchanged, even after severe irradiation ; andbrain cells are unaltered except under large doses. Thebehaviour of the same variety of cell differs in differentanimals. In the domestic cat, where fatty conditionsare common in the kidney, gamma radiation leads to aprofound fatty degeneration in the secreting cells ofthat organ, which has no parallel in any other speciesof animal hitherto examined. In the rat and in manvoluntary muscle shows a marked proneness todegenerative changes of a fatty nature that does notoccur in the frog, the rabbit, or the cat,.

Differences of a like kind obtain even with cellscommonly regarded as belonging to a single class.Endothelial cells lining blood-vessels show a fewchanges, while those lining certain of the large spacesof the body, or covering the stomach and intestines,show intense desquamation, and this in the sameanimal exposed to a single dose of gamma radiation.

Besides these injurious or destructive effects ofradiations upon cells, in certain instances it hasbeen found possible, by using minute doses of rays,to stimulate cells to increased rapidity of division.There is some evidence also that a muscle and nerve,under slight radiation, are stimulated, so that themuscle is rendered capable of putting out more work.The point is one of great importance in the radio-therapy of cancer.

Effects of Radiations upon Cells of Malignant andNon-Malignant New Growths.

Just as the lymphocyte has been found to bentensely radio-sensitive, so new growths built upof masses of lymphocytes, whether non-malignant(lymphoma) or malignant (lymphosarcoma), respond torradiation by enormous destruction of the constituentells. In the same way, the three varieties of carcino-nata show alterations under radium or X raysanalogous to those undergone by their normalprototypes. In the case of the sarcomata, the cells,ike their prototypes, show general rather thanparticular changes after irradiation. It is undoubtedhat death of the cells and an intense mucoid degenera-tion take place, often over large areas.It would appear that the effects of irradiating

iarcoma cells depend rather upon the youth of thelells themselves, and the rapidity with which theyattain full size and undergo division, than upon any)eculiar radio-sensibility of that variety of cell as such.’t is in accord with this view that wide differences’btain between the amenability to radio-therapy ofhe numerous different varieties of sarcoma.As to endotheliomata, it has been noted above that

he reaction of endothelium to gamma radiationsappears to differ in different parts of the system. Fromobservations made on the differences between the

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reaction of the lymphocyte and of the endothelial cellunder identical radiation it would appear, not onlythat a radiation treatment which would be effectivefor a new growth built up of lymphocytes wouldalmost certainly be ineffective for one built up ofendothelial cells, but also that in the case of endo-thelial growths themselves amenability to radiationtreatment would vary within wide limits. This isfound to be true, some endotheliomata respondingwell to radiotherapy, others hardly at all.Under irradiation the fibromyoma often shows

remarkable diminution in size, but it is not yet certainwhether the rays directly influence the tumour cells,or whether the effect is indirect and dependent uponovarian changes resulting from participation of theovary in the irradiation to which the tumour wassubjected.

Effects of Radiations in Cancer as a Disease.The necessity for effective treatment, not only of

the central growth, but of the peripheral cancer cells,implies that in order to irradiate a small number ofmalignant cells great numbers of normal healthy cellsof the part are coincidently irradiated, and to thatextent damaged. The desideratum for all radiationtreatment is maximal damage for the malignant cellsand minimal damage for the body cells amongst whichthose malignant cells lie. It is usual to consider thenormal tissue cells as being less radio-sensitive thanthe malignant cell but the margin is not great, and somuch damage to normal tissues may accompanyvigorous radiation of a new growth that an extensiveintractable ulcer results. By some authors it is heldthat the poor results of radiotherapy when cancer hasinvaded bone depends essentially upon the coincidentdeath of bone which the irradiation has brought about.

In yet another direction normal cells are involvedwhen a case of cancer is undergoing treatment byradiations, particularly if the irradiated area be large.The blood circulating through the part is itself underirradiation, and lymphocytic blood changes, owing tothe repeated access of fresh blood to the part, in courseof time involve the entire circulating blood. Inaddition, the lymphatic glands may come under theinfluence of the rays, with the result that the totalnumber of lymphocytes in the body suffers a diminu-tion. Where the patient’s blood was normal beforeirradiation the reduction of lymphocytic numbers may be relatively small, and return to normal takesplace after an interval. But where the cancerousdisease has already led to blood changes, irradiation,if sufficiently heavy for satisfactory treatment of thenew growth, would lead to a grave augmentation ofthe blood condition and proportionate harm to thepatient.Many authors have described a

" flaring-up " of

cancer-particularly in distant parts of the body-after irradiation treatment, and have ascribed thephenomenon to operation of a stimulative action byminute doses of rays. Indeed, some authors have goneso far as to suggest that cancer may be originated innon-cancerous tissues in this way. As a matter ofpractical experience, it would appear that the riskof inducing cancer in a non-cancerous individualduring treatment is negligible.

Prof. Lazarus-Barlow proceeds to discuss the variousmethods of applying radium and X rays in conjunctionwith each other and with surgery, and concludesas follows :-

" One thing is certain : the mental attitude of thosemost interested in radiotherapy has changed. Notonly do they recognise that the radiations themselves,the cancerous conditions upon which they cause thoserays to act, and the influence of the rays upon thenormal tissues of the patient are far more complicatedthan was suspected at first, but also they envisage theradiation treatment in a fundamentally different way.At first the rays were regarded in the light of aspecialised variety of caustic. As such they wereinferior to many caustics in the surgeon’s arma-mentarium. Then it was seen that cells vary in

radio-sensibility, and a directly selective destructionof cancer cells was the goal, but was barely attainableby reason of the insufficient delicacy of our methods.Last of all, there has arrived in the minds of someauthorities the conception of radiations as an agentwhereby the cancer cells are altered in such a way thatthey evoke, within the patient’s body and through theagency of his normal tissues, an increased productionof some substance or substances antagonistic to them-selves. The formation of such antagonistic substanceswithin the patient, upon this view, characterises everycase of cancer, and the course of the disease variesaccording to the degree in which they are present.In all but the rarest instances, however, they areinsufficient, so that the cancerous process sooner orlater gains and maintains the upper hand and leadsto death. If by means of subjecting cancer cells toradiations one is able to imitate and enhance thisnatural process, the hope lies near that a productionof antagonistic substances would be induced sufficientto hold the cancerous growth in check, then gain theupper hand, and ultimately destroy the cancer cellsthemselves."

PARIS.

(FROM OUR OWN CORRESPONDENT.)

The Inauguration of the Anti-Cancer Centre atM ontpellier.

THE Minister of Hygiene and Public Welfarepresided at the recent inauguration of the anti-cancercentre of Montpellier. Three similar provincial centresalready exist at Bordeaux, Strasbourg, and Lyons,which are undertaking the specialised study andtreatment of cancerous conditions. The Montpelliercentre serves the district of the Languedoc andRoussillon, and is under the direction of Prof. Forgue,assisted by a carefully chosen staff, which includesProf. Pech, Prof. agrégé Lamarque, for the physicalcauses of the disease, with Prof. Grynfeltt and Prof.agrégé Turchini for the study of pathological anatomy.Research work will be conducted in conjunctionwith the heads of the schools of medicine of Montpellier,and since the hospitals of the town have a largeclientele of patients suffering from cancer, it is to beexpected that this centre will become one of the mostactive schools for the study and the treatment ofmalignant disease.

Shell-fish Control.Since the introduction of preventive inoculation

the clinical aspect of typhoid fever has changedconsiderably. In a paper read recently before theFrench Academy of Medicine, Mr. Courtois-Suffit gavea detailed study of 328 cases of typhoid and para-typhoid fever which had come under his observationduring the last four years, and in which he expressedthe opinion that the disease as it appeared at presentwas rarely due to water, but was to be traced chieflyto the consumption of infected food, mainly shell-fish,and in particular oysters. The Government has addedwhat amounts to a corollary to this communication,by publishing a circular addressed to local authorities,with the object of controlling the trade in oysters andother shell-fish. Establishments trading in oysterswill be listed in future, and only those which have beenproved to be conducted on hygienic principles will bepermitted to sell their wares. Shell-fish may not besent from distributing centres unless they are accom-panied by an official statement as to the cleanliness oftheir source of origin, while consignments of shell-fishwhich are not disposed of in a short space of time willbe summarily seized and destroyed.

* " Le Salon des Médecins."The Salon des Médecins was recently opened for the

first time since the war, under the presidency ofMr. Paul Strauss, Minister of Hygiene. In this salonare exhibited works of art created by contemporarymedical men. The number and variety of these works