Book Reviews
Radiophysiologie et Radiotherapie [Radiophysiology and Radiotherapy],
Vol. 11, fasc. 111, Archives de 1'Institut du Radium de l'Universit6 de
Paris et de la Fondation Curie, 1931.
This publication of the Archives of the Radium Institute of Paris continues the interesting reports which come from the Laboratories and Clinic
directed by Professor Claude Regaud.
The first paper, by Regaud and Ferroux, has already appeared in the
Zeitschrift fiir Krebsforschung (32: 10, 1930) but has been somewhat
modified since its original publication. I t concerns the variety of reactions which tissues undergo when treated by x-rays, in relation to the
time factor, and sensitivity to the biological dosage in the therapy of
malignant growths. The biological material used is the testicle of the
rabbit. An histologic study of the changes produced by radiation of
different quantities is included. I t was found that it was impossible to
sterilize the testicles of the rabbit by the administration of a single
massive dose without producing severe skin lesions, confirming work previously published in this series of monographs. On the other hand, complete sterilization is easily obtained without cutaneous lesions when the
dose is divided and spread over a certain period of time. The amount of
x-ray necessary to cause sterilization is about 2000 to 2200 r, and such an
amount, spread over a period of four to nine days, causes no damage to
the skin. These facts have been applied for the past twelve years a t the
Radium Institute in the treatment of human tumors with both radium
and x-ray, for there is an analogy between the reaction of the mammalian
testicle and that of malignant tumors. The practical result of all this
laborattory and clinical experience is that when the treatment is given as
indicated, unsatisfactory results are much less frequent. The sclerosis
and atrophy of the skin and the tendency to late necrosis, the stenosis and
induration of the vagina, and the serious lesions of the rectum which follow massive doses of x-ray are not induced. These lesions might be
overlooked if a cure resulted, but Regaud believes that the fractional
method spread over a moderate time cures more patients. The same results have been obtained in the treatment of cancers of the mouth,
pharynx, and larynx, which do not yield to single large doses. A massive
dose which produces sterilization, but severe lesions of the skin of the
ano-genital region is between 4,000 and 4,400 Solomon units (since the
Solomon unit is about .44 of the international r, these doses are approximately 2000 r.). If the x-ray is produced at about 180 K. V. variations in
filtration from between 0 to 8 mm. aluminum modify very slightly the
relation between the testicle dose and the biological reaction. When the
radiation is distributed over a longer time, the threshold for skin necrosis
increstses proportionately. The optimum time factor for the skin of the
rabbit appears to be the equidistant distribution of four or five equal
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BOOK REVIEWS
fractions of a t,otal dose of 2200 r over four to nine days. The selectivity
on the tissues is far greater when the dose is divided and spread over a
considerable time, as indicated. The biological effects have no significance independent of the time and, therefore, cannot serve to define the
absolute doses of radiation. Hence, the erythema dose is of practically
no value, for it varies with the quantity and the time of treatment,. This
does not mean, however, that small biological units, such as Drosophila
eggs, cannot under fixed c~ndit~ions
measure with considerable accuracy
the absolute doses of radiation.
The second paper, also by Regaud, has appeared in the Acta Radiologica (2: 455, 1930). This, too, has been changed slightly since its original
publication. Regaud discusses the question of the direct or indirect act,ion of rays. He concludes that in general the effect is primarily direct,,
but that secondary effects, due to the damage of the vessels and the connective tissue, may play a part. There is no question, he t,hinks,that there
are very marked differences in the radiosensitivity of various types of
tumor. Thus it may be possible to cure a carcinoma of the cervix, but
not a carcinoma of the prostate or rectum, though their topographical
sit.uation is the same. As to the basis of this difference we know but lit,t,le.
In discussing the time factor Regaud points out that when tjhe doses are
small and too widely spaced, what has been t8ermedradio-immunity of the
cancer tissue is produced. Such a change in the tissues has long been
recognized clinically, but the explanation of the phenomenon is not yet,
available. If the dose is given, however, within the proper length of
time, such radio-immunity is not observed. The same is true of radium.
If the quantity used is too large and the filtration not sufficient, necrosis
is produced rather than a cure and restoration of the normal ti, ssues.
Nevertheless, in an organ like the tongue, either a cure or necrosis may be
observed with the same treatment. Syphilis is one of the factors which
contributes t,o t,he bad results of radiotherapy in this situation. On the
other hand, skin epit,heliomata may be perfectly well handled by caustic
exposures, causing severe local lesions, but the limited area damaged
permits of good restorat,ion of the normal tissues.
The third paper is by Coutard and appeared earlier in Strahlentherapie (37: 50, 1930). In it are discussed the practical aspects of prolonged radiation with filtration of 2 mm, of zinc or copper, and a voltage of
180 to 200 I<. V. The focal distance for superficial growths like those of
the larynx or pharynx is from 50 to 60 cm.; for deep lesions, such as those
of the uterus, it is 100 cm. The portals may be small, about 50 sq. cm.
for the pharynx. With node invasion fields of 200 sq, cm. may be necessary. The chest and pelvis can be rayed with larger fields, for they are
much less sensitive than the cervical region. The dose given is from
5000 to 8000 r, administered in ten days in daily exposures of two hours
each. Larger quantities give no better results.
The remaining papers have less general interest, with the exception of
one by Regaud on the treatment of cancer of the breast by radiation.
The tone of this paper, rather than its printed conclusions, would lead one
to believe that Professor Regaud is extremely doubtful as to the ultimat,e value of radiation in cancer of t,he breast. H e calls attention in tlhe
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219
first place to the fact that no conclusions can be drawn as to the radiotherapeutic prognosis from the histology of the tumors. Secondly he
points out the wide distribution of the drainage channels, which necessitates very large areas of radiation. Thirdly he discusses the difficulties
of obtaining satisfactory cross-fire exposures, and finally he states in no
doubtful terms his opinion that, while nothing is easier than to insert
radium needles into the breast, and while the results are often extremely
satisfactory as regards local improvement, he feels that there is no quest'ion that such puncture of cancerous tissues is dangerous, just as is
any traumatism applied to a breast tumor. The insertion of radium
tubes is apt to tear the delicate walls of the lymph and blood vessels, and
thus permit the entrance of cancer cells into the circulation. The possibility is mentioned, but without approval, that some of these dangers
may be eliminated by sterilization of the tissues traversed by the needle
by connecting them with a high-frequency machine. The technic is that
recommended by Butler of Montevideo.
Regaud points out that patients who will submit to the Wertheim
operation without argument will refuse amputation of the breast, believing that radium or x-ray will cure the lesion without leaving any damage,
but this, he says, is a serious error, for if quantities of radium or x-ray
which are sufficient t o be effectual are used, atrophy of the breast is
caused and serious damage to the skin is inevitable, with pigmentation
and telttngiectasia. He believes that the operation should be carried out
by high-frequency instruments, rather than the scalpel, as he thinks it
has been definitely proved that with the former method local recurrences
are less frequent. In advanced cases with node involvement he thinks it
is better to remove the breast and treat the nodes by radium or x-rays.
The same is true of supraclavicular involvement. Regaud confesses no
experience with preoperative radiation, and uses postoperative radiation
only when evidences of recurrence are apparent.
The last paper is one by Dobrovolska'ia-Zavadska'ia, made up of a
few short reports concerning her observations on a strain of cancer mice.
The work is not completed, but she believes that there is an argument in
favor of the importance of an intrinsic hereditary factor in the origin of
cancer of the mamma in mice.
I t will be unfortunate if these articles are not translated and thus
made available to those who are not familiar with the French language.
Pie Allgemeinerscheinungen der Hirngeschwalste [The General Symptoms of
Brain Tumors], by F. I ~ E H I ~ E R
Georg
.
Thieme, Leipzig, 1931. pp.
116.
The writer has been induced to publish this small monograph because
he has found that some of the general symptoms of cerebral tumors are
not currently recognized. The first part is taken up with an analysis of
the well known symptoms of brain tumor, as headache, dizziness, changes
in the optic nerve, nystagmus, alterations in the spinal fluid, various
symptoms dependent upon neuro-vegetative interference, and so on.
The question of puncturing the brain in order to obtain samples for histological study is discussed, but as only ten cases were so investigated in
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BOOK REVIEWS
the author's large material, it is evident that the procedure is very limited
in scope. The diagnostic results were none too satisfactory, though no
bad effects from the puncture were reported.
The second portion of t,he monograph takes up the question of the
various sensory reactions, as pain on pressure in the region of the trigeminal and occipital nerves, increase in the trigeminus reflex in the eye, alt,erations in the sense of smell, together with a discussion of some of the
peripheral phenomena, as Bikeles' reflex and the LasBgue-Kernig sign.
The volume forms a useful summary of the experience of one who has had
access to a large clinical material.
Maliyne Pharynx- und Larynxtumoren [Malignant Tumors of the Pharynx
and Larynx], by A. ZUPPINC:ER..Georg Thieme, Leipzig, 1931
(S~pplement~ary
volume 40 to Fortschritte auf dem Gebiete der
RBntgenstrahlen). pp. 188.
This monograph is an analysis of the material from 1919 to 1928 of
the Ziirich University Roentgen Institute. The purpose of the study is
to sketch the normal and pathological anatomy of malignant tumors of
the pharynx and larynx, their diagnosis, and results of treatment.
I t is granted that tonsillar and pharyngeal tumors have hitherto
furnished very discouraging material, both for surgery and for radiation,
but recently the results of prolonged highly filtered radiation, as proposed
by Coutard, have led to the hope that further therapeutic efforts may not
be hopeless. The larynx material is different, since there is the possibility
of laryngectomy producing a permanent cure. The number of larynx
tumors reported here, however, is small, only 23, of which 6 are still free
from symptoms. Among these larynx cases the operative mortality was
about 33 per cent, while 8 received no benefit from radiation, and 3 were
not treated. Of the total 280 patients discussed, only 11 are now alive,
5 with pharyngeal sarcoma and 6 with laryngeal carcinoma. The insertion of radium in the hypopharynx tumors caused severe reactions and
was rarely of real value. Palliation was fairly frequent, but lasted only
for a relatively short time.
The volume is well illustrated, and a very complete bibliography is
appended. I t is well worth perusal by all optimists on cancer therapy.
Die Elektrochirurgie [Electr~~surgery],by Franz Iieysser. Fischcr's
Medizinische Buchhandlung, Leipzig, 193 1. pp. 238.
This most beautifully printed and illustrated volume cont,ains a large
amount of information on the history of electrosurgery, the development
of the apparatus, the operative technic, the action of high-frequency currents on the tissues, and long series of case reports illustrating the treatment of inflammatory conditions. I t is chiefly, however, devoted to the
treatment of malignant tumors. The last section, on the biological
relations of inoperable tumors, is on a less sound footing than the rest.
Tceys~erhas always had a firm belief that the body possesses certain protective qualities, and he leans toward the somewhat heretical notion that
a n infectious agent is responsible for neoplasms. He classifies tumors into
BOOK REVIEWS
221
groups with high virulence and no protective powers on the part of the
body; those with average virulence with and without protective action,
and so on. He apparently believes in small doses of x-ray as stimulating
the protective powers of the body, recommends isamine blue as useful, and
commends the injection of crushed tumor cells as leading to an increase in
the bodily resistance to tumor growth. This last suggestion has been so
thoroughly discredited by observations both on man and animals that it
is a mistake to include it in a book containing much really valuable
material. The practising surgeon obviously will be more interested in
the description of the author's clinical results than in his theoretical conclusions and will find much practical information if he can read German
with any facility.
Krebs und seine wahre Ursache [Cancer and Its True Cause] by J. WINKELHAGEN. Published by the Author, 1927. pp. 75.
The author believes that the facts so far available compel one t o assume two separate susceptibilities for cancer, one of which is constitutional and the other local. Irritation can cause cancer only if the constitutional susceptibility is present. This does not mean, however, that
everyone who possesses the general susceptibility to cancer will be afflicted
with the disease. The best evidence of this, according to the author, is
that the savage races are completely free of cancer, and that the human
race has acquired this disposition under conditions of civilization, and it
has been inherited. (The increasing frequency with which large numbers
of neoplasms are being reported among native races by competent investigators casts doubt upon this argument. I t seems impossible to free the
medical profession from the views which were so assiduously propagated
from the time of Rousseau that the noble savage was a creature who
suffered from none of the diseases of civilization, even though there is
much evidence that this same noble savage had and still has a very short
expectation of life, that he suffers from many afflictions which do not
burden the civilized man, and that his civilized rival lives a t least twice
as long on the average, and hence has much more cancer.)
The author goes on adding up his evidence that, for example, coffee
and tea must be regarded as specific poisons which predispose to cancer,
and even resuscitates our old friend Barker, though he points out some of
Barker's mistakes. We may well agree to the statement that "it is quite
possible that the cause of cancer lies immediately under our eyes, and that
investigators are on a wholly incorrect path," but it is by no means certain
that the direction suggested in this little pamphlet will lead t o a solution
of the problem.
Travaux ScientiJiques [Scienti$c Reports], by ALBERTPEYRON. Paris,
1930. pp. 118.
This pamphlet contains short summaries of the numerous papers which
have been published by Peyron and his collaborators since 1906. Its interest lies in the author's originality and industry in the study of a great
variety of tumors, both in man and animals, with careful histologic
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BOOK REVIEWS
technic. Peyron has always been interested in teratomata, and has
studied a large amount of animal material, which he believes t o be of
value in the interpretation of some of the obscure human teratomata.
The book is well printed and admirably illustrated with diagrams and
drawings of microscopic findings. It furnishes a survey of a very interesting group of tumors.
La Culture des Tissus en Biologie Experimentale [Tissue Culture i n Experimental Biology], by EMILEC. CRACIUN. Masson et Cie, Paris.
pp. 436.
It is just about twenty-five years since Harrison first showed that the
nerve cells of a frog would throw out fibers in an artificial culture medium.
Three years later Carrel and Burrows, and Lambert and Hanes, stimulated by Harrison's discovery, took up the cultivation of mammalian
material. The technical development of this most important phase of
biological study of the growth and reaction of cells uninfluenced by the
nervous system and separated from other cellular aggregates has been
slow. The most important technical addition to the method was perhaps
that of Carrel, who showed that embryo juice exerted an extraordinarily
stimulating power upon mammalian cells in vitro. While it has been
found that embryonic tissues grow easily and rapidly in fairly simple
culture media, the growth of more highly organized tissue, such as thyroid,
liver, kidney and similar structures, requires more specialized and delicate
technic.
It was early shown that transplantable animal tumors grew with considerable freedom in a variety of plasma mixtures, and one of the interesting facts which Lambert and Hanes brought forward was that tumors of
animals would grow in immune sera, showing that if there is any immunity
to cancer it must lie in cellular activity rather than in the blood.
Although Carrel early grew human carcinoma and sarcoma, these
cultures were difficult to obtain and very frequently failed of any growth.
Despite every effort in the modification of the media this situation still
obtains in regard t o human carcinoma. Sarcoma seems to be easier to
grow, though it is often difficult to be certain that the growing cells are not
normal connective tissue rather than the malignant cells of the tumor.
I n other lines important observations have been made, such as the
formation of tubercle tissue in vitro and the study of the relation of the
various connective-tissue cells to the formation of such tubercles. This
has been largely the work of the Lewises. The transformatjons of monocytes into macrophages and fibroblasts have shown the great adaptive
capacity of the connective-tissue group.
While everyone will acknowledge that cells in culture are, in all probability, far from normal, the production of glycogen has been observed
in liver cells, of thyroid products in growing thyroid cells, and of bile pigment in the liver cells. The latest and most spectacular phenomena
have been the growth of embryo bone in culture, the development of a
chick embryo to a considerable size in artificial media, and the segmentation of the rabbit ovum.
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223
The introduction of methods of cinematography has rendered all of
these phenomena public property.
Of the important summaries of the subject, that of Fischer has been
reviewed in the previous number of this journal (15: 2822, 1931). A
later publication is the present one by Craciun, who summarizes in French
our present knowledge of the material. This volume of some 425 pages
complements the work of Fischer and presents the subject in a somewhat
different aspect from that of the Danish investigator. The volume contains more a summary of what has been done than a complete exposition
of the technical methods such as is contained in Fischer's work. The two
volumes, then, contain about all that we know concerning tissue cultures.
Craciun's book contains, in addition, an extremely complete and valuable
bibliography, which reveals the international character of the researches
which have been published.
Das Wesen der Krebskrankheit und Ihre Kausale Behandlung [The Nature
of Cancer and Its Etiologic Treatment], by RUDOLFROOSEN. Curt
Kabitsch, Leipzig, 1931. pp. 56.
I n this small monograph Roosen has collected his scattered publications on the subject of the treatment of malignant tumors with isamine
blue. He prefaces his discussion of the therapeutic results with a theoretical outline of his views on the nature of cancer. Whether his theory will
be accepted by the majority of students of the subject is somewhat questionable, but a t least it offers an interesting new suggestion as to the underlying causes of the disease.
There follows a very considerable amount of material concerning the
technic and results of isamine blue therapy. On the whole, the writer
has kept his enthusiasm for the method fairly well within bounds. There
seems to be no question that many of the patients who received a considerable quantity of this dyestuff are improved as regards many of their
symptoms. Further benefit may be obtained by the simultaneous administration of diathermy or of short wave-length radiation. It seems
probable that only palliative results will be obtained in any proportion of
the patients treated, and the author makes no claims that the dye injection method in any sense replaces surgery in the operable cases. He recommends it chiefly as an adjuvant in the advanced and hopeless type of
the disease. He advises against its use as a prophylactic method, and
calls attention to one serious objection to the therapy, the deep blue
staining of the skin which is temporarily produced.
The Genesis of Cancer, by W. SAMPSON
HANDLEY.Kegan Paul, Trench,
Trubner & Co., Ltd., London, 1931.
The latest volume of the Anglo-French Library of Medical and Biological Science is from the hand of an eminent English surgeon long active
at the Middlesex Hospital, London. His thesis that "local lymph stasis is
a constant precursory factor in malignant disease," he explains, has been
forced upon him by twenty-five years of clinical and histologic work on
cancer, and his defense for writing a book merely to establish one con-
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BOOK REVIEWS
clusion is that "it offers the master key to the etiology of cancer." He
rightly defends the position of clinical observation as one of great importance and points out that a piece of research is not necessarily scientific
because it is done on a rabbit instead of a human being. He weakens his
argument, however, by the statement that "the fallacy that investigation
to be exact must be experimental is sufficiently refuted by astronomy, a
science to which the experimental method is denied."
As a matter of fact, Galileo is regarded by many as the father of the
experimental method, though his putting together of two pieces of glass
with which to observe the heavenly bodies may perhaps be classed as
invention rather than investigation. Any one familiar with modern
astronomy, however, will know that it sprang from the laboratory observation of Fraunhofer, who noted, about 1820, that the yellow spectrum line obtained from the light of a spirit lamp when common salt
was placed upon the wick is identical in position with the D line of the
solar spectrum which he had previously measured. Foucault, in 1848,
noticed the reversal of these D lines and finally Kirchhoff, in 1859, observed that many of the black lines in the spectrum of the sun corresponded in position with the bright lines produced in his laboratory when
certain of the elements were introduced into a Bunsen flame or an electric
arc. Up to this point astronomy in a practical sense was chiefly a handmaiden of navigation, but how much navigation can be found in Jeans or
Eddington? The use of Doppler's laboratory discovery in 1842 of a
change of note from a moving source explained the shifting of the Fraunhofer lines in the spectrum of the stars and made it possible to measure
the rate of motion of the most distant nebulae. Thus the observations
made in the laboratory attached to an astronomical observatory are often
more important to the science of astronomy than telescopic observations.
I n support of his idea, Sampson Handley begins with a description of
the chronic form of lymphangitis seen in a great variety of conditionsinfection, chemical irritation, radiation, syphilis, lupus. He holds that
an infectious lymphangitis is the cause of common warts and concludes
that the transition from papilloma to carcinoma is a frequent one. He
would like to have it that carcinomata of the stomach, rectum, and other
sites are preceded by polypoid growths. This is all very well, but he has
not proved that papillomata are due to lymph stasis. Apparently he
regards the mechanism as an anoxemia. H e discusses Warburg's views
but rejects them. He tries to marshal evidence from the experimental
side but in the reviewer's mind does not succeed in making out a very
strong case.
On the whole, the impression gained is that the author has wasted a
good deal of powder and shot on the theories of others but on the whole has
not succeeded in establishing his own lymph-stasis theory that "the carcinogenic action of irritants upon the epithelium is exerted indirectly
through the obstructive lymphangitis they set up in the lymphatic vessels of the sub-epithelial connective tissue."
It is an ancient jest that, in the case of the scientist who rejected as
groundless 262 hypotheses of others, nothing was more certain than that
his own formed the 263d.
BOOK REVIEWB
225
Sampson Handley has put up a brave fight for his idea and realizes
that it is only an idea, but its rejection or acceptance will depend upon
those experimentalists whose work he depreciates in one place and
accepts in another.
Die Impedinerscheinung, by R. Torikata. GUSTAVFISCHER,
Jena, 1930.
pp. 871.
This volume contains the work of Professor Torikata and his pupils
on the subject of certain antagonistic immune substances. I t contains
a new method for the investigation of phagocytosis, as well as a method of
judging the value of antigen avidity, and the toxicity of bacterial vaccines,
as well as studies on impedin.
Torikata believes that these studies on impedin render a fundamental
improvement in the substances at present used for inoculation therapy
absolutely necessary. The foundations for his observations were made in
1915. They were that filtrates of pure cultures of various microbes, or a
saline emulsion of tissue infected by microbes, when heated to 100' C.
for thirty minutes, gave a very much larger amount of precipitate in a
suitable homologous serum than the corresponding untreated filtrate.
The conclusion drawn from this was that in the untreated filtrate of bacterial cultures there are two antagonistic biological factors-one which
hinders the antigenic or immunizing processes, and another which facilitates them. The first agent he calls impedin, and the last he considers as
an antigen.
He believes that he has shown that microbic antigens, which resist
heating very effectively, are dissolved during such heating from the bodies
of the organisms, so that the fluid obtained, which contains no impedin
nor bacterial sediment, is practically much preferable to the common
vaccines.
The first paper is devoted to the paralysing action of impedin on
phagocytosis. Following this there is a series of articles by Torikata and
his pupils in which a vast series of observations are collected concerning
bacteria of various types and the presence of impedin in the bacterial
extracts.
The author then turns to the subject of malignant growths. He
points out that the generally assumed relationship between irritation and
the production of a tumor has never been accurately measured, and, in
fact, can scarcely be considered as proved. It was, therefore, important
to determine whether tumors contain impedin as an evidence of microbic
influence. Extracts of various tumors were made and heated and the
effect of such a heated extract on phagocytosis of dead staphylococci was
tested. It was found that in a chicken myxosarcoma an impedin was
present which stimulated phagocytosis and was therefore microbiotic,
although the infectious agent has never yet been determined. A considerable number of animal and human tumors were also investigated and
found to contain impedin. The author regards this as demonstrating
that in tumors there is a group of lipoproteins which stimulate phagocytosis, and hence furnish a definite proof of the correlation between
neoplasia and micro-organisms.