undoubtedly be found, careful investigation will show it to be true in
the main; for it must be remembered that even among the poorer classes
gluttony, especially in regard to proteids, is not at all uncommon, and
indolence, with impeded metabolism, is not at all unusual. Dr. Latham
found that the mortality from cancer in England, from 1881‒1890, was
more than twice as great among well-to-do men having no specific
occupation, as among occupied males in general, the respective mortality
ratios being 96 for the former and only 44 for the latter. Sir William
Banks confirms the steady increase in cancer very strongly, which he
attributes to richer and more abundant food, of which males eat more
than females, and consequently cancer is increasing proportionately more
among men, as all statistics show.
Switzerland is reported to have the highest death rate from cancer of
any country, it having augmented from 114 per 100,000 living in 1889, to
132 in 1898. There again the cancer mortality varies greatly in the
different sections or cantons: thus, in wealthy Lucerne it is 204 per
100,000 living, and only 36 in poverty stricken Valais. In the city of
Geneva it is 177 per 100,000 living.
Denmark, next to Switzerland, is reputed to have the highest cancer
death rate of any country in Europe, viz.: 130 per 100,000 living in
1900. But here the statistics are only from the towns, which comprise
but a quarter of the whole population: the per capita wealth is said to
be higher there than any other country in Europe except France.
France shows a high cancer mortality, with a constantly increasing death
rate; and, next to England, France is the richest country in Europe, and
wealth is much more widely diffused: the French workers own nearly 8
times, per capita, more than those in England. In Paris the cancer death
rate has increased as follows, for each 100,000 living, in 1865, 84; in
1870, 91; in 1880, 94; in 1890, 108; in 1900, 120.
Italy, a comparatively poor country, shows a low cancer mortality, but
even here it is increasing from 20 per 100,000 living in 1880, to 52 in
1899, and 58 in 1905. The consumption of meat is there the smallest in
any European nation, namely 23 pounds per capita in 1895. In the chief
towns the rate of death from cancer is high: thus for each 100,000
living, in Florence 137, Ravenna 120, Venice 103, Milan 101, and Rome
77.
Time does not permit a wider survey of the field of distribution of
cancer, as presented so remarkably from official statistics by Williams,
and Wolff; but in connection with the high percentages of deaths above
quoted among the richer classes it may be interesting to mention some of
the lowest records. Thus, in the poor country of Kerry, Ireland, it was
27 per 100,000 living, in the province of Dalmaltia 19, in the Shetland
Islands 16, in Servia 8 (from 1895 to 1904), and in Ceylon in 1903 the
mortality from cancer was about 6 for each 100,000 living.
The United States, unfortunately, has not kept the vital statistics of
the country in years past with anything like the fullness and accuracy
which has obtained in England, nor even at the present time is it
possible to learn definitely the frequency and increase of cancer in
every locality. But all the statistics which have been gathered show
unequivocally that the disease has steadily increased in a manner which
is alarming. Analyzing the recorded deaths from cancer in thirty-one
cities, and the percentage of increase in four years, one writer
estimates that, if the same increase is continued, by the end of the
century there will be a death rate, approximately, of 1000 in every
100,000 inhabitants, or one in every hundred.
In a recent Bulletin of the Board of Health of New York City the
following statements are made in regard to the mortality from cancer in
1913: “The statistics of our seven largest cities recently tabulated,
show that the cancer death rate was the highest on record. For New York
City the rate was 82 per 100,000 of the population, against an average
of 79, for the last five years: for Boston 118 against an average of
110: for Pittsburgh 79, against an average of 70: for Baltimore 105,
against an average of 94: for Chicago 86, against an average of 81: for
Philadelphia 95, against an average of 88: for St. Louis 95, against an
average of 85.” This average increase of almost 8 per cent. of deaths
from cancer in the combined population of these seven cities, during the
last five years is certainly an alarming fact, and cannot be explained
on the ground of greater accuracy of diagnosis: for it is not to be
presumed that there has been such great improvement along diagnostic
lines during the single year 1913.
It is difficult to state the exact prevalence of cancer in the entire
United States, as the “registration areas” include only about two-thirds
of the total population: much can be learned, however, from the annual
volumes published since 1900. According to these Mortality Statistics of
the United States, the deaths from cancer and other malignant tumors per
100,000 population were as follows: in 1900, 63, in 1904, 70.2, in 1909,
73.8; and in 1912 there were 46,531 deaths from cancer, or 77 per
100,000 population, an increase in the death rate from this disease of
almost 25 per cent. since 1900; while, as before stated the tuberculosis
mortality had fallen a little over 25 per cent. in the same period.
As in other countries, which might also be expected from the statements
already made, the disease varies in frequency in different localities
and communities. Thus, cancer is stated to be much more prevalent in the
northern than in the southern states, and as already stated, the negroes
are much less subject to the disease than whites, especially when they
are living their own natural home life; but when they come to the
cities, as waiters, etc., in hotels, their cancer death rate increases.
But even in New York City in 1912 the deaths from cancer in negroes was
1 in 32.2 total deaths, against 1 in 17.7 in whites; the mass of negroes
here, of course, live plainly and work hard. The North American Indians
also are believed to be almost exempt from cancer in their primitive
savage condition, but as they have come under the influence of
civilization they are more affected. It has also been noted by several
observers that immigrants and their descendants present a very much
higher mortality from malignant diseases than prevails in their native
countries; from these and other considerations Williams suggests that
abrupt change of environment may also be a factor in the causation of
this disease.
We have thus seen while cancer is very widely distributed over the globe
it is present in varying degrees of severity in different localities,
and careful analysis shows that the disease affects different classes of
persons with unlike severity. All these statistical studies and
observations serve to confirm the statement made earlier that cancer is
a disease of so-called civilization, and that it has increased in
proportion as human beings have come under the influence of wealth, and
consequent luxury and overindulgence, with bodily inactivity; all these
elements lead to a disturbed metabolism, which as we shall see later,
is, at least, a contributing cause to the deviation from normal of some
of the cellular elements of the body. It also appears that some of these
metabolic shortcomings have to do with a disturbed nitrogenous balance,
which is due to the constantly increased consumption of meat. In 1909
the meat consumption in the United States had reached the high figure of
172 pounds per capita, as I learned recently from Washington, a far
greater amount than in England, 130 pounds, as already stated; and with
this steady increase in the use of nitrogenous food cancer has also
increased by leaps and bounds in both countries.
LECTURE III
METABOLISM OF CANCER
In the first lecture we saw that cancer was an alteration of the normal
cells of the body, whereby they take on a malignant action and continue
to do so, destroying contiguous tissues and leading to a lowered
vitality, with an apparent poisoning of the system, which finally causes
death. As the cells of various organs furnish different secretions,
which in health contribute to proper metabolism, resulting in growth or
maintenance of the tissues, so these disordered cells are believed to
secrete a toxic substance, or malignant hormone, which has a prejudicial
action on the body, and hæmolytic action on the blood, as has been
brought out pretty clearly by Troisier and others.
We saw that as yet the definite cause had not been determined, why at
some period certain cells take on the action which we call cancer, nor
why they persist in their destructive course. Long continued and
abundant laboratory and clinical research have about decided certain
questions negatively in regard to its etiology, so that in a measure the
field is cleared for the study of some of the possible basic causes of
the disease in question. Thus, all are pretty well agreed that cancer is
_not_ contagious or infectious, that it is _not_ caused by a
micro-organism or parasite, that it is _not_ wholly due to local injury,
that it does _not_ appertain to any particular occupation, that it is
_not_ hereditary to any great degree, that it does _not_ especially
belong to or affect any particular sex, race or class of persons, _nor_
is it confined to any location or section of the earth, and that it is
_not_ wholly a disease of older age.
We saw further that there appeared to be good evidence that certain
misplaced “embryonal rests” were the original starting points of
diseased cell action, but as these are now known to exist in every one
from birth, this offers no real explanation of the occurrence of the
disease at different times in life. It is, of course, quite possible
that local injury of one kind or another may be the exciting cause which
determines that a cell or group of cells shall revert to its original
reproductive activity, as Williams contends that the process is one of
agamogenesis, dependent upon excessive and faulty nutrition. The
question as to the relation of uricacidæmia, or lithæmia, to cancer has
never been fully studied, and it is worth considering whether, as in
gout and rheumatism, to which cancer is often associated and perhaps
closely allied, the exciting cause may not be the lodgment somewhere of
uratic deposit, which is further excited and fed by effete or
imperfectly oxidized nitrogenous elements; for later we shall see that
perverted metabolism, largely of proteid elements, is closely associated
with cancer.
We noted also that some attributed cancer to independent cell action,
relating to the polarity of cells, etc.; but it is inconceivable that a
cell or cells can idiopathically start out on a rampant course and
pursue it with increasing severity, even until death results, without,
at least, some definite pre-disposing cause, even though diligent and
earnest work has not as yet determined just what that cause may be. The
error has been, we believe, in searching too exclusively by the
microscope and by certain laboratory methods, and not sufficiently along
clinical and bio-chemical lines. For it must be recognized that all the
cells of the body are continually bathed in the vitalizing fluid of the
blood, whence they derive their nutriment, and into which, with the
lymphatics, they return the products of their vital action, by anabolism
and catabolism.
By exclusion, therefore, we are reduced to seek the etiology of cancer
along other lines, and about all that is left is metabolism, as
influenced by advancing, so-called civilization, which relates very
largely to diet and mode of life. This we will take up later, but will
first examine some of the scientific findings in regard to the blood in
cancer, and data relating to the various secretions and excretions of
the body bearing upon metabolism in this disease.
That the blood shows great changes in advanced cancer is recognized by
all, as is clinically manifested by the intense cachexia and anæmia
commonly present and always strongly marked toward the end, of which the
cytology has been very fully studied and presented by Türk. When then
examined there is found to be a marked reduction of red cells, low
hæmoglobin index, and distinct leucocytosis, with greatly diminished
alkalescence.
The reported changes in the blood have also varied with the location of
the malignant disease, according as it may interfere mechanically or
otherwise with the function of certain organs, which fact naturally
obscures the question of the true relationship of the blood to cancer.
Thus, it is stated that in cancer of the liver and pancreas there is
always leucocytosis and glycogen, and that “cancer appears to interfere
greatly with the function of the liver as a destroyer of intestinal
toxins, they pass into the general circulation, probably cause the
glycogen reaction, and at least part of the leucocytosis, and very often
give rise to fever.” There are also other microscopical alterations in
the blood in late cancer. Thus, degenerative change in the leucocytes
are common, with derangement in the normal proportion of their different
forms, as also changes in the erythrocytes, with nucleated red cells and
megalocytes in severest cases.
Price Jones in a study of the blood in 30 cases of cancer (9 of the
breast) found the red blood cells diminished on an average of 6 per
cent., the white blood cells increased 38 per cent., lymphocytes
increased by 10 per cent., large mononuclear cells increased 164 per
cent. and polynuclears 42 per cent. Burnham states that in the severe
grades of anæmia with malignant disease, poikilocytosis is marked, and
nucleated cells of both normoblastic and megaloblastic type may be
present. The red corpuscles may be reduced to 2,500,000, and
exceptionally to 1,000,000. Cohnreich in a very technical study of blood
from cancer subjects, observed very great increase in the resisting
power of the red blood cells to osmotic tension, that is, in regard to
their hæmoglobin, which he believed to be of diagnostic value in
doubtful cases.
Unfortunately, there have been relatively few studies of the plasma of
the blood in this or other diseases; and yet the condition of this fluid
must be of the utmost importance, as from it are derived the nutrient
principles not only of the solid constituents of the blood, but also
those of the entire system, about 8 per cent. of it being serum albumen
and serum globulin. It also holds in solution the phosphates,
carbonates, sulphates, and chlorides, the latter often varying greatly,
and being chiefly responsible for the isotonic relation of cells and
serum. In cancerous cachexia a diminution of carbonic acid, a constantly
diminished alkalinity, and an increase of acid principles of the blood
have been fully demonstrated, pointing in all probability to the
existence of an acid intoxication. The formation of the corpuscular
elements of the blood must be greatly interfered with when metastases
occur in the blood making organs, the lymphatic tissue, bone, marrow,
and spleen, which probably occur more frequently than is generally
recognized. It seems that the toxic secretion from a cancerous mass has
a distinct action upon the blood, for after complete removal there is
often observed an increase of hæmoglobin, as I have witnessed, and a
high leucocytosis has disappeared after the removal of schirrus of the
breast, only to return again with the recurrence of the tumor.
Abderhalden states that in from two to three weeks after the operative
removal of cancer, certain defensive ferments can no longer be found in
the serum.
Many laboratory studies have been made upon the chemistry of cancer
tissue, seeking to determine the nature of the toxin produced, and its
experimental effect on animals, but thus far no great results have been
obtained. It has been observed, however, by Gruner that when cancer
juice is injected intra-venously a marked lymphocytosis arises, which is
followed by the appearance of large mast cell myelocytes in the blood.
This cancer juice is supposed to be autotoxic in cancer patients, and to
comprise toxic albuminoids, which being in quantities too great to be
quickly neutralized poison the system, especially the blood and the
hæmatopoietic organs.
In regard to the real bio-chemistry of cancer, we are still greatly in
the dark. Vast numbers of studies and researches have been made to
determine the real character and nature of the bio-chemical changes
which occur in cancerous tissue, and the mere recounting of the reported
findings and theories elaborated from them would occupy far more time
than can be profitably given in these lectures. Some have claimed very
positive findings which account in a measure, at least, for the
pathological conditions, while others, as Beebe, state that “the
chemical study of tumors is in its infancy. We have scarcely proceeded
far enough to know where the medical problems are, nor have methods now
available been perfected to such an extent as to enable a decisive
experiment to be made.” “No phase of metabolism,” says he, “has been
described in cancer which does not have a counterpart in non-cancerous
conditions. This applies to such questions as the nutritive relations
between the cancer cells and the normal body tissue, to the nitrogenous
balance, retention, elimination of sodium chloride, excretion of
acetone, the relation of ammonia excretion, and a possible acidosis.” He
adds, however, “Diet doubtless forms an important part in the growth of
cancer, possibly even in the origin of the disease.” It is encouraging,
therefore, to find that this able and careful laboratory investigator
recognizes, in a measure, the basic cause of diet, toward which all
evidence points so strongly, although the definite connection may not
yet have been established by laboratory methods.
In all our study in regard to the relation of diet to cancer it must be
remembered that there are divers elements and agencies which combine to
produce the many and various disordered conditions of the body, to which
we give the names of different diseases, and that cancer is no exception
to this general rule. For instance, in old-fashioned gout the patient
may have consumed an excess of Port and Madeira wine for years before
the system finally rebelled and acute gout resulted; and among the
causes for the systemic reaction we know that frequently it is great
mental strain or shock which has so disturbed metabolism that the wine
was no longer tolerated. Much the same is true in regard to cancer and
nitrogenous diet. And we will see later that mental disturbance and
nerve strain or shock often seem to be causative elements; also that
constipation, or intestinal stasis, is so common in cancer subjects that
it must be looked upon as one of the contributing causes among others,
to be mentioned later.
Although it is quite possible that many of the reported bio-chemical
changes found in primary cancerous tissue and metastases may not be of
etiological importance, it may be interesting to briefly refer to some
of them as indicating the vital alteration in tissues connected with
what we recognize as malignancy; even as in acute and chronic gout the
affected tissues exhibit abnormal conditions in regard to uratic
deposit.
Many writers, some of them dating back many years, agree that albuminous
constituents predominate in cancer tissue, and, as in actively growing
structures in general, sugar forming substances abound. Wolter states
that cancer of the breast contains 20 per cent. more nucleo-proteids
than the normal breast. Casein is also present in breast cancers, and
the abundance of fatty matters, contained in the cells of such
neoplasms, is well known. In regard to the proteids, Wolff, after many
studies, concludes that their character is identical with that of normal
tissues, and it is only the quantitative distribution of these that
differentiates the tumor from the physiological tissue. Wells agrees
with others that there is no very distinctive character in the
bio-chemistry of malignant tumors, but by reason of their excessive
chemical component, as compared with benign tumors, they naturally show
a high content of nuclear proteins; they, therefore, contain a high
proportion of phosphorus and iron.
Interesting observations have also been made on other characteristics of
cancerous tissues, such as the great abundance of enzymes of great
variety which are actively autolytic, also in regard to certain
relations of cholesterin, in regard to which Ewing has recently said,
“There appears to be something in the chemical or mechanical nature of
the irritation of cholesterin which is peculiarly effective in producing
atypical proliferation of epithelium”; this has been found to be no less
than 65 per cent. greater in quantity in fatty deposits, as in the
mesentery, in subjects of cancer than in healthy persons, etc., etc. It
would weary you to no purpose to attempt to refer further to the
bewildering mass of research studies in connection with the
bio-chemistry of cancer which are found in special literature: much of
it is fragmentary and some of it contradictory, but all has its value as
contributory to our knowledge of the actual conditions developed in
connection with cancer growth; but up to the present time it cannot be
claimed that any very practical results have been thus attained which
will aid us in treating the disease.
As all cell life and proliferation of tissue depends on the activity of
the cell nuclei, much attention has been paid to the changes found in
them and the behavior of the centrosomes and chromosomes, all of which
is too technical for us to consider here: suffice to say, however, that
several observers have demonstrated heterotypic mitosis in malignant
tumors, and that histologic examination confirms what other judgment has
indicated, namely, that the cancer cell differs from a normal tissue
cell mainly in its aberrant action under some stimulus, probably derived
from the animal fluids by which it is surrounded. Thus we come back to
our original proposition, for these fluids are, of course, but a
reflection of the nutrition of the body or diet, as modified by the
action of the various organs, including the internal secretions; all
this is influenced again by the action of the nervous system.
It is difficult to produce definite proof in regard to the influence of
nervous and mental strain and shock in the production of cancer, but
careful observers have long claimed that there is such an influence, and
from what I have seen I am firmly convinced that in some way these
conditions often do so disturb the metabolism, or otherwise operate, in
such a manner that cancer results. The influence of the mind upon the
body is unquestionable, as has been so fully illustrated by Tuke, and
from what I have observed I cannot doubt but that the mental depression
common in those with the beginning of a process which they fear might
result in active cancer, has much to do with accelerating its growth;
whereas, on the other hand, the hopefulness which can arise with the
attempt to change the diseased process by diet and proper medication,
has much to do with the favorable results which may follow in suitable
cases. In the same way the constant fear of recurrence after operative
removal can have its share in inducing and perpetuating the metabolic
error which excites the tissues to renewed cancerous action. I know that
some of you will think that this is fanciful theorizing, but many a
scientific fact, in many branches of science, has been worked out from a
theory which at first has seemed fanciful.
We will now consider some of the data which have been recorded in regard
to the relation of the secretions and excretions of the body to cancer,
including the internal secretions.