putrefactive decomposition within the usual period. The tissues are
more or less {1031} deeply stained by bile-pigment, and this coloration
extends to pathological fluids as well. The serous and mucous membranes
contain points of blood-extravasation, but they are especially numerous
in the serous membranes. Hemorrhages of this kind are due to two
causes--to the disorganization of the blood, and to fatty degeneration
of the arterioles. The heart is also more or less advanced in fatty
degeneration, the muscles granular, the striations obscure or
obliterated, and the whole soft and easily torn. The spleen is usually
enlarged--often, indeed, to twice its natural size. The liver presents
highly-characteristic alterations. When death occurs early the organ is
generally enlarged, infiltrated with fat, the connective tissue
undergoing hyperplasia; but in more advanced cases atrophy has taken
place, the cells have disappeared and are replaced by fat-granules,
crystals of leucin and tyrosin, connective tissue, etc.--in fact, the
changes characteristic of acute yellow atrophy. The jaundice has been
variously interpreted. As the bile-ducts in advanced cases are found to
contain no bile, but only a colorless mucus, the advocates of a
hæmatogenic jaundice hold that the jaundice is due to a failure of the
liver to excrete the biliary principles in the blood; whilst the
opponents of this view maintain the existence of an obstruction in the
ultimate ducts. Harley[136] has recently brought forward some strong
facts and arguments--which we believe can be successfully
controverted--maintaining the former view. The jaundice of
phosphorus-poisoning, if Harley's opinion prove to be correct, must be
regarded as a hæmatogenic jaundice.
[Footnote 136: _Diseases of the Liver_, _loc. cit._]
The mucous membrane of the stomach, as might be supposed, is more or
less ulcerated or in an advanced state of catarrh, and the gastric
glands are affected by fatty degeneration.
The kidneys are affected in a similar manner to the liver; the
epithelium is fatty and sometimes detached, and the same process is
found to occur in the vessels and epithelium of the cortex.
SYMPTOMS.--Not only in the morbid anatomy, but in the symptoms, do we
find that a very remarkable resemblance exists between acute yellow
atrophy and phosphorus-poisoning. As phosphorus is usually swallowed in
bulk, some hours may elapse before the local symptoms begin, for the
contents of the stomach and the tough mucus lining the mucous membrane
may, and usually do, prevent immediate contact of the poison with the
mucous membrane. When the stomach is entirely empty the symptoms may
begin in an hour or two. The symptoms produced may be arranged in two
groups--those due to the local irritation excited by the poison; those
due to its systemic impression. In the first group belong burning in
the gullet, pain, nausea, and vomiting. According to Lewin,[137] who
has collected a number of cases for analysis, vomiting occurs in 26 out
of 32 instances of poisoning. Some hours--often, indeed, three or four
days--then elapse before the systemic symptoms begin. Vomiting, which
was for the time being suspended, occurs again, and instead of the mere
contents of the stomach, containing more or less phosphorus, blood,
somewhat changed by the gastric juice--chocolate-colored or as
coffee-grounds--appears in the vomited matters. The evacuations from
the bowels may at first, as the contents of the stomach, appear
phosphorescent, and afterward exhibit the appearances due to the
presence in them {1032} of altered blood. At this time, if the liver be
examined it will be found somewhat enlarged and tender to pressure, and
on or about the third day jaundice appears; but it should not be
overlooked that jaundice, as Bamberger[138] has shown, may be postponed
to the second or third week after the phosphorus has been taken.
[Footnote 137: _Virchow's Archiv für path. Anat., etc._, Band xxi. p.
514 _et seq._]
[Footnote 138: Legg, _On the Bile, Jaundice, and Bilious Diseases_,
_loc. cit._]
In favorable cases the area of hepatic dulness decreases and the
jaundice declines. In the fatal cases certain nervous phenomena become
prominent. There occur drowsiness, developing into coma, with
intercurrent attacks of delirium which may be of a maniacal character;
convulsions, spasmodic attacks, dilated pupils, and involuntary
evacuations. The disorganization of the blood and the fatty change in
the vessels are exhibited in the hemorrhages from the gastro-intestinal
mucous membrane. The nervous phenomena are due chiefly to the retention
in the blood of various excrementitious matters which it is the
function of the liver to separate from the blood. Flint's theory of
cholesteræmia has been so abundantly disproved that no one upholds it
at the present time, but the cerebral symptoms are properly referred to
the retention of all hepatic excrement.
The temperature in phosphorus-poisoning rises from 99° to 102° F., but
it may reach in severe cases to 103° to 105° F., and at death or
immediately afterward to 105°, even to 107° F. The same fact is true of
acute yellow atrophy. With the jaundice the pulse declines, but in the
further progress of the case, especially toward the close, the pulse
becomes rapid and small.
The changes occurring in the urine are highly significant. The amount
of urea decreases as the symptoms increase in severity, and leucin and
tyrosin take its place. If the case tends to recovery the urea again
increases in amount, but if the tendency is in the opposite direction
the quantity of urea steadily diminishes. Bile acids and bile-pigment
are found in quantity, and albumen is present in small amount.
COURSE, DURATION, AND TERMINATION.--Phosphorus-poisoning is necessarily
an acute affection, but the duration of cases is much influenced by the
form in which the poison is taken. If in a liquid and diffusible form,
as oleum phosphoratum, the local and systemic symptoms will develop in
a few hours, but if in solid masses, as particles of match-heads, many
hours (six to ten) may elapse before the local irritation begins. The
proportion of cures in phosphorus-poisoning varies from one-fourth to
one-half of the cases. Much depends, however, on the promptness and
efficiency of the treatment. The prognosis is the more favorable the
earlier proper measures of relief have been instituted. If the case has
proceeded to jaundice, hemorrhages, black vomit, etc. without the
administration of suitable antidotes, little can be expected from any
kind of treatment.
DIAGNOSIS.--The history of any case involved in doubt is indispensable
to a correct conclusion. The phosphorescent appearance of the matters
vomited or passed by stool may make the differentiation comparatively
easy; but if the case has passed beyond this stage,
phosphorus-poisoning can be separated from acute yellow atrophy only by
the history of the case. If the fact of the administration of
phosphorus is successfully concealed, no differentiation can be made,
since {1033} even the best authorities hold to the identity of the
toxic symptoms produced by this poison and of the morbid anatomy, with
the symptoms and lesions of acute yellow atrophy.
TREATMENT.--The poison should be evacuated as quickly as possible by
emetics and proper diluents. The best emetics are sulphate of copper,
apomorphia, and ipecacuanha, the antimonial and mercurial emetics being
unsuited, since their effects are similar to those of phosphorus.
Oleaginous protectives do not prevent, but really favor, the absorption
of phosphorus. Decoctions of flaxseed, slippery elm, acacia, etc. are
suitable demulcents and protectives. The fatty matter in food, eggs,
etc. will have an injurious effect by promoting the solution and
absorption of the phosphorus, and should hence be excluded from the
diet. The most effective antidote is oleum terebinthinæ, and the most
suitable preparation is the French acid oil. Freshly-distilled
turpentine appears to be almost if not entirely useless. It is probable
that the American oil which is old and has been exposed to the air for
many months will answer the purpose, but it cannot be too strongly
insisted on that the turpentine which has proved to be efficient in
phosphorus-poisoning is the French acid oil. Turpentine when exposed to
the air absorbs oxygen as ozone, and to this principle are probably due
the curative effects of old turpentine. Phosphorus when acted on by
this agent is converted into a spermaceti-like substance entirely
devoid of toxic power. As rapidly as possible the poison should be
acted on by the antidote, and then the stomach should be evacuated,
using, cæteris paribus, the sulphate of copper, since this forms an
insoluble phosphide with any portion of free phosphorus, whilst at the
same time it empties the stomach of its contents. Although the
immediate results of the poison may be thus removed, the damage to the
red corpuscles and to the whole mass of the blood requires special
management. The success of transfusion, as practised by Jürgensen,[139]
proves that the substitution of fresh blood may save life when the
existing blood-supply is inadequate to the performance of its proper
functions. It follows that if the toxic effects of phosphorus have
continued for several days, blood-transfusion will be necessary in
those cases characterized by an inability to recuperate notwithstanding
the successful removal of the poison.
[Footnote 139: _Berliner klinische Wochenschrift_, No. 21, 1871.]
For the inflammatory symptoms produced by the local action of
phosphorus, opium in some form is indispensable. This remedy is equally
valuable as a means of maintaining the vital resources and to prevent
the evil results of shock and inflammation.
Carcinoma of the Liver.
DEFINITION.--Under the term carcinoma of the liver are included primary
and secondary cancer of the liver. The malady with which we are now
concerned is the primary affection, occurring in the organ proper or in
some pathological new formation connected with it.
ETIOLOGY.--Heredity is the most important factor. A careful
investigation of the reported examples demonstrates that from 15 to 20
per cent. owe their origin to hereditary influence clearly, and
probably {1034} considerably more are indirectly derived in this way
when the immediate connection may not be demonstrable. Next to
heredity, age must be regarded as the most important pathogenetic
influence, much the largest number occurring at from forty to sixty
years of age. It is a malady of advanced life, therefore, rather than
of youth or middle age. Excluding the female organs from consideration,
it is quite certain that sex has little special influence, and that
males and females are affected about equally.
Primary cancer of the liver is comparatively infrequent, occurring in
not more than one-fourth of the cases. Frerichs collected 91 cases, and
of these 46 were secondary to cancer in organs having vascular
communication with the liver.
PATHOLOGICAL ANATOMY.--Under the term cancer of the liver are included
several distinct forms of morbid growth, but united in the
characteristic of malignancy. From the merely clinical standpoint this
characteristic is the most decisive bond of union between them, and
serves as the point of departure in the study of this affection.
Primary cancer of the liver is divisible into two forms: 1, as a
single, defined tumor; 2, as an infiltration through the whole mass of
the organ.[140] Secondary cancer occurs in nodular masses, and with
extreme rarity as an infiltration. The form of cancer is really the
same; the differences in structure are only apparent, the variations
being due to the relative proportion of cells, fibres, and vessels. If
the fibrous stroma is abundant and the cells small in quantity, the
form of structure approaches scirrhus; on the other hand, if the cells
largely preponderate, the type is encephaloid; if vessels predominate,
it is called telangiectatic. The usual form in cancer of the liver is
the soft, cellular variety, encephaloid or medullary. When the
cancerous new formation is nodular, the masses vary in size from a pea
to a child's head,[141] and are numerous inversely as their size. When
the cancer occurs as a solitary tumor, it may attain to enormous
dimensions. It has a spherical shape usually, protrudes from the
surface of the organ somewhat irregularly, and the overlying peritoneum
is thickened, cloudy, and adherent from a local inflammation. The
central portion, whether there be one, several, or many nodules, is
depressed, giving an umbilicated appearance to the tumor; and this
central depression is found to be soft, almost diffluent, and full of
juice. The fibrous stroma which extends through this central soft
material has a reticulated arrangement and a shining, fibrous
appearance. The cancerous masses are not confined to these nodules, but
extend into the surrounding hepatic structure, push their way into the
portal (especially the hepatic) veins, block the ducts, and invade the
lymphatic glands in the fissure of the liver.
[Footnote 140: Virchow, _Krankhaften Geschwülste_, _loc. cit._; Perls,
_Virchow's Archiv für path. Anat., etc._, Band lvi. p. 448 _et seq._;
Frerichs, _A Clinical Treatise, etc._, Syd. Soc. ed., _loc. cit._, vol.
ii. p. 281 _et seq._]
[Footnote 141: Förster, _Lehrbuch der Pathologischen Anatomie_, by
Seibert, Jena, 1873.]
When the cancerous new formation takes the form of an infiltration of
the organ instead of distinct nodules, the liver is usually uniformly
enlarged and its outlines preserved.[142] The peritoneum is opaque,
thickened, and adherent. The organ is traversed by fibrous bands, and
the {1035} intervening portion is a soft, juicy pulp, stained by the
imbibition of bile. In extreme cases hardly any portion of the proper
hepatic tissue remains, but is replaced by a cancerous new formation
having the same shape.
[Footnote 142: Perls, _Virchow's Archiv_, Band lvi. p. 448 _et seq._]
As regards the minute structure of cancer of the liver, it may be
regarded as a degeneration (cancerous) of the proper gland-cells and of
the epithelium of the bile-ducts. As cancer develops in the liver it is
to be noted that the cellular elements preponderate over the fibrous or
the stroma, and hence the new formation presents the characteristics of
softness, rapid growth, and a multitudinous cellular hyperplasia. As
regards the form of the new cells, it cannot now be doubted that they
are descendants of the secretory gland-cells and of the epithelial
lining of the ducts. According to some observers, it is to the
proliferation of the proper gland-cells that the new formations owe
their origin; according to others, to the hyperplasia of the cells
lining the ducts. As the growth of the new formation can take place
only through an adequate blood-supply, it becomes very important to
ascertain its source. There can be little doubt that primary cancer of
the liver receives its nutrient supply through the hepatic artery, in
connection with which new capillaries form in the pathological tissue.
Secondary cancer of the liver is the usual form of the specific
manifestation. From the merely clinical standpoint the primary
affection is the more important. From the pathological point of view
the secondary implication of the liver may be a true metastasis or a
mere communication by contiguity of tissue. The most usual metastasis
occurs from epithelial cancer of the face (Schüppel), but the ordinary
communication of the new formation is from primary cancer of the
stomach, intestine, pancreas, mesentery, etc. The cancer elements, as
the author has several times verified, crowd the lymphatics and veins,
and through these channels reach the liver and other parts. As the
cancer elements in the case of secondary implication of the liver are
distributed chiefly by the portal vein, it follows that there must be
numerous secondary foci and multiple nodes. Cancerous infiltration
under these circumstances is the rarest possible form for the new
growth to take. The size and number of nodes forming in these cases of
secondary implication of the organ vary greatly--from two or three to
twenty, or a hundred, or even more. As regards the form, structure, and
ultimate behavior of the secondary formation, they do not differ from
the primary. As respects the relative proportion of stroma and cellular
elements--fibres and cells--they vary greatly, some presenting the firm
texture of a predominating fibrous stroma, others the softness and
ready diffluence of the excessive cellular production. The latter is
undoubtedly the usual condition, and when the nodular masses are
incised an abundant creamy juice exudes. With the development of these
nodules an increase in the size of the liver takes place and the organ
has an uneven and indurated feel. As the cancerous masses develop the
proper hepatic structure undergoes atrophy, and finally little is left
of the organ but the cancerous new formation. The blood-vessels,
lymphatics, and peritoneal investment are invaded, the first mentioned
most decidedly; and especially are organized exudations the favorite
seats of cancer new formations, those, for example, about the
gall-bladder and cystic duct resulting from repeated attacks of passage
of calculi.
{1036} Secondary changes take place in the cancerous nodes. As the
cells develop pressure is brought to bear on the vessels supplying them
and on each other, with the result of fatty degeneration of the central
portion, which effects the change in the form of the nodules and in
their consistence, already mentioned. The blood-supply to the cancerous
nodes in the liver is derived from the hepatic artery, as Frerichs has
determined by carefully-made injections; they also are new formations
of exceedingly delicate structure, and form a network about the
periphery of each mass or node. By reference to these anatomical
considerations it is easy to understand the failure of nutrition of the
central portions of the nodes.
Pigment cancers of the liver are rare as secondary formations, and
excessively infrequent as primary formations. They are, properly
speaking, melano-sarcomas (Schüppel). They are more often metastatic
than merely secondary--that is, transferred from different parts, as in
the case of melanotic sarcoma of the choroid--than due to neighboring
disease transferred by contiguity of tissue. This variety of cancer, so
called, takes the form of multiple nodes or of diffused infiltration,
the former more frequently; but both modes of development may go on at
the same time. The nodes vary in size from a pea to a child's head,
have a grayish, brownish, or blackish tint, and exude on section a
fluid not creamy like true cancer-juice, but rather watery and
containing black particles floating in it. In the case of diffuse
infiltration the pigment masses are thoroughly distributed through the
original hepatic tissue. In both forms the size and weight of the organ
are enormously increased. In the case of the melanotic infiltration the
whole organ is uniformly enlarged, reaching in a few months the
enormous size of twelve to twenty pounds.
Sarcomas also occur very rarely as primary growths in the liver, but
secondary sarcomas are more frequent. There are fibro-sarcoma,
lympho-sarcoma, and osteo-sarcoma as secondary deposits, the first
being very firm in consistence, the second soft and medullary, and the
last of hard, bony consistence.
SYMPTOMS.--We are especially concerned here with primary cancer of the
liver. The secondary disease is so obscured by the main and primary
lesion that a diagnosis may be impossible. Furthermore, the progress of
the original disease is that which demands immediate consideration. As,
therefore, the secondary implication of the liver is of relatively
trifling importance, and only an incident in the course of the main
disease, the matter for consideration now is primary cancer of the
liver.
It is the fact that in some, even a considerable proportion, of the
cases the onset and progress of cancer of the liver are very obscure.
For some time the symptoms may be of the vaguest description. The usual
history is this: A person of forty to sixty years begins to fail in
flesh and strength, becomes sallow, has disorders of digestion, pain
and uneasiness in the right hypochondrium, and the bowels are now
confined, now relaxed. The abdomen, notwithstanding the general loss of
flesh, increases in size, and the superficial veins are enlarged; very
considerable pain is experienced in the right hypochondrium, and often
extreme tenderness to pressure is a pronounced symptom. The pains are
not limited to the hepatic region, out extend widely from this point in
all directions. On palpation the {1037} liver is found to be enlarged,
its texture indurated, and its outline irregular and nodular, and
pain--often, indeed, quite severe--is developed by pressure.
The condition of the liver on palpation is best ascertained by suddenly
depressing the abdominal wall with the tips of the fingers arranged in
a line. Displacing thus the movable bodies in the cavity, the liver is
quickly reached, and nodules, if they exist, are readily felt. If the
new formation has developed from exudations about the gall-bladder and
cystic duct, it may be felt by suddenly depressing the walls of the
abdomen over this organ in the usual position of the fissure.
In the case of general cancerous infiltration of the organ, with the
remarkable enlargement which occurs in such cases, there will be
present an obvious distension of the right hypochondrium; the
intercostal spaces will be forced outward and the arches of the ribs
rendered more prominent; the area of hepatic dulness, both vertical and
transverse, will be increased; and the limits of dulness will move with
a full inspiration downward, and with a full expiration upward. This
mobility of cancer-nodules of the liver with the inspiratory and
expiratory changes serves to distinguish them from tumors of the
abdominal walls. Seen early, the changes in the size of a nodule or of
the liver itself may be noted from week to week,[143] especially in
cases of rapidly-growing cancer.
[Footnote 143: Murchison, _Clinical Lectures_, p. 187.]
As the cancerous new formations extend into the portal system within
the liver, obstruction to the portal circulation results from the
blocking of the blood-current. Also, interference in the portal
circulation arises by compression of the vessels from without, either
through the accumulation of cancer-products in the liver or by the
enlargement of the lymphatics in the fissure of the organ. In what way
soever it may be produced, the practical fact remains that ascites is a
frequent symptom, occurring in somewhat more than one-half of the
cases. The character of the fluid varies. It may be a clear serum
containing a small proportion of albumen; it may be colored by bile or
be of a deeper greenish or reddish hue; it may contain flocculi of
lymph and numerous leucocytes floating in it; and the ordinary serum
may be rendered cloudy and be filled with shreds of exudation in
consequence of peritonitis, or bloody because of hemorrhage from a
softening nodule. When the fluid is considerable in amount the
difficulty of ascertaining the condition of the liver is greatly
enhanced, and symptoms due to the interference of the fluid with the
action of various organs are introduced into the complexus of morbid
signs. Especially is the upward pressure of the ascitic fluid, and the
consequent interference in the movements of the lungs and heart, a
source of considerable distress. First, a local and afterward a general
peritonitis ensues as a consequence of the extension outwardly of the
new formations to the peritoneal layer, and its implication by
contiguity of tissue or the rupture of a spreading fungous growth and
hemorrhagic extravasation into the cavity. The peritoneal complication
is not only a serious addition to the sufferings experienced by the
patient, but it adds to the difficulties of a diagnosis. In the case of
a celebrated savant who died of cancer of the liver (seen by the
writer) there was such a pronounced peritonitis that the diagnosis made
by the attending physician was chronic peritonitis. When this
complication occurs, there takes place {1038} a decided increase in the
local tenderness, and this increased sensibility to pressure quickly
extends over the abdomen, causing a general exquisite tenderness.
Besides this tenderness characteristic of most cases of peritonitis,
distension of the abdomen and the decubitus peculiar to this state are
obvious symptoms. It is therefore clear that the occurrence of
peritonitis not only contributes to the severity and painfulness of the
case, but seriously complicates the diagnosis.