nearly constant symptom in cancer of the liver. With the initial
symptoms, uneasiness, heaviness, a sense of pressure in the hepatic
region are experienced, and as the case progresses more or less acute
pain develops as a rule. But there are exceptions. In cases of cancer
involving the deeper portion of the liver there may be little pain, and
in some rare cases of cancer involving the external part of the
liver--the capsule and peritoneum--but little pain is experienced. In
much the largest proportion of cases the pain is severe, and the
production of any considerable pain means the implication of the
hepatic plexus of nerves or the hepatic peritoneum. It follows, then,
that the pain in the former case is not limited to the locality of the
disease, but is more or less widely distributed through the anatomical
relations of the hepatic plexus, being felt in the epigastrium, the
walls of the chest, the shoulders, etc.
In secondary cancer of the liver, following cancer of the stomach,
vomiting is a constant symptom, but also in those cases of primary
disease in which the left lobe is especially enlarged, relatively, are
nausea and vomiting pronounced symptoms. At the onset of the malady the
appetite fails and a gastro-intestinal catarrh is set up. More or less
catarrh of the bile-ducts also ensues. The interference with nutrition
thus occasioned is enhanced in those cases in which the obstruction of
the ducts is sufficient to prevent the escape of bile into the
intestine. Jaundice is not a constant symptom, occurring in little more
than one-third of the cases. When it occurs, the peculiar stools are
present and the intestinal digestion is deranged, as in cases of
ordinary obstruction to the ducts. In two cases of cancer of the liver
occurring in the writer's practice, and examined by post-mortem, there
were calculi present in the gall-bladder; in one case the principal
calculus was egg-shaped and the size of a pullet's egg.
The nutrition rapidly fails from the beginning of cancer of the liver.
The downward pace is accelerated when the gastro-intestinal digestion
fails and vomiting occurs after taking food. The skin becomes dry and
wrinkled, and if not jaundiced has a peculiar tint, varying in depth of
color from an earthy or fawn-like hue to a deep bronze. Failure of
strength is a pronounced symptom from the beginning, and is out of
proportion to the loss of flesh. As the wasting advances the decline of
strength is accounted for, but the feeling of weakness and the distaste
for exertion which occur so early are very significant signs of
internal cancer, although they do not indicate the position of the
neoplasm. Emaciation finally becomes extreme.
The urine declines in amount as the case progresses. It is usually very
high-colored, contains bile-pigment when jaundice is present, and other
forms of pigment produced by conditions not at present known. Sometimes
albumen is present, and leucin and tyrosin rarely.
{1039} COURSE, DURATION, AND TERMINATION.--As has been already set
forth, cancer of the liver may present so few really distinctive
symptoms as to escape recognition. Under favorable circumstances the
diagnosis may be comparatively easy. In forming an opinion it is useful
to review the whole course of the malady and draw conclusions not only
from the characteristic signs, but from the development of the symptoms
as a whole.
A case of cancer of the liver occurs usually after the middle period of
life. The person so affected begins to decline in flesh and strength,
has uneasiness in the right hypochondrium, disorders of digestion, and
begins to have a pallid or earthy hue of the countenance. Presently,
much pain is felt in the hepatic region, the organ distinctly enlarges,
and some effusion of fluid and much flatus increase the dimensions of
the abdomen. Much tenderness, often exquisite sensibility, is produced
by pressure over the liver, and often over the whole abdomen. By
careful palpation nodules can be made out and their growth noted in
those cases free from peritoneal inflammation. The abdominal swelling
and tenderness incommodes the lungs, and a semi-erect decubitus is
assumed to relieve the pressure on them; the breathing becomes short,
catching, hurried, and painful, and sometimes a most distressing
hiccough is superadded to the other sufferings. Great wasting and
weakness ensue. Jaundice appears, or the earthy hue of the skin deepens
into a bronze discoloration. The case may be terminated by some
intercurrent disease--by an attack of pleuritis, pneumonia, by
peritonitis from rupture or perforation, by intra-peritoneal
hemorrhage, by an exhausting diarrhoea. The natural termination is by
gradual failure of the powers, by marasmus, the immediate cause of
death being due to cerebral anæmia, to failure of the heart from fatty
degeneration of the cardiac muscle, from thrombosis of the portal vein,
from the development of a hemorrhagic state, and hemorrhages from the
various mucous surfaces, etc. The duration is much influenced also by
the character of the cancer, whether scirrhous or medullary. The latter
are not only more rapidly growing, more destructive of the hepatic
tissue, and more rapidly distributed to neighboring organs, but more
quickly perforate the capsule and excite a fatal result by hemorrhage
or by peritonitis. The average duration of cancer of the liver is
variously stated. Having reference to my own personal observation,
controlled by the experience of other observers, the duration is from
three to nine months, one year being exceptional. There are cases in
which the symptoms are very acute, the progress rapid, the whole course
from the initial symptoms to the termination being completed in from
two to three months. It need hardly be observed that no case of cancer
of the liver has been cured. The invariable termination is in death. If
any case has seemed to be cured, it may be asserted with confidence
that cancer of the liver did not exist.
DIAGNOSIS.--The differential diagnosis is concerned, first, with the
existence of cancer; second, with its form. As cancer causes
enlargement of the liver in two textural conditions--namely, uniformly
smooth, and nodular--it must be differentiated from other diseases
producing similar results. Amyloid disease and echinococcus cysts
present us types of the former; cirrhosis and syphilis, of the latter.
The history of the amyloid disease and of the echinococcus cyst is very
different, and both {1040} develop much more slowly. Amyloid disease of
the liver arises simultaneously with the same form of degeneration in
other organs, and is connected with suppurative disease of some kind,
with syphilis, with chronic malarial poisoning, etc., and may occur at
any age. Echinococcus cysts enlarge painlessly and do not impair the
vital forces; the liver is elastic, and under favorable circumstances
presents by palpation the purring-tremor symptom. Cirrhosis may have to
be differentiated at two periods--during the time of enlargement,
which, however, is rather brief; and during the stage of contraction
and nodulation. The history in cancer and in cirrhosis is different:
the age, the habits of life, the rate of hepatic change, are opposed in
the two diseases; the diminution in size with nodulation is
characteristic of cirrhosis; enlargement with nodulation belongs to
cancer. The rapid progress of cancer, the wasting, the debility, the
cachexia, serve to distinguish it from all other affections of the
liver except acute yellow atrophy and phosphorus-poisoning; both,
however, are so different in history and development as not to require
differentiation. It may be quite impossible in latent cases to
distinguish primary cancer of the liver from secondary, but in those
examples of the disease occurring in the stomach, intestines, and
pancreas there is usually an antecedent history of the primary malady
which distinctly separates it in point of time and the character of the
symptoms from the secondary implication of the liver. Cancer of the
gall-bladder, and especially of the organized exudation about it, may
not be readily separated from cancer of the pancreas or of the
duodenum. In doubtful cases the history of attacks of hepatic colic
becomes an important element in making the differentiation.
TREATMENT.--As we are not in possession of a cure for cancer, the
treatment of cancer of the liver must be palliative. Anodynes to
relieve pain, paracentesis of the abdomen to remove accumulation of
fluid which causes distress, carbolic acid to check nausea and
vomiting, and the usual hæmostatics for hemorrhage, are the measures
most necessary. In fact, the treatment must be throughout
symptomatic--for the relief of symptoms as they arise.
Amyloid Liver.
DEFINITION.--By amyloid liver is meant a deposit in the cells of the
organ, in its vessels and interstitial tissue, of a peculiar albuminoid
matter called amyloid because of a superficial resemblance to
starch-granules. Various designations have been applied to this
condition of the organ; thus it has been entitled waxy liver and
lardaceous liver, because of the apparent resemblance to wax and lard
respectively.
CAUSES.--There exists in the blood a peculiar material, albuminoid in
form, applied in the normal state to the structure of
tissue--dystropodextrin, as it is called by Seegen--which, when
precipitated under certain conditions not now known, assumes the
peculiar appearance with which we are now familiar under the term
amyloid. The character of the amyloid matter was first distinctly set
forth in 1858 by Virchow, who also discovered the characteristic
reaction by which it can always be detected. The reaction to iodine
gave to the material the designation amyloid, or starch-like, by which
it is chiefly known. The {1041} circumstances inducing the deposit of
this material are by no means clearly understood. It has long been
known that suppuration, especially in connection with bone, has had a
distinct influence. Syphilis, especially the tertiary lesions
accompanied by pus-formation, has an evident causative relation.
Chronic malarial infection has a more distant and doubtful, but still
recognized, power to develop this morbid state. Of the various causes
above mentioned, the most frequent is the suppuration of pulmonary
cavities. In regard to the influence of this, however, it must be
remembered that no form of suppurative disease is so common. The
relative frequency of the association between suppurating cavities and
amyloid disease is not greater than long-standing necrosis with an
extensive sequestrum is with the same state; but the actual number of
the former is greater. Amyloid disease of the liver is most frequent
between the ages of ten and thirty, but it may occur at any age, the
period in life being determined by the operation of the causes. Thus,
Frerichs' statistics are: under ten there were 3 cases, from ten to
twenty there were 19, and from twenty to fifty there were 37 cases. Men
are, relatively to sex, more frequently attacked, and in the proportion
of three-fourths, but this difference means, of course, the character
of men's occupations and their greater liability thereby to the
accidents and diseases incident to such employments.
Besides the pathogenetic factors above mentioned, it may be well to
refer in this connection to the effect of long-standing neoplasms. It
has been found that amyloid disease is produced in some subjects by the
cachexia resulting from the slow development and persistence of such a
new formation. The special character of the neoplasm is of less
importance in respect to this condition than the constitutional
condition--the cachexia--induced by its slow growth and interference
with nutrition. Although long-standing disease, especially of a
suppurative kind, is known to be necessary to cause amyloid disease,
Cohnheim[144] has lately published some facts which seem to prove that
the degeneration may occur more speedily than has been heretofore
supposed. He has shown, contrary to the previously-accepted view, that
amyloid degeneration may follow in three months after the reception of
a gunshot wound. He records three cases in which the amyloid deposits
ensued in six, five, and three months, respectively.
[Footnote 144: _Virchow's Archiv_, vol. liv. p. 271 _et seq._, "Zur
Kentniss der Amyloidentartung."]
According to the author's observation, a peculiar somatic type is
either necessary to, or at least is greatly promotive of, the amyloid
degeneration. If, for example, the same suppurative process occurs in a
person of a blond and lymphatic type and in another of brunette and
nervo-muscular type, the former will be much more likely to suffer from
amyloid change than the latter. "The gelatinous progeny of albuminous
parents" is the mode of expression used to designate this particular
type.
PATHOLOGICAL ANATOMY.--To use the term amyloid liver is rather
misleading, since this indicates the restriction of the morbid process
to the liver, whereas it is perfectly well known to be rather widely
distributed through various organs and tissues of the body. The term
amyloid is itself confusing, since the albuminoid material so
designated is not really starch-like. The corpora amylacea, so called,
differ materially from starch-granules, and still more from the amyloid
matter. According to {1042} Wagner,[145] these substances "have nothing
in common." In the study of the amyloid deposit it has not been
possible to separate it from the tissue in which it is imbedded; hence
the published analyses of this peculiar material are probably far from
correct. However, it has been rendered probable that the amyloid
deposit has close affinities with fibrin. One of the theories--that of
Dickinson of London--assumes that this material is fibrin deprived of
the potash associated intimately with it. According to Seegen,
dystropodextrin, a material existing in normal blood, agrees with
amyloid matter in its most essential characteristics. Although
Dickinson's theory is not tenable, it has served a useful purpose in
showing the close affinity of fibrin with this pathological product.
What view soever may be entertained of its nature, it is certain that
the material to which we apply the term amyloid is of albuminous
origin. Under circumstances with which we are now unacquainted this
material is deposited from the vessels, and, instead of undergoing
organization and contributing to the structure of tissues, remains
unorganized and unappropriated. It is known that this deposition of the
amyloid material is related to the process of suppuration and to
certain cachexiæ, but the intermediate steps remain unknown and
inexplicable.
[Footnote 145: _A Manual of General Pathology_, by Prof. Dr. E. Wagner,
p. 325 _et seq._]
The amyloid matter is first exuded into the coats of the finest
ramifications of the hepatic artery, and therefore the first appearance
of the disease is in the middle zone of the lobules. In this respect
pathologists are agreed: that the amyloid deposits first appear in the
walls of the vessels. Wagner maintained, in opposition to Virchow, that
the exudation is limited to the vessels and does not extend to the
hepatic cells, which perish by pressure and consequent atrophy. This
point has not yet been decided. It seems most probable, however, that
the ramifications of the hepatic artery and all the capillaries of the
lobule are affected, and that the deposits in them lead to atrophic
degeneration of the cells.
In consequence of this extensive implication of the vascular system of
the liver important changes occur in the size, density, and appearance
of the liver. The organ is greatly enlarged in all its diameters. When
felt through the walls of the abdomen its outline is distinct, it is
firm, even hard, to the sense of touch, and it projects from a finger's
breadth to a hand's breadth below the margin of the ribs. The increase
of size of the amyloid liver is very great, attaining in weight, on the
average, twice that of the normal organ; but this size may be largely
exceeded in exceptional instances. In respect to shape and outline the
amyloid liver does not differ from the normal organ; for although its
dimensions are increased, its relations to the parts adjacent are not
altered. The weight of the amyloid liver may reach ten, twelve, even
sixteen pounds avoirdupois. The color of the amyloid liver is very
different from that of the normal organ: instead of having the
reddish-brown tint, it becomes grayish, yellowish, or reddish-gray. In
consistence the amyloid liver is firm and rather elastic and doughy,
and on section the margins of the incision are well defined, even
sharp. A very characteristic feature of the cut surface is its
paleness, anæmia, or bloodlessness, and scarcely any blood is exuded,
even from the large vessels. The appearance of the incised surface of
the liver has been described by comparison with various substances:
according to one, it is waxy; according to another, it is lardaceous. A
thin {1043} section of a part of the liver far advanced in the amyloid
change is distinctly translucent, almost transparent; but a marked
difference is observable between the amyloid matter and the lobules
proper, even in the cases of extreme deposit. The lobules are separated
by an opaque yellow border, and the centre of each is marked by a spot
of a similar yellow color.
The amyloid material is remarkable for its power to resist the action
of chemical agents and putrefactive decomposition. The test originally
proposed by Virchow--iodine--continues to be the most characteristic.
Orth[146] suggests a method of applying it which is very excellent in
respect to the clearness with which the reaction is shown: A large,
thin section of the affected liver is placed in a saucer of water
containing some iodine, and after the reaction has taken place is laid
on a white plate. Iodine tincture, diluted or the compound solution, is
brushed over the affected region, when the amyloid matter assumes a
deep mahogany tint and the normal tissues a merely yellowish hue. The
distinctness of the reaction may be increased by brushing over the
iodized surface some dilute sulphuric acid, when the amyloid matter
takes a deep violet, almost black, color.
[Footnote 146: _Diagnosis in Pathological Anatomy_, Riverside Press,
1878, p. 321.]
Only a part of the organ--namely, the smaller vessels--may be involved
in the degeneration, and this may be restricted to patches or parts of
the organ. With the amyloid change there may be associated syphilitic
gummata, or the liver may be more or less advanced in fatty
degeneration or in cirrhosis. Those parts of the organ not invaded by
the disease are not often entirely normal; they are more or less
darkened in color by venous congestion, distinctly softer, etc. The
amyloid change is not limited to the liver, but extends to the kidneys,
lymphatic glands, the intestinal mucous membrane, etc.
SYMPTOMS.--As the amyloid change in the liver is usually coincident
with a simultaneous alteration of other organs, and as the deposits
characteristic of the affection are dependent on long-previous disease
of an exhausting kind, it is not surprising that the subjects of this
affection present the evidences of a cachexia. To the effects of a
chronic malady we have added the complications growing out of the
amyloid change in the liver, associated, as it usually is, with amyloid
degeneration of other important organs.
The symptomatic expression of amyloid liver is therefore mixed up with
various derangements that occur simultaneously, but especially with the
causes inducing the existing cachexia, with chronic suppuration of
pulmonary cavities, or in connection with diseased bone, with the
syphilitic cachexia, or with chronic malarial toxæmia. With what cause
soever the cachexia may be associated, the symptomatology of amyloid
liver is secondary to, or ingrafted on, the conditions produced by the
cachexia. The liver is enlarged in all well-marked cases from a
finger's breadth to a hand's breadth or more below the inferior margin
of the ribs; it is also firm to the touch, well defined, elastic, and
its margin rounded, but yet well defined. There is usually no
tenderness nor pain, and, without any uneasy sensations to indicate the
change taking place, the organ is found to have slowly enlarged,
sometimes to an extraordinary extent. Careful palpation may also
demonstrate an enlargement of the spleen. When the abdominal muscles
are relaxed and there is no swelling of the abdomen by flatus or
peritoneal effusion, the very considerable enlargement of {1044} the
liver can be readily ascertained. If the effusion is not so great as to
distend the abdomen unduly, the increased consistence and dimensions of
the liver can still be made out with comparative ease. The hepatic
functions are not always sufficiently disturbed to produce
characteristic symptoms. In a small proportion--scarcely one-tenth--of
the cases does jaundice appear, and when present it is due, usually, to
enlargement of the lymphatics in the hilus of the organ, and thus
directly compressing the hepatic duct. In the writer's experience,
although jaundice has not occurred, there was present a peculiar dark
earthy or bronzed tint of the skin, significant of chronic hepatic
troubles. Obstruction of the portal circulation is rather unusual, and
the explanation is to be found in the fact that the amyloid
degeneration occurs first in the radicles of the hepatic artery. In
about one-fourth of the cases ascites is present, but in a somewhat
larger proportion hemorrhoids, blackish, tarry stools, and other
evidences of portal congestion. When the intestinal arterioles are
attacked, an intractable colliquative diarrhoea comes on; the stools
are offensive, sometimes light from the absence of bile, sometimes dark
from decomposition or the presence of blood. When the stomach
arterioles are also involved, which is usual under these circumstances,
the blandest and simplest articles of diet will pass unchanged or
simply decomposed. Blood may be vomited sometimes in large quantity
from thrombic ulcers, but the matter ejected from the stomach when the
case is well advanced is a thin, watery fluid, faintly acid or neutral,
and greenish or brownish in color.
An enlarged spleen is often present, produced by the same
conditions--by amyloid degeneration. The same change taking place in
the kidney, the urine becomes pale, abundant, of low specific gravity,
and albuminous. General dropsy supervenes in a majority of the cases
finally, due largely to the hydræmia; and of this condition ascites is
a part. In some cases enlargement of the abdomen is the first step in
the dropsical effusion, and may throughout be the most prominent, as
the author has seen. In other cases oedema of the feet and legs is the
first evidence of dropsy; in still others the dropsy is general from
the beginning.
Amyloid liver may coexist with a fairly good state of the bodily
nutrition, but if digestion and assimilation be interfered with by any
of the causes above mentioned, the strength rapidly declines and
emaciation reaches an extreme degree.