Chapter II: Structural Diseases of the Liver (4)

[Footnote 134: _Ibid._]

[Footnote 135: _Diseases of the Liver_, Amer. ed., _supra_.]

Important symptoms arising during the toxæmic period require remedies to combat them. Nausea and vomiting, and also diarrhoea, are best relieved by carbolic acid and bismuth in combination. Hemorrhage requires, when intestinal, the chloride and perchloride of iron; when from other mucous surfaces, ergotin, gallic acid, and other hæmostatics. The depression of the vital forces should be treated by small and frequently-repeated doses of alcohol, by quinine, by iron, and, under some conditions, by digitalis. After the disintegration of the hepatic cells has been produced no remedies can be of any service. Until this occurs, however, it seems to the author well worth while to attempt to stay the destruction by the administration of those remedies which, by their accumulation in that organ, indicate a special affinity for its tissue. These drugs are phosphorus, antimony, gold, silver, and mercuric chloride. By the timely administration of one or more of these would it not be possible to stay the progress of the atrophic degeneration?

The Liver in Phosphorus-Poisoning.

DEFINITION.--Poisoning by phosphorus may seem to be a toxicological question rather than a merely hepatic disease, but as the morbid complexus thus induced is so similar to acute yellow atrophy that the conditions are regarded as identical by many of our German colleagues, it is necessary to enter into some details regarding it.

PATHOGENY.--Phosphorus-poisoning occurs at any period from youth to old age, but is most common from twenty to thirty years of age. Women seem more inclined to effect self-destruction in this way than are men, probably because phosphorus matches are so readily obtained. Children may munch match-heads in a spirit of mischief. That form of chronic poisoning seen in workmen in match-factories, and consisting in necrosis of bone, etc., does not come within the scope of the present inquiry.

A body poisoned by phosphorus does not exhibit a tendency to 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.

It has been already stated that pain in the right hypochondrium is a 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.

COURSE, DURATION, AND TERMINATION.--As amyloid liver is never a substantive affection, but secondary to some constitutional malady or to long-continued suppuration, its course must be considered in relation to the agency producing it. It is very silent in its origin and progress, and causes no pronounced symptoms until it attains considerable size and its functions are interfered with by the extent of the deposits. The history of the affection to which it is secondary therefore precedes the onset of the amyloid change and accompanies it throughout. The enlarged organ, with the results of its enlargement in altered functions of the abdominal organs, is a symptom superadded to existing disturbances. The period elapsing in the course of a chronic suppurative disease before the amyloid change occurs differs greatly in different cases, and may be stated as from three months (Cohnheim's case) to many years. Many of the cases terminate by an intercurrent disease; others by uræmic {1045} convulsions; a very few by hemorrhage from the stomach or intestines; and those pursuing their course uninterruptedly, by exhaustion.

The prognosis is very unfavorable. By some a cure at the beginning of the morbid deposits is regarded as possible, and examples of cures have been reported. The writer has seen supposed cases of amyloid liver terminate in recovery. There must always remain an impression that in such instances an error of diagnosis was committed. Those of syphilitic origin are probably more curable, but syphiloma of the liver may be confounded with amyloid disease, and hence the cure may be referred to the latter.

DIAGNOSIS.--Amyloid degeneration of the liver may be confounded with the various non-febrile enlargements of the organ. An important element in making the differentiation is the history of suppuration in connection with bone, with lung cavities, with constitutional syphilis, with chronic malarial toxæmia, etc. From fatty liver, amyloid degeneration is distinguished by the history as just sketched; by the fatty tendencies of the body in the former, emaciation in the latter; by the concomitant changes in the spleen, kidneys, and elsewhere; and by the subsequent history, fatty liver terminating by a weak heart usually, whilst the amyloid disease ends in the modes described in the preceding paragraph. From hydatid disease, amyloid liver is differentiated by the history, by the difference in the physical characteristics of the enlargement, by the presence of the purring tremor in the one, its absence in the other, and especially by the subsequent course. In all doubtful cases the use of an aspirator-needle and the withdrawal of some fluid containing the characteristic hooklets of the echinococcus will serve to determine the nature of the growth. From cancer, amyloid liver is separated by the previous history, by the nodular character of the enlargement, by the pain, and by the cachexia and associated derangements. Whilst amyloid liver is secondary to suppurative diseases, cancer is usually secondary to cancer of the stomach or other organ within the limits of the portal circulation.

TREATMENT.--As amyloid disease owes its origin to syphilis, to chronic malarial toxæmia, to suppuration, these, so far as they are remediable conditions, should be cured as speedily as may be, to prevent the development of the amyloid disease or to arrest it if begun. Unfortunately, the condition of the liver is not recognized until the morbid change is effected, and therefore practically irremediable.

The treatment necessarily involves that of the morbid state to which the amyloid deposits are owing. The syphilitic disease requires iodine and mercury; the malarial, quinine, iodine and the iodides, eucalyptus, iron, etc., according to the state of each case; and surgical diseases, especially necrosis of bone, should be effectively treated by suitable surgical expedients. The cause being removed if possible, what means, if any, can be resorted to to cause the absorption of the amyloid matter? The only specific plan of treatment hitherto proposed is that of Dickinson,[147] based on his theory of the constitution of amyloid matter; according to which the amyloid deposits consist of fibrin altered by the separation of the potash and soda salts, which have been eliminated in the pus. If this theory be admitted, the obvious indication is to supply the alkaline materials. The cases reported by Dickinson in which this theory was {1046} practically demonstrated were not sufficiently improved to lend any empirical support to this method.

[Footnote 147: _The Pathology and Treatment of Albuminuria_, p. 214 _et seq._]

The medicinal remedies which do any good are the iodides--notably the iodides of ammonium, of iron, of manganese, etc., the compound solution of iodine, and the double iodide of iron and manganese. As the officinal ointment of the red iodide of mercury, rubbed in over the splenic region, does so much good in chronic enlargement of the spleen, it is probable that it will prove effective in this form of enlargement of the liver. The writer has observed results from it in such cases that justify him in strongly urging its employment. The method of its application consists in rubbing perseveringly a piece of the ointment, a large pea in size, over the whole hepatic area, and repeating it daily until some irritation and desquamation of the skin is produced, when it should be suspended until the parts will bear renewed applications. Besides the topical application of the red iodide, this remedy may be given internally with advantage without reference to syphilitic infection. It seems to the writer probable that bichloride of mercury may be as useful, as it is certainly more manageable. The chloride of gold and sodium, arsenic in small doses, and the metallic tonics, so called, may be useful carefully administered, especially the first mentioned, which the writer believes has some real power over the disease.