tumor cases.

3

The serious and desperate cases are the ones that may become confused with the true tumor cases. These desperate spasm cases may occasionally, but very rarely, require surgical treatment.

The employment of the x-ray for diagnosis in these doubtful cases is likely to prove of a good deal of assistance. The behavior of the stomach in a normal baby after the milk of bismuth has been introduced into it is definitely known. The behavior of the stomach in a case of pyloric obstruction due to tumor when the milk of bis

muth is introduced is likewise known. If bismuth is introduced into the stomach of a baby having a supposed pyloric spasm, the behavior will be often different from the record in either of the other two conditions. This difference may be helpful in the differentiation of these conditions. Every suspicious case of pyloric obstruc

tion in which there is doubt as to whether there is a tumor or not should be x-rayed. The subnitrate of bismuth may be administered by mouth and the stools watched for the appearance of bismuth crystals. The appearance of these crystals in the stools will be indicative of something passing through the pylorus. If the stools are infrequent and small in amount, these facts in themselves may be significant.

The Prognosis.-The mortality of this disease is high. Most cases of congenital pyloric stenosis die of starvation. The question is how long will it take a small baby to starve to death while the family physician experiments with drugs and foods, which under the conditions are absolutely of no use? It will take about three months, and this is the usual length of life of these small babies. Of course, the degree of obstruction in these cases, as has already been pointed out, varies. A baby with considerable obstruction will live a shorter time than a baby who has less obstruction, other things being equal.

There are cases being reported each year of young adults who have suffered during infancy and childhood from partial pyloric obstruction. Such individuals reaching maturity after years of gastro-intestinal invalidism, poorly nourished and probably underdeveloped - such individuals are more frequently than formerly being recognized as instances of babies who have had a partial pyloric obstruction and have survived despite the obstruction. Hezekiah Beardsley, in 1788, reported the case of a child who had lived five years

2. Beardsley, Hezekiah: Trans. New Haven Co. Med. Soc., 1788.

2. Treatment.-I believe that the treatment of stenosis of the pylorus in infancy should be surgical as soon as the diagnosis is made and for the following reasons:

That the pure pyloric spasm obstruction can be cured by medical treatment in a large proportion of cases is true. It is also true, so far as I am able to learn, that there is no case of true tumor which has yet been cured by medical treatment. So far as I am able to determine, no so-called medically "cured" case has ever been proven to have had the disease, but on the other hand many cases of supposed "cure" have relapsed and have been subsequently treated surgically. The tumor has been demonstrated to exist and a cure by surgical means has followed. Those who advocate and practice the medical treatment of true tumor cases do so on the erroneous hypothesis that muscle spasm is the chief cause of the obstruction. They lose sight of the fact that it is the tumor that obstructs. At best, medical treatment relieves only hypothetical spasm that perhaps accompanies certain tumor cases. Medical treatment does not effectively remove the primary cause of the obstruction.

The improvement in Heubner's series of cases and in the cases of others who have thought that they have been treating tumor cases with success is to be accounted for on the basis of a mistaken diagnosis, or a temporary and not a permanent

cure.

It was about twenty-three years ago that the pyloric tumor cases were first well described. During all these twenty-three years the physician has painstakingly striven to treat such cases by medicines and by carefully prescribed feeding. The estimated mortality from an expectant medical treatment is between 80 and 90 per cent. (Monier). It is on this carefully studied medically-treated post-mortem material that much of our present pathologic knowledge of this disease. is based. The medical treatment of the tumor cases has signally failed to effect a cure.

What has surgery already accomplished in the care of these cases? Surgery has gradually lowered the mortality in the treatment of these

3. Habersohn: Diseases of the Abdomen, 1862.

4. Lebert: Diss., Tübingen, 1878.

5. Landerer: Diss., Tübingen, 1879.

6. Rudolph Maier: Virchow's Arch., 1885, Bd. cii, s. 413.

7. Dunne Jahresbericht d. Jenner'schen Kinder-Hospitals, 1881, Bd. xix.

8. Tilger: Virchow's Arch., 1893, Bd. cxxxii, s. 290. 9. Barling: The London Lancet. Jan. 25, 1913.

cases. The mortality, once high, very distinctly is decreasing. The first time surgeons attempted to treat this disease was in 1898. From 1898 to 1905 is a period of seven years. During this period gastric surgery was developing. Operative technic was unsettled. The choice of procedure adapted to certain conditions was undetermined. This was an experimental period for gastric surgery in the adult and absolutely a new field in infants. Several different operations were done. by many operators for the same condition. The cases operated on had gone almost the limit of life under medical experimentation. Is it any wonder that the mortality from surgical operation during this period on such material was very considerable? The mortality for this period was 46.5 per cent. No apology is needed here for this mortality, for more than half the babies entrusted to the surgeon were saved by operation. Even this was a great improvement over the medical mortality.

Consider now the next seven years, the period from 1905 to 1912. The lowering of the mortality under surgical treatment has been remarkable. I have not yet collected all cases operated on during this period. I have three groups, however, which are fairly representative of the period.

a. The group of ten cases operated on from the Pacific Coast, collected by Stillman. In this group six different surgeons operated. A posterior gastro-enterostomy was done in each case. Of the ten cases, only one died.

b. The group operated on by Richter1o of Chicago. There were nine cases, only one died.

c. My own group of seventeen cases with three deaths, a mortality of 17.6 per cent. A total, therefore, of thirty-six cases with five deaths, or a mortality of 13.8 per cent.

The mortality of posterior gastro-enterostomy in congenital stenosis of the pylorus is low under the above conditions.

3. There are two important problems which this group of cases helps to solve.

a. What is the effect of gastro-enterostomy on the metabolism of the body? There are those who think that a gastro-enterostomy impairs digestion. The passage of the food through the artificial stoma is looked on as a real harm to the individual. Digestion, they say, cannot proceed in the proper fashion, and the individual will suffer because of such impairment of diges

tion.

In order to determine the effect of gastroenterostomy on digestion it occurred to me that

10. Richter has had 9 cases with 2 deaths since.

11

these babies with congenital stenosis might serve for metabolism investigations. The work done by Dr. Talbot of Boston, on a series of babies who had had a posterior gastro-enterostomy done for a stenosis of the pylorus, has demonstrated that in these cases there is no impairment of the digestion of fat, starch and protein. The details of these experiments, together with the results, I have already reported with Dr. Talbot in a former paper. If to the chemical evidence thus obtained be added the clinical fact that all these babies, without exception, are apparently thriving and in perfect health, have lived several years following the operation and gained in weight and height, the evidence is overwhelming that in these human babies gastro-enterostomy has no deleterious effect on the metabolism as measured by the digestion of fat, protein and starch and the normal development.

These experiments serve to confirm the work of Cameron and Paterson and make it absolutely conclusive that in the otherwise normal individual a posterior gastro-enterostomy has no harmful effect on digestion, so that the opposition to this operation cannot be based on any such conception as stated above.

b. The second question that arises in connection with these cases is what becomes of the muscle tumor at the pylorus; does it disappear as the child grows older? I think from the evidence at hand that it probably persists and does not disappear, and for the following reasons:

a. Through the assistance of Dr. W. J. Dodd of Boston, Skiagrapher at the Massachusetts General Hospital, and Instructor in Roentgenology in the Harvard Medical School, I have been able to obtain further x-rays on this series of stenosis of the pylorus cases operated on by me, and these x-rays show uniform findings. In every case, no matter how many years following operation, the bismuth meal is seen to pass through the stoma, and in only a very few is it seen to pass in slight amount through the pylorus. In other words, the obstruction at the pylorus, which has been proved in each of these cases to have existed, is demonstrated by the x-ray to still exist. The tumor is still present and still obstructs.

b. It has been demonstrated by certain physiologists that if the pylorus remains open and is unobstructed the stomach contents will be forced through the pylorus, even though an artificial stoma be present. On the other hand, it has been demonstrated that if the pylorus has been closed by some form of obstruction either par

287.

11. Surg., Gynec. and Obst., September, 1910, pp. 275

tially or completely, the food will be forced through the artificial stoma in whole or in part. In these cases the food is seen to be going through the stoma, and it is reasonable to suppose, therefore, that the obstruction still persists. In other words, the physiologic evidence confirms the evidence from the x-ray.

c. Bearing on the persistence of the pyloric tumor after operation mention must be made here of the pathologic evidence in the unique case of Morse-Murphy-Wolbach.12 The facts are these: A boy baby with pyloric stenosis diagnosed by Dr. J. L. Morse, was operated on by Dr. F. T. Murphy by a posterior gastro-enterostomy. The The pyloric tumor was seen and palpated. The child lived 72 months weighing then 19 pounds. During this time the baby had developed as a normal child, was breast fed, had not vomited, and had had normal movements. When 8 months old, the baby died of nothing connected with the operation. Fortunately, a complete autopsy by Dr. Wolbach was secured. The artificial stoma was found patent and functionally efficient. The pyloric tumor-and this is the point of present especial interest-persisted and appeared as at the time of operation. Microscopical study found the tumor to be a true tumor of circular musclefiber hypertrophy. This is the only instance of congenital pyloric stenosis that has been studied so long as six and one-half months following a successful gastro-enterostomy.

d. Attention should be called to the increasing group of adult cases of partial obstruction reported by Beardsley, Landerer and Barling and others, who have had symptoms of pyloric obstruction for many years and have reached young adult life with all the evidences of difficult feeding and impaired nutrition. These are cases with a pyloric tumor which has partially obstructed the lumen of the pylorus, not sufficiently to have caused death from starvation, but only sufficiently to have caused impaired diges

tion and malnutrition.

This evidence, then, from the x-ray, from physiology, from the post-mortem table, and from clinical observation, this evidence points pretty conclusively to the fact that the muscle tumor at the pylorus does not materially change. This is not a mere academic question, but it has, of course, a practical bearing, and places the surgical treatment of this condition on a very firm basis.

4. I wish to report here in detail the seventeen cases treated by me surgically and to call attention to the fact that whereas the first twelve cases

12. Boston Med. and Surg. Jour., 1908. clviii, 480.

were operated on without a death, there have been three deaths in the last four cases, the deaths being dependent on the starved condition of the baby at the time of operation. This experience only serves to emphasize the importance of as early a diagnosis as possible in order that the surgical operative measures may be undertaken with the very greatest chance of the baby's recovery.

I operated during the past eight years on two babies who were thought to have a pyloric tumor, and it was found at operation that they had no tumor. One case recovered from the exploration and is well to-day. One case died of some strange skin eruption unconnected with the operation. I have never operated on a case of supposed pyloric spasm.

In order to facilitate the discussion of the etiology of bronchial asthma, the disease may be divided into two clinical forms. In one, the paroxysms of dyspnea first make their appearance in early childhood, and henceforth occur with varying degrees of periodicity. They are knows will excite his asthma, as e. g., animal induced by some irritant which the sufferer emanations, odors of plants, some particular article of food, indiscretions in diet, etc. The paroxysms last a variable length of time and usually are arrested by some particular remedy, as the fumes of some asthma powder, a hypodermic of morphin, etc. During the asthma-free intervals the patient is free from dyspnea and may feel entirely well. Lastly, the individual may be permanently relieved of his asthma by change of climate, especially when the exciting agent is found to be the pollen of some particular plant, although in some cases mere change of locality proves remedial even when no especial irritant can be identified.

These peculiarities have led clinicians to assume a neurosis as the underlying basis of the disorder, while the often prompt amelioration of symptoms afforded by some favorite remedy seemed to warrant the assumption of spasm of the bronchi as well as the theory that the action. of the exciting agent was brought about reflexly either by stimulation of the circular bronchial

*Read before the North Side Branch of the Chicago Medical Society, April 11, 1913.

muscles or through the vasomotor system and consequent hyperemia and edema of the bronchial and nasal mucosa. It is not necessary to consider other theories, such as inspiratory spasm of the diaphragm, Kurschman's catarrhal bronchiolitis and the presence of Charcot-Leyden crystals, since these are but symptoms or manifestations of the underlying disorder.

Until within the last few years these manifestly inadequate attempts at explanation of the etiology of asthma were accepted and dominated our therapeutics. We were able to relieve the paroxysms, but not to effect a permanent cure; or if by chance this latter did occur, we were not able to account satisfactorily for the fortunate result. But there now has come to the front an explanation of the phenomena of disease which rests not on hypothesis, but on demonstrated, scientific facts, and which not only enable us to understand the symptomatology of bronchial asthma, but in many cases provides a rational method of treatment. This new conception of the nature of asthma, as many of you may know, is found in what has received the name "anaphylaxis."

Before elaborating this theory in its application to bronchial asthma, let me describe briefly the second form in which we recognize this distressing malady. This type does not begin in early life, and there seems to be no inherited predisposition. It develops ordinarily after the individual has reached adult age, and, according to my observation, very soon assumes the clinical features of chronic bronchitis with emphysema, but with paroxysmal exacerbations of the dyspnea. The individual is distressed all the time, but frequently, perhaps daily or nightly, suffers from such an aggravation of his dyspnea that it then truly merits the term, bronchial asthma. The disease is in essence the same as the distinctly spasmodic or nervous form, but intervals of entire freedom from a sense of respiratory distress do not occur, or are abbreviated to a few hours, it may be, instead of days or weeks. Measures addressed to relief of the sufferer may be still efficient, but their effect is transient or less pronounced.

How now does the principle of anaphylaxis apply to these cases? In order to make this entirely intelligible, let me give a concise statement of the essential facts of this enlightening view of the phenomena of disease.

By anaphylaxis is meant a protein sensitization or hypersensitiveness on the part of the animal to protein introduced into the system either by way of the alimentary canal or paren

terally, that is, by some other channel which permits absorption. This foreign protein may be labile and active in the form of bacteria or protozoa, or it may be stable as egg albumin, and hence may be of animal or vegetable origin. So soon as this foreign protein enters the system of the animal, certain body cells develop a proteolytic ferment whose specific function is to attack, split up and destroy, that is, digest the protein. In this cleavage process two groups of elements of the protein molecule are liberated, a poisonous or primary group which Vaughan' likens to the acid portion of a neutral salt, and another or secondary group which is not toxic. This secondary group, according to Vaughan, gives the distinctive characters to the protein molecule, and by him is likened to the basic element of a salt.

one

The splitting up then of the protein frees the poisonous portion of the molecule, and if this be in sufficiently large amounts, produces toxic symptoms. The secondary and characteristic portion of the protein molecule, also set free, is that which sensitizes the animal to this particular protein. The next fact to be remembered is that the proteolytic ferment generated by the body cells is capable of destroying only the one kind. of protein that called it into being, and no other. For instance, if the protein be egg white or a certain bacterium, the ferment can split up only the egg albumin or the particular germ, and nothing else. Furthermore, this proteolytic ferment which is developed for a definite and specific purpose, becomes stored up in the body cells in the form of what Vaughan designates zymogen or enzyme-producer, and in some instances the cells may undergo such profound changes that this zymogen may persist for a long time, possibly for years, and may even be transmitted from the sensitized mother to her offspring.

When now a foreign protein is attacked and destroyed by the specific proteolytic ferment of an animal's cells, that animal has become sensitized to that particular protein, but not to any other. If, after a sufficient lapse of time, usually twelve or more days, a second dose of the same protein be introduced into the animal's body, the specific ferment at once attacks and splits up the protein with the production of the phenomena of anaphylaxis. If the protein poison be sufficiently abundant and the proteolytic ferment be capable of liberating a sufficiently large amount of the poison, fatal anaphylactic shock takes

1. The Relation of Anaphylaxis to Immunity and Disease, Am. Jour. Med. Sc.,cxlv, No. 2, 1913.

place. Otherwise, the symptoms may be severe, but not fatal. Bacteria are themselves cells, and as such are able to generate a ferment which is capable of attacking and splitting up the protein of the body cells. Hence, if bacteria, on entering the blood, are capable of multiplying more rapidly, then they can be attacked and digested by the fighting or proteolytic cells of the animal's body, symptoms of disease appear. But if, on the contrary, they can be destroyed before they can multiply to a dangerous number, then immunity is produced in that animal.

What now are the reasons for concluding that bronchial asthma is a manifestation of anaphylaxis? Of these the most convincing are the observations of Auer and Lewis in experiments on guinea-pigs. These investigators found that when these animals were sensitized to a protein, as e. g. horse serum, and then after a sufficient length of time were again injected with this protein, they at once manifested phenomena identical in all clinical features with spasmodic asthma and died with extreme respiratory distress. On post mortem examination the lungs were greatly distended and the bronchi were so stenosed that air could not be forced through the contracted tubes. Furthermore, by suitable operative procedures it was proven that this extreme dyspnea was not of central but of peripheral origin. In other words, the bronchial stenosis was due to peripheral stimulation or contraction of the circular or constrictor muscles of the air tubes. In short, anaphylactic shock in guinea-pigs is manifested by typical asthmatic seizure indistinguishable from the disease seen in man.

Additional arguments for the anaphylactic theory of bronchial asthma are found in the effects of the injection of horse serum on individuals who have suffered from asthma when in proximity to horses. Gillette has reported instances of severe and even fatal symptoms from the administration of diphtheria antitoxin ta asthmatics whose paroxysms had been evoked by exposure to the emanations from horses. Indeed, Rosenau and Anderson warn explicitly against the danger of intense and even fatal anaphylactic shock from the administration of this remedy to persons sensitive to emanations from horses.

That such emanations are capable of producing anaphylaxis in sensitized individuals is found in the fact that such emanations contain suffi

cient protein to effect powerfully a previously sensitized person. This being the case, it is reasonable to conclude that the pollen of plants

2. Jour. Exper. Med., 1910, xii, 151.

3. See Bronchial Asthma as a Phenomenon of Anaphylaxis, by Meltzer, Jour. A. M. A., Sept. 17, 1910.

may contain enough toxalbumin to produce the same sort of symptoms. All that is needed is a previous sensitization, and this may be acquired in early childhood or it may be inherited.

The explanation of the cases in which an asthmatic paroxysm follows the taking of some special article of food or a hearty meal is not quite so easy, but yet can be found in anaphylaxis if we consider the chemistry of digestion. When food is taken into the stomach its various constituents are broken up by the digestive juices. The protein is attacked and split up by the digestive enzymes with the separation and liberation of the two elements of the molecule, that is, the poisonous and non-poisonous or secondary group, as classified by Vaughan. They are absorbed as amino-acids, and after absorption are reunited to form a protein that can be utilized by the animal for the construction of its own tissues. It is quite possible that, owing to a relatively too great amount of protein in proportion to the digestive capability of the enzymes, some of the protein is absorbed. Then two things will happen, namely, the first dose of protein thus passing into the circulation will sensitize the animal to that protein, cheese or shell-fish, or what not. Then if, after a sufficiently prolonged interval, this same protein be eaten again, and again be absorbed, the phenomena of anaphylaxis will occur.

In this same manner any foreign protein that gets into the blood or lymph from whatever source in the animal body, the colon, pelvic organs, or some focus, as an infected gall-bladder or pus-tube, may be capable of inducing the symptoms of anaphylaxis in a sensitized individual.

This brings me at once to the consideration of those cases of asthma which develop years after birth and present no traceable hereditary predisposition. I refer particularly to cases with some disease of the upper air tract or the accessory nasal sinuses. Ever since Hack and others called. attention to an etiologic connection between rhinological abnormalities and bronchial asthma, patients have been subjected to innumerable operations, sometimes with benefit, but more often without relief. My experience with this class of cases has not been extensive, and yet it has convinced me of the correctness of the view that nasopharyngeal and sinus disease does play a most important rôle in the causation of asthma. My observation is, therefore, in perfect accord with such reports as have been made, and quite recently by Justus Matthew from the Mayo clinic at Rochester, Minn.

4. Jour. A. M. A., Sept. 21, 1912.