19. Erik Ask-Upmark, Lund.

The Fate of Splenectomized Individuals. A Contribution to the Pathophysiology of the Spleen.

Our knowledge about the functional importance of the spleen in man is hardly very exhaustive in spite of the vivid interest that has been devoted to this organ throughout the history of medicine. The evidence hitherto ascertained has mainly been assembled on the one hand from experiments in animals, on the other hand from the clinical and pathological study of instances suffering from diseases of the spleen. I t is obvious that a more correct knowledge about the importance of the spleen in man is to be obtained from a study of cases in whom the normal spleen has been removed, i. e. in traumatic ruptures. Such observations have been made repeatedly in the literature but it may be said that most of the accounts hence avail- able do concerne the preliminary result of the operation, that reports on the remote results until recently only have been published as solitary observations, scattered over the literature, and that most of these instances are described cursorily. The present investigation is an attempt t o map out this if not absolute so yet relative white spot in our knowledge. Besides being a contribution to the general physiology of the spleen the study intends to form a basis for our consideration of splenectomized individuals from the point of view of insurance medicine. An inquiry (made in 1933) to 30 leading insurance corporations in the United States representing together about 100 millions polices has clearly demonstrated to me that we hitherto have been lacking a basis for a proper judgement of the prognosis of people deprived of their spleen. In a recently published paper BAUMECKER (1934) has collected the informations available in this regard from Germany and Switzerland but his investigation is rather cursorily, being based exclusively upon more general reports from the hospitals, The best account of this matter hitherto

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published is apparently the paper of RENFER (1934), but his material was confined to 15 cases.

My own study (made in 1932 although circumstances have pre- vented publication hitherto) has concerned the ultimate fate of persons operated upon in Sweden for rupture of the spleen with splenectomy and surviving the operation for a period which in no case was less than 1 year. In all 100 cases were obtained, representing practically all hence conditioned splenectomies carried out in Sweden up to and including 1930. (Only 2 cases could not be traced). I am indebted to the surgeons in chief of 43 hospitals for their kindness in allowing me to dispose the material. The period elapsed since the operation was a t least 1, when most 27, on an average 8 years. The age of the patients a t the time of the splenectomy was when lowest 3, when highest 70 years: 64 cases were 20 years or less. The cases were traced by letters and asked to fill up a very detailed questionary which they generally did in a quite satisfactory manner. In a minor number of instances (10 cases) a control-examination was made in the Medical Clinic a t Lund but the distribution of the material all over our large country made i t necessary in most cases to confine the investigation t o the follow-up examination by mail.

Mortality: Out of 100 cases 5 had died, the cause of death being the following:

1 case accident. 1 case the Spanish disease. 1 case appendicitis. 2 cases pulmonary tuberculosis. Among 94 cases followed up in the literature by 47 different

authors 6 deaths were to be noted. 1 case cause unknown (FERRERIUS 1711). 1 case pneumonia (RERTHAT 1844). 1 case coronary thrombosis (KUTTNER-BENEKE 1910). 3 cases pulmonary tuberculosis (CONNORS 1921, BRUGSCH and

GROSS 1932, RENFER 1934). If these two materials are added the following cases may be

excluded as of no significant importance for the consideration :- the accident case, the Spanish disease (in itself a “medical acci- dent”!), the unknown case, the case with coronary thrombosis (where i t was found a t the autopsy that numerous splenoids were scattered over the peritoneum, reasonably substituting the spleen).

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Hence, among the 7 cases left 5 died in pulmonary tuberculosis and 1 in appendicitis-the pneumonia case is for different reasons diffi- cult to evaluate.

Morbidi ty: If no regard is taken to the fact, per se, that death occurred in 5 of the cases the morbidity will occur as follows. 47 patients, or approximately the half of the cases, reported to have had a good health without any of several diseases indicated in the questionary. 53 cases had a t one time or another suffered from various disorders :

1) Local disturbances, with certainty or great probability con- nected with the injury or the abdominal operation per se were noted in 10 cases (8 ileus or subileus, 1 rupture of the diaphragm, 1 postoperative thrombosis).

a) Infections : tuberculosis 6 cases 2) More general disorders were observed, too

appendicitis 6 cases1) various respiratory infections 9 cases rheumatic arthritis or pyarthrosis 4 cases herpes zoster 1 case

b) tumours: 1 case of fibroadenoma mammae and cysta ovarii, c) various other disorders such as

disturbances from the digestive tract not directly to be accounted for by any adherence mechanism: 10 cases (dyspepsia, constipation),

pronounced tiredness in 10 cases mental depression, melancholy in 4 cases marked increase or decrease in weight 4 cases susceptibility to low temperatures 1 case nephrolithiasis 1 case.

The experiences in the literature material of 94 cases are only to be used with reservation when it deals with judging the morbidity, since they obviously do not include all cases splenectomized for rupture and surviving 1 year or more-several of these cases have reasonably escaped a follow-up examination and of their fate we know nothing2). Briefly summarized, however, 31 cases were reported as healthy, in 28 cases there were only laboratory records available

1) in 2 more patients the appendix was removed previous to the injury of

2) The same is course true about the mortality. the spleen.

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and no statement given about their general condition and in 34 cases various disorders were noted : local disturbances in 9, tuberculosis in 4, appendicitis in 1, rheumetics in 7, tiredness in 10, clinical polycytemia in 1, marked increase or reduction in weight in 4, attacks of fever not to be accounted for in 2, hyperhidrosis in 2l).

Tuberculosis :-although the mortality rate is striking the morbidity is hardly so since the disease anyway is common. I t may be re- called, however, tha t a protective r61e of the spleen against tuberculosis has been assumed on account of experiments in vitro (Phipps Institute) and in animals and also because of certain clinical observations (alleged improvement of the tuberculosis when spleen is therapeutically administered, e. g. as injections). One is tempted to ask whether not the recent discovery of FAHRAEUS and his collaborators (1935) of a lipolytic activity in the spleen may have some bearing upon this subject (enga- ging the capsules of the T. B.?).

Appendicitis:-7% of the Swedish population are said to attract appendicitis, most of the instances appearing in the younger adults, the rate among the students, for example, is indicated as 1 case a year out of a stock of 200. Nevertheless, if we re- member on the one hand tha t 2 of the 100 cases here studied had suffered from appendicitis years before the splenectomy and ac- cordingly been operated upon, and, on the other hand, tha t the average follow-up period in this material is limited to 8 years the occurrence of 6 cases of appendicitis seems high (2 would have been expected), although admittedly not conclusively increased. The increased reaction of the lymphatic tissue which sometimes has been observed in the literature in connection with splenectomy (enlargement of the lymph nodes) might possibly be a related phenomenon.

Turnours:-It is an old observation (which I have essentially con- firmed statistically) that macroscopical metastasis of malignant tumours rarely occurs in the spleen. Experimental evidence although in part contradictory (also own experiments with tar carcinoma), has been furnished to the effect that the spleen might exert a protective influence against malignancy. The

l) Since some cases did present more than one of the symptons mentioned

A few words about some of the diseases noted:-

the figures, if added, will exceed 34.

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present investigation (which originally was undertaken to settle this very question) seems to indicate that no clinical evidence for this opinion so far is available. I t should however be remembered that in my own material of 100 observatings only 19 cases were older than 40 a t the time of the follow up examination and that the corresponding figure for the collected material of the literature was 15. The problem obviously remains open to further research.

Tiredness :-This symptom is too often noted to be merely accidental and i t does not appear to be of neurotic character, I t is usually most pronounced during the years next after the operation and then gradually subsides but i t may also last for decades, pos- sibly for ever. The explanation rests in suspense: BENHAMOUE (1933) refers to the removed reservoir of the spleen and the less adequate adaptability to exertions, heat etc. that should be the consequence (as judged from animal experiments) but his deduc- tions are hardly convincing and the same may be said about the explanation suggested by ISAAC and RAY that the hemoglobin should be less efficient as oxygen carrier after splenectomy (DEUTSCH denies this).

Dyspeptic disturbances :-part of these instances may be due to the local surgical intervention, but in another part the character of the troubles is hardly compatible with this: pains appearing in connection with the food, especially meat, and combined with a constipation. Functional tests of the stomach and particularly of the liver have, however, hitherto not been carried out in such instances. In 4 cases the bilirubin was normal, in one case (which did not suffer from dyspepsia) i t was 1.3/200000. Urobilinogen was observed in the urine in two instances and missed in two. The content of urobilin in faeces was normal in 2 cases, decreased in one, increased in one.

Alterations of the body weight :-Both in my own material and in the literature there were a few cases with a quite considerable alteration of their body weight (increase in some, decrease in other cases). We cannot at present account for these observations. If they are not incidental (and I do not think they are) i t is poss- ible that they may be connected with the influence that the spleen almost unanimously is considered to exert upon the fat metabolism. The basal metabolic rate has been measured only occasionally (by DIAX, SINGER, SIMON-WAITZ, ASK-UPMARK), it

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was within normal limits but i t may be mentioned that these registrations did not concern the individuals affected by a change of their weight.

The blood was studied microscopically in 10 cases of my own, and the observations connected with those in the literature. The results run as follows: Index is in the very majority of the cases < 1, in a few cases > 1. The red count (in all some 40 cases con- sidered) exceeded 6 millions in 6 cases and was below 4 millions in 2. Clinical symptoms of polycytemia were noted only twice (by BREMER and by BRIEGER-FORSCHBACH). The resistance of the red blood cells to differently concentrated salt-solutions was, when investigated, within normal limits. The white count was fairly normal, usually > 5000, < 10000, more often > 10000 than < 5000. The blood platelets were essentially normal. JOLLY bodies may be noted, as may reticulocytes but none of these observations is the rule. A mononucleosis is common and so is eosinophilia (considered to exist when exceeding 4% ; maximum noted: 25%).

Briefly summarizing the mortality in tuberculosis has been re- markable. The morbidity does not show any definite difference against that of spleen possessors, if local abdominal complications are excluded, although the number of instances of appendicitis may or may not mean something, and a pronounced tiredness not infre- quently was to be noted which appears to have a real background even if for the present unfeasible. Occasionally remarkable alterations of the weight may be observed. No evidence has been obtained suggesting a greater susceptibility for malignant tumours in splenec- tomized individuals. Changes of the morphology of the blood are frequently met with several years after the splenectomy, indicating reasonably a profound alteration of the body.

The results arrived a t may appear meagre but on the one hand this investigation had to be undertaken not being made before, on the other hand i t may yet have yielded some modest contribution to our knowledge of the spleen. I t seems reasonable with regard to the hazards encountered (local complications, tiredness, possibly other disorders) to be a little reticent with the insurance of an in- dividual in whom the normal spleen has been removed, at least for the first year following the splenectomy when the readjustment of the body is going on. When this period, the length of which

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must be considered from case to case, has passed, a splenectomized person should be accepted for insurance as at least a fairly good risk.

The universal occurrence of the spleen in the animal’s kingdom, the extreme rareness of aplasia lienis, the equipment of the compara- tively small spleen with a strikingly large artery, the general histo- logical structure specific for this organ (the ellipsoids !), the liability of the body, a t least under circumstances, to regenerate or substitute removed splenic tissue (the “splenoid” cases of FALTIN, KUTTNER- BENEKE, STUBENRAUCH and LEE) and the functions of the organ as hitherto ascertained (BARCROFT reservoir, F ~ H R A E U S endopaus al- teration of the blood, etc) are all evidences in favour of the opinion that this organ of mystery, as Galen rightly termed it, should not be removed unless vitally indicated. This conclusion is entirely in line with the plea for conservative surgery of the spleen put forward on the international congress in Rome in 1926 and the present investiga- tion seems to bear that out.