l^C S'd'^ CA-^ ANATOMICAL RESEARCHES ON THE SO-CALLED "PROSTATIC HYPERTROPHY" AND ALLIED PROCESSES IN THE BLADDER AND KIDNEYS. BY 6Ty\N15LAU5 C!ECHy\N0W5Kl Assistant Professor of Pathological Anatomy, University of Krakait, Austria. y\UTliORlZED TRAN6Ly\T10N EDITED BY ROBERT HOLMES GREENE, A.M., M.D. Genito- Urinary Siirgeon to French Hospital. Sicrgeon to Work/iojtse and Penitentiary Hospitals, N^cw York City. Member of A?ner- ican Association of Genito-Urinary Surgeons, etc. 1903 E. R. PELTON NEW YORK EDITOR'S PREFACE TO AMERICAN EDITION. This book has been translated as the result of an agree- ment made with Prof. Ciechanowski some months ago. It is to be regetted that the beautiful plates that accompanied the foreign edition have been destroyed by the German pub- lishers. The views of the Author on the nature of the pros- tatic hypertrophy have been confirmed by the editor \vith the valuable aid of Dr. Harlow Brooks — see "Fallacies in the Treatment of Urethral Diseases," Journal American Medical Association, 1901, and "The Nature of Prostatic Hypertrophy, Journal American Medical Association, 1902. A large sale of so technical a work as this is not expected, but it is be- lieved that encouragement should be given to the production of articles on pathological anatomy. The Bibliography at the end of the book being so extensive it is hoped may prove of assistance to others interested in these or topics of a similar character to those of which this work treats. Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/anatomicalresearOOciec INTRODUCTION Functional disturbances of the bladder are of very frequent occurrence in old people. In most cases the trouble lies only in the necessity of urinating oftener than is usual; but in many cases there appear much more serious symptoms, either there remains in the bladder a smaller or larger amount of residual urine, or an absolute retention of urine takes place, or there is an involuntary overflow of urine from the overfilled bladder. This functional disturbance is usually at- tributed to an enlargement of the prostate gland. But it is a well-known fact that such functional disturbances take place also in cases where the prostate is of normal size; yes, even when it is below normal size. This functional disturbance, which I shall indicate as bladder insufficiency of the aged, appears then not to be in absolute connection with enlargement of the pros- tate, which is commonly called "prostatic hypertrophy." Cases have even been observed where the bladder has functioned normally in spite of a marked enlargement of the prostate. Furthermore, it is proven that the prostate is by no means enlarged in all aged men. On the contrary, from several quarters stress is laid upon the fact that disturbances of the bladder are not at all a general condition, but occur in only one-fifteenth to one-twentieth part of the cases where there is prostatic hypertrophy. The different varieties of bladder insuf- ficiencv in the aged have a great many similar clinical symptoms. It has, however, especially in recent years, become the custom to group all these varieties together and call them by one name. People were even con- vinced that all these diseased conditions really differed very little from each other, and that they only represented different stages of the same disease. The main repre- sentatives of this view are Guyon and his pupils, who, for the last twenty years, have given the well-known name "le prostatisme" to this disease. This name is meant to represent senile bladder disturbances in men and in women as well. The choice of the same proves, however, that the author is convinced that such bladder troubles are most frequently concurrent with enlarge- ment of the prostate in the aged. The characteristics of the clinical picture are only to be obtained by presenting them on a uniform general anatomical basis. The Guyon school tries accordingly to connect all urinary symptoms observed in a lifetime with similar anatomical changes in the whole genito- urinary apparatus. The characteristic of these changes is said to consist of sclerosis of all the tissues and parts of this apparatus. They state the sclerosis attacks mainly the bladder wall, but it exists at the same time in the kid- ney, testicle and prostatic tissues, by which the prostate gland in most of the cases can become enlarged. With the exception of the process of inflammation, which is con- sidered an accidental complication, all changes in the different divisions of the genito-urinary apparatus are then, according to their school, one and the same thing. They are all called forth by the same general cause which lies outside of the genito-urinary apparatus, and which influences the whole human organism. According to the older statement of the French in- vestigators, this general and common cause of the anatomical changes in the bladder, the kidneys, the testicles, and, in certain cases, also in "prostatic hyper- trophy," is a pure influence of senile changes. Never- -theless, the following- sentence can be found in the famous work of Guyon, in the year 1885 (40 2d ed., p. 119): "C'est sans doute I'age des malades, qui peut expliquer les inegales conditions de la resistance de la vessie * * * " (namely by the comparison of the bladder function in prostatic hypertrophy with that in the cicatrical chronic gonorrhoeal stricture of the urethra). This explanation was, however, according to all appearances, insufficient even for Guyon himself, because he then took refuge in the overwhelming in- fluence of the local conditions, i. e., in the obstructions to the free emptying of the bladder placed by the pros- tatic hypertrophy in the orificium vesicale urethra. "Jamais ou n'a signale chez la femme de la retention senile, jamais ou n'a vu sa vessie atteinte d'inertie primitive. A quoi peuvent tenir ces immunites, se ce n'est a la rectitude et a la permeabilite de I'urethre qui restent intactes malgre les progres de I'age" (1. c, p. 120). At this time there came an important change in the views of the Guyon school, the first sign of which ap- pears in the same year (1885) in the publication of the thesis of Launois [72]. Launois, who did not take the influence of old age into consideration, was the first one who expressly in- dicated general arterio sclerosis as a comimon, general cause of the anatomical changes in the whole of the genito-urinary apparatus. Like the well-known my- ocardic cicatrix, caused by the influence of the at'hero- mata of the coronary arteries, analogous changes in several other organs, among them changes also in all parts of the genito-urinary apparatus, appear, according to Launois, as a consequence of a general atheroma — i. e., one which attacks all or the greater part of the arterial branches. In tlie kidney, in such cases, there is always developed a connective tissue hyperplasia and sclerosis, which cannot be differentiated from the usual interstitial nephritis. In the bladder wall there appears an active connective tissue proliferation at the expense of the bladder muscles. In the prostate gland the connective tissue has an active part in the growth of the so-called fiibromyoadenomata, which really, as a rule, is the con- sequence of the arterial atheroma and a cause of the so- called "prostatic hypertrophy." This theory of Launois' was not only accepted by his teacher in its full extent, but was even drawn with still sharper lines and stronger colors. Since then it has been maintained and enlarged from many quarters, and has counted followers ever increasing from day to day and becoming less conservative, although very soon weighty objections were heaped up, first in Germany and then in France. In opposition to the close ranks of the pupils and fol- lowers of Guyon stood a large group of investigators, who remained faithful to an older view, or who at least gave it more or less value. It was in general always emphasized by this group that the cause of the bladder disturbance in all cases lay in purely local changes in a part of the urinary or genital apparatus respectively. To such local causes the senile bladder insufficiency has even from olden time been attributed. By them the changes of the orificium internum and of the pars prostatica urethra which occur in the great majority of cases were mainly emphasized. For example, Civiale emphasized the importance of th,e condition of the blad- der muscles for the origin of interference with micturi- tion. It is Mercier's great merit that he has called atten- tion to the previously neglected changes in the so-called bladder neck. He was the first to recognize fully their importance, although it cannot be denied that he has gone a little too far, and seems to have forgotten other conservative factors. Civiale's half-forgotten view has in its main lines been renewed by Harrison (58-60, 390-395). Harrison pre- sents it in a way which is much too fantastic to gain any followers. Harrison asserts that the main object of the prostate is to lift the bladder fundus, and that the prostate must suffer a working hypertrophy as a consequence of primary sclerosis of the bladder wall, which brings with it a relaxation and deepening of the fundus of the bladder. But even without the theory of Harrison the views of Civiale would not have been completely forgotten, "mutatis mutandis." They are still in many details preserved in the Guyon theory. Mercier's views have generally answered for this in the literature, even if they were more or less modified. The enlargement of the prostate gland then is by many investigators regarded as a local, primary cause which stands at the head of all other changes, and on which these are dependent. But they by no means agree on the questions in what way and on what anatomical changes this enlargement, which usually goes by the name of "prostatic hypertrophy," depends. Some in- vestigators seek the cause of the hypertrophy outside the prostate gland proper — namely, in the influence of the activity of the testes. Others think that the cause lies within the compass ,of the tissues of the prostate itself; while they either endeavor to draw only a vaguely marked parallel between the uterus and the prostate, or point to a previous inflammatory process as the most important etiological factor. The theory which has the m.ost followers is that all anatomical forms of enlarge- ment of the prostate are a kind of new growth; they only argue over whether this new growth comes from the epithelial gland elements, or from the interstitial muscle, or connective tissue. The matter is still more complicated by the fact that the great majority of in- vestigators describe several special, well-characterized forms of the so-called "hypertrophy." So much is certain, that prostatic hypertrophy is by no means the only cause of bladder insufficiency in old people. There remains a large number of cases which are not accompanied by enlargement of the pros- tate, the so-called cases of "Prostatisme vesical." For this reason it seemed to me proper to renew the investigation of bladder insufficiency in old people. I began this in the fall of 1894, and continued for two successive years, and was assisted in it by my much revered chief and teacher. Prof. Browicz. May I be permitted here to express my gratitude to him, not only for abundant material, but also for the strong in- terest with which he followed my work. Originally, it was my intention merely to verify the statements made by the Guyon school; but the work brought forth in the course of time some peculiarities, but little known, which seemed to me adapted to throw some light on the pathogenesis and etiology of the whole clinical picture of "bladder insufihciency in the aged," as well as on the question of the so-called "pros- tatic hypertrophy." In the first part of my work I shall consider the alleged g"eneral causes of the changes in the genito- urinary system in the course. of the so-called "prosta- tismus," and at the same time I shall give the re- sults of my investigation, which to some extent will clear up the question of senile bladder weakness. In the second part, I shall deal with the pathological histology and the etiologv of the enlargement of the prostate, to which the name "hypertrophy" has been given. CHAPTER I. ANATOMICAL RESEARCHES ON THE 50=CALLED "PROSTATIC HYPERTROPHY" AND ALLIED PROCESSES IN THE BLADDER AND KIDNEYS THE SIGNIFICANCE FCR THE ORGANISM IN GENERAL OF ATHEROMA. The theon- of the French school of the importance of athromatons changes is really not a new thought. It originated at the time when the teaching in France, about the intiuence of general atheromata upon the condition of all the organs, found its development and maturity. And since that time the atheroma has been recognized as a very important and far-reaching factor; and this process as the common cause of a great group of diseases, which were looked upon before as due to different disturbances. At that time a new pathogenetic group was formed to which the name of "'Sclerose gen- eralisee" was given. Guvon and his pupils had at hand, therefore, a model to follow, but they had only what was at that time a general rule to use for the special cases. The pathogenetic significance of the atheromatous processes received very little attention before the forma- tion of a definite understanding of the general scleroses of the internal organs. Nearly all investigators were of different opinions in regard to the local cause and development of the athero- mata. Rokitansky (286), Schnopfhagen (289), Talma ^293), Ehrenreich (264). Mrchow (296), Langhans ii-ji), Koster (270-271). Friedlander (265), Heubner-Traube (295), Stroganow (288), Koster (269), Lancereux {2'ji), Sternfeld (292), Thoma (294). These questions, although very important, have no interest for us at present. But, to get a correct understanding in order to ap- preciate the pathogenetic significance of the atheromata, it is necessary to recollect how far the current literature recognizes the active part played by the small arteries and arterioles in atheromatous processes, and how this question of the localization of atheromatous changes in the different arterial ramifications of the aorta corre- sponds to the question of the relative frequency of the atheromata in the different parts. Some of the investigators, as, for instance, von Cornil and Ranvier (260-298), Friedlander (265), and others, separated atheromata of the arterial branches from the changes in the small arteries in which the retrograde disturbances of nutrition with atheromatous characteris- tics never occur; but in which, on the other hand, the proliferative and hj'perplastic processes in the intima play a very important part. It is beyond doubt that such proliferation, which often leads to complete obliteration in the small and small- est arterioles, often stands in no relation to the athero- mata of the large arterial branches. It is a well-known fact that the arterioles which are in the neighborhood of an organ suffering from chronic productive inflammation, share after a time in the same pathological processes, under the influence of the same pathological irritation which sets up the inflammation in the organ primarily attacked, and will be obliterated in time. Similar processes are observed, as is well known during chronic infectious processes, such as tuberculosis and syphilis. On the other hand, it is generally known nowadays that the pathological picture of general athe- roma with the proliferation of the intima of the small arteries is intimately connected with that of atheroma of the aorta. Truly the obliterating endarteritis of the small vessels is not an inevitable result of the atheroma, because we find that there may be atheroma of the larger vessels without the smaller ones being involved. Be- sides this,-we must remember that in old people there is, as a rule, a moderate, diffuse thickening of the ar- terial intima which must be regarded as physiological 14 and within certain limits a normal change of advanced life. For this reason it would be very desirable to know how far this senile, diffuse thickening of the in- tima can be taken for a normal symptom, and at what point the pathological changes begin to appear; al- though a mathematically correct border-line cannot be drawn. It is well known, however, that the intima in every part of the arterial system generally appears very thin and that even in the great vessels its thickness does not exceed .03 mm. (Vierordt, Anatomisch-physiolo- gische Daten u. Tabellen Jena, 1893). We find in the arteries of different caliber that the relative proportions of the thickening of the intima to that of the whole of the vessel wall, as well as of the thickness of the intima to the diameter of the lumen are very different; just as the thickness of the wall of the arteries differs very much in different organs, although their lumen is the same. (Stahel. Archiv f. Anatomic u. Physiologic. Anat. Abt. 1886, p. 45.) For this reason alone, no one up to the present day has tried to find the absolute measure by which the physiological thick- ening of the senile intima may be differentiated from the moderate pathological changes. It is, however, wholly unnecessary to find such a measure, inasmuch as we examine the arterioles of identically the same organs, and for comparative group- ing we only select arteries of nearly the same caliber. A relative measure is more than sufficient for our in- vestigation, since we shall consider only the advanced and undisputable intima thickenings. In the small arterioles we find that the lumen be- comes narrower in proportion to the degree of the atheromatous proliferative obliteration, and that the wall becomes continually thicker at the expense of the lumen. This fact, which is considered correct by all other iti- vestigators, is disputed only by Thoma (294), (Virchow's Arch. Bd. 71). Through this narrowing of the small arterioles we can best explain the influence of the atheroma upon the condition of the affected organs. A slow diminu- tion of the nutritive supply, which often results in the complete shutting off of the blood supply, must nec- 15 essarily produce a retrograde disturbance of nutrition with atrophy O'f the component parts of the organ, which are replaced by connective tissue and cicatrices (infarction). We see every day on the dissecting table advanced examples of these processes in the form of myocarditis disseminata fibrosa. The results of the arterial atheroma upon the organ- ism depend entirely on whether the atheromatous changes which have taken place in the large arteries have also involved the smaller ones. If in addition the small arteries are involved in this process, the physio- logical function of the organ will suffer damage, which will be greater the more numerous the branches which are affected. In every text-book we find a few lines at least about the different and irregular localization of the atheroma. Rokitansky in his table of frequency (p. 310 and 227) places the common iliac fourth and the hypogastric twelfth in frequency. This statement has often been confirmed: Curci (259), for example. He found in 93 cases of atheroma only 5 cases of the hypogastric. Von Bregmann (258), and Mehnert (281), made the state- ment, founded on similar experiences, that the athero- mata in the peripheral arteries decrease in frequency as the distance from the heart is increased. It will be seen from this that the localization of the atheromata is very irregular, and that those arteries of the small pelvis which especially interest us have only a small tendency toward atheromatous disease, and lastly, that it is very rare to find a general arterial sclerosis in the true meaning of the word. For this reason alone it seems impossible to accept the statement of the French investigators in its full extent, without criticism, inasmuch as they regard the general degeneration of the connective tissue of the internal organs (sclerose generalisee) as due frequently and solely to the changes produced by arterial atheroma. Even to-day, when no one denies the pathogenetic importance of the arterial atheromata, especially of the proliferative, atheromatous changes in the small ves- sels; the number of pathological processes .which are actually caused by atheroma is, notwithstanding this fact, very small. Even if we cross the borderline of the 16 fibrous deg-eneration, we shall find, besides the euce- phalo-malachial processes, the fibrous myocarditis, some forms of kidney-atrophy and the so-called senile gan- grene, no other disease which stands in direct and un- disputable dependence upon the atheroma. Also the senile atrophies, so often encountered, cannot be con- sidered without much ado as belonging to the clinical picture of the so-called "sclerose-generalisee." These simple atrophies could as well be a process independent of an atheroma; at the most, perhaps, one coordinated to it. There are, therefore, considerations "a. priori" against the causative connection maintained by the Guyon school, of the hypertrophy of the prostate gland and the accompanying symptoms of the arterial athe- roma. In order to prove the lack of foundation for this the- ory, which at any rate is intelligent and clever, there is call for direct proof that hypertrophy of the prostate gland and bladder insufficiency are not constantly ac- companied by atheroma of the vessels supplying the genito-urinary apparatus. At the outset it is not to be disregarded that atheroma of the pelvic and renal arteries occurs with a certain regularity, in spite of the fact that the vessels in other parts of the body may be normal. The irregularity and unevenness in the localization of the atheromatous processes in different branches of the arterial system makes this seem, at least, iiot im- possible. 17 CHAPTER 11. THE inPORTANCE OF ARTERIAL ATHEROflA IN THE GENITOURINARY ORGANS The number of investig-ations up to the present day which treat directly of the frequency and locahzation of the atheromatous process in the dominion oif the genito- urinary apparatus is very small indeed. In the thesis of Launois {y2) it is tO' be regretted that nothing definite concerning the subject is to be found. Also in the works of Bohdanowicz (7), and Motz (89B), there are very few details. Motz says that he found among 30 cases of hypertrophy of the prostate gland 9 cases oi sclerosis of the small arteries within the gland itself. Really correct investigation is only to be found in Casipar's work (16). Among 24 cases of hypertrophy of the prostate gland with atheroma of the aorta he found atheroma in the renal arteries and in the main branches of bladder vessels in 8 cases ; in the small arteries within the bladder-wall in 9 cases ; but changes in the small prostatic arteries in only 4 cases. A general atheromatous process of all the arteries of the genito-urinary system he found only in 2 cases. The results of my own investigation are shown in table No. I. This group relates to 42 male and 5 female cadavers of old people with a condition of more or less high-grade arterial atheroma. In one-half of the male bodies examined, all of Which except 4 were over 50, and the majority between 60 and 70 years old, a hypertrophy of the prostrate gland was found going beyond the normal dimensions. Among these 21 cases with hypertrophy of the prostate 18 gland I found atheromatous, atheromatously-prolifera- tive changes, respectively, in 21 cases in the aorta, in 18 cases in the common ihac and hypogastric, in 7 in the TABLE I. The co-incidence of the Arterial Atheroma, Kidney Degenerations and Enlarge- ment of the Prostate. V X 1 "5 5; a: ^:\ 1 th Org kin Condition 0/ Kidneys. Formed 1 NOTE 1 "6- 1 3 4 I 7 8 •3 il ■7 ■s 58 59 69 76 68 67 77 72 75 80 69 78 63 60 67 74 78 70 65 75 77 1 [ ; Atrophia senilis Cirrhos. e arterioscl Cicalr. post infarct. Atrophia senilis A. sen. et Nephr. apost. .Atrophia senilis Cicatr. post intarct. Pyelitis calculosa Nephritis chronica Degeneratio cystica 31.2 25.0 13-5 ■5-3 15.6 26,6 26.0 39 -o 30.8 36.2 28.7 30.0 27.3 40.4 Atheroma of art. 0.' extremities and brain " " all art. except pulmonary " " covonai7 art. " the whole art. system " " covonary arteries " " ■'■ " and cerebral art. " " " cerebral an. " ■' " covonary and extrem. an. ^ 2, ■ 8 1 8 7 7 8 2 7 21 ^3 25 26 27 28 -9 30 3' 32 33 34 11 37 38 39 4<: 65 75 45 57 67 59 40 53 75 40 57 70 62 68 72 70 11 60 74 \ '' ■ ■ ' ■ Cirrhos. e arterioscl. Atrophia senilis Nephritis chronica Cirrhos. e arterioscl. Atrophia senilis Nephritis acuta Nephritis acuta Amyloidosis Hyperaemia passiva Nephritis chronica Cirrhos. e arterioscl. ■7 '7 '3 13 16 18 '9 '9 15 la '9 5 5 3 4 4 6 4 6 5 8 8 Atheroma of arteries of extremities " " covonary arteries Atheroma generalisatum " covonary and extrem. an. " Covonary art. " generalisatum -a ■■ 8 8 9 8 3 21 iS 43 29 8.5 15 ■ 7 lo 10 Cirrhos. e arterioscl. 4 Nephritis chronica ■ Atrophia senilis 7 (8) Other degen. 10 No " 18 21 21 Atheroma generalisatum 4 cerebral art. i U) , covonary art. 9 (13) Art. otherwise normal 22 5 4 4 4 go 70 70 74 8r ; I j 1 1 I Atropliia senilis Cirrhosis e arterioscleros (^ 4 5 5 3 ■• 4 Cirrh. e arterioscl. i, A. 4 arteries of the bladder and prostrate gland (before they entered the substance of this gland), in 8 in arteries 19 within the bladder-wall, in 2 in the arterioles of the pros- tate gland, and in 7 in the renal arteries. In the other half O'f the cases, those without hypertrophy of the prostrate gland, I found arterio-sclerosis 19 times in the aorta, 11 times in the common iliac and hypogastric, 8 times in the main branches of the bladder and the pros- tate gland, 9 times in the arterioles of the bladder-wall, 8 times in the arteries within the prostate gland, and only 3 times in the renal arteries. In this place stress must be laid upon the fact that I reckoned only those vessels affected by atheromatous de- generation, in which there existed either an indisputable endarteritis nodosa or a thickening of the intima, quite regular and diffuse, but overstepping the normal limits of the pathological, as was proven 'by miscroscopic meas- urements. In all the five female cadavers I found arterio-sclerosis in the common iliac and hypogastric ; in four I found it in the renal vessels, in the small vessels of the bladder and in the aorta ; in three of the cases the main branches of the vessels of the bladder were attacked by the arterio- sclerosis. To sum up, the investigation of the forty-two cases showed arterio-sclerosis in : Aorta 40 times Common iliac ; 29 Hypogastric 29 " Main branches of vesicle 15 Large branches of prostate 15 " Vesicular branches within bladder wall 17 " Prostatic vessels within the gland 10 " Renal arteries 10 " Besides these I found atheroma in : Coronary arteries 13 " Basilar arteries 4 " Arteries of extremities 4 " Finally there was a general atheromatous process in four cases, in two of which (case 2 and 6) there was at the same time an hypertrophy of the prostate gland. The concurrent appearance of the arterio-scherosis in the renal, vesicular and prostatic arteries was found seven times; among these, four times together, with an hyper- trophy of the prostate gland. (Case 2, 6, 15, 17.) All vessels, with the exception of the arterioles, of the genito-urinary system, showed a general arterio-sclerotic change in three cases (case 20, 28, 40) ; in none of which a hypertrophy of the prostate glared could be proven. Among the fifteen cases in which there were athero- matous changes in the larger vesicular and prostatic ar- teries, the prostate gland was found of normal size in five cases (case 24, 28, 38, 39, 40) ; small, atrophic, and fromi twelve to twelve and a half grams in weight and in three cases (case 20, 31, 33; and large in seven cases. In the remaining fourteen cases of hypertrophy of the prostate gland all signs of arterio-sclerosis of the pros- tatic vessels were missing. This table, which was formed by myself, does not ex- actly coincide with the results of Curci, Mehnert and Bregman ; but the small difference existing cannot over- throw the rule formulated by these investigations, that the frequency of the atheroma in the peripheral vessels decreases the further they are from the heart. Exception to this rule is found in my cases in the renal arteries only. Even if this general rule, confirmed once more by my investigation, seems to weaken the Guyon theory, yet we cannot entirely forsake it. von Launois (72 p. 102) lays stress upon the fact that the changes in the kidneys, blad- der and prostate gland are only synchronous, co-ordinated and anatomical consequences of one and the same cause, i. e., an endoperiarteritis of the small vessels, and that be- tween the changes in the vessels and the "sclerose" of these three organs there is a strong parallelism ; in other words, that the extent and intensity of these changes of the organs get to be more marked the more the vessels are attacked by this atheromatous process. On the basis of the cited results, obtained by myself, it can at most be stated that the changes in the vessels of the entire genito-urinary system are neither constant nor synchron- ous with each other in cases of hypertrophy of the pros- tate gland. The question whether the changes in the tissues of the genito-urinary system are really analogous, and whether there exists a strong parallelism between the extent and intensity of atheromatous changes in the vessels and the fibrous degeneration of the kidney, bladder and prostate must still remain undecided. The decision of these questions is possible only through a careful investig'ation of the condition of the vessels and the condition of the organs, i, e., the kidneys, bladder and prostate. CHAPTER III. RELATION OF ARTERIAL ATHEROMA TO THE POST ATE GLAND It is is not difficult to prove that no causative connec- tion exists between the enlargement of the prostate gland, which is cornmonly known as hypertrophy of the prostate gland, and the arterio-sclerosis. It seems a "priori" hardly possible to find such causa- tive connection, because, as was first pointed out by Cas- par (i6), the disease processes, in which, on account of arterial sclerosis, an enlargement of the involved organ might take place, are altogether not known and not possi- ble. Moreover, even by the Guyon school itself protest was made against the conception. See Bohdanowicz (7), Motz (89B p. 43), It is really hard to understand why Launois, who followed a road made by his coumtr^-men, seemed to forget a very important part of the French theory. Martin, Duplaix, Martha, Lancereux and others mention, in their teachings of the so-called "sclero'se generalisee," only cirrhosis, atrophy, and such atrophic conditions of the organs as are accompanied by shrinkage and are entirely due to a general arterial sclerosis. The condition of the larger prostatic arteries, which I mentioned before, and which we shall lay aside for the present, will only point out that, among my forty-two cases of really advanced arterial sclerosis, in ten cases only was there found an atheromatous, proliferative change of the same vessels within the prostate gland. Among these ten cases of atheroma of the smaller of the prostatic vessels the prostate gland was only once atro- phic (case 20), and twice hypertrophied (case 2.19); the weight was 25 and 27.3 grams respectively. In all 23 the other cases of even advanced prostatic hypertrophy the intra-prostatic vessels were found normal. In the re- maining- seven cases of atheroma the prostate gland was found unchanged (case 23, 28, 29, 37, 38, 39, 40). Among the cases of Bohdanowicz we find one (No. II) which treats of an old man of seventy-five years with intense hypertrophy of the prostate gland zvithout any sign of ar- terio-sclerosis. An analogous observation was made by myself (case 8). A man, 80 years old, had atheroma in the ascending aorta, arch of the aorta and coronary arteries ; the pros- tate g'land was visibly enlarged, weighing 34 grams, and showed a pathological change in structure. These two observations alone are sufficient to conti*a- dict the statement of Guyon, that persons who escape the atheromatous process will have no enlargement of the prostate gland (85, p. 1.09). The conclusions w'hich may easily be drawn from the facts already cited appear to be better justified if one con- siders that in these cases, in which the atheromatous changes in the intra-prostatic arteries were met, the changes were very irregular among the arterial branches and differently supplied parts. The one, and only, rule (and this is open to very many exceptions) is the relatively frequent localization of the atheromatous processes in the larger arterial branches, which terminate in the periphery of the prostate gland. In contradistinction arterio-sclerotic changes were less frequently observed among the ramifications of the •arterial system within the parenchyma of the prostate gland. It deserves to be mentioned, in addition, that I counted among the pathological cases of the prostate gland, not 'Only those cases in which the arterio-sclerotic changes were very pronounced, but also those in which only a ■few or even a single arteriole showed atheromatous Owing to the fact that a border-line cannot be sharply drawn between the physiological-senile, and the patho- logical, thickening of the intima ; I counted also as patho- logical all the prostatic arterioles in which the intima thickening and narrowing of the lumen was small, but still reached beyond the highest limit, which was found hy measurinsf the thickness of the int'.ma and the 24 diameter of the lumen of vessels of young people, who surely were not attacked by atheroma. In considering atheromatous changes I intentionally left the condition of the adventitia unregarded. It is easy lor one to satisfy oneself as to the fact that the adventitia of the intra-prosratic vessels, especially of the vessels of the periphery, is normally conspicuously thick. We are therefore not justified in assuming that the thickening of the adventitia is a sign of arterial sclerosis. Besides this it is well known that the thickness of the adventitia is very irregular in the normal state ; on the one hand, with regard to the region of the body and the arterial branches of one and the same individual, and on the other hand as regards the same arterial branches in different individ- uals. For this reason I came to the conclusion that it is not sufdcient for the diagnosis of atheromatous changes to take the thickness of the adventitia into account. One must base one's diagnosis upon the proof of calcification or other retrograde metamorphoses, or on the round-cell infiltration within the adventitia. Launois, on the con- trar}^, took the thickening of the adventitia as a charac- teristic matter of principle in his account of the arterio- sclerosis O'f the vessels of the genito-urinary apparatus even in those vessels in which there was no intima thick- ening. He says that every artery which terminates in the periphery of a hypertrophied prostate gland, "toutes sans exception," is surrounded by a ring of connective tissue. This assertion is very remarkable. I am inclined to assume that for Launois a normal condition was soane- thing pathological, and that he was led through this mis- take oil a wrong track, at least with regard to the pros- tate gland. 25 CHAPTER IV. RELATION OF THE ARTERIAL SCLEROSIS TO THE KIDNEYS Gull and Sutton (202), in the year 1872, first called at- tention to the changes in the kidneys produced by the disease processes in the arteries ; but they did not define the relation of the well-known "arterio-capillary fibrosis" to the arteriol sclerosis. The teaching of Gull and Sut- ton, which for 10 years was the starting-point for numer- ous debates, found only a few followers in its original form. Notwithstanding this it had a great influence on the completion and development of the teaching of the so-called "sclerose generalisee" and also on the defini- tion of the idea O'f arterio-sclerotic shrinkage of the kid- ney. The most important arguments against the Gull- Sutton teaching were made by Grainger-Stewart (206-209), and Hood (218), then by Rindfleisch (311), Cohnheim (299) and Bartels (181). The latter believed that Gull and Sutton had "evidently confounded the senile changes of the kidneys wath the real and genuine shrinkage of the kidney, from affection for their newly created Morbus-Brighti-Idea" (1 c. p. 371.) If I be not mistaken, Henouille (217), a pupil of Lancereux, em- phasized What had already appeared in some works, but was established by Henouille, is a clear etiological under- standing, and has nothing to do with an anatomically limited form of disease. The majority of investigators, with the exception of Ewald (200) and Thoma (252), who in the following years have concerned themselves with this subject, have, in this sense, accepted the arterio- sclerotic shrunken kidney as a purely etiological idea. In this connection the works of Erault (185), Cornil (192, 26 I93)> Mahomed (234), Senator (245), Petrone (240), Lemcke (227), Amburger (178), Meigs (237, 238), a. 0., should be read. In the anatOimical picture entire tlie simple senile atrophy of the kidney is still added, and this means that the conviction is expressed, especially in the old French works, that all atrophic conditions of the kidney, as found in old people, are identical with the in- flamed shrunken kidney, and without exception caused by arterio-sclerosis. As followers of this view it is suf- ficient to mention Lemoine (231), Dumange (196), De- bove and Letulle (195), but especially Sadler (248). Launois accepted Sadler's views in their full extent/ although he was familiar with the divergent and well- founded ideas of Ballet (179), as well as with the ideas of Cornil and Brault (192). The border-line between the senile kidney atrophy and the arterio-sclerotic shrunken kidney was likewise missing in the later works of Lancereux (233) and Grancher (213), and in the monographs of Bull (180) and Lowenfeld. The development O'f the anatomical conception of the arterio-sclerotic shrunken kidney and its exact separa- tion from the related forms, i. e., the simple senile atro- phy and the inflamed and genuine shrunken kidney, is especially due to the German investigators, Weigert (256) and Leyden (229), but particularly to Ziegler (257). To the excellent anatomical characteristics of these three conditions, as tabulated by the latter, nothing can even now be added. It was confirmed by Rosenstein (244). Biermer (186), Dunin (194), Lemcke (227), o. a.; and will finallv be incorporated in all newer manuals and textbooks' (at least, in the German books). In the man- ual of Orth (310), there is toesides a very exact — per- haps the most exact — description of the differential di- agnostical characteristics of these three forms. The number of the treatises which in the widest sense of the word treat of the atrophic charges of the kidneys is very large indeed. , The relation between the arterial sclerosis and the atrophy O'f the kidney with its accompanying changes was for a long time a "terra incognita." The majority of the chronic processes O'f these organs were treated as belonging to a common group. They were called bv different names with the same luraning, 27 as : Cirrhosis of the kidney, sclerosis of the kidney, granu- lar atrophy of the kidney, chroiiic inflammation of the kidney, interstitial nephritis, shrunken kidney, etc. Only through the efiforts of later years has it been pos- sible to classify the real renal atrophies "sensu stricto" and set them apart from those occurrences which accom- pany the shrinking of the organ, but are never due to simple disturbance in nutrition. Among the simple atro- phies there is a well-characterized and well-limited form, the so-called "arterio-schlerotische Schrumpfmere (atro- phia e origine vasculosa, ren arterioskleroticus). It is directly due to the atheromatous process in the renal arteries and their branches. A strict dififerential diagnosis is, in spite of this, some- times ver}^ difficult, and now and then even impossible. In such cases, which are, by the way, very rare, noth- ing remains but to diagnosticate them as a transitional form. In the great majority of cases we meet with clear, and, as a rule, easily diagnosed forms. Simple senile atrophies of the kidney belong to the dailv finds of the dissecting room. Both kidneys are in svich cases uniformly small. Their weight is generally 20-30 grams less than ihat of the normal kidneys (left 80-90, instead of 100-120; right 70-80, instead of 90-ioog.). The form of the kidneys remains unchanged. The covering of fat increases often in thickness, es- pecially in the region of the hilus. The capsule proper is easily torn ofT, and is thin. The surface of the kid- ney is, in the simple senile atrophy, either smooth, or, what is more frequent, uniformly finely granular and of a uniform, reddish-brown color. The cortical sub- stance appears in the cut section uniformly smaller, but its characteristic radiating lines, as well as the boundary line between it and the medulla, are pre- served. Sometimes small cysts are seen, which are lo- cated either on the surface, or in the parenchyma; and contain a clear serum or a gelatinous, transparent, yel- lowish mass. The arterial branches in the parenchyma, which can be seen with the naked eye, are unchanged. The main trunk of the renal artery may either be normal, or it may be the seat of atheromatous changes of varying intensity and extent. In my investigation, I have recorded these cases just 28 described as simple senile atrophy, provided that no symptoims of albuminuria were present during lifetime. The atrophic condition of the uriniferous tubules and the malphigian bodies is very characteristic under the mi- croscope, in the cases of simple senile atrophy. The malphigian bodies become smaller and their characteris- tic outline becomes gradually lost; their capillaries lose the endothelial cells, are now and then attacked by hya- line degeneration, and finally collapse and lose their lumen. The final outcome of this process is a hyaline de- generation and a complete wasting away of the shrunken glomerulus to a homogeneous ball. The decrease in size of the senile kidney is mainly caused by the atrophic condition of the uriniferous tubules. The lumen of these becomes gradually narrower: the epi- thelial cells lose their characteristic, differentiating marks; they become flatter, smaller, cuboidal; they lose their sharp outline, and their nuclei are smaller and stain more strongly. The interstitial connective tissue is as a rule un- changed: Sometimes we find the capsule of the glome- rulus slightly thickened, and, still rarer, we now and then observe a few rotmd-cell infiltrations. It is beyond doubt that these characteristic changes of a senile kidney atroph}^ are due to a disturbance in nutrition — a de- creased blood supply. But one should, as Ziegler cor- rectly states, in every individual case, consider as to whether the general senile involution of the tissue and the decrease in the entire blood supply is due to decrease in the activity of the heart, a diseased main branch of the aorta, or to the condition of the cells of the parenchyma of the kidneys. The main importance may lie in the changes in the heart, or in the main arterial branches, or in a general marasmus (1. c. p. 6oi). Corre- sponding to the main factor that attacks the whole organ- ism both Kidneys are, almost without exception, at- tacked by simple senile atrophy when it exists, and in each kidney the atrophic changes are diffuse, i. e., evenly dis- tributed in all its component parts. The arterio-sclerotic shrunken kidney, which in its pure form is to be classi- fied among the senile kidneys, as both are due to sim- ple retrograde disturt)ances of nutrition, differs only 29 from tlie senile kidney in that it is caused by certain local inlluences. According to whether the left or the rig'ht renal artery is attacked by an atheromatous proc- ess of greater intensity and extent, the left or the right kidney will suffer the greater changes. Thus we will sometimes find an arterio-sclerotic shrunken kid- ney on one side; while the kidney on the other side sho'ws little or no changes, or only a simple senile atrophy. Besides this, corresponding to the irregular localization and intensity of the arterial sclerosis in the individual branches of one of the renal arteries, wie find that the localization and the degree of the arterio- sclerotic parenchymatous changes are uneven in the different parts of the same kidney. Therefore, the an- atomical picture of an arterio-sclerotic shrunken kidney is more varied than that of a simple senile atrophy of the kidney. In those cases in which the atheromatous process attacks evenly the smallest branches of the renal artery, the kidney will become evenly smaller. Tlie somewhat thickened capsule generally found in such cases is easily removed from the coarse, granular surface. Those projecting granules are generally of a palvT color than the grooves between them. The pa- renchyma is of a dark-red color, and its characteristic contour is very indistinct. The section of the arteries in tlic parenchyma which are visible to the naked eye is rigid and does not collapse. The arterial walls are very unevenly thickened, and the lumen is also greatly increased, especially in the larger arteries, less in the smaller ones. Sometimes we find small cysts, the size of a pea, within the connective tissue. If the artificial sclerosis attacks individual branches only, or if the arterio-sclerotic process is of different intensity, then the kidneys 'become unevenly smaller. On the surface we observe broad, flat, intersecting grooves of dark-red color. Besides these large grooves, there are smaller ones, which give a coarsely granular appearance to the surface. The thickness of the cortex is very uneven; at one place it may be normal, while at another it is very much thinner; the characteristic outline of the parenchyma is well preserved at the nor- mal places. The rigidity of the thickened arterial walls is a constant feature in the arterio-sclerotic shrunken 30 kidney. The uneven thickening of the walls is_ es- pecially pronounced in the arterial branches which lie in the broadest and deepest grooves of the surface of the corresponding part of the parenchyma. The high-grade atheromatous, arterial changes, which are sometimes fohowed by a complete obliteration of the lumen, are especially conspicuous under the microscope. The histological peculiarities _ of the atrophic, parenchymatous changes are very similar to those of the senile kidney atrophy. Here and there is regularly observed the destruction of the malphigian tufts, whereby these often become the seat of a calcifica- tion;' here and there the epithelium^ of the uriniferous tubules becomes smaller, flatter, more uniform, and color more intensely, whereby the uriniferous tubules suffer a narrowing before, finally, here and there, col- lapsing completely. The difference between the his- tological changes of the simple senile atrophy of the kidney and the arterio-sclerotic shrunken kidney con- sists in the different localization and intensity of the disease processes. While these occur more diffusely, and are quite insignificant in the senile kidney, they occur in groups in the arterio-sclerotic kidney, and reach a much higher degree. It seems, for this reason, that there is an^ increase in the interstitial connective tissue in the vicinity of the atrophic foci in the arterio-sclerotic kid- ney. This, however, is only apparently so, and is due to the collapse of the uriniferous tubules, because in the pure forms of arterio-sclerotic shrunken kidney there is really no proliferation or hyperplasia taking place. A different picture appears when, in addition to the simple atrophic processes in the arterio-sclerotic shrunken kidney, there really is a proliferation of the interstitial connective tissue. In such cases the dif- ferential diagnosis between the arterio-sclerotic kidney and some forms of the inflammatory shrinkage is rather difhcult. Such kidneys only are to be regarded as arterio-sclerotic in which the changes in the uriniferous tubules are evident, and where the proliferatipn of the connective tissue is insignificant and is exclusively con- nected with the atrophic foci. A high-grade hyper- plastic involvement of the inter-tubular connective 31 tissue, a marked thickening of the capsule of the glom- eruli, numerous and extensive round-cell infiltrations, and finally necrosis and desquamation of the epithelium of the uriniferous tubules, all these must be regarded as symptoms only of a different condition, namely, the inflammatory shrunken kidney. The changes which are seen with the naked eye are not sufificient for a differential diagnosis. The extent and intensity of the changes in the vessels must be treated very carefully, therefore, when considering the verified observations on the great arterial branches. One must not for- get that the vessels which lie within the chronic- ally inflamed kidney may suffer a thickening of their walls and a narrowing of their lumen, and even an obliteration, due to a proliferation in the intima. For this reason I kept in mind, during my investiga- tion of the diagnosis of the arterio-sclerotic shrunken kidney, the short but excellent remark of Orth (310, p. 128): "If we find the interstitial tissue unchanged or only slightly changed, or changed in spots, then we must regard the change in the vessels as primary, and diagnose it as an arterio-sclerotic atrophy." The proportion of frequency of the arterio-sclerosis, the inflammatory shrunken kidney, the arterio-sclerotic and the simple senile atrophy is illustrated by the fol- lowing table of 1,106 dissections in the pathological anatomical Institute of Krakau. TABLE II. The frequency of arterial atheroma and kidney degener- ations (exclusive of acute alterations, amyloid and engorged kidney) ace. to the journals of the Pathologico-anatomical Institute Krakau, of in the year 1895. A GE PERIOD TOTAL Nephritis chronica Cirrhosis from arteriosclerosis Atrophia senilis simplex (no Albuminurie) 29 12 I 12 14 16 67 55 17 79 Sum of kidney degenerations 29 25 97 151 32 Percentage of cases to autop sies AGE PERIOD 1-40 40-30 50-90 Generally Atheroma cases Nephritis chronica Cirrhosis from arteriosclerosis Atrophia senilis simplex I .eg 4.00 22.65 9-37 0.78 9-37 58.89 5.53 6.32 26.47 16.82 4-97 1-53 7-14 Percentage of kidney degenerations among each other AGE PERIOD 1—40 40-30 50-go Generally Nephritis chronica Cirrhosis from arte-iosclerosis Atrophia senilis simplex 100 48 4 48 14-43 16.39 69.08 36.43 H.26 52.31 In each one hundred dissections there are, therefore: cases of atheroma, 16.82 per cent. ; chronic, inflamed, shrunken kidney, 4.97 per cent. ; arterio-sclerotic kidneys, 1.53 per cent.; simple senile atrophy of the kidney, 7.14 per cent. From this table we can draw the conclusion that the kidney changes due to arterio-sclerosis are by no means frequent. In old people they are surely found much less frequently than the simple senile atrophy. In- deed, both of the other forms of the retrogade disturb- ances of nutrition of the kidney are only found about one-half as frequently as the arterio-sclerosis of the ves- sels in the aged. Launois maintains on the contrary (72, p. 17), that atrophy of the kidneys is the rule in old people; under the microscope one finds constantly in all cases that: "II s'agit la . . . d'une nephrite interstitielle, d'une sclerose renale (p. 19)." The starting point of the latter is again regularly found in the atheromatous changes of the ves- sels (p. 27). 7\lso Guyon (comp. 85, p. 108), literaUy confirm'3 this statement of his pupil. Guyon and Launois maintain at the same time, that the arterial sclerosis and its consequences are constantly to be found in individuals with hypertrophy of the prostate gland. The climax of the Guyon theory is the well-known sen- tence, always and everywhere quoted: "Sous les prosta- tiques sont atheromateux {^2, p. 9-85, p. 108). Hypertrophy of the prostate is a wide-spread disease which, as is well known, is observed in every third or fourth okl man. It can, however, be seen from the above 33 table of the i,io6 dissections, that ani'ong all the disease processes forced by the French school into a nnirorm clinical picture, the arterio-sclerosis is the one most fre- quently observed; that is, on an average in every second person a'bove fifty years of age, the prostatic hyper- trophy is rarer, and the arterio-sclerotic shrunken kidney is found in only seven per cent, of the aged. Guyon's views are therefore contradicted by these purely statis- tical data. The following facts speak still more deci- sively against them: Among my forty-two cases of extensive arterial sclero- sis there were only ten cases in which the renal vessels were atheromatous. In seven cases of arterial sclerosis of the nenal vessels I observed at the same time hyper- trophy of the prostate. The condition of the kidneys may be stated as follows (compare table I) : arterio- sclerotic shrunken kidney only once, inflammatory shrunken kidney once, simple senile atrophy of the kid- ney twice, infarction-cicatrix once, and finally, in two cases, no pathological changes were found in the kidneys. Even if we disregard the differing of the arterio-sclero- tic shrunken kidney and inflammatory shrunken kidney from the simple senile kidney atrophy, there still remains as a final result of my investigation, that among twenty- one cases of hypertrophy of the prostate (in seven cases concurrent with atheroma of the renal arteries) the changes in the kidneys, accompanied by decrease in size, were observed only four times ; in the remaining seven- teen cases of hypertrophy of the prostate the kidney changes alleged by Launois to be constantly observed were not found at all. In female individuals I found among five cases of gen- eral arterial sclerosis four cases of arterio-sclerotic changes in the renal vessels, and among these the arterio- sclerotic shrunken kidney was only observed once ; while in the remaining three cases there was only a simple senile atrophy. In the aged male I found, on the other hand, among forty-two cases of general or extensive arterial sclerosis (of which in ten cases the renal arteries also were changed) the following condition of the kidnevs : simple senile athropy of the kidney seven times, inflamimatorv shrinkage two times, chronic inflammation of the kid- 34 ney without shrinkag'e one time, arterio-sclerotic shrunk- en kidney four times. Among the latter four cases the prostatic gland — what I consider necessary again to lay stress upon — was only once enlarged, and that only to a small degree. (Weight, 25 g. ; case 2.) In two other cases the prostate gland was of normal size and weight (case 28 and 40) ; in the fourth case (20) it was 'even smaller, atrophic (weight, 12 g.). Besides this, I found, in the forty-two cases mentioned, the following pathological changes in the kidneys : Acute inflammation of the kidney. ... 3 times Infarction citrix of the kidney 2 times Pyelitis calciilosa of the kidney i time Amyloid deg-eneration of the kidney, i time Cystic degeneration of the kidney. ... 1 time Passive hypersemia of the kidney. ... 2 times In the remaining 18, that is to say, in nearly one-half of my cases, there were neither macro nor microscopical pathological changes to be observed in the kidneys. In- deed, among these 18 cases, there were only 2 in which the existence of the arterio-sclerotic changes could be demonstrated in the proximal end of the main branches of the renal arteries. In consideration of these facts one is fully justified in asking, upon what does the Guyon school support its assertion, that changes in all the genito-urinary organs appear synchronously, are similar everywhere, and are everywhere produced by arterio-sclerosis? One remem- bers involuntarily the remark of Charcot (190): "Dans la vieillesse, les organes semblent rester en quelque (sorte independants les uns des autres ; ils souf- frent isolement et les), diverses lesions dont ils peuvent devenir le siege ne ressentissent guere sur I'ensemble de I'economie." 35 CHAPTER V. RELATION OF THE ARTERIAL ATHERCflA TO THE BLADDER As may be judged from the preceding chapter I have drawn the conclusion that the Guyon theory with regard to the prostate and the kidney cannot sustain a serious criticism, and therefore must fall to the ground. Notwithstanding this, it seemed to me necessary that the significance of the arterial sclerosis as affecting the bladder should be given a thorough examination ; because it might be possible that arterial sclerosis of the bladder vessels should exist entirely independently of a concurrent atheroma of the other vessels, and ex- ercise an injurious influence upon the condition and ef- ficacy of the muscles of the bladder. This possibility might explain the puzzling bladder weakness in old people. The question then arises whether, in the cases under consideration, such anatomical changes in the bladder muscles can be proven, and whether these changes would sufficiently explain the possibility of bladder insufficiency being due to arterial sclerosis. The answer to this ques- tion is by no means easy; mainly because we have here to deal with a relative, numerical proportion, and next with a comparison of the strength of the bladder muscles to that of the inter- and intra-muscular con- nective tissue; and in addition we must make sure of the proportion between the alleged structural changes within the bladder wall and the manifest arterio-sclerotic processes in the smallest intra-parietal arteries. Before the appearance of the works of the Parisian school, hardly anvbody had ever made an attempt to search for an anatomical basis for bladder nisufificiency. 36 It was considered enough to look upon the oibserved bladder insufficiency. Whether spontaneous or due to a hypertroiphy of the prostate, as a disease produced by . "Paresis," "Atony/' "Weakening," etc. First, so far as I know, in 1872 Dittel (24) called attention to the fatty degeneration of the bladder mus- cles as a cause of senile bladder insufficiency. A few years later, in 1881, we find a short remark by Maas (84 p. 522), in which he pointed out the fatty degen- eration of the hypertrophic muscles of the bladder as a cause of the rarely observed rupture of the bladder. This statement of Maas found a place in the major- ity of the text-fbooks and manuals of surgery. Now and then the colloid degener?tion of the muscle bundles, as first demonstrated b_v Rokitansky (112), was mentioned as supposed to lessen the conitractility of the bladder (Kautschukblase). Bohdanowicz (7) does not mention the fatty degenera- tion of the muscle cells ("Degeneratio adiposa"). He occupied himself inore with the distributio'n of the true fat tissue in the bladder wall. In young and healthy individuals one should find small collections of true fat tissue exclusively in the sub- serous connective tissue layer of the bladder wall, and in proportion to the general condition of nutrition. In the fibrous degeneration of the bladder wall (sclerotic), which is often seen in muscle hypertrophy, the fat tis- sue is in a preponderance. Not only is it found in the subserous layer, but it also extends from this into the external muscle bundles. In the highest degree of these changes fat is seen in places where it is never found in normal individuals; that is, between the muscle bundles of the innermost layers and even in the sub-mucous membrane. This pathological increase of fat tissue (to which, in my opinioTi, the name "Lipomatosis" 'belongs) bas nothing in common with the physiological collection of fat tissue, but is a symptom independent of the nutritive condition of the individual and co-ordinated with the sclerosis of the bladder wall. In a part of my cases I had to refrain from the microscopical examination of the material in a fresh condition (frozen section) as well as from fixation of 37 the pieces in mixtures of osmic acid. For this reason I am not justified in making a definite statement with regard to the true fatty degeneration of the muscle- cells mentioned by Dittel and Maas (Degeneratio adi- posa). Still, it seems to me that the true fatty degen- eration of the bladder muscles is not a very frequent and, where it really exists, not a very extensive phenom- enon; at least, this seems to be proven by those of my cases which were thoroughly examined for it. It is b}' no means denied that such changes do occur, and that they occur in cases in whic'h the bladder wall has an extraordinary friability. The number of such cases cannot possibly be great, because I never encountered such friable bladder walls in any of my cases. Besides, it seems probable that prev iling severe in- flammatory processes must be held responsible for the possibility of the occurrence of such bladder walls. Such inflammatory processes of the bladder must be looked upon as accidental complications, which over- step the limits of the conception of a spontaneous simple bladder insufficiency. Be it as it may, one thing is certain rbove all doubt; that is, that the cause of bladder insui^ciency in old people is certainly not to be sought in the fatty degen- eration of the bladder muscle, because, if this were so, the fatty degeneration must appear in all cases, and in the great majority of muscle cells. Much less can a colloid degeneration of the muscle cells be looked upon as of causative significance with regard to bladder insufficiency. These changes are sometimes met with in very pro- tracted inflammatory processes of the urinary bladder, in which the walls have lost their elasticity. But such urinary bladders I have intentionally excluded from my investigation because of their inflammatory complica- tions. But Bohdanowicz's statement, too, I can by no means verify. I have in every case paid particular attention to the changes described by him, and I came to the conclusion that the quantity and localization, as well as the presence of true fat tissue within the bladder wall, is in direct proportion to the nutrition of the individual. 38 The better the nutrition and the richer the layer of fat of the epidermis, the more frequent and the richer are the fat tissue collections in the muscles of the urinary bladder. For this reason one is not justified, in my opinion, in paying much attention, to the increase of fat tissue in the bladder wall. This Lipomatosis is a phenomenon which has no intimate relationship to the pathological conditions of the bladder wall. In a few cases in which a microscopic investigation of the hypertrop-hic bladder-wall was carried on prior to 1884 little attention was paid to the condition of the in- terstitial connective tissue o-f the 'bladder-wall. Nothing can be gathered from either the work ol Jean (62) or that of Robelin (109). In Germany Maas only (84, p. 521) mentions — and he but briefly — the thickening of the mucosa and submucosa in hypertrophy of the bladder and in catarrh of the bladder; and Orth (310) mentions the occurring atrophy of the muscles in certain cases of protracted dilatation of bladder (1. c. p. 220). Launois {'/2) was the first one who considered this question more in detail. He maintains that by the working hypertrophy of the bladder muscles occurring in consequence of prostatic hypertrophy, "les elements con- tractiles . . . se trouvent englobes dans une gaine de tissu conjonctif dense et serre, qui gene d'abord leur action et qui, par son developpemient, la supprime com- pletement" (1. c. p. 51). The miain cause of this con- nective tissue proliferation, which occurs actively in these sclerotic processes, is always to be found in the athero- matous, degenerated arteries. To this "sclerosis" of the bladder-wall we 'have to refer the forms of bladder insufficiency which are spontaneous, i. e., occurring without prostatic hypertrophy. Still greater stress is laid upon these assertions in the numer- ous works o'f Guy on (40, 41, 44, 46). All clinical manifestations of the so-called "proistatis- mus" could, as he maintains (45), occur, not only in old people w'ho are not suiTering fro;m prostatic hypertrophy, but also in females, provided that there were a pre-exist- ing sclerosis of the bladder-wall produced by the arterial sclerosis. As proof of this can be cited a few cases puljlis-hcd l)y Guyon's pupils; as, for instance, Recaaiiier's 39 case (ii6 "P'rostatisme vesical" in a 40-year-old man), or the case of Ohevalier (17). A proof of the same is in the case of a woman 43 years of age who (what deserves mention) had passed through a persistent and protracted inflammation of the bladder, and who was examined only during" her lifetime.* In other works published by the pupils of Guyon, as for instance in that by Desnos (27), as well as in the Ger- man compilations and essays of Mendelsohn (97), and Giiterbock (50, 51), and in a treatise of Assmuth (4 two microscopically examined cases), as well as in the Polish compilation of Misiewicz (86), etc., nothing essentially new is to be found. The statements of the Parisian school and its followers were first attacked by Casper (16). His investigations concerning the fibrous degeneration of the bladder-wall were not finished when his work was published, and a later publication of it is not known to me. However, on account of the fact that he found atheromata in the small arteries of the bladder only 8 times among 24 cases of prostatic hypertrophy with arterial sclerosis, Caspar be- lieves that he may draw the following negative conclu- sion: "Therefore the explanation remains . . . still hypothetical for the cases considered of dysuria and the atrophy related to degeneration of the bladder muscles." The puzzling occurrence of the functional power of the bladder which lately was observed in certain cases of prostatic hypertrophy after castration seems not only to strengthen the doubt, especially brought to notice by Caspar, but points to the conclusion that in these cases in question the bladder muscle did not suffer at all from a retrograde disturbance of nutrition, be it atrophy or perhaps a degeneration (vide Frisch, 379). Bo'hdanowicz (7) is in complete accord with Caspar in the belief that the arterial sclerosis is of no great im- portance for the condition of the bladder-wall, but yet he takes it as proven that the "sclerosis" of the bladder muscles exists. He believes that it is not necessary to search ihere for another cause, as the overworking "sur- *In this place a work by Croom (18) deserves mention. In It he rightly pointed out that the difficulty of urination in women is mostly a consequence of a disease process, not oc- curring in the urinary apparatus itself, but in its neighborhooa 40 menage" in the first place has a muscle hypertrophy as a consequence, and later often produces a state of sclerotic degeneration. (1. c. p. 68.) Bolidanowicz makes the hypothesis that the fibrous degeneration of the bladder-wall occurs only when the bladder muscles cease tO' be hypertrophied. Bohdanowicz does not furnish sufificient explanation, in the connection of the fibrous degeneration of the bladder- wall with the muscle hypertrophy, for thiose cases in which, besides a bladder insufficiency, no changes could be proven which would be capable of causing a bladder hypertrophy. Among the cases investigated by Bohdanowicz, one of so-called "prostatisme vesical" is found (No. xxi.), in which a fibrous degeneration of the bladder wall was confirmed, in addition to a general sclerosis. The result of the investigation of this case was summed up in the following way: "La vessie (scleroisee), que I'on pourrait attribuer a un vieux pros- tatique atheromateux, suivant les idees regnantes." But I must here call attention to one circumst mce, in my opinion, important; namely, in this case cited there existed for years a chronic suppurative inflamma- tion of the bladder, and the microscopical examination proved that there existed a high-grade sclerotic change in the neighboThood of the muscle layer next to the mucosa. One cannot, therefore, disregard the thought that in this case the bladder inflammation was primary, and that the fibrous degeneration of the bladder, ex- tending fromi within outward, was a secondary symp- tom caused by the bladder inflammation. Finally Miquet (87) has concerned himself with these questions; but his thesis is almost solely a compilation of the previously published facts. Against all cited investigations of the influence of the arterio-sclerosis upon the condition of the bladder mus- cle we must make a double objection. Firstly, only such cases as were obscured by an already extensive inflammatory complication were used in all these investi- gations. These cases should have been put aside, because a chronic inflammatory process is regularly followed by a fibrous degreneration of the submucosa. 41 I can maintain that the latter is really the case on the evidence of a few cases cited in this work, as well as of a few cases which have not been considered here. It is also easy to convince one's self of the fact, in cases of chronic infiammation of the bladder in young female individuals, that the fibrous degeneration pro- duced by inflammatory irritation, progresses more ex- tensively in time, till, finally, after years of persisting bladder catarrh, it involves the whole thickness of the wall. In such cases, in which we of course cannot speak of the influence of the arterial sclerosis, nor of the effects produced by obstruction to micturition — in which there was not even the least hypertrophy of the bladder muscles — in such cases the fibrous degeneration of the bladder wall can only be considered as being due to the efl^ect of a chronic inflammatory irritation. As a proof of this statement, the distribution of the sclerotic changes may also be easily ascertained. Here the fibrous degeneration is undoubtedly produced by an active connective tissue proliferation. This is proven by the circumstance that the bladder wall in these cases shows a high degree of thickening. Al- though, as I had an opportunity to prove to myself by microscopical measurements, the muscles showed no hypertrophy worth mentioning, the mode of origin of the fibrous degeneration pointed, on the other hand, to the presence of inflammatory round-cell infiltration wdthin the thickened connective tissue bands. It seems, therefore, not admissible to draw any con- chisions from the superficial histological investigation of the condition of the bladder w?ll in cases of bladder insufficiency of old people complicated with inflamma- tory processes, because it is impossible to decide in such cases whether the condition of the bladder wall is a consequence of the afore-mentioned inflammatorv com- plications or whether it is a consequence of still other causes. This claim holds good also for those cases of blad- der insufficiency produced by prostatic hypertrophy as well as for the "spontaneous" cases to which the name "prostatisme vesical" is given. For this reason we can- not make use of the cases of Bohdanowicz before men- tioned, nor of other similar ones, when we deal with 42 the explanation of the question where to search for the cause of "spontaneous" 'bladder insufftciency. The second deficiency which was noticed, in the works referred to above, may be summed up in this: The decision of all investigators was based upon a very superficial estimation of the strength of the bladder muscles and of the interstitial connective tissue. But it is also well known how difficult it is to avoid gross mistakes if one does not resort to micrometric measure- ments. Although such measurements are not sufficient to eliminate all sources of mistakes, they are sufficient to reduce the number of these mistakes. In my investigation forty bladders of old men were utilized. All of them had been attacked by arterio- sclerosis and in about one-half (nineteen times) there was at the same time a prostatic hypertrophy. Besides these, I examined five urinary bladders of old female individuals with high-grade and extensive arterial sclerosis, and, finally, for comparison, eleven bladders of young men, in which there were no changes in the arterial system or in the prostate glands. In all cases I tried to determine as accurately as pos- sible with the micrometer the relation of the bladder muscle to the interstitial connective tissue of the bladder wall. To be absolutely correct one should compute the relation between these two components of the bladder wall in cubic units. This, however, cannot be carried out, for the reason that the microscope gives us only two dimensions lying in one plane. But I have also refrained from the calculation in quadratic units; first for want of suitable measuring instruments, and sec- ondly, because the linear measurements of the thickness of the bladder wall seemed to be sufficient for my pur- pose. I was soon convinced of the fact that the main connective tissue bands in which the quantitative changes are first apparent run exclusively longitud- inally. If one, therefore, measures the transverse di- mensions (in the microscopic preparation the vertical) of these main connective tissue bands, data will be ob- tained which are entirely sufficient to measure the de- gree of thickening of these bands. The narrow con- nective tissue bands which stand vertically to the surface of the mucous membrane, running respectively 43 obliquely, can be left out without great consequence, because their thickening never reaches a considerable degree. I paid attention especially to investigating how the interstitial connective tissue is made up; whether it is loose or dense or compact. I also paid attention to the behaviotr of the smaller interfascicular and inter- fibrillar connective tissue septa. The linear measure- ments were also sufficient for my purpose, because I, in all my comparisons and compilations, made use of relative values, while I regarded the numerical value of the connective tissue as a unit of measure. Next I computed the absolute thickness of all the muscular layers, then the thickness of all connective tissue bands which lay in the direction of the same straight line which connected the mucous membrane with the ex- ternal surface of the bladder. These two numbers were divided by each other, and the quotient showed how many times the muscles are thicker than the con- nective tissue. We can also represent this relationship in the form of a proportion: Connective tissue i Muscle X The hypertrophy as well as the atrophy of the muscle is in the first place expressed in the thickness of the muscular bundles. The more the muscle develops in proportion to the interstitial connective tissue, the greater will be the difference in the thickness of the muscle bundles and the connective tissue, and the greater will be the x of our proportion. Of course it is impossible on the basis of these calcu- lation's to decide whether there is a true hypertrophy of the muscle, or wlhether there really is an increase in the interstitial connective tissue. In this connection I must point out that I succeeded in demonstrating, in a manner to be mentioned later, the existence of a true hypertrophy of the bladder muscle. Moreover, it is not pertinent re- specting the function of the bladder whether the muscle becomes a victim of an atrophy whereby the connective tissue of the bladder wall is relatively increased, or again, whether the connective tissire undergoes active prolifera- . 44 tion and increase whereby the bladder muscle, ciuantita- tively unchanged or even hypertrophied is rendered rela- tively less. In both cases the number of the contractile elements be- com/es smaller in a given cubic unit, and the working ca- pacity of the section of the wall under consideration must of course suffer an encroachment. Even if this be not the case, the functional final result remains one and the same : through the atrophy of the muscles for wanit of contractile elements, and throtigh the active proliferation of the connective tissue on account of the preponderance of the brittle, unyielding wall elements. The first case is not in need of a further explanation ; as a striking illus- tration of the latter possi'bility one can notice those brit- tle non-comtractile urinary bladders which are often ob- served in chronic inflammation. I have intentionally left tmconsidered the mucous membrane, the submucosa and the subserosa in the mensuration of the component parts of the bladder, because, as already mentioned, they suf- fer a thickening in mild chronic inflammatory processes. The thickness of the subserosa and of the connective and adipose tissue on the external surface of the bladder re- spectively ranges very much in different individuals and in different parts of the bladder wall. That I might utilize for comparison the degree of atheromatous changes in the arteries, I was compelled to resort to relative numerical values to establish, once for all, a common unit. As such a unit I took, on the one hand, the thickness of the intima, to which I compared the thickness of the muscularis and adventitia; and, on the other, I took the lumen of the vessels, to which I com- pared the thickness of the walls. By these means the results of the measurements are represented in the form of the following equations : I. I, Intima i, i 2, Media ^= 2, x 3, Adventitia 3, y II. Lumen diameter i Wall thickness 45 These two different units were taken because some in- vestigators denied the existence of a narrowing of the lumen produced by atheromatosis of the small arteries. Although I observed exactly the opposite, yet, to pre- vent all objections, I will for the present leave this question undecided. It seems almost unnecessary to add that in each individual case numerous measurements of numerous preparations were made of all the arteries which were cut longitudinally; also that the calcula- tion of the proportions of the components of the bladder wall, the different layers of the arterial walls, the wall thickness and lumen respectively, was executed sepa- rately in different places in every individual case; and finally that all comparisons were made on a basis of average numbers. For the investigation only cases of high-grade and extensive arterio-sclerosis in male and female individuals were made use of. From the numerous collection of normal bladders only those were used in which there was nothing which could influence the accuracy of the investigation. All cases in which there was any inflammatory com- plication within the genito-urinary system, and especially withm the bladder wall, were excluded. Exceptionally only I took up a few cases which might serve in the shape of examples to elucidate sonie question, or which offered a particularly interesting find regarding the prostate gland. As I desired to examine the begin- ning stages of the processes consequent to a so-called prostatic hvpertrophy, I intentionally excluded all those cases in which the enlargement of the prostate reached a higher degree (weight of the prostate over 50 grams). It is interesting to note that it was found that the pro- portion between the two components of the bladder wall, namely, the muscle and the connective tissue, undergoes rather great individual fluctuation. Thus we meet cases in which the connective tissue is very scanty and the mus- cle tissue very abundant in the bladder wall, and vice versa, or the connective tissue may quantitatively equal the muscle tissue. The extreme proportion may be expressed by the following equation: 46 Connective tissue i — — = — as minimum muscle 4 Connective tissue i = — as maximum muscle 1.2 Between these two extremes lie all the other cases. In this place, it may be mentioned that, according to Bohdanowicz (1. c. p. i8), in the normal urinary bladder the mucous membrane with the submucosa rep- resents 2-IO, the intermuscular connective tissue 2-10, and the entire muscle-layer 6-io of the thickness of the wall. The numerical proportion of the main component parts of the bladder wall (without mucosa, submucosa and subserosa), according to the statement of this au- thor, is as I ;3. My micrometric investigations coincide entirely with the latter statement; that is, I found in the normal bladder the proportions fon an average) i :2.9 to 1 :3.2. (Compare table 5, left half.) The structure of the interstitial connective tissue of the bladder wall is in different individuals just as dififerent as its quantitv. As a rule it is only in cases of chronic cystitis that it is strikingly dense and compact; otherwise it does not became more dense nor more compact in its quantitative increase. In case 19, for instance, in w'liich a chronic bladder catarrh existed, the proportion of the connective tissue to the muscle was i :t.2, and at the same time the connective tissue was more dense and more compact than in norma) bladders. In case 47, in which, on the other hand, no signs of inflammatory complications could be found, and in which the proportion of the bladder wall components was exactly like that of case 19, the connective tissue was very loose and apparently increased. In case 38, for instance, there was, with absence of in- flammatory complication, a proportion of the bladder wall connective tissue to the muscle of 1 :2.2. The first was only slightly increased in density, and the behavior of the connective tissue was similar also in case 39, w'here the proportion was 1 :2.2i a. s. f. Altho'Ugh the distribution of the Connective tissue fol- lows no constant rule, it may be characterized for the majority of cases in the following way : The longest and 47 thickest connective tissue bands are found, in the vicinity of the stronger venous and arterial ramifications, between the muscle layers, if these be well limited (w.hich is not always the case). These strong- connective tissue bands should be named "perivascular" connective tissue. Smaller connective tissue septa lie between the main layers o'f the muscular bundles, and should be named "interfascicular" connective tissue; finally between the muscle fibrilla lie very fine connective tissue septa (inter- fibrillar connective tissue), which can, in normal bladders, only be dififerentiated with high magnifying power as something independent, otherwise not quite percepti'ble and only indicated by a fine, light line or gap running between two related muscle cells. I have already mentioned that the relative increase in the quantity of the connective tissue of the bladder wall becomes most conspicuous in the "perivascular" con- nective tissue bands. Less prominent is such an increase in quantity in the "interfascicular" connective tissue, al- though 'here also it can be quite exactly estimated by micrometric measurements and used in the final results of the mensuration. On the other hand, the relative in- crease of the "interfibrillar" connective tissue is not aic- cessible for micrometric investigation ; for this reason the condition of these very fine "interfibrillar" connective tissue bands must be explored separately, and tlierefore the estimation of their extension and thickness, respec- tively, is of course very inaccurate. In order to gain a certain foothold (anhaltspunkt), I judged the strength of the "interfibrillar" connective tis- sue by the test whether I hsd to use a strong or a weak magnifying lens to make them visible. To cite the ob- servations under consideration more in detail is not nec- essary. I believe I can here limit myself to the remark that certain regularities in the behavior of the different parts of the connective tissue stroma can be demon- strated, namely, that the relative increase of the con- nective tissue in the interfascicular and interfibrillar bands is in a pretty constant proportion to that of the perivascular connective tissue bands. In all cases in which the perivascular connective tissue appeared to be increased, there the finest interfibrillar connective tissue septa were easily visible with weak magnifying lenses. 48 When the connective tissue within the bhdder wall was very predominant, the interfibrillar connective tissue could be differentiated with 'the weakest lenses as some- thing independent. Without exception the co^nnective tissue showed in all places a loose structure; likewise in those places in which there was an apparent extensive in- crease. Once more I lay stress upon the fact that I saw a pronounced increase in density in inflammatory condi- tionis of the bladder only. For this reason alone I am inclined to assume that the preponderance of the connective tissue within the bladder wall is only apparent in cases not complicated by in- flammatory processes, and that it does not depend on a real increase of connective tissue, but on an, atrophy of the bladder muscle. A further support for my opinion will be found in the discussion of the question of bladder hypertrophy. If we then disregard the exceptions oc- curring with inflammatory complications, I must deny the existence of a primary bladder sclerosis in the sense of the French investigators. At least my investigations did not furnish me wich proof of the correctness of the statement, that the changes in proportion of the bladder muscle to the connective tissue in simple, uncomplicated cases, were related to active processes in the connective tissue framework. The observation of a "tissu conjonctif dense et serre, qui etoufife les elements contractiles," as described by French investigators, was possible only in cases with chronic bladder catarrli, which of course is the most fre- quent complication of prostatic hypertrophy. On the other hand, it is not to be denied that in some cases of very old individuals there occurs a conspicuous chiange in the reciprocal proportion of the coimponenits of the bladder wall at the expense of the muscle, and in favor of the connective tissue framework. Now the question is whether this change can be esteemed as the real anatomical basis for bladder insufficiency in old peo- ple, and whether it is sufficient to explain the clinical symptoms? A priori it seems as if this question can be answered in the affirmative. The relative decrease of. the contrac- tile elements, in whatever way it may be produced, must necessarily cause a decrease in the functional power of 49 the involved muscular organs. The true relationship of bladder insufficiency to the decrease of the muscle can then only be assumed as proven, if we prove that the in- tensity of the clinical phenomena actually coincides with the intensity of the anatomical changes. This proof is supplied by a few of my cases, namely those in which there existed duringlife symptoms of blad- der insufficiency (i), and in which it was verified by micrometric measurements that the proportion of the blad- der wall connective tissue to the bladder muscle did not exceed i :2.3. In the history of case six, for instance, there was noted only only a mild disturbance in the ex- cretion of urine, which nearly corresponded to the so- called "first stage" of Guyon's prostatism-us ; the propor- tion of the components of the posterior wall of the blad- der (containing 340 c.c. of urine) was in this case i :2.3. In case 44, an old female individual, who suffered from a high-grade, extensive arterio-sclerosis, there was observed during her lifetime a retention of urine ("second stage," according to Guyon) ; at the autopsy 320 c.c. of urine were found in the bladder, and the proportion of the com- ponents of the posterior bladder wall was from i :i.i8 to 1:1.43. In case 47, a man suffering from retention of urine, the proportion of the bladder wall components was only 1:1.2. (Contents of bladder 360 c.c). The last two correspond exactly to the idea of Guyon's "Pros- tatisme vesical." They are, therefore, especially impor- tant, because in neither of the two was the clinical picture obscured by chronic inflammatory complications, which deprive the only corresponding case of Bohdanowicz of its importance. The first of my two observations (case 44) is very similar in all respects to the universally cited observa- tion of Chevalier (17), which it would be very easy to regard wrongly as a striking proof of the causative re- lationship of arterio-sclerosis to bladder insufficiency. The second of my two observations (case 47) stands in a strong contrast to the first; because there was no (1) To Chief Physician Prof. Dr. Parenski and to Dr. Pasz- kowslci, who have supplied me with all the necessary histories, I express my sincere thanks. 5° sign of arterial sclerosis to be discovered in the or- ganism, and still the proportion of the bladder wall com- ponents corresponded to a high-grade pathological change. But the cases are appropriate for comparison with one another, because in the second case (case 47) there was neither a prostatic enlargement nor any ob- struction to the flow of urine. There is still another valuable observation at my dis- posal (case 5); in this .case there was incontinence of urine with a full bladder during lifetime ("overflowing of the bladder," corresponding to the third stage of Guyon's "Ischuria paradoxa"). At the autopsy I found the bladder greatly dilated (it contained 62og. of urine); while the proportion of the bladder wall com- ponents was only 1:1.7. The apparent increase of the connective tissue of the bladder wall at the expense of the muscle was in this case less pronounced than in the two cases previously mentioned. This circumstance is, however, by no means capable of lessening the im- portance of the observations already cited; because, at any rate, the lencroachment on the normal function of the bladder sphincters, during the formation of the so-called Ischuria paradoxa, plays also a main role. The efflcien- cy of the bladder sphincter was in the present case en- tirely nullified by a tumor growing from the posterior lip of the orificium internum urethra, at the level of the orifice, and pressing the sphincter muscle apart. Both the previously mentioned cases 0)f primary bladder inisuiificiency (Prostatisme vesical) could without further consideration be used for the elucidation of the patho- genesis of this condition, if it were not that they differ absolutely in one point. Both cases showed the sam.e symptoms during life and the same structural changes of the bladder wall. But in the first case (case 44). we find in addition a nearly gen- eral arterial sclerosis, especially attacking the smallest arterial branches ramified in the bladder wall. In the second case (case 47) we encountered nowhere any atheromatous changes in the arteries, neither in the ves- sels of the genito-urinary apparatus, nor anywhere else in fhe organism ; and still the clinical manifestations and the anatomical changes, as far as the bladder was concerned, were just as pronounced as in the first case, and perhaps 51 even more so. The antithesis which occurs in these cases is only to be explained when it is possible, through the verifying investigation of a larger number of cases, to find how far the changes in the structure of the bladder wall run parallel with the atheromatous changes in the smallest intro-parietal arteries of the bladder. By em- ploying the methods of investigation utilized in the pres- ent work, it was proven that the maximum and mini- mum' relative numerical values of the arterial media, on the one hand, and the thickness of the wall on the other, were nearly equal to the maximum and minimum numer- ical values respectively of the bladder muscle. At least, I found this to be the fact in the cases investigated by my- self. I ihave already mentioned that the maximum of the proportion between the connective tissue framework and the bladder muscle is 1:1.2; the minimum, On the other hand, is 1 14. The proportion of the intima thickness to that of the media ranges between the following limits : Maximum about 1:1, minimum (ca) 1:5. The proportion of the lumen diameter to the thickness of the walls oif the vessels is expressed by different num- bers, but its quotient is alike the maximum and minimum respectively of the other two numerical proportions. In general this quotient amounts in all these three nu- merical proportions to, maximum average i, minimum average 0.25. This can be expressed in other words, as follows : The amount of connective tissue, in the highest degree of changes in the structure of the bladder wall, is the same as the amount of muscle. In the highest degree of atheromatous vessel changes (in my cases) the thick- ness oif the intima and media is the same, and the lumen, equals the wall thickness. In minimum changes (which comes near to the normal condition) the amount of the connective tissue, the thickness of the intima, or the thick- ness of the wall of the vessels, respectively, amounts- to one-quarter of the amount of the muscle, the width of the media or the lumen of the corresponding artery, respect- ively. This rule refers, of course, especially in its second part, only to the intra-parietal bladder arteries, and ariiong these especially to the ones which have an equal caliber. 52 It does not seem practicable to enumerate here the simall synoptical row of figures which contain the results of the micrometric measurements. I think it wiser to recapitu- late the results of my investigation' in graphic tables. (See Tables III. and IV., page 174.) If the statement of Launois, that "que plus les vaisseaux sont modifies, plus la degemerescence de I'appareil urinaire est accen- tuee," were correct, then the curve, which indicates the increase of the changes of the structures of the bladder wall, must run nearly parallel to that which represents the increase in the intensity of the atheromatosis of the vessels. The courses of these two curves are essentially dififerent in the accompanying tables. In Table I II., the intensity of the atheromatous changes in the vessels is expressed by the relative increase of the thickness of the wall of the vessel (the lumen of the vessel is taken, as the unit). I rely here upon the fact, almost universally accepted, that the lumen of the small arteries gets continually narrower with the increase of the in- tensity of the atherematous changes following a progres- sive thickening of the vessel wall. The relative numerical values of the wall thickness of the arteries are arranged in arithmetical order in Table III. According to it, the connecting curve declines uni- formly with the increasing intensity of the atheromatosis. The relative numerical value of the normal arterial wall stands at the beginning of the curve. One sees that in the normal intra-parietal arteries of the bladder the lumen amounts to three times as much as the thickness of the wall ; the arteries which are changed the most and in which the thickness of the wall equals the diameter of the lumen are grouped at the end of the curve. The relative numerical value of the blad'der muscle stands in the same vertical column in which the numeri- cal value of the arterial walls of the same case is recorded. The curve representing the muscle, and which at the same time shows the change in the relation of the bladder wall components, runs by no means parallel with the arterial curve; it is represented by a quite irregular, broken line. The contrast in the behavior of the two curves is very striking. Even if we reconsider the in- dividual fluctuations in the relation of the components of the bladder wall, it still remains impossible to discover 53 a connection of this change with the behavior of the vessels. On the left side of the table, for instance, where the arteries are nearly unchanged, we find, among others, cases also in which the changes m the structure of the bladder wall were most strikingly pronounced (case 19, 47). On the right of the table, which, on the other hand, expresses the high-grade, atheromatously changed ar- teries, we encounter among others the highest numerical values of the bladder muscle which I have had the oppor- tunity to demonstrate (case 51, 56). Table IV was made up in a similar way ; only here the intensity of the atheromatous changes in the arteries was measured on a basis of the basis of the relationship of the thickness of the intima and media. We also observe in table IV that the uniformly de- scending curve of the arterio-sclerotic changes in no way expresses the course of the line representing the bladder muscle; this line is very irregular, now ascending, now descending. A difference between these two tables is to be noted in only one respect, namely, one sees that in table IV the higher numerical values of the muscle are mainly (although not exclusively) at the beginning of the table; that is, in the vicinity of the normal behavior of the vessels. The cases in question refer tO' young, and to a certain extent normal, individuals, without any prostate enlargement. The final result of our micrometric meas- urements seems, therefore, to speak against the most im- portant, and, at the same time, last support of Guyon's theory. The statement that bladder insufficiency in old people stands in intimate and exclusive relationship to arterial sclerosis is without any foundation. Although I also, by other means, came to the same conclusion with regard to Guyon's theory, as Caspar and Bohdanowicz, I do not at all agree in the other state- ments made by these two investigators. On the basis of my investigations, I believe I can maintain that senile bladder insufficiency has a well- demonstrable anatomical foundation in the form of structural changes in the bladder wall, which circum- stance was put down by Caspar as being open to criti- cism. These structural changes c-'nnot be brought into a causative relationship to the bladder hypertrophy, con- 54 trary to the view of Bohdanowicz. In one-half of my observations of aged male individ- uals, and in all my cases ol aged female individuals, I could discover no trace of bladder hypertrophy, nor a cause for it. Later on this will be considered more in detail. And still, a change in the relationship of the com- ponents of the bladder wall was demonstrable in the majority of cases, sometimes of a high degree, and in some instances it was even the cause of disturbances of micturition during life time. As the result then of my investigations as set forth in the preceding chapters I came to the following conclu- sions : First, the changes of the prostate gland of the urinary bladder and of the kidneys are, in the cases of so-called "prostatismus," neither synchronous nor co-ordinated, and stand in no relation to arterio-sclerosis; neither are they if one, two or all of the changes of the organ be present in the same individual, concurrent with arterio- sclerosis. Second, the anatomical basis for the bladder insuffi- ciency which occurs concurrently with so-called "prostate hypertrophy," is to be sought in a quantitative change of the component parts of the bladder at the expense of the muscle tissue. The latter change does not stand in a causative relationship, either with the arterio-sclerosis of the small intra-parietal arterial branches of the bladder, or with the hypertrophy of the bladder muscle. 55 CHAPTER VI. CAUSES OF THE ANATOMICAL CHANGES IN THE WALL OF THE URINARY BLADDER The guide to find one of the most important causes of the changes in the structure of the bladder wall is given us by the fact, made clear by Table IV, that, in young male individuals with normal genito-urinary apparatus and normal vascular system, the bladder wall is constantly very rich in muscular elements. Furthermore it is proven that the thickness of the intima gives us a much more reliable measure of the normal condition of the arteries than does the proportion of the lumen diam- eter to the thickness of the wall. The cause of this is probablv that the adventitia, which ranges inside very broad limits, was always added to the thickness of the wall. That the proportion might be looked over more clearly, I arranged all my cases according to age. From the ac- companying table (Table V), which shows this compila- tion in the form of a curve, one can see that, leaving indi- vidual fluctuations aside, the quantitative changes in the hladder-ivaU components run parallel with the increase in age, and become more pronounced with the increase in age, this is especially so above the sixtieth year. The influence of age is made still more evident by the second curve, in which the average values of the different periods of age are grouped together. It is clearly shown by these average numbers that the muscle tissue occupies about i of the bladder wall in young individuals, while in very old people it makes up hardly 2-^^ and sometimes even only |. From this fact we must conclude that the quantitative changes in the components of the bladder zvall, in which ' 56 the anatomical basis for bladder insufificiency is to be soug-ht, is produced by the influence of age and develops in the majority of cases parallel with the increase of age. This rule is of course by no^ means without exception. In a fraction of the number of cases, even in cases of very old individuals (cases 8 and 41), the structure of the bladder wall is only insignificantly changed : above the limits formed by the fiftieth to the sixtieth year of life the muscle tissue does not exceed the connective-tissue framework as much as it has been observed to exceed this in many young individuals in whom the muscle tissue sometimes makes up 4-5 of the bladder wall. On the other hand, we meet sometimes with a very marked decrease in the musculatures of the bladder in young individuals, where it exceptionally makes up only 2-3 of the bladder wall. But it is easy to verify the fact that this lower limit is never exceeded before the fiftieth year of life. The border-line is formed by the ten-year period between the fiftieth and sixtieth year. In this period are to be found the highest as well as the lowest numerical values of the bladder muscle : the connecting line of this period with its marked curve points to- the fact that this ten- year period is a critical one for the bladder. If we overlook the fluctuations which occur within the normal limits, we shall find that the changes in the struc- ture of the bladder wall, also in old people, are by no means always marked. The diminution in the physiolog- ical function of the organism does not necessarily coincide with the number of years which mark the beginning of the senile state; and, just as the senile atrophy of some inter- nal organs is by no means a constant occurrence in old age, just as little do the changes in the structure of the bladcler wall, which must be attributed to the senile retro- grade occurrences, coincide with a certain age. For this reason these changes are also more pronounced in individ- uals who are weak, badly nourished, or for any other reasons are emaciated, than in others of the same age but strongly built and well nourished. Similarly to other organs, changes in the bladder wall may appear earlier in these emaciated individuals and may even in early youth reach an exceptionally high grade, and may even cause disturbances during lifetime. An example of such an early atrophy of a single organ is often met with in the 57 dissecting' room in the form of an early muscle atrophy of the heart, as is daily observed in emaciated individuals. In a similar way such an early atrophy of the bladder muscle may also occur, producing a "spontaneous" bladder insufficiency, the so-called "prostatisme vesical." We cannot discard the hypothesis that such conditions occur more easily and sooner in individuals who are born with a bladder wall poor in muscle tissue. The early changes in the structure of the bladder wall may of course occur without any senile atrophy in another organ, just as the senile or the early atrophies of the heart or the kid- neys occur individually. As an example of such an early atrophy, case 47 may be cited, in which it occurred in a 56-year-old man. Now the important question presents itself to us, what changes occur in the bladder wall if the prostate suffers a pathological change ? In what way is bladder insufficiency produced in such cases? It cannot be denied that bladder insufficiency occurs often in old people attacked by a so-called "prostate hy- pertrophy." The "spontaneous" bladder insufficiency, on the other hand, is a rare exception. In consideration of this circumstance it seems "a priori" very probable that there must still he other causes for the disurbances of micturition in cases of enlargement of the prostate gland. This question becomes complicated by the fact that the enlargement of the prostate gland as a rule produces a working (compensating?) hypertrophv of the bladder; it is also to be decided in what relation bladder hypertrophy stands to bladder insufficiency. Still further the question, why in some cases of en- largement of the prostate there occurs no disturbance of micturition, must also be elucidated ; because precisely these cases were brought up by the Parisian school as a proof that prostate hvpertrophy is not to be regarded as a primary cause in the clinical picture of the so-called "prostatismus." I shall first give closer attention to the compensating hy- pertrophy of the bladder caused by the enlargement of the prostate, because hy this I hope soonest to find a start- ing-point for the solution of other not less important ques- tions. An enlargement of the orostate was observed in one half of the cases (21) of old men which I examined. The 5S degree of this enlargement was different in the different parts of the prostate, and therefore the form of the pros- tate on the one hand and of the orificium vesicale and the pars prO'Statica urethra on the other showed various de- viations. To save space, I shall not enumerate in detail all these changes, as they are concisely recorded in the ac- companying table TABLE VI. The frequency of hypertrophy of the bladder wall. ion to the emptying of the bladder. Its relation to the obstruct-»; ^ /I thiroma 0/ the priMciph ll Weight Observed condition 0/ the Prostite respecting || II p; tranches 0/ the 5 « 0/ the th£ manner 0/ the obstruction disturbing ^i g.^ ■^ h 1 btadtUr arteries. 11 frostate the 'outjiow 0/ Urine. |i ■%4 ^ £1 li :; ^ 1 J 31.2 Turn Excresc on side; muse. valve;dev. led 580 , », 3 4 Calcination 25.J Dev. toward posterior in the pars prosl. ureth. 760 4 ' «[> Slight degree 1 33.5 High grade deviation toward the left 160 6 I •1 1 Bladder-neck valve 620 3 I 6 Atheroma 1 247 340 5 ••l 7 8 9 • ' 34.0 •5-3 " " Int. orifice elevated. 420 450 590 5 T I 21.2 540 4.5 IJ 26.6 .5.6 Deviation toward the right; blad. neck valve 310 6 5 "%> >3 , 26.0 on right; muac. " " " 280 3.5 t 4 1 '4 Wall thickened t 39.0 Bladder-neck valve 780 3 Calcination 30.8 290 8 ); i6 36.2 *' " 430 6 « ■7 '* 23.7 Deviation on right; bladder-neck valve 400 7 ^ i8 30.0 300 3 < !l 1 11 27.3 toward the right 280 7 42. 5 " posterior; high gr. deformity left; bladder-neck valve 700 8 59 44 -o 900? 5 7 "i" ■ 8 16 5 .3 1 ~ Atheroma _ 12.0 320 3 .i 21 Wall thickened ■ 2.5 9 •^ 24 1 ■7.5 210 5 =3 14.0 190 4-5 24 Mod. thickened t 17.0 5-5 4? 25 26 2? ■3-3 13.2 80 8 6 5 I 4 28 '9 Calcination 1 18^3 '5.4 190 60 5-5 6 ■j 30 12.4 100 5 •^ 31 .9.0 500 3 "!' 32 33 Atheroma 12.6 260 8 5 1 34 I ■9-4 300 3 11 "5-5 ■ 4.6 310 8 3 37 ■ 2.8 5-5 ■^ 38 1 14.2 300 ,4 1 39 Wall thickened 16.8 130 S.5 40 Calcination ■ 19. 1 5 4" Slight degree I 250 4 1 42 1 140 5 1 43 Wall thickened 1 100 5 ^ 44 1 320 3-5 JtL. Calcination 44° 2-5 i 46 47 18.0 •7.5 (Average Volume of the Bladder in an Adult 300 360 3 \l 12.6 200-400 ccm. Thickness of the contracted 6 1 49 8.3 wall of the bladder 12mm. Thickness of 260 4 i 50 11.9 15,5 the Bladder wall when moderately fill- 80 7 6 t 52 <5.o ed 3—4 tnm (inclusive of submucous 5 T 53 ■7-3 7-7 ■ T'.o and the subserous). 60 ' 1 54 55 (ViEBORDT, Anal. Datcn) 150 *■} jL ■9-5 8 .^ 58 '9 IT 16 42 <» 59 In general I demonstrated such anatomical changes in the orifiicium vesicale and in the pars prostatica urethra in i8 of the 21 cases of prostate enlargement; and these changes, either only one of them or all combined, were capable of producing a disturbance in the free outflow of urine. In the three remaining cases (cases 3, 13 and 18) such changes were not to be found. The question whether these changes could really pro- duce an obstruction to the free outflow of urine can find its solution only in the behavior of the bladder. Bladder hypertrophy was present in 16 of the 18 cases; it was missing in two cases, although in these two cases there were well-marked changes in the ori- ficium vesicale and in the pars prostatic urethra. In one of these cases (case 4) the prostate gland was greatly enlarged (weight 33.5 grms). As this enlargement oc- curred mainly in the right lobe the course of the prostatic urethra showed a marked angular, left-sided, pathological deviation. The frequency of hypertrophy of the bladder zvall. Its relation to the obstruction to the emptying of the bladder. In the other case (case 5) the prostate weighed only 20.2 grms. ; but a polypoid tumor, of the size of a hazel- nut, extended from the orificium internum, and seemed to have its origin in the posterior lip of the orifice. As this tumor was pedienculated and freely movable, there is no doubt that it was capable of acting as a valve during the contractions of the bladder and of shutting off the outflow of the collected urine during the contractions of the bladder. Why a compensating hypertrophy of the bladder muscle was not developed in both these cases is easily answered. Both cases were very old and very emaciated men (one was 67, the other yy years old). In one of the cases there was present a marked anaemia, due to hemorrhages from an ulcus rotundum ventriculi, while in the other extensive tubercular changes were present; in both cases I found senile atrophy of the internal or- gans. The organism in both cases was under the poor- est conditions of life and its vital powers had greatly suf- fered during a long period of diminution. From this it is apparent that hypertrophy of the bladder musculature could no longer occur. Correspondingly there occurred also in the second of the cases cited, the older and more 60 debilitated individual, during lifetime an involuntary- Voiding of urine by reason of an overdistended bladder ("Ischuria paradoxa"). I think that I must here cite the axiom which served as my guide in the decision of the question whether the bladder wall was hypertrophic or not. I have already mentioned that from the results of the micrometric meas- urements executed by myself neither positive nor nega- tive conclusions can be drawn in regard to an increase in the bladder muscle. That this increase really occurs can only indirectly be inferred from the thickness of the wall. I take it as a well-known and indisputable fact that as the bladder becomes stretched it becomes to a certain extent thinner. Viervordt states (Anat. Daten und Tabellen) that the entire bladder wall, i. e., the muscle with its con- nective-tissue framework, the mucous membrane, the submucosa and subserosa, measures in the adult on an average, with a moderately filled bladder (200-400 c.c), 3-4 m.m in thickness ; in a completely contracted bladder the wall thickness reaches almost 12 m.m. By numerous measurements of the muscle with its connective-tissue framework (with hand lens) in young individuals in whom there was no pathological deviation in the genito urinary system, I obtained the following values of the thickness of the bladder wall (compare also Table VI). In a completely contracted bladder,, y-d> m.m Containing 60-80 c.c. of urine, about 6 m.m " 100-150 c.c. *' '' 4-5 m.m. " 260 c.c. " " 4 m.m. " 300-360 c.c. " " 3 m.m. If in consequence of an obstruction to the free out- flow of urine a compensating hypertrophy is formed, then the bladder wall must, of course, increase in thickness. If the connective-tissue framework of the bladder wall has not by this suffered an increase, then the relative value of the bladder muscle must^ of course, be correspond- ingly larger. (N. B. in uncomplicated cases.) It is easy to convince oneself of the correctness of this supposition by appropriate examples. In case 11, for instance, the bladder contained 310 c.c. of urine. The bladder wall was 6 m.m thick. The pro- portion of the amount of the connective-tissue frame- work to that of the muscle was i :3.i4. 61 Normally the bladder wall measures, with a correspond- ing amount (300-360 c.c.J onh' 2-3 m.m in thickness. The proportion here, as previously mentioned, averages 1 :2.8, at the most i :3. In this case there was thus formed, as proved by measurements, an indisputable blad- der h3'-pertrophy, due to an obstruction to the free out- flow of urine. Likewise in case 14. In a well-nourished, and by no means old, indiviaual there was a marked obstruction to the outflow of urine ; the bladder extremely dilated and overfilled with urine, with contents of 780 c.c. The thickness of the bladder wall was 3 m.m. The proportion of the components of the bladder wall was i :3. From the quoted empirical scale it may be on the other hand seen that when the bladder contains 360 c.c. the bladder wall measures less than 2-3 m.m. in thickness. From this one would assume that, presupposing the possibility of such a phenomenon, the normal bladder wall, in a bladder containing 800 c.c. would be as thin as paper. In our case it is, on the contrary, fully 3 m.m. thick, therefore indisputably hypertrophic. This thickening is without doubt to be referred to an increase in the muscle tissue itself, because the proportion of the components of the bladder wall in our case amounts to just as much as in the bladders of healthy and young individuals ; considering the advanced age of the individual, the preponderance of the connective-tissue was rather to be expected. On the basis of other similar cases, in which there was no inflammatory complication which would have been capable of producing a thickening of the bladder wall without hypertrophy of the muscle through a genuine, -active proliferation of the connective-tissue, I believe I can maintain that the existence or the absence of a true hypertrophy of the bladder muscle can be demonstrated with some correctness by my method of investigation. I presumed before this, on account of the structure of the connective-tissue framework of the bladder wall, that the connective-tissue did not play an active part in the changes in the proportion of the components of the blad- der wall, i. e., it was not hypertrophied. Evidence in favor of this supposition was given in a comparison of the state of normal bladders to bladders of very old individuals in which there was neither obstruction to the outflow of 63 urine nor hypertrophy of the bladder. In cases 48 and 30, for instance, the bladder contents was in each 100 c.c. ; in the first the bladder wall was 6 m.m. thick, in the second 5 m.m. The proportion of the components of the bladder wall in the first was i :3, in the second i :2. If, as I assume, in the change in the proportion of components of the bladder wall the atrophy of the muscle tissue, and not the active proliferation and increase of the connective- tissue framework, plays the main role, then the bladder wall in the uncomplicated cases, under similar conditions (an equal amount of urine), must sufi:er a thinning-out parallel to the degree of this change ; at any rate, it can- not become thicker. The two cases cited establish this presupposition com- pletely. Far be it from me to maintain that the changes in the structure of the bladder wall that have been con- sidered are exclusively formed without the active partici- pation of the connective-tissue framework. I believe only that this is the rule for the uncompUcatcd cases. One must not forget in judging these conditions that in every case we have to figure with individual fluctuations; that these fluctuations are also found to a great extent in young individuals, and their existence must therefore also be taken into consideration in old people. I have already mentioned that the connective-tissue framework in the bladder wall becomes denser and more compact in consequence of chronic inflammatory compli- cations. I emphasize here that this manifestation is regu- larly to be observed in young individuals suffering from chronic inflammation of the bladder who have no obstruc- tion to the outflow of urine. In these cases we have to deal with a real, absolute increase of the connective-tissue of the bladder wall, which expresses itself in the relative preponderance of the former and at the same time pro- duces a marked thickening of the bladder wall. These conditions allow us to solve directly -the question whether such an inflammatory complication alone, without the assistance of other influences, is capable of producing a change in the proportion of the components of the bladder wall. The chronic bladder inflammations are, therefore, aside from the influence of age, of the greatest impor- tance for the structure of the bladder wall. As examples of this, cases 19 and 47 may be not quoted. 63 In the latter case inflammatory complication was present, and the influence of old age was responsible for the occur- rence of the disturbance of the equilibrium of the com- ponents of the bladder wall. Entirely different is case 19, in which the relative preponderance of the connective- tissue of the bladder wall reached an equal degree. Other factors besides the influence of age were here at play — either an inflammatory complication or an obstruction to the outflow of urine. Correspondingly, the bladder, wall in case 19 was 7 m.m. thick (instead of 4 m.m., as nor- mally), with a bladder contents of 280 c.c. ; while in case 47 the thickness of the bladder wall was only 2 m.m. (instead of the normal 3 m.m.) In both cases the bladder musculature itself was atrophic. Consequently, in case 47 the bladder wall showed a thinning-out, while the connective-tissue framework remained "in statu quo." In case 19, on the contrar}^ the bladder wall was very much thickened, due mainly to an active increase of the con- nective-tissue. These two cases illustrate clearly what an important role the inflammatory complications play in the production of bladder insufficiency. The intimate con- nection of this inflammatory complication with bladder insufficiency is proved, however, by the long-known, un- yielding- sclerotic bladders, which the clinician, as well as the anatomist, often meets. The foregoing analyses make it clear to us why in some cases even with a very extensive prostate enlargement there is no bladder insufficiency. This insufificiency does not happen when the proportion of the components of the bladder wall remains within the normal physiological limits, or else when it oversteps these limits exclusively in favor of the muscle. In the latter case the obstruction to the outflow of urine is entirely compensated for by the compensatory hypertrophy of the bladder musculature. This happens, however, very seldom in the diseases which we are now considering, because the prostate enlargement is generally found in old people, in whom the capability for an active hypertrophy of the musculature is lost. The other possibility seems to- be much more frequent ; that is, the proportion of the components of the bladder wall re- mains within the normal limits, or there is a very insig- nificant disturbance, which is not capable of influencing the functional ability of the bladder. However, this is 64 possible only under two conditions, namely, when the hy- pertrophy of the prostate causes only a very small ob- struction to the outflow of urine, as, for instance, in some cases of symmetrical and regular enlargement of both lobes; or when the damages which we refer directly to the influence of age did not act long enough to affect the function of the bladder. These two conditions are pres- ent in cases 3, 13 and 18. The absence of hypertrophy of the bladder and the behavior of the enlarged prostate prove that in these cases no obstruction to the outflow of urine existed. The age not at all advanced ; a good gen- eral condition of nutrition; the behavior of all the in- ternal organs ; the fact that in none of these cases was there to be observed any sign of senile atrophy, while in all three death was caused by an acute disease — all these circumstances explain the behavior of the bladder wall, which structure Avas only insignificantly altered. In judging the complicated cases of the so-called pro- statismus it was necessary to decide whether the presence of an obstruction disturbing the outflow of urine had any, and then what, significance for the condition of the blad- der wall, and that at a time when the bladder muscle had partially or entirely lost the capability of becoming hyper- trophied. Furthermore, we had to judge what relation exists between the influence of an established obstruction and the influence of age. For this purpose I separated the cases in which there was an obstruction to the outflow of urine due to a pros- tate enlargement from the cases without any disturbances. The proportion of the components of the bladder wall in each individual case was represented graphically, simi- larly as in the previous Tables. It will be seen from Table VII that in both groups the influence of age is very pronounced. In both groups the average numerical value of the bladder musculature is very low for the higher ages ; these values were much smaller with established obstructions than in cases in which no obstruction could be demonstrated. From this we may conclude that the average numerical value of the bladder muscle, measured with the numerical value of the connective-tissue of the bladder wall as a unit, is smaller under conditions otherwise similar if, besides the influence of age, changes in the vicinity of the orificium 65 and the prostatic urethra produce their injurious efifects upon the bladder wall. P'rom this it is clear that bladder insufficiency is more easily and more frequently formed in old people with prostate enlargement than in those in whom the prostate is not enlarged, or is respectively smaller. In the first cases this is to be referred to the higher degree of the changes in the structure of the blad- der wall. The cause of the more frequent appearance of bladder insufficiency in old people with prostate enlargement is by no means to be sought exclusively in the more pro- nounced changes in the bladder wall. Undeniably, also, the degree of the obstruction to the outflow of the urine is very significant. The more disturbing the operation of such an obstruction is upon the outflow of urine, the less important the changes in the structure of the bladder wall that will be necessary to cause symptoms during life- time. Vice versa, with more pronounced changes in the bladder wall a relatively small obstruction is capable of nullifying the functional equilibrium. The final result of all the injurious factors is therefore different in each in- dividual case, and one is hardly capable of determining it beforehand from the anatomical conditions. In one case, for instance, the structure of the bladder wall may re- main nearly unchanged, and the cause of the disturbance of micturition lies here exclusively in the important local obstruction to the outflow of urine. A surgical inter- ference which removes this local obstruction is in this case capable of restoring the function of the bladder with- out any trouble. Of two individuals in which the changes in the bladder wall reach a similar degree, one in whom there exists no enlargement of the prostate will not suiTer from any disturbance of micturition, while the other with prostate enlarged will show pronounced symp- toms of retention. In a fourth case, finally, there exists nO' obstruction disturbing to the outflow of urine, and the disturbance of micturition in this cas'e has its origin in a high-grade atrophy of the bladder muscle. It is to such cases that the name "prostatisme vesical" is given. This, in part at least, answers the question why the function of the bladder is restored in a few cases only after castration. Provided that the prostate atrophies in some c^ses after castration, then the proposition that sometimes just those 66 parts of the prostate become smaller which formed the main ohstrnction to the outflow of urine is not to be cast aside. The final result of a castration with regard to the . function of the bladder depends only on the momentary condition of the bladder wall in such cases. If the struc- ture of the bladder wall be relatively little changed, then the function of the bladder — though obscured to a certain extent by the local obstruction, but otherwise only little attacked — will be entirely restored; in another case the result of a surgical interference will be unsatisfactory, and the condition of the patient is slightly or else not at all changed. In this respect there is no essential difi^erence between the castration and the interferences which aim at a direct removal of the obstruction to the outflow of urine, that is, operations executed on the prostate itself. The restora- tion of the function of the bladder after castration is therefore not a mystery, and it is also entirely unnecessary to search for other forced explanations. My investigations show satisfactorily that the term "prostatismus," convenient as it may be, does not corre- spond to a uniform clinical and anatomical picture. It gives no basis for a uniform anatomical change composed of co-ordinated symptoms produced by a conditio-nal^ single, general cause. The sym.ptoms of bladder insuffi- ciency, as occurring in some old people, are more related to anatomical changes O'f different kinds, and are to be regarded as sequels of different causes. It cannot be de- nied, in cases where a bladder insufficiencv occurs con- currently with a prostate enlargement, that the latter is by no means tO' be regarded as insignificant. I may summ.arize the results of my investigation in the following sentences : (i) The clinical symptoms of the so-called "prostatis- mus" are without a uniform anatomical basis, no matter whether they occur in old men suffering from hypertrophy of the prostate gland, or in individuals in whom the pros- tate is of normal size or atrophic, or in female subjects. The anatomical changes which are expressed by these clinical symptoms are neither co-ordinated nor uniform ; nor are they produced by a uniform general cause. Espe- cially is it true that we cannot look upon arterio-sclerosis as a common cause for the changes which occur in the 67 kidneys, the bladder and the prostate during the course of the so-called "prostatismus." (2) One of the anatomical bases of bladder insuffi- ciency is to be sought in a quantitative change in the pro- portion of the muscle tissue and connective-tissue of the bladder. This change seems in the majority of cases to have its cause in the atrophy of the muscles of the blad- der. A real, active increase of the connective-tissue of the bladder wall seems only to follow frequently occur- ring chronic inflammation of the bladder. In the cases in which there is a change in the form of the orificium vesicale urethra and a change in the course of the prostatic urethra due to the hypertrophy of the prostate gland, part of the symptoms may be directly ascribed to this mechanical interference. After remov- ing this obstacle the function of the bladder may be brought to normal, provided the wall of the bladder suf- fered no marked changes in structure. (3) The changes mentioned in the structure of the bladder wall occur more frequently with the increase in age. In the individuals examined by myself the degree of these changes was parallel with the age. A higher de- gree of these changes is reached in those cases only in which, in addition to the influence of old age, there is an injurious effect of mechanical interference with the out- flow of urine, and in which at the same time the muscle has lost its capability to become hypertrophic ; but the highest degree is only reached when to these injurious in- fluences is added a chronic, inflammatory process. In the majority of the cases of bladder insufficiency in old people all these three injurious influences occur at the same time. In rarer cases two, and exceptionally even one, of these injurious influences may produce a high de- gree of anatomical and clinical disturbances. In cases in which there is an ostacle to the outflow of urine due to an enlargement of the prostate gland, this may be partly or wholly compensated for by the compensating hvper- trophy of the bladder, which is only exceptionally absent. 68 CHAPTER VII. THE CHANGES IN THE ORIFICIUn VESICALE URETHRAE PRODUCED BY THE EN= LARGEflENT OF THE PRO= STATE GLAND THE ORIGIN OF THE SO-CALLED "SENILE BLADDER WEAKNESS. The kind of the obstruction to the outflow of urine de- pends upon what part of the prostate gland is the most enlarged. In an insignificant enlargement which uniformly in- volves both lateral lobes of the prostate, and which does not produce a special prominence of the so-called "middle lobe," the prostatic urethra may be only slightly changed, and the free outflow of urine may not be interfered with to any extent. This was observed in three of my cases (3, 13 and 18). As soon as one part of the prostate is en- larged more than the others, and as soon as the "hyper- trophy" of the two lateral lobes reaches a higher degree, then either the orificium vesicale or the pars prostatica urethra, or both, must undergo changes in form, which are not without effect on the free outflow of urine. Far be it from me to take up a consideration in detail of all the kinds of changes to which the urethra is exposed in consequence of an enlargement of the prostate. I would then have to go over things which have been thor- oughly investigated, and which have long been generally known. Pathological anatomv has in this respect brought out all that was to be l)rought out, and the excellent investiga- 69 tions of Socin (i 19), Guyon (40, 41, 44, 47 ) and Thomp- son (130, 132, 133), aside from their predecessors and successors, will always form the basis for further work in diis field. The changes in the orificium vesicale still up to the present time, give cause for divergent views, especially in so far as regards the meaning of certain clinical symp- toms. In particular it was argued for a long time that in anatomical changes of the orifice the cause of retention of urine (Ischuria) is to be sought. In the previous chapters I tried to explain how great a part the^ structural changes in the bladder well play in the production of symptoms of the so-called prostatismus. I came to the conclusion that sometimes the bladder wall may remain entirely unchanged, or may suffer only slight change. The cause of the disturbance in micturiton is, then, to be sought exclusively in the local changes in the orificium and the pars prostatica urethrse. I am willing to assume, then, on the basis of my own observations and of numerous casualties, that cases in which the disturb- ances of micturition are entirely and only due to changes in the orificium internum, "sensu stricto," do not exist at all or are at most rarities. This view is verified by well- known statistics. Thompson, in his comipilation of 125 cases of prostate hypertrophy, states that he saw only three cases of isolated changes in the orificium vesicale in the form of a so-called hypertrophy of the middle lobe. Motz (89a), who collected sixty cases in all, from the literature, found only four similar observations. Also Sversen (64), who examined 203 prostates, noted among fifty-two hypertrophied glands only four in which the en- largement attacked exclusively the so-called middle lobe [1. c. p. 32(1)]. Among my own observations there is really not a single one in which the changes were ex- clusively confined to the orincium without attacking at the same time the prostatic urethra. At any rate, we must maintain firmly the position that Ischuria has its cause in different kinds of changes in the orificium internum, and that different mechanisms play a role here. Busck (10) constructed from the investigation which he performed, together with Koster in 1877, the following mechanism. The orificium vesicale in a prostate hyper- trophy projects forward against the lumen of the bladder 70 in the form of an obtuse cone. During the moment of a contraction of the bladder a hydrostatic pressure against the orificium is formed, which affects the whole upper •surface of the cone-shaped projecting orificium. By these means the lumen of the urethra is compressed, and an emptying of the bladder becomes impossible. Op- posing Busch's statements, Jurie (67) replied that the anatomical changes of the orificium vesicale that have been describe occur relatively seldom in proportion to the frequency of senile (fisturbances in micturition. On the other hand, Jurie lays stress upon the importance of other causative movements for the development or retention of urine, especially the weakening of the muscle fibres of the base of the bladder antagonistic to the sphincter. Without attempting to decide this dispute, I shall re- strict m.yself to mentioning that I certainly obsei'ved in a few of my cases changes in the orificium corresponding to the description of Busch. In this respect case 7 is most characteristic. The changes, however, were at the same time combined with other deviations in the orificium and in the prostatic urethra. For this reason they have, according to my opinion, only a subordinate importance so long as the prostate enlargement remains within at least moderate limits. I am not competent to decide to what extent Busch's theory is sufficient to explain the phenomena of cases that have extensive prostate enlarge- ment, because I never saw pure, uncomplicated cases of this kind. At any rate, it seems to me that the "mechan- ism" of Busch occurs not too frequently, and when it oc- curs it is hardly the only cause of Ischuria. According to it, a very important meaning must be given to the so-called "valve-mechanism"" in the develop- ment of urine retention, provided that aside from it, as I have explained before, other causative factors display their effects. I believe that these valve-mechanisms, of whatever kind they may be, are at play more frequently than is generally assumed, inasmuch as thev probably come into action also ift the cases of so-called "general uniform hypertrophy," and apparently are missing only at the isolated enlargement of both lateral lobes. If we add the cases of general uniform prostate enlargement of all three lobes to those in which, aside from the^ enlarge- ment of both lateral lobes, a greater hypertrophy of the 71 "middle" lobe is observed, we shall have then a group to which the same opportunity of a development for ihe valve-mechanism is given as in the isolated enlargement of the middle lobe alone. A second group will be formed by all those cases in which the enlargement is expressly described as an isolated hypertrophy of both lateral lobes without an active participation of the middle lobe, whereby we shall not take into account whether both lateral lobes are uniformly or irregularly enlarged. By this means the following compilation is formed : No. of cases ThOMP?ON 125 MOTZ (Sga) 60 IVERSEN (64) 52 My own cases iS of all three lobes of the middle lobe a 98 34 31 15 or lone Enlargement Isolated (enlargement) of both lateral lobes It 21 3 The Anterior commissure 3 Total 255 or per cent 178 69.8 74 29.1 3 I.I In the more extensive statistics cited are contained also the cases of Messer (94), Guyan (40, Ed. 2, 1885, p. 121) and Launois (72). The casual contributions scattered in the literature are hardly needed for our purpose, and for this reason were not used. However, the following com- pilation of Iversen (1. c. p. 32) may here be cited indi- vidually : Thompson & Messer IvERSE^f from 49 cases 52 cases Hypertrophy of the Prostate (without more definate marks) 34.7 per cent 25.0 per c. All 3 Lobes Enlarged 36.6 " 26.9 " Isolated enlargement of both lateral lobes 32.7 " 40.4 " " ■• " the middle lobe 2.0 " 7.7 " From this compilation it will be seen that during the course of a disturbance in micturition during lifetime the valve-mechanism exists in at least one-third of the cases. Key and Santesson (126) also believe that this mechan- ism is more frequently formed than can be assumed on a basis of the statistical compilations. In what way the valve-mechanism is formed is not estabhshed with sufficient clearness up to the present time. Formerly much stress was laid upon the so-called mus- cular bladder-neck valves. By some these muscular valves are described as polypoid myomata of the pos- terior lip of the orificium ; others, especially the old French aiithors (Alercier [92]), define them as trans- verse (or oblique) or crescent-shaped folds or pads, cov- 72 ering the posterior division of the orificium and formed by the hypertrophic "sphincter." As a second kind of bladder-neck valves, all those more or less movable tumors are described which contain in their interior a certain quantity of gland tissue, and which take their origin in the so-called commisure posterior, or "Portio intermedia,'' of the prostate gland, i. e., in that posterior and upper part of the prostate gland which lies between the sphincter and the vasa differentia, and which connects the two lateral lobes with each other. As is well known, the middle lobe does not exist in the normal condition. That part of the prostate which lies be- hind the urethra has the significance only of a posterior commisure, so that all tumors observed at the posterior lips of the orificium are to be regarded as a pathological phenomenon. The existence of the muscular bladder-neck valves in the sense of Mercier was emphatically denied by Rokitausky (112). Dittel (23) maintains that the hypertrophic middle lobe does not project behind the sphincter into the lumen of the bladder, but originates from the "portia intermedia" in front of the sphincter, and encroaches during its growth between the mucous membrane of the urethra and the posterior, half-ring of the sphincter; by which pro- cedure the sphincter comes to lie behind as a tumor func- tionating like a valve (1. c. p. 147). Neither were Mer- cier's muscular bladder-neck valves ("Barriere vesicale") accepted by Dittel, as it seems. Also Klebs (305, p. 1121) denies any pathological importance in the muscular trans- verse ridges of the orificium, and questions the existence of the "Barriere vesicale." Even if other investigators do not go so far (compare Pitha 106, p. 109), the con- viction prevails generally that the muscular folds of the orificium are less frequently met with than is maintained by Mercier. The already cited view of Dittel is disputed by Socin (119, p. 45), who is of the opinion that the sphinc- ter always takes a part also in the formation of the valve- like excrescence of the orificium, at least in so far as the hypertrophic "portio mediana" displaces the muscles up- ward and forward. Even after the muscular ring is in- filtrated with the glandular tissue and partly lost (which process will be considered later on), the posterior segment 73 of the sphincter, according to Socin, still remains intact, and expands as a more or less projecting fold (obstruct- ing the outflow of urine) between the lateral lobes. Also, according to Maas (84, p. 591), Fenwick (37) and Al- bert (i, pp. T92-194), there exists a purely muscular valve, "even if, perhaps, it seldom occurs" (as is added by Albert). The authors of the pathological-anatomical and surgical manuals take mostl_v a mediate position (com- pare in this respect, for instance, Orth 310, p. 298, Till- manns, 128, p. 369 [i]). From the older literature I shall also cite the views of Virchow (135), because he characterizes most clearly the different subdivisions of the bladder-neck valves and justly differentiates them sharply one from another. Virchow confirms the positicii that a thickening is sometimes formed in the muscular bundles of the bladder- neck, which, especially in old people, projects in the form of a flat, transverse ridge, the so-called "valvula vesico- urethralis se sen noula/' which also hypertrophies and thereb}' interfere with the micturition and catheterization (Barriere vesicale). This is to be sharply differentiated, however, from the so-called "hypertrophic middle lobe," i. e., from the myomatous or glandular tumor projecting from the posterior circumference of the orificium ( 1. c. p. 137). These tumors are generally not pure myomata; "even if they are fibromuscular for the greater part, we find certain segments which still contain glandular struc- tures, from which a certain amount of epithelium may be exDressed in the form of a turbid, whitish fluid" (P- 138). The incontinence of urine was generally referred to this cause, namely, that the hypertrophic "middle lobe" projected into the lumen of the urethra in the vicinity of the orificium, and thereby made the orificium incapable of closing. A chief representative of this view is Dittel (2^1), who believed that he saw during an extensive enlarge- ment of the "middle lobe" the half-ring of the sphincter assume, when displaced upwards and backwards, the form of a thin, flat' muscular layer, hardly visible behind the valve-like tumors and therefore with insufficient power to close the urethra. This contention of Dittel's was opposed by Socin (119) and Orth (310). Socin supports his theor}' with the fact that in most cases, especially in a high-grade hypertrophy of the "middle lobe," there is no sign of a sphincter to be de- tected behind the latter, even in the form of a very thin and flat muscle layer. On the other hand, Socin believes he has demonstrated that the sphincter is not only pushed forwards and upwards by the hypertrophic "middle lobe," but that it is also infiltrated with glandular tissue, which pushes itself between the muscle bundles of the sphincter and through the middle lobe; and at last the sphincter is entirely destroyed (1. c. p. 41). The orificium is either not at all closed (absolute incontinence) or only passivelv closed (complete retention) by the valve-mech- anism (1. c. p. 45). But before it comes to either of these extremes the insufficiency of the sphincter and the ob- struction to the outflow of urine may, during a long period, form different combinations. Guyon takes an indifferent position as regards the ex- planation of the involtmtary outflow of urine, inasmuch as he refers it to the extensive fibrous degeneration of the bladder muscles, which also ultimately attacks the sphincter. Lately, Jores (68), has occupied himself with these questions. His work closes with the statement that the polypoid bladder-neck valves have nothing to do with the so-called posterior commissure, or "portio intermedia" oi the prostate, which always lies behind the sphincter, be- tween it and the vas deferns. Such valve-like orificium tumors are akvays, according to Jores, composed of pros- tate tissue; i. c, they always contain besides muscular tissues also glandular tissue. They take their origin, not from the prostate gland itself, but from the glandular tissue, which is already normally present, in most indi- viduals, above the colliculus seminalis, just below the mu- cous membrane of the urethra and orificium respectively; at any rate, in front of the sphincter. The existence of this glandular collection was later demonstrated also by Aschoff (2). The pediculator valve-like myomata have not been in- vestigated by Jores himself, but he believes that the myo- matous form of the bladder-neck valves may originate out of the glandular through atrophy of the gland and says : *'The fibromuscular form must be related in its develop- 75 ment to the existence of glandular tissue." This sen- tence is synonimous with the statement of Griffith's (53), that the local prostrate hypertrophy in the neighborhood of the orificium internum is only when the glandular tissue was already present above the colliculus seminalis in the vicinity of the latter middle lobe. In the descrip- tions of the behavior of the sphincter during the highest degree of prostate hypertrophy, the statement of Dit- tel, that the sphincter is pushed backward and upward was at last confirmed by Jores. On the other hand, he lays stress upon the agreeing position of Socin that the sphincter at the same time grows through the glandular tissue and is destroyed, and that it is not at all to be found posteriorly above (1. t. p. 233). In agreement with Virchow, one must sharply limit the "Barriere vesicale" of Mercier, i. e., that transverse fold covering the orificium form, behind which it is un- doubtedly able to hinder, to a great extent, the free out- flow of urine by the valve-like, more or less pedunculate tumors, which project from the posterior circumference of the orificium, i. e., from the bladder-neck valves of the "sensu stricto." Among the latter one must strictly dif- ferentiate the tumors composed chiefly of muscle tissue from the tumors composed of muscle and glandular tissue. The existence of Mercier's folds is by no means to be denied, but it seems to me that they are not of frequent oc- currence, because I had opportunity to observe them in only two of my cases (i and 14). From such observa- tions, those cases ought to be differentiated, in which the post, lip of the orificium is pushed slightly forward and upward by the enlarged "portio intermedia." From the sagittal section it is easy to establish here the proposition that the sphincter is really pushed slightly upward and forward, and lies just beneath the mucous membrane; but in front of this membrane either there are an accessory gland (lores and Aschofif ), or, if they be present, at least they have suffered no pathological changes. Such a con- dition is illustrated in Table VI. I do not believe that a similar condition is of serious im- portance ; it is in my opinion pretty insignificant if it be present without additional complications. If I mentioned it, it was only because it more easily explains, at least in 76 some cases, the development of the inabihty to close the orificium, with the assistance of other conservative factors. This condition has only a superficial similarity to Mer- cier's bladder-neck valve, in that in both changes the shpincter lies just beneath the muc. membr. of the orifice. The origin of the Mercier fold is not explained sufficiently up to the present time. Of the attempts at elucidation which refer the Mercier fold to a hypertrophy of the sphincter, I take no account ; the existence_ of such a hvpertrophy is not proved by anybody, and it is on the whole hard to understand how such a hypertrophy could originate. Neither is a clear anatomical picture furnished by the statements of some investigators that the Mercier fold is a "sphincter stretched between the lateral lobes of the prostate." It has long been known that the prostatic urethra is pulled longitudinally during a hypertrophy ex- tending in a sagittal direction, whereby it is transferred from a small, triangular slit into a long, straight line. This change in the form of the urethra has its cause, without doubt, in that the hypertrophic lateral lobes of the prostate enlarge entirely posteriorly as they find re- sistance in front at the symphysis, to which they are strongly attached. With the lateral lobes growing in the sagittal direction, the lining of the urethra is of course, in the same sense, longitudinally pulled. If now there were no glands present in the neighborhood of the ori- ficium in front of the sphincter, or, at least, if they suf- fered no change, and if the portio intermedia was not en- larged to a higher degree; in short, if in the lumen of the orifice, either in front of or behind the sphincter, any pathological excrescence projects, then the powerful ring muscle will remain more or less normal during a prostate hypertrophy in spite of the changes in the part of the prostatic urethra which lies outside its vicinity, and the orifice itself will retain its normal form. It is proved: that the orifice will not be pushed by it in any direction, because the anterior half-ring of the sphincter is strongly attached to the symphysis, and the prostate, as it en- larges posteriorlv, is not capable of pushing it away from this situation. The displacement of the sphincter pos- teriorlv (reallv its posterior half-ring), and its removal from the symphysis-and anterior bladder wall respectively would only be possible if the sphincter were pushed apart 77 by a tumor lying zviiJiiii the orifice, or if the physiological tone of the sphincter were overcome by a posteriorly di- rected pull of the hypertrophic prostate. In an isolated hypertrophy of the lateral lobe of the prostate, this oc- currence must be either entirely excluded, in view of the strength of the ring muscle, or must at least be regarded as an exceedingly rare exception. Therefore, in an isolated enlargement of both lateral prostate lobes, neither the form nor the situation of the orifice will be changed. Below the sphincter, on the other hand, to which the effect does not reach, the lining of the urethra will be pulled lengthwise posteriorly and will have the form of a slit. The more the lateral lobes enlarges, the more is the lining of the prostatic urethra pushed behind, beneath the posterior half-ring of the sphincter. Of course the pos- terior lip of the orifice, which contains only the posterior half-ring, will in this way form a transverse fold, which comes to lie above the lining (pulled from behind), of the urethra. It is. in m.y opinion, not necessary to consider in this regard the unfounded hypothesis of a hypertrophy of the ring muscle, nor to assume that a special stretching of the sphincter between the lateral lobes of the prostate takes place. On the contrary, the Mercier fold is found only when the prostatic urethra beneath the ring muscle is changed, while the behavior of the latter is still normal. Yes, furthermore, it is found only because the sphincter re- mains normal. The Mercier "valve-mechanism," in the true sense of the word (Barriere vesicale), has, therefore, as a sequel only an increase in the curvature of the urethra. I have mentioned before that the catheterization is just as much interfered with and the disturbance of micturi- tion is just as easily produced by the Mercier fold as by the real valve-mechanism. If one wishes to include the Mercier fold in the patho- genesis of retention of urine in the sense of a bladder-neck valve in a tinder meaning of the words, nothing is to be said against it ; in this sense we must admit that also in isolated enlargement of the lateral lobes the valve-mechan- ism may sometimes play a role. 78 More exactly and better than the foregoing analysis the drawings Figs. 6 and 8 in Tables VI. and VII. illus- trate the formation of Mercier's fold. As regards .the real "bladder-neck valves." i. e., the pedunculated tumors of the posterior lip of the orifice, I am not able to decide whether such tumors are sometimes really true myomata, free from glandular tissue, because I never met with a single similar case during my investi- gatiou. Of course "a priori" it cannot be denied that true mvomata may originate in the vicinity of the ori- fice just as well as in other parts of the organism, where they take their origin, either from pre-existing muscular tissue or from scattered blyastodermic membrane. Still it seems to me that such true myomata of the ori- fice, free from glandular tissue, is a very great rarity. All the later authors lay stress especially upon the state- ment that they saw more or less abundant glandular tissue in the apparent myomata (under, if not with the naked eve, then at least the microscope). ( Klebs [305], Socin [119], Griffiths [53], Jores [68], and others). The cases in which true myomata of the orifice were ap- parently met with date back to a time during which histo- logical investigation was only little used, and, therefore, they lost their entire value. I have already cited a state- ment of Virchow, made in 1863, from which it will be .seen that this greal investigator has demonstrated the presence of glandular epithelium in the vicinity of the myom.ata of the orifice. Truly only a single myoma of the orifice was especially mentioned by Virchow. Of this he said : " . . . glandular tissue was not contained in it." (1. c. p. 138). Even in this case the microscopical investigation is not especially m_entioned ; therefore, it also is not freed from objection. In spite of careful search, I did not find, in all the literature within reach, another case of myoma free from objection. In all my observations in which I found pedunculated tumors in the orifice, I could demonstrate with the mi- croscope that for tile greater part they consisted oi glandular tissue. In this regard I can absolutely testify the view of Jores. These glandular tumors always had their seat in front of the posterior half-ring of the sphinc- ter, just beneath the muc. membr., and, therefore, in a 79 place where glandular tissue is often found normally. In my opinion, there is no doubt that just these accessory glandular groups are really to be regarded as the point of origin for those pedunculated excrescences. The state- ment of Jores that these orifice tumors have nothing to do with the posterior commisure of the prostate ("portio intermedia") seems to me to be correct. Let us now turn to the involuntary outflow of urine, and the role which the ring muscle plays in regard to this. Of the prevailing views of this matter no one seems to me to be absolutely correct. Either of them can only ex- plain a certain group of cases ; neither suffices as an ex- planation of all the cases of incontinence. It is without doubt that the cause of incontinence is always to be sought in the failure of the sphincter to contract. All the investigators are entirely unanimous in this respect. In those rare cases in which sphincter insufficiency is not accompanied by an enlargement of the prostate (the so-called "prostatisure vesical"), the condition of incon- tinence could only be referred to the changes in the stricture of the sphincter itself, as Guyon thought it should be. The structural changes of the sphincter are in all probability analogous to those which take place in the bladder wall, as already described in the first part of my work; and here^ as well as there, they are not to be referred to arterial schrosis, but to a simple atrophy of the bladder muscle. The strength of the sphincter sur- rounding the orifice gives a sufficient explanation why these structural changes of the sphincter, which probably go hand in hand with the structural changes in the blad- der wall, nevertheless produce their injurious effect much later than these. Here, as well as in the bladder wall, the chronic inflammatory complications may take a part in the formation of changes, and thereby, as they cause an active proliferation of the con-tis. framework, they may increase the serious consequences of the atrophic process. Also in the cases in which a so-called "Prostate hyper- trophy" is present, similar pathological processes prob- ably play a certain role, especially where no high-grade form of change in the orifice exists. But when the latter are also involved, these processes have generally only a subordinate importance. I cannot quite understand why, to some investigators, 80 Mecier's old explanation of ithe incontinence of urine ap- pears to be wrong and forced ; to me, for a certain group of cases, it has by no means lost its value. The tumors situated on the posterior lip of the orifice project, as a rule, only to a certain extent beyond the orifice into the interior of the bladder ; but if they, in their early growth, or right from the start, force themselves into the lumen of the orifice, whereby the latter is deformed and the sphincter pushed apart, then the function of the sphincter must certainly suffer damage. Under such circumstances the time at which the urine begins to flow involuntarily depends entirely on the con- dition of the muscles of the bladder wall, as these are, to a certain extent, antagonistic to the sphincter. If during the time of the functional ability of the sphincter this is interfered with by an interposing tumor and the bladder wall still retains its normal structure, then the incontinence will be developed very quickly. If on the contrary the bladder wall be atrophic, then the be- ginning of the incontinence will alwa3^s occur at a later period, according tO' the structural changes in the bladder wall, which on their side give rise to a retention of urine, because the sphincter, although interfered with in its function, is capable for a certain time of working against the bladder wall, which is just as weak, and is able to maintain the physiological equilibrium. If, lastly, the elasticity and contractility of the bladder wall be almost entirely lost in consequence of very extensive structural changes, then, "ceteris paribus," the incontinence will oc- cur very late and only after the bladder is dilated to its utmost limit and its inelastic and non-contractile walls exert a passive resistance to a further dilatation. Thus even comparatively small tumors may produce greatly differing degrees of incontinence, from the sim- ple incontinence to a true "Ischuria paradoxa," providing that they project into the lumen of the orifice. The in- continence is "ceteris paribus" more easily produced, the more the tumor situated in the orifice enlarges ; i. e., the wider the muscular ring is pushed apart, the more will its function be interfered with and the more extensively will the orifice be deformed. In such cases the posterior half- ring of the sphincter is always pushed behind, as observed by Dittel and verified by Jores. I have also verified this 8r by my own investigation of insignificant and moderately large tumors of this kind. With a large tumor of this kind it is hardly possible to find a sphincter at the place indicated by Dittel and in the form described by him. In this regard the statement of Socin is correct, inasmuch as behind the greater tumors there is really no sign of a sphincter half-ring to be de- tected. This fact was also observed by Jores, since he found no sufficient explanation in his cases which would correspond to the views of Dittel he resorted to Socin's theory, according to which the sphincter is entirely de- stroyed by the ingrowing new-formed glandular tissue. From my own experiences I can verify the facts ob- served by Dittel as well as the discoveries of Socin ; yet with the restriction that the former are observed only in the insignificant and moderate, the latter exclusively in the higher degrees of tumors which push apart the orifice. On the other hand, I cannot possibly affirm the general conclusions drawn from the observations of both these investigators; neither can I join in the mediate explana- tion of Jores. By the investigation of the starting period and of the moderate prostate hypertrophy, I was con- vinced that the glandular tissue present in the enlarged parts of 'the prostate never projects between the muscle bundles, and, too, it neither infiltrates the sphincter nor destroys it. The borders of the sphincter are always in a cross-sec- tion in a straight line and sharply defined ; they are never uneven nor indistinct. On the other hand, it seems to me that without doubt the posterior sphincter half-ring which is entirely free from glandular tissue is simply pushed upward from below and behind by the hypertrophic "por- tio intermedia," and from below and in front by the grow- ing submucous tumor. Of course this can only happen when not only the submucous tumor, but also the true "portio intermedia" enlarges. That is in the cases in which there really exists a general "prostate hypertrophy." The post, sphincter half-ring has, in a sagittal section, the form of a sharp wedge, the apex of which points down- wards, and the ant. border of which lies normally just be- neath the mucous membrane of the orifice and the pos- terior part of the prostatic urethra (excluding the ac- cessory glands), and the posterior bower of which is 82 touched by the "portio intermedia" and its short basis is related to the post wall of the bladder. The perpendicular which connects the base of the wedge with the apex re- mains unchanged as long as no pathological tumors press upon the anterior and posterior surface of the prismatic muscular half-ring. It remains unchanged even when the "portio intermedia" is moderately enlarged. When now a glandular tumor develops beneath the mucous mem- brane of the orifice and when the "portio intermedia" begins at the same time to enlarge, and when later the tumors growing on either side and beneath the sphincter take on greater dimensions, then it is easy to demonstrate macnescopically as well as microscopically that the wedge-shaped cross-section of the sphincter be- comes more blunt and shorter, whereby its borders lose nothing of their distinctiveness. By the pressure of the growing tumors the sphincter visibly changes its form, is pushed upward and projects slowly above the level of the original orifice. The two tu- mors which push the sphincter upward approach each other slowly and finally coalesce into a single mass. The pos- terior half-ring, which is always pushed higher, comes little by little to lie in the neighborhood of the bladder wall proper. Finally we see the pictures observed by Socin ; i. c, the sphincter apparently exists no more. If one does not know the origin of such pictures, it is easy to confound the deformed and displaced posterior half-ring of the sphincter with a component of the pos- terior bladder wall (or rather the base of the bladder). And yet the sphincter, from an anatomical standpoint, is not lost, and all the muscle bundles which compose it are still retained. From a physiological standpoint, to be sure, the sphinc- ter does not exist any more because in this form and in this place it cannot functionate normally; whereby the orifice is made entirely incapable of closing. "If the bladder still be closed, sometimes in such cases it is be- cause a passive valve-mechanism is eventually present;" as Socin rightly says (1. c. p. 45), although he gives no specific anatomical reason for it. The Socin theory, in other words, stands in opposition to the prevailing be- havior of the "hypertrophic" prostate gland, inasmuch as 83 Socin assumes that the sphincter is destroyed by the glandular tissue he alleges that hypertrophy of the pros- tate gland has the nature of a malignent adenoma, with which the hypertrophy of the prostate has really nothing to do. The ways and means by which the different symptoms of senile bladder insufficiency are formed, whether it be with or without an existing prostate enlargement, have been discussed several times in this work. As I have only touched upon the contested points, so far as in my investigation material was found for their elucidation, the representation of the symptomatology of the senile blad- der insufficiency could not be executed either systematic- ally or exhaustively. The attempt would also have been unnecessary, because an exhaustive statement may be found easily, not only in the excellent monograph of Socin Thompson, etc., but also in every thorough manual of surgery. It was my aim to call attention to a few anatomical pe- culiarities based upon my own investigations. Therefore, I must put aside the question whether the clinical picture of "prostatismus," drawn by Guyon's master hand is really constant or at least to be observed as a rule. I could at most resort to Socin's authority, as this investigator, in his excellent monograph, describes dif- ferent clinical pictures of the "Prostatismus" and leaves unmentioned a constant series of clinical symptoms. Only a short time ago he stated : 'T do not believe that a 'Pros- tatiker,' in the sense of Guyon, exists."^ As I have no right to decide this purely clinical ques- tion, I must limit myself to the investigation whether the Guyon picture of the "prostatismus" can be sufficiently sustained from an anatomical standpoint, by the results of my investigation. Really only one point is involved, namely, the explana- tion of in what way the incontinence can occur after re- tention of urine. The succession in which the retention of urine appears after the insignificant beginning of disturbance of mic- turition is exhaustively explained on the one hand by the structural changes of the bladder wall, and on the other by the pathological changes of the orifice and the pros- tatic urethra. Regarding the question why sometimes 84 before the period of retention of urine a quickly disap- pearing incontinence of urine is to be observed, partly it has been answered already, for instance, by the work of Socin (1. c. p. 56) ; and partly it may easily be dismissed on account of my previous discussion. If the incontinence of urine follows the retention of urine in cases in which the prostate is not all enlarged and no signs of any valve-mechanism are to be observed in the orifice, then this phenomenon can be explained in only one way ; that is, it must be referred to the structural changes in the sphincter.' But it must be taken into considera- tion that if these structural changes in the vicinity of the bladder wall and the sphincter develop parallels to one another, then the relative proportion of the function of both muscles, which, to a certain extent, act antagonistic- ally to each another, must remain unchanged for a long time, even though the absolute function of each of the muscles may have suffered greatly. As I have mentioned before, and as is generally recog- nized, the changes in the prostatic urethra are capable, without the assistance of the valve-mechanism, of pro- ducing at least partial retention of urine. The bladder-muscle, which is continually more and more altered, offers to the residual urine, which con- tinually becomes weaker and weaker, whereby the bladder gradually becomes more and more dilated, and is finally dilated to its maximum and overfilled; and there is formed solely through the passive resistance of its wall a ture "Ischuria paradoxa." Under such circumstances the "Ischuria paradoxa" will be formed the earlier the sooner the structural changes in the bladder wall reach their maximum, whereby the dila- tation of the bladder reaches its uttermost limit. But, be- cause the time at which the structural changes of the blad- der wall develop depends, among other things, upon the degree of the obstruction hindering the outflow of urine, as I have explained before, the degree of the change of the prostatic urethra may also be of importance for the beginning of the incontinence. The more extensive they are, "ceteris varvus," the more quickly will the amount of residual urine increase. Quite different is the matter in cases of "valve-mechanism" in the true sense of the word ; in such cases the incontinence may be developed much 85 earlier, even before the dilatation of the bladder has reached its utmost limit, because quite different influences are at work here. They are the previously described changes in the sphincter, which directly cause the inability of the orifice to close and cause the posterior half-ring of the sphincter to lie above the level of the orifice proper. The change in the valve-mechanism in such a condition is, at least in part of the cases, easy to understand. The tumor lying between the mucous membrane and the sphinc- ter, as was first demonstrated by Jores, takes its origin from the accessory prostatic glandular tissue scattered be- neath the mucous membrane of the posterior lips of the orifice. As long as the groups of glands enlarge that lie in the upper division of this part, the growing tumor will project only into the interior of the bladder; but if this process also attacks the inferior division and extends for- ward in the neighborhood of the lumen of the orihce proper, then the tumor begins to project anteriorly into the lumen of the urethra, whereby the opening of the orifice is deform.ed and the sphincter pushed apart. It will now depend on the form and size of the tumor whether the valve-mechanism is partly to be retained, at any rate without closing the orifice as promptly and ex- actly as before, or whether it will entirely lose its effect. The time at which the incontinence appears will now mainlv depend upon the condition of the bladder wall. I believe I can now sav that the results of my investiga- tion are proved to be sufficient for the explanation of the clinical picture, as characterized by Guycn. 86 CHAPTER VIII. PATHOLOGICAL HISTOLOGY OF THE S0= CALLED "PROSTATIC HYPERTROPHY" AND PROSTATIC ATROPHY The nature of the process to which the name "prostatic hypertrophy" is generally given has been defined in dif- ferent ways, according to whether the one or the other of the observed pathological changes was taken up as the main issue. There has been a great difference of opinion, although the characteristics of the histological changes were represented in the same way by the authors. Some investigators take no account of the decision of the question whether the name "hypertrophy" really fits for the enlargement of the prostate occurring during ad- vanced age. This is especially so in the older works (for instance, Pitha [io6]) ; but in most old works as neither an exact representation is furnished of the histo-patho- logical changes, nor the views of the structure of the nor- mal prostate are correct, no notice of these wroks need be taken. The opinion of many modern authors is analogous to the older views, since they regard the "hypertrophy" of the prostate as a kind of physiological senile process or as a physiological involution. The latter opinion is also closely related to the view that the development of the prostate progresses parallel with the development of the testicle, and that it is in this parallelism that the cause of a "hyper- trophy" of the prostate is to be sought. This view is also in intimate relation to the representation originated by Launois (72, 73) of the histology of the "senile" and the "hypertrophic" prostate. Together with other teachings of tlie Parisian schools, it found a very extensive circula- 8-7 ticn throf.^h Giiyon's works. Liunois {y2) rinas no sharp distinction between the so- called "diffuse'' form of prostate hypertrophy and the true prostate adenoma. According to him, a "hyper- trophy" of the prostate is to be regarded as the nodular form (1. c. p. 87). Aside from the works of Launois there are none in which it is not demonstrated tJiat "hy- pertrophy" of the prostate occurs as well in a nodular as in a diffuse form. These nodules, i. e., the easily enu- cleated tumors, develop, according to Launois, constantly beween the forty-fifth and the fiftieth year of life during the course of the physiological development of the pros- tate ; on account of their structure, Launois proposes to call these nodules "adeno-fibromyomes," or "fibromes glandulaires" (1. c. p. 77-81'. The origin of these nodules is to be referred to the con- nective-tissue in the neighborhood of the glandular tubules. "Dans le prostate des viellards, il se passe un veritable travail de sclerose annulaire" (1. c. p. 79). This hyper- trophy of the prostate may be a consequence of the in- crease and enlargement of these nodules "normally" pres- ent (comp. 1. c. pp. 87-89). The supposed connection be- tween the "hypertrophy" of the prostate by "sclerose an- nulaire" to arterial sclerosis I have already refuted in the first part of my work. Launois still, ten years later, upholds his view (which in the main was accepted by Guyon [85, pp. 105, 106]) without making further in- vestigation (73 p. 730). Bv the great majority of other investigators the "hyper- trophv" of the prostate is regarded as a kind of new growth (Neoplasm), whereby in the main the two well- known forms of this process are differentiated, the my- omatous and glandular ; and these subdivided into a nod- ular and a diffuse form. The classification cited dates back to the fundamental works of Virchow (135) ; but, although thirty years have elapsed since that time, we have made no progress in research in this pathological condi- tion. The idea of the "hypertrophy" of the prostate gland as a neoplasmatic process "sensu stricto" was perhaps most thoroughly worked out by Cohnheim (299 II, p. 74), as he speaks about myomata and adenomata without any further remark; while Thompson' ( 133, pp. 80-81) leans more toward the older views, which regarded the "pros- tatic hypertrophy" as a "genuine" hypertrophy. Socin (119, pp. 30-31) expresses most exacly what we should understand by a hypertrophy of the prostate. Ac- cording to him, this is a collective name by which processes that differ somewhat are gathered together, inasmuch as the entire enlargements of the prostate gland which neither have an inflammatory origin nor a malignant new growth (sarcoma carcinoma) are meant by it. At any rate, we have here to deal with no genuine 'hypertrophy," but with a tumefaction. This view seems to be most generally accepted. The description of both main forms of hypertrophy of the prostate, the myomatous and glandular, is repeated with a well-nigh pedantic monotomy in most mono- graphs and manuals (Socin [119], Iversen [64], Maas [84], Albert [i], Tillmans [128], Klebs [305], Birch- Hirschfeld [297], Orth [310], Kaufmann [303], Ziegler [314], Jores [68], &c., &c.) and by some authors the mixed form is still added (Socin [1. c. p. 37], Orth [1. c. p. 299], Kaufmann [1. c. p. 668]) or only the names were changed (Casper [16, p. 154]). For this reason I desist from the description of these forms in the sense of the authors cited ; but I beg to be allowed to call attention to the difference of opinion re- garding the relative frequency of the individual forms. Billroth, for instance, thinks (Discussion of Dittel's Lec- ture [360] ) that in the hypertrophy of the prostate the increase of glandular tissue never plays a part ; on the other hand, the hyperplasia of the connective-tissue and of the muscle constantly does. According to this the myoma of the prostate, since Virchow (135, p. 136), is regarded by most of the in- vestigators as a phenomenon at any rate rare. Socin (119, p. 38), Casper (15, pp. 154-155) and Jores (68, p. 240) have not a single case of a genuine myoma of the pros- tate among their observations; Motz (89b, p. 41) cites only a single corresponding case. Griffiths (53) assumes that the otherwise verv rare genuine myomata are to be differentiated principally from the occurrence of a hyper- trophv. Also those investigators who lay stress upon the observations of hypertrophy of the prostate with stronger activitv of the muscle stroma declared particu- larly that this form is rarely to be observed ; or they set 89 up, especially in the more recent work, the hypothesis, ac- cording to the example of Klebs (Prag. Viertel-jahr- schrift, Bd. 124, cited in 305, p. 1119), that this form is only brought about during the later stages of hypertrophy by the destruction of the glandular elements. These views find their verification mainly in the circumstance that the dififerent forms of "hypertrophy" of the prostate are difficult to differentiate, and that innumerable transi- tional pictures exist, which, according to my opinion, point to the conclusion that the common division of the "hypertrophy" of the prostate into different forms and subdivisions, is forced and unjustified. Some inves- tigators go still farther than Klebs, since they place the origin of the "prostate hypertrophy" of all forms in the glandular tissue alone. Even Virchow (135) expressed a view in this regard which was overlooked by most in- vestigators : "According to my opinion, tJie process he- gins, as a ride, in the glandular parts and connects itself only after a while with an increase in the stroma" (1. c. p. 135). Nearly at the same time Dodeuil (22) mentioned that the glandular acini in the hypertrophic prostate suffer an enlargement of their exterior layer of the walls only in consequence of an extensive formation of embryonal con- nective-tissue elements. The echoes of such views are still to be found in the works oi Mausell-Moullin (431) and Griffiths (53), and to a certain extent also in the works of Jores (68). The views of Motz ( [89b] p. 42 f) are related to those of Dodeuil. By the authors cited lastly the hypertrophy of the pros- tate is in the main not regarded in a collective sense, but as an individual disease process, and its different forms as different periods of development of one and the same process, or at least as different results of an originally in- dividual process. But, as well, those who regard the "glandular" form as a specific subdivision of the hypertrophy of the pros- tate do not agree as to where in such cases the neoplas- matic process takes its origin. A few authors, as, for in- stance, Birch-Hirschfeld ([297], Bd. II), think that the epithelium of the ghndular tubules plays an active role in the new formation and branching of new solid glandu- lar plugs and tubules. However, I have nowhere found data from which proof can be obtained for the new for- 90 mation and sprouting of glandular tubules. Even though the proliferating of the glandular epithelium be men- tioned by the French authors, as, for instance, Launois {72), Guyon (41), Miquet (87), von Motz (896), and in addition Cornie and Ravier (298, p'. 677), yet this is to be solely referred to the pre-existing alveoli of the gland in which the epithelium is said to proliferate to- ward the free surface, whereby it becomes transformed from a single layer to a stratified layer. Quite differently from Birch-Hirschfeld this matter is regarded by Rindfleisch (311, p. 581), and most of the authors, as, for instance, Orth (310), Albert (i) and Socin ( 1 19, p. 40) follow him in this. The starting point of the new growth is placed by these authors in the sub- epithelial connective tissue, and this proliferation causes secondarily an enlargement of the glandular acini. The histology of the prostatic atrophy offers much less room for contention. Furthermore, up to the present day this process is very little investigated. Neither did the atrophy of the prostate awaken much practical interest before castration was proposed as a treatment for "hyper- trophy" of the prostate. If we look away entirely from the cases of eunuchs and of non-development of the testicles which were diligently gathered from the literature by Launois (73), then the atrophy of the prostate is possibly more frequently found in old people than the so-called "hypertrophy." Socin (119, p. 109) states that atrophy of the prostate is ob- served in 20-30 per cent, of men above the fiftieth year of life. This was verified by Orth (310, p. 303), Klebs (05, p. 1 106), Iversen, anatomical examination (64, pp. 15-17) and Dittels, clinical examination (23). The numbers given by Thompson, two per cent, atrophy as against twenty-two per cent, hypertrophy, are undoubtedly too low an estimate. Among the twenty-one old people (without hypertrophy of the prostate) whom I ex- amined, I found an atrophy in nearly one-half of the cases (the weight below 13.5 grm. As a well-charac- terized subdivision the local focal atrophv of the pros- tate can be placed beside the general atrophy of the pros- tate. To the first may be added the cysts of the prostate formed by dilatation of the glandular ducts, due to an obstruction to the outflow of the secretion. Such cvsts 91 seem to be of very rare occurrence. Aside from the observation of Cruveilhier ( [300] Livv. 39 T. 2 f. 2), who saw a cystic degeneration of the whole prostate, and the one of Enghsch ([32] p. 71), who places the origin of the submucous cysts of the "pars supramantana prostatae," measuring 1.5x1.3 cm., in the foetal life and first years of life, respectively, I found in the literature within my reach only one case of Desnos (26) and Le Dentu (83). Perhaps we may include here the slit-like recess of the "pars supramantana prostatse" also observed by Englisch, which was possibly formed by a destruction of the anterior wall of the cysts (1. c. p. 77). Klebs (1. c. p. 1 106) thinks that by blocking one of the glandular ducts with amyfoid bodies a cyst may be formed in the prostate, but they never, as a rule, reach such a size as to be diagnosticated macroscopically. In this place my own observation might be cited (case 60) as to a few cysts measuring as much as 8 m.m. in diam- eter, which were found in the neighborhood of a peduncu- lated orificial tumor. Aside from the histological investi- gations performed by Launois in the hypoplastic and atrophic prostate, respectively, in two cases of Monorchis ( [73] P- 733) a'^d in one case of syphillitic changes in both testicles (1. c. p. 743), I was not able to find corresponding data in the literature within my reach. In the first two cases there were almost no glands present in the half of the prostate corresponding to the missing testicle ; in the third case none in the entire gland. The atrophic pros- tate of old people were, according to my knowledge, never histologically examined by any one. Besides, histological investigations of atrophic prostates after castration are not numerous. On a human subject these investigations were performed in one case by Griffiths (55), and, ac- cording to Casper (i6a), in one case by Gueillot and in one by Bryson. Casper (1. c.) makes the appropriate statement with re- gard to these observations that the cases were altogether obscured by existing complications, and it is therefore not possible to decide which histological changes were due to the complication and which were due to the influence of castration.- I wish to call attention here to one of my observations (esse 58), in which a castration was per- formed on the right side and a vasectomv on the left eight 92 days before death. The histological investigation gave here also no clear results, because in the histological pic- ture everything else was overshadowed by the charac- teristic changes of the so-called "hypertrophy of the pros- tate. The histological investigations of atrophic prostates artificially produced by castration in animals are also not numerous, but give results which agree almost com- pletely. It was proved that in castrated animals the glandular tissue proper atrophies first, and, too, very quickly. Casper (i6a), to whom we are indebted for the thorough descriptions of the corresponding investigations, writes that in these experiments "the changes in the glandular part of the prostate amount to an entire destruc- tion." (I.e. p. 584). The atrophy of the glandular ducts after castration was more pronounced in rabbits than in dogs, according to the experiments of Casper; this pe- culiar difference deserves especially to be mentioned. It is proved that genuine myomata as well as genuine ade- nomata may occur in the prostate ; these two kinds of tumors have, according to my opinion, nothing to do with the so-called "hypertrophy" of the prostate. In the "path- ological-anatomical Institute of Krakau" a preparation of a genuine myoma and of a genuine adenoma of the pros- tate is preserved; the latter possesses all the character- istics of a malignant growth ("adenoma destruens") ; other similar examples could neither be found in the prep- arations of high-grade "hypertrophy" of the prostates preserved in the same Institute nor in the statistics of dis- sections kept since 1852. I myself have not during the last three school years dissected a single similar case in a material of 1100-1200 bodies. Among the observations used as a basis for the work under consideration there is, therefore, not a single analogous case. Also, according to the literature previously collected, one must assume that bv "hypertrophy" is meant the "mixed" form of prostatic hypertrophy, that is, the one which is formed by a uniform participation of the glandu- lar tissue proper and of the fibromusculostroma. That there really does not exist a "pure" form of "prostatic hvpertrophv" was unmistakably shown by one of the most prominent investigators in this domain, Socin. In my investigation before becoming acquainted with tlie literature I came to the conviction that the histo- 93 logical pictures of the "hypertrophy" observed in my cases could be arranged naturally in a coherent line of different degrees of one and the same process. Should I press the mode observed by myself into the extensive pattern of to-day, then I would have to say that, without exception, in every case of "prostate hypertrophy" investi- gated by myself the "mixed" form could be demonstrated, and that the enlarged prostates were in the main com- posed of glandular tissue proper. Later on it will be proved how forced such a definition would be. Not only in one and the same prostate, but alsO' in the vicinity of one and the same microscopical section, I frequently found all the forms of structural changes with their tran- sitional pictures. They are therefore in no way to be differentiated from each other. Moreover, my investiga- tion cannot be brought into conformiy with the well- known differentiation of a diffuse, focal or nodular sub- class. This differentiation would by all means be justi- fied, to a certain extent, according to the macroscopical view of the preparation, but under the microscope there exists no difference of any account between the two sub- classes. As the histological changes observed by myself of the hypertrophic prostates deviate to a certain extent from those of the manuals. I have gone into detail with regard to my investigations. The character of the changes which take part in the "hypertrophic prostate" will be best understood by a separate representa- tion of the changes observed in its structural component parts, taken singly, i. e., the changes observed in the glands, in the muscle fihrUlce, and in the connectiz'e-fisstte framezvork. The changes in these three component parts •were in every one of my cases zvithout any exception in- variably alike; the existing differences betzveen this or that case consisted in the main only in a different locali- zation of these otherzvise identical processes. Most con- spicuous of all is the enlargement, in all cases, constantly observed, of 'the glandular lumen in the glandular tissue proper ; this enlargement appears by no means uniformly in all parts of the enlarged prostate gland, but is found only here and there, and reaches a high grade at one place and is only indicated at another. In the lumen of the enlarged glandular ducts there is nearly constantly a pathological contents present, which is mainly composed 94 of desquamated epithelial cells, occurring either singly or in rows. These desquamated cells are most frequently of a polygonal or of a cuboidal form, therefore visibly flatter than the normal lining of the glands of the prostate. Very frequently retrograde changes are to be observed, since their nuclei do not stain any longer with the basic dyes or become only pale and hazy; the death of the cells is also proved by the behavior of the cell-plasma, which loses its normal appearance and ap- pears either entirely homogeneous or separated into ir- regular lumps of different sizes. In other still more largely altered cells the cell online is indistinct, hazy or uneven as mentioned. Finally, the entire collection of enucleated cells is changed into a heap of irregular, equally colored lumps and grains of plasma. They are scattered irregularly in the lumen of the enlarged glandu- lar ducts, found now alone, now in little heaps. In very many glandular ducts such cell remains quite dead ; cells form into homogeneous, often concentrical, layers, or they form into a mass impregnated with lime-salts. One can then meet the so-called amyloid bodies in their differ- ent states of development. But sometimes no amyloid bodies will be formed from such desquamated cells and cell remains. In the lumen of some dilated glandular ducts only a single lump is found, to fill it entirely or almost entirely and consists of an amorphous, homogeneous or finely granulated mass. Such amorphous, homogeneous masses seem to be related to the genuine amyloid bodies, because similar but small amorphous lumps are met with in the other glandular acini, aside from the desquamated epithelium and genuine amyloid bodies. Between such amorphous lumps and the homogeneous or finely granu- lated concretions often lying beside it, which remind one by their polygonal form and blunt edges of the non- striated, non-calcified amyloid bodies, there exists only an insignificant difference. Finally, it is easy to find such places in which, in the interior of the homogeneous mass, there are enclosed here and there either smaller or greater, mostly non-calcified but clearly striated, amyloid bodies; then we shall find cell remains characterized by chromatic lumps, and then more or less changed sometimes, through apparently normal but desquamated epithelial cells. 95 These different sub-classes of a pathological contents composed mainly of desquamated and dying epithelial cells — cell remains, loose plasma lumps and the homo- geneous masses probably formed by these — will be cpn- stanly found in the enlarged glandular acini of every en- larged prostate gland. As this picture repeated itself throughout my entire observation in manifold combina- tions, I believe it is not necessary to cite the individual cases. Besides the component parts already mentioned of the pathological contents of the glands there is some- times still another to be found. This other is the leuco- cyte, which is easy to be differentiated by its characteristic polymorphous nucleus from the other kind of cells. These polynuclear leucocytes make up only a fraction of the pathological, glandular contents. They are mostly found at scattered places of the proparation without any regularity. Much more rarely it occurs that the contents of the enlarged glandular acini consists ex- clusively of leucocytes and has the characteristics of a genuine suppurating exudate. Between the amount of the leucocytes, to a greater or less extent in the enlarged pros- tate gland of cases i, 5, 14 and 60. Much more rarely it occurs that the contents of the enlarged glandular acini consists exclusively of leucocytes and has the character- istics of a genuine suppurating exudate, as was observed, for instance, in case 15. Between the amount of the leucocyte-containing glandular acini and the proportion of the leucocytes to the remaining contents there seems to exist a relation. The nearer the pathological glandular contents stand in a morphological respect to a genuine suppurating exudate, the more numerous are the en- larged glandular acini, which, as a rule, are filled with such leucocyte-containing masses. If on account of the morphological characteristics, one should call this process a suppurating glandular inflam- mation, then we might say that the intensity of the sup- puration runs parallel, to a certain extent, with its de- velopment. I have already mentioned that the glandular lumen is for the most part entirely and densely filled with the pathological masses, and that the corresponding glandular acini are in most cases dilated. I never had the opportunity to observe dilated but empty glandular acini. On the contrary, these acini were on«ly dilated when there 96 was present in their lumen an increased mass of epithelial cells, mostly pathological, and in the mildest cases des- quamated and pretty well preserved. A contents of the composition last mentioned occurs by no means fre- quently. As I have stated before, the cells contained in the mass are mostly changed pathologically. As long as the glandular lumen is not entirely filled with this mass the normal form of the gland is preserved, because the compound tubular form characteristic of the normal gland suffers no extensive changes. As soon as the mass be- comes more extensive and begins to fill out the glandu- lar lumen, then the characteristic glandular structure is gradually lost. The walls of the glandular trbuli move always more and more apart ; the intervening walls which limit the ramification become gradually thinner and flatter (shorter), until they are trans- formed into a kind of a ridge, which projects from the wall into the lumen. These ridges become gradually flatter in the more strongly dilated acini. Finally they are no longer visible ; and the corresponding glandular part, but especially the ramification of the tubules with their lateral and terminal dome-shaped outlets, assume the form of roundish microscopical cysts. The more the in- dividual glandular acini are dilated by the pathological contents, and the more numerous the terminal branches of a single glandular system that suffer a dilation, the more pronounced will be the cystic changes in the glandular acini. After all the interlining walls of the enlarged tubuli become gradually thinned out until thev disappear com- pletely. By this means there may result a formation of greater, macroscopically visible cysts, whereby many enlarged prostates, especially the so-called "diffuse" form, take on in section the well-known spongy appear- ance with an extremely fine outlme. It can hardly be doubted that if this process has lasted a suflicientlv long time and is always progressing, there will finally be formed greater macroscopical cysts. Probably this will occur easily if the glands suffer from the supouratinaf in- flammation already mentioned, as under such conditions the pathological contents of the gland increase rapidly. The supposition that the suppurating process in a glandular part mav, under certain conditions, produce the origin of proportionally large cysts, becomes verv likely 9.7 by reason of the fact that the cysts observed in my cases were constantly filled with pure pus, or at least with a contents holding many leucocytes. To complete the picture of the changes in the gland of the "hypertrophic" prostate, I must describe the behavior of the epithelium lining the glandular acini, as far as this epithelium is preserved. One can often observe that the wall of the dilated acini is here and there deprived of its epithelial lining. Rarely it is missing to a greater extent, and then mainly in the highest degrees of dilatation in the cystically changed acini and especially when to the mass in the glands a relatively great quantity of leuco- cyes is added. For the most part the epithelial lining is missing in small portions of the wall ; one can often ob- serve the bits of clesauamated epithelium cast off in a con- tinuous row and lying near its place of origin. Som_etimes it approaches in such a connected layer the middle of the glandular lumen, but mostly only individual, usually dying, loose cells or their remains are present in the neighborhood of the uncovered wall. But as well the epithelium becomes altered at places where it is not missing. The more the gland becomes di- lated, the flatter will be the epithelium. From the cylin- dric it is changed to a cuboidal form and finally becomes flat. At this stage of the changes, which coincides mostly with a very high degree of glandular enlargement, the normal structure of the epithelial lining becomes gradu- ally lost, as the compensating cells push themselves through little by little between the flattened-out and pushed-apart cells of the superficial layer. These com- pensating cells are called by those who assume the pros- tate epithelium to be a double layer — "the deeper layer." By this means these cells are forced into the epithelial layer proper, and disappear gradually. In such cases the existence of those compensating cell layers can only be demonstrated at individual places in the wall. If finally the dilatation of the grandular acini has reached the highest degree, the epithelium becomes a scale-like thin membrane, in which here and there only flat nuclei are to be found. These are at last entirelv de- stroyed, so that the pathological conten'-'= of ^he gfland com.es to lie apparently loose in a space within the stroma. 98 The origin of such a space situated within the stroma is the harder to recognize, since the prostate gland, as is known, has no "membrana propria." The histological facts regarding the "hypertrophic" prostate cited above demonstrate that the glandular acini suffer a passive dila- tation through the accumulation of a physiological secre- tion, or, what occurs more frequently, of a pathological contents which has sometimes indisputable characteristics of an inflammatory exudate. In this regard I am entirely in accord with the views of Socin (119, p. 39) : "Still more one gets the impression of a passive enlargement and dilatation of the normal glandular tubuli * * *," with the only difference that I do not consider the dilated glands in the majority of cases as normal. The frequent occurrence of desquamated epithelial cells in the contents of the dilated glandular acini seems to speak very defi- nitely for the proposition that the secretory processes in the prostate glands do not functionate normally. We must assume an increased and a vigorous proliferation of the epithelium, whereby the loss caused by the desqua- mation of the epithelial cells is compensated. We have to deal here with a process very similar to a catarrh of the mucous membrane. I could never observe the changes in the epithelium which might be taken as a neoplasmatic proliferation. By other authors two kinds of prolifera- tion in this sense were described. One should, apparently, depend upon the fact that the epithelium becomes strati- fied, whereby the superficial cells which are lying opposite the center of the glandular lumen lose their nuclei and become more polygonal and big-ger than the peripheral cells. The other kind of changes depend, apparently, upon a sprouting of new, partly solid, partly hollow cell plugs, from which later on new glandular tubules are formed. In spite of very careful researches, neither the one nor the other kind of this proliferation could I find in the enlarged prostate glands e:^amined by me, provided that the preparation was cut correspondingly thin (not above 0.01 = 104 thickness). On the other hand, it is not hard to find such pictures as are described by Birch- Hirschfeld and Jores in thicker preparations, in which a few layers of cells were arranged above each other. Jores constantly observed a lumen in the cell plugs that were apparently solid. In the thinner preparation it is 99 easy to convince onself that these lumina are just as wide as those of the normal glandular tubuli, and that they are constantly lined with a normal, single layer of high, cylindrical epithelium. In the serial sections one can, furthermore, easily observe that in the following section this lumen apparently becomes narrower, and that the epithelium apparently comes stratified. These pictures have their origin in this fact, that the following cuts always include more of the tubular wall, so that a few layers of cells fall within the section. Also in the trans- verse section of the tubuli a similar state of afifairs is to be observed, provided the preparation be sufficiently thick. The apparent striation of the epithelium is pro- duced by the wave-like course of the prostatic glandular tubuli. For this reason they are very rarely cut exactly transversely. By using the corresponding thin section one can easily convince himself that that which was looked upon as a new-formed glandular tubule by Birch-Hirsch- feld and Jores was nothing but an altogether normal glandular branch, which was not yet enlarged by the accumulated pathological contents. By similar technical mistakes the incorrect conclusion of the French investi- gators is to be explained, only with the difference that here the faulty observation was referred to the enlarged glandular acini. If such a glandular acinus be opened by a cut at its greatest diameter or near it, then its pe- ripheral epithelial lining will be divided longitudinally, i. e., vertically, and will appear in its real form, i. e., as a single layer. But the case will be entirely different if the cut open a cystically enlarged gland near its wall parallel with and near a tangent surface. The part of the glandular wall divided by this forms a very shallow, dome-shaped sphere or cylindrical section. Then it may easily occur that the cut may not at all reach the lumen of the gland, but may «ink itself in its whole extent in the epithelial lining. But the peripheral epithelial cells are cut through at different heights : the ones lying in the middle are cut near the summit ; the others lying nearer the periphery are cut near the base, that is, the part which contains the nucleus. For this reason we find that the cells lying in the middle of the corresponding section of the glandular wall have no nuclei, while those -at the pe- riphery have, and the whole makes the impression of a glandular acinus filled with the proliferating cells of the stirated epithelium. That this is so is demonstrated by the difference in size between the peripheral and the cen- tral cells, as mentioned by the French investigators, which difference is only apparent. The changes in the glandular tissue proper already de- scribed are, as has been mentioned, very irregularly dis- tributed in the enlarged prostate gland : one can observe in one and the same preparation, besides the high-grade and differently changed parts of the gland, also entirely normal parts. The variety of combinations caused by this irregular distribution of changes is so great that it seems impossible to enumerate them all. In this respect there is no regularity, except that each individual group of similarly changed glandular acini belongs to one and the same main duct. The changes localized in a glandular system do by no means constantly occupy the whole ex- tent of such duct ; on the contrary, it may often be ob- served that certain parts of a glandular system gi-p- now greatly changed, now only a little or not at all. We see here a row of transitional pictures. The highest grades of the changes are generally to be observed in those enu- cleatable, in some enlarged prostate glands even macro- scopical nodules. These nodules are called, as is known, by a variety of names, as, for instance, "Fibromyoma," "Adeno-mvoma Adenoma," &c., &c. From the foregoing representation it will be seen that we cannot speak of a genuine neoplasmatic proliferation of the glandular tissue proper of the enlarged prostate glands ; and, as the majority of these well-defined nod- ules that can be enucleated consist exclusively of the much dilated glandular acini, I gave to these nodules, without seaiching for other names, the name of "pseiido- adenoma." The number of the changed glandular acini is, in certain cases of prostatic enlargement, very varying, but in general it can be said that the number is greater the higher the grade which the enlargement of the pros- tate as a whole reaches. At first glance it seems as if the number of the glands in the enlarged prostate — that is, the amount of glandular tissue proper — were absolutelv increased in proportion to the normal condition. Sometimes it is by no means easy to avoifl this impression, especially if one encounters the dilated glandular acini in places of the preparation where normally they are less numerous and where generally only a few excretory ducts with short dilatations lie in an abundant stroma, as is the case especially in the central parts of the prostate in the neighborhood of the urethra. By an investigation of my cases, made as exact as pos- sible, I was convinced that in no one of them is the glandular tissue absolutely increased. The increase of the glandular tissue is only apparent, and arises wholly through the dilatation of the lumen. The circumstance that we frequently encounter the glandular tissue of the enlarged prostate gland in the form of "pseudo-adenoma" at uncommon places in the close vicinity of the urethra depends, as I shall later dem- onstrate, upon a displacement and a storing up respec- tively of a ''pseudo-adenoma" that is already formed and is still growing. It is known that the enlargement of the so-called an- terior commissure is a very rare occurrence. Aside from the cases cited by Klebs (305, p. 1123 R), Quain's (108), and the three observations mentioned in Thompson's statistics, I found in the literature within my reach only three other cases. These last cases were published by Sahlange (123). From anatomical investigations, espe- cially the one of Aschoff (2), it may be seen that in the majority of cases only a few small and but little ramified gland tubules are present in the vicinity of the anterior prostatic commissure; that sometimes none exist at this place, and that only exceptionally abundant glandular tissue is present, which then forms a kind of anterior lobe of the prostate, and which exceptionally may be placed below as far as the dorsal side of the cavernous urethra (Luschka [75]). The fact that the enlargement of the anterior prostatic commissure occurs very rarely corre- sponds entirely with my investigation. If in the so- called "hypertrophy" of the prostate the genuine new formation and the increase of the gland tubules play a main role, then the enlargement of the anterior prostatic commissure should occur much more frequently. The gland groups lying in front of the urethra do not differ with regard to their origin nor with regard to their structure from other gland tubules of the prostate. Gen- erally they have too small dimensions and are not nu- merous enough to produce by their dilatation changes which can be recognized macroscopically. In those ex- ceptional cases, on the other hand, in which at the anterior commissure there are more numerous and more richly branched gland collections, their dilatation is capable of producing a macroscopic and even a high-grade enlarge- ment of the anterior commissure. One can raise objection that it is altogether inconceiv- able that the dilatation of the glandular acini alone should be capable of producing such an extensive enlargement of the entire prostate gland as is sometimes observed. To this I must reply that pronounced extensive enlargements of the prostate occur only exceptionally, and that in the majority of cases the enlargement of the prostate does not exceed a mild degree ; furthermore, that even the greatest cases of hypertrophy of the prostate up to the present time published do not exceed the size of an apple, while gen- uine neoplasmata, as for instance the wrongly included uterus myomata, are not restricted in their growth. Finally, we have to consider that, even if the glandular dilatation plays here a main role, one can hardly maintain that this dilatation is the only cause of enlargement of the prostate. This holds good only for the beginning stages. That the passive dilatation of the glandular acini alone is able to cause a considerable enlargement of the entire prostate gland is nothing remarkabte. Long before all the glandular acini suffer from the changes previously mentioned the prostate gland may reach very great dimensions and still steadily grow larger. A similar process occurs in all retention cysts which enlarge, as long as the epithelial lining is so far preserved as to be still capable of secreting." To select an example in which we cannot as a rule speak of an active proliferative process, hydromphrosis mav here be mentioned, which enlargernent ceases only with the final atrophy of the renal epithelium; but before this occurs the organ may reach the size of a man's head. If one wishes to find out exactly the role which the 'In the prostate the dilatation of the acini may even pro- gress after the loss of the epithelium, if the additional accumu- lation of the secretions in a given case be caused by suppura- tion. ro^ passive enlargement of the acini plays here, it is not suffi- cient to examine several or more preparations of any part of the prostate gland, but one must carefully go over the preparations of the main parts and of every one of the main planes/ The passive dilatation of the glandular acini is un- doubtedly a consequence of pathological processes taking place within them, whereby a great accumulation of their contents is produced. The cause of the obstruction is referred to the presence of the amyloid bodies. It is easy to demonstrate the real and primary causes of the passive glandular dilatation in the changes localized in the stroma. In all the cases of "hypertrophy of the prostate" examined by myself I met, ivithout exception, with such changes in the vicinity of the stroma as were able to clear up all the phenomena. These changes de- pend upon a proliferative coniiective-tissue process. As the first stage of these processes, may be designated the appearance of infiltrations, which consist of small, round cells poor in protoplasm, with dark-colored nuclei, and similar to granulation tissue. I shall leave it unde- cided where these infiltrations take their origins, whether they generate from the fixed con.-tis. elements or from lymphocytes, which, however, are regarded by Ribbert as a special kind of cell. (Comp. "Das Patholojische Wachstum der Gervebe. Bonn, 1896.) As a matter of fact, such infiltrations appear mainly in organs suffering from a chronic, productive process, and it is demonstrated indisputably that genuine con.-tis. is found to replace these infiltrates in the more advanced stages, and this con.-tis. becomes finally cicatricial tissue, poor in vessels, firm and compact. The small-cell infiltrates observed by myself in the enlarged prostate gland are of different ex- tent and are varying in density, now small, now large, now compact and now very loose. There is apparently no regularity to be noted in their localization, except that for the greater part they have their seat just beneath the gland epithelium or quite close to it.. "It is essentially necessary to examine the entire horizontal section of the whole prostate gland to obtain certain land- marks, for which a magnifying glass (Preparation microscope) and the weakecst objectives are well adapted. 104 Sometimes, however, these infiltrations appear loose in the stroma far away from the glandular wall, but they are rather rare, and there are constantly beside them nu- merous subepithelial infiltrations. The latter appear, as a rule, in groups irregularly scattered in the different parts of the prostate gland ; they are most frequently met with in the zone of the prostate gland, which is equally distant from the superficial capsule and from the urethra. Less often they are found in the central parts of the pros- tate related to the urethra, beneath the epithelium of the main excretory ducts. Neither are they missing in the most peripheral parts lying very near the capsule, where they also attach themselves to the wall of the terminal branches of the glands. Such infiltrates lying quite in the periphery occur rather rarely in the enlarged prostate gland and do^ not reach any large size. Aside from these infiltrates, there are found in the pros- tate gland, beneath the epithelium of the gland tubules, older groups of con.-tis. composed of spindle-shaped cells with elongated nuclei, which groups here and there begin to assume the characteristics of fibrous con.-tis. By such con.-tis. groups a gland tubule or a group of tubules is generally surrounded. The tubuli enclosed in such con.-tis. groups have sometimes a narrow lumen, even narrower than normal. Within the con.-tis. group itself there is generally no sign of muscular cells to be detected, or else we see only a very few, which are scattered exclusively in the peripheral parts of the groups. They are therefore either destroyed by atrophy or they are displaced outward by the connective-tissue abundantly formed in the sub- epithelial stroma. The extent of such a con.-tis. group is very varied. Some gland tubuli are hardly surrounded by a few rows of con.-tis. cells. In other cases, on the other hand, the latter form a compact mass composed of nu- merous cell layers, by which the intertubular septa ap- pear to be much thickened. This thickening of the glandular walls is also capable of adding to the enlarge- ment of the prostate gland, aside from the passive dilata- tion of the glandular acini ; but it is by no means so pro- nounced and extensive as to gain an essential impor- tance for the size of the prostate : it plays here, in my opinion, a relatively subordinate role. The connective-tissue groups described occur also in the wall of even highly dilated gland acini ; there is only a part of the glandular wall included by them, as they do not surround the glandular acini uniformly. The thick- ness of the connective-tissue layers is in such a place, at any rate, very variable ; for the greater part they consist, however, of at most two to three cell layers. These con.-tis. groups appear in the same way as the infiltrates, that is, in groups in the different parts of the prostate. They are more easily and more frequently to be found in the parts that are central with relation to the urethra than in the peripheral parts. In the latter they are, however, much more rare than the infiltrates. In some preparations only such con.-tis. groups will be found; in the majority of cases, on the other hand, there are at the same time in the vicinity of the same section, aside from the con.-tis. groups, numerous small-cell in- filtrates which often lie next to these con.-tis. groups. The extent of these changes, in the infiltrates as well as in the con.-tis. groups, is as different in the different pros- tate glands as the passive gland changes. In general there exists between the two kinds of changes a certain parallelism, though this is by no means constant. So we shall find in a prostate gland relatively little change in the stroma, while the passive gland dilatation has a great extent, and vice versa. Of frequent occurrence are the genuine cicatrices of the enlarged prostate glands, which are composed of nearly homogeneous, weakly-staining con.-tis. groups poor in nuclei. Within such cicatrices there is often found a very narrow lumen lined with epithelium. The form of the epithelial cells is here sometimes still normal, but oftenest they are flattened. It sometimes happens that the flattened cells fuse together into a homo- geneous, glass-like ring; sometimes this is no more visible, and then the origin of the very narrow lumen which lies loose m the cicatricial tissue is divined with difficulty. The meaning of such lumina is sometimes ex- plained by the presence of amyloid bodies. In the vicinity of such groups of cicatrices there occurs sometimes in- sulas of new con.-tis. composed of spindle-shaped cells, or even isle-like small-cell infiltrates. The former as well as the latter lie now beneath the epithelium of the atrophic glands, now somewhat further, with the cicatricial pro- io6 longations. These cicatricial groups are found, however, just as is the group of new con.-tis., mainly in the central portions of the prostate; and they occur isle-like in the neighbor- hood of the gland tubuli. It seems hardly necessary to demonstrate that the stroma changes described are noth- ing else but different stages of development of a pro- liferated con.-tis. and a result of a very chronic productive process. They appear, as a rule, in the form of sharply limited groups in the central parts of the prostate glands, and then mostly in the immediate or very near neighbor- hood of the gland tubuli, but usually just beneath the epi- thelial lining. Such periglandular changes are undoubt- edly capable of hindering the emptying of the glandular contents, provided that they localize themselves in the neighborhood of the greater excretory ducts of the pros- tate. The small-cell infiltrate surrounding a small ex- cretory duct is capable even alone of producing a certain narrowing of the excretory duct and with it an obstruc- tion to the outflow of the secretion from the peripheral, glandular parts. The dilatation of the latter will be the more quickly formed the more abundant the contents are, which especially happens in consequence of the patho- logical epithelial changes already described. In a like manner the narrowing of the excretory duct and the blocking of the secretion is produced by the ring-like cicatrices of the stroma, which, under certain conditions, may produce an absolute closure of the gland duct. But it may also come to a genuine obliteration of the gland duct if the epithelium of the surrounding glandular septa (which is infiltrated with small cells and thereby pushed apart) or if the epithelium of the excretory duct be des- quamated. (Table X, Fig. i8, 12, u). Then the sur- rounding, denuded, small-cell infiltrate fuses together and fills entirely the lumen of the already narrowed excretory duct. This will finally be entirely obliterated in conse- quence of the transformation of the infiltrate into cica- tricial tissue. One can comparatively often observe the most varied stages of obliteration. Even if it should happen that one should demonstrate that in some cases of "prostatic hj^pertrophy," contrary to my statements, an active neoplasmatic proliferation of the glandular tissue really takes places, the circumstance 107 that the smah-cell infiltrates sometimes break through the glandular wall and force themselves into the lumen of the gland at any rate would not be without importance. By the cells of such an infiltrate not only the individual parts of the gland ducts are separated from each other, but the individual epithelial cells are also pushed apart, which, in the opinion of Ribbert (Das Pathologische Wachstum der Gewebe. Bonn, 1896), might be a cause of the neoplas- matic proliferation and growth of the epithelium. The great importance of the changes of the stroma already described is not only to be learned from their kind and localization, but also, so to speak, to be directly observed from the following representation. In some enlarged prostate glands one sees wedge-shaped sections composed of dilated glandular acini and lying with their bases against the periphery of the prostate, and at the cen- trally-pointed apices we find an excretory duct, narrowed by a ring-shaped, small-cell infiltrate, or by a ring- formed cicatrix, or obliterated. The relation of the changes in the con. -tis. -like peri- glandular stroma to the passive dilatation of the pe- ripheral, glandular ramifications is not at all doubtful in such pictures. These sometimes include a very great part of the prostate gland ; the new infiltrate or the obliterating cicatrix lies not seldom at the outlet of the excretory duct in the urethra. Thus we learn to understand how it is possible that the primarv changes of the stroma, which are rela- tively unimportant and only slightlv extensive, should have such great consequences and should be capable of producing enlargement of the prostate gland. The patho- genetic importance of the changes in the stroma lies mainly in its localization. The dilatation of the glandular acini and the prostatic enlargement produced through this is only possible when the changes in the stroma have their seat in the vicinity of the excretorv ducts ; and it becomes more quickly and more extensively developed the nearer to the urethra the excretory ducts are when they become narrowed and obliterated. In some cases, especially in high-grade prostate en- largements, it seems impossible to demonstrate DI- RECTLY the causative relations between the changes in the stroma and those in the glands in one and the same 1.08. preparation. This is due to the fact that the gland-tubuli of the prostate run twisted, whereby the individual sec- tions never come to lie at the same level. This twisting is more pronounced in older individuals than in 3'ounger ones. For this reason the cut executed at the level of a certain gland duct is never able to divide it parallel with its axis throughout its whole length, but it opens the lumen of the duct, mostly at different places, in an oblique direction. For the same reason the histo- logical picture of the prostate gland does not correspond to the schematic representation of its structure. In gen- eral the excretory ducts of the prostate gland and their tubular ramifications run in the direction of the radii of a half-sphere, the center of which lies somewhere in the neighborhood of the colliculus seminalis. The surfaces of the section running horizontally (i. e., vertically tO' the axis of the urethra) divide those glandular systems throughout their whole extent whose ramifications lie at the level of the colliculus seminalis. The relation of stroma and glandular changes in one and the same prepa- ration can therefore only be demonstrated in sections made at the level of the colliculus seminalis. In preparations made from sections above and below this, this relation can only be demonstrated by serial sections, since the changes, as before mentioned, are extremely irregularly distributed, because now this now that part of the pros- tate gland is changed. If, therefore, the glandular system which branches posteriorly at the level of the colliculus seminalis accidentally remained normal, then only will the dififerent kinds of stroma changes be found, aside from the glandular dilatation, in one and the same prepara- tion ; but one does not succeed (aside fro-m the senile sec- tions) in demonstrating the direct relation of both types of the changes in one and the same preparation. In the greater and also in the milder grades of enlargement of the prostate there are still other processes at play by which the picture is obscured. It is the deposit of certain tissue sections due to the development of the previously men- tioned pseudo-adenomata, by which in certain cases it be- comes impossible to find the excretory ducts belonging to a group of dilated glands and to recognize where the cause of the glandular dilatation lies to which the stroma changes are respectively to be referred. This shows that 109 the explanation of the process of the prostate enlarge- ment becomes impossible without the investigation of the incipient stages of this process. In it, in my opinion, is to be sought the reason why the views of the different investigators differ so much with regard to the histo- genesis of the "hypertrophy" of the prostate; it could not be otherwise as long as one examined only the advanced cases in which the original, relatively simple conditions were long ago eradicated. I have already mentioned that the "pseudo-adenomata" are in the main to be referred to the passive glandular changes. The observation was made long ago that these growths consist mainly of glandular tissue. They are predominantly composed of the dilated and more or less cystically changed acini. The gland septa are at these places mostly very thin, and contain very few muscular elements. On the other hand, there occur in the neigh- borhood of the pseudo-adenomata places in which the glandular septa are thickened. The gland tubuli them- selves show no dilatation, and the stroma seems to be composed of closely packed, spindle-shaped con".-tis. cells. Such places were wrongly assumed to be a proof of a proliferation of the muscle elements of the stroma ; also the spindle-shaped con.-tis. cells were wronglv taken for muscle cells. Many years ago the same remark was made by an investigator of even the prominence of Rindfleisch, when he said : "Most authors take these spindle-cells for muscular, and therefore designate the new growth as fiibro-muscular. I have some hesitation in accepting this nomenclature ..." (311, p. 581). Possibly the view originated in thf^ fact that the tumors that can be enu- cleated are nothing but genuine m\omata ; by the usage of the faulty lenses employed in former times it was easy to overlook the narrow glandular lumina included within the soindle-cell groups. In the neighborhood of these spindle-cell groups I could never demonstrate a greater accumulation of muscle cells ; on the contrarv, such groups are always verv poor in muscular elements; sometimes these are entirely missing. Furthermore one can essih- convince oneself on serial sections that, aside from spindle-cell groups, there are also constantly present dilated acini in the pseudo-adenoma. The pseudo-adenomata observed in the so-caJled nodular form of the hypertrophy of the prostate develop, there- fore, from processes which do not qualitatively differ from the characteristic conditions of the so-called "dif- fuse" form of hypertrophy of the prostate. The macro- scopical dift'erence so striking between these two forms proves under the microscope to be mainly quantitative. I have mentioned before that the most extensive glandular dilatations are to be found in the vicinity of the pseudo- adenomata. Besides, the difference is further conditioned by a circumstance which gives the characeristic macro- scopic appearance to the pseudo-adenomata ; it is that the capsule which surrounds the pseudo-adenomata consists of concentric layers of muscle elements. By the examination of the early stages of the process one can demonstrate that this capsule is by no means a new-formed component part of the pseudo-adenomata, but is formed from already present none-proliferative ele- ments. The muscle bundles which surround the glandular rami- fications running in different directions are, according to the increasing glandular dilatation, gradually pushed out- side, together with the walls of the acini, and arrange themselves in concentric rows around the cystically dilated, empty spaces. If at the same time a larger group of glands which terminate in a common excretory duct suffers a dilatation, then gradually there will be formed at the periphery of the gland group, which assumes a more and more sphere-like form, a concentric muscle ring, which, together with the connective-tissue elements, becomes a kind of capsule. In consequence of its composition, the capsule thus formed is elastic and exerts a certain counter-pressure on the accumulated contents in the dilated acini ; for this reason the capsule retroacts on section and the contents swell out. But if the capsule remain intact during sec- tion of the prostate, then the corresponding part will be represented bv a well-limited, round and hard nodule (the capsule remaining tense). It is these "tumors"' which wrongly carrv the names of "adenoma" and "adenomvoma," respectivelv. To decide why sometimes (in the so-called diffuse form of hvpertrophy) no or only very few pseudo-adenomata are formed, one must make investigations especially directed to the subject. As a cause of the so-called diffuse form may, in my opinion, be taken a uniform, very ex- tensive but relatively weak dilatation of the gland, such as is formed in consequence of a very early narrowing of the main excretory duct, just at its outlet. If several pseudo-adenomata be formed in the same part of the prostate, then the remaining prostatic will be pushed apart by them, but the tissue lying between them will be compressed. In such cases a portion of the gland ducts still at the end absolutely unchanged, which lie next to the pseudo-adenomata, will be in layers, sometimes much so ; the glandular parts lying between two growing pseudo-adenomata will be compressed and narrowed ; and it may lead to a complete obliteration : in the latter case a gland dilatation in the peripheral ramification may be the consequence, or a new pseudo-adenoma may be formed. In this way a pseudo-adenoma may cause a further enlargement of the prostate gland. But the pseudo-adenomata may themselves be displaced, they may partly leave their point of origin and extend into the neighborhood of the urethra, i. e., at a place where normally very little glandular tissue is present. Why and how the pseudo-adenomata come to lie in the neighborhood of the urethra will be made plain by study- ing the normal prostate gland, which was especially fully investigated by Aschoff (2) (on complete serial section). Aschoff demonstrated that the main excretory ducts of the lateral lobes of the prostate describe a long curve in a direction from before backwards and inwards, i. e., from the symphysis to the wall of the rectum, before they tc- minate in both posterior angles of the urethra, which at this level is triangular. If the obstruction to the outflow of the glandular contents be situated at some place in the main excretory duct, then the gland group terminating in the main duct and posteriorly to the obstruction, generally a great part of the glandular acini of one of the lateral lobes, will suffer a dilatation and under certain circum- stances may be transformed into an encapsulated "pseudo- adenoma." The pseudo-adenoma enlarges them more and more, in that it grows uniformly in all directions, pushing apart the surrounding tissue. But finally there comes a time at which the further growth of the pseudo-edenoma meets with great resistance from without ; this is produced by the capsule of the prostate, which is thick and yields only slightly. The pseudo-adenoma will in its further growth be displaced in the direction of the lesser resistance, i. e., toward the lumen of the urethra, which is pushed in front. Little by little it fills the curve formed by the main excretory duct, and finally com- presses the main duct in its whole length, whereby the out- flow of the secretions becomes more and more hindered. I. Fig. 2, Fig. 3. Fig. I. Sche7natic Horizontal section through the principal excretory ducts of the normal prostate. Fig. 2. Growing Psendo-adeno7na. (y^ Directio7i of Growth) Fig. J. A large Pseudo-adenoma ( Displacement, Arching over of the wall of the urethra. On further growth the pseudo-adenoma causes addi- tional changes. If in the opposite lobe of the prostate (at the same level) analogous process occurs, then the pseudo-adenomata protruding into the lumen of the urethra must both flatten themselves against each other, and, by further enlargement, must draw the lumen length- wise in a sagittal direction ; but if the opposite lobe of the prostate be slightly or not at all changed, then a lateral deviation of the urethra at the level of the pseudo- adenoma will be the consequence. The tumors present in the vicinity of the orificium internum urethra were also formed in consequence of the dilatation of the glandular acini (which in the majority of cases are to be found normal at the place under consideration) as a result of the restriction or obliteration of the corresponding ex- cretory ducts. The relation of the stroma changes to the secondary glandular changes is more difficult to demonstrate a this place than in other parts of the prostate gland, except with the help of complete serial sections. As demon- strated by Aschoff (1. c), the excretory ducts of the gland groups imbedded in the submucosa above the col- liculus seminalis describe a long way beneath the mucou^ membrane of the orifice obliquely, downward, forward "3 and outward, before they terminate in one of the two posterior angles of the urethra. But ahhough for this reason the proof of the causative relation of the stroma and glandular changes does not always succeed here, still both will be found side by side in one and the same preparation. The stroma changes are most easily to be detected when they appear in the form of periglandular subepithelial infiltrates ; the glandular changes have also here all the characteristics as described before. It still remains to discuss the behavior of the stroma muscle tissue of the enlarged prostate gland. In this re- gard I could demonstrate absolutely only two conditions: the absence of muscle cells in the vicinity of the con.-tis. groups scattered in the stroma and the transformation of the muscle bundles that were outwardly displaced into a kind of concentric capsule enveloping the pseudo-ade- noma. Both these conditions seem to indicate that the muscle elements play an entirely passive role in the en- largement of the prostate. The function of the prostate is in intimate relation to the sexual function ; the muscle tissue of the stroma seems to take an important part in this function. To it falls the work of propelling the contents of the gland acini outward. If the outflow of the secretion meets with any obstruction, the muscle tissue of the corresponding part of the prostate must then suffer a working hypertrophy, provided that the sexual func- tions and with them the specific function of the prostate be retained within physiological limits. It is to be re- gretted that no method is at our disposal by which we might detect if and in what way such a working hyper- trophy is really formed here ; however, I have the impres- sion that in prostate glands that are much enlarged the peripheral fibromuscular capsule, which envelops the whole organ, is much thicker than in the normal ones. The view is quite common that the individuals afflicted with "hypertrophy" of the prostate are too old to expect in them any function of the already atrophic sexual or- g"ans. In particular the adherents of castration as the treatment for prostate hypertrophy seek justification for the mutilating operation in this view. If this were the ease, it were then, "a. priori," to be presumed that an active hypertrophy. of the muscle tissue of the prostate is not at all conceivable in an enlargement of the prostate. Such a 114 conclusion would be just as wrong as the premises which serve as its support. In this regard it may suffice to refer to the results cited by Hoffmann (Lehrb. der gerichtl. Medizin, 6 aufl., 1893, p. 59) of the investigations made by Duplay (Arch. gen. de Med., Decembre, 1852) and Dien (Journ. de I'anatomie et de la physiologic. 1867, p. 449). Duplay found among 51 corpses of old people spermatozoa in 37, occurring in 23 of these in consider- able amounts. Dien, who examined 105 corpses of old men, demonstrated the presence of spermatozoa : Between the 64th and the 70th Year of life 14 cases in 64.3 percent 70 " " 80 " " " 4Q " ■' 44. S " " " 80 " " 90 " " " 38 " " 26.3 " 9° " " 97 " " " 4 " " not once From this investig^.tion it can be seen that atrophy of the sexual organs and the cessation of the function in old men neither occurs so frequently nor appears so early as is generally assumed. The possibility of the active hyper- trophy of the muscle tissue of the prostate must not, therefore, "a priori," be cast aside. There even exists in the literature a hypothesis verified, however, by no one, that the "hypertrophy" of the prostate gland depends upon an active hypertrophy of the muscle tissue of the prostate. Stilling- (120), during his investigations of the causes of the formation and enlargement of the amyloid bodies, conceived the idea that they stand in an intimate relation to the stagnation of the elements which serve to build up the amyloid bodies in the lumen of the prostate gland, whether it be in consequence of a hyaline degeneration, or whether it he in consequence of the narrozving or ohlitera^ tion of the excretory ducts (1. c. p. 19). These changes which produce a narrowing or an obliteration of the ex- cretory ducts were regarded by Stilling as a process re- lated to the "Myxangoitis hyalinosa" of Recklinghausen (Virch., Arch.. Bd. 84. p. 479) ; imder certain conditions, according to Stilling, in the obstruction produced by it to the outflow of the prostate secretion is to be sought the cause of an active hypertrophy of the muscle tissue of the prostate, followed by an enlargement of the entire prostate gland (1. c. p. 20-21). The latter hypothesis of Stilling is on no point verified by my investigations. On the con- trary, from the description and the accompanying illus- trations, it is unquestionably to be seen that the changes observed by Stilling (Myxangoitis hyalinosa) are entirely identical with the periglandular cicatricial groups de- scribed by me. Neither were the stroma changes de- scribed by me entirely overlooked by some other investi- gators, but still no importance was attributed to them. Aside from the views already mentioned (p. iii) of Rindfleisch (311), "round-cell accumulations" find only a superficial mention in the works of Casper (16, p. 157), Jores (63, p. 241) and Motz (89b). This is all I could find about it in the literature. During my studies I also examined a series of twenty- two apparently normal prostate glands, of normal weight, normal form and normal dimensions, which were taken either from old individuals attacked by an extensive atheromatosis or from young men : in several of these cases I could not demonstrate any pathological changes. There were twelve in which the prostate gland proved to be entirely normal, and two in which, aside from a subepithelial, round-cell infiltrate distributed patch- like in the urethra no other changes were found in the vicinity of the prostate gland ; that is, in 14 cases all told. Aside from these I met with a few examples which did not exceed the upper normal limit, but the structure of which nevertheless showed pathological changes. Case No. 22 45 Years old Weight of the Prostate 17.5 g 1' " ,, c '< '< n " " " jgo n " " " 15.5 " " " 16.8 " " " 19.1 " " 17.5 2 " 3 " 4 " ' 31 57 " ' 36 70 " ' 39 60 " ' 5 6 ' 4° 70 " ' 47 56 " 7 8 " ' 29 75 " 15-4 18.0 One served as a type of the first stage of the "hypertrophy" of the prostate. In the remaining cases an entirely analogous condition might be demonstrated partly, as, for instance, one case, in which one likewise en- countered a wedge-shaped part of the gland : in the vicin- ity of this part the empty spaces were moderately dilated and, in the apex, pointed toward the centre of the pros- tate, a round-cell infiltrate was visible surrounding the excretory duct. In three other cases the changes were still more insignificant, in that they consisted en- tirely of a few moderately small round-cell infiltrates, which were situated mainly in the neighborhood of the ramifications of the peripheral gland. Therefore it cannot be decided whether in these three cases a 116 high-grade glandular dilatation could have been formed later on, in consequence of a damming back of the secre- tion. The possibility of such an outcome could not be passed over unnoticed, at least in young individuals, as there already existed in the prostate gland a related pathogenetic irritation, and a further spreading is quite conceivable. Of the three remaining cases, in one there were to be found changes which, although insignificant, are yet especially interesting. In the kimen of the dilated glandular acini (of which there were only a few) one encountered numerous leucocytes ; the contents of one of the gland acini had even the characteristics of a genuine suppurative exudate. Finally, in the two cases high-grade changes were encountered ; in both a few small pseudo-adenomata were formed. Although they were still in so early a stage of development that they could not influence the dimensions of the pros- tate gland, yet these two cases, as well as the other six, must be regarded as pathological. It has been already demonstrated, however, by Thompson that sometimes limited, easily enucleated nodules were found in prostate glands not at all enlarged ; similar cases were also ob- served by Iversen ( [64] schematic review of cases, p. 18, a. s. f.) The cases last mentioned seem to prove that the spe- cific changes for the "hypertrophy" of the prostate may persist for a long time in their low grades before they become visible to the naked eye. This also conforms to the view of some investigators who place the beginning of the "hypertrophy" of the prostate gland at a much earlier time than is generally assumed. Among the individuals in whom I was able to demonstrate the histological changes in a prostate gland that was not enlarged were a few who had hardly passed the forty-fifth year of life; one of them was even not quite forty years old. By further exact investigation of prostate glands that are not enlarged the proof will without doubt be obtained that the cases in which the pathological changes already exist, although they are not discerned with the naked eye, are much more frequent than would appear from the statistical data of Thomson and Iverson. One will in all probability find that the beginning of the changes is to 117 be placed at a much earlier time than would appear from my investigation. Among the prostate glands examined by me there were nine (from individuals well developed sexually) which weighed less than normal : among these three weighed I4-I4.6g., the remaining hardly i2-i3g. In four of these small prostate glands I encountered changes which were entirely in conformity with the prevailing views of the simple atrophy of the prostate. No. 20 Age 65 Years. Weight of the Prostate 12.0 g " 21 " 75 " " " ■• " 12.5 " 26 " 42 " " " " " 13.2 " " 33 " 62 " " " " " 12.0 " The changes here observed consisted exclusively in a diminution of the glandular ramifications ( decrease of the gland tubuli) and in the presence of amyloid bodies. The gland tubuli still preserved were nowhere plainly dilated ; in the stroma there were no changes of any importance. The histological picture corresponds in the main to that of an atrophy of the prostate gland, which is experi- mentally produced in animals by castration ; and this seems to indicate that under ordinary circumstances trophy attacks first the gland tubuli. But the matter was dififerent in the remaining five cases. I was much surprised when it appeared that in No. 23 Age 57 Years, Weight of the Prostate 14.0 g " 30 40 •' '■ " " •■ 12.4 " " 32 " 70 " " " " " 12.5 " " 35 " 38 '•' 72 " 62 " " " " " 14.6 " " " " " 14.2 " these five cases the changes in the individual parts of the structure were exactly like those observed in the "hyper- trophy" of the prostate. Here, as there, at least in some parts of the gland, a pathological contents was present composed of changed, desquamated epithelium, sometimes with an addition of leucocytes. Likewise we also en- counter, at least here and there, dilated glandular acini or small pseudo-adenomata, although in a mild degree. Above all, we encountered similar stroma changes, which appear sometimes in the form of small-cell infiltrates, sometimes as spindle-cell con.-tis. groups ; but usually in the form of numerous patchy cicatrices, which we have learned to know in the enlarged prostate ghnd. In the cicatricial groups were sometimes found remains of gland tumuli with a few epithelial cells or narrowed lumina de- prived of their epithelium, or apparently loosely deposited 118 amyloid bodies; but these cicatrices had, for the greater part, a uniform structure. At first I was not able to find a sufficient explanation for such pictures. The supposition ready to hand^ that this is the remains of the processes of the specific changes for the enlargement of the prostate after a spontaneous reversion, is, however, hardly tenable ; because nobody ever observed, to my knowledge, that a "hypertrophy" of the prostate spontaneously reversed ; yes, even more, was able to change to an opposite condition, namelv, atrophy. Only after an exact consideration of all the histological facts was I convinced that the presence of these changes in the individual structures of the stroma stands in no opposition to the diminution of the WHOLE prostate gland ; yes, further, they may, on the contrary, be useful for the elucidation of hypertrophv of the prostate, al- though these changes are apparently inseparably con- nected with "hypertrophy." In other words, it is proved that the localisation of the changes and their distribution between the two main component parts of the prostate, the glandular tissue and the stroma, is different in cases of atrophy of the prostate from the "hypertrophy," and that the main difference lies in the location of the lesions. One encounters here mainly the cicatricial tissue, to the shrinkage of which the diminution of the whole of the prostate gland is to be referred : these cicatri- cial groups are very numerous. The shrinkage is a consequence of the changes in the stroma, which have left unaffected the vicinity of the main excretory ducts and have mainly extended to the neig-h'^orhood of the terminal ramifications of the gland tubuli. The stroma changes have here, as everywhere else where they are formed, the narrowing, the obliteration and the atrophy of the glandular acini as a consequence. But because all these changes mainly, or perhaps exclusively, include the blind ends of the glandular systems, they were not able to hinder the outflow of the contents from the still pre- served central parts of the gland tubuli. The dilated gland acini are therefore found onlv in a few places, where a scattered con.-tis. group had sur- rounded accidentally one of the larger excretorv ducts. A gland dilatation which included onlv a verv small part of the prostate was not able to produce a visible enlarge- 119 merit of the whole organ. To this it is due that an in- significant increase m the volume of individual glandular systems could be compensated by the atrophic changes in other parts of the prostate, and finally that these could more tnan counterbalance it. By this it is made more clear why in some prostate glands quite extensive "hypertrophic" changes, i. e., the relatively great dilatation of several glandular acini and a relatively abundant formation of con.-tis. masses, could be present in the stroma without the weight and size of the whole prostate gland exceeding the normal limits. The so-called hypertrophy of the prostate gland, as well as certain forms of prostatic atrophy which are histo- genetically related to it, have a common origin. Both these processes differentiate themselves from each other not through the quality of the changes of their structures, but onlv through the different extension, intensity, and, above all, through the different distribution and localiza- tion of otherwise analogous changes. The common starting-point of the hypertrophy of the prostate gland and certain forms of atrophy must be sought in the productive connective-tissue processes which have their seat in the stroma of the organ ; and, according to the stages of their development, they may show the different forms of organization of the connective-tissue which occur constantly multiple and mainly close by the glandular epithelium. If the productive stroma changes localize themselves in the central parts of the prostate in the vicinity of the main excretory duct, then it may be possible that they produce a narrowing or obliteration of the lumen of this duct, which may cause an accumulation of the secretion and an enlargement of the peripheral lobules. The enlargement of the lobules is produced more quickly and is of a higher degree according as the excretory ducts are more nu- merous and are nearer to the obstacle ; furthermore, the greater the extent and intensity of the endoglandular pathological process, which is adjacent and is always pres- ent at the same time, the greater is the enlargement. These processes consist of a very active proliferation, besides a desquamation and degeneration of the epithelium which characterize it as a catarrhal process ; sometimes there is in addition a suppurative process which causes an addition of leucocytes to the excretion of the gland. The enlargement of the prostate gland is nearly always to be referred to the enlargement of the acini; the relatively large masses of new-formed connective-tissue play a sub- ordinate part in the pathological growth of the prostate gland. The active role of the prostatic muscle in forms of hypertrophy of the prostate gland, without formation of genume myomata— and that is the condition in the ma- jority of cases — is not proved and is very doubtful. If the connective-tissue changes in the stroma occupy mamly the peripheral part, and if they localize themselves m the neighborhood of the terminal branches of the tubules of the acini ; then, by the adhesion and atrophy of the compressed tubules and by a shrinkage of the connec- tive-tissue in the stroma— a prostatic atrophy— there will be produced a diminution of the whole organ. This dimi- nution will be the quicker and more intense if no endo- glandular pathological process, which increases the con- tents of the acini, be present. Besides there are also simple atrophies of the prostate gland, which may be referred to a process of involution within the glandular tissue. If the pathological changes take up about evenlv both main divisions of the prostatic tissue, and if they are situated partly in the periphery antd partly in the central portion of the prostate gland, then it may be possible that the different localized processes may compensate each other and may retain the normal weight of the prostate ; or if one of these two processes gains the upper hand, the prostate gland as a whole will become smaller or larger, as the case may be. ^^ The intimate histogenetic relationship of the so-called hypertrophy" of the prostate gland and certains forms of prostatic atrophy tends to show that between these two processes there may exist an etiological intimate relation- ship. CHAPTER IX. ETIOLOGY OF THE SO=CALLED "HYPER= TROPHY OF THE PROSTATE" AND CERTAIN FORnS OF ATROPHY OF THE PROSTATE Since it was demonstrated in the last chapter that the hypertrophy of the prostate in the majority of cases has nothing to do with a new formation, in a hmited sense of the words, it does not seem necessary to recapitulate the views in regard to it as held by the different investigators (Cohnheim [29a], Socin [119], -Birch-Hirschfeld [297], Iversen [64], Maas [84], Kleb [305], Albert [i], Thomp- son [133], Jores [68], Griffith, and many others). The statement that the hypertrophy of the prostate is to be regarded as a senile involution of the prostate gland in a physiological sense is mainly advocated by the French authors (Cornil and Rauvier [289], Regnault [114], Launois [72], Guyon [406], Miguel [87], the last three with regard to the arterio-athernoma, and further Stock- ton-Hough [125] and many others). One would think that such views were long ago discarded in consideration of the statistics of Dittel (23) and Thompson (132) and the daily experiences. As the "hypertrophy" of the pros- tate is not constantly to be observed in old age, and, on the other hand, is sometimes demonstrated in relatively young individuals (40-45 years), it can by no means pass for a physiological, senile phenomenon. Nevertheless, this view, although in a quite modified form, begins to take hold anew. For instance, it was demonstrated by the clinical observations and anatomical investigations of Launois {/t,) and Englisch (374) that the development and function of the prostate stand in a certain relation to the testicle. The experiments on animals executed by Griffiths (55, 386), Ramm (comp. 447-478}, White (comp. 521-6), Leyuen (81), Pavone (after 81), Latis (19), Lesine (71a), Przewalski (107), Casper (16a), Sackuhr (after i6a) and Floderus (35a) furnished the proof that cas- tration nearly constantly, and resection of the vas deferens in a fraction of the cases, have an atrophy of the normal prostate as a consecjuence. Finally, it was proved by clinical observations that in a part of the cases the hyper- trophy of the prostate could be decreased in man by cas- tration. It is proved by all these facts that the period of development of the prostate is parallel, up to a certain time, with that of the testicle, and is dependent on it ; and that the function of the prostate may be brought to a stop by castration, but only if the prostate gland was pre- viously unchanged (experiments, on animals). To this conclusion all cautious investigators come without de- ducing any further consequence. But not all are so cau- tious. Some authors believe, namely, that they are justi- fied by the facts cited in making the statement that the testicles alone are capable of producing the "hyper- trophy" of the prostate gland (Moullin Mansell [93, 436], Latis [79], Launois [73], and with the addition of the influences of sexual excess, Lydston [80]).. At present MacEwan (89c, p. 769) refers the prostate hypertrophy to the atrophy of the testicles apparently oc- curring in old age and to the insufficiency resulting from it of an "internal secretion" of the testicle, which is sup- posed to regulate the period of development and function of the prostate. In general, the etiology of the "hyper- trophy" of the prostate is also referred by this investigator to senile influences, and between these two ideas a con- necting link is introduced, namely, the senile atrophy of the testicle. Through another still unfinished work I might dem- onstrate that the development of the prostate really runs parallel with that of the testicle, and that the atrophy of the testicle really causes changes in the prostate which later by no means take the form of a paradoxical phe- nomenon, i. e., the enlargement of the prostate, but take the -form cif the simj^le atrophy already described. 123 The enlargement of the prostate in old people sometimes, but by no means constantly encountered, is, as I shall have the opportunity to demonstrate in another way, an entirely accidental morbid complication, which covers only the normal period of development and the simple atrophy, re- spectively, of the sexual organs. But before I give the results of my investigations on this point, the facts already known and demonstrated may be of use for the elucida- tion of the question under consideration. One can, of course, overlook the statement that the human prostate is in a state of continuous growth up to the highest age (Regnault [114], Launois [73]), as this statement is in plain opposition to the fact that the pros- tate gland shows no enlargement in the majority of old people. The investigation based on the statistics taken from living persons by Englisch (374) cannot, for obvious rea- sons, be regarded as exact. By the observation that above a certain age there is a prostate enlargement in every second or third individual, no proof is furnished that the greater "development" of the prostate gland, in proportion to the size of the testicle, is physiological. The adherents of the theory according to which the "hypertrophy" of the prostate is caused by a weakening and cessation, respectively, of the function of the testicle, contradict themselves with their own views. First, they give as proof of an intimate relation between the period of development of 'the prostate and the testicles, the fact that castration causes an atrophy of the prostate by elimi- nating the sexual function, and then, again, they main- tain that the hypertrophy of the prostate is a consequence of the elimination of the sexual function. How can the adherents of this theory explain the observation of Moses (444), who demonstrated in a sixty-eight-year-old man a "hypertrophv'' of the prostate occurring several years after a double castration ? Where, in this case, is the cause of the "hypertrophy" to be sought, when the cessa- tion of the sexual function should have caused an atrophy already several years before? This case does not seem at all mysterious if we look back to our previously repre- sented histological investigation. The characteristic changes in the tissues of the prostate have developed in- 124 dependently of the presence or absence of the testicles. In the discussion of the importance of the cessation of the functions and atrophy of the testicles for the origin of the hypertrophy of the prostate Launois (73) cites the works of Monod and Serillon (88, 89) and Arthaud (3), who dealt with the senile changes of the testicles. But he does not mention the work of Desnos (25), who dem- onstrated that among one hundred and twenty old people living spermatozoa were found in one-half of the cases. If the spermatozoa were missing in one of the seminal vesicles, then this was not dependent upon an atrophy of the testicle, but upon an obliteration of the seminal ducts. The atrophy of the testicle itself is not produced, how- ever, by the influence of age, but probably by other very varied causes. These investigations coincide with the older investigations already mentioned (cit. after Hoff- mann . See p. 121 in MS.). By them it is at any rate proved that the atrophy of the testicles and the cessa- tion of the sexual function is much rarer than the "hyper- trophy" of the prostate in old people, and, therefore, can- not be regarded as a cause for the enlargement of the prostate. The fact was also put forth that the prostate gland in animals normally enlarges continually up to the highest_ age (Regnault [114)]. Disregarding the fact that it is not allowable to transfer to man the results of investigations made on animals, it must be considered that the obsevations were entirely based upon investiga- tions made on dogs. This species of animals seems to occupy an exceptional place with regard to the prostate, as castration, which constantly produces pronounced atrophy of the prostate in other animals (rabbits), gave very varied and sometimes even directly contradicting re- sults in dogs. I have already mentioned (p. 58 in MS.) the fact demonstrated by Casper (i6a), that the atrophy of the prostate after castration is less pronounced in dogs than in rabbits. Leguen (81) did not succeed in pro- ducing an atrophy of the prostate gland by a double vasectomy in five out of six dogs operated upon. A very old dog, killed five months after the operation, had after as well as before the operation a very large prostate gland. This failure seems not to be dependent on the kind of operation, as in the sixth dog a pronounced atrophy of the prostate occurred several days after the operation. "5 It seems from these experiments that dogs really occupy a special place among the mammals. Agreeing with this, it is stated in several veterinary manuals (Bruckmiiller [315], Forster [317], Koch [318], Konhaiiser [319], Moller [320], Roll [321], Stockfleth [322]) that inflam- mation of the prostate and hypertrophy of the prostate, similar in several respects to the human, are among all the domestic animals observed only in dogs. In the other domestic animals the "hypertrophy" of the prostate has not been generally observed, and the prostate enlarge- ments — by the way, very rare — were to be referred to genuine, mostly malignant, tumors. "Hypertrophy" of the prostate gland seems, then, to be a specific disease found solely in man and in dogs ; where- fore the experiments made on dogs must give just as am- biguous results as the experiences gained from man. But, at any rate, these results were not adapted to prove that the prostate of animals continues to enlarge up to the time of death ; because the large prostate glands found in old dogs were only pathologically '"hypertrophied," and the physiological enlargement of the prostate in advanced age of other species of animal is still not proved by any one. Therefore, the assertion that the "hypertrophy" of the prostate is produced by the cessation of the sexual function due to an atrophy of the testicles must be aban- doned. Finally, the opinion advocated in the literature here and there may be cited that inflammatory processes play a causative role in the formation of the "hypertrophy" of the prostate. Such influences were formerly very fre- quently cited among the causes of the "hypertrophy of the prostate" ; but as later on the chronic inflammation of the prostate (prostatitis chronica) was separated from the "hypertrophy" of the prostate, from a clinical stand- point it was almost generally accepted that the latter never stands in a causative relation with the passed in- flammatory processes. This exclusive standpoint is very energetically taken and defended by all clinicians, al- though it really is no longer attacked by any one. Once in a while we encounter in some manual or in a casuistic work a cursorv remark that, besides other influences, pcv- haps inflammatory factors also may sometimes play a role in the etiology of "hypertrophy of the prostate." The 126 objection advanced from a clinical standpoint against the causative relation of the "hypertrophy of the prostate" to inflammatory processes can be summed up in the follow- ing sentences : ( i ) The anamnestic data which would point to passed inflammatory processes are missing in the patients suffering from "hypertrophy" of the prostate. No great importance should, in my opinion, be given to this circumstance, as the anamnestic data may be incom- plete or inexact ; because, as I shall demonstrate later, the inflammatory processes of the sexual organs may run a latent course. (2) The clinical course of the chronic prostatitis is entirely different from that of the hyper- trophy of the prostate gland. How little weight can be laid upon such an objection is shown by the countless diseases of other organs, generally known, which may have a common etiology and an entirely different clinical picture. As an example we may cite a valvular lesion, caused by articular rheumatism, and first noticed several years later. I believe that a causative relation between these two processes will hardly be doubted by any one. Or has, for example, syphilis of the central nervous sys- tem, any similarity to the common manifestations of this infection? (3) The third objection rests upon a conclu- sion from analogy : "Other experiences also show that repeated acute or chronic inflammatory processes of glandular tissue, after they have run their course, will lead to an atrophy sooner than to a hyperplastic tumor formation" (Socin [119, p. 51])- This view, which is in the main correct, can find no special application with re- gard to the prostate gland : first, because, as has been dem- onstrated in this work, the "hypertrophy" of the pros- tate must not be regarded as a "hyperplastic tumor for- mation," and, secondly, because the prostate is undoubt- edly a gland, but a gland the structure of which is not comparable to any others found in the organism. The contraction of the cicatricial tissue may here, as anywhere else, have very different consequences, accord- ing to the extent and localization of the cicatrices. Here may be mentioned the cicatricial strictures of the pylorus after a round ulcer, which are followed by a dilatation and compensating hypertrophy; while a cicatrix at any other place of the stomach is not followed by similar con- ditions. 127 To my knowledge, only Casper tried to refute, on the basis of anatomical investigations, the relation of the "hypertrophy" of the prostate (that, namely, which he described as "Hypertrophia prostat?e fibromyomatosa vel fibroma diffusum prostatse") to inflammatory processes. He demonstrated, referring to Socin (119), that the "Prostatitis chronica," which in general has been very little investigated, is a chronic catarrh of the mucous mem- brane, extending from the mucous membrane of the ure- thra toward the interior of the prostate gland ; and that the stroma takes a part in severe cases only of inflamma- tory processes. The "prostatis chronica" might thus be regarded as a "parenchymatous" process, while the "fibroma dififusum prostatae" should be regarded as a process mainly "interstitial." Regardingthe possibility that the "parenchymatous" process early involves the "inter- stitial" tissues and the view advocated by many investi- gators that the "hypertrophy" takes its origin in the parenchyma, it is admitted by Casper himself : "These ob- jections can hardly be refuted, as the pathological anatomy belongs really to the most poorly investigated part of the pathology, and too little is known on this point." (1. c. p. 156). A greater importance might be laid to Casper's view on account of the fact that only exceptionally can an enlarge- ment of the prostate, which, however, again disappears, be caused by chronic inflammatory processes. "On the con- trary, as a product of the round-cell accumulation, which is clearly an inflammation, they have everywhere, as also here, a tendency to contraction on account of their trans- formation into cicatricial tissue. In the hypertrophy also the latter is not missing, but it is a continually advancing, ever new, tissue-producing process, from which finally an enlargement of the prostate results." (1. c. p. 157). These doubts raised by Casper are removed by the pe- culiar structure of the prostate gland and the peculiar de- velopment of its changes, which have already been treated in the previous chapter. There at once arises the objection that such an extensive connective-tissue proliferation as is sometimes to be ob- served in the enlarged prostate gland can never be pro- duced by an inflammatory irritation. Leaving aside the abundant connective-tissue proliferations produced by 128 certain chronically acting infectious irritations (for in- stance, tuberculosis), and which often appear directly to one as tumors, we may point to the quantities of con- nective-tissue, sometimes very great, which are formed during the course of a chronic inflammation, or are the re- sults of some acute inflammation. The fibrous thickening of the pleura, which sometimes gives rise to the formation of a connective-tissue layer as much as i cu. thick; the so-called organization of the para and peris-metritic ex- udates, which may lead to the formation of compact con- nective-tissue masses, and the post-inflammatory indura- tion of some organs, which sometimes lead not to a shrink- age, but on the contrary, to an enlargement of the organs — these examples may suffice to show that, aside from the so-called infectious granulation tumors, there exist still other post-inflammatory processes, which occur together with a connective-tissue production and enlargement of the alTected organ. The changes which I observed in the "hypertrophy ing" prostate, if one wishes to make this distinction, are to be regarded as parenchymatous as well as interstitial. The changes in the glandular epithelium, together with the endoglandular suppurative processes which are some- times encountered, may in this sense be designated as parenchymatous, either catarrhal or catarrhal-suppura- tive inflammation ; and the changes in the stroma may be regarded as a chronic interstitial inflammation. The objection that the inflammatory processes which I observed in the enlarged prostate glands do not stand in an intimate causative relation to the "hypertrophy," but are an accidental complication, due to inflammation of the neisfhboringf orsrans, as for instance the bladder, I can easily dispute, as I selected for my investigation, with a few exceptions, only such cases as were free from such complications of the urinary duct. Finally the objection might still be possible that the changes observed by my- self are a process "sui generis ;'' that even if they have the characteristics of inflammatorv processes, still they are different from the chronic inflammation of the prostate which occur during middle life. Between these two in- flammatorv processes there is really a difference. Just this difference explains to us the relatively late formation of the "hypertrophy" and its slow course. The difference, 129 however, is not a qualitative, but entirely a quantitative one. The inflammatory processes producing the prostate enlargement show a ver}' chronic, extremely insidious course ; and they possess a relatively insignificant extent and intensity. For this reason the whole process develops only step by step, and it lasts many years before it pro- duces the symptoms which may be recognized by the clinicial. Since the publication of the excellent and ex- haustive investigations of Fenger (148-155), the pre- viously dark field of the pathological histology of chronic prostatitis (aside from its cause), has now become more clear. From the detailed description of the cases ex- amined by Fenger, and, furthermore, from the accom- panying illustration, it appears tJ.at the changes found by him produced by the chronic inflammation of the pros- tate are entirely identical zvith those zvhich I found in the enlarged prostate gland. Here, as there, occurs a ca- tarrh, or a suppurating glandular inflammation ; here, as there, subepithelial, peri-glandular round-cell infiltrations are to be observed ; finally, in both instances, the process appears in groups and irregularly, in that it appears now only in the gland tubuli, now only in the stroma, and finally in both in one and the same place. Between Fen- ger's observation and mine there exists a double differ- ence : First, in regard to the extent and intensity of the inflammatory processes ; and, secondly, in regard to their relative frequency. The second difference depends, how- ever, on the first. The changes described by Fenger have a greater extent than those of the prostate hypertrophy. Fenger, for instance, encountered in his specimens round- cell infiltrations which include the whole extent of the vera-montanum. In the stroma of the prostate the in- filtrates were more numerous, of a larger size, and densely crowded. In my specimens, on the other hand, one could hardly encounter two or three small, loosely packed in- filtrates in a section ; sometimes none were to be found, if the specimen came from an unchanged part of the prostate gland. In certain prostate glands (especially those only slightly enlarged and those apparently normal, i. e., not enlarged), I was forced to explore whole serial sections to detect the changes which had been overlooked in a superficial in- vestigation. In Fenger 's specimens there was often pres- 130 ent in the glandular lumina a pure suppurative contents of a contents with numerous leucocytes intermingled, which seem to indicate that in his cases the cause of the process was quite acute, that it at any rate ran a more intense course than in my cases, in which the suppurative contents, intermingling with the glandular, were to be found only very rarely, and in small cjuantities, and that a pure sup- purative exudate was the exception. The importance of these dififerences regarding the extent and intensity of both inflammatory processes is obvious ; by it is explained the difference between the clinical symptoms of both dis- ease processes, especially the relatively late occurrence of the prostate hypertrophy. But they are also capable of explaining ano^ther circumstance ; they seem to indicate, namely, that the hypertrophy of the prostate gland must by no means always be a consequence of such inflamma- tory processes as give clinical symptoms, and that they are not always preceded by anamnestic data zvhich zvoitld prove to the physician the diagnosis of prostatitis. On the contrary, the insignificant extent and intensity of the process which leads only after many years of existence to "hypertrophy" is so characteristic for the anatomical pic- ture of the prostate hypertrophy, that we may conclude the absence of any subjective symptoms at the beginning of the disease. But as well the subjective symptoms may, in consequence of insignificant changes, be so unimportant that they escape the attention of the physician, even when a special examination is made for them. The ''prostate hypertrophy" is probably, as a rule, a consequence of inflammatory processes zvhich are latent for years and produce no symptoms or very insignificant ones. In regard to the chronic prostatitis, "sensu stricto," it is generally known that the inflammatory irritation has its point of origin in the urinary ducts, especially in the urethra. In regard to the starting-point of the inflamma- tory irritation producing hypertrophy of the prostate, it might perhaps be sought anywhere else — for instance, in the blood vessels. However, the histological changes ob- served by me contradict this hypothesis. The inflamma- tory processes following the course of the blood vessels settle first of all, according to experiences, in the imme- diate neighborhood of the vessels. But in my cases there was never a sign of inflammatory changes to be detected 131 in the neighborhood of the vessels. Against this, the locaHzation of these changes in the glands themselves (endoglandular catarrh and suppuration) seems to argue that the inflammatory process has extended along the glandular ducts from the urethra toward the periphery of the prostate, with which the constant localization of the stroma changes just beneath the epithelium in complete harmony. Aside from this, I found in the ma- jority of cases evident signs of inflammatory changes in the urethra in the form of subepithelial round-cell infil- tration, which was situated either in the vicinity of the veramontamun or at other places of the mucous mem- brane of the prostatic urethra. That such infiltrates were not found aways and everywhere in the urethra is not strange. I have frequently mentioned that a verv characteristic symptom of the inflammatory processes observed by me is that they are very irregular and occur onlv in groups. Besides, the later stages of the process, i. e., the cicatrices, are here easily overlooked because they are not surrounded by muscle tissue in the neighborhood of the mucous mem- brane of the urethra, with which muscle tissue they con- trast very clearly in the prostate, and for this reason they are more easily recognizable. If we now question ourselves of what kind the inflam- matory process assumed by us is, it is easy to take it for a gonorrheal. But I must openly confess that direct proofs of this are not at my disposal. Such proofs must, first of all, be sought in anamnistic data. Among several histories of typical "prostatica"^ I found only a few such data which pointed with a reason- able certainty to a passed gonorrhea. In two patients, for instance, a cicatricial stricture w^as demonstrated : in the posterior of the urethra in another was found a diffuse narrowing of the anterior part of the urethra, etc. In a similar situation were also the other investi- g-ators (for inst.. Stilling [122, p. 21]). Casper and Jores do not mention at all the course of the disease. Only in the work of Bohdanowicz (7) a few cases of passed gonorrheal processes are specially ^The consent to examine the histories I received from the late Prof. Obalinsky, and I wish to express my gratitude to Dr. Rutkowskl for his assistance. 133 pointed out : in other works they are entirely absent ; to which, with regard to the previous discussion (p. 150 in MS.), however, not too much importance is to be given. According to Neisser and Putzler (120) PezzoH (173) and GrosgHk (159), it is proved nowadays that the gonorrheal may be located primarily in the prostate gland without including other parts of the genito-urinary ap- paratus, and that from the very first it may run a chronic course. On the other hand, it is to be seen from the in- vestigations of Eraud (119) and Guiard (156) that the gonorrhea of the posterior part of the urethra may some- times remain entirely latent. There are to-day numerous observations, as those of Tengy, Ghon and Schlagen- haufifer ( 147), which prove that in the prostate gland an inflammation may develop which is clinically hardly capable of diagnosis. Through these facts, the views ad- vocated by me and deduced only from histological inves- tigation find verification. On the other hand, it is proved thereby that a negative anamnesis by no means argues against the gonorrheal origin of the disease. A further immediate proof for the gonorrheal nature of the "hyper- trophy" of the prostate and the inflammatory processes respectively producing it is to be sought in the presence of gonococci in the changed parts of the prostatic tissue. But in this regard my investigations have furnished no results. T was not able to demonstrate gonococci in the parts of the prostate gland in cases examined especially for it ; consequently an important factor is missing to prove definitely the relation of a passed gonorrhea to the "hypertrophy" of the prostate, but, in nw opinion, the possibility of a relation is not to be excluded. I made the investigations under consideration only in a small part of the cases and here only in a very few sec- tions. It is, therefore possible that I simply overlooked the gonococci-containing tissue. The proof of the pres- ence of gonococci in microscopic specimens seems, how- ever, to be very difficult, even in the prostatic inflamma- tion which is undoubtedly gonorrheal, as for a long time it proved to be a failure. Only Councilman succeeded ("Gonorrheal Myocarditis." Amer. Jour, of the Med. Sci. Vol. 56, 1893. No. 3, cit. after 1766) in demonstrating the presence of gonococci in the glandular ducts of the prostate. Aside from this author, the immediate relation ^33 of the prostate inflammation to the gonorrheal infection was proved by von Sehlen (Lur Diagnostic and Therapic der Prostatitis Chronica. Centralbl. f. Phys, and Path. d. Ham. and Sexualog. 1893. H. 6-8, cit. after 1766), by Neisser and Putzler (170). finally by Feleki (146)1 but entirely by clinical examinations, since the gonococci were found in the prostatic secretions expressed "per rectum." Since, therefore, it is so difficult to prove the presence of gonococci in the gonorrheal prostatitis, which passes relatively quickly and with proportionally greater extent and intensity, it is not strange that it has failed so far in a process of such a slow course and of such an in- significant extent as is the case with the "hypertrophy" of the prostate. Undoubtedly certain post-gonorrheal proc- esses may be formed without the direct assistance of the gonococci, and it is not impossible that the prostate "hy- pertrophy" also belongs to these post-gonorrheal proc- esses. In one part of the cases of the chronic urethral gonorrhea, which remains as a residue of an acute in- flammation produced undoubtedly by gonococci, one can- not by any means succeed, as is known, in proving the presence of gonococci. Gozzoli (173), for instance, states that in a chronic gonorrhea of the posterior part of the urethra the gonococci are found in only eighty per cent, of the cases (mostly they can be demonstrated also in the secretion of the prostate) ; while the acute gonorrhea shows the presence of gonococci in the full hundred per cent. Be this as it may, it seems to be proved that neither the absence of positive anamnestic data nor the absence of gonococci in the tissue of the enlarged prostate gland_ argues against the possibility of an etiological relation of our disease to the gonorrheal processes. Since preparatory to this the immediate proof of this relation is still wanting, the facts may at least be cited briefly which speak indirectly, with a certain probability for it. First of all may be mentioned the extremely fre- quent occurrence of gonorrhea in man, and especially the circumstance that even at the beginning of the disease in the acute state the gonorrhea settles very frequently in the posterior part of the urethra and the prostate, and assumes here very easily a chronic character. Some authors maintain that the gonorrhea attacks very rarely the Pars posterior urethrse and the prostate (Jamin[i62], 134 ;^ Guyon, etc.) ; but the majority of the investigators agree in the conclusion that the gonorrhea is very frequent in the Pars posterior and the prostate, respectively. (Jadas- sohn, 163 [up to 88 per cent.] ; Koch, 166 [60-70 per cent.] ; Lang, 167 [80 per cent.] ; Dind [90 per cent.] ; Pezzoli, 173 [60 per cent.] ; Heisler, 161 ; Le Provost, Lesser, Rona, Letzel and others.) But, too, the frequent inflammation of the bladder and the accessory testicle in gonorrhea speaks for the frequency oi its localization in the posterior part of the urethra (Aubert [141] and Eraud [ 144] ) : finally may be mentioned the statistics of Haslund (160), who found the involvement of the deeper part of the urethra occurring 424 times among 1,070 cases of gonorrhea. At any rate, we may assume that in at least 50 to 60 per cent, of all the cases of gonorrhea the process extends to the deeper parts of the urethra. But, according to more recent investigations, it seems to be above all doubt that the prostate also without exception suffers at the same time. (v. Sehlen, Neisser and Putzler, Feleki, Andry [140], Eraud [144], Guiard [156], Neumann [172], Neisser and Schaffer [a76bi], Ferger,. Pezzoili [173], Montagnon' [163] and Grosglik [159]). Another circumstance which points to- the gonorrheal origin of the "hypertrophy" of the prostate and certain forms of prostate atrophy, is the similarity of the ana- tomical changes characteristic of the gonorrheal processes to those which we found, and, furthermore, to certain complications which are sometimes observed in the gonorrhea as well as in our affection. To the latter oc- currences belong, among others, the obliteration of the "Vasa deferentia" observed in the "hypertrophy" of the prostate; first pointed out by Socin (119), and also by several other investigators, which obliteration is also fre- quently formed in the course of the gonorrhea, and is proved anatomically by Fenger (150-153). The common characteristic of the "hypertrophy" of the prostate and of certain consequences of the gonorrhea is, furthermore, the relatively late development after the gonorrheal infection. I shall mention- especiallv here the cicatricial post-gonorrheal strictures of the urethra. Sta- tistics compiled by Krzysztalowicz' embrace 121 observa- tions of stricture of the urethra in 99 individuals, of whom 60 acknowledged a passed gonorrhea and 5 were 1.35 still suffering from it ; the most of those are between 40- 60 years of age ; in the greater part of the cases the prob- able symptoms of a stricture begins after the 50th year. The data collected by Kdzystalowicz furnish the proof that frequently years pass after a cured gonorrhea before the narrowing of the urethra produced by the gonorrhea is felt by the patient. The matter is by no means different in the "hypertrophy" of the prostate ; the period of the latent course of the disease is here only a little longer. At this opportunity it must not remain unmentioned that, according to the investigation of Wassermann and Halle (176), the cicatricial changes of the mucous mem- brane of the urethra produced by chronic gonorrhea are by no means restricted to the vicinity of the stricture, but are also found in groups at many other places of the urethra. This fact finds its verification in the investigation of Fenger (150-153) ; this investigation has proved also that, although post-g'onorrheal strictures are still unobserved in the prostatic urethra, this section is by no means free from the post-gonorrheal cicatricial groups. Much more cer- tain landmarks for the etiological relation of the gon- orrhea to the h3^pertrophy of the prostate gland seem to be furnished by the similarity of the histological changes in both processes. The characteristic effect of the gonococci upon the living tissue consists, as is maintained by Fenger (155), and Teuton (175), in that, from pus-exciting prop- erties, they have also the ability to produce a proliferative connective-tissue process with a tendency to cicatricial shrinkage. A very characteristic symptom in all proc- esses produced by the gonococci, according to the har- monious statement of all investigators from Nelson (171), to Fenger (1. c), is to be sought in the circumstance that gonorrheal changes progress by no means "per continuita- tem," but sporadically. But as I have already mentioned, inflammatory processes specific to the "hypertrophy" of the prostate have the same characteristics ; and during the comparison between the changes produced by this latter process with those which were observed by Fenger in the chronic gonorrheal inflammations of the prostate, I have ^statistical view of the strictures of the urethra, which were treated in the surgical division of the Krakau General Hosp. in the years 1871-1892 (Dir. Prof. Obalinsky), 1893, Polish. 136 already found opportunity to point out that these two kinds of changes do by no means differ from each^ other in a morphological respect, if we overlook the quantitative differences. Finally, still another circumstance may be cited, which, although of no value as an indirect proof of the etiological importance of gonorrhea in prostate "hyper- trophy," is at any rate worth noticing. In the veterinary literature I found the data already mentioned (p. 147 in MS. bot. pge.), from which it appears that the hypertrophy of the prostate occurs among the domestic animals only in dogs. The only observation noted in the literature within my reach, of a cystic degeneration of the prostate glands in animals refers also to a dog (Csokor [316]). But from my investigation it seems to appear that the origin of cysts in the human prostate stands in a certain relation to the changes leading to a "hypertrophy'' of the organ. In this regard there seems to exist a certain rela- tion between the human pathology and that of anirnals. Aside from the balanitis which occurs in different kinds of animals from the most different causes, there exists, as it seems, a genuine suppurative inflammation of the urethra, and again only in dogs. (Bruckmuller [315, p. 675]). Although Moller (320, p. 447), maintains that such urethritis is only observedin male dogs, it is stated from other investigators as for in- stance Konhauser (319, p. 120), and Roll (321, p. 446), that the urethritis mentioned is capable of being trans- ferred from one animal to another, which seems, at any rate, to point to the infectious character of this disease. It would surely be worth while to subject this condition with regard to the similarity to the human gonorrhea to a more exact investigation. According to Neisser and Schiiffer (176B), all experiments in cultivating the gono- coccus in the organism of different animals have been without result. The only real positive result from in- oculation was obtained apparently by Turro (176a), and again only in dogs, in which, by the effect of the virulent gonococci grown upon acid culture-media, a suppurative inflammation of the urethra progressing to the higher parts of the urethra was supposed to be formed. As much as my views upon the nature of the so-called prostate "hypertrophy" differ from the views at present prevaihng, still they are nothing but a modest completion 137 of the following- view long ago cited by Virchow : "The chronic catarrh of the pars prostatica urethrse and of the prostate itself, especially after a gonorrhea, are more fre- quently the irritating causes of the enlargement." ("Die krankhaften Geschwiilote," 135, p. 139). ETIOLOGY. For the present we must limit ourselves to the following conclusions : The foundation for the "hypertrophy" of the prostate g"land and certain forms of prostatic atrophy in my cases at least consisted in chronic inflammatory processes, the etiological relation of which to the virulent g"onorrhea is not sufficiently proved at the present. The great fre- quency of gonorrhea in general, and especially the great frequency of chronic prostatic inflammation even due to it in the absence of acute inflammations of the urinary passages, and more particularly in view of the conspicu- ous similarity of the observations made by myself of the anatomical data of gonorrheal processes, makes it possible that such a relation exists. If the gonorrhea really is the most frequent and most important cause of the "hypertrophy" of the prostate gland, it will be the work of the future to decide this question once for all. 138 APPENIDX Methods of Investigations After the internal organs were dissected in the usual way, the bladder was opened "in situ" in each individual case in the upper part of the anterior wall. The state of the base of the bladder and of the urethral opening was examined, the urine was drawn and its quantity measured. Then the aorta, with its lateral branches, was dissected,, and the extent and intensity respectively of the arterio- sclerotic changes in every individual branch were macro- scopically considered, and the renal and bladder arteries, also the hypergastric with its smaller branches, were sub- jected to a more special attention and, if need required, parts of the vessel were saved for microscopical investiga- tion. In addition, the condition of the arteries of the base of the brain, of the extremities and of the arterial coronariae cordis was considered in each individual case. The genito- urinary organs were removed as a whole ; their anatomical relations to the orificium vesicale were exactly noted ; the prostate gland was very carefuUy'dissected out, measured and weighed, and finally divided in horizontal sections (sometimes after a sagittal diameter), to judge of the state of the prostatic urethra. For the microscopic in- vestigation, parts of both kidneys and of the bladder (from the upper, anterior, posterior and inferior wall), were cut out, aside from the parts taken from the ar- teries and from the prostate glands. Hardening : As a rule 4 per cent, formalin partly a mix- ture of sublimate and osmic acid. Hardening in Alcohol : Imbedding in celluloidin stains. Ehrlich's Hamotoxylin, or P. Mayer's Hamatein (diluted solutions during 24 hours. Afterstain : Eosin, orange, G). Grenscher-Pisenti's carmin, 139 Orth's Picrolithionkarmin, Van Gieson's stain, Knhne's goccocci stain. The material was also partly investigated on frozen sections treated with anilin dyes or unstained, as well as after the formalin freezing method (first worked out by Doc. Dr. Nowak-Krakau and introduced in 1894 to the Congress of Polish investigators of natural science and physicians in Lemberg, and published later by Plenge, Cullen and others). Each part of the bladder wall was cut in its longi- tudinal and transverse direction, and the prostate gland throughout its whole right and left halves respectively in a horizontal plane (vertical to the axis of the urethra). After the removal of the greater amyloid bodies, such sec- tions of the prostate are to be obtained quite thin, mostly 10-15 thick. (The thickness of the section is, under no condition, by no means indifferent.) The manner of the microscopical investigation was repeatedlv mentioned dur- ing the course of the previous treaties. The micro-metric measurements of every preparation at 10-15 places in a di- rection vertical to the bladder wall (parallel with the di- am,eter of its thickness), and 10-15 arterioles, respectively, of the bladder wall or of the prostate, were made with the ocular micrometers with objective systems 2 and 8a (Reichert, constant length of the tube 160 mm.). The following compilation, taken from case No. i, may serve as an example : Vertical / 2 3 4 1 J 1 6 7 8 q\ 10 A vei-age Anterior Con. tissue 1615 I SIC '785 1275 850 1530 1700 1360 1 I 105 1360 1 400-1 .4 mm. Blad. wall Musculature 40S0 493° 2040 240 S 3^30 30D0 3230 2720 3400 4250 3309-3 .3 mm. Upper Con. tissue 76s 1105 Q2S IS^o 1360 1020 1360 850 1360 1 105 1 1 59 Wall Musculature 28QU 2210 22qs ^82S 3060 28Q0 2550 3400 2380 3060 2856 Posterior Con. tissue lies 76^ 76s 8 SO 765 1020 850 7D5 705 850 850 Wall Musculature 2720 2040 2125 2040 2210 2550 2210 2210 2040 2125 2227 Base of Con . tissue 1020 1020 1020 1105 8so 92 s 1020 1 190 850 1020 1003 Bladder Musculature 2S90 2805 2805 297 s 2465 289c 2890 2720 3060 2380 27SS Measurements executed with oc. 3 obj. 3 Reichert (160 mm. length of tlie tube). The relative proportions calculated from the average numbers Anterior wall Upper wall Posterior wall Base of blad. Connect, tissue : Musculature— 1:2.37 1:2.5 1:2.62 1:2.77 For histological material I had at my disposal over 3,500 slides (not counting the frozen sections and the formalin frozen section). For examining the prostate sections for the making of the drawing I used Leiss' Ap- 140 pochromate (Leiss lamera lucida? [Zeichenkammer] ). In consideration of the circumstances that in the coin^se of the previous treaties all the investigated cases were compiled in several Tables, and that the more important cases were furthermore particularly discussed in the proper places, I think, contrary to my original intention, it is not necessary to add to the treaties a detailed descrip- tion of the cases examined. Better to illustrate the man- ner of the investigation in individual cases. I cite here as an example one case (i) Wl. Carl, 69 years old (clinical diagnosis: Arteriosclerosis). Section diagnosis (Nov. 12, 1895). Haemorrhagia cerebelli atheroma arteriarum. Hypertrophic cordis sin- istri. Atrophia renum senilis cystitis v pyelitis catar- rhalis. General Nutrition : Fair. I. Macroscopical investiga- tion (a) arterial system; i, thoracis and abdominal aorta; 2, a common iliac ; 3, hypogastric atheroma, decreasing in intensity toward the periphry ; 4, vesical arteries ; 5, pros- tatic arteries ; 6, renal arteries ; wall thin, intima smooth. Atheroma of the arteries at the base of the brain and the extremities (b) i, kidneys simple senile artrophy with catarrhal pyelitis (for want of space the schematic de- scription was referred to the text of the work) ; 2, bladder contains 580 c.cm. turbid urine^ mucous membrane slightly injected lusterless, at places slate-colored, here and there hemorrhagic spots, numerous large muscular ridges, no diverticuli. The base of the bladder behind the prostate pathologically deepened. Posterior lip of the orificium projects forward in the form of a transverse mound. To the right a polypoid tu- mor of half the size of a hazelnut. Orificium itself de- formed, forming an irregular crescesitic opening pointed with the convexity to the left. 3. Prostate gland en- larged of increased consistency ; the right lateral lobe much larger than the left, a left lateral deviation of the prostatic urethra, in addition a strong deviation to- ward the posterior. The right projection at the orificium mentioned proves to be a part of the enlarged right pros- tate lobe. In the cross-section of the prostate numerous tu- mors project, especially on the right side (pseutoadeno- mata), which have in places a delicate cavernous struc- ture. Weight of the prostate 31.2 grams. Length (from 141 basis to apex), 4.5 cm. Greatest width (at the base), 3.9 cm. Greatest thickness, 3.4 cm. ; 4, urethra outside of the prostatic part otherwise unchanged. II. Adicroscopic Examination. a. Arteries. In the | fnal, vesical and prostatic arteries outside of the organs nf sign of atheromatosis is to be de- tected, the arterioles of- the bladder wall and of the pros- tate unchanged. The relative, numerical proportions calculated by micrometic measurement (made in the way mentioned). Anterior wall Upper wall Posterior wall Base of bladder Intima i i i i 3 = 2.7 =. Adventitia 2.5 2.0 2.S 2.8 Seemen i i i i Wall 0.4 0-39 0-34 0.41 b. Genito-urinary apparatus, i, Kidneys: The micro- scopical picture corresponds on the whole to the simple senile atrophy ; ( for want of space the schematic de- scription was referred to the text of the work). 2. Blad- der. The thickness of the wall, leaving out the subserous tissue, is 44—5 mm. at the upper and anterior wall, at the base of the bladder 3^-4 mm., at the posterior wall 4 mm. The mucous membranes moderately thrown into folds, epithetum missing nearlv everywhere, here and there small and loose round-cell infiltrates. The submucosa is broad, composed of quite loose tissue; here and there sparingly loose, round-cell infiltrates, situated mainly in the neigh- borhood of the dilated vessel filled with blood corpuscles. At the upper wall (in the vicinity of the apex of the blad- der), extensive extravasations within the reach of the submucosa. The bladder muscle forms two layers in the vicinity of the anterior wall and base of the bladder, which layers are mainly to be differentiated by the different di- rection of the courses of the muscle bundles, as they are not limited by any connective-tissue layer worth men- tioning. The thickness of both layers is very variable in dif- ferent places, but as a whole the external layer is broader than the internal. To these two layers is added a third in the posterior wall which lies mnermost, and is distributed irregularly (it forms net-like trabeculae running in dif- ferent directions) ; this layer is much narrower than the other two. In the neighborhood of these three layers in 142 the posterior wall, one is able to distinguish several smaller layers of the second class. In the neighborhood o£ the apex of the bladder no clear regularity can be demonstrated in the distribution ^f the muscle tissue ; here exist several small layers inter] ced with each other in different directions and of diffe -ent and variable thick- ness. The peri and inter-itiuscular connective-tissue framework is quite scarce and as a whole loosely formed. The perivascular and interfascicular connective-tissue septa [ziige?] are of equal width, with the exception of the latter in the neighborhood of the most external muscular layer of the anterior wall. Here they are broader than the connective tissue septa [ziige] which separate the two muscular layers from each other. With weaker lenses (Reichert 3" III.), the interfibrillar connective-tissue is visible only on the transverse section of the muscle bundles, and only in the neighborhood of the apex and base of the bladder. In sections of the anterior and pos- terior wall nothing can be seen with this lens. The sub- serous connective-tissue most external to the bladder wall is scarce and loosely joined, the fat tissue insulas are pres- ent only here and there in its vicinity, nowhere joined out- side it, i. e., between the muscle bundles. The relative proportions of the components of the bladder wall cal- culated by micrometric measurements : Anterior wall Upper wall Posterior wall Base of bladder Connective-tissue _ i _ i _ J _ ^ Musculation ~ 2.37 2-5 3-"^ 2.77 3. Prostate Gland. In the section made horizontal to the level of the vera montamum containing the entire right lateral half of the prostate, numerous "pseudo-adenomata" show the largest of which bulges with its internal circum- ference into the lateral wall of the urethra. Externally, as regards the pseudo-adenomata excretory ducts bent more sharply than is normal. At the periphery of the specimen smaller and, as a whole, unchanged gland- ular branches with a normal stroma. The pseudo-adenomata are composed of numerous glandular acini, dilated in different degrees, in which the epithelium is now flattened, now missing in places or en- tirelv, and the contents of which consists of desquamated epithelial cells, amyloid bodies and a few leucocytes. The microscopical picture is very varied. (On account of lack 14.3 of space the reader is referred for the details to the text of the work). In some dilated glandular acini the con- tents consists of a homog-eneous amorphous mass. (Table XL, Fig-, ly). In the stroma of the pseudo-adenomata the muscular elements are mostly missing, while very com- pact cicatricial-like or new connective-tissue appears, com- posed of densely packed spindle-cells. Here and there subepithelial round-cell infiltrates and subepithelial ring- formed cicatricial groups narrowing the lumen of the glandular ducts. (For details see text v/ork). The changes in the stroma are, as a whole, not particularly numerous ; the clearest changes lie in the neighborhood of the distal ends of the main excretory ducts of the right lateral lobe at the external border of the largest pseudo- adenomata near the proximal end, i. c, the termination of main ducts narrowed throughout, the neighboring stroma is composed exclusively of cicatricial tissue, which forms a broad band ; this band lies on both sides of the duct. In the left lateral lobe similar changes, with the dif- ference that the pseudo-adenomata are smaller and more scarce and that the transitional pictures between the pseudo-adenomata and the more or less normal tissue parts are more easily to be found. A hard pseudo- adenoma lying at the distal end of the main duct corres- ponds to the connective-tissue type described on p. iii (in ms.), otherwise the nodules are composed of cystic- ally-dilated, glandular acini with thin septae. The pro- jecting tumor at the right side of the orificium vesicale was divided in connection with the neighboring part of the right prostate lobe in an entire section series in a sagittal, vertical plane. By this it will be shown that the tumor lies internally to the triangular vertical section of the sphincter, i. e., in the center of the muscular ring ; this tumor consists entirely of glandular tissue, which is in connection with the glandular tissue of the upper part of the right prostate lobe, and unites with the glandular tissue at the external side of the muscle below the inferior edge of the sphincter. The muscle tissue of the sphincter is sharply united everywhere with glandular tissue ; its wedge-shaped transverse section blunt. The top of the tumor consists of very dilated glandular acini, with a mixed contents, and of relatively 144 broad septae composed of abundant spindle-cell tissue. Below the top of the tumor the space between the lumen of the urethra and the sphincter is occupied by a sing-le cyst measuring- 5x3 mm. ; in it the same homogeneous mass, epithelium extremely flattened. In the stroma around the cyst big, dense, subepithelial, round-cell infiltrates, mostly in streaks. Below this big syst highly dilated glandular acini filled with a mixed contents and few (jedoch) pseudo-adenomata. At the posterior lip of the orificium (entire serial sec- tion), the sphincter lies immediately beneath the mucous membrane ; between the sphincter and the vasa-deferentia (i. e., the posterior commissure proper), greatly dilated glandular acini a few small pseudo-ademonata, etc. The anterior border of the horizontal section of the sphincter bulges forward in the upper part (macroscopical, visible, transverse tumors of the posterior lip of the orificium). 4. Vasa deferentia outside of the prostate unchanged. M5 BiPLIEQi^APHY. A. Bladder 1 Albert, Ed., Lehrbuch der Chirurgie und Operationslehre, Bd. 4, 1879, p. 181 ff. 2 AscHOFF, Ein Beitrag zur normalen und pathologischen Anatomie der Schleimhaut der Harnwege und iiirer drusigen Anhange. Virchow's Arch., Bd. 138, 1894, Heft i u. 2, p. 119 — 160 u. 195 — 220. 3 Arthaud, Etude sur le testicule senile. These de Paris, 1883; Annal. des malad. des org. genito-urin., 1885, p. 307, cf. 73. 4 AssMUTH, J., Ueber senile Dysurie. Petersb. med. Woch- enschr., 1893, No. 3. 5 Anderson, W., A case of chronic prostatitis: a pathological contribution to the study of the physiology of the prostate gland. Brit. med. Journ., 1887, p. 237 u. 483. VH. II 312. 6 Beraud, Des maladies de la prostate. These agreg., Paris 1857, cf. 314. 7 BoHDANOWicz, A., Contribution a I'etude de la pathologie du muscle vesical. These doctorat. Paris, 1892. 8 Besancon, P., Etude sur I'ectopie testiculaire du jeune age et son traitement. These doctorat. Paris 1892, cf. 73. 9 Bourneville et Solier, Des anomalies des organes geni- taux chez les idiots et les epileptiques. Progr. med., 1888, p. 125, cf. 73. 10 BuscH, W., Ueber den Mechanismus, welcher am hauiigsten bei alten Leuten die Urinentleerung behindert. Arch. f. klin. Chir., Bd. 20, p. 461. 11 Burckhardt, Das Epithelium der ableitenden Harnwege. Virchow's Arch., Bd. 17., 1859. 12 V. Brunn, Ueber drusenahnliche Bildungen in der Schleim- haut des Nierenbeckens, des Urethers und der Harnblase des Menschen. Arch. f. mikroskop. Anat., Bd. 41, 1893. 13 Barkow, Anatomische Untersuchungen uber die Harnblase des Menschen. Breslau 1858. 14 Budge, Zur Physiologic des Blasenschlieszmuskels. Pfluger's Archiv, Bd. 6, p. 306, cf. 119. 15 BiLHARZ, A.B, eschreibung der Genitalorgane einiger schwarzer Eunuchen. Zeitschr. f. wiss. Zoologie, Bd. 10, i860, p. 287, cf. 73, 310. x6 Casper, L., Zur Pathologie des Tractus urogenitalis senilis. 146 ViRCHOw's Arch., Bd. 126, 1891, Heft i, p. 139. 1 6a Casper, L., Experimentelle Untersuchungen uber die Prostata mit Rucksicht auf die modernen Behandlungs- methoden der Prostatahypertrophie. Berl. klin. Wochen- schr., 1897, No. 27. 17 Chevalier, E, Prostatisme vesical chez una femme. 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Nowiny lekarskie, 1S95, ^o- 2, p. 50 (polnisch) . 87 MiQUET, A., L'apparcil urinaire chez I'adulte et chez les vieillards. These Paris, 1894. 88 MoNOD et Terillon, Traite des maladies du testicule. Paris 1889, ef. 73. 89 Idem et Arthaud, Contribtition a I'etude des alterations du testicule ectopique et de leurs consequences. Arch. gen. de med., T. 2, 1887, p. 641, naeh 73. 89a MoTZ, B., O przeroscie gruczolukrokowego. Gaz. lek., 1895, No. ^^ (polnisch). 896 Idem, Przyczynek do nauki o budowie histologieznej przeroslego gruczolu krokowego. Przeglad lek., 1S97, No. 2, 4, 5 (polnisch). 8gc Mac Ewan, D., Die operative Behandlung der Prostata- hypertrophic. Wien. med. Presse, 1897, No. 24 — 27. 90 Monod, Hypertrophic de la levre postericur du col de la vessie (valvule de Mercier). Prog, med., 1S80, No. 26. VH. II 233. 91 Idem, Hjrpertrophie de la prostate. Saillie enorme du lobe moyen etc. Ibid. VH. 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Joum. de I'anat. et de la physiol., 1874, p. 514, nach 40. 111 Rudinger, Zur Anatomie der Prostata etc. Festschr. d. arztl. Ver. Munchcn, 1883, cf. 68. 112 RoKiTANSKY, Lchrbuch der pathologischen Anatomie, Bd. 3, 1 86 1, p. 368. 113 Reichel, Die Entwickelung der Harnblase und Harnrohre. Verhandl. d. Wurzburger med.-phys. Gcsellsch., N. F., Bd. 27, 1893, cf. 2. 114 Regnault, Etude sur revolution de la prostate chez le chien et chez I'homme. Journ. de I'anat., T. 28, 1892, No. I, p. 109. VH. I 113. 115 Reinert, Ueber Ganglienzellen der Prostata. Zeitschr. f. ration. Med. Bd. 34, p. 194, cf. 119. 116 Recamier, Atherome arteriel. Prostatisme chez un homme jeune. Ann. des nial. des org. gen.-urin., 1889, p. 100. 117 Sappey, Traite d'anatomie descriptive. Tome 4, 1879, p. 669, 689, cf. 2, 7, 40. 118 Strauch, Ph., Ein Beitrag zur Kasuistik der Prostataa- trophie. Centralblatt f . d. Krankh. d. Harn- u. Sexualorg. Bd. 5, 1894, Heft 5, p. 227. VH. 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Nordiskt med. Arkiv., Bd. 2, No. 27. VH. 70 II 791- 127 TouRNEAUX, Sur le developpement et revolution du tuberc. genit. chez le foetus humain avcc remarques con- cern, le developpement des glandes prostatiques. Journ. de I'anat. et de la phys., Tome 25, 1889, p. 229, cf. 2. 128 Tillmann's Lehrbuch der Chirurgie. Leipzig 1892, 2. Aufi., Bd. 2, Tcil 2, p. 249. 362. 129 TuFFiER, Du role de la congestion dans les maladies des voies urinaires. These 1885. Ann. des mal. des org. gen.-urin., 1886, p. 436. VH. II 239. 130 Thompson, H., The enlarged prostate, its pathologj-^ and treatment. Lcndon 1858, cf. Transact, of the pathol. Soc, Vol. 9, p. 298, cf. 119, 136 — Some observat. on the anatomy and pathology of the adult prostate. Med. -chir. Trans., Vol. 40, 1857, cf. 119. — Rare form of enlargement of the prostate. Lancet, 1857, V^l. 2, p. 24, cf. 119. 131 Thompson, H., On the nature of the so-called hypertrophy 152 of the prostate. Brit. med. Joum., 1886, Vol. i, p. 1156. VH. 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Syphil., Bd. 28, Heft i u. 2. — Weiterer Beitrag ibid., Bd. ?,5 P- 141- 148 Finger, E., Wien. med. Wochenschr., 1890, No. 2 — 4. 149 Finger, F., Beitrage zur pathologischen Anatomic der chronischen Urethritis posterior und der chronischen Prostatitis blennorrhagica. Verdandl. d. 2. internal, der- 153 matol. Kongr. in Wien, 1892. Wien 1893, p. 748 — 754. 150 Idem, Beitrage zur pathologischen Anatomie der Blen- norrhoe der mannlichen Sexualorgane. I. Die chronische Urethralblennorrhoe. Arch. f. Dennat. u. Syph., 1891, Erganzungsheft i, p. i — 55. 151 Idem, Beitrage zur pathologischen Anatomie der Blen- norrhoe der mannlichen Sexualorgane. II. Die chronische Urethritis posterior und die chronische Prostatis. Ibid., 1893, Heft I, p. 27 — 69. 152 Idem, Zur pathologischen Anatomie und Klinik der Prostatitis blennorrhagica acuta. Allgem. Wiener med. Ztg., 1893, No. 7 — 8. — Zur pathologischen Anatomie und Klinik der Prostatitis blennorrhagica chronica. Ibid., 1893 (Sep.-Abdr.). — Wieaer med. 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Monatsh., 1895, No. 5. 491 SouTHAM, F. A., A case of prostatic retention of urine treated by suprapubic prostatectomy. Brit. med. Journ., 1890, p.^ 507. VH. II 308. 492 Schmidt, Hans, Prostatectomia alta. Festschr. z. Feier d. 70. Geburtstages F. v. Esmarch's. Kiel u. Leipzig, 1893, P- 445- VH. II 326. 493 Schmidt, Meinhardt, Zur operativen Behandlung der obturierenden Prostatahypertrophie. Deutsche Zeitshcrift f. Chir., Bd. 28, p. 391, Centralbl. f. Chir., 1889, No. K. VH. 88 II 334. 494 Schmidt, Benno, Operative Behandlung der hypertro- phischen Prostata. Arbeiten a. d. chir. Univei-sitats- Poliklinik zu Leipzig, Heft i, p. 75. VH. 88 II 334. 495 Senn, N., Self-retaining drainage-tube after suprapubic cystotomy for chronic cystite and prostatic obstruction. Med. News-, 1894, p. 667. VH, II 524. 496 Szuman, L., Leczenie przerostu gruczolu krokowego u starcow zapomoca operacyi Ramma, przez Isnardiego zmodyfikowanej. Now. lek., 1896, No. i u. 2 (polnisch). 497 Sacaze, Dc la cystotomie suspubienne dans I'hypertrophie prostatique. Montpellier med., 1891, Mars i. VH. II 171 239- 498 ScHUSTLER, M., Zur opcrativen Bchandlung dcr Prostata- hvpertrophie. Wien. klin. Wochenschr., 1888, No. 17. VH. II 334. 499 Sansini, Iscuria permanentc da ipertrofia prostatica, cauterisazione tcrmogalvanica della prostata. Guarigione. Gaz. lombard., 188S, No. 23. VH. II 333. 499a Sawicki, B., O leczeniu przerostu gruczolu krokowego zapomoca rekoczynow operacyjnych. Gaz. lek., 1895, No. 23 i 24 (polnisch). 500 SussKiND, A., Ueber die Behandlung der Prostatahyper- trophie. Wurttemb. Korresp. -Blatter, 1885, Nov. 2. VH. II 231. 501 Spanton, Large sarcomatous tumour of prostate gland; excision; fatal result, remarks. Lancet, 1882, p. 1033. VH. II 205. 502 ToBiN, R., Resection of the prostate gland for enlarge- ment causing retention of urine. Brit. med. Journ., 1891, March 14. 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Ann. des mal. des org. gen.-urin., 1890, Nov., p. 649. VH. II 311. 511 Idem, De la prostatatomie et de la prostatectomie et en particulier de leurs indications. These Paris 1890. VH. II 309. 512 Watson, S. F., The operative treatment of the hyper- trophied prostate. Ann. of Surgery, Vol. 9, 1889, p. i — 29, Centralbl. f. Chir., 1889, No. 24. VH. II 309. 513 Idem, A case suggesting the advantage of repeated supra- pubic aspirations of the bladder as compared with cathe- terisation for the relief of retention of urine due to prostatic hypertrophic. Boston Journ., 1891, p. 687. VH. II 239- 514 WiESiNGER, A., Dtsch. Zeitschr. f. Chir., Bd. 42, Heft 2. 172 515 Wattelet, Ponction de la vessie par aspiration. Paris 1871, cf. 40. 516 Weir, On cystotomy for cystitis in the male. New York med. Rec, Vol. 17, 1880, cf. 72. 517 Williams, Brit. med. Journ., 1S78, cf. 72. 518 Weller, van Hook, Two prostatectomies. Amer. News, 1893, Nov. 25. VH. II 326. 519 Wassilieff, Cystostomie ideale. 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Chir., 1895, No. 40. Med. News, 8. VI. 1895. 527 ZiEMBicKi, Retention d'urine traitee par la taille hypo- gastrique et la resection des trois lobes de la prostate. Ann. des mal. des org. gen.-urin., 1891, p. 409. (VH. II 238, 241.) Separatabdruck. 528 Zaleski, a., Leczenie doszczetne przerostu starczego gruczolu krokowego. Kronika lekarska, 1896, Heft 11 — 13 (polnisch). 173 TABLE III FaUm IS 1 is « 9 JB Z ff iS « i9 tf +7 « ^ id 13 39 W 5i a? 3i 33 Jif // 5? 56 J» 25 5 35 tu W3i 51 'fS Vi- f; i 22 13 V. 29^3 6 2S » ¥t i- 7 3 21 1 % w i8 ^ n, g 36 ' \, , 0} o 3i A \ fl 01 ^ i 3Si — '^ l\ _ ^ — — _ _ _ _ ft _ i — — _ _ _ y _ _ L _ _ _ _ _ _ OA ,1 if % 1 M 28 — -j — ^ -1 — T — — - U — ■^^ n r (— — \ — it i -^ - -7^ IS - - -^ - - - no 26 1 1 ,^ A 1 1 \ \ ) '■ ./ V- ...\ A or Zit \ ' 1 j / \ ' , A na 22 / ^ / 1 / 1 ' ^0 1 09 W V V A 1 , 1 ^ 1 J f \ "■■ / \ 10 /A- /' / 1 \ / \ 1.1 W I 1 \ \l 1.2 -;+ V / \ / V' 1.S ;.? \/ \/ f. to _ _ =_ _ _ _ _ _ .^ ,„ ^ ^ ,„ _ _ _ _ _ 1 _ _ _ _ _ _ J 1.3 «:; TABLE IV Fall m ^ jj 5J X ',S 27 i ?}i 3/i >■/(> ^ 3 « S/ IS 'A 25 d' 3S » •i 37 ^ i» i? 3j & S /5 29 9 f 22 33 // « ■/$ // 7 23 5 39 (? « 3S W V 1 § a s 1 1 1 nn S./I \ S6 i.if •. .12 iO M \ 4(5 .^ >* • « \ 40 \ 3.S /\ '..^ 36 1 \ ■w. -.. A ■■54 \ l\ S 1 32 \ r \ 30 \ 1 / '.. A ZS \ \ / A A A ^ V \ \ / 1 \" -/ -5 A J \ 2.J, V i V ■• y -^ ^ '\ V ( 22 J A / \ ' f 1 t-.\ /\ / ^\ 20 (/ \ \ / \ / \ J f -. -\ ... / H \ 1.8 V \. / / V / • . 1 1.6 V \/ ' 1.1, ' \ ■\> 12 V V 1.0 m as •■ at 02 .^ ^_ _ __ 1 J 1 ._ __ 3a; _ ^^ ^ _ _ _ 174 TABLE V AUer 19 Ijj 5/ IS pT" p5 p p Uo iO « r~ ■M lij pj X 52 53 55 56 57 57 59 60 60 62 62 63 65 6A67 67 6S m 69 70 70 70 70 70 » n 71 7i » » [w [» IF [»■ [^ [w wrl,® p9 [^ p Falim. % 55 « i? •w V) sr fl iS « « « so 56 2S 'f7 35 31 25 « 39 33 3S li td U 21, n 3 ■M y M « 32 36 37 17 6 35 M W » 7 « /? .c » « * « 4? '.n It! 1 J6_ A t\ l\ A 1 \\ .W \, ' , 1 \ in t \i ■"/ \ "■■ -.. 1 \ h IK ... \ 1 \ "- ^ \ \ ifi \ -.. , \ I \ A -?it V ... - \ \ l\ ^ /\ j\ A >? I \ 1 \l \ ... "T _. {^ 1 \ ■■ / \ \ l\ / - 3n ' y \ y 1 \ I \ — L. / m \ V ' \, \J \ \ ... .. / / \ V i_ /s / 7 Ih S J r / ^T 1? s/ V ^ in as 06 a: 02 \ ■ Zahlenrverth des Blasenmandbindegen/ebes, als Maaselnheit genommen. TABLE VII Kein Hinderniss i/orhanden Mechanisches Hinderniss vorhmden \ Alter 19 J?i 27 2S 31 36 W 1,0 w « ',5 i5 « 52 56 57 57 59 6U 62 63 65 or «r e,i 70 70 70 72 Th 75 63 67 67 66 69 70 72 T, 7S 75 75 76 77 7S 7S so fallJ^ 5h 55 W S3 \ \ \ 1 / V ^ A 9n 1 , N J I \l 1 1.x V j ■i.fi 1 r- 1 1.1^ 1 1.1 1 / 1.0 0.1! (16 0', 0.? . _ _ _J _| _| _| J _1 _| A _ _l _J _j A J_ _ _1 A A _ A _ 175 Date Due "'H»i MUir 5 iii4^ — — ^ — f)