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Acute and chronic cicatrizing enteritis (regional ileitis)
ACUTE AND CHRONIC CICATRIZING ENTERITIS (REGIONAL ILEITIS) ARTHUR M.
ALBERT VANDERVEER, II, M.D.
DICKINSON, M.D. P.A.C.S.
Attending Surgeon, MemoriaI HospitaI
Associate Attending Surgeon, St. Peter’s Hospital AND
JOHN
J.
CLEMMER,
M.D.
Director, Bender Hygienic Laboratory ALBANY,
NEW YORK
T
HE term regiona iIeitis was first used by Crohn et a1.l to describe a condition of non-specific inff ammatory disease occurring in the dista1 portion of the iIeum. SubsequentIy, with more widespread recognition of the condition, a variety of names have been given to this process. Erb and Farmer2 describe their cases under the caption iIeocoIitis; Meyer and Rosi3 under the titIe regiona enteritis (non-specific) ; GaIambos and MitteImann4 as termina1 iIeitis; antedating a11 of them are the oId terms, infectious granuIoma and sarcoid. Eliology. RegionaI iIeitis is most frequent in young aduIts, but it has been reported in patients of various ages. Koster, Kosman and SheinfeId,5 in a detaiIed review, noted its occurrence in each of the first seven decades. EarIy reports’ indicated a ratio of two maIes to one femaIe, but of the seventeen cases reported with the by Koster et a1.,6 combined sixty-two cases in which the sex was mentioned, which they coIIected from the there were forty-four maIes Iiterature, and thirty-five femaIes, not a significant difference. Occupation does not appear to be a factor. Crohn, Ginzburg and Oppenheimer’ noted that members of the Hebrew race appeared to be more susceptibIe than others, and their observation has been confirmed in subsequent reports. However, Bargen and Dixon 6 faiIed to note a prevaIence of Jews among the numerous cases of regiona iIeitis observed at the Mayo CIinic. 714
AIthough the condition appears to be definiteIy infectious, various cuItura1 methods, anima1 inocuIations, immunoIogic procedures and detaiIed histoIogic studies have faiIed to revea1 a specific etioIogic infectious agent. FeIsen’s investigations,7~s~g indicating that the condition is initiated by acute baciIIary dysentery, are an exception to this statement. He obtained positive aggIutination titers against organisms of the EbertheIIa dysenteri group (SonnbDuvaI type, especiaIIy) in sixty-two consecutive cases of chronic uIcerative coIitis, in fourteen cases of chronic dista1 iIeitis, and in two cases of non-specific iIeoceca1 granuIoma. Diagnostic bacteriophage reactions and positive feca1 cuItures for dysentery baciIIi were obtained in some of the cases. Control studies of 300 bIood sera resuIted in 4.6 per cent positive aggIutination reactions with E. dysenteri. Acute dista1 iIeitis was observed in fourteen cases of acute baciIFeIsen conchrded that Iary dysentery. dysentery in this atypica1 form at times progressed into a chronic phase and with the aid of secondary non-specific infection resuIted in “regiona iIeitis.” In discussing “A Combined Form of IIeitis and the paper, CoIitis,” presented by Crohn and RosenakrO at the 1933 session of the American MedicaI Association, FeIsen stated that “chronic non-specific uIcerative coIitis and distal re iona1) iIeitis, either aIone or as asso( g ciated Iesions, and non-specific iIeoceca1 granuIoma are a11 manifestations of baciICrohn rephed that careful Iary dysentery.”
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studies of the cases of regiona iIeitis observed at the Mount Sinai HospitaI failed to substantiate this view. The majority of the authors reporting this condition appear to have had simiIar diffIcuIties in proving a B. dysentery etioIogy. Koster et aI., observing a certain simiIarity of regional iIeitis to lymphogranuIoma inguinale, appIied the Frei test to six of their cases but with uniformIy negative resuIts. Mockll has reported a number of cases of “infective granuIoma” of various IeveIs of the gastrointestina1 tract incIuding Iesions of the “regional iIeitis” type. He attributed the conditions to various non-specific factors, such as appendicitis, foreign bodies, uIcers, extra peritonea1 infections, trauma and so forth, and stated that the “condition is directIy due to Iow grade infection causing an impairment of circuIation or to an impairment of circulation foIIowed by Iow grade infection.” Barbour and Stokes12 suggested that a chronic recurrent intussusception might initiate the process by impairing the circuIation and vitaIity of the gut waI1 and aIIowing bacteria1 invasion from the Iumen. SeveraI authors have submitted statistics indicating that about 50 per cent of these patients previousIy have had an appendectomy. ObviousIy, appendectomy in itseIf wouId not be an etioIogic factor although early symptoms of iIeitis are frequentIy mistaken for appendicitis. Homans and Hass13 suggest an association between appendicitis and ileitis, stating that in both of their cases there was definite evidence of disease of the appendix. Mixter,l” among others, expresses himseIf as opposed to any such reIationship. We must concIude that the exact etioIogy and pathogenesis of regiona iIeitis has not been determined; that it appears to be a non-specific inff ammatory process initiated perhaps by a variety of factors and aggravated by various constituents, bacteria1 and otherwise, of the intestina1 content. The patbology of regiona ileitis is that of a- progressive non-specific proIiferative inf-lammatory process .5,15 In the earIy phase
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the invoIved segment of bowe1 and its mesentery are edematous and congested. The muscIe fibers of the bowel waI1 are separated by edema, and moderate diffuse Ieucocytic infiltration is present. FocaI hemorrhages occur, particuIarIy near the serosa. There is a hyperplasia of Iymphoid tissue in the submucosa and in the adjacent mesenteric nodes. The mucosa aIong the mesenteric attachment of the gut exhibits IongitudinaI uIcers. The vaIvuIae conniventes are bIunted and indistinct, depending upon the degree of edema. As the process progresses, the mucosa1 uIcers extend into the wall and fistuIae may form. These often end bIindIy in the attached mesentery, but, at times, they communicate with another viscus or drain externaIIy. Generalized peritonitis is usuaIIy prevented by extensive adhesions. Foci of necrosis with abscess formation are found in the bowe1 waI1 and the mesentery. The centra1 part of these foci shows many neutrophiIes, endotheIia1 Ieucocytes and foreign body giant ceIIs, and toward the periphery Iymphocytes and pIasma ceIIs predominate. OccasionaIIy particIes of foreign materia1, presumabIy from the Iumen of the intestine,‘j are demonstrabIe. SmaII foci of inffammation superficiaIIy resembIing tubercIes may be present just beneath the serosa. Coexistent with the injury and destruction of tissue, there is marked proIiferation and repair. GranuIation tissue forms at the sites of the uIcers and abscesses, and dense fibrosis of the intestina1 waI1 and adjacent mesentery occurs. Regenerated simpIe columnar epitheIium may cover the uIcerated areas, resuhing in a flattened, smooth epitheIia1 surface with no evidence of mucosa1 foIds. In other areas edematous vaIvuIae conniventes form sessiIe poIypi. EventuaIIy, stenosis of the bowe1 occurs, and the proxima1 intestine diIates and hypertrophies. OriginaIIy, the Iesion was beIieved to incIude onIy the termina1 iIeum, beginning at the iIeoceca1 vaIve and progressing proximaIIy for 25 to 35 cm. in the __. . _ _ .. t1eum.l It IS now recogmzed that a non-
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specific chronic inflammatory this type may invoIve any intestinal tract.“, 10s11,138 15,16,17
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process of part of the
FIG. I. Case I. X-ray taken six hours after oral barium suIfate. Note typica string sign, representing the terminal ileum and diIatation of proximal ileum.
Symptoms. The symptoms of regiona iIeitis vary with the Iocation of the process in the intestina1 tract, its acuteness or chronicity, the duration and extent of the lesion and the presence or absence of compIications such as abscesses, fistulae, etc. In the Iarge majority of reported cases the history of the iIIness is measured by years, ten or more not being unusua1. As most commonIy the Iesion is Iocated in the dista1 iIeum, the majority of symptoms and to the right Iower signs are referred quadrant of the abdomen. Crohn et a1.l have divided the symptoms into four groups. In Group I the symptoms resembIe those of acute appendicitis, with pain and tenderness in the right Iower quadrant, fever and vomiting, aIthough the onset is usuaIIy somewhat sIower than that of typica acute appendicitis. NevertheIess, that many of the earIy acute cases are mistaken for appendicitis both pre- and postoperativeIy is attested by the reports
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in the Iiterature. The postoperative deveIopment of obstructive symptoms or persistence of fistuIae finaIIy has indicated the correct diagnosis. It is easy to understand that if an abscess about the cecum is drained, with minimum disturbance of the intestines, detection of the basic process may be missed. Meyer and Rosi16 reported such an instance in which the persistence of a f%tuIa foIIowing drainage of an abscess Ied to further study. On the other hand, where operation discIoses “chronic appendicitis” in a patient who presents symptoms suggesting an acute process, it is d&uIt to understand how a competent surgeon shouId miss the rea1 pathoIogy. Group II incIudes those cases presenting symptoms of uIcerative enteritis. There is a history of coIicky abdomina1 pain, frequent stooIs with mucus and sometimes bIood. There is aIso Ioss of weight and secondary anemia. Repeated stoo1 and proctoscopic studies show nothing de6nite. Often these patients have a history Iasting for years. GaIambos and MittIemann4 reported a case of this type, the patient having suffered with diarrhea and pain for fifteen years; the persistence of a fistuIa foIIowing appendectomy finaIIy attracted attention to the underIying condition. Group III comprises those cases with obstructive symptoms which usuaIIy occur Iate in the course of the disease, but in some instances appear suddenIy without previous compIaints. The symptoms are generaIIy those of an incompIete obstruction of the smaI1 intestine. There are cramps, pain, borborygmi, distention and perhaps nausea and vomiting. Often there is a history of recurring attacks of diarrhea. In Group IV are those cases with fistuIae. The fistuIae may be of the externa1 type and foIIow expIoration and drainage or they may be of the interna type with a fistuIous tract connecting the iIeum with the coIon or sigmoid. Symptoms occurring in this group of cases vary greatIy, but commonIy there are diarrhea, Ioss of weight, anemia and abdomina1 cramps. There may be intervaIs of fever during periods of activity.
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Individual symptoms occurring in the course of the disease warrant further discussion. AbdominaI pain seems to be the
FIG. 2. Case I. MuscuIaris of terminal iIeum. (X62.) Note separation of smooth mu&e fibers by edema and diffuse Ieucocytic infiftration.
most outstanding symptom. It is usuaIIy of a colicky or cramp-Iike type and is more commonIy Iocated in the Iower right quadrant, although it may be diffuse. It may be duI1, and it is often reIieved by defecation. In the presence of abscesses or fistuIae, naturaIIy the pain wiI1 be of a different type and Iocation. In some instances, the pain is acute and severe, simiIar to that seen in appendicitis. CarefuI review of the reported cases shows a record of pain in nearIy every one and the recurring descriptive terms ‘coIicky’ or ‘cramplike’ are significant. Diarrhea is aIso a common symptom aIthough by no means so constant as pain. UsuaIIy there is a history of from four to six soft stooIs per day. It is uncommon to obtain a history of many movements aIthough Homans and Hass’3 reported the case of a patient who had twenty to thirty stooIs daiIy over a period of six years. OccasionaIIy mucus appears in the stooIs, but
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bIood is a rare finding. Diarrhea is absent in about one-third of the reported cases. Nausea and vomiting are reIativeIy in-
FIG. 3. Case I. Acute uIcer of terminal iIeum. (X62.) Observe f?brinopuruIent exudate on uIcer base and marked hyperpIasia of Iymphoid tissue of Peyer’s patch.
frequent symptoms. However, there is often a history of indigestion and eructation of gas. Fever is a variabIe factor. High temperatures are uncommon except in the acute type of case or with the deveIopment of complications. A moderate fever of 99 to 102 degrees is present in about 35 per cent of the cases, and periods of fever foIIowed by apyretic intervaIs are often observed. Loss of weight is commonly noted, varying from a few pounds to 20 or 30. At times, these patients become markedIy emaciated and dehydrated. Secondary anemia is an aImost constant finding, the degree depending upon the extent and duration of the disease. Leucocytosis is the ruIe, with a count of about 14,000, although norma Ieucocyte counts are not infrequent. The abdomina1 findings are quite constant. UsuaIIy there is moderate distention of the abdomen. Rigidity is absent except in the compIicated case. Often there is an
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area of tympany due to dilated gut proxima1 to the Iesion. In at Ieast 50 per cent of the reported cases, a mass is
FIG. 4. Case I. Serosa of termina1 ileum. (X 140.) Observe extravasated cIoseIy packed erythrocytes in subserosal adipose tissue with smaIIer hemorrhages on serosa1 surface.
paIpabIe. UsuaIIy the mass is Iocated in the Iower right quadrant, aIthough it may be in the mid-abdomen. It is tender, rather firm, somewhat irreguIar in outIine and sIightIy mobiIe. The size varies from IO to 40 cm. in Iength and 5 to IO cm. in width. In some instances the mass may be paIpated through the rectum or vagina. Where partia1 obstruction exists, peristaItic waves are occasionaIIy visibIe and audible. Diagnosis. RoentgenoIogy is of considerabIe assistance in diagnosing this condition. Crohn and his associates’ discussed the findings in their origina report, and Kantorl* has described the Roentgen signs in detai1. According to him, the ora contrast medium is IikeIy to demonstrate one or more of the foIIowing : (I > a fiIIing defect of the iIeum (or coIon), the size depending upon the extent of the Iesion; (2) an area of tapering off immediateIy proximaI to the defect, rather than a sharp change; (3)
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diIatation of the gut proximaI to the Iesion with or without a demonstrable Auid IeveI; (4) the string sign in which a thin Iinear
FIG. 5. Case I. Lymph node from iIiac mesentery. (X28.) GerminaI centers are enIarged and hyperpIastic. sinusoids diIated and HIed with exudate.
shadow resembIing cotton string extends through the obstruction. Barium enema aIone is of IittIe vaIue in most cases as it faiIs to show the Iesion. RegionaI iIeitis is to be differentiated from uIcerative colitis. This can usuaIIy be accompIished by proctoscopic examination and a barium enema which wiI1 be negative in the former and positive in the Iatter condition. The history and physica examination, especiaIIy of the chest, aIong with gastrointestina1 x-rays wiI1 assist in ruIing out tubercuIous Iesions of the intestine. Differentiation from acute appendicitis can usuaIIy be made by the clinical findings, aIthough carefuI examination of the abdomen at operation may be necessary. Great assistance can be obtained from the roentgenoIogist in ruIing out actinomycosis and neopIasms of this region. FinaIIy the condition may be confused with so caIIed “idiopathic spastic enteritis.” UsuaIIy the symptoms in spastic enteritis are
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less marked and are transitory; the roentgenogram is quite different aIso. The mortaIity rate of regional ileitis
FIG. 6. Case II. Roentgenogram of colon foIlowing barium sulfate enema. Observe low position of right half of transverse colon and compare concavity of its inferior margin with diagram of operative findings in Figure 8.
varies with the severity of the process, its duration, magnitude of any operative procedures, etc. AccordingIy from the Iiterature one may gather very high as we11 as Low mortaIity statistics. Binney17 reviewed twenty-six cases with onIy one death in the series; Mixter,14 on the other hand, reported eIeven cases with a mortaIity rate of 36 per cent. A review of a considerably larger number of cases by the present writers discIoses a mortality rate of about 12 per cent. It shouId be noted that recurrences folIowing incompIete eradication of the process are quite frequent. The treatment of regiona ileitis depends upon the extent of the disease and the condition of the patient. Meyer and Rosi’” limited themseIves to expIoration and appendectomy in three of their eight cases; and carefuI observation over long periods reveaIed no further evidence of the disease. These authors suggest that when the edema
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is limited to the intestina1 waII, infection is IocaIized to this region and probably wiI1 resolve spontaneousIy. If thickening of the
FIG. 7. Cast II. Roentgenogram, six hours after oraI barium sulfate. Narrowing of distal 8 cm. of ikum and obliteration of mucosa1 pattern. Large opaque mass in midline represents dilated proximal ileum.
mesentery and hyperpIasia of the neighboring Iymph nodes exist, however, this indicates a spread of the infection and makes more radica1 procedures necessary. Likewise, Probstein and GruenfeId’g reported three cases in which the operative procedures consisted of appendectomy with iIeostomy; and the uItimate results were satisfactory. We must be cautious in our appraisa1 of such conservative treatment, for up to the present, insuffIcient cIinica1 materia1 is avaitable to warrant finaI concIusions. We do know that recurrences are moderately frequent even after resection. If abscesses exist, these must be drained before any further surgery is contempIated. When there is considerabIe stenosis of gut, resection is indicated if the patient’s condition wiI1 permit. In some instances, an iIeocoIostomy seems to afford permanent reIief, but usuaIIy this procedure is con-
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sidered a temporary measure to be foIIowed by resection when the patient’s condition is suffrcientIy good. Meyer and
Moe6 consieting 0i 69 cm. of terminal ileum, adherent to colon. FIG.
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pain in the right Iower quadrant. The pain was steady and accompanied by nausea and vomiting. The patient had noticed a gradually in-
of Ileum,
16 cm.
in length,
greatly (Circum- 11 cm.)
dilated. ference circwn. 0
#
5 centimetero.
10
Q
8. Case II. Schematic drawing of operative findings. Excised bowel consisted of g8 cm. of ileum attached to 26 cm. of Iarge intestine.
Rosi16 point out that simpIe iIeocoIostomy is foIIowed by recurrence in at Ieast 50 per cent of cases. When resection is done, the Iine of excision must be we11 away from diseased tissue, for recurrences are considered to be the resuIt of Ieaving behind invoIved areas. FistuIae have to be treated by resection of the tract and excision of the area of the gut involved; perhaps resection may be indicated. Transfusion has found favor as a means of preparing many of these patients for operation. We present the foIIowing two cases to iIIustrate the cIinica1 and pathoIogic findings of the acute and chronic phases of regiona iIeitis. CASEI. A young, maIe Hebrew twenty-two years of age was first admitted to St. Peter’s HospitaI in December 1935, compIaining of
creasing constipation over a period of six months before entrance into the hospital. The famiIy history and past history were negative except for severa simiIar attacks during the past year, aIways reIieved by rest and hot packs. There was no diarrhea nor Ioss of weight. The physical examination revealed a rather thin, young maIe aduIt apparentIy in some pain. Heart and Iungs were negative. There was definite tenderness over McBurney’s point in the right Iower quadrant. No masses were paIpabIe, nor was there any marked rigidity. The temperature was 99.2”F., the puIse 88 and respirations 20. Blood count revealed 22,000 Ieucocytes per c. mm. with go per cent poIymorphonuclears and IO per cent lymphocytes. Wassermann examination was negative, as reported Iater. The patient was operated upon about four hours after admission, the preoperative diagnosis being acute exacerbation of a chronic
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appendicitis. A Iower right rectus incision was made and opening of the peritonea1 cavity discIosed a smaI1 amount of free ffuid. The appendix was deIivered and found to be sIightIy swoIIen and edematous, but not apparentIy acuteIy infIamed. Further exploration showed some edema and thickening of the termina1 portion of the iIeum, which was regarded at the time as no doubt secondary to the appendix. We considered that this would subside foIIowing the appendectomy. The patient’s convalescence was uneventful, the wound heaIing by primary union, and he was discharged as cured on the eleventh postoperative day. He was eating well, his boweIs were regular, and he complained of no pain. The pathoIogic report was chronic obIiterative and acute appendicitis. The patient was home for ten days, and during this time he began to compIain of vague, transient abdomina1 pain beginning in the region of the umbiIicus and radiating in a11 directions. The pain was not constant, but was fairly sharp when present. Some beIching of gas and constipation were also present. There was no nausea nor vomiting. He re&ntered the hospita1, this time on the medical service. The temperature on admission was normaI, but varied between gg and IOO degrees during his stay in the hospita1. The puIse varied between 72 and 84. Barium enema reveaIed a fixation and distortion of the cecum, apparently the resuIt of adhesions from the previous operation. There seemed to be considerable spasm about the cecum. The patient was put on atropine, and this pIus rest in bed brought about marked improvement. He was discharged as cured after eight days. The diagnosis was postoperative adhesions and spasm. However, after about two months at home, he was again admitted to the hospita1 on March 5, 1936. During the interva1 he had Iost considerabIe weight and strength. Intermittent pain in the right Iower quadrant had recurred in association with nausea and vomiting. For one week before admission he had been unabIe to retain anything except fIuids, and these onIy in small amounts. Constipation had become more and more severe. PhysicaI examination at this time showed a somewhat emaciated, highIy nervous, young male adult. Temperature was 99.2%., puIse 88 and respirations 20. There were definite tenderness and muscIe spasm in the
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right Iower quadrant, but no masses were paIpabIe. Examination otherwise was negative. The urine was negative; bIood sugar was 80 mg. per IOO C.C. of bIood; N.P.N. 36.6; urea N. 15.3; chIorides 433; hemoglobin 70 per cent; erythrocytes 4,256,ooo per c. mm.; Ieucocytes 14,000 per c. mm. with 80 per cent neutrophiIes and 20 per cent Iymphocytes. Under hot packs and rest in bed the temperature returned to normaI, the bowels started and the patient feIt considerabIy moving, better. A gastrointestina1 series was done by Dr. I. J. Murnane, roentgenoIogist, and revealed the typica string sign of termina1 iIeitis. (Fig. I.) A diagnosis of this condition was made, and after an attempt to get the patient in as good condition as possibIe, operation was done. The terminal IO to 15 cm. of the iIeum and the cecum made up a large mass of acuteIy inflamed tissue bound cIoseIy together with old and fresh adhesions. The mass in some respects resembIed a neopIasm. Resection was done and IateraI anastomosis performed between the transverse coIon and the iIeum. The patient’s condition was poor and his postoperative course was steadiIy downhi despite intravenous therapy, etc. Death occurred on the third postoperative day. PathoIogic description of the excised intestine foIIows: GrossIy, the specimen consisted of a segment of terminal iIeum measuring 24 cm., with a portion of the cecum and ascending coIon measuring 14 cm. The proxima1 7 cm. of the iIeum showed a reIativeIy normal mucosa, although the serosa1, surface over part of this area was congested and granuIar. From this point to the iIeoceca1 vaIve, the waI1 of the ileum became progressively thickened, measuring I .I cm. in thickness near the cecum. The most marked thickening was near the mesenteric attachment. The vaIvulae conniventes became graduaIIy more edematous and bIunted toward the iIeoceca1 vaIve, and were unrecognizabIe in the termina1 12 cm., where the mucosa showed edematous rounded eIevations. An ulcerated groove 1.5 cm. in width extended aIong the mesenteric attachment of the distal 12 cm. of iIeum. OraI to this for 5 cm., there were patches of mucosa at the mesentery with IongitudinaI acute uIcerations. SmalI mucosal uIcers were distributed irreguIarIy at points away from the mesenteric attachment. AI-
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though the mesentery of the iIeum had been cut cIose to the bowe1 attachment, a few enIarged hyperpIastic Iymph nodes couId be observed in the remaining indurated, thickened mesentery. The serosal surface showed hemorrhage, whiIe the mucosa of the cecum reveaIed an irreguIar uIcer 4 cm. in greatest diameter. The inflammatory process was, however, very much Iess marked here than in the iIeum. The waI1 of the cecum, which was thinner than that of the termina1 ileum, measured 0.6 cm. at its thickest point. Its serosa was congested and roughened by fatty fibrous tags. SeveraI hyperpIastic Iymph nodes were attached. The appendix was absent. Microscopic examination of sections through the termina1 iIeum discIosed edema throughout the waI1. (Fig. 2.) In pIaces the mucosa was ulcerated, with the denuded areas showing young granuIation tissue containing many thin-waIIed capiIIaries and heaviIy infiltrated with leucocytes, the majority of them neutrophiles. (Fig. 3.) Recent foca1 hemorrhages were evident beneath the serosa (Fig. 4) and in the submucosa. The waI1 was diffuseIy infiltrated with Ieucocytes, incIuding lymphocytes, pIasma ceIIs, neutrophiles, eosinophiIes and occasiona giant cells. Scattered dense accumulations of neutrophiles were observed in the iIiac waI1 and the mesentery. The mesentery showed diffuse fibrosis with intermingIed areas of fat. Edema, foca1 hemorrhages and smaI1 abscesses were observed, and occasiona foreign body giant ceIIs were present in the abscesses. Many of the smaI1 arterioIes, capiIIaries, and veins in the serosa and mesenr tery were acuteIy inflamed, whiIe the mesenteric Iymph nodes were hyperpIastic and acuteIy infIamed. (Fig. 5.) Sections through the uIcer in the cecum indicated that the base was covered with young vascuIar granulation tissue heaviIy infiItrated with Ieucocytes. The muscIe was edematous and infiItrated with moderate numbers of Ieucocytes. There were coIIections of Iymphocytes beneath the serosa. The fina diagnosis was acute and chronic uIcerative iIeitis and typhIitis, with acute hyperpIastic Iymphadenitis, most prominent in the termina1 ileum. CASE II. A male Hebrew, age 24, entered the MemoriaI HospitaI February 27, 1936 with compIaints of diarrhea, Ioss of weight and weakness, of severa years’ standing.
According to his parents, his infancy and early chiIdhood had been uneventfu1; he had grown normaIIy and seemed entireIy weI1. At age 14, he had had an intestina1 infection, characterized by diarrhea and Ioss of weight, From then on, he continued to have simiIar attacks every two to three weeks, each lasting one to two days. No bIood or mucus was noted. At age 14 he weighed g8 pounds, and at 20, 84 pounds. His appetite had aIways been fairIy good. There had been no nausea or vomiting, but of Iate he had had considerable flatulence. Six weeks previous to admission, the patient suffered with an infectious process foIlowed by jaundice, subsequentIy proved to be the resuIt of choIeIithiasis. At the age of 2 I, the patient was graduated from an exceIIent engineering college, but found himseIf physicaIIy unabIe to foIIow reguIar empIoyment. Examination of the patient upon admission reveaIed a smaI1, asthenic, paIIid male who weighed 75 pounds and was 5 feet I inch in height. His skin was sIightIy yeIIow, dry and parchment-Iike due to a minimum of subcutaneous fat. The head was negative except for prominence of the fronta bones which was a famiIy characteristic. The mucous membranes of the mouth were of norma color; there was a hard tumor mass, 2 cm. by I cm., Iocated in the center of the hard paIate. The teeth exhibited severa cavities. The neck was essentiaIIy negative. The chest was of the asthenic type with narrow apices and prominent ribs. The heart and Iungs appeared normal. The abdomen was soft and flat with a very sIight panniculus. The Iiver duIness was increased to 2 cm. beIow the Costa1 margin, but its edge was smooth and not tender. The spIeen was not enIarged. No free fluid couId be demonstrated. In the right Iower quadrant of the abdomen, a movabIe and moderateIy tender mass about 15 cm. in greatest diameter was visibIe and paIpabIe, and an unusua1, tympanitic area, suggestive of a Ioop of diIated bowel, was noted to the Ieft of the mass. Recta1 examination was negative. The temperature was g8”F., the pulse 80, and the bIood pressure I IO systoIic and 80 diastolic. The urine exhibited no abnormaIities. Study of the bIood reveaIed the following: erythrocytes 4,040,000 per c.mm.; hemogIobin 14 Gm. (96 per cent HeIIige) ; Ieucocytes 8,160 per c.mm. with 70 per cent neutrophiIes, 25 per cent smaI1 lymphocytes, 4 per cent endothelial cells
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and I per cent eosinophiIes; Wassermann reaction negative; non-protein nitrogen 35.5 mg.; creattinine r .zz mg. ; sugar 74.1 mg. ; chlorides
FIG. 9. Case II. Densely scarred muscularis of termina1 iIeum. (~62.) Note dense mar1 of collagen fibers, moderateIy intiltrated with Ieucocytes, repIacing smooth muscle Iayer. I 1.3 mg. ; cholestero1 104 mg.; icteric index 21.6. AggIutination tests for B. typhosus, paratyphosus A, paratyphosus B and B. abortus were negative. Examination of stooIs faiIed to revea1 ova or parasites and stoo1 cuItures yieIded no significant organisms. Radiographs of the gall-bladder reveaIed poor concentration of the dye and showed many shadows resembIing caIcuIi. Barium enema fiIled the Iarge bowel compIeteIy. The right haIf of the transverse coIon was Iow and its inferior margin presented a concavity suggesting pressure from an extrinsic mass. There was some smoothing out of the descending coIon and sigmoid. (Fig. 6.) Barium mea1 showed the eosophagus and stomach to be normaI. At six hours, the stomach was empty and the head of the coIumn was at the cecum. There was a definite narrowing of the distal 8 cm. of the iIeum with obIiteration of the norma mucosal pattern. The lumen of this portion of the ileum measured 5 mm. in diameter. ProximaI to this was a large dense shadow apparentIy due to diIated Ioops of iIeum. (Fig. 7.) The roent-
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genologist, Dr. C. Carter Hamilton, repor-ted a diagnosis of regional ileitis. On March 2, 1936, under avertin ether anes-
FIG. IO. Case II. MuscuIaris of terminal ileum. (X 140.) GranuIation tissue denseIy infiItrated with plasma ceIIs, Iymphocytes, neutrophiles, eosinophiIes and occasiona foreign body giant ceIIs. A few fragmented smooth muscle bundks remain.
472 mg.; caIcium
the abdomen was opened through a 5 inch right paramedian incision. No increase of free fluid was noted. Occupying the Iower right portion of the abdomen was a congIomerate mass of intestine adherent to the posterior peritoneum and to the greater omentum. After the Iatter was dissected off, the detaiIs became evident. In places the mass was hard and noduIar. It was almost impossible to differentiate afferent and efferent Ioops, but included in the mass were a segment of distal iIeum, the cecum, the ascending colon and part of the transverse colon. There were many paIpabIe glands in the mesentery. The ileum proxima1 to the mass was diIated. (Fig. 8.) A resection of the dista1 IOOcm. of the iIeum with the cecum, ascending coIon and proximaI haIf of the transverse coIon was then done. An end to end anastomosis was estabIished and tube enterostomy made above the site of union. The tube was brought out through a stab wound of the right loin and the abdomina1 waII was cIosed in Iayers without drainage. At the conthesia,
724
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elusion
of operation, the patient was given of titrated bIood. This was foIIowed by continuous intravenous administration of 5 per 500 C.C.
FIG. I I. Case II. Lining of termina1 ileum. (X140.) Norma1 mucosa and submucosa are absent. Regenerated simpIe columnar epitheIium covers chronic granulation tissue.
cent gIucose in norma saIine at the rate of 3,000 cc. in twenty-four hours. The postoperative course was not remarkabIe. Two days after operation, the enterostomy tube commenced to drain and auscuItation reveaIed feebIe peristaItic sounds. The abdomen was soft. The temperature went to IOI’F. and the puIse to IIO. EarIy on the morning of the third postoperative day, the patient had a spontaneous bowel movement. He was then aIIowed water by mouth in smaI1 amounts. On the fourth postoperative day, the abdomen was ffat and the patient had two more spontaneous Iiquid stooIs. On the seventh day the enterostomy tube came out. Two days Iater the sutures were removed and the wound heaIed by primary intention. On the eIeventh postoperative day the patient was aIIowed to sit out of bed. His diet had been graduaIIy increased and he was ravenousIy hungry. Nineteen days after operation the patient was discharged from the hospita1. At that time, he was having eight to ten bowel movements per day, most of which were partIy formed. Following discharge from
MARCH,,939
the hospital, the patient continued to gain in weight and strength and in two months resumed empIoyment.
FIG. 12. Case II. Focus of necrosis in iIiac mesentery. (X62.) CentraI necrosis with numerous foreign body giant cells, endotheIia1 Ieucocytes, Iymphocytes and pIasma ceIIs. Outer zone of fibrosis. ResembIance to tubercle formation is sIight.
One year after operation, the patient appeared greatly improved. He reported that he was eating weI1, had had no indigestion nor pain, but did have four to six formed stooIs in twenty-four hours; his weight was I IO pounds. The specimen removed consisted of the termina1 g8 cm. of the iIeum attached to 26 cm. of Iarge bowe1, incIuding cecum, ascending coIon, and part of the transverse colon. Ap70 cm. of the termina1 iIeum was proximateIy bound together as a mass of adherent Ioops. Over the lower anterior surface of this mass, an appendix g cm. Iong was densely adherent. Fibrous adhesions aIso were present between the coiIs of iIeum and the transverse and ascending coIon and the cecum. The appendix was sharpIy kinked I cm. from its base. The opening of the appendix reveaIed a mucosal poIyp covering a perforation which extended compIeteIy through the appendix into the adjacent indurated mass of mesentery and coiIs of iIeum. After freeing the iIeum from adhesions and extending it at fuI1 Iength, it was found that
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the tip of the appendix was adherent to a point on the iIeum 57 cm. from the cecum. For a distance of 17 cm. from the ileocecal vaIve, the mucosa of the ileum was smooth, pale and granular, with complete obliteration of valvuIae conniventes. The Iumen of this portion was greatIy narrowed, the bowe1 circumference being 3.5 cm. The waI1 was moderateIy thickened at the mesenteric attachment, measuring 0.7 cm., but onIy sIightIy thickened over other parts of the circumference. ProximaI to this for 23 cm., the mucosa1 foIds were visibIe, but were bIunted and edematous. The bowe1 at this point measured 0.4 cm. in thickness and 4.5 cm. in circumference. An uIcerated gutter extended along the mesenteric attachment of this portion. ProximaI to this for 29 cm. the wal1 was markedIy indurated, measuring I. I cm. in thickness, with the circumference about the same. The mucosa1 pIicae were obIiterated and the lining showed a coarseIy granular, duI1 white surface. At the proxima1 limit of this segment, the Iumen became markedly constricted, and in this region there were two perforations which couId be probed into the thickened mesentery. ProximaI to this, there was a Ioop of iIeum 16 cm. in Iength and greatIy diIated, the circumference being I 1.0 cm. The waI1 of this portion was denseIy scarred and measured 0.7 cm. in thickness. The mucosa was coarseIy granuIar and showed no vaIvuIae. ProximaI to this for I I cm., the ileum was constricted to a circumference of 4.5 cm. and the waI1 thickened to I cm. A gutter-like uIcer was present aIong the mesenteric attachment and irreguIar uIcers were scattered over the rest of the mucosa, but the mucosa1 foIds remained indistinctIy visible. The proxima12 cm. of the specimen showed reIativeIy normal ileum. The attached mesentery was greatly hypertrophied and scarred; it was 2 cm. in thickness, and contained enlarged, hyperpIastic Iymph nodes. Scattered small abscesses fiIIed with yellow purulent materia1 were present in the dense fibrous tissue. The mucosa of the appendix, except in the neighborhood of the perforation, appeared reIativeIy normal, as did also that of the cecum and colon. The muscularis was not remarkabIe. The serosa of the large bowe1 was roughened by fatty fibrous tags. Of the severa sections of the iIeum studied, some showed the muscIe obscured by dense scar tissue (Fig. 9) and the mucosa almost compIeteIy absent. In its pIace was a layer of
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granulation tissue denseIy infiItrated with pIasma ceIIs, Iymphocytes, neutrophiIes and eosinophiles, with scattered foreign body giant ceIIs present in pIaces. Such granuIation tissue extended deepIy into the bowe1 waI1 at various points. (Fig. IO.) OccasionaIIy, it was covered bv a Iayer of regenerated simpIe cohrmnar epitheIium. (Fig. I I.) Other sections showed Iess of the muscIe coat repIaced by fibrosis and more intact mucosa. The serosa and mesentery were denseIy scarred and hyperpIastic, chronicaIIy inff amed lymph nodes were observed. Some sections reveaIed smaI1 foci of necrosis surrounded by dense Iymphocytic and pIasma ceI1 infiltration with an outer zone of dense Fibrosis. In the centra1 part, endotheIia1 ceIIs and numerous foreign body giant ceIIs were present. (Fig. 12.) The resembIance to tubercie formation was very superficia1. The appendix was not sectioned at the site of the perforation, but sections near this area showed intact mucosa with moderate scarring and Ieucocytic infiltration of the waI1. The serosa was covered by fibrous tags. The coIon appeared reIativeIy normal in the sections studied. The serosa1 surface was covered by congested, fatty, fibrous tags inhItrated with Iymphocytes and piasma ceIIs plus a few neutrophiIes. CuItures and smears made by the surgeon, and cuItures, smears and anima1 inocuIations of macerated tissue seIected by the pathoIogist from iIeum, Iymph nodes and mesentery, reveaIed no significant organisms. The pathoIogic diagnosis made was: chronic stenosing uIcerative termina1 iIeitis; perforations of appendix and ileum with fistulous tracts into iIiac mesentery; chronic localized peritonitis; chronic hyperplastic lymphadenitis. Two years after the primary operation, this patient was readmitted to hospital with an incomplete intestinal obstruction; there was some vomiting, moderate abdominal distention, but not compIete obstipation. He was treated by continuous duodena1 drainage, hot packs and intravenous fluids, but did not improve. Three days Iater, under spina anesthesia, a jejunostomy was done but no attempt at exploration of the abdomen was made. This procedure afforded but temporary reIief and the patient expired forty-eight hours after the jejunostomy. At post-mortem, the peritoneal cavity contained about 200 C.C. of thin, cloudy reddish-
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brown ffuid which had penetrated to all portions of the sac. The serous surfaces of the bowe1 and the parieta1 peritoneum were duII
MARCH, ICJW
The Iarge bowel, 74 cm. Iong, had a circumference of 4.5 cm. Its mucosa showed no ulcerations, but at the site of anastomosis of
FIG. 13. Case II. Portion of intestina1 tract removed at post-mortem. The longer segment is smaI1 intestine and the short one is colon. Note the comparative size of iIeum and colon, the ulcers of the mucosa of the iIeum and probe passed through stenosed site of anastomosis.
and covered with a thin layer of fibrin. The dista1 portion of the termina1 iIeum was adherent to the right anterior aspect of the peIvic brim by fibrinous adhesions. Very sIight traction on the bowe1 caused Iacerations in the bowe1 waI1 at the sites of severa Iarge ulcers. The bases of the uIcers remained attached to the parieta1 peritoneum and a Iarge amount of thin, dark brown intestina1 fIuid ran out through the perforation. The combined length of the Iarge and smaI1 125 cm., bowe1 was 200 cm. The smaII intestine, was markedIy dilated and Wed with a thin, dark brown intestina1 -fluid. Its serosa had a bIuish color. The upper third was g cm. in circumference, the middIe third IO cm., and the Iower third 12 cm., whiIe the bowe1 was 0.3 to 0.4 cm. thick. The dista1 third had many Iarge ulcers varying in size from 0.3 to 3 cm. in diameter and tending to have their Iong axes perpendicuIar to the Iong axis of the bowel. The edges of the uIcers were cIean and free of tubercIes. The uIcers were so numerous that they covered about 30 per cent of the mucous surface in the Iower third of the smalI intestine. The mesentery was sIightIy thickened and edematous and contained a few enIarged Iymph nodes.
the iIeum and coIon there was a stenotic region I cm. wide with an internal diameter of 0.4 cm. (Fig. 12.) The other abdomina1 viscera were not remarkabIe. MicroscopicaIIy, the mucosa of the iIeum showed many uIcers which in some pIaces extended down to the muscIe Iayer, and even the remaining mucosa was edematous and infiItrated with poIymorphonucIears and some monocytic ceIIs in pIaces, especiaIIy beneath the uIcers. The gangIion ceIIs of the mesenteric plexus were granuIar and swoIIen. Many large coIIections of Iarge and smaI1 monocytic cells were present between circuIar and Iongitudinal muscIe Iayers. The serosa was thickened, edematous, infiItrated in some pIaces with many poIymorphonucIears and monocytic ceIIs and was,covered by a thin Iayer of fibrin. FinaI diagnoses were: acute and chronic ulcerating enteritis; sero-tibrinous peritonitis; iIeocoIostomy (oId) with stenosis at site of union; intestina1 obstruction. DISCUSSION
CIinicaIly, these two cases agree in aImost every respect with the disease entity, regiona iIeitis, as described by
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Crohn and associates.’ Case I ran a more acute course than most of those described, and Case II a much more chronic course, but wide variations in this respect are mentioned. Case II indicates the tendency to recurrence months after an apparently compIete excision of the diseased intestine. The pathoIogy of these cases varied in certain detinite ways from that first described by Crohn. Case I reveaIed typical invoIvement of the iIeum and mesentery, but an acute uIcer of the cecum was present. The appendix in this case was probabIy “ free from guiIt” but its Iumen was partialIy obIiterated by fibrosis. The acute changes observed were peri-appendicitis, apparentIy secondary to the iIeitis. Case II exhibited typica chronic uIcerating cicatrizing iIeitis, or the “stenotic phase of regional iIeitis,” but the process irreguIarIy invoIved the termina1 g6 cm. of the iIeum and an old perforation in the appendix might IogicaIIy expIain the entire pathogenesis. Demonstration of a specific etiology for either of these cases was impossibIe. We beIieve they are further proof in support of the statement of Homans and Hass13 who, after carefuIIy studying two cases of this group, concIuded: “We agree that a terminai iIeitis presents a rather characteristic cIinica1 picture, but acceptance of the local Iesion as a pathoIogic entity is certainIy premature, since criteria are Iacking by which one can segregate this granuIomatous process from simiIar Iesions occurring eIsewhere in the intestina1 tract.” CONCLUSIONS I. We beIieve regiona iIeitis to be a definite cIinica1 but not a definite pathoIogic entity. 2. The terminal iIeum, cecum and other parts of the smaI1 or Iarge intestine may be invoIved in the process. 3. Diagnosis rests on the history, finding of a mass in the right Iower quadrant, pIus the typica string sign shown by x-ray. _2. CompIete gastrointestina1 series shouId be done in any suspected case, as the
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lesion does not aIways show up with a simpIe barium enema. 3. Treatment depends on the findings in each individua1 case and varies according to the acuteness or chronicity of the process. Resection eventuaIIy may be necessary in order to bring about a compIete cure, but in the acute cases it is sometimes better to do a preIiminary iIeostomy, coIostomy or anastomosis, with resection at a later date. REFERENCES I.
CROHN,
BURRELL, B., GINZBURG, LEON, and GORDON D. RegionaI iteitis. A pathologica and clinica entity. J. A. M. A., 99: ‘323, 1932. ERB, I. H., and FARMER, A. W. IIeo-coIitis. Surg., Gynec. @ Oh., 61: 6, 1935. MEYER, KARL A., and ROSI, PETER A. RegionaI enteritis (non-specific). S. C[in. Nortb America, 15: 697, ‘935. GALAMBOS, A., and MITTELMANN, W. Typical and atvoical termina1 Ileitis. Am. J. Diees. Dis. P? Ntirition, 2: 442. 1935. KOSTER, HARRY, KOSMAN, LOUIS P., and SHEINFELD, WILLIAM. RegionaI ileitis. Arch. Surg., 32: $39, 1936. BARGEN, J. A., and DIXON, C. F. Regional ileitis. Proc. .%$&feet. Mayo Cl&., IO: 814, 1935. FELSEN, JOSEPH. Acute and chronic baciIlary dysentery. Am. J. Patb., 12: 395, 1936. FELSEN, JOSEPH. ClinicaI notes concerning dista1 iIeitis as a manifestation of bacilIary dysentery. Am. J. Diges. Dis. @ Nutrition, I: 782, 1935. FELSEN, JOSEPH. Non-specific utcerative colitis, terminal (distal) iIeitis, and bacihary dysentery. Their common pathogenesis. New York State J. Med., 35: 576, 1935. CROHN, BURRELL B., and ROSENAK, BERNARD D. A combined form of ileitis and colitis. J. A. M. A., 106: I, 1936. MOCK, HARRY E. Infective granuloma. Surg., Gynec. Ed Obst., 52: 672, 1g31.BARBOUR, R. F.. and STOKES. A. B. Chronic cicatrising enteiitis. Lancet, I : igg, 1936. HOMANS, JOHN, and HASS, GEO. M. RegionaI iIeitis; a cIinica1, not a pathological entity. New England J. Med., 209: 1315, 1933. MIXTER, CHARLES G. RegionaI iIeitis. Ann. Surg., 102: 674, 1935. GINZBURG, LEON, and OPPENHEIMER, GEOR<;~. Non-specific granmomata of the intestines. Ann. Surg., 98: 1046, 1933. MEYER, KARL A., and ROSI, PETER A. Regional iIeitis (non-specific). Surg., Gynec. ti Oh., 62: 977, 1936. BINNEY, HORACE. Non-specific granuIoma of the iIeo-ceca1 region. Ann. Surg., 102: 695, 1935. KANTOR, JOHN L. RegionaI (termina1) iIeitis; its roentgen diagnosis. J. A. M. A., 103: 2016, 1934. PROBSTEIN, JACOB, and GRUENFELD, GERHARD E. Acute regiona iIeitis. Ann. Surg., 103: 273, 1936. OPPENHEIMER,
2.
3.
4.
5.
6. 7. 8.
9.
10.
II. 12.
‘3.
‘4. 15.
16.
17. IS. ‘9.
ALBERT VANDERVEER, II, M.D.
DICKINSON, M.D. P.A.C.S.
Attending Surgeon, MemoriaI HospitaI
Associate Attending Surgeon, St. Peter’s Hospital AND
JOHN
J.
CLEMMER,
M.D.
Director, Bender Hygienic Laboratory ALBANY,
NEW YORK
T
HE term regiona iIeitis was first used by Crohn et a1.l to describe a condition of non-specific inff ammatory disease occurring in the dista1 portion of the iIeum. SubsequentIy, with more widespread recognition of the condition, a variety of names have been given to this process. Erb and Farmer2 describe their cases under the caption iIeocoIitis; Meyer and Rosi3 under the titIe regiona enteritis (non-specific) ; GaIambos and MitteImann4 as termina1 iIeitis; antedating a11 of them are the oId terms, infectious granuIoma and sarcoid. Eliology. RegionaI iIeitis is most frequent in young aduIts, but it has been reported in patients of various ages. Koster, Kosman and SheinfeId,5 in a detaiIed review, noted its occurrence in each of the first seven decades. EarIy reports’ indicated a ratio of two maIes to one femaIe, but of the seventeen cases reported with the by Koster et a1.,6 combined sixty-two cases in which the sex was mentioned, which they coIIected from the there were forty-four maIes Iiterature, and thirty-five femaIes, not a significant difference. Occupation does not appear to be a factor. Crohn, Ginzburg and Oppenheimer’ noted that members of the Hebrew race appeared to be more susceptibIe than others, and their observation has been confirmed in subsequent reports. However, Bargen and Dixon 6 faiIed to note a prevaIence of Jews among the numerous cases of regiona iIeitis observed at the Mayo CIinic. 714
AIthough the condition appears to be definiteIy infectious, various cuItura1 methods, anima1 inocuIations, immunoIogic procedures and detaiIed histoIogic studies have faiIed to revea1 a specific etioIogic infectious agent. FeIsen’s investigations,7~s~g indicating that the condition is initiated by acute baciIIary dysentery, are an exception to this statement. He obtained positive aggIutination titers against organisms of the EbertheIIa dysenteri group (SonnbDuvaI type, especiaIIy) in sixty-two consecutive cases of chronic uIcerative coIitis, in fourteen cases of chronic dista1 iIeitis, and in two cases of non-specific iIeoceca1 granuIoma. Diagnostic bacteriophage reactions and positive feca1 cuItures for dysentery baciIIi were obtained in some of the cases. Control studies of 300 bIood sera resuIted in 4.6 per cent positive aggIutination reactions with E. dysenteri. Acute dista1 iIeitis was observed in fourteen cases of acute baciIFeIsen conchrded that Iary dysentery. dysentery in this atypica1 form at times progressed into a chronic phase and with the aid of secondary non-specific infection resuIted in “regiona iIeitis.” In discussing “A Combined Form of IIeitis and the paper, CoIitis,” presented by Crohn and RosenakrO at the 1933 session of the American MedicaI Association, FeIsen stated that “chronic non-specific uIcerative coIitis and distal re iona1) iIeitis, either aIone or as asso( g ciated Iesions, and non-specific iIeoceca1 granuIoma are a11 manifestations of baciICrohn rephed that careful Iary dysentery.”
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studies of the cases of regiona iIeitis observed at the Mount Sinai HospitaI failed to substantiate this view. The majority of the authors reporting this condition appear to have had simiIar diffIcuIties in proving a B. dysentery etioIogy. Koster et aI., observing a certain simiIarity of regional iIeitis to lymphogranuIoma inguinale, appIied the Frei test to six of their cases but with uniformIy negative resuIts. Mockll has reported a number of cases of “infective granuIoma” of various IeveIs of the gastrointestina1 tract incIuding Iesions of the “regional iIeitis” type. He attributed the conditions to various non-specific factors, such as appendicitis, foreign bodies, uIcers, extra peritonea1 infections, trauma and so forth, and stated that the “condition is directIy due to Iow grade infection causing an impairment of circuIation or to an impairment of circulation foIIowed by Iow grade infection.” Barbour and Stokes12 suggested that a chronic recurrent intussusception might initiate the process by impairing the circuIation and vitaIity of the gut waI1 and aIIowing bacteria1 invasion from the Iumen. SeveraI authors have submitted statistics indicating that about 50 per cent of these patients previousIy have had an appendectomy. ObviousIy, appendectomy in itseIf wouId not be an etioIogic factor although early symptoms of iIeitis are frequentIy mistaken for appendicitis. Homans and Hass13 suggest an association between appendicitis and ileitis, stating that in both of their cases there was definite evidence of disease of the appendix. Mixter,l” among others, expresses himseIf as opposed to any such reIationship. We must concIude that the exact etioIogy and pathogenesis of regiona iIeitis has not been determined; that it appears to be a non-specific inff ammatory process initiated perhaps by a variety of factors and aggravated by various constituents, bacteria1 and otherwise, of the intestina1 content. The patbology of regiona ileitis is that of a- progressive non-specific proIiferative inf-lammatory process .5,15 In the earIy phase
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the invoIved segment of bowe1 and its mesentery are edematous and congested. The muscIe fibers of the bowel waI1 are separated by edema, and moderate diffuse Ieucocytic infiltration is present. FocaI hemorrhages occur, particuIarIy near the serosa. There is a hyperplasia of Iymphoid tissue in the submucosa and in the adjacent mesenteric nodes. The mucosa aIong the mesenteric attachment of the gut exhibits IongitudinaI uIcers. The vaIvuIae conniventes are bIunted and indistinct, depending upon the degree of edema. As the process progresses, the mucosa1 uIcers extend into the wall and fistuIae may form. These often end bIindIy in the attached mesentery, but, at times, they communicate with another viscus or drain externaIIy. Generalized peritonitis is usuaIIy prevented by extensive adhesions. Foci of necrosis with abscess formation are found in the bowe1 waI1 and the mesentery. The centra1 part of these foci shows many neutrophiIes, endotheIia1 Ieucocytes and foreign body giant ceIIs, and toward the periphery Iymphocytes and pIasma ceIIs predominate. OccasionaIIy particIes of foreign materia1, presumabIy from the Iumen of the intestine,‘j are demonstrabIe. SmaII foci of inffammation superficiaIIy resembIing tubercIes may be present just beneath the serosa. Coexistent with the injury and destruction of tissue, there is marked proIiferation and repair. GranuIation tissue forms at the sites of the uIcers and abscesses, and dense fibrosis of the intestina1 waI1 and adjacent mesentery occurs. Regenerated simpIe columnar epitheIium may cover the uIcerated areas, resuhing in a flattened, smooth epitheIia1 surface with no evidence of mucosa1 foIds. In other areas edematous vaIvuIae conniventes form sessiIe poIypi. EventuaIIy, stenosis of the bowe1 occurs, and the proxima1 intestine diIates and hypertrophies. OriginaIIy, the Iesion was beIieved to incIude onIy the termina1 iIeum, beginning at the iIeoceca1 vaIve and progressing proximaIIy for 25 to 35 cm. in the __. . _ _ .. t1eum.l It IS now recogmzed that a non-
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specific chronic inflammatory this type may invoIve any intestinal tract.“, 10s11,138 15,16,17
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process of part of the
FIG. I. Case I. X-ray taken six hours after oral barium suIfate. Note typica string sign, representing the terminal ileum and diIatation of proximal ileum.
Symptoms. The symptoms of regiona iIeitis vary with the Iocation of the process in the intestina1 tract, its acuteness or chronicity, the duration and extent of the lesion and the presence or absence of compIications such as abscesses, fistulae, etc. In the Iarge majority of reported cases the history of the iIIness is measured by years, ten or more not being unusua1. As most commonIy the Iesion is Iocated in the dista1 iIeum, the majority of symptoms and to the right Iower signs are referred quadrant of the abdomen. Crohn et a1.l have divided the symptoms into four groups. In Group I the symptoms resembIe those of acute appendicitis, with pain and tenderness in the right Iower quadrant, fever and vomiting, aIthough the onset is usuaIIy somewhat sIower than that of typica acute appendicitis. NevertheIess, that many of the earIy acute cases are mistaken for appendicitis both pre- and postoperativeIy is attested by the reports
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in the Iiterature. The postoperative deveIopment of obstructive symptoms or persistence of fistuIae finaIIy has indicated the correct diagnosis. It is easy to understand that if an abscess about the cecum is drained, with minimum disturbance of the intestines, detection of the basic process may be missed. Meyer and Rosi16 reported such an instance in which the persistence of a f%tuIa foIIowing drainage of an abscess Ied to further study. On the other hand, where operation discIoses “chronic appendicitis” in a patient who presents symptoms suggesting an acute process, it is d&uIt to understand how a competent surgeon shouId miss the rea1 pathoIogy. Group II incIudes those cases presenting symptoms of uIcerative enteritis. There is a history of coIicky abdomina1 pain, frequent stooIs with mucus and sometimes bIood. There is aIso Ioss of weight and secondary anemia. Repeated stoo1 and proctoscopic studies show nothing de6nite. Often these patients have a history Iasting for years. GaIambos and MittIemann4 reported a case of this type, the patient having suffered with diarrhea and pain for fifteen years; the persistence of a fistuIa foIIowing appendectomy finaIIy attracted attention to the underIying condition. Group III comprises those cases with obstructive symptoms which usuaIIy occur Iate in the course of the disease, but in some instances appear suddenIy without previous compIaints. The symptoms are generaIIy those of an incompIete obstruction of the smaI1 intestine. There are cramps, pain, borborygmi, distention and perhaps nausea and vomiting. Often there is a history of recurring attacks of diarrhea. In Group IV are those cases with fistuIae. The fistuIae may be of the externa1 type and foIIow expIoration and drainage or they may be of the interna type with a fistuIous tract connecting the iIeum with the coIon or sigmoid. Symptoms occurring in this group of cases vary greatIy, but commonIy there are diarrhea, Ioss of weight, anemia and abdomina1 cramps. There may be intervaIs of fever during periods of activity.
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Individual symptoms occurring in the course of the disease warrant further discussion. AbdominaI pain seems to be the
FIG. 2. Case I. MuscuIaris of terminal iIeum. (X62.) Note separation of smooth mu&e fibers by edema and diffuse Ieucocytic infiftration.
most outstanding symptom. It is usuaIIy of a colicky or cramp-Iike type and is more commonIy Iocated in the Iower right quadrant, although it may be diffuse. It may be duI1, and it is often reIieved by defecation. In the presence of abscesses or fistuIae, naturaIIy the pain wiI1 be of a different type and Iocation. In some instances, the pain is acute and severe, simiIar to that seen in appendicitis. CarefuI review of the reported cases shows a record of pain in nearIy every one and the recurring descriptive terms ‘coIicky’ or ‘cramplike’ are significant. Diarrhea is aIso a common symptom aIthough by no means so constant as pain. UsuaIIy there is a history of from four to six soft stooIs per day. It is uncommon to obtain a history of many movements aIthough Homans and Hass’3 reported the case of a patient who had twenty to thirty stooIs daiIy over a period of six years. OccasionaIIy mucus appears in the stooIs, but
American Journal of Surgery
717
bIood is a rare finding. Diarrhea is absent in about one-third of the reported cases. Nausea and vomiting are reIativeIy in-
FIG. 3. Case I. Acute uIcer of terminal iIeum. (X62.) Observe f?brinopuruIent exudate on uIcer base and marked hyperpIasia of Iymphoid tissue of Peyer’s patch.
frequent symptoms. However, there is often a history of indigestion and eructation of gas. Fever is a variabIe factor. High temperatures are uncommon except in the acute type of case or with the deveIopment of complications. A moderate fever of 99 to 102 degrees is present in about 35 per cent of the cases, and periods of fever foIIowed by apyretic intervaIs are often observed. Loss of weight is commonly noted, varying from a few pounds to 20 or 30. At times, these patients become markedIy emaciated and dehydrated. Secondary anemia is an aImost constant finding, the degree depending upon the extent and duration of the disease. Leucocytosis is the ruIe, with a count of about 14,000, although norma Ieucocyte counts are not infrequent. The abdomina1 findings are quite constant. UsuaIIy there is moderate distention of the abdomen. Rigidity is absent except in the compIicated case. Often there is an
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et al.-Enteritis
area of tympany due to dilated gut proxima1 to the Iesion. In at Ieast 50 per cent of the reported cases, a mass is
FIG. 4. Case I. Serosa of termina1 ileum. (X 140.) Observe extravasated cIoseIy packed erythrocytes in subserosal adipose tissue with smaIIer hemorrhages on serosa1 surface.
paIpabIe. UsuaIIy the mass is Iocated in the Iower right quadrant, aIthough it may be in the mid-abdomen. It is tender, rather firm, somewhat irreguIar in outIine and sIightIy mobiIe. The size varies from IO to 40 cm. in Iength and 5 to IO cm. in width. In some instances the mass may be paIpated through the rectum or vagina. Where partia1 obstruction exists, peristaItic waves are occasionaIIy visibIe and audible. Diagnosis. RoentgenoIogy is of considerabIe assistance in diagnosing this condition. Crohn and his associates’ discussed the findings in their origina report, and Kantorl* has described the Roentgen signs in detai1. According to him, the ora contrast medium is IikeIy to demonstrate one or more of the foIIowing : (I > a fiIIing defect of the iIeum (or coIon), the size depending upon the extent of the Iesion; (2) an area of tapering off immediateIy proximaI to the defect, rather than a sharp change; (3)
MARCH, 1939
diIatation of the gut proximaI to the Iesion with or without a demonstrable Auid IeveI; (4) the string sign in which a thin Iinear
FIG. 5. Case I. Lymph node from iIiac mesentery. (X28.) GerminaI centers are enIarged and hyperpIastic. sinusoids diIated and HIed with exudate.
shadow resembIing cotton string extends through the obstruction. Barium enema aIone is of IittIe vaIue in most cases as it faiIs to show the Iesion. RegionaI iIeitis is to be differentiated from uIcerative colitis. This can usuaIIy be accompIished by proctoscopic examination and a barium enema which wiI1 be negative in the former and positive in the Iatter condition. The history and physica examination, especiaIIy of the chest, aIong with gastrointestina1 x-rays wiI1 assist in ruIing out tubercuIous Iesions of the intestine. Differentiation from acute appendicitis can usuaIIy be made by the clinical findings, aIthough carefuI examination of the abdomen at operation may be necessary. Great assistance can be obtained from the roentgenoIogist in ruIing out actinomycosis and neopIasms of this region. FinaIIy the condition may be confused with so caIIed “idiopathic spastic enteritis.” UsuaIIy the symptoms in spastic enteritis are
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less marked and are transitory; the roentgenogram is quite different aIso. The mortaIity rate of regional ileitis
FIG. 6. Case II. Roentgenogram of colon foIlowing barium sulfate enema. Observe low position of right half of transverse colon and compare concavity of its inferior margin with diagram of operative findings in Figure 8.
varies with the severity of the process, its duration, magnitude of any operative procedures, etc. AccordingIy from the Iiterature one may gather very high as we11 as Low mortaIity statistics. Binney17 reviewed twenty-six cases with onIy one death in the series; Mixter,14 on the other hand, reported eIeven cases with a mortaIity rate of 36 per cent. A review of a considerably larger number of cases by the present writers discIoses a mortality rate of about 12 per cent. It shouId be noted that recurrences folIowing incompIete eradication of the process are quite frequent. The treatment of regiona ileitis depends upon the extent of the disease and the condition of the patient. Meyer and Rosi’” limited themseIves to expIoration and appendectomy in three of their eight cases; and carefuI observation over long periods reveaIed no further evidence of the disease. These authors suggest that when the edema
American
Journd
of Surgery
719
is limited to the intestina1 waII, infection is IocaIized to this region and probably wiI1 resolve spontaneousIy. If thickening of the
FIG. 7. Cast II. Roentgenogram, six hours after oraI barium sulfate. Narrowing of distal 8 cm. of ikum and obliteration of mucosa1 pattern. Large opaque mass in midline represents dilated proximal ileum.
mesentery and hyperpIasia of the neighboring Iymph nodes exist, however, this indicates a spread of the infection and makes more radica1 procedures necessary. Likewise, Probstein and GruenfeId’g reported three cases in which the operative procedures consisted of appendectomy with iIeostomy; and the uItimate results were satisfactory. We must be cautious in our appraisa1 of such conservative treatment, for up to the present, insuffIcient cIinica1 materia1 is avaitable to warrant finaI concIusions. We do know that recurrences are moderately frequent even after resection. If abscesses exist, these must be drained before any further surgery is contempIated. When there is considerabIe stenosis of gut, resection is indicated if the patient’s condition wiI1 permit. In some instances, an iIeocoIostomy seems to afford permanent reIief, but usuaIIy this procedure is con-
720
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sidered a temporary measure to be foIIowed by resection when the patient’s condition is suffrcientIy good. Meyer and
Moe6 consieting 0i 69 cm. of terminal ileum, adherent to colon. FIG.
MARCH. ,939
pain in the right Iower quadrant. The pain was steady and accompanied by nausea and vomiting. The patient had noticed a gradually in-
of Ileum,
16 cm.
in length,
greatly (Circum- 11 cm.)
dilated. ference circwn. 0
#
5 centimetero.
10
Q
8. Case II. Schematic drawing of operative findings. Excised bowel consisted of g8 cm. of ileum attached to 26 cm. of Iarge intestine.
Rosi16 point out that simpIe iIeocoIostomy is foIIowed by recurrence in at Ieast 50 per cent of cases. When resection is done, the Iine of excision must be we11 away from diseased tissue, for recurrences are considered to be the resuIt of Ieaving behind invoIved areas. FistuIae have to be treated by resection of the tract and excision of the area of the gut involved; perhaps resection may be indicated. Transfusion has found favor as a means of preparing many of these patients for operation. We present the foIIowing two cases to iIIustrate the cIinica1 and pathoIogic findings of the acute and chronic phases of regiona iIeitis. CASEI. A young, maIe Hebrew twenty-two years of age was first admitted to St. Peter’s HospitaI in December 1935, compIaining of
creasing constipation over a period of six months before entrance into the hospital. The famiIy history and past history were negative except for severa simiIar attacks during the past year, aIways reIieved by rest and hot packs. There was no diarrhea nor Ioss of weight. The physical examination revealed a rather thin, young maIe aduIt apparentIy in some pain. Heart and Iungs were negative. There was definite tenderness over McBurney’s point in the right Iower quadrant. No masses were paIpabIe, nor was there any marked rigidity. The temperature was 99.2”F., the puIse 88 and respirations 20. Blood count revealed 22,000 Ieucocytes per c. mm. with go per cent poIymorphonuclears and IO per cent lymphocytes. Wassermann examination was negative, as reported Iater. The patient was operated upon about four hours after admission, the preoperative diagnosis being acute exacerbation of a chronic
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appendicitis. A Iower right rectus incision was made and opening of the peritonea1 cavity discIosed a smaI1 amount of free ffuid. The appendix was deIivered and found to be sIightIy swoIIen and edematous, but not apparentIy acuteIy infIamed. Further exploration showed some edema and thickening of the termina1 portion of the iIeum, which was regarded at the time as no doubt secondary to the appendix. We considered that this would subside foIIowing the appendectomy. The patient’s convalescence was uneventful, the wound heaIing by primary union, and he was discharged as cured on the eleventh postoperative day. He was eating well, his boweIs were regular, and he complained of no pain. The pathoIogic report was chronic obIiterative and acute appendicitis. The patient was home for ten days, and during this time he began to compIain of vague, transient abdomina1 pain beginning in the region of the umbiIicus and radiating in a11 directions. The pain was not constant, but was fairly sharp when present. Some beIching of gas and constipation were also present. There was no nausea nor vomiting. He re&ntered the hospita1, this time on the medical service. The temperature on admission was normaI, but varied between gg and IOO degrees during his stay in the hospita1. The puIse varied between 72 and 84. Barium enema reveaIed a fixation and distortion of the cecum, apparently the resuIt of adhesions from the previous operation. There seemed to be considerable spasm about the cecum. The patient was put on atropine, and this pIus rest in bed brought about marked improvement. He was discharged as cured after eight days. The diagnosis was postoperative adhesions and spasm. However, after about two months at home, he was again admitted to the hospita1 on March 5, 1936. During the interva1 he had Iost considerabIe weight and strength. Intermittent pain in the right Iower quadrant had recurred in association with nausea and vomiting. For one week before admission he had been unabIe to retain anything except fIuids, and these onIy in small amounts. Constipation had become more and more severe. PhysicaI examination at this time showed a somewhat emaciated, highIy nervous, young male adult. Temperature was 99.2%., puIse 88 and respirations 20. There were definite tenderness and muscIe spasm in the
Amercian Journal of Surgery
721
right Iower quadrant, but no masses were paIpabIe. Examination otherwise was negative. The urine was negative; bIood sugar was 80 mg. per IOO C.C. of bIood; N.P.N. 36.6; urea N. 15.3; chIorides 433; hemoglobin 70 per cent; erythrocytes 4,256,ooo per c. mm.; Ieucocytes 14,000 per c. mm. with 80 per cent neutrophiIes and 20 per cent Iymphocytes. Under hot packs and rest in bed the temperature returned to normaI, the bowels started and the patient feIt considerabIy moving, better. A gastrointestina1 series was done by Dr. I. J. Murnane, roentgenoIogist, and revealed the typica string sign of termina1 iIeitis. (Fig. I.) A diagnosis of this condition was made, and after an attempt to get the patient in as good condition as possibIe, operation was done. The terminal IO to 15 cm. of the iIeum and the cecum made up a large mass of acuteIy inflamed tissue bound cIoseIy together with old and fresh adhesions. The mass in some respects resembIed a neopIasm. Resection was done and IateraI anastomosis performed between the transverse coIon and the iIeum. The patient’s condition was poor and his postoperative course was steadiIy downhi despite intravenous therapy, etc. Death occurred on the third postoperative day. PathoIogic description of the excised intestine foIIows: GrossIy, the specimen consisted of a segment of terminal iIeum measuring 24 cm., with a portion of the cecum and ascending coIon measuring 14 cm. The proxima1 7 cm. of the iIeum showed a reIativeIy normal mucosa, although the serosa1, surface over part of this area was congested and granuIar. From this point to the iIeoceca1 vaIve, the waI1 of the ileum became progressively thickened, measuring I .I cm. in thickness near the cecum. The most marked thickening was near the mesenteric attachment. The vaIvulae conniventes became graduaIIy more edematous and bIunted toward the iIeoceca1 vaIve, and were unrecognizabIe in the termina1 12 cm., where the mucosa showed edematous rounded eIevations. An ulcerated groove 1.5 cm. in width extended aIong the mesenteric attachment of the distal 12 cm. of iIeum. OraI to this for 5 cm., there were patches of mucosa at the mesentery with IongitudinaI acute uIcerations. SmalI mucosal uIcers were distributed irreguIarIy at points away from the mesenteric attachment. AI-
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et aI.-Enteritis
though the mesentery of the iIeum had been cut cIose to the bowe1 attachment, a few enIarged hyperpIastic Iymph nodes couId be observed in the remaining indurated, thickened mesentery. The serosal surface showed hemorrhage, whiIe the mucosa of the cecum reveaIed an irreguIar uIcer 4 cm. in greatest diameter. The inflammatory process was, however, very much Iess marked here than in the iIeum. The waI1 of the cecum, which was thinner than that of the termina1 ileum, measured 0.6 cm. at its thickest point. Its serosa was congested and roughened by fatty fibrous tags. SeveraI hyperpIastic Iymph nodes were attached. The appendix was absent. Microscopic examination of sections through the termina1 iIeum discIosed edema throughout the waI1. (Fig. 2.) In pIaces the mucosa was ulcerated, with the denuded areas showing young granuIation tissue containing many thin-waIIed capiIIaries and heaviIy infiltrated with leucocytes, the majority of them neutrophiles. (Fig. 3.) Recent foca1 hemorrhages were evident beneath the serosa (Fig. 4) and in the submucosa. The waI1 was diffuseIy infiltrated with Ieucocytes, incIuding lymphocytes, pIasma ceIIs, neutrophiles, eosinophiIes and occasiona giant cells. Scattered dense accumulations of neutrophiles were observed in the iIiac waI1 and the mesentery. The mesentery showed diffuse fibrosis with intermingIed areas of fat. Edema, foca1 hemorrhages and smaI1 abscesses were observed, and occasiona foreign body giant ceIIs were present in the abscesses. Many of the smaI1 arterioIes, capiIIaries, and veins in the serosa and mesenr tery were acuteIy inflamed, whiIe the mesenteric Iymph nodes were hyperpIastic and acuteIy infIamed. (Fig. 5.) Sections through the uIcer in the cecum indicated that the base was covered with young vascuIar granulation tissue heaviIy infiItrated with Ieucocytes. The muscIe was edematous and infiItrated with moderate numbers of Ieucocytes. There were coIIections of Iymphocytes beneath the serosa. The fina diagnosis was acute and chronic uIcerative iIeitis and typhIitis, with acute hyperpIastic Iymphadenitis, most prominent in the termina1 ileum. CASE II. A male Hebrew, age 24, entered the MemoriaI HospitaI February 27, 1936 with compIaints of diarrhea, Ioss of weight and weakness, of severa years’ standing.
According to his parents, his infancy and early chiIdhood had been uneventfu1; he had grown normaIIy and seemed entireIy weI1. At age 14, he had had an intestina1 infection, characterized by diarrhea and Ioss of weight, From then on, he continued to have simiIar attacks every two to three weeks, each lasting one to two days. No bIood or mucus was noted. At age 14 he weighed g8 pounds, and at 20, 84 pounds. His appetite had aIways been fairIy good. There had been no nausea or vomiting, but of Iate he had had considerable flatulence. Six weeks previous to admission, the patient suffered with an infectious process foIlowed by jaundice, subsequentIy proved to be the resuIt of choIeIithiasis. At the age of 2 I, the patient was graduated from an exceIIent engineering college, but found himseIf physicaIIy unabIe to foIIow reguIar empIoyment. Examination of the patient upon admission reveaIed a smaI1, asthenic, paIIid male who weighed 75 pounds and was 5 feet I inch in height. His skin was sIightIy yeIIow, dry and parchment-Iike due to a minimum of subcutaneous fat. The head was negative except for prominence of the fronta bones which was a famiIy characteristic. The mucous membranes of the mouth were of norma color; there was a hard tumor mass, 2 cm. by I cm., Iocated in the center of the hard paIate. The teeth exhibited severa cavities. The neck was essentiaIIy negative. The chest was of the asthenic type with narrow apices and prominent ribs. The heart and Iungs appeared normal. The abdomen was soft and flat with a very sIight panniculus. The Iiver duIness was increased to 2 cm. beIow the Costa1 margin, but its edge was smooth and not tender. The spIeen was not enIarged. No free fluid couId be demonstrated. In the right Iower quadrant of the abdomen, a movabIe and moderateIy tender mass about 15 cm. in greatest diameter was visibIe and paIpabIe, and an unusua1, tympanitic area, suggestive of a Ioop of diIated bowel, was noted to the Ieft of the mass. Recta1 examination was negative. The temperature was g8”F., the pulse 80, and the bIood pressure I IO systoIic and 80 diastolic. The urine exhibited no abnormaIities. Study of the bIood reveaIed the following: erythrocytes 4,040,000 per c.mm.; hemogIobin 14 Gm. (96 per cent HeIIige) ; Ieucocytes 8,160 per c.mm. with 70 per cent neutrophiIes, 25 per cent smaI1 lymphocytes, 4 per cent endothelial cells
SERIES VOL.. XLIII,
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Dickinson
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and I per cent eosinophiIes; Wassermann reaction negative; non-protein nitrogen 35.5 mg.; creattinine r .zz mg. ; sugar 74.1 mg. ; chlorides
FIG. 9. Case II. Densely scarred muscularis of termina1 iIeum. (~62.) Note dense mar1 of collagen fibers, moderateIy intiltrated with Ieucocytes, repIacing smooth muscle Iayer. I 1.3 mg. ; cholestero1 104 mg.; icteric index 21.6. AggIutination tests for B. typhosus, paratyphosus A, paratyphosus B and B. abortus were negative. Examination of stooIs faiIed to revea1 ova or parasites and stoo1 cuItures yieIded no significant organisms. Radiographs of the gall-bladder reveaIed poor concentration of the dye and showed many shadows resembIing caIcuIi. Barium enema fiIled the Iarge bowel compIeteIy. The right haIf of the transverse coIon was Iow and its inferior margin presented a concavity suggesting pressure from an extrinsic mass. There was some smoothing out of the descending coIon and sigmoid. (Fig. 6.) Barium mea1 showed the eosophagus and stomach to be normaI. At six hours, the stomach was empty and the head of the coIumn was at the cecum. There was a definite narrowing of the distal 8 cm. of the iIeum with obIiteration of the norma mucosal pattern. The lumen of this portion of the ileum measured 5 mm. in diameter. ProximaI to this was a large dense shadow apparentIy due to diIated Ioops of iIeum. (Fig. 7.) The roent-
American Journal of Surgery
723
genologist, Dr. C. Carter Hamilton, repor-ted a diagnosis of regional ileitis. On March 2, 1936, under avertin ether anes-
FIG. IO. Case II. MuscuIaris of terminal ileum. (X 140.) GranuIation tissue denseIy infiItrated with plasma ceIIs, Iymphocytes, neutrophiles, eosinophiIes and occasiona foreign body giant ceIIs. A few fragmented smooth muscle bundks remain.
472 mg.; caIcium
the abdomen was opened through a 5 inch right paramedian incision. No increase of free fluid was noted. Occupying the Iower right portion of the abdomen was a congIomerate mass of intestine adherent to the posterior peritoneum and to the greater omentum. After the Iatter was dissected off, the detaiIs became evident. In places the mass was hard and noduIar. It was almost impossible to differentiate afferent and efferent Ioops, but included in the mass were a segment of distal iIeum, the cecum, the ascending colon and part of the transverse colon. There were many paIpabIe glands in the mesentery. The ileum proxima1 to the mass was diIated. (Fig. 8.) A resection of the dista1 IOOcm. of the iIeum with the cecum, ascending coIon and proximaI haIf of the transverse coIon was then done. An end to end anastomosis was estabIished and tube enterostomy made above the site of union. The tube was brought out through a stab wound of the right loin and the abdomina1 waII was cIosed in Iayers without drainage. At the conthesia,
724
American Journal of Surgery
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et aI.-Enteritis
elusion
of operation, the patient was given of titrated bIood. This was foIIowed by continuous intravenous administration of 5 per 500 C.C.
FIG. I I. Case II. Lining of termina1 ileum. (X140.) Norma1 mucosa and submucosa are absent. Regenerated simpIe columnar epitheIium covers chronic granulation tissue.
cent gIucose in norma saIine at the rate of 3,000 cc. in twenty-four hours. The postoperative course was not remarkabIe. Two days after operation, the enterostomy tube commenced to drain and auscuItation reveaIed feebIe peristaItic sounds. The abdomen was soft. The temperature went to IOI’F. and the puIse to IIO. EarIy on the morning of the third postoperative day, the patient had a spontaneous bowel movement. He was then aIIowed water by mouth in smaI1 amounts. On the fourth postoperative day, the abdomen was ffat and the patient had two more spontaneous Iiquid stooIs. On the seventh day the enterostomy tube came out. Two days Iater the sutures were removed and the wound heaIed by primary intention. On the eIeventh postoperative day the patient was aIIowed to sit out of bed. His diet had been graduaIIy increased and he was ravenousIy hungry. Nineteen days after operation the patient was discharged from the hospita1. At that time, he was having eight to ten bowel movements per day, most of which were partIy formed. Following discharge from
MARCH,,939
the hospital, the patient continued to gain in weight and strength and in two months resumed empIoyment.
FIG. 12. Case II. Focus of necrosis in iIiac mesentery. (X62.) CentraI necrosis with numerous foreign body giant cells, endotheIia1 Ieucocytes, Iymphocytes and pIasma ceIIs. Outer zone of fibrosis. ResembIance to tubercle formation is sIight.
One year after operation, the patient appeared greatly improved. He reported that he was eating weI1, had had no indigestion nor pain, but did have four to six formed stooIs in twenty-four hours; his weight was I IO pounds. The specimen removed consisted of the termina1 g8 cm. of the iIeum attached to 26 cm. of Iarge bowe1, incIuding cecum, ascending coIon, and part of the transverse colon. Ap70 cm. of the termina1 iIeum was proximateIy bound together as a mass of adherent Ioops. Over the lower anterior surface of this mass, an appendix g cm. Iong was densely adherent. Fibrous adhesions aIso were present between the coiIs of iIeum and the transverse and ascending coIon and the cecum. The appendix was sharpIy kinked I cm. from its base. The opening of the appendix reveaIed a mucosal poIyp covering a perforation which extended compIeteIy through the appendix into the adjacent indurated mass of mesentery and coiIs of iIeum. After freeing the iIeum from adhesions and extending it at fuI1 Iength, it was found that
NEW SERIES
VOL. XLIII,
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Dickinson
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the tip of the appendix was adherent to a point on the iIeum 57 cm. from the cecum. For a distance of 17 cm. from the ileocecal vaIve, the mucosa of the ileum was smooth, pale and granular, with complete obliteration of valvuIae conniventes. The Iumen of this portion was greatIy narrowed, the bowe1 circumference being 3.5 cm. The waI1 was moderateIy thickened at the mesenteric attachment, measuring 0.7 cm., but onIy sIightIy thickened over other parts of the circumference. ProximaI to this for 23 cm., the mucosa1 foIds were visibIe, but were bIunted and edematous. The bowe1 at this point measured 0.4 cm. in thickness and 4.5 cm. in circumference. An uIcerated gutter extended along the mesenteric attachment of this portion. ProximaI to this for 29 cm. the wal1 was markedIy indurated, measuring I. I cm. in thickness, with the circumference about the same. The mucosa1 pIicae were obIiterated and the lining showed a coarseIy granular, duI1 white surface. At the proxima1 limit of this segment, the Iumen became markedly constricted, and in this region there were two perforations which couId be probed into the thickened mesentery. ProximaI to this, there was a Ioop of iIeum 16 cm. in Iength and greatIy diIated, the circumference being I 1.0 cm. The waI1 of this portion was denseIy scarred and measured 0.7 cm. in thickness. The mucosa was coarseIy granuIar and showed no vaIvuIae. ProximaI to this for I I cm., the ileum was constricted to a circumference of 4.5 cm. and the waI1 thickened to I cm. A gutter-like uIcer was present aIong the mesenteric attachment and irreguIar uIcers were scattered over the rest of the mucosa, but the mucosa1 foIds remained indistinctIy visible. The proxima12 cm. of the specimen showed reIativeIy normal ileum. The attached mesentery was greatly hypertrophied and scarred; it was 2 cm. in thickness, and contained enlarged, hyperpIastic Iymph nodes. Scattered small abscesses fiIIed with yellow purulent materia1 were present in the dense fibrous tissue. The mucosa of the appendix, except in the neighborhood of the perforation, appeared reIativeIy normal, as did also that of the cecum and colon. The muscularis was not remarkabIe. The serosa of the large bowe1 was roughened by fatty fibrous tags. Of the severa sections of the iIeum studied, some showed the muscIe obscured by dense scar tissue (Fig. 9) and the mucosa almost compIeteIy absent. In its pIace was a layer of
American Journal of Surgery
72s
granulation tissue denseIy infiItrated with pIasma ceIIs, Iymphocytes, neutrophiIes and eosinophiles, with scattered foreign body giant ceIIs present in pIaces. Such granuIation tissue extended deepIy into the bowe1 waI1 at various points. (Fig. IO.) OccasionaIIy, it was covered bv a Iayer of regenerated simpIe cohrmnar epitheIium. (Fig. I I.) Other sections showed Iess of the muscIe coat repIaced by fibrosis and more intact mucosa. The serosa and mesentery were denseIy scarred and hyperpIastic, chronicaIIy inff amed lymph nodes were observed. Some sections reveaIed smaI1 foci of necrosis surrounded by dense Iymphocytic and pIasma ceI1 infiltration with an outer zone of dense Fibrosis. In the centra1 part, endotheIia1 ceIIs and numerous foreign body giant ceIIs were present. (Fig. 12.) The resembIance to tubercie formation was very superficia1. The appendix was not sectioned at the site of the perforation, but sections near this area showed intact mucosa with moderate scarring and Ieucocytic infiltration of the waI1. The serosa was covered by fibrous tags. The coIon appeared reIativeIy normal in the sections studied. The serosa1 surface was covered by congested, fatty, fibrous tags inhItrated with Iymphocytes and piasma ceIIs plus a few neutrophiIes. CuItures and smears made by the surgeon, and cuItures, smears and anima1 inocuIations of macerated tissue seIected by the pathoIogist from iIeum, Iymph nodes and mesentery, reveaIed no significant organisms. The pathoIogic diagnosis made was: chronic stenosing uIcerative termina1 iIeitis; perforations of appendix and ileum with fistulous tracts into iIiac mesentery; chronic localized peritonitis; chronic hyperplastic lymphadenitis. Two years after the primary operation, this patient was readmitted to hospital with an incomplete intestinal obstruction; there was some vomiting, moderate abdominal distention, but not compIete obstipation. He was treated by continuous duodena1 drainage, hot packs and intravenous fluids, but did not improve. Three days Iater, under spina anesthesia, a jejunostomy was done but no attempt at exploration of the abdomen was made. This procedure afforded but temporary reIief and the patient expired forty-eight hours after the jejunostomy. At post-mortem, the peritoneal cavity contained about 200 C.C. of thin, cloudy reddish-
726
American Journal of Surgery
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et aI.-Enteritis
brown ffuid which had penetrated to all portions of the sac. The serous surfaces of the bowe1 and the parieta1 peritoneum were duII
MARCH, ICJW
The Iarge bowel, 74 cm. Iong, had a circumference of 4.5 cm. Its mucosa showed no ulcerations, but at the site of anastomosis of
FIG. 13. Case II. Portion of intestina1 tract removed at post-mortem. The longer segment is smaI1 intestine and the short one is colon. Note the comparative size of iIeum and colon, the ulcers of the mucosa of the iIeum and probe passed through stenosed site of anastomosis.
and covered with a thin layer of fibrin. The dista1 portion of the termina1 iIeum was adherent to the right anterior aspect of the peIvic brim by fibrinous adhesions. Very sIight traction on the bowe1 caused Iacerations in the bowe1 waI1 at the sites of severa Iarge ulcers. The bases of the uIcers remained attached to the parieta1 peritoneum and a Iarge amount of thin, dark brown intestina1 fIuid ran out through the perforation. The combined length of the Iarge and smaI1 125 cm., bowe1 was 200 cm. The smaII intestine, was markedIy dilated and Wed with a thin, dark brown intestina1 -fluid. Its serosa had a bIuish color. The upper third was g cm. in circumference, the middIe third IO cm., and the Iower third 12 cm., whiIe the bowe1 was 0.3 to 0.4 cm. thick. The dista1 third had many Iarge ulcers varying in size from 0.3 to 3 cm. in diameter and tending to have their Iong axes perpendicuIar to the Iong axis of the bowel. The edges of the uIcers were cIean and free of tubercIes. The uIcers were so numerous that they covered about 30 per cent of the mucous surface in the Iower third of the smalI intestine. The mesentery was sIightIy thickened and edematous and contained a few enIarged Iymph nodes.
the iIeum and coIon there was a stenotic region I cm. wide with an internal diameter of 0.4 cm. (Fig. 12.) The other abdomina1 viscera were not remarkabIe. MicroscopicaIIy, the mucosa of the iIeum showed many uIcers which in some pIaces extended down to the muscIe Iayer, and even the remaining mucosa was edematous and infiItrated with poIymorphonucIears and some monocytic ceIIs in pIaces, especiaIIy beneath the uIcers. The gangIion ceIIs of the mesenteric plexus were granuIar and swoIIen. Many large coIIections of Iarge and smaI1 monocytic cells were present between circuIar and Iongitudinal muscIe Iayers. The serosa was thickened, edematous, infiItrated in some pIaces with many poIymorphonucIears and monocytic ceIIs and was,covered by a thin Iayer of fibrin. FinaI diagnoses were: acute and chronic ulcerating enteritis; sero-tibrinous peritonitis; iIeocoIostomy (oId) with stenosis at site of union; intestina1 obstruction. DISCUSSION
CIinicaIly, these two cases agree in aImost every respect with the disease entity, regiona iIeitis, as described by
NEW SERIESVOL.XLIII, No. 2
Dickinson
et aI.-Enteritis
Crohn and associates.’ Case I ran a more acute course than most of those described, and Case II a much more chronic course, but wide variations in this respect are mentioned. Case II indicates the tendency to recurrence months after an apparently compIete excision of the diseased intestine. The pathoIogy of these cases varied in certain detinite ways from that first described by Crohn. Case I reveaIed typical invoIvement of the iIeum and mesentery, but an acute uIcer of the cecum was present. The appendix in this case was probabIy “ free from guiIt” but its Iumen was partialIy obIiterated by fibrosis. The acute changes observed were peri-appendicitis, apparentIy secondary to the iIeitis. Case II exhibited typica chronic uIcerating cicatrizing iIeitis, or the “stenotic phase of regional iIeitis,” but the process irreguIarIy invoIved the termina1 g6 cm. of the iIeum and an old perforation in the appendix might IogicaIIy expIain the entire pathogenesis. Demonstration of a specific etiology for either of these cases was impossibIe. We beIieve they are further proof in support of the statement of Homans and Hass13 who, after carefuIIy studying two cases of this group, concIuded: “We agree that a terminai iIeitis presents a rather characteristic cIinica1 picture, but acceptance of the local Iesion as a pathoIogic entity is certainIy premature, since criteria are Iacking by which one can segregate this granuIomatous process from simiIar Iesions occurring eIsewhere in the intestina1 tract.” CONCLUSIONS I. We beIieve regiona iIeitis to be a definite cIinica1 but not a definite pathoIogic entity. 2. The terminal iIeum, cecum and other parts of the smaI1 or Iarge intestine may be invoIved in the process. 3. Diagnosis rests on the history, finding of a mass in the right Iower quadrant, pIus the typica string sign shown by x-ray. _2. CompIete gastrointestina1 series shouId be done in any suspected case, as the
American
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lesion does not aIways show up with a simpIe barium enema. 3. Treatment depends on the findings in each individua1 case and varies according to the acuteness or chronicity of the process. Resection eventuaIIy may be necessary in order to bring about a compIete cure, but in the acute cases it is sometimes better to do a preIiminary iIeostomy, coIostomy or anastomosis, with resection at a later date. REFERENCES I.
CROHN,
BURRELL, B., GINZBURG, LEON, and GORDON D. RegionaI iteitis. A pathologica and clinica entity. J. A. M. A., 99: ‘323, 1932. ERB, I. H., and FARMER, A. W. IIeo-coIitis. Surg., Gynec. @ Oh., 61: 6, 1935. MEYER, KARL A., and ROSI, PETER A. RegionaI enteritis (non-specific). S. C[in. Nortb America, 15: 697, ‘935. GALAMBOS, A., and MITTELMANN, W. Typical and atvoical termina1 Ileitis. Am. J. Diees. Dis. P? Ntirition, 2: 442. 1935. KOSTER, HARRY, KOSMAN, LOUIS P., and SHEINFELD, WILLIAM. RegionaI ileitis. Arch. Surg., 32: $39, 1936. BARGEN, J. A., and DIXON, C. F. Regional ileitis. Proc. .%$&feet. Mayo Cl&., IO: 814, 1935. FELSEN, JOSEPH. Acute and chronic baciIlary dysentery. Am. J. Patb., 12: 395, 1936. FELSEN, JOSEPH. ClinicaI notes concerning dista1 iIeitis as a manifestation of bacilIary dysentery. Am. J. Diges. Dis. @ Nutrition, I: 782, 1935. FELSEN, JOSEPH. Non-specific utcerative colitis, terminal (distal) iIeitis, and bacihary dysentery. Their common pathogenesis. New York State J. Med., 35: 576, 1935. CROHN, BURRELL B., and ROSENAK, BERNARD D. A combined form of ileitis and colitis. J. A. M. A., 106: I, 1936. MOCK, HARRY E. Infective granuloma. Surg., Gynec. Ed Obst., 52: 672, 1g31.BARBOUR, R. F.. and STOKES. A. B. Chronic cicatrising enteiitis. Lancet, I : igg, 1936. HOMANS, JOHN, and HASS, GEO. M. RegionaI iIeitis; a cIinica1, not a pathological entity. New England J. Med., 209: 1315, 1933. MIXTER, CHARLES G. RegionaI iIeitis. Ann. Surg., 102: 674, 1935. GINZBURG, LEON, and OPPENHEIMER, GEOR<;~. Non-specific granmomata of the intestines. Ann. Surg., 98: 1046, 1933. MEYER, KARL A., and ROSI, PETER A. Regional iIeitis (non-specific). Surg., Gynec. ti Oh., 62: 977, 1936. BINNEY, HORACE. Non-specific granuIoma of the iIeo-ceca1 region. Ann. Surg., 102: 695, 1935. KANTOR, JOHN L. RegionaI (termina1) iIeitis; its roentgen diagnosis. J. A. M. A., 103: 2016, 1934. PROBSTEIN, JACOB, and GRUENFELD, GERHARD E. Acute regiona iIeitis. Ann. Surg., 103: 273, 1936. OPPENHEIMER,
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