Primary Nonpeptic Ulcer of the Jejunum

MARTIN S. LITWIN, * M.D., CHILTON CRANE,* * * M.D.

Boston, Massachusetts

PRIMARY, nonpeptic ulcer of the jejunum is a little known and easily overlooked disease entity which may cause acute peritonitis of obscure origin, subacute or massive gastro-intestinal bleeding, or partial small bowel obstruction. This is a subtle lesion. Only two reported cases have been diagnosed preoperatively by x-ray demonstration.12' 27 Moreover, at exploratory laparotomy the small size and lack of surrounding induration of these ulcers can render them most difficult to discover. Several perforated primary jejunal ulcers with pinpoint openings have been demonstrated at autopsy following negative surgical exploration for peritonitis.'5 18,27 In a case recently explored for massive gastro-intestinal bleeding, the ulcer was not found on the first examination of the small intestine, and even with a wide enterotomy later on it was sufficiently well concealed between the high folds of jejunal mucosa as to nearly escape detection. If less than considerable care were used during inspection of the jejunum at postmortem examination, many of these small, unperforated lesions would not be noted. Since negative abdominal exploration for gastro-intestinal hemorrhage poses a recurring surgical dilemma, it seems desirable to report a case of massive bleeding caused by primary jejunal ulcer to emphasize this

Case Reports
Case 1. E. T., PBBH #3M874, an 87-year-old white woman, a retired schoolteacher, was admitted to the hospital semi-conscious at 3:00 a.m., June 13, 1958. Four hours previously an episode of bright red hematemesis and dark red melena had led to syncope and collapse. Physical examination on admission disclosed a pale, acutely-ill, elderly woman, complaining of faintness. The blood pressure was 100/55, the pulse was thready at 116, the respirations were 28. The rectal temperature was 35.5 C. Abdominal examination revealed only slight distension and increased peristalsis. Arterial pulsations in the extremities were normal. The white blood cell count was 21,700/cu. mm. with 86 per cent polymorphonuclear leukocytes; the hematocrit was 33 per cent. Urinalysis, liver function tests, serum electrolytes, and bleeding studies were all normal. A moderate amount of free acid was present in the gastric juice together with flecks of red blood. The electrocardiogram was suggestive of myocardial ischemia. Abdominal x-rays showed only gaseous distension of the colon. The blood Hinton was later reported as negative. By five hours after admission, the patient had received 2,000 cc. of whole blood. The hematocrit, however, had fallen to 28 per cent and the blood pressure to 76/20. Over the next six hours she received another 1,000 cc. of whole blood with stabilization of the blood pressure at 100/50 and the pulse rate at 84; however, she continued to pass large amounts of reddish-black blood by rectum. A diagnosis of bleeding duodenal ulcer was made and the patient was operated upon. At exploratory laparotomy 18 hours after admission, large quantities of blood were noted throughout the small bowel and colon. Preliminary inspection and palpation of the stomach and duodenum disclosed no ulcer or tumor, nor did similar examination of the small intestine. Through a large anterior gastrotomy, a most satisfactory inspection of the interior of the stomach and the first portion of the doudenum disclosed no blood, and entirely normal appearing pale mucosal surfaces. This finding led to a second, and very careful, inspection of the jejunum. Approximately 30 cm. be-

diagnostic possibility.
Submitted for publication July 20, 1959. * Assistant Resident in Surgery at the Peter Bent Brigham Hospital, Boston, Mass. * ** Senior Associate in Surgery at the Peter Bent Brigham Hospital and Assistant Clinical Professor of Surgery at Harvard Medical School, Boston, Mass.
*

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low the ligament of Treitz, a firm, flat fixed placque, measuring 1.2 cm. in greatest diameter, was barely palpable on the mesenteric border of the jejunum. A white firm artery was seen passing into the center of this lesion. The intestine was bulging with blood at this level. Through a wide enterotomy a small ulcer was found after displacing the high mucosal folds. The small white artery protruded above the ulcer base, and when fresh thrombus was removed from its tip, free pulsatile bleeding occurred. Local resection of the lesion including 6 cm. of jejunum and end-to-end anastomnosis were done. The patient convalesced well with no evidence of further bleeding, and she was discharged home on the fourteenth postoperative day. Pathology Report. "The specimen consists of a 6 cm. length of jejunum showing a smooth, glistening, normal-appearing serosal surface. A shallow mucosal ulceration with a raised reddishpurple hemorrhagic border measures 0.75 cm. in diameter and approximately 0.25 cm. in depth. The remainder of the mucosa is essentially normal in
appearance.

"Microscopic examination through this area shows ulceration of the jejunal mucosa with replacement by necrotic debris rich in neutrophils and lymphocytes. This involves the mucosa and the submucosal coat. There is edema, hemorrhage, and fibroblastic proliferation and a large submucosal artery has been eroded and appears to open into the lumen of the intestine. Pathological diagnosis: Acute ulcer of the jejunum with erosion of a submucosal artery." This case of an 87-year-old woman who was bleeding urgently from a jejunal ulcer, with no evidence of peptic ulceration and with low gastric acid values, prompted a search of the clinical and laboratory files for additional cases of primary jejunal ulcer. For the privilege of reporting the only two other cases found, the authors are much indebted to Dr. Francis C. Newton. Both of these cases exhibited low grade intestinal tract bleeding; both were symptomatic because of incomplete upper small bowel obstruction.
Case 2. T. J., PBBH #74488, a 60-year-old Scotsman was admitted to the hospital, June 11, 1931, because of epigastric distress of two weeks' duration. Four months prior to admission he had first noted inability to move his bowels without the use of laxatives. Two weeks prior to admission he had experienced a spontaneous episode of severe, colicky, abdominal pain felt chiefly in the right lower quadrant and associated with abdominal distension. This was relieved by narcotics and an

enema. Until the time of admission he noted epigastric "gas pressure distress" each night, coming on two to three hours after dinner. The patient had been diabetic for nine years. Dietary control was adequate, but he had lost 14 pounds of weight over the one month prior to admission. Physical examination at time of admission was normal. Blood counts and urinalysis were normal. Blood Wasserman was negative. Stool examinations were repeatedly positive for blood. Barium enema and cholecystogram were negative. For three days following admission the patient was asymptomatic. On June 14, he had a short episode of crampy abdominal pain associated with distension. A diagnosis of partial intestinal obstruction was made. At exploratory laparotomy on June 23, a small mass was found in the lower portion of the jejunum. It was scarred, annular in shape, and had contracted the bowel lumen. The area was resected and an end-to-end anastomosis done. The postoperative course was uneventful. The patient was discharged July 8, 1931, to be followed in the out-patient department. Pathology Report. "The specimen consists of a portion of jejunum measuring 7 cm. in length. In the center, the lumen is constricted to about half its width; the mucosa in this area is ulcerated. The ulcer measures 0.8 by 1.0 cm. on the mucosal surface. The base of the ulcer is covered by granulation tissue. "On section the active portion of the ulcer extends to the muscle layer. The border of the ulcer is rather sharply defined and not markedly thickened. This lesion is not suggestive of tuberculosis, typhoid fever, or dysentery. The etiological factor causing the ulcer is obscure. There is no evidence of tumor formation in any section. The gross picture is that of a simple ulceration not associated with a neoplastic process. Pathological diagnosis: Ulcer of jejunum of uncertain etiology."

Case 3. J. W. K., PBBH #78064, a 65-year-old white man, a night-watchman, was admitted to the hospital, April 21, 1932, with the complaint of abdominal cramps of 10 weeks' duration. Cramping pain occurred generally throughout the abdomen without radiation. The pain was worst just after meals, was aggravated by meat and milk, and was frequently accompanied by borborygmi. He had lost about 20 pounds over the 10 weeks just prior to admission. The patient had had two previous admissions for hypertension and generalized arteriosclerosis. Physical examination disclosed an elderly white man in no acute distress. Blood pressure was 200/ 90. Pulse rate was 60/min. and irregular with a wide

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pressure. Marked sclerosis of the peripheral arteries and cardiac enlargement werie;noted. The

liver was slightly enlarged but there was no abdominal tenderness, spasm, or visible peristalsis. No masses were palpated. Blood counts and urinalysis were normal. Stool examination was strongly positive for blood. Gastric aspirate was negative for free acid on six occasions. Blood Hinton and Wasserman were negative. G. I. series showed a delay of the barium in the second and third portions of the duodenum with a dilated loop of small bowel in the left mid-

abdomen. This loop

was

thought to be

upper

jejunum. It narrowed to less than 1 cm. at a point of constriction. The outline was serrated and irregular suggesting an intrinsic lesion in the wall of the gut. Radiologic diagnosis was partial obstruction of the jejunum possibly due to carcinoma.

When fecal vomiting occurred, the patient was transferred to the surgical service on April 29. On April 30, he underwent exploratory laparotomy. The upper jejunum for a distance of two feet from the ligament of Trietz was hypertrophied and dilated. Distal to this point the jejunum and ileum were collapsed and small. The involved loop of jejunum was easily delivered into the wound and the point of obstruction found. It appeared grossly to be a small annular carcinoma. A 9-cm. segment of jejunum including the point of obstruction and the lymph nodes at the base of the mesentery was excised; an end-to-end anastomosis was done. The postoperative course was smooth. The patient was discharged, May 19, 1932, to be followed in the out-patient department. Pathology Report. "The specimen consists of a piece of jejunum 9 cm. in length with thickened edematous mucosa. In the center there is a slightly elevated constricting band distal to which there is a large ulcer measuring 3 cm. in greatest diameter. There is only slight induration. No serosal inflammation is seen. Edges of the ulcer are slightly raised but there is no evidence of tumor. "On microscopic section, a granulating ul2er and mucosa of duodenum, at least an area with deep branching glands, is seen. Evidence of healing of a previous ulceration is present. There is no evidence of malignancy, specific inflammation, or infectious process. We have, therefore, in the presence of duodenal mucosa at an unusually low situation, ulceration and repair without assignable cause. Pathological diagnosis: Anomalous distribution of duodenal mucosa in jejunum and ulcer."

cording to Robinson and Wise.22 In 1829, Sestier 26 cited jejunal ulcer perforation as a cause for peritonitis. Ravdin,20 Morrin,'8 Ebeling,12 and Evert, et al.13 have published excellent reviews of this subject. Up to 1955, Levitt and Saint 17 were able to find only 83 reported cases. Since then five more have appeared in the literature.4 23, 24 30, 33 These, together with the cases in this report, raise the total to 91. These ulcers occur about twice as frequently in men as in women and most frequently between the ages of 30 and 50 years.20' 22 The youngest case reported was that of a 46-ounce premature infant,24 and the oldest previously reported case was that of an 83-year-old woman.
Pathology Jejunal ulcers occur most frequently on the anti-mesenteric border with a definite predilection for the proximal half of the jejunum. They usually are small and chronic, ranging in size up to 2.0 cm. A punched out circular or annular appearance is typical. Most often only the mucosa and submucosa are affected. A necrotic grayish base is seen to be terraced from inside out. Induration is minimal. Should perforation occur, only a tiny pinpoint opening may be seen. On microscopic section the base of the ulcer usually shows scattered chronic and acute inflammatory cells in varying numbers. The degree of dilatation of the bowel proximal to the lesion depends on chronicity and the degree of scarring.

Incidence Primary, nonpeptic jejunal ulcer was first described by Matthew-Ballie in 1805, ac-

Etiology Numerous etiologic factors have been discussed in relation to the pathogenesis of primary jejunal ulcer. The acid-peptic theory hardly can be applied to primary jejunal ulcer. Not only is most of the gastric acid neutralized before reaching the jejunal lumen, but several cases of jejunal ulcer reported, including

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one of our own, have shown decreased or absent gastric acidity.9 12, 13 If gastric emptying time is markedly decreased and gastric hyperacidity exists, as in the ZollingerEllison syndrome, peptic ulceration of the jejunum may develop. Undoubtedly, several cases reported in the past have belonged to this group.'17 23 However, absence of gastroduodenal ulceration, the unitary lesion, and lack of recurrence after excision are conspicuous features of these primary jejunal ulcers. Certainly if a jejunal ulcer is the only ulcer, and if gastric hypoacidity or anacidity is present, the Zollinger-Ellison syndrome should not be considered etiologic. It is well known that ulceration of the small intestine occasionally develops in an area of ectopic gastric mucosa.5 12, 16, 32, 34 Such ectopic mucosa is found chiefly in the ilium, however; often in relation to Meckel's diverticulum, and none of the reported jejunal ulcer pathologic specimens have shown gastric tissue. The finding of deep branching glands in the segment of jejunum removed in Case 3 seems of scant significance in the absence of any free gastric acid. Vascular spasm,19 endarteritis,18, 28, 29 arteriosclerosis,8 or embolization 8, 14 all may cause local obstruction in any of the smaller vessels of the intestine. This can result in mucosal necrosis. The proteolytic enzymes of the upper small bowel would soon digest the necrotic jejunal mucosa and ulceration would occur.20 This could account for the greater prevalence of the lesion on the antimesenteric side of the intestine. In Case 1, while no local arteriosclerotic placque definitely was identified, the artery leading to the area of ulceration was noted grossly to be white and indurated. Indeed, in all of our cases there was good evidence for the presence of generalized arteriosclerosis. Many other possible factors, which have been mentioned in discussions of the etiology of jejunal ulcer,2, 3, 10, 12-14, 18, 21, 25, 28, 33

er, undulant fe # I sep e choler s ary jejunise, amebiasis, Ascaris lumtis, Crow bricoides infestation, thromboangiitis obliterans, uremia, and syphilis. Conclusive obvious objections to each rule out all of these. Many cases of jejunal ulceration with perforation due to trauma have been reported," 11-13, 18, 31 but it is difficult to believe that the ulceration itself did not precede the trauma. While the etiology of the process causing jejunal ulcer is unknown, the theory postulating local tissue ischemia with autodigestion and ulceration probably is the most reasonable.

include

staphylc

Signs and Symptoms

The symptoms of uncomplicated primary jejunal ulcer are essentially those of duo-

denal ulcer. The nearer the ulcer lies to the ligament of Trietz, the more closely are symptoms of duodenal ulcer simulated. The patient may have gnawing, aching, postprandial pain that may or may not be relieved by food or alkali. Pain is felt usually in the periumbilical or subumbilical area rather than in the epigastrium, with referral to the back or right upper quadrant. If marked scarring has occurred, there may be intermittent distention and vomiting due to high intestinal obstruction. Because of difficulty in diagnosis, the presenting symptoms in most cases have resulted from complications of the ulcer. The commonest complication-perforation -produces the expected classical symptoms and signs except that the initial severe pain frequently is felt on the left side of the abdomen. Melena may be acute and massive or of smaller amounts and chronic. Hematemesis, a prominent symptom in one of our cases, does not often occur. Obstruction is rare and is usually
partial.3' 9, 12, 13, 20, 22

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Diagnosis Primary jejunal ulcer has been diagnosed preoperatively on only two reported occasions. The difficulty in diagnosis lies not so much in the paucity of symptoms and signs as in the rareness of its recognized occurrence and the lack of familiarity with its manifestations. Primary jejunal ulceration should be considered as a possible diagnosis in the following groups of patients: 1. Those with recurrent postprandial pain suggestive of peptic ulcer, in whom there is no radiographic evidence of gastric or duodenal ulceration.1l 2. Those with gastro-intestinal hemorrhage, acute or chronic, in whom there is no roentgenologic evidence of abnormality in the esophagus, stomach, duodenum, or colon. 3. Those with gastro-intestinal hemorrhage or partial intermittent intestinal obstruction in whom a barium meal shows decreased motility and dilatation of the upper jejunum. 4. Those with peritonitis presumably due to a ruptured peptic ulcer in whom no gastric or duodenal perforation is discovered at laparotomy.

especially in the individual presenting with gastro-intestinal hemorrhage.

Treatment When the diagnosis of primary jejunal ulcer is made in a patient in whom no complications have occurred, a strong case can be made for early elective resection of the lesion. If the chief cause is vascular impairment, and if the complication rate is truly very high, a policy of observation and radiologic follow up would seem to be dangerous. Moreover, there is scant rationale on which to base a sound medical therapeutic program. When the complications of perforation, bleeding, or obstruction have occurred, surgical intervention becomes mandatory. Summary and Conclusions 1. Three cases of primary ulcer of the jejunum are reported. The first presented with massive gastro-intestinal bleeding; the other two with partial jejunal obstruction and low grade bleeding. 2. The literature describing the previously reported 88 cases is briefly reviewed. 3. The incidence, pathology, etiology, diagnosis, and treatment of this interesting type of ulcer are discussed. 4. The importance of nonpeptic jejunal ulcer as a cause for peritonitis, intestinal tract bleeding, and high small bowel obstruction is emphasized.

The diagnosis of primary jejunal ulcer prior to laparotomy is a roentgenologic one. A characteristic niche can at times be seen at the site of ulceration following ingestion of a barium meal. In addition a five-hour post ingestion film may demonstrate a small fleck of barium in the base of the ulcer.6, '1 An alternate sign consists of intestinal dilatation, diminished peristalsis, and barium retention proximal to a constricted area. Mucosal changes due to local inflammation may also be noted. Gastric intubation as an aid in diagnosis is to be desired. The presence or absence of free acid and of blood is of great assistance in localization of an acute lesion,

Bibliography
1. Balice, G.: Perforation of Simple Ileo-jejunal Ulcers With Report of a Case. Gion Ital., Chron., 3:665, 1947. 2. Bamer, B. O., C. E. Claugus and J. E. Hamilton: Acute Perforation of the Jejunum Secondary to Primary Jejunitis. Ann. Surg., 134: 131, 1951. 3. Berry, L. H. and U. G. Daily: Primary Ulcer of the Jejunum. Am. J. Dig. Dis., 7:63, 1940. 4. Bianchi, F.: A Case of Simple Small Bowel Ulcer. Arch. de Vecchi, 25:941, 1957. 5. Brown, P. W. and J. de J. Pemberton: Solitary Ulcer of the Ileum and Ulcer of Meckel's

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21. Richardson, E. P.: Jejunal Ulcer Without Previous Gastroenterostomy. Surg., Gyn., and Obstet., 35:1, 1922. 22. Robinson, D. R. and W. D. Wise: Simple Nonspecific Ulcer of the Jejuno-ileum. Surg., Gyn., and Obstet., 70:1097, 1949. 23. Sampsel, J. W. and F. M. Barry: Primary Jejunal Ulcer With Recurrence Following Resection. A. M. A. Arch. Surg., 70:420, 1955. 24. Schiff, C. A.: Perforation of the Small Intestine in a Newborn Infant. Arch. Surg., 70:439, 1955. 25. Schmihnski: Biologische Abteilung des Arztlichen Vereins in Hamburg. Muenchen. med. Schnschr., 57:1616, 1910. 26. Sestier, A.: Perforation of the Jejunum as a Cause of Peritonitis. Bull. Soc. Anat. de Paris, 4:33, 1829. 27. Shea, P. C.:Nonspecific Ulcer of the Small Intestine; Report of Five Cases. J. A. M. A., 146:1490, 1951. 28. Sterling, J. A.: Perforation of Small Bowel Associated With Thromboangiitis Obliterans. Am. J. Gastroent., 42:698, 1955. 29. Stitch, A. B. and E. Collier: Perforation of the Instestine. Brit. M. H., 1:1108, 1936. 30. Strouth, B. P. and J. A. Edwards: Primarv Perforated Jejunal Ulcer; a Case Report. Northwest Medicine, 55:1350, 1956. 31. Taylor, A. S.: Cases and Observations in Medical Jurisprudence. Death From Perforation of the Jejunum as a Result of Disease, Death Apparently as a Result of Violence. Guy's Hospital rep., 11:282, 1865. 32. Taylor, A. S.: The Epithelial Heterotopias of the Alimentary Tract. J. Path. and Bact., 30: 415, 1927. 33. Thomas, M. M. and H. Isel: Perforation of a Simple Ulcer of the Jejunum in a Newborn. Maroc Medical (Casablanca), 36:474, 1957. 34. Wilson, E.: Melena From Heterotopic Gastric Mucosa in the Ileum. Lancet, 2:855, 1950.