CASE REPORTS CROHN'S DISEASE OF THE STOMACH. In 1932 Crohn et ap described a granulomatous
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1 GASTROENTEROLOGY Copyright 1966 by The Williams & Wilkins Co. Vol. 50, No.4 Printed in U.S.A. CASE REPORTS CROHN'S DISEASE O THE STOACH O. ADRIAN JOHNSON,.D., DONALD W. HOSKINS,.D., JEAN TODD,.D., AND BJORN THORBJARNARSON,.D. Departments of Surgery, edicine, and Surgical Pathology of The New York Hospital. Cornell edical Center, New York, New York In 1932 Crohn et ap described a granulomatous inflammatory process of unknown etiology involving the terminal ileum and gave it the name "regional ileitis." Later, involvement of other portions of the small bowel including the jejunum and duodenum were reported, and accordingly the name was changed to "regional enteritis." In recent years there have been reports of involvement also of the stomach and large bowe As a review of the literature reveals only 12 cases of regional enteritis with concomitant gastric involvement, this case is being reported together with a review of the known features of this condition. Case Report A 35-year-old white man was admitted to another hospital with a 15-year history of peptic ulcer symptoms which had previously been well controlled by diet and antacids. Six months prior to admission, however, he had a single episode of upper abdominal crampy pain and about the same time, a return of the peptic ulcer symptoms. These symptoms were again controlled by diet and antacids but the crampy epigastric pain was not. At this time he also had two or more episodes of diarrhea and he noted the onset of persistent fever to 102 with associated weakness and fatigue. His local physician administered antibiotics with only a temporary decline in his elevated temperature. Radiological investigations in the hospital were reported to show a duodenal ulcer. His white blood count was slightly ele- Received July 14, Accepted November 26, Address requests for reprints to: Dr. Bjorn Thorbjarnarson, 525 E. 68th Street, New York, New York vated and a Brucella skin test was reported as mildly positive but the Brucella agglutination test was negative. Otherwise, an extensive examination was reported as normal. He was given several courses of chloramphenicol without a change in his symptoms except for some decrease in temperature. He subsequently began to complain of postprandial fullness and noted a weight loss of approximately 7 lb. over a 4-month period. He had no further diarrhea. He was admitted to The N ew York Hospital for the first time on ebruary 6, Physical examination was normal except for mild right upper quadrant abdominal tenderness. Complete blood count and urinalysis were unremarkable. Stools for occult blood were negative. Serological tests for syphilis, Brucella agglutination, tuberculin test, Widal Test, and Coomb's test were all negative. Gastric analysis revealed no free fasting acid but acid was present 15 min after histamine stimulation. Cytological examination of gastric chymotrypsin washings was reported as class 1. The radiological examination at this time of the esophagus, stomach, and small bowel revealed lack of distention of the antrum of the stomach and irregularity of the margins of the antrum tapering toward the pyloric canal. The small bowel showed some coarsening of the jejunal mucosa but otherwise appeared normal (see fig. 1). Chest X-rays, intravenous pyelogram, and barium enema were all normal. Gastroscopy revealed diffuse gastritis with a cobblestone appearance of the antral mucosa. The differential diagnosis before operation was between a malignant neoplasm of the stomach, thought more likely to be a lymphoma than a carcinoma, or a nonspecific inflammatory disease, possibly regional enteritis or eosinophilic gastritis. On ebruary 15, 1963, the patient was operated on and the distal one-third of the stomach was noted to have a hyperemic reddened
2 572 CASE REPORTS Vol. 50, No.4 IG. 1. Lack of distention of antrum with some irregularity of the margins and tapering towards the pylorus. serosa and a moderately thickened firm wall. Large lymph nodes were present along the greater and lesser curvatures. The jejunum and proximal ileum contained multiple areas of slight thickening of the wall with hyperemic serosa similar to but less pronounced than the changes at the distal end of the stomach. The small bowel mesentery contained large, soft lymph nodes also. On opening the stomach, we noted that the mucosa was hyperplastic with a cobblestone appearance alternating with multiple small mucosal ulcerations (see fig. 2). Rapid frozen section revealed a granulomatous inflammatory process most compatible with regional enteritis of the stomach. Because of the marked gross involvement of the distal part of the stomach, and the narrowing of the antrum seen on X-ray examination, the probability of future obstruction was considered high. Since the duodenum was not involved, a gastrectomy with gastrojejunostomy was performed to remove all the involved portions of stomach. The areas of enteritis in the small bowel were not causing obstructions and were not resected. The microscopic examination of the surgical specimen revealed multiple small ulcerations extending into the submucosa (see fig. 3). The bases of the ulcers were composed of granulation tissue covered in some areas by fibrinopurulent exudate. The granulation tissue was of the type seen in regional enteritis with palisading epithelioid cells in many areas and scattered giant cells along with large numbers of other chronic inflammatory cells. In the adjacent lamina propria were noncaseating granulomata composed of epithelioid cells and giant cells surrounded by lymphocytes (see fig. 4). Acute and chronic inflammatory cells also infiltrated all layers of the wall of the stomach. A few eosinophilic leukocytes were present. No arteritis was present. Special stains for fungi and acid-fast bacilli were all negative. The patient had an uncomplicated postoperative course and was discharged on the 11th postoperative day. Over the next 6 months the patient complained of a mild dumping syndrome, continued to feel full after small meals and had 1 to 2 soft movements daily, occasionally noting a malodorous stool. In addition he lost 15 lb. more and began to develop pains across the abdomen. A gastrointestinal and small bowel series performed on July 31, 1963, revealed several segments of the distal jejunum and ileum to be involved with a process having the X-ray appearance compatible with regional enteritis (see fig. 5). The esophagus, remaining stomach, proximal jejunum, and terminal ileum were normal. Accordingly, approximately 6 months postoperatively, prednisolone, 30 mg daily, was begun. Stools returned to normal consistency without odor and occured once daily. The abdominal pain was totally relieved and weight gain noted. The corticosteroids were tapered IG. 2. Gross appearance of the stomach showing loss of normal rugal pattern, thickening of the wall, and multiple superficial ulcerations.
3 April 1966 CASE REPORTS 573 IG. 3 (left). Low power photomicrograph of ulcer with submucosal fibrosis. IG. 4 (right). Low power photomicrograph of noncaseating granulomata in the lamina propria of the stomach. and discontinued over a 6-week period. The patient then did well for 6 months. With recurrence of abdominal pain, urgency of stool, tender palpable bowel in the right lower quadrant, and beginning weight loss, steroid therapy was reinstituted. Prednisolone, 20 mg daily, again resulted in marked rapid improvement in all symptoms. The drug was tapered over 8 weeks to a maintenance dose of 2.5 mg daily which the patient continues to take while remaining asymptomatic, carrying on full time work, and playing tennis 4 hr daily. Discussion This case demonstrates a number of features found in the previously reported cases. Some of these features are summarized in table 1. Sex. The patient reported was a male and of the 12 cases in the literature men have predominated, 8:4. Age. The average age of the reported patients is 26.1 years with a range from 9 to 48 years. Race. Of the six patients so defined, five were white and one Negro. IG. 5. Areas of narrowing and mucosal Irregularity in the distal jejunum and ileum.
4 Authors Comfort et aj.2 Goldgraber et aj.3 Hefferon and Kepkay artin and Carrs iller et al. 6 Richman et au RossS Self9 Johnson et al. (present case) TABLE 1. Reported cases in the literature of regional enteritis with concomitant gastric involvement Age Sex Organs involved Pain Stomach, duodenum, I jejunum, and ileum Stomach and duo- denum Stomach and ileum Stomach, esophagus, I duodenum, and jejunum Stomach, duodenum, and ileum Stomach, duodenum, and ileum Stomach, duodenum, jejunum, and ileum Stomach, duodenum, jejunum, and ileum Stomach, duodenu'm, and ileum Stomach, jejunum, and ileum Stomach and ileum Stomach and duodenum I Stomach, jejunum, and ileum Weight I Diar- I Gastric loss rhea retention --,--, Operation Posterior gastroenterostomy Posterior gastroenterostomy (a) Vagotomy and pyloroplasty (b) Ileotransverse colostomy (a) Resection of duodenum (b) Resection of jejunum Biopsy of stomach Resection of terminal ileum and right colon Gastroenterostomy and appendectomy Posterior gastroenterostomy Partial gastrectomy Exploratory laparotomy (a) Right colectomy (b) Ileostomy (c) Total colectomy (d) Partial gastrectomy Total gastrectomy Partial gastrectomy Results Did well 2 yr, then deteriorated over l-yr period; died suddenly Gained 50 lb. 1st yr. Only mild symptoms after 272 yr Doing well after 1 yr Died following 2nd operation (both procedures performed for massive hemorrhage) Stormy course initial few months, some improvement after '1 yr Stomach involvement 3>-2 months after surgery Doing well after 4 yr but X-ray appearance unchanged Doing well after 5 mo, only occasional diarrhea Doing well after 4 mo, no complaints Doing fairly well after a brief follow-up Progressive disease with associated chronic ulcerative colitis Only brief follow-up following gastrectomy Lost to follow-up after discharge Did well for 6 mo, then further small bowel involvement. Now asymptomatic 18 mo after surgery on 2.5 mg of prednisolone daily e;. ;: - -l>-
5 April 1966 CASE REPORTS 575 Symptoms. ild to marked weight loss and pain were present in 12 of the 13 patients. The pain is usually epigastric, as in this case, although it may be felt lower in the abdomen if the small bowel is also involved. Nausea and vomiting occur frequently, probably due to distention associated with gastric or duodenal obstruction. Vomiting in a patient with known regional enteritis should suggest gastric or duodenal involvement since this is an unusual symptom in disease confined to the ileum or jejunum. Eight patients complained of diarrhea. It was usually episodic and the stools sometimes contained blood. atigue and weakness were also common complaints. Laboratory findings. In general, the laboratory findings are of limited value in making a definite diagnosis. Gastric analysis occasionally reveals hypochlorhydria or achlorhydria, depending on the extent of involvement of the stomach. Occult blood is sometimes present in the stools. Evidence of malabsorption manifested by macrocytic anemia, hypolipemia, hypocalcemia, hypoproteinemia, and steatorrhea may be present in some patients, probably due to the extent of the process in the small bowel rather than in the stomach. X-rays. Usually only the distal portion of the stomach is involved. The typical findings include hypomotility, rigidity, deformity, delayed emptying, distention secondary to obstruction, and rugal flattening. The picture may be impossible to distinguish radiographically from a malignant process. The presence of findings in the small bowel that are characteristic of regional enteritis suggest the possibility of gastric involvement. Pathology. The gross and microscopic appearances of this disease as seen in the stomach are essentially similar to those of the disease when present elsewhere in the bowel. The appearance depends to some extent on the stage of the disease.1o In the acute stage, the serosa is reddened and hyperemic and the wall of the bowel and mesentery thickened and edematous. Enlargement of regional lymph nodes is seen. The mucosa shows ulceration alternating with hyperplastic mucosa glvmg a cobblestone appearance. As the disease progresses, fibrosis becomes more conspicuous, giving rise to rigidity of the stomach wall. The microscopic changes are those of ulceration with a granulomatous reaction and noncaseating granulomata in the lymph follicles and lymph nodes. No caseation or acid-fast bacilli were ever found. Treatment. The treatment of regional enteritis affecting the stomach is palliative and symptomatic. When the stomach becomes involved in the course of progressive established disease of the small bowel, the nature of the stomach lesion may be correctly suspected without diagnostic laparotomy. In such cases, the indications for surgery already established for lesions in the small bowel should be adhered to. The natural course of the disease in the small bowel and the colon is one of intermittent activity characterized by episodes of fever, pain, and disturbed bowel function followed by quiescence and well being. Extension to the stomach, on the other hand, is relatively uncommon, and the natural history and prognostic implications of the disease in the stomach are much less well known. Operation was essential here for diagnosis, since small bowel involvement could not be demonstrated before laparotomy. A subtotal gastric resection with a gastrojejunostomy was performed since a gastrojejunostomy alone would have placed the anastomosis between bowel and involved stomach. The areas of enteritis in the small bowel were not removed. Review of the literature makes it difficult to draw any definite conclusions as far as optimal therapy is concerned. It is apparent, however, that gastric retention and obstruction are the most common complications and the immediate results of gastric resection or gastroenterostomy have been good. Gastric resection, of course, should not be undertaken when disease is present in the duodenum since obstruction with duodenal leak may result. At least one patient was alive and well 4 years following gastroenterostomy, but this is the longest follow-up in the whole group.
6 576. CASE REPORTS Vol. 50, No.4- Results (Table 1) With so few reported cases and no long term follow-ups, it is not possible to define the course of this disease in detail or to predict the results with any given form of treatment. Two deaths have been reported. One patient reported by Comfort et al. 2 did well for 2 years following posterior gastroenterostomy and then deteriorated over a I-year period and died suddenly. Postmortem examination showed diffuse involvement of the entire stomach and small bowel. The immediate cause of death was probably attributable to bilateral adrenal vein thrombosis and hemorrhagic necrosis of the adrenal gland. The other patient, reported by Heffernon and Kepkay,4 was operated on twice for massive hemorrhage and died following the second operation. Of the survivors with a follow-up of I year or longer, iller et al. 6 reported a 9- year-old boy who underwent gastroenterostomy and who was doing well after 4 years with only one brief period of hospitalization for a recurrence of symptoms. However, X-ray studies revealed little change from the original radiographic studies. Comfort et al. 2 reported a patient who gained 50 lb. the first year following posterior gastroenterostomy and complained only of epigastric fullness and pressure after 2Y2 years, at which time the radiographic appearance of the disease was unchanged. Goldgraber et al. 3 reported their patient doing well 1 year after vagotomy, pyloroplasty, and ileotransverse colostomy. The first patient reported by artin and Carr5 had only a biopsy of the stomach and had a stormy course for several months, but was improving at the end of the year. Over a 3Y2year period, Ross8 performed on one patient a right colectomy and resection of the terminal ileum followed by a divided ileostomy, a total abdominal perineal colectomy for chronic ulcerative colitis, and a partial gastrectomy for gastric involvement by the granulomatous process which progressively involved the small bowel. Our patient felt fairly well for 6 months following partial gastrectomy and then suffered from involvement of the small bowel. At the present time his symptoms are controlled by small doses of steroids. One of the remaining five patients, reported by artin and Carr,5 developed gastric involvement 3Y2 months after right colectomy and resection of the terminal ileum. Richman et au reported three cases: one, 5 months following posterior gastroenterostomy; one, 4 months following partial gastrectomy, and one patient with only a brief follow-up following exploratory laparotomy; all were reported to be feeling well. The remaining patient reported by Self9 underwent total gastrectomy because it was thought at the surgery that she had a malignant tumor of the stomach. She was lost to follow-up upon discharge from the hospital. Summary 1. In recent years, granulomatous enteritis involving the stomach has been described. The present case is the 13th to be reported. 2. Because of the small number of reported cases and the limited follow-ups it is difficult to evaluate the results of any given form of therapy but it may be that longer follow-up will reveal a high incidence of progression of the disease regardless of the form of treatment used. 3. In the case presented here the prognosis follo!\,ing resection of the stomach seems to depend on progression of the disease in the small bowel rather than on recurrence in the stomach itself. REERENCES 1. Crohn, B. B., L. Ginzburg, and G. D. Oppenheimer Regional ileitis, A pathologic and clinical entity. J. A.. A. 99.: Comfort,. W., H.. Weber, A. H.Baggenstoss, and W.. Kiely Nonspecific granulomatous inflammation of the stomach and duodenum: Its relation to regional enteritis. Amer. J. ed. Sci. O: Goldgraber,. D., J. B. Kirsner, and H.. Raskin Nonspecific granulomatous disease of the stomach. Arch. Intern. ed. (Chicago) 10 : Heffernon, E. W., and P. H. Kepkay
7 April 1966 CASE REPORTS 577 Segmental esophagitis, gastritis and enteritis. Gastroenterology 26: artin,. R R, and R J. Carr Crohn's disease involving the stomach. Brit. ed. J. 1: iller, P. B., D. J. Sandweiss, and H. Shwachman Nonspecific granulomatous inflammation of the gastrointestinal tract. New Eng. J. ed. 255: Richman, A. R, H. D. Zeifer, A. Winkelstein, P. A. Kirschner, and R D. Steinhardt Chronic nonspecific granulomatous inflammation of the stomach, duodenum and intestine. Gastroenterology 29: Ross, J. R Cicatrizing enteritis, colitis, and gastritis. Gastroenterology 13: Self, J. B Crohn's disease of the stomach. Postgrad. ed. J. 33: Shields, W., and S. C. Sommers Cicatrizing enteritis (regional enteritis) as a pathologic entity. Amer. J. Path. 24: l. 11. Janowitz, H. D., H. E. Lindner, and R H. arshak Granulomatous colitis. J. A.. A. 191:
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