Case 24-2004 — A 48-Year-Old Man with Recurrent Gastrointestinal Bleeding
http://www.100md.com
《新英格兰医药杂志》
Presentation of Case
A 48-year-old man was admitted to the hospital for evaluation of recurrent gastrointestinal bleeding.
He had been well until 33 months earlier, when he had midepigastric pain and passed black stools that were positive for occult blood. He was found to be anemic and was admitted to the hospital for evaluation. He had been taking low doses of ibuprofen daily for the treatment of chronic shoulder pain. On examination, the abdomen was soft and nontender. Laboratory data are shown in Table 1. The results of evaluation by esophagogastroduodenoscopy and colonoscopy, including examination of the terminal ileum, were normal. No source of bleeding was identified. Two units of packed red cells were transfused, and the patient was discharged home with instructions to avoid further use of nonsteroidal antiinflammatory drugs.
Table 1. Laboratory Data.
On a follow-up visit two months later, the patient reported fatigue. A stool specimen was negative for occult blood. The hematocrit was 26.3 percent. Ferrous sulfate (325 mg three times per day) was prescribed. One month later, the hematocrit had risen to 38.0 percent. Air-contrast barium studies of the upper gastrointestinal tract with small-bowel follow-through were performed two months and eight months later; the results were normal.
Two years before admission, the patient again had midepigastric pain and came to the emergency department. The physical examination and an abdominal ultrasonographic evaluation revealed no abnormalities. A stool specimen was positive for occult blood. Laboratory data are shown in Table 1. Ranitidine was administered, and the patient was discharged home with a prescription for 20 mg of omeprazole per day. Subsequently, a serologic test for antibody to Helicobacter pylori was positive. A 10-day course of metronidazole, tetracycline, and pantoprazole was prescribed.
One year before the current admission, midepigastric pain recurred. A computed tomographic (CT) scan of the abdomen and pelvis showed a normal bowel without obstruction or inflammation. There were no masses. The pain resolved without treatment. Two and a half months before admission, the patient traveled to Mexico, where he had a two-day episode of abdominal pain associated with the frequent passage of black stools. The symptoms resolved without treatment, but during the next two weeks, recurrent knife-like epigastric pain occurred, again in association with the passage of black stools. Increasing fatigue and light-headedness developed.
When the patient returned home, he saw his primary care physician, who prescribed omeprazole. Laboratory data are shown in Table 1. During the next two weeks, the pain and passage of black stools continued; ranitidine was prescribed. Two days later he was admitted to this hospital.
The patient had been born and raised in Argentina and had emigrated to the United States seven years before admission. He worked as an automobile mechanic. He drank one glass of wine daily. On examination, the blood pressure was 120/80 mm Hg while he was standing and 138/89 mm Hg while he was supine, and the pulse was 89 and 85 beats per minute, respectively. Physical examination revealed no abnormalities. The levels of serum electrolytes, amylase, and lipase were normal, as were the results of urinalysis and liver-function studies. Other laboratory data are shown in Table 1. A stool specimen was black but not tarry and was positive for occult blood. Stool cultures were negative for enteric pathogens, protozoa, and helminths. Upper-gastrointestinal endoscopy showed a normal esophagus, striped erythematous mucosa in the cardia, a normal duodenum, and a normal jejunum to 160 cm. Colonoscopy showed no abnormalities.
A video-capsule–endoscopic study showed a small arteriovenous malformation in the mid-jejunum, which was not bleeding. There was a soft-tissue mucosal lesion in the distal ileum, which was not bleeding. The patient remained hemodynamically stable, and there was no further gastrointestinal bleeding. Esomeprazole, at a dose of 40 mg per day, was prescribed, and the patient was discharged home on the fifth hospital day.
One month before the current admission, an enteroclysis procedure had shown a pedunculated intraluminal filling defect within the distal ileum, which had smooth margins and was mobile under direct fluoroscopy. CT scanning of the abdomen and pelvis with the use of intravenous contrast material showed a soft-tissue lesion, 2 cm in diameter, within the distal small bowel; its central area had the density of fat and was surrounded by a wall with the density of soft tissue. In retrospect, this lesion had been evident on the study performed one year before admission, and had become enlarged.
The patient was readmitted to the hospital. Mesenteric angiography showed no abnormalities. A diagnostic procedure was performed.
Differential Diagnosis
Dr. Myles D. Keroack: This 48-year-old man was seen at this hospital after having recurrent episodes of acute and subacute gastrointestinal bleeding on many occasions over a period of almost three years, but endoscopic and imaging studies were unrevealing. I became involved in his care at the time of the video-capsule endoscopy. Gastrointestinal bleeding is one of the most common reasons for consultation with a gastroenterologist in a hospital setting. Usually, a diagnosis can be made with an endoscopic evaluation of the upper gastrointestinal tract (esophagus, stomach, and duodenum) and the lower gastrointestinal tract (rectum, colon, and distal small intestine). Often, the problem that is identified can be treated by a variety of endoscopic techniques. Only 3 to 5 percent of patients have a site of bleeding in the small intestine1; such problems cannot be diagnosed or treated by routine endoscopic means.
This patient had gastrointestinal bleeding with melena, which is defined as the passage of black or tarry stools containing blood that has been present in the gastrointestinal tract for at least 14 hours. The finding of melena suggests that the site of bleeding is in the upper gastrointestinal tract or small intestine. Bleeding in the ascending colon can cause melena, but usually bleeding in the colon will result in the passage of maroon-colored stools or, in the case of rectal bleeding, red blood. The normal results of the upper and lower endoscopic examinations also suggest that the small bowel is the likely source of this patient's bleeding.
Causes of Gastrointestinal Bleeding
The types of lesions that cause bleeding in the small bowel are similar to those found in other areas of the gastrointestinal tract. They include vascular abnormalities, ulcers and inflammatory lesions, neoplasms, and other, less common lesions. Finding and treating them, however, is much more difficult than with more proximal and more distal lesions.
Vascular Lesions
Vascular abnormalities are the most common cause of bleeding in the small intestine; they are responsible for 70 to 80 percent of cases.1 A variety of vascular lesions affect the small bowel. Angiodysplasias, or vascular ectasias, are small lesions characterized by dilated blood vessels with thin walls and can occur anywhere in the gastrointestinal tract. They are the most common cause of small-bowel bleeding in elderly patients. The vessels can be treated endoscopically with electrocautery or argon plasma coagulation. When these measures are unsuccessful, surgery is needed.
Telangiectasias are more diffuse than angiodysplasias, are associated with mucous-membrane and cutaneous lesions, and tend to recur after treatment. The most common cause of intestinal telangiectasias is the hereditary hemorrhagic telangiectasia syndrome (Rendu–Osler–Weber syndrome). They can also be seen in a syndrome consisting of calcinosis, Raynaud's phenomenon, sclerodactyly, and telangiectasia (known as the CRST syndrome). There is no evidence of these syndromes in this patient.
Dieulafoy's lesion, also known as caliber-persistent artery, classically occurs in the proximal portion of the stomach but has also been reported throughout the bowel. Its appearance is that of a larger-than-usual artery found in close proximity to the mucosal surface. There is often a pinpoint ulcer that causes the bleeding. This lesion can easily be missed on endoscopic examination if it is not bleeding at the time of the study. Repeated endoscopy, and some luck, are needed to find this small bleeding site and to treat it.
Aortoenteric fistulas are manifested as severe, life-threatening bleeding known as a "herald bleed." They are most often seen after surgical treatment of an aortic aneurysm. The clinical presentation is that of marked hemodynamic instability and, in many cases, syncope at the time of bleeding. Small-bowel varices are seen in the setting of portal hypertension from chronic liver disease, portal-vein thrombosis, and hepatic-vein thrombosis (i.e., the Budd–Chiari syndrome). Similar to other types of bleeding due to portal hypertension, such bleeding is dramatic and severe. This patient's bleeding was chronic and intermittent, and he had no history of aortic aneurysm or chronic liver disease.
Neoplasms
Tumors of the small bowel are the second most common cause of bleeding in the small bowel; they are the most common cause in persons between 30 and 50 years of age. Benign and malignant primary tumors as well as metastatic tumors can be found throughout the small intestine. They account for only 5 percent of all tumors in the gastrointestinal tract and for 5 to 10 percent of cases of small-bowel bleeding.2
Benign tumors are more common than malignant ones, and they tend to cause more abundant bleeding. Leiomyomas and leiomyosarcomas are the most common tumors associated with episodes of severe bleeding, such as that in this patient.3 These tumors are submucosal, but they often have a mucosal ulcer that causes bleeding. Other lesions — for example, adenomatous polyps, adenocarcinoma, lymphoma, polyps associated with syndromes such as the Peutz–Jeghers syndrome or familial polyposis, other gastrointestinal stromal tumors, and carcinoid tumors — tend to cause a more gradual blood loss than this patient had.
A variety of malignant tumors can metastasize to the small intestine. The most common are melanoma and breast cancer; others include renal-cell cancer, Kaposi's sarcoma, colon cancer, and ovarian cancer. This patient has no history of a malignant tumor, and imaging studies did not show evidence of either a primary tumor in the abdomen or a metastatic lesion in the small intestine.
Inflammatory Lesions
Ulcers and other inflammatory lesions of the small bowel can cause either brisk or slow blood loss in the gastrointestinal tract. Patients with Crohn's disease, the most common of these conditions, present with either rapid or slow blood loss. Blood loss is rarely the only manifestation of Crohn's disease, especially over a period of almost three years, as in the current case. Isolated ulcers in the small bowel, either idiopathic or due to nonsteroidal antiinflammatory drugs, tend to be associated with slow blood loss. Although this patient's initial episode of bleeding occurred while he was taking a nonsteroidal antiinflammatory drug, subsequent episodes were apparently spontaneous. Ischemic ulcers can cause acute bleeding, which is typically associated with pain, as this patient had; these ulcers, however, would be unlikely to recur over a long interval in an otherwise healthy patient. Other rare disorders, such as the Zollinger–Ellison syndrome and vasculitis, can cause blood loss from ulcerations in the small bowel. This patient had no other findings that suggested either of these disorders.
Ulceration and the surrounding edema can often be seen on radiographs of the small bowel or on computed tomographic images, but subtle lesions can be missed by these studies. According to one recent report, video-capsule endoscopy is more sensitive than traditional barium radiographic studies for detecting subtle changes of Crohn's disease.4
Small-Bowel Diverticula
Small-bowel diverticula, like colonic diverticula, occur at the site of perforating blood vessels and cause bleeding. As in colonic diverticular bleeding, the precise mechanism is not entirely clear.
Meckel's diverticulum, a remnant of the vitelline duct located in the distal ileum, is the most common cause of small-bowel bleeding in patients under the age of 25 years.5 Ectopic gastric tissue in the diverticulum causes ulceration and acute gastrointestinal bleeding. Occasionally, Meckel's diverticulum can cause intussusception that is associated with bleeding. There have also been case reports of inverted Meckel's diverticulum6 and of angiectasias and submucosal tumors within the diverticulum that caused bleeding. In addition to bleeding, pain can be one of the presenting symptoms. This patient is older than most patients who have Meckel's diverticulum, and therefore it was not initially considered a likely diagnosis.
Other Causes
Hemobilia, bleeding from the bile duct, is caused by communication between the biliary tree and the vascular network of the liver due to neoplasms, vascular aneurysms, liver abscess, or trauma; it can also occur after liver biopsy. Blood is seen coming from the ampulla of Vater at the time of endoscopy. Hemosuccus pancreaticus, bleeding into the small bowel from the pancreatic duct, can occur in the setting of pancreatic pseudocysts, pancreatitis, or neoplasms with erosion into a major vessel and communication with the pancreatic duct. In the current case, the normal results from the upper endoscopy tend to rule out these conditions.
Finally, infections such as cytomegalovirus infection, histoplasmosis, and tuberculosis can cause ulcerations throughout the gastrointestinal tract, with bleeding. However, cytomegalovirus infection is unlikely in a patient who is not immunosuppressed, and there are no risk factors for histoplasmosis in this patient. Intestinal tuberculosis is common in many parts of the world, and the fact that this patient is a recent immigrant from South America warrants questioning about possible exposures and, perhaps, skin testing.
Diagnostic Studies
Diagnosing small-bowel bleeding is always challenging. Flat, vascular lesions, which are the most common cause, may be especially difficult to find. Three-dimensional lesions such as ulcers and tumors are more likely to be found on conventional studies such as small-bowel radiography, enteroclysis, or CT. These studies provide a diagnosis in about 5 to 10 percent of cases of small-bowel bleeding.1 Angiography has a success rate of about 50 percent if there is active bleeding at a rate of 0.5 ml per minute and about 25 percent if there is no active bleeding.7 Technetium-99m scanning is approximately 75 percent accurate for the diagnosis of Meckel's diverticulum.1
Endoscopic studies provide an opportunity for both diagnosis and therapy if the lesion can be found. Between 60 and 70 percent of bleeding small-bowel lesions are within the reach of a standard endoscope.8,9 "Push" enteroscopy with a specially designed enteroscope allows examination of the entire jejunum, but often not the ileum.8 Intraoperative enteroscopy is the most invasive but the most accurate approach for this problem, with diagnostic rates of 75 to 80 percent.10 There have been a few case reports of laparoscope-assisted enteroscopy to evaluate small-bowel bleeding.
Wireless-video-capsule endoscopy is a promising technique for direct visualization of the small bowel. It provides a diagnosis in 50 to 60 percent of the cases.11,12 The patient swallows a capsule that is 20 mm long and 10 mm wide (Figure 1). It contains a light source, lens, digital receiver and transmitter, and two small batteries. It transmits 50,000 digital images over an eight-hour period to a sensor-antenna array and data recorder worn by the patient. At the end of the study, the data are downloaded and interpreted by computer, creating a video that can be viewed by the physician in about an hour. At this hospital, we have performed 72 of these procedures (Table 2). A diagnosis has been made in 43 cases (60 percent). There have been no complications.
Figure 1. Video-Capsule Endoscope.
The capsule is 20 mm long and 10 mm wide and contains an optical dome, a lens holder, a lens, illuminating light-emitting diodes (LED), a complementary metal oxide semiconductor (CMOS) imager, batteries, an application-specific integrated circuit (ASIC), and an antenna. Digital images are transmitted to a sensor-antenna array and data recorder worn by the patient. The data are downloaded and interpreted by a computer, creating a video that can be viewed by the physician in about an hour. Adapted from an image provided by Given Imaging.
Table 2. Video-Capsule–Endoscopic Findings at the Massachusetts General Hospital.
In the patient under discussion, capsule endoscopy was performed, and the video showed a lesion protruding into the lumen of the distal ileum, with overlying mucosa that appeared normal (Figure 2). A mucosal tumor would have differed in appearance from the surrounding mucosa. Therefore, the most likely diagnoses would be either a submucosal tumor, such as a leiomyoma or lipoma, or an inverted Meckel's diverticulum.
Figure 2. Image Obtained by Capsule Endoscopy.
An image recorded at 5 hours 45 minutes within the distal ileum shows a subtle lesion in the lumen, covered by normal mucosa. A video clip is in the Supplementary Appendix, available with the full text of this article at www.nejm.org.
Dr. Daniel K. Podolsky (Gastroenterology): Using this technique, how confidently can you approximate where the lesion is along the longitudinal axis of the intestine?
Dr. Keroack: I believed that this lesion was in the last third of the ileum because of its proximity to the ileocecal valve, but it is very difficult to judge the location, because the motility of the small intestine and therefore the transit time are very different from patient to patient. The physicians reviewing the study are able to divide the bowel into halves or thirds and help the surgeon identify roughly where the lesion may be found.
After detecting the lesion in this case, we recommended additional imaging studies.
Dr. Simeon D. Abramson: We first performed enteroclysis by injecting barium sulfate and methylcellulose through a nasogastric tube to allow detailed visualization of the small-bowel mucosa. This study shows an approximately 5-cm-long, pedunculated mass within the lumen of the terminal ileum (Figure 3). As seen on this compression view, the mass has smooth margins and borders and is not associated with proximal small-bowel dilatation or obstruction. Most important, the mass was found to be mobile: contrast material passed distally underneath it in the real-time fluoroscopic visualization.
Figure 3. Image Obtained by the Enteroclysis Procedure.
There is an approximately 5-cm-long, pedunculated intraluminal mass located within the terminal ileum. This compression view shows the mass to have smooth margins and borders (arrows). The mass was mobile under real-time fluoroscopic visualization.
Subsequently, CT studies obtained with the use of oral and intravenous contrast material better characterized the finding. The mass extends from the terminal ileum distally into the cecum (Figure 4). It has attenuation equal to that of fat, except for a smooth, uniform, circumferential wall of soft-tissue attenuation. In retrospect, this mass had been present on the prior CT scan but had been less conspicuous there than on the current study. The characteristics of this lesion on imaging differ from those of most malignant tumors, since it has smooth borders, does not invade the bowel wall, is not ulcerated, and is mobile. Because the mass has predominantly the attenuation of fat, tumors such as leiomyoma, hemangioma, and adenoma can also be ruled out. This leaves the differential diagnosis of fat-containing lesions, of which lipoma is the most common. However, a lipoma would not be expected to contain a wall of soft tissue. An alternative explanation is that the fat is mesenteric fat that has herniated into the bowel lumen and that the circumferential wall of soft tissue is the bowel wall. This picture might be seen if a diverticulum inverted into the bowel lumen. Other fat-containing lesions, such as a myelolipoma or angiomyolipoma, would be highly unusual in this location.
Figure 4. Axial CT Image Obtained with the Use of Oral and Intravenous Contrast Material.
The mass extends from the terminal ileum distally into the cecum. The mass has low attenuation, equal to that of fat, except for a smooth, uniform, circumferential wall of soft-tissue attenuation (arrows).
Clinical Diagnosis
Submucosal tumor or inverted Meckel's diverticulum.
Dr. Myles D. Keroack's Diagnosis
Submucosal tumor or inverted Meckel's diverticulum.
Pathological Discussion
Dr. Nancy Lee Harris (Pathology): Dr. Peralta, would you tell us about the findings at operation?
Dr. Ruben Peralta: I performed an exploratory laparotomy. There was a palpable mass in the distal ileal lumen, approximately 60 cm from the ileocecal valve, with an ileoileal intussusception (Figure 5). I resected a 20-cm-long segment of the ileum and constructed an end-to-end anastomosis. On opening the segment, we found a 5-cm-long inverted diverticulum was present, with some mucosal reddening at the tip. The postoperative recovery was unremarkable, and no further bleeding has occurred.
Figure 5. The Mass from the Distal Ileum.
A palpable mass in the distal ileum with an ileoileal intussusception was identified. Examination of the open specimen revealed a large, polypoid lesion with a long stalk and reddening of the mucosa at the tip.
This patient's intermittent abdominal pain can be attributed to a Meckel's diverticulum with recurrent episodes of intussusception.13,14 The new technological tool of capsule endoscopy was valuable in the identification of the source of bleeding in this patient.11,15 Although chronic bleeding from a Meckel's diverticulum16,17 is most commonly caused by heterotopic, acid-producing gastric tissue, which leads to ulceration of the adjacent ileal mucosa, multiple episodes of intussusception of an inverted diverticulum such as this one may cause trauma that results in mucosal ulceration and bleeding.18
The treatment for a bleeding Meckel's diverticulum is segmental resection.19,20 Diverticulectomy alone is discouraged, because it removes only the source of irritation (if heterotopic gastric mucosa is present) and not the source of bleeding, which is usually in the ileum adjacent to the diverticulum.
Dr. Harris: Dr. Joseph Misdraji will present the pathological findings.
Dr. Joseph Misdraji: On histologic examination, the inverted diverticulum contained all layers of the bowel wall, and therefore is a true diverticulum. The core consisted of adipose tissue. Much of the overlying mucosa was normal, but toward the tip of the diverticulum, it was ulcerated (Figure 6). Adjacent to the ulcer, the mucosa was hyperplastic and the muscularis mucosae was intercalated between the crypts and glands (Figure 6, inset). This smooth-muscle splaying is typical of mucosal prolapse. In a few areas, gastric pyloric glands were present. The parietal and chief cells that are necessary components of acid-producing gastric mucosa were not identified.
Figure 6. Inverted Meckel's Diverticulum (Hematoxylin and Eosin).
As shown, all layers of the bowel wall are present, including the muscularis propria, indicating that this is a true diverticulum. The center of the inverted diverticulum contains adipose tissue (black arrow), representing mesenteric fat. Inflamed and distorted intestinal mucosa is present (arrowhead), with mucosal ulceration (white arrows). There is mucosal hyperplasia and smooth muscle interdigitating between intestinal glands and crypts (inset; arrows), which are characteristic of a mucosal prolapse effect. Gastric pyloric glands are visible in the deep lamina propria (inset; arrowheads).
Pyloric-type gastric heterotopia is well described in Meckel's diverticulum. However, pyloric metaplasia is also observed in the small intestine in chronic inflammatory conditions and, in the current case, could be explained by the chronic prolapse. Gastrin-producing endocrine cells have also been described in association with Meckel's diverticulum with heterotopic gastric pyloric mucosa, but not in pyloric-type metaplasia.21 An immunohistochemical stain for gastrin was negative in this case, suggesting that the pyloric glands were metaplastic. In the absence of gastric mucosa, the ulceration in this case can be explained by local ischemia or mechanical factors related to prolapse and intussusception.22,23
Anatomical Diagnosis
Inverted Meckel's diverticulum with ulceration.
Dr. Keroack reports having received an honorarium for service as a substitute instructor at a course sponsored by Given Imaging, which manufactures video-endoscopy capsules.
Source Information
From the Gastroenterology Unit (M.D.K.) and the Departments of Surgery (R.P.), Radiology (S.D.A.), and Pathology (J.M.), Massachusetts General Hospital; and the Departments of Medicine (M.D.K.), Surgery (R.P.), Radiology (S.D.A.), and Pathology (J.M.), Harvard Medical School.
References
Lewis BS. Small intestine bleeding. Gastroenterol Clin North Am 2000;29:67-95.
Gill SS, Heuman DM, Mihas AA. Small intestinal neoplasms. J Clin Gastroenterol 2001;33:267-282.
Junquera F, Feu F, Papo M, et al. A multicenter, randomized, clinical trial of hormonal therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. Gastroenterology 2001;121:1073-1079.
Costamagna G, Shah SK, Riccioni ME, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002;123:999-1005.
St-Vil D, Brandt ML, Panic S, Bensoussan AL, Blanchard H. Meckel's diverticulum in children: a 20-year review. J Pediatr Surg 1991;26:1289-1292.
Hori K, Suzuki Y, Fujimori T. Inverted Meckel's diverticulum. Surgery 2003;133:116-117.
Lefkovitz Z, Cappell MS, Lookstein R, Mitty HA, Gerard PS. Radiologic diagnosis and treatment of gastrointestinal hemorrhage and ischemia. Med Clin North Am 2002;86:1357-1399.
Kovacs TO, Jensen DM. Recent advances in the endoscopic diagnosis and therapy of upper gastrointestinal, small intestine, and colonic bleeding. Med Clin North Am 2002;86:1319-1356.
Waye JD. Small-intestine endoscopy. Endoscopy 2001;33:24-30.
Douard R, Wind P, Panis Y, et al. Intraoperative enteroscopy for diagnosis and management of unexplained gastrointestinal bleeding. Am J Surg 2000;180:181-184.
Appleyard M, Gulkhovsky A, Swain P. Wireless-capsule endoscopy for recurrent small-bowel bleeding. N Engl J Med 2001;344:232-233.
Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002;56:349-353.
Silver B, Demos T. Symptomatic inverted Meckel's diverticulum: case report. J Can Assoc Radiol 1983;34:314-315.
Steinwald PM, Trachiotis GD, Tannebaum IR. Intussusception in an adult secondary to an inverted Meckel's diverticulum. Am Surg 1996;62:889-894.
Mylonaki M, MacLean D, Fritscher-Ravens A, Swain P. Wireless capsule endoscopic detection of Meckel's diverticulum after nondiagnostic surgery. Endoscopy 2002;34:1018-1020.
Farthing MG, Griffiths NJ, Thomas JM, Todd IP. Chronic bleeding from Meckel's diverticulum. Br J Surg 1981;68:176-176.
Thomas WEG, Williamson RCN. Chronic bleeding from Meckel's diverticulum. Br J Surg 1981;68:521-521.
Boldero JL. Inverted Meckel's diverticulum as a cause of anaemia and continuing blood loss. Br J Radiol 1978;51:829-830.
Soltero MJ, Bill AH. The natural history of Meckel's diverticulum and its relation to incidental removal: a study of 202 cases of diseased Meckel's diverticulum found in King County, Washington, over a fifteen year period. Am J Surg 1976;132:168-173.
Arnold JF, Pellicane JV. Meckel's diverticulum: a ten-year experience. Am Surg 1997;63:354-355.
Dayal Y, Wolfe HJ. Gastrin-producing cells in ectopic gastric mucosa of developmental and metaplastic origins. Gastroenterology 1978;75:655-660.
Higaki S, Saito Y, Akazawa A, et al. Bleeding Meckel's diverticulum in an adult. Hepatogastroenterology 2001;48:1628-1630.
Wong TY, Enriquez RE, Modlin IM, Soldano L, Ouellette GS, Kapadia CR. Recurrent hemorrhage from an invaginated Meckel's diverticulum in a 78-year-old man. Am J Gastroenterol 1990;85:195-198.
Related Letters:
Case 24-2004: Recurrent Gastrointestinal Bleeding in a 48-Year-Old Man
Spiro H., Friedel D. M., Keroack M.(Myles D. Keroack, M.D., R)
A 48-year-old man was admitted to the hospital for evaluation of recurrent gastrointestinal bleeding.
He had been well until 33 months earlier, when he had midepigastric pain and passed black stools that were positive for occult blood. He was found to be anemic and was admitted to the hospital for evaluation. He had been taking low doses of ibuprofen daily for the treatment of chronic shoulder pain. On examination, the abdomen was soft and nontender. Laboratory data are shown in Table 1. The results of evaluation by esophagogastroduodenoscopy and colonoscopy, including examination of the terminal ileum, were normal. No source of bleeding was identified. Two units of packed red cells were transfused, and the patient was discharged home with instructions to avoid further use of nonsteroidal antiinflammatory drugs.
Table 1. Laboratory Data.
On a follow-up visit two months later, the patient reported fatigue. A stool specimen was negative for occult blood. The hematocrit was 26.3 percent. Ferrous sulfate (325 mg three times per day) was prescribed. One month later, the hematocrit had risen to 38.0 percent. Air-contrast barium studies of the upper gastrointestinal tract with small-bowel follow-through were performed two months and eight months later; the results were normal.
Two years before admission, the patient again had midepigastric pain and came to the emergency department. The physical examination and an abdominal ultrasonographic evaluation revealed no abnormalities. A stool specimen was positive for occult blood. Laboratory data are shown in Table 1. Ranitidine was administered, and the patient was discharged home with a prescription for 20 mg of omeprazole per day. Subsequently, a serologic test for antibody to Helicobacter pylori was positive. A 10-day course of metronidazole, tetracycline, and pantoprazole was prescribed.
One year before the current admission, midepigastric pain recurred. A computed tomographic (CT) scan of the abdomen and pelvis showed a normal bowel without obstruction or inflammation. There were no masses. The pain resolved without treatment. Two and a half months before admission, the patient traveled to Mexico, where he had a two-day episode of abdominal pain associated with the frequent passage of black stools. The symptoms resolved without treatment, but during the next two weeks, recurrent knife-like epigastric pain occurred, again in association with the passage of black stools. Increasing fatigue and light-headedness developed.
When the patient returned home, he saw his primary care physician, who prescribed omeprazole. Laboratory data are shown in Table 1. During the next two weeks, the pain and passage of black stools continued; ranitidine was prescribed. Two days later he was admitted to this hospital.
The patient had been born and raised in Argentina and had emigrated to the United States seven years before admission. He worked as an automobile mechanic. He drank one glass of wine daily. On examination, the blood pressure was 120/80 mm Hg while he was standing and 138/89 mm Hg while he was supine, and the pulse was 89 and 85 beats per minute, respectively. Physical examination revealed no abnormalities. The levels of serum electrolytes, amylase, and lipase were normal, as were the results of urinalysis and liver-function studies. Other laboratory data are shown in Table 1. A stool specimen was black but not tarry and was positive for occult blood. Stool cultures were negative for enteric pathogens, protozoa, and helminths. Upper-gastrointestinal endoscopy showed a normal esophagus, striped erythematous mucosa in the cardia, a normal duodenum, and a normal jejunum to 160 cm. Colonoscopy showed no abnormalities.
A video-capsule–endoscopic study showed a small arteriovenous malformation in the mid-jejunum, which was not bleeding. There was a soft-tissue mucosal lesion in the distal ileum, which was not bleeding. The patient remained hemodynamically stable, and there was no further gastrointestinal bleeding. Esomeprazole, at a dose of 40 mg per day, was prescribed, and the patient was discharged home on the fifth hospital day.
One month before the current admission, an enteroclysis procedure had shown a pedunculated intraluminal filling defect within the distal ileum, which had smooth margins and was mobile under direct fluoroscopy. CT scanning of the abdomen and pelvis with the use of intravenous contrast material showed a soft-tissue lesion, 2 cm in diameter, within the distal small bowel; its central area had the density of fat and was surrounded by a wall with the density of soft tissue. In retrospect, this lesion had been evident on the study performed one year before admission, and had become enlarged.
The patient was readmitted to the hospital. Mesenteric angiography showed no abnormalities. A diagnostic procedure was performed.
Differential Diagnosis
Dr. Myles D. Keroack: This 48-year-old man was seen at this hospital after having recurrent episodes of acute and subacute gastrointestinal bleeding on many occasions over a period of almost three years, but endoscopic and imaging studies were unrevealing. I became involved in his care at the time of the video-capsule endoscopy. Gastrointestinal bleeding is one of the most common reasons for consultation with a gastroenterologist in a hospital setting. Usually, a diagnosis can be made with an endoscopic evaluation of the upper gastrointestinal tract (esophagus, stomach, and duodenum) and the lower gastrointestinal tract (rectum, colon, and distal small intestine). Often, the problem that is identified can be treated by a variety of endoscopic techniques. Only 3 to 5 percent of patients have a site of bleeding in the small intestine1; such problems cannot be diagnosed or treated by routine endoscopic means.
This patient had gastrointestinal bleeding with melena, which is defined as the passage of black or tarry stools containing blood that has been present in the gastrointestinal tract for at least 14 hours. The finding of melena suggests that the site of bleeding is in the upper gastrointestinal tract or small intestine. Bleeding in the ascending colon can cause melena, but usually bleeding in the colon will result in the passage of maroon-colored stools or, in the case of rectal bleeding, red blood. The normal results of the upper and lower endoscopic examinations also suggest that the small bowel is the likely source of this patient's bleeding.
Causes of Gastrointestinal Bleeding
The types of lesions that cause bleeding in the small bowel are similar to those found in other areas of the gastrointestinal tract. They include vascular abnormalities, ulcers and inflammatory lesions, neoplasms, and other, less common lesions. Finding and treating them, however, is much more difficult than with more proximal and more distal lesions.
Vascular Lesions
Vascular abnormalities are the most common cause of bleeding in the small intestine; they are responsible for 70 to 80 percent of cases.1 A variety of vascular lesions affect the small bowel. Angiodysplasias, or vascular ectasias, are small lesions characterized by dilated blood vessels with thin walls and can occur anywhere in the gastrointestinal tract. They are the most common cause of small-bowel bleeding in elderly patients. The vessels can be treated endoscopically with electrocautery or argon plasma coagulation. When these measures are unsuccessful, surgery is needed.
Telangiectasias are more diffuse than angiodysplasias, are associated with mucous-membrane and cutaneous lesions, and tend to recur after treatment. The most common cause of intestinal telangiectasias is the hereditary hemorrhagic telangiectasia syndrome (Rendu–Osler–Weber syndrome). They can also be seen in a syndrome consisting of calcinosis, Raynaud's phenomenon, sclerodactyly, and telangiectasia (known as the CRST syndrome). There is no evidence of these syndromes in this patient.
Dieulafoy's lesion, also known as caliber-persistent artery, classically occurs in the proximal portion of the stomach but has also been reported throughout the bowel. Its appearance is that of a larger-than-usual artery found in close proximity to the mucosal surface. There is often a pinpoint ulcer that causes the bleeding. This lesion can easily be missed on endoscopic examination if it is not bleeding at the time of the study. Repeated endoscopy, and some luck, are needed to find this small bleeding site and to treat it.
Aortoenteric fistulas are manifested as severe, life-threatening bleeding known as a "herald bleed." They are most often seen after surgical treatment of an aortic aneurysm. The clinical presentation is that of marked hemodynamic instability and, in many cases, syncope at the time of bleeding. Small-bowel varices are seen in the setting of portal hypertension from chronic liver disease, portal-vein thrombosis, and hepatic-vein thrombosis (i.e., the Budd–Chiari syndrome). Similar to other types of bleeding due to portal hypertension, such bleeding is dramatic and severe. This patient's bleeding was chronic and intermittent, and he had no history of aortic aneurysm or chronic liver disease.
Neoplasms
Tumors of the small bowel are the second most common cause of bleeding in the small bowel; they are the most common cause in persons between 30 and 50 years of age. Benign and malignant primary tumors as well as metastatic tumors can be found throughout the small intestine. They account for only 5 percent of all tumors in the gastrointestinal tract and for 5 to 10 percent of cases of small-bowel bleeding.2
Benign tumors are more common than malignant ones, and they tend to cause more abundant bleeding. Leiomyomas and leiomyosarcomas are the most common tumors associated with episodes of severe bleeding, such as that in this patient.3 These tumors are submucosal, but they often have a mucosal ulcer that causes bleeding. Other lesions — for example, adenomatous polyps, adenocarcinoma, lymphoma, polyps associated with syndromes such as the Peutz–Jeghers syndrome or familial polyposis, other gastrointestinal stromal tumors, and carcinoid tumors — tend to cause a more gradual blood loss than this patient had.
A variety of malignant tumors can metastasize to the small intestine. The most common are melanoma and breast cancer; others include renal-cell cancer, Kaposi's sarcoma, colon cancer, and ovarian cancer. This patient has no history of a malignant tumor, and imaging studies did not show evidence of either a primary tumor in the abdomen or a metastatic lesion in the small intestine.
Inflammatory Lesions
Ulcers and other inflammatory lesions of the small bowel can cause either brisk or slow blood loss in the gastrointestinal tract. Patients with Crohn's disease, the most common of these conditions, present with either rapid or slow blood loss. Blood loss is rarely the only manifestation of Crohn's disease, especially over a period of almost three years, as in the current case. Isolated ulcers in the small bowel, either idiopathic or due to nonsteroidal antiinflammatory drugs, tend to be associated with slow blood loss. Although this patient's initial episode of bleeding occurred while he was taking a nonsteroidal antiinflammatory drug, subsequent episodes were apparently spontaneous. Ischemic ulcers can cause acute bleeding, which is typically associated with pain, as this patient had; these ulcers, however, would be unlikely to recur over a long interval in an otherwise healthy patient. Other rare disorders, such as the Zollinger–Ellison syndrome and vasculitis, can cause blood loss from ulcerations in the small bowel. This patient had no other findings that suggested either of these disorders.
Ulceration and the surrounding edema can often be seen on radiographs of the small bowel or on computed tomographic images, but subtle lesions can be missed by these studies. According to one recent report, video-capsule endoscopy is more sensitive than traditional barium radiographic studies for detecting subtle changes of Crohn's disease.4
Small-Bowel Diverticula
Small-bowel diverticula, like colonic diverticula, occur at the site of perforating blood vessels and cause bleeding. As in colonic diverticular bleeding, the precise mechanism is not entirely clear.
Meckel's diverticulum, a remnant of the vitelline duct located in the distal ileum, is the most common cause of small-bowel bleeding in patients under the age of 25 years.5 Ectopic gastric tissue in the diverticulum causes ulceration and acute gastrointestinal bleeding. Occasionally, Meckel's diverticulum can cause intussusception that is associated with bleeding. There have also been case reports of inverted Meckel's diverticulum6 and of angiectasias and submucosal tumors within the diverticulum that caused bleeding. In addition to bleeding, pain can be one of the presenting symptoms. This patient is older than most patients who have Meckel's diverticulum, and therefore it was not initially considered a likely diagnosis.
Other Causes
Hemobilia, bleeding from the bile duct, is caused by communication between the biliary tree and the vascular network of the liver due to neoplasms, vascular aneurysms, liver abscess, or trauma; it can also occur after liver biopsy. Blood is seen coming from the ampulla of Vater at the time of endoscopy. Hemosuccus pancreaticus, bleeding into the small bowel from the pancreatic duct, can occur in the setting of pancreatic pseudocysts, pancreatitis, or neoplasms with erosion into a major vessel and communication with the pancreatic duct. In the current case, the normal results from the upper endoscopy tend to rule out these conditions.
Finally, infections such as cytomegalovirus infection, histoplasmosis, and tuberculosis can cause ulcerations throughout the gastrointestinal tract, with bleeding. However, cytomegalovirus infection is unlikely in a patient who is not immunosuppressed, and there are no risk factors for histoplasmosis in this patient. Intestinal tuberculosis is common in many parts of the world, and the fact that this patient is a recent immigrant from South America warrants questioning about possible exposures and, perhaps, skin testing.
Diagnostic Studies
Diagnosing small-bowel bleeding is always challenging. Flat, vascular lesions, which are the most common cause, may be especially difficult to find. Three-dimensional lesions such as ulcers and tumors are more likely to be found on conventional studies such as small-bowel radiography, enteroclysis, or CT. These studies provide a diagnosis in about 5 to 10 percent of cases of small-bowel bleeding.1 Angiography has a success rate of about 50 percent if there is active bleeding at a rate of 0.5 ml per minute and about 25 percent if there is no active bleeding.7 Technetium-99m scanning is approximately 75 percent accurate for the diagnosis of Meckel's diverticulum.1
Endoscopic studies provide an opportunity for both diagnosis and therapy if the lesion can be found. Between 60 and 70 percent of bleeding small-bowel lesions are within the reach of a standard endoscope.8,9 "Push" enteroscopy with a specially designed enteroscope allows examination of the entire jejunum, but often not the ileum.8 Intraoperative enteroscopy is the most invasive but the most accurate approach for this problem, with diagnostic rates of 75 to 80 percent.10 There have been a few case reports of laparoscope-assisted enteroscopy to evaluate small-bowel bleeding.
Wireless-video-capsule endoscopy is a promising technique for direct visualization of the small bowel. It provides a diagnosis in 50 to 60 percent of the cases.11,12 The patient swallows a capsule that is 20 mm long and 10 mm wide (Figure 1). It contains a light source, lens, digital receiver and transmitter, and two small batteries. It transmits 50,000 digital images over an eight-hour period to a sensor-antenna array and data recorder worn by the patient. At the end of the study, the data are downloaded and interpreted by computer, creating a video that can be viewed by the physician in about an hour. At this hospital, we have performed 72 of these procedures (Table 2). A diagnosis has been made in 43 cases (60 percent). There have been no complications.
Figure 1. Video-Capsule Endoscope.
The capsule is 20 mm long and 10 mm wide and contains an optical dome, a lens holder, a lens, illuminating light-emitting diodes (LED), a complementary metal oxide semiconductor (CMOS) imager, batteries, an application-specific integrated circuit (ASIC), and an antenna. Digital images are transmitted to a sensor-antenna array and data recorder worn by the patient. The data are downloaded and interpreted by a computer, creating a video that can be viewed by the physician in about an hour. Adapted from an image provided by Given Imaging.
Table 2. Video-Capsule–Endoscopic Findings at the Massachusetts General Hospital.
In the patient under discussion, capsule endoscopy was performed, and the video showed a lesion protruding into the lumen of the distal ileum, with overlying mucosa that appeared normal (Figure 2). A mucosal tumor would have differed in appearance from the surrounding mucosa. Therefore, the most likely diagnoses would be either a submucosal tumor, such as a leiomyoma or lipoma, or an inverted Meckel's diverticulum.
Figure 2. Image Obtained by Capsule Endoscopy.
An image recorded at 5 hours 45 minutes within the distal ileum shows a subtle lesion in the lumen, covered by normal mucosa. A video clip is in the Supplementary Appendix, available with the full text of this article at www.nejm.org.
Dr. Daniel K. Podolsky (Gastroenterology): Using this technique, how confidently can you approximate where the lesion is along the longitudinal axis of the intestine?
Dr. Keroack: I believed that this lesion was in the last third of the ileum because of its proximity to the ileocecal valve, but it is very difficult to judge the location, because the motility of the small intestine and therefore the transit time are very different from patient to patient. The physicians reviewing the study are able to divide the bowel into halves or thirds and help the surgeon identify roughly where the lesion may be found.
After detecting the lesion in this case, we recommended additional imaging studies.
Dr. Simeon D. Abramson: We first performed enteroclysis by injecting barium sulfate and methylcellulose through a nasogastric tube to allow detailed visualization of the small-bowel mucosa. This study shows an approximately 5-cm-long, pedunculated mass within the lumen of the terminal ileum (Figure 3). As seen on this compression view, the mass has smooth margins and borders and is not associated with proximal small-bowel dilatation or obstruction. Most important, the mass was found to be mobile: contrast material passed distally underneath it in the real-time fluoroscopic visualization.
Figure 3. Image Obtained by the Enteroclysis Procedure.
There is an approximately 5-cm-long, pedunculated intraluminal mass located within the terminal ileum. This compression view shows the mass to have smooth margins and borders (arrows). The mass was mobile under real-time fluoroscopic visualization.
Subsequently, CT studies obtained with the use of oral and intravenous contrast material better characterized the finding. The mass extends from the terminal ileum distally into the cecum (Figure 4). It has attenuation equal to that of fat, except for a smooth, uniform, circumferential wall of soft-tissue attenuation. In retrospect, this mass had been present on the prior CT scan but had been less conspicuous there than on the current study. The characteristics of this lesion on imaging differ from those of most malignant tumors, since it has smooth borders, does not invade the bowel wall, is not ulcerated, and is mobile. Because the mass has predominantly the attenuation of fat, tumors such as leiomyoma, hemangioma, and adenoma can also be ruled out. This leaves the differential diagnosis of fat-containing lesions, of which lipoma is the most common. However, a lipoma would not be expected to contain a wall of soft tissue. An alternative explanation is that the fat is mesenteric fat that has herniated into the bowel lumen and that the circumferential wall of soft tissue is the bowel wall. This picture might be seen if a diverticulum inverted into the bowel lumen. Other fat-containing lesions, such as a myelolipoma or angiomyolipoma, would be highly unusual in this location.
Figure 4. Axial CT Image Obtained with the Use of Oral and Intravenous Contrast Material.
The mass extends from the terminal ileum distally into the cecum. The mass has low attenuation, equal to that of fat, except for a smooth, uniform, circumferential wall of soft-tissue attenuation (arrows).
Clinical Diagnosis
Submucosal tumor or inverted Meckel's diverticulum.
Dr. Myles D. Keroack's Diagnosis
Submucosal tumor or inverted Meckel's diverticulum.
Pathological Discussion
Dr. Nancy Lee Harris (Pathology): Dr. Peralta, would you tell us about the findings at operation?
Dr. Ruben Peralta: I performed an exploratory laparotomy. There was a palpable mass in the distal ileal lumen, approximately 60 cm from the ileocecal valve, with an ileoileal intussusception (Figure 5). I resected a 20-cm-long segment of the ileum and constructed an end-to-end anastomosis. On opening the segment, we found a 5-cm-long inverted diverticulum was present, with some mucosal reddening at the tip. The postoperative recovery was unremarkable, and no further bleeding has occurred.
Figure 5. The Mass from the Distal Ileum.
A palpable mass in the distal ileum with an ileoileal intussusception was identified. Examination of the open specimen revealed a large, polypoid lesion with a long stalk and reddening of the mucosa at the tip.
This patient's intermittent abdominal pain can be attributed to a Meckel's diverticulum with recurrent episodes of intussusception.13,14 The new technological tool of capsule endoscopy was valuable in the identification of the source of bleeding in this patient.11,15 Although chronic bleeding from a Meckel's diverticulum16,17 is most commonly caused by heterotopic, acid-producing gastric tissue, which leads to ulceration of the adjacent ileal mucosa, multiple episodes of intussusception of an inverted diverticulum such as this one may cause trauma that results in mucosal ulceration and bleeding.18
The treatment for a bleeding Meckel's diverticulum is segmental resection.19,20 Diverticulectomy alone is discouraged, because it removes only the source of irritation (if heterotopic gastric mucosa is present) and not the source of bleeding, which is usually in the ileum adjacent to the diverticulum.
Dr. Harris: Dr. Joseph Misdraji will present the pathological findings.
Dr. Joseph Misdraji: On histologic examination, the inverted diverticulum contained all layers of the bowel wall, and therefore is a true diverticulum. The core consisted of adipose tissue. Much of the overlying mucosa was normal, but toward the tip of the diverticulum, it was ulcerated (Figure 6). Adjacent to the ulcer, the mucosa was hyperplastic and the muscularis mucosae was intercalated between the crypts and glands (Figure 6, inset). This smooth-muscle splaying is typical of mucosal prolapse. In a few areas, gastric pyloric glands were present. The parietal and chief cells that are necessary components of acid-producing gastric mucosa were not identified.
Figure 6. Inverted Meckel's Diverticulum (Hematoxylin and Eosin).
As shown, all layers of the bowel wall are present, including the muscularis propria, indicating that this is a true diverticulum. The center of the inverted diverticulum contains adipose tissue (black arrow), representing mesenteric fat. Inflamed and distorted intestinal mucosa is present (arrowhead), with mucosal ulceration (white arrows). There is mucosal hyperplasia and smooth muscle interdigitating between intestinal glands and crypts (inset; arrows), which are characteristic of a mucosal prolapse effect. Gastric pyloric glands are visible in the deep lamina propria (inset; arrowheads).
Pyloric-type gastric heterotopia is well described in Meckel's diverticulum. However, pyloric metaplasia is also observed in the small intestine in chronic inflammatory conditions and, in the current case, could be explained by the chronic prolapse. Gastrin-producing endocrine cells have also been described in association with Meckel's diverticulum with heterotopic gastric pyloric mucosa, but not in pyloric-type metaplasia.21 An immunohistochemical stain for gastrin was negative in this case, suggesting that the pyloric glands were metaplastic. In the absence of gastric mucosa, the ulceration in this case can be explained by local ischemia or mechanical factors related to prolapse and intussusception.22,23
Anatomical Diagnosis
Inverted Meckel's diverticulum with ulceration.
Dr. Keroack reports having received an honorarium for service as a substitute instructor at a course sponsored by Given Imaging, which manufactures video-endoscopy capsules.
Source Information
From the Gastroenterology Unit (M.D.K.) and the Departments of Surgery (R.P.), Radiology (S.D.A.), and Pathology (J.M.), Massachusetts General Hospital; and the Departments of Medicine (M.D.K.), Surgery (R.P.), Radiology (S.D.A.), and Pathology (J.M.), Harvard Medical School.
References
Lewis BS. Small intestine bleeding. Gastroenterol Clin North Am 2000;29:67-95.
Gill SS, Heuman DM, Mihas AA. Small intestinal neoplasms. J Clin Gastroenterol 2001;33:267-282.
Junquera F, Feu F, Papo M, et al. A multicenter, randomized, clinical trial of hormonal therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. Gastroenterology 2001;121:1073-1079.
Costamagna G, Shah SK, Riccioni ME, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002;123:999-1005.
St-Vil D, Brandt ML, Panic S, Bensoussan AL, Blanchard H. Meckel's diverticulum in children: a 20-year review. J Pediatr Surg 1991;26:1289-1292.
Hori K, Suzuki Y, Fujimori T. Inverted Meckel's diverticulum. Surgery 2003;133:116-117.
Lefkovitz Z, Cappell MS, Lookstein R, Mitty HA, Gerard PS. Radiologic diagnosis and treatment of gastrointestinal hemorrhage and ischemia. Med Clin North Am 2002;86:1357-1399.
Kovacs TO, Jensen DM. Recent advances in the endoscopic diagnosis and therapy of upper gastrointestinal, small intestine, and colonic bleeding. Med Clin North Am 2002;86:1319-1356.
Waye JD. Small-intestine endoscopy. Endoscopy 2001;33:24-30.
Douard R, Wind P, Panis Y, et al. Intraoperative enteroscopy for diagnosis and management of unexplained gastrointestinal bleeding. Am J Surg 2000;180:181-184.
Appleyard M, Gulkhovsky A, Swain P. Wireless-capsule endoscopy for recurrent small-bowel bleeding. N Engl J Med 2001;344:232-233.
Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002;56:349-353.
Silver B, Demos T. Symptomatic inverted Meckel's diverticulum: case report. J Can Assoc Radiol 1983;34:314-315.
Steinwald PM, Trachiotis GD, Tannebaum IR. Intussusception in an adult secondary to an inverted Meckel's diverticulum. Am Surg 1996;62:889-894.
Mylonaki M, MacLean D, Fritscher-Ravens A, Swain P. Wireless capsule endoscopic detection of Meckel's diverticulum after nondiagnostic surgery. Endoscopy 2002;34:1018-1020.
Farthing MG, Griffiths NJ, Thomas JM, Todd IP. Chronic bleeding from Meckel's diverticulum. Br J Surg 1981;68:176-176.
Thomas WEG, Williamson RCN. Chronic bleeding from Meckel's diverticulum. Br J Surg 1981;68:521-521.
Boldero JL. Inverted Meckel's diverticulum as a cause of anaemia and continuing blood loss. Br J Radiol 1978;51:829-830.
Soltero MJ, Bill AH. The natural history of Meckel's diverticulum and its relation to incidental removal: a study of 202 cases of diseased Meckel's diverticulum found in King County, Washington, over a fifteen year period. Am J Surg 1976;132:168-173.
Arnold JF, Pellicane JV. Meckel's diverticulum: a ten-year experience. Am Surg 1997;63:354-355.
Dayal Y, Wolfe HJ. Gastrin-producing cells in ectopic gastric mucosa of developmental and metaplastic origins. Gastroenterology 1978;75:655-660.
Higaki S, Saito Y, Akazawa A, et al. Bleeding Meckel's diverticulum in an adult. Hepatogastroenterology 2001;48:1628-1630.
Wong TY, Enriquez RE, Modlin IM, Soldano L, Ouellette GS, Kapadia CR. Recurrent hemorrhage from an invaginated Meckel's diverticulum in a 78-year-old man. Am J Gastroenterol 1990;85:195-198.
Related Letters:
Case 24-2004: Recurrent Gastrointestinal Bleeding in a 48-Year-Old Man
Spiro H., Friedel D. M., Keroack M.(Myles D. Keroack, M.D., R)