Alaa Abou-Saif

Zollinger-Ellison syndrome. Clinical presentation in 261 patients.

We prospectively evaluated the initial presenting symptoms in 261 patients with Zollinger-Ellison syndrome (ZES) over a 25-year period. Twenty-two percent of the patients had multiple endocrine neoplasia-type 1 (MEN-1) with ZES. Mean age at onset was 41.1 +/- 0.7 years, with MEN-1 patients presenting at a younger age than those with sporadic ZES (p < 0.0001). Three percent of the patients had onset of the disease < age 20 years, and 7% > 60 years. A mean delay to diagnosis of 5.2 +/- 0.4 years occurred in all patients. A shorter duration of symptoms was noted in female patients and in patients with liver metastases. Abdominal pain and diarrhea were the most common symptoms, present in 75% and 73% of patients, respectively. Heartburn and weight loss, which were uncommonly reported in early series, were present in 44% and 17% of patients, respectively. Gastrointestinal bleeding was the initial presentation in a quarter of the patients. Patients rarely presented with only 1 symptom (11%); pain and diarrhea was the most frequent combination, occurring in 55% of patients. An important presenting sign that should suggest ZES is prominent gastric body folds, which were noted on endoscopy in 94% of patients; however, esophageal stricture and duodenal or pyloric scarring, reported in numerous case reports, were noted in only 4%-10%. Patients with MEN-1 presented less frequently with pain and bleeding and more frequently with nephrolithiasis. Comparing the clinical presentation before the introduction of histamine H2-receptor antagonists (pre-1980, n = 36), after the introduction of histamine H2-receptor antagonists (1981-1989, n = 118), and after the introduction of proton pump inhibitors (PPIs) (> 1990, n = 106) demonstrates no change in age of onset; delay in diagnosis; frequency of pain, diarrhea, weight loss; or frequency of complications of severe peptic disease (bleeding, perforations, esophageal strictures, pyloric scarring). Since the introduction of histamine H2-receptor antagonists, fewer patients had a previous history of gastric acid-reducing surgery or total gastrectomy. Only 1 patient evaluated after 1980 had a total gastrectomy, and this was done in 1977. The location of the primary tumor in general had a minimal effect on the clinical presentation, causing no effect on the age at presentation, delay in diagnosis, frequency of nephrolithiasis, or severity of disease (strictures, perforations, peptic ulcers, pyloric scarring). Disease extent had a minimal effect on symptoms, with only bleeding being more frequent in patients with localized disease. Patients with advanced disease presented at a later age and with a shorter disease history (p = 0.001), were less likely to have MEN-1 (p = 0.0087), and tended to have diarrhea more frequently (p = 0.079). A correct diagnosis of ZES was made by the referring physician initially in only 3% of the patients. The most common misdiagnosis made were idiopathic peptic ulcer disease (71%), idiopathic gastroesophageal reflux disease (GERD) (7%), and chronic idiopathic diarrhea (7%). Other less common misdiagnosis were Crohn disease (2%) and various diarrhea diseases (celiac sprue [3%], irritable bowel syndrome [3%], infectious diarrhea [2%], and lactose intolerance [1%]). Other medical disorders were present in 55% of all patients; patients with sporadic disease had fewer other medical disorders than patients with MEN-1 (45% versus 90%, p < 0.00001). Hyperparathyroidism and a previous history of kidney stones were significantly more frequent in patients with MEN-1 than in those with sporadic ZES. Pulmonary disorders and other malignancies were also more common in patients with MEN-1. These results demonstrate that abdominal pain, diarrhea, and heartburn are the most common presenting symptoms in ZES and that heartburn and diarrhea are more common than previously reported. The presence of weight loss especially with abdominal pain, diarrhea, or heartburn is an important clue suggesting the presence of gastrinoma. The presence of prominent gastric body folds, a clinical sign that has not been appreciated, is another important clue to the diagnosis of ZES. Patients with MEN-1 presented at an earlier age; however, in general, the initial symptoms were similar to patients without MEN-1. Gastrinoma extent and location have minimal effects on the clinical presentation. Overall, neither the introduction of successful antisecretory therapy nor widespread publication about ZES, attempting to increase awareness, has shortened the delay in diagnosis or reduced the incidence of patients presenting with peptic complications. The introduction of successful antisecretory therapy, however, has dramatically decreased the rate of surgery in controlling the acid secretion and likely led to patients presenting with less severe symptoms and fewer complications. (ABSTRACT TRUNCATED)

CASE REPORT: Retained Gastric Antrum Syndrome

With the understanding of the role of H. pylori in causing peptic ulcer disease (PUD) and the development of potent gastric antisecretory drugs, the number of patients undergoing gastric acid-reducing surgery (vagotomy and drainage procedure, Billroth I and II resections) is decreasing rapidly (1). One of the welcome results of this decrease is that physicians see fewer patients with postgastrectomy problems. However, a negative aspect of this result is that they also are less familiar with treating such problems. Recurrent PUD after a Billroth II operation is uncommon (0.5–6%), but when it occurs it is a difficult management problem (1–3). It can be caused by an incomplete vagotomy, insufficient gastric resection, mechanical dysfunction of the stoma, the frequent use of aspirin or NSAIDS, incomplete excision of the gastric antrum from the detached duodenum (retained gastric antrum), or Zollinger-Ellison syndrome (ZES) (1–3). Even when gastric acid-reducing surgery with Billroth II resection was a frequent operation in the United States, retained gastric antrum (RGA) was an uncommon cause of recurrent postoperative ulcer (1–3). In the past this diagnosis was frequently not considered, resulting in delays of diagnosis longer than 20 years (4–8). With the decreasing frequency of gastric acid-reducing surgery and the decreased exposure most physicians will have to patients with recurrent ulcers postoperatively, it is likely in the future this diagnosis will be missed for an even longer period of time. This is unfortunate because this condition can cause repetitive ulceration with recurrent bleeding; however, if diagnosed, it is completely curable by surgical resection of the retained antrum. In this case report we describe a patient in whom the diagnosis of RGA was missed for 31 years and discuss techniques that are available that, if performed, will establish the diagnosis and lead to its cure.

Clinical reviewComplications of gallstone disease: Mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus

Complications of gallstone disease: mirizzi syndrome, cholecystocholedochal fistula, and gallstone ileus

3894 Prospective study of the ability of endoscopic ultrasound to localize duodenal gastrinomas.

The role of EUS in localizing duodenal gastrinomas remains controversial because of lack of prospective assessments. To address this question we prospectively studied 40 consecutive patients with Zollinger-Ellison syndrome (ZES) admitted to the NIH prior to surgery. All patients had conventional imaging studies (CT, MRI, ultrasound, angiography), somatostatin receptor scintigraphy (SRS), EUS (Olympus UM 20), catheter US [UM3R] with endoscopy [side-viewing endoscope-(TJF)] (CUS.Endo), followed by a standardized laparotomy with a Kocher maneuver, intra-operative ultrasound and duodenotomy. Seven patients had MEN-1 and ZES and 33 had sporadic ZES. Prior to surgery, at least one nonEUS imaging study localized a possible duodenal gastrinoma in 19 patients (48%); conventional imaging only in 28%; SRS in 42%; EUS alone, 35%; CUS.Endo, 45%; and EUS or CUS.Endo, 52%. At exploration duodenal gastrinomas were found in 18 patients (45%). EUS, CUS.Endo, both (EUS and CUS.Endo), and any other imaging (other imaging) had sensitivities of 47%, 64%, 71% and 61% and specificities of 65%, 58%, 52% and 64%, respectively. In the 8 patients with all other imaging negative with a duodenal gastrinoma, EUS was positive in 50% (4/8), CUS.Endo in 38%, or either in 62%. In the 22 patients without a duodenal gastrinoma a false positive localization occurred with EUS in 5/22 (23%); CUS.Endo in 32%; both, 36%; and with other imaging in 36%. The sensitivity of SRS alone for localizing a duodenal tumor was 56%; SRS + EUS, 83%; SRS + CUS.Endo, 83%; and SRS + both, 88%. These results demonstrate that EUS alone will localize 47% of duodenal gastrinomas, which is slightly less than the 61% seen with a combination of other imaging studies. However, if combined with careful endoscopy using a side-viewing endoscope and catheter ultrasound, it will localize 71%. Both procedures are complementary to SRS, correctly localizing a duodenal gastrinoma in 88% of patients; however, the combination of both endoscopic procedures also increases the false positive rate and decreases the specificity.