Praveen K. Roy

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)

Nonmalignant obstruction is a common problem with metal stents in the treatment of esophageal cancer.

BACKGROUND The use of metal stents for the treatment of dysphagia due to esophageal malignancy is an important advance because of ease of delivery and their self-expandable property. Obstruction due to tumor overgrowth is a recognized complication, but nonmalignant obstruction in patients with metal stents is rarely reported. METHODS Database records of patients who had esophageal cancer and underwent metal stent insertion were reviewed. RESULTS A total of 116 patients were seen between October 1993 and October 1997. Four types of metal stents had been used (Ultraflex, Z Stent, Wallstent, and Esophacoil). Detailed follow-up information was available for 81 patients, who constitute the study sample. Forty-nine (60%) stent obstructions were reported, 26 of the 49 (53%) were due to tumor overgrowth and 23 (47%) were not associated with malignancy. Histologic analysis of the nonmalignant obstructing tissue showed granulation tissue (56%), reactive hyperplasia (22%) and fibrosis (22%). CONCLUSIONS Nonmalignant obstruction is a common although infrequently reported complication after placement of metal stents for esophageal cancer. The tissue response of the esophageal mucosa occurred with all 4 types of stents used. No specific characteristic of the stent or prior treatment seems to be related to obstruction of the stent in patients with either nonmalignant obstruction or tumor overgrowth.

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.