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1/66. metiamide in the zollinger-ellison syndrome.

    The histamine H2-receptor antagonist metiamide is an inhibitor of endogenous and stimulated gastric-acid secretion. It appears to have therapeutic possibilities in duodenal-ulcer disease. Three patients exhibiting the zollinger-ellison syndrome have been treated with this drug for six months or more. Rapid symptomatic improvement occurred in each case, followed by ulcer healing. There were also reductions in gastric secretion and consistent changes in the fasting serum-gastrin concentration. On patient relapsed temporarily during therapy. There have been no side effects. It is concluded that, in the short term, metiamide is of benefit in the zollinger-ellison syndrome.
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2/66. 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)
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3/66. A new cause of zollinger-ellison syndrome: non-small cell lung cancer.

    Numerous epidemiologic studies suggest a relationship between lung cancer and peptic ulcer disease. Furthermore, various lung cancers synthesize and release a number of peptides such as gastrin and gastrin-releasing peptide that could cause acid hypersecretion; however, zollinger-ellison syndrome (ZES), because of a lung tumor, has never been described. We report such a patient for the first time. A 60-year-old man with a non-small cell lung carcinoma (large cell type) presented with diarrhea, heartburn, abdominal pain, and duodenal ulcers. Evaluation showed ZES was present (fasting hypergastrinemia, hyperchlorhydria) and control of all symptoms by omeprazole. No abdominal or cardiac tumor, the other known locations of gastrinomas causing ZES, was found on detailed tumor imaging studies. Resection of the lung tumor resulted in a decrease in gastrin levels to normal values. plasma radioimmunoassays showed elevated gastrin, chromogranin a and normal levels of gastrin-releasing peptide, and 9 other hormones. The tumor showed similar immunocytochemical results. The characteristics of this case are compared with 100 cases of sporadic abdominal gastrinomas, and the evidence reviewed suggests why ZES should be considered in patients with lung cancer with peptic symptoms.
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4/66. Case presentation of gastrinoma combined with gastric carcinoid with the longest survival record -- zollinger-ellison syndrome: pathophysiology, diagnosis and therapy.

    BACKGROUND: zollinger-ellison syndrome is a very rare disease caused by tumor with gastrin producing cells accompanied by hypergastrinemia leading to gastric hypersecretion and peptic ulcers and their complications.CASE STUDY: female case of gastrinoma (zollinger-ellison syndrome; Z-E) with a record of 38 yrs of survival. Acute gastro-duodenal ulcers started at 28 yr of age and Z-E was diagnosed by using gastrin assays. Basal and maximal acid outputs and ratio of basal/maximal outputs were away over normal limits. Because of ulcer recurrence and complications, patient was subjected to several gastric surgeries but refused total gastrectomy. She was also treated with many H2-receptor (R) antagonists and proton-pump inhibitors (PPI), each new drug being initially highly effective but then showing declining efficacy except when PPI, lansoprazole was used. The gastrin level rose in the course of disease from initial high value of 2000 pg/mL to the extreme 4500 ng/mL at present. During the last 2 yrs, metastasis mainly to liver developed and they were successfully treated by synthetic octapeptide derivative of somatostatin and, as a result, metastatis partly reduced and plasma gastrin drasticly decreased. biopsy taken from liver metastasis showed the presence of typical gastrinoma cells with gastrin and chromogranin, while that from oxyntic mucosa revealed the ECL-cell hyperplasia with carcinoid tumors and unexpected gastric atrophy.CONCLUSIONS: This phenomenal case described in this article might be the new proven evidence needed by gastroenterologists to overturn the traditional treatment using total gastrectomy as a treatment of choice to the partial gastrectomy combined with proton pump inhibitors.
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5/66. Osteoblastic bone metastasis in zollinger-ellison syndrome.

    The authors describe a case of osteoblastic metastasis in a patient with zollinger-ellison syndrome resulting from the presence of a pancreatic tumor, which they believe is the first such case documented. Following a total gastectomy for hyperacidity in a 53-year-old woman, a gradually enlarging liver was treated with steptozotocin. radiation therapy to the areas of bony metastases resulted in complete alleviation of pain.
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6/66. Primary lymph node gastrinoma: a case report.

    The zollinger-ellison syndrome consists of severe peptic ulceration, acid hypersecretion, and islet tumors known as gastrinomas. The discovery of gastrinomas in unusual locations such as lymph nodes, bones, ovaries, and the liver poses a diagnostic dilemma as to whether the tumor is primary or metastatic. Here we present a case of a primary gastrinoma within a lymph node.
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7/66. Focal oxyntic gland atrophy with endocrine cell hyperplasia in Zollinger-Ellison syndrome during omeprazole treatment.

    Development of focal gland atrophy of the oxyntic mucosa was found in two patients with the zollinger-ellison syndrome undergoing long-term treatment with omeprazole. The atrophic areas revealed florid proliferation of endocrine cells in the form of both intraglandular crescents and micronodular hyperplasia. This proliferation was significantly more pronounced than in the remaining non-atrophic mucosa. The possible relationship of these changes to long-standing pharmacological therapy for gastric acid suppression is discussed.
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keywords = gastric acid, acid
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8/66. zollinger-ellison syndrome: special considerations.

    Twelve patients with zollinger-ellison syndrome and one patient with WDHA syndrome are reviewed. Three of the Z-E patients exhibited MEA, two having hyperinsulinism and one hyperparathyroidism. Ages ranged from nine to 71 years. diagnosis of Z-E syndrome was established from history, gastric acid secretion, radiologic studies, serum gastrin measurements and from actual tissue biopsy in 10 of the 12 patients. Total gastrectomy was performed in 8 of the 12 Z-E patients, with abolition of the ulcer diathesis in all. However, in none of our patients was there objective evidence of subsequent tumor regression. Three patients remain alive. Four died of tumor, one from post-total gastrectomy complications, one from post-subtotal gastrectomy in another hospital, two from ulcer hemorrhage, and one from electrolyte imbalance with autopsy diagnosis of Z-E tumor. A patient is recorded in detail who exhibited both hyperinsulinemia and hypergastrinemia from a malignant islet cell tumor, had the tumor "debulked" four times over a 14 year period and whose hepatic metastases were temporarily abolished by streptozotocin infusion. The question is raised regarding relationships between chronic organic hyperinsulinism and subsequent hypergastrinemia.
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keywords = gastric acid, acid
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9/66. Supergastrinoma: simultaneous peptic ulceration of esophagus, stomach, and small intestine.

    Synchronous involvement of the esophagus, stomach, and small intestine by peptic ulceration has not been previously described in the zollinger-ellison syndrome. Two patients presented with abdominal pain, diarrhea, weight loss, and dysphagia while on acid suppressants. fasting hypergastrinemia was confirmed. endoscopy revealed peptic stricture of the esophagus with ulcerations in the stomach, duodenum, and jejunum. Imaging showed a mass in the head of pancreas. The first patient underwent distal esophagectomy, total gastrectomy, and resection of the head of pancreas for a pancreatic primary. Resection of the third and fourth parts of the duodenum and proximal jejunum was undertaken in the second patient with a duodenal primary. Malignant gastrinoma was confirmed histologically. "Supergastrinoma" describes a tumor causing synchronous peptic ulceration and/or stricture extending from the esophagus to the jejunum. Operative management entails customized resection of the areas irretrievably damaged by the ulceration together with the tumor.
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10/66. Treating patients with acute gastrointestinal bleeding or rebleeding.

    Despite advances in medical management, gastrointestinal bleeding remains a substantial cause of morbidity and mortality. At risk are patients with history of the event, those taking nonsteroidal antiinflammatory agents, and those with active peptic ulcer disease. endoscopy may be performed for diagnosis and treatment. Antisecretory therapy may be employed to control gastric acid secretion, treat active peptic ulcer disease, and control symptoms such as diarrhea and abdominal pain. Options for antisecretory therapy include histamine2-receptor antagonists (H2RAs) that target the histamine pathway, and proton pump inhibitors (PPIs) that target the final step in acid secretion. The H2RAs generally are ineffective at reaching a target pH of 6 in patients with gastrointestinal bleeding because of tachyphylaxis. The PPIs are more effective and do not lead to tachyphylaxis. With the availability of an intravenous PPI, pantoprazole, options for managing hospitalized patients with gastrointestinal bleeding are expanding.
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keywords = gastric acid, acid
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