Diagnosis Of Zollinger-Ellison Syndrome Research Articles

Diagnosis and management of Zollinger-Ellison syndrome in 2018.

Zollinger-Ellison syndrome (ZES) is a clinical syndrome characterized by gastric acid hypersecretion due to the ectopic secretion of gastrin by a gastrinoma, a neuroendocrine tumor (NET) which mostly develops in the duodenum and in the pancreas. This syndrome was first described by Zollinger and Ellison in 1964; if left untreated, ZES can lead to multiple complications mainly due to gastric hypersecretion and some patients can suffer from the complications of an advanced metastatic disease. Although its clinical features are considered typical, the diagnosis of ZES is often challenging for the clinician. A previous review was published in 2005 by our group, but in 12 years many things have changed: the diagnostic tools have been improved and many different therapeutical options are now available.

A Perplexing Case of Abdominal Pain That Led to the Diagnosis of Zollinger-Ellison Syndrome

Zollinger-Ellison Syndrome (ZES) is a rare clinical disorder, characterized by hypersecretion of gastric acid and multiple ulcers distal to the duodenal bulb. This occurs via the release of gastrin by neuroendocrine tumors known as gastrinomas. Patients with ZES present with nonspecific GI symptoms, which often leads to a delay in diagnosis. We present a case that highlights the importance of increased awareness of ZES in patients with chronic GI complaints. The patient is a 55 year-old female with a history of chronic pancreatitis, who had been following in the GI clinic for several years, secondary to abdominal pain, nausea, and diarrhea. However, despite extensive testing, an etiology of her symptoms had not been determined. She initially underwent esophagogastroduodenoscopy (EGD) and endoscopic ultrasound (EUS), which only showed gastropathy and chronic pancreatitis. Magnetic resonance cholangiopancreatography was unremarkable. She underwent cholecystectomy, but continued to have symptoms, which prompted a repeat EGD. This showed a deep ulceration at the gastro-esophageal junction (LA Grade D), a 2 cm deeply cratered ulcer in the second portion of the duodenum, and a stricture in the third portion of the duodenum (Figure 1). Biopsies showed gastritis and duodenitis without evidence of malignancy. These findings were suspicious for ZES, and work up was initiated. Serum gastrin level was elevated at 1639 pg/mL, but repeat EUS and CT abdomen/pelvis did not reveal any pancreatic or duodenal masses. Somatostain receptor scintigraphy (SRS) was obtained, which showed two small lesions in the gastrinoma triangle (Figure 2). She subsequently underwent a Whipple pancreaticoduodenectomy. Pathology was positive for four microscopic foci (largest 0.1 cm) of a well-differentiated neuroendocrine tumor with evidence of metastasis to two peri-pancreatic nodes. She reported improvement in her symptoms after surgery. This case highlights the need for increased awareness of ZES in patients with unexplained GI complaints. The time to diagnosis in this patient was over seven years, which may have been reduced if ZES was considered earlier. This case also emphasizes the use of multiple modalities in the diagnosis of ZES. SRS, which ultimately detected the gastrinoma in this patient, has a higher sensitivity than CT/MRI. EUS also has a high sensitivity; however, a pancreatic mass was not identified with EUS in our patient, possibly secondary to the small size of the tumor.Figure 1Figure 2

Complicated Zollinger-Ellison Syndrome: 365 Days in Hospital

Background: Zollinger-Ellison (ZE) syndrome is a neuroendocrine tumor with hypersecretion of gastrin leading to resistant peptic ulcers. We are reporting a case of Z-E syndrome with extremely complex hospitalization course lasted around one year. Case: A 50-year-old lady presented to the emergency department with anemia, melena and diarrhea. Upper endoscopy showed multiple ulcerations at gastroesophageal junction, duodenal blub and second part of the duodenum. H. pylori was negative. The patient was started on optimum proton pump inhibitors (PPI) with improvement. Couple of months later she relapsed and another endoscopy revealed the same findings. Gastrin level was 700 pg\ml. CT, MRI of the abdomen and video capsule endoscopy were inconclusive for any pancreatic or small bowel masses. One month later she had duodenal perforation. Since that time the patient had complicated hospital course that lasted for more than one year. She required 16 surgeries for management of perforations, peritonitis, gastric outlet obstruction and managing fistulas and strictures. She was admitted to the ICU for 3 months in which she developed acute renal failure that needed dialysis for three months. She was also on Total parenteral nutrition (TPN) for few months then on tube feeding later on. She had 8 upper endoscopies during her hospitalization. Her fasting gastrin level was found to be more than 10,000 pg/ml when she had the perforation, hence the diagnosis of ZE syndrome. She was discharged one year after her admission on regular PO diet with gastrostomy- jejunostomy tube in place. Her enterocutaneous fistula was healing well. Discussion: ZE syndrome is a rare cause of PUD. Ulcers' perforation and bleeding are life threating complications. Our patient presented initially with multiple ulcers in the context of negative H.Pylori, Gastrin level initially was indeterminate (700pg/ml) and was treated with Pantoprazole 40mg twice daily. Thereafter she developed multiple complications needed very complicated hospital course extended over one year. ZE syndrome was diagnosed later with gastrin level of more than 10,000pg/ml. There were no evidence of MEN I features. The tumor site was not identified and the patient with these extensive surgeries was not a candidate for another surgical intervention at time of discharge. Conclusion: ZE syndrome can lead to multiple life threatening complications. High index of suspicion in the right clinical context is needed to prevent complications and the associated morbidities.

Importance of Surveillance for Multiple Endocrine Neoplasia-1 and Surgery in Patients With Sporadic Zollinger–Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is a rare disorder characterized by gastrin-secreting tumors of the gastrointestinal tract and gastric acid hypersecretion. There is controversy over the best way to manage these patients; we investigated outcomes of patients with different forms of the disease, who did and did not undergo surgery. We performed a retrospective chart review of patients with ZES associated with multiple endocrine neoplasia type 1 (MEN-1) (n = 16) and those with sporadic ZES (n = 33) seen at a tertiary care center from August 1994 to January 2012. Cox proportional hazards modeling was used to compare survival times among groups, based on treatment with surgery (n = 34) and the presence of MEN-1 (n = 9 with surgery; n = 7 without surgery). Differences were compared using the unpaired Student t test and the Fisher exact test. Patients with MEN-1 syndrome-associated ZES presented at a younger age than patients with sporadic ZES (34.9 vs 45.7 y, respectively; P < .05) and were diagnosed at a younger age (39.3 vs 49.7 y, respectively; P < .01), yet lived a similar number of years (55.9 vs 55.1 y, respectively; P = .91). None of the patients with MEN-1-associated ZES died of progressive disease, compared with 86% of deaths among patients with sporadic ZES (P < .05). Lymph node involvement, detected during surgery, increased the risk of metastasis to liver (P = .13) and lack of cure by surgery (P = .01). Surgery reduced all-cause mortality (hazard ratio, 0.11; 95% confidence interval, 0.2-0.6; P = .011) and disease-related mortality (hazard ratio, 0.14; 95% confidence interval, 0.2-0.84; P = .032) of patients with sporadic, but not MEN-1 syndrome-associated, ZES. The presence of MEN-1 is associated with earlier onset and diagnosis of ZES, but a benign clinical course that rarely results in disease-related death; surgery therefore can be deferred for these patients. However, 86% of deaths among patients with sporadic ZES are attributed to disease-related causes, and mortality is reduced by early surgical intervention. Patients with sporadic ZES should undergo surgery soon after diagnosis.

Abdominal Pain and Liver Lesions in Zollinger‐Ellison Syndrome

van Os, Erim Schrama, Martijn Kamphuis, Karin de Herder, Wouter W Damen, Gerard M Case Reports United States J Pediatr Gastroenterol Nutr. 2012 Mar;54(3):435-7.

Long-Term Results of a Selective Surgical Approach to Management of Zollinger-Ellison Syndrome in Patients with MEN-1

The role of operation in patients with Multiple Endocrine Neoplasia Type 1 (MEN-1) and Zollinger-Ellison Syndrome (ZES) is controversial. Our institutional bias for this disease has, in general, been towards aggressive imaging and operative removal of localized gastrinomas. Few studies have reported long-term outcomes in patients with MEN-1 and ZES. A single institution retrospective review of all patients with MEN-1 and ZES from 1970 to present was performed. Twelve patients were identified (median age = 37 years at diagnosis). The median follow-up was 18 years from diagnosis of ZES. Common symptoms associated with gastrinoma in these patients were diarrhea (n = 6), abdominal pain (n = 4), and nausea/vomiting (n = 4). Most commonly identified sites of gastrinoma were: pancreas (n = 10), duodenum (n = 4), lymph nodes (n = 3), and liver (n = 1). Fifteen celiotomies were performed in total (median = 1; range 0-3). Operative procedures performed included: distal pancreatectomy (n = 4), acid reducing procedure (n = 4), enucleation of pancreatic gastrinoma (n = 3), duodenal resection (n = 3), pancreaticoduodenectomy (n = 1), and other (n = 7). One patient had a transient biochemical cure after operation lasting 3 years. Only one patient in this series had documented liver metastases of gastrinoma and no patients expired of metastatic gastrinoma. There was one postoperative patient death, secondary to respiratory arrest thought to be a result of aspiration or pulmonary embolus. Three patients died of nondisease related causes, and seven patients were alive at the time of last follow-up. Operations rarely result in biochemical cures in patients with MEN-1 and ZES. In our experience, resection of localized gastrinomas often did not require extended surgical resection and were associated with excellent long-term outcomes.

Zollinger-Ellison syndrome revisited: Diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion

Despite general awareness of Zollinger-Ellison syndrome (ZES) by most physicians and more than 3000 articles written about it since 1955, the diagnosis of ZES is still delayed for a mean of 5 years. Recent studies show it is being delayed even more with the widespread use of proton pump inhibitors. A number of tumor markers, in addition to assessing serum gastrin, such as chromogranin A, neuron-specific enolase, and subunits of chorionic gonadotropin, have been proposed for use in either the diagnosis of pancreatic endocrine tumors, such as gastrinomas, or for assessment of tumor extent and growth. In this article important recent insights into the diagnosis of ZES as well as the clinical usefulness of assessing tumor markers for diagnosis and determination of disease extent and growth are discussed. Approximately 25% of ZES cases are due to multiple endocrine neoplasia type 1 (MEN1). A number of important studies in this group of patients are also reviewed. Finally, almost every patient with ZES has marked gastric acid hypersecretion, and its current treatment as well as the long-term possible side effects are reviewed briefly.

ZOLLINGER-ELLISON SYNDROME WITH NORMAL SERUM GASTRIN LEVEL

Introduction: Zollinger-Ellison syndrome is characterized by gastric acid hypersecretion leading to refractory/recurrent peptic ulceration due to non-beta islet cell tumor. Diagnosis of Zollinger-Ellison syndrome is made by elevated serum gastrin levels or secretin stimulation test in appropriate clinical setting. We describe a case of Zollinger-Ellison that had near normal serum gastrin levels. Diagnosis was made with endoscopic ultrasound and confirmed by octreotide receptor scintigraphy and histopathology. Case Report: 53-year-old white male with history of 40 lbs weight loss over four months and peptic stricture was referred for evaluation of abdominal pain, diarrhea and symptoms of gastroesophageal reflux despite being on omeprazole 40 mg twice daily. Abdominal exam did not show any evidence of fluid or masses. The patient underwent an esophageal gastroduodenoscopy, which showed diffuse ulceration of esophagus, erosions in the stomach, ulceration in the duodenal bulb and second part of the duodenum. Liver enzymes were elevated and a trans abdominal ultrasound showed dilated pancreatic duct. A CT scan obtained at the same time did not reveal any abnormalities. Serum gastrin level initially was 37 pg/ml and later rose to 161 pg/ml; normal (40–200 pg/ml). Patient refused secretin stimulation test because of fear of symptoms off proton pump inhibitors. An endoscopic ultrasound (EUS) was performed which showed a 25 mm × 30 mm mass in the head of the pancreas. Fine needle aspirate of that mass suggested endocrine tumor. Octerotide scan showed high uptake in the mid epigastric area consistent with gastrinoma. The patient underwent a Whipple procedure and resection of low grade neuroendocrine tumor of the pancreas which stained positive for chromogranin, synaptophysin and pancytokeratin consistent with gastrinoma. The patient was discharged home after one week stay in the hospital. Currently patient is doing well without any complaints of gastroesophageal reflux, one-month post surgery. Discussion: Our case illustrates the fact that normal serum gastrin levels do not rule out the diagnosis of Zollinger-Ellison syndrome. When clinical suspicion of Zollinger- Ellison syndrome is high additional testing i.e. secretin stimulation test (which shows a paradoxical rise in the gastrin levels) or EUS should be done to confirm or refute the diagnosis. A EUS can be very helpful in such situations by not only establishing the diagnosis but also localizing the tumor for surgery.

Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly patients.

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumour of the pancreas (gastrinoma). The true incidence and prevalence of this rare disease is unknown; in the US, the frequency is one per one million people and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of Zollinger-Ellison syndrome is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when this hypergastrinemia is associated with a pH <2. The treatment is based on control of gastric acid hypersecretion and of the malignant tumour and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered in the elderly at high dosages without drug-related adverse effects. As an initial therapy, daily dosages of omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term treatment the doses can be greatly reduced once effective control of the gastric output has been established. Intravenous proton pump inhibitors may be administered when patients cannot take oral therapy, particularly in acute conditions. All sporadic localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like (ECL) cells and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy is not the therapy of choice in patients with gastrinomas and is indicated only in those with malignant progressive disease; interferon alpha, embolisation and chemoembolisation are not advisable for the elderly. The treatment of elderly Zollinger-Ellison syndrome patients, similarly to all elderly oncological patients, should be based on the use of comprehensive geriatric assessment. This will enable the clinician to define the functional status of the elderly person, to decide whether the patient can tolerate surgery and/or the stress of antineoplastic therapy, and finally, to determine whether this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome or whether the only possible choice is palliative relief of symptoms.

Evaluation of proposed gastric acid secretory criteria for diagnosis of Zollinger-Ellison syndrome (ZES): a prospective study of 235 patients

Evaluation of proposed gastric acid secretory criteria for diagnosis of Zollinger-Ellison syndrome (ZES): a prospective study of 235 patients

Evaluation of proposed gastric acid secretory criteria for diagnosis of Zollinger-Ellison syndrome (ZES): a prospective study of 235 patients

Evaluation of proposed gastric acid secretory criteria for diagnosis of Zollinger-Ellison syndrome (ZES): a prospective study of 235 patients

Prospective evaluation of proposed gastric acid secretory criteria for diagnosis of zollinger-ellison syndrome (ZES)

Prospective evaluation of proposed gastric acid secretory criteria for diagnosis of zollinger-ellison syndrome (ZES)

Gastrin-producing tumors.

Strictly defined, gastrin-producing tumors include any tumor that produces gastrin. A gastrin-producing tumor in this strict definition would not be synonymous with the term Zollinger-Ellison syndrome. Gastrin can be detected in tumors by immunocytochemistry or by various molecular biological methods (in situ hybridization, PCR, Northern analysis, etc) and not cause any clinical syndrome or be associated with hypergastrinemia [1–4]. Whether hypergastrinemia and gastric hypersecretion are present or not, the tumor is still a gastrin-producing neoplasm. However, the diagnosis of Zollinger-Ellison syndrome is generally only made if the patient has the appropriate clinical findings (i.e., hypergastrinemia with simultaneous gastric acid hypersecretion), as discussed later. Strictly speaking a gastrin-producing tumor is synonymous with the term gastrinoma; however, generally the term gastrinoma is equated with Zollinger-Ellison syndrome. In this chapter this general usage will be retained. Therefore, a tumor in which gastrin is detected, without associated hypergastrinemia or gastric hypersecretion, would not be included in the general use of this term. Tumors that produce gastrin but are not associated with hypergastrinemia clinically present no unique hormonal features and thus clinically should be classified in a separate category than functional tumors (Table 1).

Management of the Zollinger-Ellison syndrome in pregnancy

OBJECTIVE: There is almost no information on the management of patients with functional pancreatic endocrine tumors such as Zollinger-Ellison syndrome during pregnancy. The purpose of this study was to develop an approach for the management of such cases during pregnancy on the basis of experience with five recent cases. STUDY DESIGN: Five women with Zollinger-Ellison syndrome who had seven pregnancies were the subject of this study. Each patient had an initial evaluation to confirm the diagnosis and to establish gastrinoma location and for the presence or absence of multiple endocrine neoplasia type I. In patients with Zollinger-Ellison syndrome diagnosed before conception, various medical or surgical treatments were established before conception and were used to control acid secretion throughout the pregnancy. The presence of upper gastrointestinal symptoms during pregnancy, maternal and fetal complications, gender, and weight of the infant were determined in all cases. Acid control was determined in four of the five patients during six pregnancies. RESULTS: The interval between the onset of Zollinger-Ellison syndrome and the subsequent pregnancy varied from 0.6 to 9.9 years (mean 6.9 ± 1.7 years). Zollinger-Ellison syndrome was unrecognized before pregnancy in two patients (40%); it was diagnosed between 0.2 and 2.4 years after the pregnancy. In three patients the time of diagnosis varied from 2.6 to 9 years before pregnancy. All patients had symptoms from gastric hypersecretion and elevated fasting serum gastrin levels that varied from 20% above normal to 37-fold above normal with mean of 2536 pg/ml (range 124 to 6970 pg/ml). Four of the five patients (80%) had positive secretin and calcium provocative tests. Two patients had multiple endocrine neoplasia type I. The five patients had seven pregnancies. Acid secretion was treated during pregnancy with antacids only (one patient), ranitidine alone (one patient), prior curative gastrinoma resection (one patient, two pregnancies), prior parietal cell vagotomy with incomplete tumor resection (one patient, two pregnancies), and prior parathyroidectomy and use of ranitidine in a patient with multiple endocrine neoplasia type I. In five pregnancies in three of the cases, no gastric antisecretory medications were needed during pregnancy. The mean acid secretion during pregnancy was 11.9 mEq/hr (range 0 to 42 mEq/hr). In the two cases with poor acid control and unrecognized Zollinger-Ellison syndrome mild fetal complications occurred. CONCLUSIONS: It is possible for patients with Zollinger-Ellison syndrome to have pregnancies that are not complicated by gastric acid hypersecretion. If the Zollinger-Ellison syndrome is diagnosed before pregnancy, curative resection or resection with parietal cell vagotomy may obviate the need for gastric antisecretory drugs. If metastases are present or the diagnosis of Zollinger-Ellison syndrome is made after conception, ranitidine in the lowest possible dose should be used to control acid secretion. If acid secretion in uncontrolled, the dose may be increased or omeprazole may be used. (Am J Obstet Gynecol 1997;176:224-33.)

Zollinger-Ellison Syndrome

<h3>Case 1</h3> A 56-year-old man had an 8-year history of heartburn and diarrhea (three to four loose bowel movements a day) and a 3-year history of epigastric pain with two episodes of melena. Upper gastrointestinal endoscopy demonstrated a duodenal ulcer; however, no<i>Helicobacter pylon</i>was seen on the biopsy specimen. He was treated with ranitidine. Pain recurred when ranitidine administration was stopped. Despite visits to a number of physicians, the diagnosis of Zollinger-Ellison syndrome (ZES) was not made until 1 month before he was referred to the National Institutes of Health (NIH), when he was found to have an elevated fasting gastrin level and a gastric pH less than 2.5. Fasting gastrin at the NIH was elevated at 363 ng/L (normal, &lt;100 ng/L), and basal acid output (BAO) was 46 mEq/h (normal, &lt;10 mEq/h). Results of the secretin-provocative test were positive, with a baseline value of 352 ng/L increasing to

Long-term prognosis of Zollinger-Ellison syndrome in multiple endocrine neoplasia.

The long-term prognosis of Zollinger-Ellison Syndrome (ZES) is not well defined. The findings of other endocrinopathies, the need for long-term surveillance, and the role of surgical treatment are controversial. To help provide more information about these topics the records of 76 patients with ZES were reviewed. Nineteen patients with gastrinoma had multiple endocrine neoplasia (MEN). Fifteen had hyperparathyroidism from 14 years before to 38 years after the diagnosis of ZES. Three patients had pituitary adenomas. The unusual findings of pheochromocytoma were also seen in three patients. Sixteen patients were followed at least 10 years and 12 were followed for more than 20 years. Surgical cure was achieved in only one patient after a 12-year follow-up. The actual 5-, 10-, 15-, and 20-year survival rates of 94%, 75%, 61%, and 58%, respectively, were compared with patients with sporadic ZES with 5-, 10-, 15-, and 20-year survival rates of 62%, 50%, 37%, and 31%, respectively. Multiple endocrinopathies are common but are rarely diagnosed synchronously, mandating life-long surveillance for patients with ZES. Long-term prognosis is good. Survival is longer for patients with ZES and MEN compared with patients with sporadic ZES. Surgical cure is rare. Surgical excision without a single localized lesion does not seem justified.

Zollinger-Ellison Syndrome and Pheochromocytoma

A 49-year-old woman was diagnosed in 1985 as having pheochromocytoma because of hypertension with high levels of plasma catecholamine concentration and 24-hour urine excretion of vanillyl-mandelic acid and metanephrine together with a right adrenal mass. The excised tumor cells had fine granular basophilic cytoplasm with argyrophilic granules by Grimelius' method. Four years later, she was diagnosed as having a duodenal bulb ulcer. Serum gastrin showed an abnormally high level of 1900 pg/ml. Abdominal echogram and computed tomography revealed a hypoechoic lesion in the pancreas and intrahepatic multiple tumors. A needle biopsy specimen of the liver tumor was compatible with the histology of metastatic islet cell tumor. A diagnosis of Zollinger-Ellison syndrome was made due to malignant gastrinoma with multiple liver metastases. The patient had no family history of endocrinological or neoplastic disorders. The present case indicates the possibility that pheochromocytoma and gastrinoma, that is, endocrine tumors characteristic of multiple endocrine neoplasia (MEN) I and MEN II, may be coincident even in a person without MEN. A continued awareness of previously rare or undescribed manifestations is important in patients with islet cell tumors or pheochromocytoma.

Role of acid suppressants in patients with Zollinger–Ellison Syndrome

Virtually all symptoms in patients with Zollinger-Ellison syndrome are due to acid hypersecretion, thus the control of acid secretion is the first and most important step in the management of patients with this syndrome. Antisecretory medication is prescribed as soon as the diagnosis of Zollinger-Ellison syndrome is made, as patients may bleed or perforate with little warning. Acid output is reduced to less than 10 mmol/h to heal mucosal lesions, but in patients with a Billroth I or II gastrectomy and those with severe oesophagitis and stricture formation, acid output is reduced to less than 5 or less than 1 mmol/h. Acid output and not symptomatic response is a reliable guide of the adequacy of therapy. In sufficient doses, all H2-receptor antagonists are useful; however, side effects associated with cimetidine therapy limit its use. The ratio of potencies of cimetidine:ranitidine:famotidine is 1:4:32. Ranitidine given as a 50-mg intravenous bolus, followed by a continuous infusion of 0.5 mg.kg/h, controls acid hypersecretion acutely in patients with Zollinger-Ellison syndrome. Acid output is checked after 4 h, and the dose increased until acid output is less than 10 mmol/h. In 70% of patients with Zollinger-Ellison syndrome, 1 mg.kg/h reduces acid output to less than 10 mmol/h; however, doses up to 4 mg.kg/h have been used. When patients are switched to oral ranitidine, a useful dosage conversion is to administer 1.5 times the total daily intravenous dose in four equal doses every 6 h. Four doses of oral drug are given before the infusion is stopped. Six hours after the first/last oral dose, acid output is checked. In our patients, the mean dose of ranitidine was 2100 mg/day (range, 450-9200 mg/day). No serious toxicity was observed. Omeprazole, which has a long duration of action and is a potent inhibitor of gastric acid secretion, has simplified management. Once-daily dosing is sufficient in most patients, and a reasonable starting dose is 60 mg daily. The dose may be increased to 120 mg once daily; if this dosage fails to control acid secretion, 60 mg is administered every 12 h. In our studies, the median dose was 90 mg/day (range, 20-120 mg/day). Omeprazole was more effective than H2-receptor antagonists in providing symptom relief and mucosal healing and did not cause significant toxicity. In particular, no gastric carcinoid tumours developed during four years of use. Omeprazole is, therefore, the treatment of choice for control of acid secretion in patients with Zollinger-Ellison syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Secretin provocation test in the diagnosis of Zollinger-Ellison syndrome.

The secretin stimulation test has become the preferred provocative test in suspected cases of Zollinger-Ellison syndrome. A pure secretin preparation, a gastrin-specific radioimmunoassay, and an appropriate sampling sequence are important for the proper interpretation of this test. Gastric acid analysis is necessary in the assessment of hypergastrinemia to confirm acid hypersecretion and exclude achlorhydria. When properly performed and interpreted, the secretin provocation test offers a safe, expeditious, and reliable means of evaluating patients with hypergastrinemia.

Peptic ulcer perforation as the presentation of Zollinger-Ellison syndrome

We examined the characteristics of patients with Zollinger-Ellison syndrome who developed a perforation prior to diagnosis to determine whether any clinical features were useful markers of the syndrome. Of 160 patients with Zollinger-Ellison syndrome, perforation occurred prior to the diagnosis being made in 11 (7%). At surgery, perforations were found in the duodenum in six cases and in the jejunum in five. In no case was tumor identified at emergency surgery, and the diagnosis of Zollinger-Ellison syndrome was made only in the postoperative period when excessive gastric secretions were noted. Neither acid output nor serum gastrin concentration were useful predictors for perforation. The patients, six men and five women, were 27-61 years old (median 48) and one had MEN-1. Three patients had no symptoms prior to the perforation. The other eight had symptoms for 1-15 years, with diarrhea occurring in 45% of the cases. Following the diagnosis of Zollinger-Ellison syndrome, patients were given medication to control gastric acid hypersecretion. Eight patients remained well, but the three patients who had had a partial gastrectomy had a complicated course despite medical therapy. Although features of perforation in Zollinger-Ellison syndrome are not specific, jejunal perforation or perforation associated with a history of diarrhea is suggestive of the diagnosis. Serum gastrin should be measured in every case and a partial gastrectomy avoided.