The "serendipitous" surgical cure of the Zollinger-Ellison syndrome in a patient with multiple endocrine neoplasia type 1 despite an unsuspected diagnosis of either disease

Zollinger-Ellison syndrome (ZES) is a relatively uncommon disease that usually presents with peptic ulcer disease or refractory diarrhea. It occurs as a component of multiple endocrine neoplasia type 1 (MEN-1) syndrome in more than 25% of cases. Surgical management of MEN-1 ZES remains controversial. In this case report, we describe the serendipitous cure of ZES in a patient with recurrent peptic ulcer disease who underwent two surgical procedures. The diagnosis of MEN-1 ZES syndrome was neither suspected nor recognized during either operation. This case is presented to highlight the important principles in the diagnosis and current management of patients with MEN-1 ZES.     

Gastrinomas associated with MEN-1 syndrome: new insights for the diagnosis and management in a series of 11 patients

BACKGROUND/AIMS: Approximately, 25-30% of patients (pts) have gastrinomas, (Zollinger-Ellison syndrome, ZES), as part of the inherited syndrome, multiple endocrine neoplasia 1 (MEN-1). The identification of MEN-1 syndrome in these pts is always important, as there are some differences in their management and prognosis. Among 33 pts with ZES, we present in this study 11 pts with ZES and MEN-1 syndrome, describing our diagnostic and therapeutic approach. METHODOLOGY: Eleven pts with ZES and MEN-1 syndrome (6 females and 5 males) were included (mean age 51.8 years). The diagnosis of ZES was based upon: a) clinical features and b) high serum gastrin levels, while in 7/11 pts diagnosis was confirmed histopathologically. A variety of other gastrointestinal peptides, as well as the general neuroendocrine tumor marker, Chromogranin-A (CgA) were also estimated. All pts underwent conventional imaging methods (CT, MRI) and OCTREOSCAN or EUS when necessary, in order to localize the primary lesion or the metastases. The diagnosis of MEN-1 was based upon the presence of the other two MEN-1 related endocrinopathies (hyperparathyroidism, pituitary adenomas), revealed by estimation of several hormones (PTH, Prolactin, ACTH etc.) and performance of imaging studies of the pituitary and parathyroid glands. When MEN-1 syndrome was established, a familiar screening of pts was also performed, when possible. The mean duration of pts' follow-up was 6.1 years (range: 2.1-8.5 years). RESULTS: At the time of presentation, 91% pts, had symptoms of peptic ulcer disease, refractory to treatment, while a history of colicky abdominal pain due to nephrolithiasis was also reported by 45% pts. Four of our pts had a blood relation. Serum gastrin levels at the time of diagnosis were greater than 1000pg/mL in 63.5% pts, while at the same time serum CgA levels were greater than 10 times the upper normal limit (<98ng/mL) in all pts. OCTREOSCAN and EUS revealed the primary tumor (in duodenum or pancreas) in 64% pts, in whom conventional methods showed no abnormalities at the same time. Parathyroid adenomas, pituitary adenomas and bronchial carcinoids were revealed in 11, 3 and 1 pts respectively, which were treated surgically. Also, surgical treatment of pancreatic or duodenal gastrinomas was performed in 54.5% pts, while pts who already had metastases (45%), or developed them during the follow-up period (18%), were treated by somatostatin analogues (63.6%) and chemotherapy (27.3%). Ten out of 11 pts are alive and in a good condition, whereas 1 patient died 2.8 years after diagnosis. Familiar screening revealed parathyroid adenomas in 4 children of our pts, which were treated surgically. CONCLUSIONS: MEN-1 syndrome should always be considered in pts with ZES. A precise preoperative localization of all pancreaticoduodenal lesions, in combination with a surgical exploration and management by experienced surgeons, seems to be curative in pts without distal metastases. Non-surgical treatment with somatostatin analogues and chemotherapy in pts with progressive disease seem to stabilize the disease, although further studies are needed. A close clinical and biochemical follow-up of all pts, as well as their family members, is necessary in order to reveal and treat all MEN-1 related endocrinopathies and especially PETs, in an early stage.     

Zollinger-Ellison syndrome

Opinion statement Zollinger-Ellison syndrome (ZES) is caused by a gastrin-producing tumor called a gastrinoma, which results in gastric acid hypersecretion. Gastrin stimulates the parietal cell to secrete acid directly and indirectly by releasing histamine from enterochromaffin-like (ECL) cells, and induces hyperplasia of parietal and ECL cells. ZES should be suspected in patients with severe erosive or ulcerative esophagitis, multiple peptic ulcers, peptic ulcers in unusual locations, refractory peptic ulcers, complicated peptic ulcers, peptic ulcers associated with diarrhea, and a family history of multiple endocrine neoplasia type 1 (MEN-1) or any of the endocrinopathies associated with MEN-1. The initial diagnostic test for ZES should be a fasting serum gastrin level when antisecretory medications are discontinued. If the gastrin level is elevated, gastric acidity should be assessed through pH or gastric analysis. It should be noted that hypochlorhydria causes feedback stimulation of antral gastrin secretion. In suspected cases of ZES with mild hypergastrinemia, the secretin stimulation test may be useful. Initial treatment for ZES should be oral high-dose proton pump inhibitors. If parenteral therapy is needed, intermittent bolus injection of pantoprazole is recommended. Total gastrectomy and antisecretory surgery is rarely required. Somatostatin receptor scintigraphy (SRS) is the initial localization study of choice. Endoscopic ultrasound (EUS) may have a similar sensitivity for identifying primary tumors. A combination of SRS and EUS detects greater than 90% of gastrinomas. In patients without metastasis and without MEN-1, surgical cure is possible in 30%. It has been suggested that patients with gastrinomas larger than 2.5 cm, irrespective of whether they have MEN-1, should undergo surgical resection in an effort to decrease the risk for metastasis.     

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.     

Peptic ulcer in geriatric long-term care medicine

This study was based upon deceased patients in a geriatric university hospital with a high autopsy rate (81%). Of 6200 autopsied patients, 333 (5.4%) had had an active peptic ulcer; agonal and other acute erosions were not included. 257 cases were selected for the study (average age 83.8 yr). The diagnostic accuracy, and the symptoms of peptic ulcer in stationary, elderly, chronically ill patients were studied retrospectively. Only 16% of cases with duodenal ulcer and 29% with gastric ulcer had been correctly diagnosed antemortem. The clinical features of ulcer disease in the elderly may often differ from the standard presentation in younger people. Prior to death, appetite and weight loss, nausea/vomiting, anaemia and positive occult blood test had been more common among patients with ulcer, than abdominal pain and heartburn. The predictive values of single symptoms and of combined findings were low (range 2-21%), thus supporting observations from clinical practice that diagnosis is difficult in geriatric medicine. Prospective studies of ulcer disease in living elderly are needed.     

Zollinger-Ellison phenotype in the absence of hypergastrinemia and islet-cell tumor

Patients with the Zollinger-Ellison syndrome are characterized by islet-cell tumors, striking gastric acid hypersecretion, and peptic ulcer disease. They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences. It is a rare syndrome caused by nonbeta cell islet-cell tumors (gastrinomas) located in or in proximity to the pancreas. These tumors freely secrete gastrin, a peptide hormone that serves as a powerful stimulant of gastric acid secretion. Exuberant secretion of gastrin from the gastrinomas produces severe gastric acid hypersecretion that often leads to impressive peptic ulcer disease and the constellation of symptoms listed above. We describe a patient presenting with clinical manifestations characteristic of the ZES with strikingly elevated gastric acid secretion, multiple ulcers in the first and second portions of the duodenum and diarrhea, but in absence of islet-cell tumor and/or hypergastrinemia.     

Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger–Ellison syndrome, hypoglycaemia or both

Thompson NW (University of Michigan, Ann Arbor, MI, USA). Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger– Ellison syndrome, hypoglycaemia or both (Minisymposium: MEN & VHL). J Intern Med 1998; 243 : 495–500.
The management of multiple endocrine neoplasia type 1 (MEN-1) pancreatic-duodenal disease, particularly when the Zollinger–Ellison syndrome (ZES) is the presenting manifestation, has remained controversial. The management of hypoglycaemia and other syndromes as well as large tumours detected by imaging is less controversial, although standardized surgical techniques have not been generally adapted. The rationale for an aggressive operative management plan for ZES and other syndromes is based on the facts that neuroendocrine tumours of both the pancreas and the duodenum have malignant potential and that the functional manifestations can be controlled with appropriate surgical procedures based on current concepts of the MEN-1 disease. Of the ten concepts presented, the one critical to the surgical treatment of ZES is that a duodenotomy is essential in detecting the source of hypergastrinaemia in most MEN-1 patients. The complete operation is multifaceted and includes peripancreatic lymph node dissection (ZES), enucleation of any head or uncinate tumours and a distal pancreatectomy. Our results in 40 MEN-1 patients with functional syndromes treated with these procedures are encouraging. Ten patients with hypoglycaemia (four with concomitant ZES) have been 'cured' with follow-up as long as 18 years. Sixty-eight per cent of 34 patients with ZES have remained eugastrinaemic during follow-up as long as 19 years. One patient developed a solitary liver metastasis that was excised a year ago without other evidence of recurrence. There has been no operative mortality and three subsequent deaths were due to unrelated disease.     

Patients with multiple endocrine neoplasia type 1 with gastrinomas have an increased risk of severe esophageal disease including stricture and the premalignant condition, Barrett's esophagus

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus (BE). OBJECTIVE: The objective of the study was to prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with and without MEN1. SETTING: The study was conducted at a tertiary care research center. PATIENTS: Two hundred ninety-five patients (80 = MEN1/ZES, 215 = sporadic ZES) participated in a prospective study. INTERVENTIONS AND OUTCOME MEASURES: Assessment of MEN1, acid hypersecretion, upper gastrointestinal endoscopy/biopsies, and tumor status were measured initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency and type of esophageal disease were correlated with clinical/laboratory/tumoral features of ZES/MEN1. RESULTS: In MEN1/ZES patients, esophageal stricture was 3-fold higher, BE 5-fold higher, and dysplasia 8-fold higher, and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent or severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES-specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES, the onset of ZES was 10 yr earlier, and H2-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent or severe, hiatal hernias were more frequent, esophagitis or pyloric scarring was more common, basal acid output was higher, and hyperparathyroidism was underdiagnosed. CONCLUSIONS: This study shows that MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment.     

Surgical treatment and prognosis of gastrinoma

Zollinger-Ellison syndrome (ZES) is a clinical syndrome with severe peptic ulcer disease and diarrhea caused by gastric acid hypersecretion secondary to a neuroendocrine tumour that secretes excessive amounts of the hormone gastrin (gastrinoma). Gastrinomas occur in a familial and a sporadic form. Patients with gastrinoma in the familial setting of Multiple Endocrine Neoplasia type 1 (MEN-1) are seldom, if ever, cured of Zollinger-Ellison syndrome by the current non-Whipple operations to remove duodenal and pancreatic gastrinoma. Surgery is currently used in these patients to deal with the malignant nature of pancreatic or duodenal neuroendocrine tumours. Malignant potential is best determined by tumour size. Tumours that are greater than 2 cm in size should be excised. In the sporadic setting, cure occurs in a significant proportion of patients (50%) by surgical resection of gastrinoma. Duodenotomy has improved both the tumour detection rate and the cure rate and should be routinely done. Whipple pancreaticoduodenectomy results in the highest probability of cure in both sporadic and MEN-1 gastrinoma patients as it removes the entire gastrinoma triangle. However, the excellent long-term survival of these patients with lesser operations and the increased operative mortality and long-term morbidity of Whipple make its current role unclear until further studies are done.     

Role of clinical presentation in diagnosing reflux-related non-cardiac chest pain

INTRODUCTION: Non-cardiac chest pain (NCCP) presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health-care resources. Gastroesophageal reflux disease (GERD) is the most frequent cause of NCCP. Thus the typical symptoms of reflux, such as heartburn and regurgitation, when present as predominant symptoms are quite specific for diagnosing GERD but in patients with NCCP the clinical diagnosis of reflux is difficult, and invasive methods or the omeprazole test are required for its detection. The aim of the present study was to evaluate the role of clinical presentation when diagnosing GERD among patients with NCCP. METHODS: Patients with NCCP underwent upper endoscopy, Bernstein and omeprazole tests. The patients were divided into two groups based on GER- or non-GER-related chest pain, and clinical presentation was compared between these two groups. Gastroesophageal reflux disease was considered positive when at least two methods were positive. RESULTS: From 78 NCCP patients (41 male; mean age 50.4 +/- 2.3 years), the chest pain was related to GERD in 35 patients (44.8%). The two groups were the same based on sex and age. The chest pain severity, site, radiation and relation to food, exercise, and sleep were equal in the two groups, except for two symptoms: pain that was relieved by antacid (P < 0.031) and presence of classical reflux symptoms (P < 0.009), seen in the GERD patients. With regard to recent patient history, heartburn and regurgitation symptoms were seen more frequently in GERD patients (P < 0.036 and P < 0.002, respectively). DISCUSSION: Clinical presentation is important in diagnosing GERD in NCCP. Although the chest pain is the same in reflux- and non-reflux-related NCCP, the symptoms of heartburn or regurgitation in the present or recent patient history are diagnostic for GERD-related chest pain.     

Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1

Jensen RT (Bethesda, MD, USA). Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1 (Minisymposium: MEN & VHL). J Intern Med 1998; 243 : 477–88. Zollinger–Ellison syndrome (ZES) is the most common symptomatic pancreatic endocrine tumour in patients with MEN-1. Besides the treatment of the usual endocrinopathies seen in patients with MEN-1, the treatment of the ZES requires attention be paid to controlling the gastric acid hypersecretion, to dealing with the gastrinomas per se which are malignant in 18–60% of cases, and to the diagnosis and treatment of gastric carcinoid tumours, that are increasingly seen in these patients. In this article the current management of each of the areas is reviewed and what is known or uncertain discussed, based on our studies at the NIH and data from others. Data from 231 patients including 45 with MEN-1 and 186 without MEN-1 is contrasted in this report. Gastric acid hypersecretion has been controlled in all patients medically with MEN-1 and ZES at the NIH for up to 22 years. The current drugs of choice are H⁺-K⁺ ATPase inhibitors and twice a day dosing is recommended. Periods of parenteral drug therapy (surgery, etc.) and pregnancy require important modifications. The appropriate surgical therapy of the gastrinoma is controversial. Eighty per cent of patients have a duodenal gastrinoma and 20–30% have a pancreatic tumour. Recent studies suggest gastrinoma enucleation combined with duodenotomy rarely results in cure. Aggressive surgery (Whipple resection) can result in cure of gastrinoma but effect on survival is unclear. There are important differences in gastrinoma location, extent, and percentage with aggressive disease in patients with or without MEN-1, which are discussed. Confusion has occurred because of lack of information on the natural history of the gastrinoma compared to the other pancreatic endocrine tumours that occur in MEN-1 and survival data from patients with and without MEN-1 is contrasted. The occurrence of gastric carcinoids in patients with and without MEN-1 with ZES is contrasted and the areas of certainty and disagreement reviewed.     

Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies

Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.     

Diagnostic and therapeutic criteria in patients with Zollinger–Ellison syndrome and multiple endocrine neoplasia type 1

: Mignon M, Cadiot G (Bichat and Claude Bernard Hospital, Paris, France). Diagnostic and therapeutic criteria in patients with Zollinger–Ellison syndrome and multiple endocrine neoplasia type 1 (Minisymposium: MEN & VHL). J Intern Med 1998; 243 : 489–94. About 25% of patients with ZES have MEN-1. Except for diarrhoea, less frequent in patients with ZES MEN-1 than in sporadic ZES, and specific MEN-1-related signs, clinical characteristics are similar in both ZES types. Acid output and gastrin level are also similar whether in the basal state or after secretin. Primary hyperparathyroidism (pHPT) exists in the majority of ZES MEN-1 patients, 30% have pituitary adenoma (prolactinomas for half), 30% adrenal involvement, 25–30% have ECLomas: bronchial and thymic carcinoids have probably been underevaluated. Gastrinomas are multiple predominantly located in the duodenal wall, but also in the pancreas in association with clinically silent endocrine tumours. The spread of the disease metastases to the liver (LM), mediastinum, bones, is evaluated best by Octreoscan. Associated endoscopic ultrasonography evaluates the number, size and anatomical characteristics of gastrinomas. Patients without LM have an excellent prognosis. Surgery never cures ZES, but is necessary in cases of associated life-threatening conditions such as insulinoma. Although the size of the tumour, when located in the pancreas >3 cm, favours metachronous LM occurrence, surgery in our experience has not been able to prevent LM development.     

Trends in the presentation of celiac disease

Purpose

Screening studies have revealed that celiac disease is common in the United States; however, there are scant data on the mode of presentation. We analyzed the trends in clinical presentation over the last 52 years in a large cohort of biopsy-proven patients seen in 1 center.

Subjects and methods

Patients (n = 590) were divided into 6 groups based on the year of diagnosis (1952-2004). Groups were compared for trends in age at diagnosis, childhood diagnosis, duration of symptoms, mode of presentation (diarrhea, bone disease, anemia, incidental at esophagogastroduodenoscopy, screening), and presence of malignancy.

Results

Diagnosis was at an older age since 1980 (P = .007), and there was a significant negative linear trend in patients presenting with diarrhea (P<.001) over time and a positive linear trend in asymptomatic patients detected on screening (P<.001). There was a significant negative linear trend in patients with a malignancy (P = .02) and duration of symptoms before diagnosis of celiac disease (P = .001), although only the subgroup without diarrhea had improvement in delay of diagnosis of celiac disease (assessed by a shorter duration of symptoms) (P = .05). Comparison of patients with and without diarrhea showed no significant difference in age (42.9 years vs 43.7 years, P = .59), gender (29.3% M vs 34.6%, P = .59), and presence of childhood disease (8.0% vs 9.8%, P = .43) or malignancies (9.8% vs 8.9%, P = .71).

Conclusion

There is a trend toward fewer patients presenting with symptomatic celiac disease characterized by diarrhea and a significant shift toward more patients presenting as asymptomatic adults detected at screening.     

Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger–Ellison Syndrome

Zollinger–Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. While early recognition portends an excellent prognosis with >80% survival at 15 years, symptoms are often nonspecific making the diagnosis difficult to establish. Diagnosis involves a series of tests, including fasting gastrin, gastric pH, chromogranin A, and secretin stimulation. Performing these tests in the correct sequence and at the proper time is essential to avoid inaccurate results. Tumor localization is equally nuanced. Although providers have classically used ¹¹¹indium-radiolabeled octreotide with somatostatin receptor scintigraphy to evaluate tumor size and metastases, recent studies have shown superior results with newer imaging modalities. In particular, ⁶⁸gallium (⁶⁸Ga)-labeled somatostatin radiotracers (i.e., ⁶⁸Ga-DOTATOC, ⁶⁸Ga-DOTANOC and ⁶⁸Ga-DOTATATE) used with positron emission tomography/computed tomography can provide excellent results. Endoscopic ultrasound is another useful modality, particularly in patients with ZES in the setting of multiple endocrine neoplasia type 1. This review aims to provide clinicians with an overview of ZES with a focus on both clinical presentation and the proper utilization of the various biochemical and imaging tests available.     

Clinical course of symptomatic duodeno-jejunal Crohn's disease

AIMS: To describe retrospectively the characteristics of inaugural, symptomatic Crohn's disease of the upper gastrointestinal tract. METHODS: Eighteen patients (12 male and 6 female) with symptomatic Crohn's disease of the upper intestinal tract and without previous distal localisation were studied. RESULTS: Mean age of patients at diagnosis (21.3 years) was less than that usually reported in Crohn's disease. The time elapsed from first symptoms to diagnosis (mean = 29.8 months) was remarkably long for some patients, mainly as a result of an unusual clinical presentation. Abdominal pain and weight loss were the most common presenting features; diarrhea was rarely the main symptom. Persistent anorexia and weight loss without digestive symptoms had led to a diagnosis of anorexia nervosa in 4 patients. Zollinger-Ellison syndrome was the initial diagnosis in 3 other patients. Sixteen patients were followed during at least 2 years. All were treated with steroids for their first attack and 75 % required immunosuppressive therapy for steroid dependence. At the end of follow-up, 6 patients only were in remission without treatment or under mesalamine. CONCLUSION: Crohn's disease with initial symptomatic lesions of the upper gastrointestinal tract occurs mainly in young male patients. The clinical presentation may be very unusual, leading to misdiagnosis. The clinical course is close to that of diffuse jejunoileitis.     

Sporadic versus hereditary gastrinomas of the duodenum and pancreas： Distinct clinico-pathological and epidemiological features

INTRODUCTION Gastrinomas are de?ned as gastrin-producing tumors that are associated with Zollinger-Ellison syndrome (ZES) due to inappropriate gastrin secretion. ZES is characterized by elevated fasting gastrin serum levels, positive gastrin secretin stim…     

Profile of chronic small-bowel diarrhea in adults in Western India: a hospital-based study.

BACKGROUND: Small-bowel diarrhea is reported to account for 10% of all cases of chronic diarrhea. Data on the etiology and clinical presentation of chronic small-bowel diarrhea in adult Indians is scarce. METHODS: 50 patients (mean age 32.8 years; 26 men) with chronic small bowel diarrhea were evaluated clinically, and investigated to determine etiology. The diagnosis of small-bowel diarrhea was based on history, stool volume and associated symptoms. RESULTS: Abdominal pain (n=22, 44%) and weight loss (n=37, 74%) were the most common symptoms, apart from diarrhea. Anemia (70%) and hypoalbuminemia (48%) were other important biochemical abnormalities. Intestinal tuberculosis (26%) and celiac disease (26%) were the most common causes of chronic small-bowel diarrhea. CONCLUSION: Tuberculosis of intestine and celiac disease are common causes of small-bowel diarrhea in our population. Tropical sprue seems to be a rare cause.     

A follow-up study of patients with Zollinger-Ellison syndrome in the period 1966-2002: effects of surgical and medical treatments on long-term survival

AIM: To evaluate the clinical history of a series of patients with Zollinger-Ellison syndrome (ZES) in the period 1966 to 2002, before and after the introduction of the current antisecretive H2 receptor antagonists and proton pump inhibitors into clinical practice. PATIENTS AND METHODS: The study involved 18 ZES patients (9 males; mean age, 43 years; range, 12-70 years), 8 with Type 1 multiple endocrine neoplasia (MEN-1), diagnosed on the basis of standard criteria. We considered the type, number and effectiveness of surgical interventions before and after appropriate treatment, the localization of the gastrinoma, the presence of associated diseases, the causes of death, and the duration of survival. RESULTS: Total gastrectomy (but not antrectomy and vagotomy) and full compliance to antisecretory treatment reduced the number of operations from 29 to 9. One patient was cured (5.5%), whereas relapsing gastrinomas occurred in 4 patients and associated diseases or complications in ten. Death was related to ZES in 5 patients and to other causes in 4. CONCLUSIONS: Curing gastrinoma or appropriately inhibiting gastric acid hypersecretion in ZES patients prevent death and favors long-term survival, regardless of gastrin levels and the size or number of tumors.     

Empirical treatment based on "typical" reflux symptoms is inappropriate in a population with a high prevalence of Helicobacter pylori infection

BACKGROUND: Empirical therapy or early endoscopy have been recommended as acceptable management options for GERD. The objective of this study was to determine whether diagnosis and empirical treatment based on reflux symptoms alone are appropriate as initial management for patients with gastroesophageal reflux. METHOD: Consecutive patients presenting with weekly reflux symptoms were evaluated with a structured questionnaire followed by endoscopy. Patients with dyspepsia as the predominant symptom, "alarm" symptoms (weight loss, dysphagia, or bleeding), history of peptic ulcer or gastric surgery, or recent nonsteroidal anti-inflammatory drugs intake were excluded. RESULTS: Four hundred sixty patients were studied: 82 (18%) were found to have peptic ulcer disease and 78 (95%) were infected with Helicobacter pylori. Concomitant erosive esophagitis was found in 26 (32%) of these patients with peptic ulcer disease. In the remaining 378 patients, 218 (58%) had erosive esophagitis and 1 had esophageal cancer. Among the 159 patients with no endoscopic lesion, 148 (93%) had relief of symptoms when treated with a proton pump inhibitor. Multivariate analysis showed that male gender (OR: 1.8, p = 0.03), age greater than 60 years (OR: 2.2, p = 0.01) and H pylori infection (OR: 3.6, p = 0.008) were significantly associated with a diagnosis of peptic ulcer disease. Coexisting dyspeptic symptom was not a predictor (p = 0.13) for peptic ulcer disease. CONCLUSIONS: In populations with a high prevalence of H pylori infection, a significant proportion of patients with GERD have concomitant peptic ulcer disease. Empirical treatment based on "typical" GERD symptoms alone may not be appropriate.