Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated.Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous.3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not.Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study.

Gastric neuroendocrine neoplasms (NENs) are increasing in frequency and have a varied spectrum with regard to histology, clinicopathologic background, stage, and prognosis. They are usually discovered incidentally, are for the most part benign and are associated with hypergastrinaemia (secondary either to chronic atrophic gastritis or rarely Zollinger-Ellison syndrome; types 1 and 2, respectively) or more rarely sporadic type 3. Applications of recent staging and grading systems - namely using Ki-67 proliferative indices - (from ENETS and WHO 2010) can be particularly helpful in further categorising these tumours. The natural history of Type 1 gastric carcinoids is generally (>95%) favourable and simple surveillance is usually recommended for small (<1 cm) T1 tumours, with local (endoscopic or surgical) resection for larger lesions. Other potential therapies such as somatostatin analogues and gastrin receptor antagonists may offer newer therapeutic possibilities. Rarely, gastric NENs have a malignant course and this is usually confined to Type 2 and especially Type 3 tumours; the latter mimic the biological course of gastric adenocarcinoma and require radical oncological therapies. Most duodenal NENs, apart from gastrinomas (that are not dealt with here) are sporadic and non functional. They are also increasing in frequency probably due to incidental discovery at endoscopy or imaging for other reasons and this may account for their overall good prognosis. Peri-ampullary and ampullary NENs may have a more aggressive outcome and should be carefully appraised and treated (often with surgical resection).

Carcinoid tumors are uncommon, slow-growing neoplasms. These tumors are capable of secreting numerous bioactive substances, which results in significant potential challenges in the management of patients afflicted with carcinoid syndrome. Over the past two decades, both surgical and medical therapeutic options have broadened, resulting in improved outcomes. The pathophysiology, clinical signs and symptoms, diagnosis, treatment options, and perioperative management, including anesthetic considerations, of carcinoid syndrome are presented.

1-4% of patients who undergo gastric biopsy have gastric polyps. These lesions may be true epithelial polyps, heterotopias, lymphoid tissue, or stromal lesions. Hyperplastic polyps, which arise in patients with underlying gastritis, and fundic-gland polyps, which are associated with PPI therapy, are the most common gastric polyps; however, prevalence varies widely relative to the local prevalence of Helicobacter pylori infection and use of PPI therapy. Some polyps have characteristic topography, size, and endoscopic appearance. Approximately 20% of biopsy specimens identified endoscopically as polyps have no definite pathological diagnosis. Evaluation of the phenotype of the gastric mucosa that surrounds a lesion will provide significant information crucial to the evaluation, diagnosis and management of a patient. The presence of a gastric adenoma should prompt the search for a coexistent carcinoma. The endoscopic characteristics, histopathology, pathogenesis, and management recommendations of polyps and common polypoid lesions in the stomach are discussed in this Review.

The hormone gastrin plays 2 important roles in gastrointestinal physiology--1 as a major factor in meal-stimulated gastric acid secretion and the other as a trophic hormone for epithelial and enterochromaffin cells. These roles are exaggerated to the point of pathology under conditions of chronic hypergastrinemia as exemplified by the Zollinger-Ellison syndrome and pernicious anemia. More recently, the concern about the potential risk of chronic hypergastrinemia has risen because of the widespread use of proton pump inhibitors for maintenance therapy in reflux esophagitis. For this reason, we present a concise overview of the origin, causes, and potential risks of chronic hypergastrinemia.

The generally indolent nature of neuroendocrine tumors is an advantage in the management of patients who have localized disease, and surgery alone is often curative. This same property presents a challenge in the treatment of patients who have metastatic disease, in whom standard cytotoxic chemotherapy has a limited benefit. In such patients, the use of somatostatin analogs, interferon, and the treatment of hepatic metastases may provide effective palliation. The highly vascular nature of carcinoid tumors has led to the investigation of antiangiogenic agents in this setting. Preliminary reports of activity associated with agents targeting the vascular endothelial growth factor pathway suggest that such strategies may play a role in the future treatment of patients who have this disease.

A 70-year-old man was found to have at least 12 type I gastric carcinoids and microcarcinoidosis. We performed an extended octreotide suppression test to determine if the tumors were gastrin-dependent and would likely regress after antrectomy. He was given an octreotide infusion at 12.5-25 mcg/h for 86 hr followed by depot octreotide 20 mg intramuscularly every four weeks for eight months. Fasting serum gastrin and chromogranin A levels were measured, and endoscopy with biopsies was performed before and after the infusion and at five months and eight months. Total RNA was extracted for quantitation of histidine decarboxylase mRNA using real-time PCR. Fasting serum gastrin decreased from 306 pg/ml pretreatment to 31 pg/ml at the end of infusion and 115 pg/ml at eight months. Chromogranin A decreased from four to six times the upper limit of normal to normal. Tissue histidine decarboxylase mRNA decreased 50-fold. At eight months, only a few diminutive nodules were present on endoscopy. These results demonstrated that the carcinoid tumors in this patient were under neuroendocrine control and were expected to respond to antrectomy.

Gastric carcinoid tumours are rare, but are increasing in incidence.

To discuss tumour pathogenesis and outline current approaches to patient management.

Review of published articles following a Pubmed search.

Although interest in gastric carcinoids has increased since it was recognized that they are associated with achlorhydria, to date there is no definite evidence that humans taking long-term acid suppressing medication are at increased risk. Type I tumours are associated with autoimmune atrophic gastritis and hypergastrinaemia, type II are associated with Zollinger-Ellison syndrome, multiple endocrine neoplasia-1 and hypergastrinaemia and sporadic type III carcinoids are gastrin-independent and carry the worst prognosis. Careful investigation of these patients is required, particularly to identify the tumour type, the source of hypergastrinaemia and the presence of metastases. Treatment can be directed at the source of hypergastrinaemia if type I or II tumours are still gastrin responsive and not growing autonomously. Type III tumours should be treated surgically.

Advances in our understanding of the pathogenesis of gastric carcinoids have led to recent improvements in investigation and management. Challenges remain in identifying the genetic and environmental factors, in addition to hypergastrinaemia, that are responsible for tumour development in susceptible patients.

Carcinoid tumors can present a difficult diagnostic and therapeutic dilemma. Despite their reputation as indolent tumors, they frequently metastasize and can cause significant symptomatology. The only curative therapy remains surgical resection. The prognosis and treatment of carcinoids vary based on location and histology, and therapy must be tailored to each patient.

This study shares Asian clinical experiences of carcinoid tumors that originated in the upper gastrointestinal tract.

From May 1987 to June 2002, we had found only 13 cases of histologically confirmed carcinoid tumors in the upper gastrointestinal tract by endoscopic examinations. There were eight males and five females. The mean age was 53.16+/-20.51 years that ranged from 26 to 82 years. Each of their clinical presentations, locations, tumor morphology, and size and the treatment outcome were analyzed and discussed.

One patient had a polypoid lesion at the lower esophagus, nine were stomach lesions and three located at the duodenum. All patients with polypoid and submucosal tumor types were of small size (<1.7 cm) and all patients survived after simple excision or polypectomy. Four of the five patients in tumor mass forms died and the tumors were more than 2.0 cm in size.

Carcinoid tumors rarely originated from the upper gastrointestinal tract and are usually found accidentally after endoscopic study. Bigger size (more than 2 cm) tumor masses may indicate a more severe disease and poor prognosis.

The aim of this study was to review the presentation, treatment, and outcome of patients with Type 1 gastric carcinoid tumors.

A retrospective review of 1,600 carcinoid patients was analyzed to identify patients with gastric carcinoid tumors.

Eighteen patients were found to have biopsy-confirmed Type 1 gastric carcinoid tumors on upper endoscopy. Reasons for endoscopy included abdominal pain (n = 4), gastrointestinal bleeding (n = 4), surveillance for pernicious anemia (n = 8), and other (n = 2). The mean pre-treatment serum gastrin and chromogranin A levels were 1,436 ng/ml (+/-771 ng/ml) and 91.6 ng/ml (+/-68.6 ng/ml), respectively. Imaging revealed evidence of gastric carcinoid in 4 of 10 patients undergoing CT scanning and 3 of 10 patients undergoing octreotide scintigraphy. Of the 18 patients, 8 were treated medically (acidification or octreotide) and 10 were treated with surgery (laparoscopic antrectomy or partial gastrectomy). Mean gastrin levels decreased by 37.2% in the medically treated group (median follow-up 6 months), versus 94.0% in the surgically treated patients (median follow-up 5 months). Mean chromogranin A levels decreased by 56.2% in patients undergoing surgery.

Gastric antrectomy is the most efficacious treatment for Type 1 gastric carcinoid, leading to a significant reduction in serum gastrin levels and regression of carcinoid tumors.

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.

Gastrointestinal neuroendocrine tumors are characterized by generally slow growth rates and the ability to secrete a variety of hormones and biogenic amines. For patients with localized disease, surgical resection alone is often curative; however, patients with metastatic disease often present a therapeutic challenge. Although somatostatin analogs are highly effective in controlling symptoms of hormonal secretion, they are rarely associated with tumor regression. Selected patients with hepatic metastases may benefit from surgical debulking, embolization, or other ablative therapies. The clinical benefit associated with the administration of systemic agents such as alpha interferon or cytotoxic chemotherapy is less clear, and the widespread use of such regimens has been limited by their relatively modest antitumor activity as well as by concerns regarding their potential toxicity. The highly vascular nature of neuroendocrine tumors has led to interest in angiogenesis inhibition as a potentially novel treatment strategy. In addition, several small molecule tyrosine kinase inhibitors are currently being evaluated in a Phase II setting. The naturally indolent growth of neuroendocrine tumors presents a challenge in interpreting efficacy endpoints from small Phase II studies. Larger, randomized trials, along with the evaluation of surrogate endpoints of biologic activity, may be necessary to establish the potential clinical benefit of these novel agents.

Patients with chronic atrophic gastritis (CAG) and hypergastrinaemia are at risk of developing hyperplasia of the enterochromaffin-like (ECL) cells and ECL-cell-derived tumours. The effect of the somatostatin analogue octreotide on ECL cell carcinoids is examined.

Five patients with hypergastrinaemia and ECL cell carcinoids were enrolled in a 1-year study of octreotide LAR (long-acting release) 20 mg given at monthly intervals. Biopsies from tumours and from flat oxyntic mucosa were done at the start and 3, 6 and 12 months thereafter. Sections were stained with haematoxylin-erythrosin, immunostained with chromogranin A (CgA) and doublestained with CgA and Ki-67. Serum gastrin and CgA were measured.

The number of visible tumours was reduced by more than 50 %. Sections from both tumours and flat mucosa showed a reduced number of CgA immunoreactive cells. Mean serum gastrin decreased from 421 to 186 pM (normal <40 pM); P > 0.05, and serum CgA from 73 to 25 ng/ml (normal < 30 ng/ml); P < 0.001.

During treatment the patients were still markedly hypergastrinaemic, whereas the serum CgA showed normalization. A diminished tumour load and reduced ECL cell density were found, indicating an antiproliferative effect of octreotide directly on the ECL cells.

Neuroendocrine tumours often present a diagnostic and therapeutic challenge. They can arise almost anywhere in the body, and are therefore associated with a broad range of local symptoms. The systemic manifestations of neuroendocrine tumours are also diverse, and are related to the secretion of numerous hormones and biogenic amines. In recent years, improved diagnostic techniques, increased recognition of neuroendocrine tumour subtypes, and new therapeutic modalities have enhanced clinicians' ability to detect and appropriately treat these malignancies.

Minimally invasive laparoscopic wedge resection for gastric mucosal carcinoma and submucosal tumor was first performed in Keio University hospital in 1992. Since then, 172 gastric tumor patients, including four cases of carcinoid tumor, have been successfully treated at the Keio University hospital using this procedure. No local disease recurrence or distant metastases have been observed in follow-ups over as long as 10 years. Chronic atrophic gastritis patients with carcinoid tumors occurring secondary to hypergastrinemia are candidates for the minimally invasive surgery. With careful patient selection according to tumor size, depth of invasion, and histopathological findings of malignancy grade, endoscopic and laparoscopic therapy for these patients can be a safe, curative, and minimally invasive procedure.

Gastric carcinoid is a rare tumour that is associated with chronic atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th decade of life and is rarely diagnosed in patients under 30 years of age.

We describe a case of multiple gastric carcinoids in a 23-year-old woman with systemic lupus erythematosus and atrophic autoimmune gastritis--an association that has not been reported previously.

The combination of atrophic autoimmune gastritis and gastric carcinoid with other autoimmune disorders has rarely been reported in the English medical literature.

The fact that it mostly concerns (relatively) young patients may suggest a potential causative relation between those autoimmune disorders and the early development of atrophic gastritis with hypergastrinaemia, which subsequently leads to the occurrence of gastric carcinoid tumours at a young age.

Familial adenomatous polyposis (FAP) is associated with upper gastrointestinal adenomas and adenocarcinomas. A carcinoid tumor in the base of a duodenal adenoma in a patient with FAP was documented only once before. We report a patient with FAP who has multiple gastric carcinoids plus pernicious anemia as a coexisting disease. Genetic analysis and studies of other FAP patients are necessary to establish whether an association exists between FAP and carcinoid tumors. Optimal management of this type of gastric carcinoid is uncertain.

The role of gastrin in the pathophysiology of two diseases affecting the human stomach, the Zollinger Ellison syndrome (ZES) and the pernicious anemia (PA), is reviewed. Both diseases present chronic hypergastrinemia but from different origins. The ZES is characterized by the occurrence of ectopic endocrine gastrin-secreting tumors and PA by a fundic atrophic gastritis leading to complete atrophy of fundus and resulting in achlorhydria. In PA, the lack of acid induces continuous gastrin cell activation and is responsible for the subsequent gastrin hypersynthesis and secretion. In ZES, hypergastrinemia causes hypertrophy of the oxyntic mucosa, which, in addition, displays hyperplasia of parietal and mucus cells. In both diseases, hypergastrinemia also induces the hyperproliferation of enterochromaffin-like endocrine cells in the fundic mucosa, which can offer all aspects from hyperplasia, then dysplasia, until true carcinoid tumor. The influence of antisecretory treatments and MEN 1 in the ZES as well as that of several other factors and antrectomy in PA on the behavior of the different gastric cells is evoked. Finally, the role that gastrin and its receptor play in the maintenance of the normal development of gastric mucosa and gastric acid secretion is emphasized by results observed in gene knockout models.

gastroenteropancreatic (GEP) neuroendocrine tumors, suspected on clinical basis, are often difficult to localize. We report our experience with endoscopic ultrasonography (EUS) in the preoperative localization of pancreatic endocrine tumors (PETs), compared to other imaging modalities, and in staging and following up carcinoid tumors (CTs) of the gastrointestinal (GI) wall.

50 patients (20 males; mean age 54 years), 39 with suspected PETs and 11 with GI CTs underwent EUS (Olympus GF-UM2 or GF-UM3). EUS data could be compared with resected specimens in 25 out of the 39 PETs and five out of the 11 CTs.

in the PETs group 42 tumors (35<20 mm) were removed: 23 in the pancreas, eight in the duodenum, and 11 in the lymph nodes. EUS correctly localized 20 out of the 23 (87%) pancreatic tumors, included 11 out of the 12 (91.6%) insulinomas, three out of the eight (37.5%) duodenal gastrinomas, and ten out of the 11 (90.9%) metastatic lymph nodes. Furthermore EUS accurately evaluated the depth of parietal invasion of CTs in three out of four patients (75%) (two after and one prior to endoscopic resection). In three patients EUS was confirmed as normal on resected specimens (two pancreas and one stomach). In the PETs group, a correct localization was obtained by ultrasonography (US) only in 17.4% of cases, by computed tomography (CT) in 30.4%, by magnetic resonance imaging (MRI) in 25%, by angiography in 26.6%, and by somatostatin receptor scintigraphy in 15.4%.

EUS must be considered the first-intention method in localizing PETs and is helpful in decision making and management of GEP endocrine tumors.

Carcinoid tumours are enigmatic, slow growing malignancies which occur most frequently (74%) in the gastrointestinal tract. In recent years, it has become apparent that the term 'carcinoid' represents a wide spectrum of different neoplasms originating from a variety of different neuroendocrine cell types. Carcinoid lesions are usually identified histologically by their affinity for silver salts, by general neuroendocrine markers, or more specifically by immunocytochemistry using antibodies against their specific cellular products. Within the gut, the most frequent sites are the small bowel (29%), the appendix (19%) and rectum (13%). Clinical manifestations are often vague or absent. Nevertheless, in approximately 10% of patients the tumours secrete bioactive mediators which may engender various elements of characteristic carcinoid syndrome. In many instances the neoplasms are detected incidentally at the time of surgery for other gastrointestinal disorders. The tendency for metastatic spread correlates with tumour size, and is substantially higher in lesions larger than 2.0 cm. An association with noncarcinoid neoplasms is ascribed in 8-17% of lesions. Treatment consists of radical surgical excision of the tumour, although gastric (type I and II) and rectal carcinoids may be managed with local excision. Overall 5-year survival is excellent for carcinoids of the appendix (86%) and rectum (72%), whereas small intestinal (55%), gastric (49%) and colonic carcinoids (42%) exhibit a far worse prognosis.

Multiple gastric carcinoids are a well-recognized complication of hypergastrinemia associated with chronic atrophic gastritis. However, the management of large tumors (>2 cm in diameter) remains uncertain, with the decision between antrectomy or total gastrectomy being empirical. This report describes the investigation of a patient with chronic atrophic gastritis and multiple large gastric carcinoid tumors. Before surgery, octreotide was infused for 72 hours to suppress enterochromaffin-like (ECL) cell and gastrin cell function. The infusion decreased plasma gastrin and gastrin synthesis; moreover, there were marked reductions in markers of ECL cell function, e.g., histidine decarboxylase and chromogranin A messenger RNA abundance, in carcinoid tumor tissue and macroscopically normal corpus mucosa. An antrectomy was performed, after which the patient made an uneventful recovery. Six months after surgery, a single residual polyp, enriched with smooth muscle cells but not ECL cells, was removed. One year after antrectomy, the remaining stomach was normal. The response of ECL cell markers in carcinoid tissue to octreotide suggested that these cells were under neuroendocrine control and, therefore, predicted a beneficial outcome for antrectomy. It is suggested that an octreotide supression test coupled with assay of histidine decarboxylase or chromogranin A gene expression is useful in the assessment of gastric carcinoid tumors.

In recent classifications of gastric endocrine tumors, tumors arising in patients with multiple endocrine neoplasia type 1 (MEN-1) are regarded to be regulated by the concomitant hypergastrinemia resulting from to pancreatic or, most commonly, duodenal gastrinomas and to have a benign behavior. In this article, we report on two cases of MEN-1 gastric neuroendocrine tumors having a fatal course. Case 1 was a young male with hyperparathyroidism and Zollinger-Ellison syndrome and with florid development of multiple gastric carcinoids and multiple duodenal gastrinomas. Metastases occurred in the liver, of exclusive gastric origin, in periduodenal lymph nodes, of exclusive duodenal origin, and in perigastric lymph nodes, of mixed origin. The patient died 48 months after diagnosis. Case 2 was an adult female patient with hyperparathyroidism, adrenocortical disorders, and gastric tumors but no hypergastrinemia. The patient died 3 months after tumor diagnosis. At autopsy, the stomach showed multiple benign carcinoids and two independent neuroendocrine carcinomas not reported before in MEN-1 and massively metastatizing to lymph nodes, liver, and peritoneum. Multiple islet cell tumors mostly producing pancreatic polypeptide were found, whereas gastrinomas were seen in neither the pancreas nor the duodenum. Allelic losses at the MEN-1 gene locus in chromosome 11q13, the mechanism responsible for tumor development in MEN-1 syndrome, were demonstrated in the carcinoid tumors of case 1 and in the neuroendocrine carcinoma of case 2. We conclude that gastric neuroendocrine tumors in patients with MEN-1 may have a poor outcome, they have the same genetic mechanism as MEN-1 tumors in other organs, and they may be independent of the trophic effect of hypergastrinemia.

Carcinoid syndrome is the product of a rare but fascinating malignant neoplasm. Carcinoid syndrome was described more than 100 years ago, and recent advances in diagnostic localization, elucidation of the mechanisms of oncogenesis, treatment options, and, consequently, patient prognosis have been made. Current modalities of treatment, possible therapeutic implications of new avenues of research, and current literature on the chemotherapeutic combinations used are reviewed.