Gastrointestinal Intervention 2016; 5(3): 159-169  https://doi.org/10.18528/gii150035
How to manage gastric polyps
Gandhi Lanke1, Atin Agarwal2, and Jeffrey H. Lee1,*
1Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson CancerCenter, 1515 Holcombe Blvd, Houston, TX 77030, USA. E-mail address:Jefflee@mdanderson.org (J.H. Lee).
Received: December 9, 2015; Revised: January 18, 2016; Accepted: January 19, 2016; Published online: October 31, 2016.
© Society of Gastrointestinal Intervention. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Gastric cancer is the second leading cause of cancer related death in the world. In United States, gastric polyps are found in approximately 6% of upper endoscopy. The incidence of gastric polyps increased with widespread use of esophagogastroduodenoscopy and more liberal use of proton pump inhibitors. They are usually asymptomatic, but infrequently cause symptoms of bleeding, pain and gastric outlet obstruction. It is important to distinguish premalignant conditions and mimickers of malignancy. Helicobacter pylori eradication therapy leads to regression of hyperplastic polyps but it is not clear for adenoma. Endoscopy plays key role not only in diagnosis but also in surveillance. With narrow band imaging and chromo endoscopy, we are much better today in detecting and discerning these. Also, with endoscopic mucosal resection and endoscopic submucosal dissection, we can manage these better. In this review article we will discuss the various diagnostic tools and therapeutic options for hyperplastic polyp, fundic gland polyp, gastrointestinal stromal tumor, adenoma, neuroendocrine tumor, linitis plastica, and intestinal metaplasia.

Keywords: Carcinoid tumor, Endosonography, Helicobacter pylori, Narrow band imaging, Proton pump inhibitors
Introduction

Gastric polyps are found incidentally for an unrelated condition with increasing use of upper gastrointestinal endoscopy. Gastric polyps are either mucosal or submucosal and benign or malignant. They rarely cause symptoms. Management of gastric polyps is quite challenging. Early and accurate diagnosis and effective management may prevent the malignant transformation of these lesions, thus resulting in improved survival in some cases. This manuscript encompasses all types of gastric polyps we encounter in gastroenterology practice, providing the invaluable information regarding how to promptly make the diagnosis and manage them.

Proton Pump Inhibitors and Gastric Mucosa

Proton pump inhibitors (PPI) are used more often than indicated, and there is concern about long term effects.1 They are overused because of over the counter availability and affordable cost. There is no consensus on the definition of duration of chronic use and while most agree that 4 to 12 months is considered a long term use.2 Both microscopic and macroscopic changes from proliferation in the mucosa of fundus and gastric body were described secondary to chronic PPI use. Microscopic changes like cystic gland formation, parietal cell hyperplasia, protrusion of parietal cells in to the oxyntic glands and macroscopic changes like formation of sporadic fundic polyps were described.1 In a retrospective study of 599 patients, of which 322 patients used PPI, the authors concluded that a long term use of PPI for 1 to 5 years was associated with fundic gland polyps (FGPs) when compared to less than 1 year (short term) use of PPI.3

Non-Neoplastic polyps (Benign)

Hyperplastic polyp

They are the second most common gastric polyps (Fig. 1). They can be single, multiple, sessile, or pedunculated. They are composed of elongated and distorted pits lined by foveolar epithelium, inflamed and edematous lamina propria.4 They have a wide age range distribution and increases between ages of 60 to 80 years.5 The patient is commonly asymptomatic, but hyperplastic polyps can cause anemia, bleeding due to ulceration, dyspepsia, and gastric outlet obstruction.6,7 Although they are found most commonly in the antrum, they can be found anywhere in the stomach. Histologically, it shows dilated, marked elongation of the foveolae with branching, infiltrated by neutrophils, plasma cells, lymphocytes, mast cells, and macrophages resulting in corkscrew appearance.4 The stimuli for hyperplastic gastric polyps is not known but they are thought to arise from mucosal damage due to chronic inflammatory conditions leading to hyper regenerative epithelium. They are commonly encountered in the setting of Helicobacter pylori, pernicious anemia, chronic atrophic gastritis, adjacent to ulcers and at sites of gastroenterostomies.8,9 Development of hyperplastic gastric polyps is also associated with argon plasma coagulation (APC) treatment of gastric antral vascular ectasia as a result of mucosal reaction from thermal injury.10 In approximately 2% of the gastric hyperplastic polyps malignant transformation occurs11 and the mechanism of carcinogenesis is unknown. It is hypothesized that they arise either in dysplastic lesion or adjacent to dysplastic lesion. There is a high prevalence of immunoreactivity found in dysplasia, and p53 overexpression is associated with early carcinogenesis.12

Neoplastic Polyps (Malignant)

Fundic gland polyps

They occur predominantly in gastric fundus composed of normal gastric cell types (small glandular cell islands with parietal and chief cells) arranged in a disorderly or microcystic configuration (Fig. 2).13 They are more commonly seen in western countries because of the low prevalence of H. pylori and more liberal use of PPI. They are sporadic but can occur as polyposis syndromes like familial adenomatous polyposis (FAP), MUTYH-associated polyposis, gastric adenocarcinoma, and proximal polyposis of the stomach.14 A long term use of PPI (more than 1 year) is associated with FGP.3 Regression of FGPs is seen after discontinuation of PPI.15 Sporadic FGPs are more commonly seen in females than in males and the patients are middle aged. In FAP, males and females are equally affected and the patients are affected at early age. They are usually asymptomatic but can cause symptoms of obstruction like nausea, vomiting, and abdominal pain if they are large. Alteration in beta-catenin mutation is seen in sporadic FGP while germ line APC mutation and subsequent somatic mutation are seen in syndromic FGP.16,17 Endoscopically, they are seen in fundus and upper body of stomach as small (less than 1 cm), hyperemic, multiple, and sessile with smooth contour. Microscopically, they are seen as dilated cystic glands lined by fundic epithelium. A long-term treatment of PPI is associated with hypertrophy and hyperplasia of parietal cells with protrusion in to the lumen of the pits. Management of FGPs usually involves biopsy of the polyps. Polyps which are ulcerated or located in antrum, greater than 1 cm should be resected and dysplasia or neoplasia should be ruled out. In sporadic FGPs attributed to PPI, discontinuation of PPI is encouraged. FAP should be ruled out if FGP are seen in a multitude (20 or greater), located in the antrum, at an early age (younger than 40 years), or concurrent duodenal adenoma is present, colonoscopy should be recommended. Surveillance with esophagogastroduodenoscopy (EGD) is not recommended in sporadic FGP as gastric cancer is rare, but in FAP, it is recommended because 30% to 50% of them may be associated with low grade dysplasia.18,19

Gastrointestinal stromal tumors

These are mesenchymal tumors which arise from the subepithelial layers (muscularis mucosa or muscularis propria) of the gastrointestinal tract (Fig. 3). The etiology is not clear. The phenotypic resemblance to interstitial cells of cajal (ICCs) suggests that the origin is from ICCs.20 They can arise anywhere in the Gastrointestinal tract but the most common location is the stomach.21 They are more common in middle age and older individuals.22 Both familial and sporadic gastrointestinal stromal tumors (GISTs) are seen. Although familial and sporadic GISTs are indistinguishable both in phenotype and molecular features,23 familial GISTs are more predisposed to development of multiple gastric and small intestinal GIST. In GIST, there is an over-expression of c-KIT, a growth factor tyrosine-kinase receptor that is normally expressed in myenteric plexus of adult gastrointestinal tract, melanocytes, and hematopoietic stem cells.24 Conversely, in about 5% of GISTs, c-KIT is not expressed; however, mutation in platelet derived growth factor receptor-alpha (PDGFRA) is seen.25 Prognostic factors include size, location, and mitotic rate.26,27 Size less than 2 cm and origin in the stomach are favorable prognostic factors as the risk of malignancy is extremely low.28,29 Clinical symptoms depend on size and location of the tumor. Iron deficiency anemia, melena, and hematemesis are seen with ulcerated lesions. In larger tumors, abdominal pain and early satiety27 are present. The liver and peritoneum are the most common metastatic sites.

Histologically, they are spindle cells with elongated nuclei and eosinophilic cytoplasm arranged in whorls or short fascicles.30 Epithelioid type is seen in KIT negative GIST tumors that harbor PDGFRA mutation.31 Radiological features of GIST tumors vary depending on their size. Tumors larger than 2 cm develop focal ulceration of the underlying mucosa because of pressure necrosis which is referred to “bulls eye” on radiology.32 They tend to invade adjacent structures like the pancreas, colon and diaphragm with increase in size. Differential diagnosis for GIST includes schwannoma, leiomyoma, type 1 carcinoid, metastasis to the stomach from breast cancer and melanoma. Computed tomography (CT) with oral and intravenous contrast is the initial imaging of choice to characterize the mass, evaluate the extent and spread of tumor. It appears as smoothly contoured solid mass that enhances with intravenous contrast. On upper endoscopy both GIST and leiomyoma appear as a subepithelial mass with smooth margins and occasional ulceration. Endoscopic ultrasonography (EUS) can help differentiate subepithelial lesions based on the layer of origin and also in obtaining biopsy for cytological analysis and immunohistochemistry. Treatment for localized GIST is surgical resection if feasible. Although there are no clear guidelines, NCCN (National Comprehensive Cancer Network) recommends a follow-up with CT abdomen and pelvis, every 3 to 6 months for 3 to 5 years and then annually, for completely resected GIST tumors. For locally advanced or metastatic GIST tumors receiving imatinib, the patients should have a CT abdomen and pelvis every 3 to 6 months. Adjuvant therapy with imatinib is recommended for tumors greater than 3 cm in size or if the margins are positive after surgical resection. In addition, neoadjuvant therapy with imatinib is recommended for tumors that are unresectable, borderline resectable with locally advanced or tumors that require extensive organ disruption. The goal of neoadjuvant therapy is to reduce the tumor size thereby making it potentially resectable with organ preservation.

Gastric adenoma (raised intraepithelial neoplasia)

They are polypoid, circumscribed lesions lined by dysplastic epithelium composed of either tubular and or villous structures (Fig. 4). They account for 6% to 10% of gastric polyps in western populations.33 Atrophic gastritis and intestinal metaplasia are associated with the development of gastric adenoma.34 They may occur in individuals with familial adenomatous polyps and their incidence increases with age.35 They are frequently solitary and commonly found in the antrum. Histologically, they are classified into tubular, villous, or tubulovillous. Polyps that have villous histology and size greater than 2 cm have a 28% to 40% increased risk of malignancy.36 High grade dysplasia predisposes to invasive cancer, not only within the polyp but also in synchronous areas of the stomach.37 Differentiating between low and high dysplasia of gastric adenoma is based on degree of mitotic activity, cytoplasmic differentiation, nuclear crowding, hyperchromasia, stratification, and architectural distortion.38 Gastric adenomas may have combined gastric and intestinal features39 and minority of them contain foveolar or pyloric gland epithelium. The pyloric adenoma is more common in older patients (women > men) and carries a 30% risk of malignant transformation.40

Gastric neuroendocrine tumors (carcinoids)

Gastric neuroendocrine tumors (NETs) formerly known as carcinoids are well differentiated arising in the oxyntic mucosa of corpus or fundus composed of nonfunctioning enterochromaffin cells (Fig. 5). There are three types of carcinoid in the stomach. Type 1 carcinoids are most common and usually found in middle-aged women with autoimmune gastritis. The pathogenesis involves autoimmune destruction of parietal cells which leads to loss of feedback inhibition of gastrin and enterochromaffin cell proliferation appearing as small nodules in the body of the stomach.41 Type 2 carcinoids are rare and they occur in multiple endocrine neoplasia type 1 (MEN1), Zollinger-Ellison syndrome, or gastrin secreting tumors. They metastasize in approximately 30%42 of cases and have a worse prognosis compared to type 1 carcinoids. Treatment for type 2 involves evaluation for metastasis, resection of local tumor, and removal of gastrin secreting tumor. Type 3 carcinoids are usually solitary arising anywhere in the stomach and are sporadic. Lymph node metastasis is found in approximately 71% of cases measuring more than 2 cm and the treatment involves surgical resection.43

Symptoms include nonspecific epigastric pain or carcinoid syndrome caused by the release of histamine and tachykinin (flushing, lacrimation, facial edema, lacrimation, bronchoconstriction, and headache). A barium contrast study helps in identifying polypoid lesions and abdominal CT can assist in identifying lymph node spread and liver metastasis.44 Radiolabeled somatostatin analogues like pentatreotide are helpful in identifying local vs metastatic foci of carcinoid tumors having somatostatin receptors.45 Histolopathologically, they contain variety of cell types which include enterochromaffin like, enterochromaffin, and X cells.46 They are immunoreactive for synaptophysin, neuron specific enolase, and chromogranin; exhibit different growth patterns like trabecular, solid, rosette or combination of these types. Antrectomy is recommended for multiple lesions and for recurrence after removal since it decreases the stimulus for growth by removing hypergastrinemia.47 For sporadic lesions, en bloc surgical resection with lymph node dissection is recommended.48 Hepatic metastasis can be treated by hepatic artery ligation or embolization, which decreases the symptoms and improves survival. Octreotide that is a somatostatin analogue is used to decrease the symptoms of carcinoid syndrome. Metastatic carcinoids are treated with chemotherapeutic agents like streptozocin, fluorouracil, doxorubicin and cyclophosphamide which produce tumor response in 20% to 40% of patients.49

Gastric linitis plastica

It is a diffuse type of gastric cancer characterized by diffuse thickening and it accounts for 3% to 19% of gastric adenocarcinoma (Fig. 6).50 Most are asymptomatic but symptoms arise at an advanced stage.51 Metastasis from breast should be excluded as infiltrative lobular cancer of breast tends to metastasize to the stomach, mimicking gastric linitis plastica (GLP).52 Common symptoms when present include early satiety, abdominal discomfort, weight loss, dysphagia, dyspepsia and vomiting.53 Often there is regurgitation of food into the esophagus because of infiltration of tumor cells decreasing the volume of stomach and hence interfering with peristalsis. Linitis plastica usually involves the lower third of the mucosa; thus and biopsy of mucosa can be negative because the mucosa is not infiltrated. Multiple biopsy samples from the same site or using diathermic snare can increase the yield of diagnosing GLP. Preoperative staging is important in the diagnosis and treatment. CT scan and gastroscopy are the two important tools in evaluating the extent of cancer. Histopathologically, GLP consists of atypical cells which often has a signet ring cell appearance and are diffusely infiltrating.54 CT scan findings include thickened stomach wall, diffuse gastric wall thickening, perigastric stranding, lung nodules, mediastinal lymphadenopathy, local lymphadenopathy and liver metastasis. Primary gastric adenocarcinoma has a low fluorodeoxyglucose (FDG) uptake because of non-intestinal type, signet ring cells, high mucous content, and low cellularity.55 For distant metastasis, the sensitivity and specificity of positron emission tomography (PET) are 35% to 74% and 74% to 99%, respectively.56 PET FDG activity of standardized uptake value less than 4 was reported not associated with esophagogastric neoplasia57 but associated with physiologic smooth muscle activity or non-neoplastic inflammation in the stomach. A complete preoperative staging is composed of diagnostic laparoscopy, CT, endoscopy, endoscopic ultrasound, and ultrasound abdomen. Serum tumor markers such as carcinoembryonic antigen, CA 19-9 and CA 72-4 are frequently done before treatment. Elevated CA 19-9 is elevated in patients with peritoneal spread and lymph node involvement and associated with a poor prognosis.58 Treatment is a complete resection, but only 20% of them benefit from total gastrectomy59 because peritoneal seeding, extension to surrounding organs and metastasis to lymph nodes is common. A role of postoperative radiation with or without chemotherapy should be further evaluated in future studies since complete resection is not possible in the majority of cases.

Gastric intestinal metaplasia

It is the most frequently encountered precancerous lesion of the stomach (Fig. 7).60 The sequence of gastric adenocarcinoma of intestinal type includes nonatrophic gastritis, multifocal atrophic gastritis, metaplasia, and dysplasia.61 It is more common in populations at high risk for gastric cancer, as in Eastern Asia, Eastern Europe, and Andean Latin America. In United States, high-risk populations include African Americans, Native Americans, and immigrants from Asia and Latin America.62 Risk factors for gastric intestinal metaplasia (GIM) include H. pylori infection, high salt intake, smoking, alcohol consumption, and chronic bile reflux.63 It is classified histopathologically into complete and incomplete based on the presence of small intestinal enzymes.64 Complete type intestinal metaplasia (IM) contains the enzymes resembles the small intestinal epithelium with presence of the eosinophil enterocytes, goblet cells, and paneth cells. Incomplete IM contains either a small amount or none of the enzymes resembling the colonic epithelium with absent brush border. Filipe et al65 proposed another classification based on the type of mucins. In IM, acid mucins replace original gastric mucins. In type 1 (incomplete), it is sialomucins; type 2 (incomplete) contains mixed gastrin and intestinal mucins; type 3 (complete) contains sulphomucins. Samloff et al66 proposed that the extent of gastric atrophy and intestinal metaplasia could be assessed by the measurement of the serum pepsinogen levels. Pepsinogen levels reflect the morphology and functional status of the gastric mucosa.66,67 As precancerous focus starts from the antral- corpus region and advances to the antrum and corpus, the serum levels of pepsinogen decrease from the atrophy of the corpus. If the pepsinogen levels are not affected, it is probably because only the antrum is affected and not the corpus.

In gastric cancer screening of high risk patients, pepsinogen was found to be useful as it is cost effective, less invasive, and provides faster results.68H. pylori colonization is seen in incomplete IM and areas adjacent to nonmetaplastic gastric mucosa of complete IM.69 False negative test with rapid urease test for H. pylori can be seen in IM patients taking PPI, and hence other tests, such as serology, stool antigen and C13 urea breath test should be considered. Eradicating H. pylori will attenuate the precancerous process of gastric adenocarcinoma since H. pylori plays a role in IM.70 It is still unclear whether eradicating H. pylori infection will prevent cancer if IM has already developed.71

Diagnostic Tools and Endoscopic Management

Computed tomography

It is helpful in preoperative staging of gastric cancer and also detection of both benign and malignant tumors. When compared to gastroscopy, it provides additional information not only about the gastric wall but also the entire abdomen.72 Multidetector CT allows three dimensional images and creates thinner or thicker sections in a shorter acquisition time.73 CT manifestation of gastric cancer can be a polypoid lesion, focal or diffuse (linitis plastica) mural thickening with or without ulceration. D’Elia et al74 evaluated the diagnostic accuracy of CT in preoperative staging of gastric cancer when compared to pathology. The diagnostic accuracy was 80% and 99% in an early and advanced gastric cancer respectively. Diagnostic accuracy of tumor stage was 78%; depth of invasion was 20% in early and 87% in advanced cancer. The sensitivity and specificity of liver metastasis were 87.5% and99%, respectively.

In another prospective study by Kim et al,75 they evaluated the diagnostic accuracy of multiplanar CT in preoperative staging of gastric cancer when compared to pathology. Both virtual endoscopy (volumetric CT) and transverse CT is used. Volumetric images give added advantage of endoluminal perspective when compared to transverse CT. For tumor stage, diagnostic accuracy for transverse CT vs volumetric CT were 77% vs 84%; for lymph node detection 62% vs 64%; and for metastasis 86% for both respectively.75 Kwee and Kwee76 reviewed five multidetector row CT studies for staging of gastric cancer and the overall accuracy for T-staging was 77.1% to 88.9%. Sensitivity and specificity for the serosa involvement were 82.8% to 100% and 80% to 96.8%, respectively.76

Binstock et al77 evaluated the radiologic features of carcinoid tumors in CT. Carcinoids can be detected as small submucosal or mucosal polyp in patients with history of chronic atrophic gastritis and hypergastrinemia. In patients with MEN1, they can be identified as multiple gastric polypoid masses and diffuse gastric wall thickening. In type 3 carcinoids, it can be seen with metastatic lymph node involvement of the liver, spleen, and perigastric region, and localized thickening of posterior gastric wall.77

Hyperplastic polyps on CT can be detected as multiple small, round, sessile polyps in fundus or gastric body and they usually range in 5 to 10 mm size. Gastric adenomas are usually solitary, found adjacent to the antrum; they are sessile or pedunculated and are lobulated in appearance, sometimes with size > 2 cm.

Magnetic resonance imaging

It is preferred over CT in renally compromised patients as gadolinium contrast is not nephrotoxic. It also has the advantage of no radiation. In a study of 189 patients, Jang et al78 compared the diagnostic accuracy of magnetic resonance imaging (MRI) vs two-dimensional CT for gastric cancer. They showed that the diagnostic accuracy and sensitivity of MRI (combined conventional, diffusion weighted) vs CT were 77.8% to 78.3% vs 67.7% to 71.4% and 75.3% to 75.9% vs 64.1% to 68.2%, respectively. The diagnostic accuracy and sensitivity for conventional MRI alone were 72% to 73% and 68.8% to 70%, respectively.78 In another study by Kim et al,79 the authors looked at 20 patients with gastric cancer and they compared MRI vs pathology to determine the accuracy of T-staging and N-staging. The accuracy of T-staging and N-staging for gastric cancer with MRI vs pathology were 74% and 47%, respectively.79 MRI has certain limitations stemming from its high cost, motion artifacts, and lack of stable contrast medium.80 Use of abdominal binders, antiperistalitic agents, phased-coil arrays, and breath-hold imaging techniques can reduce motion artifacts and improve the quality of images.81

In a prospective study involving 64 patients, Dromain et al82 evaluated the sensitivity of CT, MRI and somatostatin receptor scintigraphy (SRS) for the detection of liver metastasis from well differentiated gastroenteropancreatic tumors; the sensitivity of SRS, CT, and MRI were 49.3%, 78.5%, and 95.2%, respectively.82

Positron emission tomography

18F-FDG PET is sensitive for NETs with high proliferation index when compared to low proliferation index.83 In a prospective study of 96 patients, Binderup et al84 compared the sensitivity of SRS with 111 In-Diethylenetriaminepentaacetic acid-octreotide, scintigraphy with 123I-metaiodobenzylguanidine (MIBG) and 18F-FDG PET for diagnosing NETs. The sensitivity of SRS, 123I-MIBG scintigraphy, and 18F-FDG PET were 89%, 52%, and 58%, respectively.84 In a study of 124 patients investigating the sensitivity and positive predictive value of 18F-FDG PET for screening early gastric cancer (EGC) in Japan, the authors found the sensitivity 37.9% and specificity 33.6%.85

Probe-based confocal laser microscopy

Probe-based confocal laser microscopy (pCLE) has an advantage over high definition white light endoscopy (WLE) and chromo endoscopy in identifying mucosal dysplasia and EGC by direct histological visualization of the tissue, thus allowing targeted biopsy.86 There are 2 types of CLE, endoscopy-based CLE (eCLE) and pCLE. While pCLE is convenient to use through the endoscopes, eCLE may provide a higher resolution and deeper depth penetration when compared to pCLE. In a prospective study of 46 patients, the authors reported that the accuracy of pCLE, conventional endoscopic biopsy, combined pCLE and conventional endoscopic biopsy for diagnosis of early gastric adenocarcinoma were 91.7%, 85.2%, and 98.1%, respectively.87 In another prospective study of 182 patients, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CLE for detection of superficial gastric cancer when compared to white-light endoscopy were found to be 88.9% vs 72.2%, 99.3% vs 95.1%, 85.3% vs 41.6%, 99.5% vs 98.6%, and 98.1% vs 94.1%, respectively.88

Narrow band imaging

Narrow band imaging (NBI) provides clear images of microvasculature and gastrointestinal mucosa and can enhance early detection of gastric cancer. In a retrospective study of 51 patients, Horiuchi et al89 looked at the sensitivity and specificity of detection of coexistence of gastric cancer in hyperplastic gastric polyps with WLE and magnifying endoscopy-NBI (ME-NBI). The sensitivity and specificity for WLE were 66.7% and 96.2%, respectively. The sensitivity and specificity of ME-NBI were 83.3% and 84.6% for fine mucosal structure, and 54.5% and 92.3% for irregularity of micro vessels, respectively.89 In a retrospective study of 99 patients, the sensitivity, specificity, diagnostic accuracy of NBI vs chromoendoscopy for gastric cancer smaller than 5 mm in size were found to be 78% vs 43.7%, 92.9% vs 81.6%, 88.3% vs 69.9%, respectively.90

Chromo-endoscopy

It enhances tumor localization and characterization by application of various dyes. Absorptive, contrast, and reactive stains are different types of stains used. Absorptive stains include methylene blue and Lugol’s iodine that are useful in detecting gastric metaplasia and EGC. Reactive stains like congo red and phenol help in detection of gastric cancer and H. pylori infection. Contrast stains like Indigo carmine are used to detect EGC and delineate the margins of gastric cancer before endoscopic submucosal dissection (ESD).91 In a prospective study of 104 patients by Kawahara et al,92 the diagnostic accuracy of white light, indigo carmine, and acetic acid-indigo carmine mixture for detecting EGC were 50.0%, 75.9%, and 90.7%, respectively.92 Dye based chromo endoscopy is limited by uneven staining of the mucosal areas resulting in overstraining or under staining of lesions thereby affecting the diagnosis and treatment. Dye-less chromo endoscopy is introduced to overcome this limitation, which includes Fujifilm Intelligent Color Enhancement (FICE; Fujifilm, Tokyo, Japan) and I-scan (Pentax, Tokyo, Japan). Mouri etal prospectively studied 100 patients with EGC and they showed that flexible spectral imaging color enhancement improved visualization of EGC in 46% of cases.93

Esophagogastroduodenoscopy

Hyperplastic polyps are usually less than 1 cm, smooth, domeshaped, or stalked. Endoscopic finding of white opaque substance in a gastric hyperplastic polyp is suggestive of neoplastic transformation.94 There are no endoscopic guidelines for follow up of hyperplastic gastric polyp without dysplasia, but, if polyp persists or dysplasia is present, polypectomy is recommended with repeat EGD in one year.41 Whenever hyperplastic polyps are seen, examination of the whole stomach should be made to look for mucosal abnormalities and biopsy should be done to look for a synchronous cancer.95 There are no standard guidelines for endoscopic removal of hyperplastic polyps. Although polyps greater than 2 cm should be removed,96 carcinoma can arise in polyps smaller than 2 cm.97 When hyperplastic polyps arise from chronic atrophic gastritis, the severity should be assessed based on the Operative Link for Gastritis Assessment (OLGA) or the Operative Link on Gastritis/Intestinal Metaplasia Assessment staging systems.98 In general, 5 to 7 biopsy specimens (3 from the antrum, 2 from the lesser curvature of corpus and 2 from the greater curvature of the corpus) should be obtained to assess the severity of atrophic gastritis. Endoscopic surveillance should be considered for stage 3 or stage 4 OLGA but the guidelines are not standardized.

Gastric adenomas range in size from few millimeters to 4 cm in size99 and are flat or sessile. Endoscopic follow-up for gastric adenoma should be done 6 months after incomplete polypectomy or for high grade dysplasia and 1 year for all other polyps.41 High grade dysplasia predisposes to invasive cancer not only within the polyp but also in synchronous areas of the stomach.37 Operative resection should be considered for those not amenable for endoscopic resection.

Gastric NETs on upper gastrointestinal endoscopy are visible as submucosal masses that have yellow color, small, and rounded.100 For type 1 and type 2 carcinoids measuring less than 1 cm and fewer than 3 to 5 in number, endoscopic polypectomy with follow-up every 6 months is recommended.101

Endoscopic features of GLP include prominent gastric folds, thickened area of irregular gastric mucosa at greater curvature, circumferential thickening of the proximal stomach, fungating lesion extending form the esophagogastric junction to the antrum and diffuse gastric mucosal inflammation with normal biopsy.

As aforementioned, GIM is classified histologically into complete and incomplete intestinal types. Incomplete IM should undergo endoscopic mapping to identify multifocal areas of IM because several studies showed progression of IM to gastric adeno carcinoma.102 Typically, biopsies are obtained from the antrum, corpus, incisura angularis, and any visible lesions.103 For complete IM, endoscopic surveillance is not indicated unless there are other risk factors for gastric cancer.

Endoscopic ultrasonography

EUS can help in differentiating submucosal and mucosal gastric polyps.104 It also helps in determining the feasibility of endoscopic resection by assessing the depth of involvement. In general, endoscopic resection is not indicated if it involves muscularis propria.105,106 EUS can further differentiate submucosal tumors from extrinsic compressions and cystic from solid masses.107 Carcinoids usually arise from deep mucosal or submucosal layers and spread deeper to submucosal area. While performing endoscopy, resection can be performed for type 1 and type 2 gastric carcinoids measuring 1 to 2 cm and confined within the mucosa and submucosal layers.108 However, for gastric carcinoids > 2 cm, surgical resection should be considered109113 rather than endoscopic attempt. EUS can also help in identifying the blood vessel near the carcinoid, which can potentially help prevent bleeding during endoscopic resection.114

Endoscopic mucosal resection and endoscopic submucosal dissection

One of the indications for endoscopic mucosal resection (EMR) and ESD is curative resection of the EGC. Gastric lesions confined to the mucosa, papillary or tubular (differentiated) adenocarcinoma, less than 2 cm for elevated lesions, less than 1 cm for flat or depressed lesions, no venous or lymph node involvement, no ulcer or ulcer scar are ideal candidates for EMR.115 Identifying lymph node metastasis is important prior to attempting EMR or ESD. Paris and Kudo classifications describe shape and pit-pattern of the lesions. Paris 1 incudes protruded lesions; Paris 2 is subdivided into 2a slightly elevated, 2b completely flat, 2c depressed lesions; and Paris 3 lesions have ulceration in the mucosa.116 According to pit-patterns, Kudos classification is subdivided into type 1 (round), type 2 (stellar or papillary) which are nonneoplastic, type 3 (tubular or small roundish), type 4 (branch-like or gyrus-like), and type 5 (irregular or nonstructural pits) neoplastic.117 Type 5 usually involves the submucosal layer and portends higher lymph node metastasis.118 ESD has the advantage of en bloc resection and better histological assessment of lymphovascular invasion compared to EMR which employs a piece-meal resection.119 Catalano et al120 compared EMR and ESD for EGC in 45 patients. En bloc resection for EMR vs ESD was reported in 26/32 patients (76%) and 11/12 patients (92%), respectively. Curative resection for EMR vs ESD was 20/36 patients (56%) vs 11/12 patients (92%), respectively. Complications of EMR vs ESD included bleeding (8% vs 8%), stenosis (3% vs 0%) and perforation (0% vs 8%), respectively.120

EMR is recommended for both type 1 and type 2 gastric carcinoids associated with hypergastrinemia, less than 1 cm in diameter and presence of 3 to 5 tumors.121 EUS is performed before treatment to assess the depth of invasion. Tumors confined to submucosa are treated endoscopically (EMR) and with deeper invasion are treated surgically. Endoscopic surveillance with bio-spy at 6 months interval is performed after complete resection to evaluate for recurrence.

Gastric adenoma (low grade dysplasia and high grade dysplasia) can progress to invasive carcinoma122 or advanced cancer123 at the time of follow-up. Treatment for gastric adenoma is endoscopic en bloc resection and complete resection. ESD is preferred than EMR because of the advantage of en bloc resection and complete resection regardless of lesion size.124 In a retrospective study done by Kim et al,125 they evaluated 252 patients with low grade dysplasia who have undergone EMR (77.8%) and ESD (22.2%), respectively. They concluded that en bloc resection was significantly lower in the EMR group (31.1%) when compared to ESD group (75%) (P < 0.001) and no significant difference in prevalence of remnant lesions or recurrence rate (P = 0.911) of gastric adenoma.125

Perforation with ESD (1.2%–5.2%) usually occurs in the upper and middle parts of the stomach because of the thin wall and ret-ro flexion position of the endoscope. The risk for perforation further increases with increasing size of the lesion and ulceration.126 Submucosal injection is paramount of importance in creating a safety net in ESD by providing an adequate space for dissection between the mucosa and muscularis propria layers. Single-closure and omental patch using endoclips are utilized in endoscopic closure. Single-closure is used for smaller defects and omental patch is used for larger defects.127 Bleeding can be immediate (intraoperative) or delayed (within 24 hours of procedure). For the control of bleeding, there are many in the armamentarium, electric cautery, injection therapy, placement of hemoclips, or combinations thereof. However, delayed bleeding can be prevented by carefully inspecting the resection bed and applying coagulation to the visible vessels while performing EMR or ESD.128 Stenosis usually occurs when the mucosal defect is greater than 75% of the circumference and/or longitudinal defect is more than 5 cm; a serial dilation with balloon inflation is often required to treat the stenosis.

Conclusion

With increasing incidence of gastric lesions detected, the prompt differentiation between benign from malignant gastric lesions is essential to successful, efficient, and cost-effective management. Careful inspection and biopsy of the lesion and perhaps the surrounding mucosa will prevent missing hidden cancers. Clearly, accurate diagnosis and staging, complete resection, and meticulous follow-up are the principles in preventing invasive surgery and potentially improving survival. Good judgment of endoscopists and close collaboration with pathologists are priceless in this challenging endeavor.

Figures
Fig. 1. (A) Hyperplastic polyp. (B) Hyperplastic polyp shows superficial ulceration with elongated foveolar epithelium and edematousstroma (H&E stain, × 4).
Fig. 2. (A) Fundic gland polyp. (B) Fundic gland polyp with dilated oxyntic glands and low grade foveolar epithelial dysplasia (H&E stain, × 10).
Fig. 3. Gastrointestinal stromal tumor.
Fig. 4. (A) Gastric adenoma. (B) Gastric tubular adenoma with intestinal metaplasia (H&E stain, × 10).
Fig. 5. (A) Gastric carcinoid. (B) Gastric submucosal carcinoid with nests of bland neuroendocrine cells (H&E stain, × 10).
Fig. 6. (A) Gastric linitis plastica. (B) Diffuse type gastric carcinoma with signet ring cells (H&E stain, × 10).
Fig. 7. (A) Gastric intestinal metaplasia. (B) Antral type gastric mucosa with intestinal metaplasia (H&E stain, × 10).
References
  1. Camilo, SM, Almeida, ?C, Miranzi, BA, Silva, JC, Nomelini, RS, and Etchebehere, RM (2015). Endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors. Arq Gastroenterol. 52, 59-64.
    Pubmed CrossRef
  2. Raghunath, AS, O’Morain, C, and McLoughlin, RC (2005). Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 22, S55-63.
    CrossRef
  3. Jalving, M, Koornstra, JJ, Wesseling, J, Boezen, HM, DE Jong, S, and Kleibeuker, JH (2006). Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy. Aliment Pharmacol Ther. 24, 1341-8.
    Pubmed CrossRef
  4. Park do, Y, and Lauwers, GY (2008). Gastric polyps: classification and management. Arch Pathol Lab Med. 132, 633-40.
    Pubmed
  5. Dirschmid, K, Platz-Baudin, C, and Stolte, M (2006). Why is the hyperplasticpolyp a marker for the precancerous condition of the gastric mucosa?. Virchows Arch. 448, 80-4.
    CrossRef
  6. Jayawardena, S, Anandacoomaraswamy, D, Burzyantseva, O, and Abdullah, M (2008). Isolated diffuse hyperplastic gastric polyposis presenting with severe anemia. Cases J. 1, 130.
    Pubmed KoreaMed CrossRef
  7. Aydin, I, Ozer, E, Rakici, H, Sehitoglu, I, Yucel, AF, and Pergel, A (2014). Antral hyperplastic polyp: a rare cause of gastric outlet obstruction. Int J Surg Case Rep. 5, 287-9.
    Pubmed KoreaMed CrossRef
  8. Veereman Wauters, G, Ferrell, L, Ostroff, JW, and Heyman, MB (1990). Hyperplastic gastric polyps associated with persistent Helicobacter pylori infection and active gastritis. Am J Gastroenterol. 85, 1395-7.
    Pubmed
  9. Mori, K, Shinya, H, and Wolff, WI (1971). Polypoid reparative mucosal proliferation at the site of a healed gastric ulcer: sequential gastroscopic, radiological, and histological observations. Gastroenterology. 61, 523-9.
    Pubmed
  10. Baudet, JS, Salata, H, Soler, M, Castro, V, D?az-Bethencourt, D, and Vela, M (2007). Hyper -plastic gastric polyps after argon plasma coagulation treatment of gastric antral vascular ectasia (GAVE). Endoscopy. 39, E320.
    CrossRef
  11. Hizawa, K, Fuchigami, T, Iida, M, Aoyagi, K, Iwashita, A, and Daimaru, Y (1995). Possible neoplastic transformation within gastric hyperplastic polyp. Application of endoscopic polypectomy. Surg Endosc. 9, 714-8.
    Pubmed CrossRef
  12. Yao, T, Kajiwara, M, Kuroiwa, S, Iwashita, A, Oya, M, and Kabashima, A (2002). Malignant transformation of gastric hyperplastic polyps: alteration of phenotypes, proliferative activity, and p53 expression. Hum Pathol. 33, 1016-22.
    Pubmed CrossRef
  13. Odze, RD, Marcial, MA, and Antonioli, D (1996). Gastric fundic gland polyps: a morphological study including mucin histochemistry, stereometry, and MIB-1 immunohistochemistry. Hum Pathol. 27, 896-903.
    Pubmed CrossRef
  14. Lynch, HT, Smyrk, T, McGinn, T, Lanspa, S, Cavalieri, J, and Lynch, J (1995). Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer. 76, 2427-33.
    Pubmed CrossRef
  15. Kim, JS, Chae, HS, Kim, HK, Cho, YS, Park, YW, and Son, HS (2008). Spontaneous resolution of multiple fundic gland polyps after cessation of treatment with omeprazole. Korean J Gastroenterol. 51, 305-8.
    Pubmed
  16. Sekine, S, Shibata, T, Yamauchi, Y, Nakanishi, Y, Shimoda, T, and Sakamoto, M (2002). Beta-catenin mutations in sporadic fundic gland polyps. Virchows Arch. 440, 381-6.
    Pubmed CrossRef
  17. Abraham, SC, Nobukawa, B, Giardiello, FM, Hamilton, SR, and Wu, TT (2000). Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations. Am J Pathol. 157, 747-54.
    Pubmed KoreaMed CrossRef
  18. Bertoni, G, Sassatelli, R, Nigrisoli, E, Pennazio, M, Tansini, P, and Arrigoni, A (1999). Dysplastic changes in gastric fundic gland polyps of patients with familial adenomatous polyposis. Ital J Gastroenterol Hepatol. 31, 192-7.
    Pubmed
  19. Wu, TT, Kornacki, S, Rashid, A, Yardley, JH, and Hamilton, SR (1998). Dysplasia and dysregulation of proliferation in foveolar and surface epithelia of fundic gland polyps from patients with familial adenomatous polyposis. Am J Surg Pathol. 22, 293-8.
    Pubmed CrossRef
  20. Miettinen, M, Sobin, LH, and Sarlomo-Rikala, M (2000). Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol. 13, 1134-42.
    Pubmed CrossRef
  21. Emory, TS, Sobin, LH, Lukes, L, Lee, DH, and O’Leary, TJ (1999). Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol. 23, 82-7.
    Pubmed CrossRef
  22. Tran, T, Davila, JA, and El-Serag, HB (2005). The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 100, 162-8.
    Pubmed CrossRef
  23. Mussi, C, Schildhaus, HU, Gronchi, A, Wardelmann, E, and Hohenberger, P (2008). Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1. Clin Cancer Res. 14, 4550-5.
    Pubmed CrossRef
  24. Hirota, S, Isozaki, K, Moriyama, Y, Hashimoto, K, Nishida, T, and Ishiguro, S (1998). Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 279, 577-80.
    Pubmed CrossRef
  25. Corless, CL, Schroeder, A, Griffith, D, Town, A, McGreevey, L, and Harrell, P (2005). PDG-FRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 23, 5357-64.
    Pubmed CrossRef
  26. Singer, S, Rubin, BP, Lux, ML, Chen, CJ, Demetri, GD, and Fletcher, CD (2002). Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol. 20, 3898-905.
    Pubmed CrossRef
  27. DeMatteo, RP, Lewis, JJ, Leung, D, Mudan, SS, Woodruff, JM, and Brennan, MF (2000). Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 231, 51-8.
    Pubmed KoreaMed CrossRef
  28. Miettinen, M, Makhlouf, H, Sobin, LH, and Lasota, J (2006). Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol. 30, 477-89.
    Pubmed CrossRef
  29. Miettinen, M, Sobin, LH, and Lasota, J (2005). Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol. 29, 52-68.
    CrossRef
  30. Fletcher, CD, Berman, JJ, Corless, C, Gorstein, F, Lasota, J, and Longley, BJ (2002). Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol. 10, 81-9.
    Pubmed CrossRef
  31. Medeiros, F, Corless, CL, Duensing, A, Hornick, JL, Oliveira, AM, and Heinrich, MC (2004). KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol. 28, 889-94.
    Pubmed CrossRef
  32. Pinaikul, S, Woodtichartpreecha, P, Kanngurn, S, and Leelakiatpaiboon, S (2014). 1189 Gastrointestinal stromal tumor (GIST): computed tomographic features and correlation of CT findings with histologic grade. J Med Assoc Thai. 97, 1189-98.
  33. Archimandritis, A, Spiliadis, C, Tzivras, M, Vamvakousis, B, Davaris, P, and Manika, Z (1996). Gastric epithelial polyps: a retrospective endoscopic study of 12974 symptomatic patients. Ital J Gastroenterol. 28, 387-90.
    Pubmed
  34. Kamiya, T, Morishita, T, Asakura, H, Miura, S, Munakata, Y, and Tsuchiya, M (1982). Long-term follow-up study on gastric adenoma and its relation to gastric protruded carcinoma. Cancer. 50, 2496-503.
    Pubmed CrossRef
  35. Iida, M, Yao, T, Itoh, H, Watanabe, H, Matsui, T, and Iwashita, A (1988). Natural history of gastric adenomas in patients with familial adenomatosis coli/Gardner’s syndrome. Cancer. 61, 605-11.
    Pubmed CrossRef
  36. Tomasulo, J (1971). Gastric polyps. Histologic types and their relationship to gastric carcinoma. Cancer. 27, 1346-55.
    Pubmed CrossRef
  37. Orlowska, J, Jarosz, D, Pachlewski, J, and Butruk, E (1995). Malignant transformation of benign epithelial gastric polyps. Am J Gastroenterol. 90, 2152-9.
    Pubmed
  38. Nakamura, T, and Nakano, G (1985). Histopathological classification and malignant change in gastric polyps. J Clin Pathol. 38, 754-64.
    Pubmed KoreaMed CrossRef
  39. Kushima, R, M?ller, W, Stolte, M, and Borchard, F (1996). Differential p53 protein expression in stomach adenomas of gastric and intestinal phenotypes: possible sequences of p53 alteration in stomach carcinogenesis. Virchows Arch. 428, 223-7.
    Pubmed
  40. Vieth, M, Kushima, R, Borchard, F, and Stolte, M (2003). Pyloric gland adenoma: a clinicopathological analysis of 90 cases. Virchows Arch. 442, 317-21.
    Pubmed
  41. Islam, RS, Patel, NC, Lam-Himlin, D, and Nguyen, CC (2013). Gastric polyps: a review of clinical, endoscopic, and histopathologic features and management decisions. Gastroenterol Hepatol (N Y). 9, 640-51.
  42. Borch, K, Ahr?n, B, Ahlman, H, Falkmer, S, Gran?rus, G, and Grimelius, L (2005). Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 242, 64-73.
    Pubmed KoreaMed CrossRef
  43. Rorstad, O (2005). Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol. 89, 151-60.
    Pubmed CrossRef
  44. Picus, D, Glazer, HS, Levitt, RG, and Husband, JE (1984). Computed tomography of abdominal carcinoid tumors. AJR Am J Roentgenol. 143, 581-4.
    Pubmed CrossRef
  45. Hurst, RD, and Modlin, IM (1993). Use of radiolabeled somatostatin analogs in the identification and treatment of somatostatin receptor-bearing tumors. Digestion. 54, S88-91.
    CrossRef
  46. Rindi, G, Luinetti, O, Cornaggia, M, Capella, C, and Solcia, E (1993). Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology. 104, 994-1006.
    Pubmed CrossRef
  47. Hirschowitz, BI, Griffith, J, Pellegrin, D, and Cummings, OW (1992). Rapid regression of enterochromaffinlike cell gastric carcinoids in pernicious anemia after antrectomy. Gastroenterology. 102, 1409-18.
    Pubmed CrossRef
  48. Moertel, CG, Johnson, CM, McKusick, MA, Martin, JK, Nagorney, DM, and Kvols, LK (1994). The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med. 120, 302-9.
    Pubmed CrossRef
  49. Kvols, LK, and Buck, M (1987). Chemotherapy of metastatic carcinoid and islet cell tumors: a review. Am J Med. 82, 77-83.
    Pubmed CrossRef
  50. Sah, BK, Zhu, ZG, Chen, MM, Yan, M, Yin, HR, and Zhen, LY (2008). Gastric cancer surgery and its hazards: post operative infection is the most important complication. Hepatogastroenterology. 55, 2259-63.
  51. Yu, J, Yang, D, Wei, F, Sui, Y, Li, H, and Shao, F (2008). The staging system of metastatic lymph node ratio in gastric cancer. Hepatogastroenterology. 55, 2287-90.
  52. Ferri, LE, Onerheim, R, and Emond, C (1999). Linitis plastica as the first indication of metastatic lobular carcinoma of the breast: case report and literature review. Can J Surg. 42, 466-9.
    Pubmed KoreaMed
  53. Jafferbhoy, S, Shiwani, H, and Rustum, Q (2013). Managing gastric linitis plastica: keep the scalpel sheathed. Sultan Qaboos Univ Med J. 13, 451-3.
    Pubmed KoreaMed CrossRef
  54. Mastoraki, A, Papanikolaou, IS, Sakorafas, G, and Safioleas, M (2009). Facing the challenge of managing linitis plastica: review of the literature. Hepatogastroenterology. 56, 1773-8.
  55. Herrmann, K, Ott, K, Buck, AK, Lordick, F, Wilhelm, D, and Souvatzoglou, M (2007). Imaging gastric cancer with PET and the radiotracers 18F-FLT and 18F-FDG: a comparative analysis. J Nucl Med. 48, 1945-50.
    Pubmed CrossRef
  56. Shimada, H, Okazumi, S, Koyama, M, and Murakami, K (2011). Japanese Gastric Cancer Association Task Force for Research Promotion: clinical utility of 18F-fluoro-2-deoxyglucose positron emission tomography in gastric cancer. A systematic review of the literature. Gastric Cancer. 14, 13-21.
    Pubmed CrossRef
  57. Salaun, PY, Grewal, RK, Dodamane, I, Yeung, HW, Larson, SM, and Strauss, HW (2005). An analysis of the 18F-FDG uptake pattern in the stomach. J Nucl Med. 46, 48-51.
    Pubmed
  58. Park, JC, Lee, YC, Kim, JH, Kim, YJ, Lee, SK, and Hyung, WJ (2009). Clinicopathological aspects and prognostic value with respect to age: an analysis of 3,362 consecutive gastric cancer patients. J Surg Oncol. 99, 395-401.
    Pubmed CrossRef
  59. Webb, A, and Cunningham, D (1996). Curing gastric cancer: hone the scalpel with magic?. Br J Cancer. 73, 418-9.
    Pubmed KoreaMed CrossRef
  60. de Vries, AC, and Kuipers, EJ (2007). Epidemiology of premalignant gastric lesions: implications for the development of screening and surveillance strategies. Helicobacter. 12, S22-31.
    CrossRef
  61. Correa, P (1992). Human gastric carcinogenesis: a multistep and multifactorial process: First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 52, 6735-40.
    Pubmed
  62. Wu, X, Chen, VW, Andrews, PA, Ruiz, B, and Correa, P (2007). Incidence of esophageal and gastric cancers among Hispanics, non-Hispanic whites and non-Hispanic blacks in the United States: subsite and histology differences. Cancer Causes Control. 18, 585-93.
    Pubmed CrossRef
  63. Kneller, RW, You, WC, Chang, YS, Liu, WD, Zhang, L, and Zhao, L (1992). Cigarette smoking and other risk factors for progression of precancerous stomach lesions. J Natl Cancer Inst. 84, 1261-6.
    Pubmed CrossRef
  64. Matsukura, N, Suzuki, K, Kawachi, T, Aoyagi, M, Sugimura, T, and Kitaoka, H (1980). Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas. J Natl Cancer Inst. 65, 231-40.
    Pubmed
  65. Filipe, MI, Mu?oz, N, Matko, I, Kato, I, Pompe-Kirn, V, and Jutersek, A (1994). Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer. 57, 324-9.
    Pubmed CrossRef
  66. Samloff, IM, Varis, K, Ihamaki, T, Siurala, M, and Rotter, JI (1982). Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology. 83, 204-9.
    Pubmed
  67. Miki, K (2006). Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer. 9, 245-53.
    CrossRef
  68. Miki, K, and Urita, Y (2007). Using serum pepsinogens wisely in a clinical practice. J Dig Dis. 8, 8-14.
    Pubmed CrossRef
  69. Bravo, JC, and Correa, P (1999). Sulphomucins favour adhesion of Helicobacter pylori to metaplastic gastric mucosa. J Clin Pathol. 52, 137-40.
    Pubmed KoreaMed CrossRef
  70. Leung, WK, Lin, SR, Ching, JY, To, KF, Ng, EK, and Chan, FK (2004). Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication. Gut. 53, 1244-9.
    Pubmed KoreaMed CrossRef
  71. de Vries, AC, Kuipers, EJ, and Rauws, EA (2009). Helicobacter pylori eradication and gastric cancer: when is the horse out of the barn?. Am J Gastroenterol. 104, 1342-5.
    Pubmed CrossRef
  72. Ba-Ssalamah, A, Prokop, M, Uffmann, M, Pokieser, P, Teleky, B, and Lechner, G (2003). Dedicated multidetector CT of the stomach: spectrum of diseases. Radiographics. 23, 625-44.
    Pubmed CrossRef
  73. Prokop, M (2003). Multislice CT: technical principles and future trends. Eur Radiol. 13, M3-13.
    CrossRef
  74. D’Elia, F, Zingarelli, A, Palli, D, and Grani, M (2000). Hydro-dynamic CT preoperative staging of gastric cancer: correlation with pathological findings. A prospective study of 107 cases. Eur Radiol. 10, 1877-85.
    CrossRef
  75. Kim, HJ, Kim, AY, Oh, ST, Kim, JS, Kim, KW, and Kim, PN (2005). Gastric ancer staging at multi-detector row CT gastrography: comparison of transverse and volumetric CT scanning. Radiology. 236, 879-85.
    Pubmed CrossRef
  76. Kwee, RM, and Kwee, TC (2007). Imaging in local staging of gastric cancer: a systematic review. J Clin Oncol. 25, 2107-16.
    Pubmed CrossRef
  77. Binstock, AJ, Johnson, CD, Stephens, DH, Lloyd, RV, and Fletcher, JG (2001). Carcinoid tumors of the stomach: a clinical and radiographic study. AJR Am J Roentgenol. 176, 947-51.
    Pubmed CrossRef
  78. Jang, KM, Kim, SH, Lee, SJ, Lee, MW, Choi, D, and Kim, KM (2014). Upper abdominal gadoxetic acid-enhanced and diffusion-weighted MRI for the detection of gastric cancer: comparison with two-dimensional multidetector row CT. Clin Radiol. 69, 827-35.
    Pubmed CrossRef
  79. Kim, IY, Kim, SW, Shin, HC, Lee, MS, Jeong, DJ, and Kim, CJ (2009). MRI of gastric carcinoma: results of T and N-staging in an in vitro study. World J Gastroenterol. 15, 3992-8.
    Pubmed KoreaMed CrossRef
  80. Halvorsen, RA, and Thompson, WM (1991). Primary neoplasms of the hollow organs of the gastrointestinal tract. Staging and follow-up. Cancer. 67, S1181-8.
    CrossRef
  81. Campeau, NG, Johnson, CD, Felmlee, JP, Rydberg, JN, Butts, RK, and Ehman, RL (1995). MR imaging of the abdomen with a phased-array multicoil: prospective clinical evaluation. Radiology. 195, 769-76.
    Pubmed CrossRef
  82. Dromain, C, de Baere, T, Lumbroso, J, Caillet, H, Laplanche, A, and Boige, V (2005). Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol. 23, 70-8.
    CrossRef
  83. Kayani, I, Bomanji, JB, Groves, A, Conway, G, Gacinovic, S, and Win, T (2008). Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOT-ATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer. 112, 2447-55.
    Pubmed CrossRef
  84. Binderup, T, Knigge, U, Loft, A, Mortensen, J, Pfeifer, A, and Federspiel, B (2010). Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med. 51, 704-12.
    Pubmed CrossRef
  85. Minamimoto, R, Senda, M, Jinnouchi, S, Terauchi, T, Yoshida, T, and Inoue, T (2014). Performance profile of a FDG-PET cancer screening program for detecting gastric cancer: results from a nationwide Japanese survey. Jpn J Radiol. 32, 253-9.
    Pubmed CrossRef
  86. Templeton, A, and Hwang, JH (2013). Confocal microscopy in the esophagus and stomach. Clin Endosc. 46, 445-9.
    Pubmed KoreaMed CrossRef
  87. Bok, GH, Jeon, SR, Cho, JY, Cho, JH, Lee, WC, and Jin, SY (2013). The accuracy of probe-based confocal endomicroscopy versus conventional endoscopic biopsies for the diagnosis of superficial gastric neoplasia (with videos). Gastrointest Endosc. 77, 899-908.
    Pubmed CrossRef
  88. Li, WB, Zuo, XL, Li, CQ, Zuo, F, Gu, XM, and Yu, T (2011). Diagnostic value of confocal laser endomicroscopy for gastric superficial cancerous lesions. Gut. 60, 299-306.
    Pubmed CrossRef
  89. Horiuchi, H, Kaise, M, Inomata, H, Yoshida, Y, Kato, M, and Toyoizumi, H (2013). Magnifying endoscopy combined with narrow band imaging may help to predict neoplasia coexisting with gastric hyperplastic polyps. Scand J Gastroenterol. 48, 626-32.
    Pubmed CrossRef
  90. Fujiwara, S, Yao, K, Nagahama, T, Uchita, K, Kanemitsu, T, and Tsurumi, K (2015). Can we accurately diagnose minute gastric cancers (≤5 mm)? Chromoendoscopy (CE) vs magnifying endoscopy with narrow band imaging (M-NBI). Gastric Cancer. 18, 590-6.
    CrossRef
  91. Sakai, Y, Eto, R, Kasanuki, J, Kondo, F, Kato, K, and Arai, M (2008). Chromoendoscopy with indigo carmine dye added to acetic acid in the diagnosis of gastric neoplasia: a prospective comparative study. Gastrointest Endosc. 68, 635-41.
    Pubmed CrossRef
  92. Kawahara, Y, Takenaka, R, Okada, H, Kawano, S, Inoue, M, and Tsuzuki, T (2009). Novel chromoendoscopic method using an acetic acid-indigocarmine mixture for diagnostic accuracy in delineating the margin of early gastric cancers. Dig Endosc. 21, 14-9.
    Pubmed CrossRef
  93. Mouri, R, Yoshida, S, Tanaka, S, Oka, S, Yoshihara, M, and Chayama, K (2009). Evaluation and validation of computed virtual chromoendoscopy in early gastric cancer. Gastrointest Endosc. 69, 1052-8.
    Pubmed CrossRef
  94. Ueyama, H, Matsumoto, K, Nagahara, A, Gushima, R, Hayashi, T, and Yao, T (2013). A white opaque substance-positive gastric hyperplastic polyp with dysplasia. World J Gastroenterol. 19, 4262-6.
    Pubmed KoreaMed CrossRef
  95. Hattori, T (1985). Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of the stomach. J Clin Pathol. 38, 622-30.
    Pubmed KoreaMed CrossRef
  96. Rosen, S, and Hoak, D (1993). Intramucosal carcinoma developing in a hyperplastic gastric polyp. Gastrointest Endosc. 39, 830-3.
    Pubmed CrossRef
  97. Ginsberg, GG, Al-Kawas, FH, Fleischer, DE, Reilly, HF, and Benjamin, SB (1996). Gastric polyps: relationship of size and histology to cancer risk. Am J Gastroenterol. 91, 714-7.
    Pubmed
  98. Capelle, LG, de Vries, AC, Haringsma, J, Ter Borg, F, de Vries, RA, and Bruno, MJ (2010). The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 71, 1150-8.
    Pubmed CrossRef
  99. Lax?n, F, Sipponen, P, Iham?ki, T, Hakkiluoto, A, and Dortscheva, Z (1982). Gastric polyps; their morphological and endoscopical characteristics and relation to gastric carcinoma. Acta Pathol Microbiol Immunol Scand A. 90, 221-8.
    Pubmed
  100. Nakamura, S, Iida, M, Yao, T, and Fujishima, M (1991). Endoscopic features of gastric carcinoids. Gastrointest Endosc. 37, 535-8.
    Pubmed CrossRef
  101. Davies, MG, O’Dowd, G, McEntee, GP, and Hennessy, TP (1990). Primary gastric carcinoids: a view on management. Br J Surg. 77, 1013-4.
    Pubmed CrossRef
  102. Rokkas, T, Filipe, MI, and Sladen, GE (1991). Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up. Gut. 32, 1110-3.
    Pubmed KoreaMed CrossRef
  103. Rugge, M, Correa, P, Di Mario, F, El-Omar, E, Fiocca, R, and Geboes, K (2008). OLGA staging for gastritis: a tutorial. Dig Liver Dis. 40, 650-8.
    Pubmed CrossRef
  104. Białek, A, Wiechowska-Kozłowska, A, Pertkiewicz, J, Polkowski, M, Milkiewicz, P, and Karpi?ska, K (2012). Endoscopic submucosal dissection for treatment of gastric subepithelial tumors (with video). Gastrointest Endosc. 75, 276-86.
    CrossRef
  105. R?sch, T (1995). Endoscopic ultrasonography in upper gastrointestinal submucosal tumors: a literature review. Gastrointest Endosc Clin N Am. 5, 609-14.
    Pubmed
  106. Palazzo, L, Landi, B, Cellier, C, Cuillerier, E, Roseau, G, and Barbier, JP (2000). Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours. Gut. 46, 88-92.
    CrossRef
  107. Arg?ello, L, Pellis?, M, and Miquel, R (2002). Utility of echoendoscopy in the evaluation of submucosal tumors and extrinsic compressions of the digestive tract. Gastroenterol Hepatol. 25, 13-8.
  108. Menon, L, and Buscaglia, JM (2014). Endoscopic approach to subepithelial lesions. Therap Adv Gastroenterol. 7, 123-30.
    Pubmed KoreaMed CrossRef
  109. Ruszniewski, P, Delle Fave, G, Cadiot, G, Komminoth, P, Chung, D, and Kos-Kudla, B (2006). Well-differentiated gastric tumors/carcinomas. Neuroendocrinology. 84, 158-64.
    CrossRef
  110. Soga, J (2005). Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 103, 1587-95.
    Pubmed CrossRef
  111. Hosokawa, O, Kaizaki, Y, Hattori, M, Douden, K, Hayashi, H, and Morishita, M (2005). Long-term follow up of patients with multiple gastric carcinoids associated with type A gastritis. Gastric Cancer. 8, 42-6.
    Pubmed CrossRef
  112. Dakin, GF, Warner, RR, Pomp, A, Salky, B, and Inabnet, WB (2006). Presentation, treatment, and outcome of type 1 gastric carcinoid tumors. J Surg Oncol. 93, 368-72.
    Pubmed CrossRef
  113. W?ngberg, B, Grimelius, L, Gran?rus, G, Conradi, N, Jansson, S, and Ahlman, H (1990). The role of gastric resection in the management of multicentric argyrophil gastric carcinoids. Surgery. 108, 851-7.
    Pubmed
  114. Mart?nez-Ares, D, Souto-Ruzo, J, Varas Lorenzo, MJ, Espin?s P?rez, JC, Y??ez L?pez, J, and Abad Belando, R (2004). Endoscopic ultrasound-assisted endoscopic resection of carcinoid tumors of the gastrointestinal tract. Rev Esp Enferm Dig. 96, 847-55.
    CrossRef
  115. Tsujitani, S, Oka, S, Saito, H, Kondo, A, Ikeguchi, M, and Maeta, M (1999). Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis. Surgery. 125, 148-54.
    Pubmed CrossRef
  116. (2003). The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 58, S3-43.
    Pubmed CrossRef
  117. Kudo, S, Rubio, CA, Teixeira, CR, Kashida, H, and Kogure, E (2001). Pit pattern in colorectal neoplasia: endoscopic magnifying view. Endoscopy. 33, 367-73.
    Pubmed CrossRef
  118. Hurlstone, DP, Cross, SS, Adam, I, Shorthouse, AJ, Brown, S, and Sanders, DS (2004). Endoscopic morphological anticipation of submucosal invasion in flat and depressed colorectal lesions: clinical implications and subtype analysis of the kudo type V pit pattern using high-magnification-chromoscopic colonoscopy. Colorectal Dis. 6, 369-75.
    Pubmed CrossRef
  119. Saito, Y, Fukuzawa, M, Matsuda, T, Fukunaga, S, Sakamoto, T, and Uraoka, T (2010). Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection. Surg Endosc. 24, 343-52.
    CrossRef
  120. Catalano, F, Trecca, A, Rodella, L, Lombardo, F, Tomezzoli, A, and Battista, S (2009). The modern treatment of early gastric cancer: our experience in an Italian cohort. Surg Endosc. 23, 1581-6.
    Pubmed CrossRef
  121. Ichikawa, J, Tanabe, S, Koizumi, W, Kida, Y, Imaizumi, H, and Kida, M (2003). Endoscopic mucosal resection in the management of gastric carcinoid tumors. Endoscopy. 35, 203-6.
    Pubmed CrossRef
  122. Rugge, M, Farinati, F, Baffa, R, Sonego, F, Di Mario, F, Leandro, G, and Interdisciplinary Group on Gastric Epithelial Dysplasia (1994). Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Gastroenterology. 107, 1288-96.
    Pubmed CrossRef
  123. Rugge, M, Cassaro, M, Di Mario, F, Leo, G, Leandro, G, Russo, VM, and Interdisciplinary Group on Gastric Epithelial Dysplasia (IGGED) (2003). The long term outcome of gastric non-invasive neoplasia. Gut. 52, 1111-6.
    Pubmed KoreaMed CrossRef
  124. Min, BH, Lee, JH, Kim, JJ, Shim, SG, Chang, DK, and Kim, YH (2009). Clinical outcomes of endoscopic submucosal dissection (ESD) for treating early gastric cancer: comparison with endoscopic mucosal resection after circumferential precutting (EMR-P). Dig Liver Dis. 41, 201-9.
    CrossRef
  125. Kim, SY, Sung, JK, Moon, HS, Kim, KS, Jung, IS, and Yoon, BY (2012). Is endoscopic mucosal resection a sufficient treatment for low-grade gastric epithelial dysplasia. Gut Liver. 6, 446-51.
    Pubmed KoreaMed CrossRef
  126. Oda, I, Suzuki, H, Nonaka, S, and Yoshinaga, S (2013). Complications of gastric endoscopic submucosal dissection. Dig Endosc. 25, S71-8.
    CrossRef
  127. Minami, S, Gotoda, T, Ono, H, Oda, I, and Hamanaka, H (2006). Complete endoscopic closure of gastric perforation induced by endoscopic resection of early gastric cancer using endoclips can prevent surgery (with video). Gastrointest Endosc. 63, 596-601.
    Pubmed CrossRef
  128. Takizawa, K, Oda, I, Gotoda, T, Yokoi, C, Matsuda, T, and Saito, Y (2008). Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection--an analysis of risk factors. Endoscopy. 40, 179-83.
    Pubmed CrossRef


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