Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda.

Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa injury due to operations, biopsy or polypectomy, chronic active and atrophic gastritis may also lead to the development of GCPs. By carefully examining the stomach and taking biopsy samples from the susceptible regions, the stage of atrophy can be determined. Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation. GCPs frequently occur close to early gastric cancers (EGCs) or EGC can arise from the cystic glands. Endoscopic resection is an effective and minimally invasive treatment in GCP.

Factors affecting survival in operated gastric cancer.

In this study, our aim was to determine the possible effects of Helicobacter pylori(HP), chronic atrophic gastritis (CAG), and gastrointestinal metaplasia (GIM) on survival in operated bowel type gastric cancer patients (INT-GC). Among 548 patients, 347(63.3%) were male. The median age was 57 years. Disease-free survival (DFS) and overall survival (OS) were significantly shorter in patients with GIM than those in patients without GIM (log rank, P = 0.003 and log rank P = 0.003, respectively). Multivariate analysis showed that presence of GIM (HR, 2.1) was found to be an independent factor of worse DFS. In our study, stage pIII patients with GIM had significantly shorter DFS and OS than those without GIM (log rank p = 0.008 and log rank p = 0.001, respectively). However, in subgroup analysis of patients with GIM, there was no significant DFS and OS difference between patients with stage pI and pII disease (log rank p = 0.999, log rank p = 0.184 vs. log rank p = 0.409, log rank p = 0.281, respectively).

Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin.

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.

[Gastric neuroendocrine tumors]. / Neiroéndokrinnye opukholi zheludka.

Gastrointestinal neuroendocrine tumors are rare neoplasms. Currently, incidence of gastric neuroendocrine tumors (gNETs) is being significantly increased. There are 3 groups of gNETs: types I, II and III. Each type has important features regarding clinical picture, prognosis and treatment strategy. Type I is the most common (70-80%) and associated with chronic atrophic gastritis including autoimmune gastritis and Helicobacter associated atrophic gastritis. Type II (5-6%) is associated with multiple endocrine neoplasia type I and Zollinger-Ellison syndrome (MEN I - ZES). Both types are characterized by hypergastrinemia and small tumor dimension. These neoplasms are multiple and mostly benign. On the contrary, NETs type III (10-15%) is not associated with hypergastrinemia and represented by single large neoplasms. Tumors are malignant as a rule. Therefore, surgical resection and chemotherapy are preferred for these tumors. Endoscopic surgery followed by observation is acceptable for almost all NETS type I and II. At the same time, this approach is advisable only for small and highly differentiated neoplasms type III.

British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma.

Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer-in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.

The pathological findings seen in laparoscopic sleeve gastrectomies for weight loss.

Sleeve gastrectomy specimens are increasingly common surgical specimens received for examination following bariatric surgery for weight loss. The spectrum of pathological changes seen in these cases is not well documented. Retrospective examination was undertaken of 1463 consecutive sleeve gastrectomy specimens received at Envoi Specialist Pathologists. Most cases showed no pathological changes (80.2%). The most common changes seen were non-specific, non-Helicobacter associated chronic gastritis (7.2%), Helicobacter associated gastritis (6.8%) and benign fundic gland polyps (4.0%). Other, rarer changes were lymphocytic gastritis, autoimmune atrophic gastritis, chronic gastritis with intestinal metaplasia, hyperplastic polyps, pancreatic heterotopia, gastrointestinal stromal tumours (GISTs) and a leiomyoma. A wide range of pathological changes are seen in resection specimens following sleeve gastrectomies for weight loss. Many cases will require further treatment or ongoing investigation and surveillance.

Management and clinical outcomes of type I gastric carcinoid patients: retrospective, multicenter study in Japan.

BACKGROUND AND AIM: Type I gastric carcinoids (TIGC) are associated with chronic atrophic gastritis (CAG) with hypergastrinemia and hyperplasia of enterochromaffin-like cells. Several treatment options are currently available for these tumors including total gastrectomy, partial resection, antrectomy, endoscopic resection and endoscopic surveillance. The present study evaluated different treatment approaches and clinical outcomes of patients with TIGC in Japan. METHODS: Between 1991 and 2011, 82 patients with TIGC were identified at multicenter institutions in Japan. Patient demographics, tumor size, depth of invasion, vessel involvement, treatment approach, Helicobacter pylori infection, serum gastrin level, recurrence-free survival (RFS) and disease-specific survival (DSS) were analyzed. RESULTS: Median age of all patients at the time of diagnosis was 56 years (range, 24-79 years). There were 44 males and 38 females. Patients underwent endoscopic surveillance (n=25), endoscopic resection (n=41) or surgical resection (n=16). Intramucosal invasion was found in 19 patients, submucosal invasion in 44 patients and muscularis propria invasion in one patient. Tumor diameter was ≤ 10 mm in 71 patients, 11-20mm in five patients and ≥ 21 mm in five patients. None of the patients showed rapidly growing tumors, local recurrence or metastasis. The median (range) follow-up period was 7(0-20) years. RFS was 97.6% and DSS was 100% in all the patients. CONCLUSION: The prognosis of TIGC patients treated by different modalities in Japan is favorable regardless of the generational change of management for TIGC.

Multifocal gastric cancer with a variety of histological findings coexisting with hyperplastic polyps: report of a case.

We report a case of multifocal gastric cancer with a variety of macroscopic and histological findings. A 65-year-old woman was admitted with upper abdominal pain. Her familial history was remarkable in that her mother had died of gastric cancer. The hematological and blood biochemical values were normal, but the serum was positive for Helicobacter pylori immunoglobulin G, and the serum pepsinogen test was also positive. Gastrointestinal fiberscopy showed many granulomatous lesions coexisting with pedunculated polypoid lesions and marked atrophic gastritis throughout the stomach. We performed total gastrectomy with regional lymph node dissection. There were four separate cancers and three hyperplastic polyps with entire intestinal metaplasia. The pathological findings of these multifocal gastric cancers varied, with coexisting differentiated and undifferentiated types, and early and advanced types. One of the pedunculated polypoid lesions was accompanied by papillary adenocarcinoma. Although multifocal gastric cancer is not uncommon, the present case is considered an extremely unusual example of gastric cancer.

Review of the pathogenesis, diagnosis, and management of type I gastric carcinoid tumor.

Gastric carcinoid tumors comprise 7% of all gastrointestinal carcinoids and have significantly increased in incidence over the past few decades. Seventy to 80% of gastric carcinoids are type I, which usually are clinically asymptomatic and found incidentally at endoscopic evaluation for abdominal pain or anemia. In this review, advances in understanding the pathophysiology of type I gastric carcinoid are highlighted. In addition, various current diagnostic and treatment options are discussed. Although type I carcinoids generally hold a benign course, rigorous investigation is needed to ensure accurate diagnosis and optimal treatment. This includes appropriate diagnostic procedures and imaging and accurate staging of tumor. Tumor size, depth of invasion, presence of metastasis, and the tumor's gastrin dependency dictate treatment options. Appropriate treatments can consist of endoscopic resection, antrectomy, medical management, or frequent follow-up. This article provides a systematic method of evaluating and treating type I gastric carcinoid.

Gastric lesions in patients with autoimmune metaplastic atrophic gastritis (AMAG) in a tertiary care setting.

Autoimmune metaplastic atrophic gastritis (AMAG) is an early manifestation of pernicious anemia that precedes the hematologic changes by years to decades. It is associated with metaplastic changes and neoplasms, including pyloric gland adenomas (PGAs). We investigated the frequency of PGAs and other lesions in all nonconsultation gastric biopsies and resections (1988 to 2008) diagnosed as AMAG. We further selected cases confirmed as AMAG by immunohistochemical identification of the gastric body (negative gastrin) and linear and nodular enterochromaffin-like cell hyperplasia (chromogranin). From this subset, all polyps and neoplasms were reviewed. We identified a total of 41,245 patients with gastric biopsies or resections from 46.7% males and 53.3% females comprising patients self-identified as 67.0% white, 23.6% African-American, 1.4% Asian, 0.8% non-White Hispanic, and 7.2% other or unknown. AMAG was diagnosed in 461 patients (1.1%), and had the following percentages based on race: 1.1% White, 1.3% African-American, 1.4% Asian, and 2.7% non-White Hispanic. The female:male ratio was 2:1 with an overall median age at presentation of 67.0 years. Of the 461 patients with AMAG, 143 had endoscopically identifiable lesions. These lesions (n=240) consisted of 179 polyps (138 hyperplastic polyps, 20 oxyntic mucosa pseudopolyps, 18 intestinal-type gastric adenomas, and 3 PGAs), 46 well-differentiated neuroendocrine neoplasms (carcinoid), 1 gastrointestinal stromal tumor, 3 lymphomas, and 11 adenocarcinomas. In summary, AMAG occurred with similar frequency across all racial groups. Although PGAs are associated with AMAG, they remain rare in the setting of AMAG.

The establishment and clinical appliance of technique of mucosa marking targeting biopsy.

BACKGROUND/AIMS: Mucosa marking targeting biopsy (MTB) technique has been tested and verified in animal model. For multi-focal atrophic gastritis, random biopsy may miss the point of atrophy, intestinal metaplasia or dysplasia. In order to monitor chronic atrophic gastritis on gastroscopy, get the proper biopsy sample is very important. METHODOLOGY: Fifty-three atrophic gastritis patients were enrolled prospectively in this study. India ink was tattooed at five points of stomach. Endoscopy was repeated at 3, 9, 15 and 24 months. RESULTS: Tattoos (96.2%) produced with 1:10 concertrations were visible with a good to excellent tattoo persistence at 3 months. Only two patients (3.8%) had poor tattoo persistence and were retattooed at 3-months interval. Tattoos did not disappear in patients who repeated for more than two gastroscopies at 24 months or even long. There were no complications related to India ink tattooing including abdominal pain, bleeding or perforation. At follow-up gastroscopy, no ulcers, inflammation, break in the mucosa, or pain was noted. CONCLUSIONS: Clinical use of MTB technique is safe and persistence and may be used as an effective method for longitudinal follow-up in atrophic gastritis and other precancerous lesions.

Combined carcinoid and mixed (composite) glandular - endocrine cell carcinoma of the stomach in atrophic gastritis.

We describe a case of gastric carcinoid and inflammatory fibroid polyp concomitant with a composite tumor of the gastric antrum composed of poorly differentiated adenocarcinoma - endocrine carcinoma with immunohistochemical documentation of endocrine and non endocrine differentiation in a 67-year-old man with atrophic gastritis and intestinal metaplasia. When gastrectomy was carried out, two lymph nodes along the greater curvature harbored metastasis from carcinoid. The same occurrence is reported in several cases in the literature, which suggests that the association of gastric carcinoid to adenocarcinoma could point to the malignant nature of carcinoid. Furthermore, the findings in this patient reinforce the concept that the epithelial and neuroendocrine cells of the gastrointestinal tract both result from multidirectional differentiation of a primitive cell.

Significance of (18)F-2-deoxy-2-fluoro-glucose accumulation in the stomach on positron emission tomography.

OBJECTIVE: To explain the accumulation of (18)F-2-deoxy-2-fluoro-glucose ((18)FDG) on positron emission tomography (PET) in the stomach and differences in its pattern, we focus on the accumulation pattern in association with endoscopic findings of the gastric mucosa and Helicobacter pylori (Hp) infection. METHODS: Of 599 cases undergoing (18)FDG-PET examinations, we retrospectively analyzed the pattern of (18)FDG accumulation in the stomach, findings of upper gastrointestinal endoscopy, and Hp infection. The pattern of (18)FDG accumulation was classified into three groups: localized accumulation only in the fornix (Group A, 32 patients), diffuse accumulation throughout the entire stomach (Group B, 49 patients), and no accumulation (Group C, 191 patients). RESULTS: Regarding the relation between Hp infection and (18)FDG accumulation, Hp infection was positive in 56.3% of Group A, 73.5% of Group B, and 24.1% of Group C, with significant differences (p < 0.001). Regarding the relation between (18)FDG accumulation and gastric mucosal inflammation, when Groups A and B were compared with Group C, nearly half of the cases in the former groups had papular redness with a significantly higher frequency of redness and erosion. Three cases found to have malignant tumor were limited to the former groups. One MALT lymphoma case was also found in the same group. Accumulation of (18)FDG largely corresponded to mucosal inflammation including superficial gastritis and erosive gastritis, and therefore the main cause of non-specific (18)FDG accumulation was considered to be inflammatory mucosa (mainly redness). The accumulation pattern was not associated with atrophic changes of the gastric mucosa or with Hp infection, but with mucosal inflammatory changes, including redness and erosion localized to the fornix. CONCLUSIONS: Accumulation of (18)FDG in the stomach suggests a high probability of the presence of inflammatory change in the gastric mucosa forming a background for the development of cancer or malignant lymphoma, and thus requires further endoscopic examinations.

Multiple early gastric cancer with gastritis cystica profunda showing various histological types.

We report a case of multiple early gastric cancer showing varied histological types associated with gastritis cystica profunda (GCP). A 61-year-old man who had early gastric cancer associated with GCP underwent a distal gastrectomy with lymphadenectomy. Histological examination showed various histological types of cancer -well differentiated, moderately differentiated, poorly differentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma- that had developed independently in the mucosal and submucosal layers of the resected specimen. Furthermore, multiple cysts with a single layer of columnar epithelium were present in the submucosa around the cancerous lesions. However, no neoplastic changes were found in those epithelial cells. Helicobacter pylori was detected in the residual stomach 3 months after surgery. Although the mechanism of the relationship between gastric carcinoma and GCPs is obscure, we speculate that repeated erosion and regeneration induced by chronic inflammation causes multicentric carcinogenesis as well as an aberration of the gastric glands. GCPs may be a risk factor for multiple gastric cancer.

Multiple gastric carcinoids associated with parietal cell hyperplasia: intraoperative detection with a radiolabeled somatostatin analog.

We describe a 30-year-old man in whom upper endoscopy revealed multiple gastric carcinoids. The peripheral blood gastrin level was 2400 ng/ml (normal range, <200 ng/ml). Mucosal biopsy of the gastric body and fundus showed no atrophy; typical type A chronic atrophic gastritis was thus unlikely. Neither abdominal computed tomography nor selective angiography showed any evidence of tumor in the pancreas or at its periphery. However, the possibility of microgastrinoma could not be ruled out. We performed radioguided surgery with a somatostatin analog, diethylenetriamine pentaacetic acid-D-Phe1-octreotide labeled with (111)In (Octreo Scan). The location of the carcinoids was confirmed. Gastrinoma was ruled out. Total gastrectomy was performed, and the gastrin level decreased to the normal range. Macroscopically, 20 carcinoid tumors, measuring 30 mm in maximum diameter, were confirmed. Microscopic examination showed large numbers of endocrine cell micronests. Hyperplasia of parietal cells was observed, suggesting early-stage type A chronic atrophic gastritis. The antrum contained increased numbers of gastrin-positive cells, which probably caused the preoperative hypergastrinemia.