Gastric dysplastic lesions in Helicobacter pylori-naïve stomach: Foveolar-type adenoma and intestinal-type dysplasia.

Reports of Helicobacter pylori (Hp)-naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp-naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar-type gastric adenoma (FGA) and intestinal-type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA-RA). The flat type is a large, whitish flatly elevated lesion while FGA-RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA-RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single-nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow-growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis-like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.

Association between low-dose aspirin and the risk of gastric cancer and adenoma according to a family history of gastric cancer.

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65-0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69-0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86-0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90-1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC.

Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Risk of gastric adenoma and adenocarcinoma in patients with familial adenomatous polyposis in Japan: a nationwide multicenter study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) have an increased risk of developing gastric neoplasms. However, the clinical course of FAP with these gastric lesions has not yet been fully clarified. The present study aimed to clarify the changes in the incidence risk of developing gastric adenoma or gastric cancer during the lifespan of patients with FAP. METHODS: Four hundred forty-three patients with data regarding gastric adenoma and gastric cancer retrospectively registered in a nationwide Japanese multicenter study were enrolled. The cumulative incidences and hazard rates (HRs) of gastric neoplasms were evaluated. RESULTS: The cumulative incidence rates in 50-year-old patients with FAP were 22.8% for gastric adenoma and 7.6% for gastric cancer, respectively. No significant association was found between gastric neoplasms and the colonic phenotype. The peak age for the HR of gastric adenoma was 65 years, with the highest HR (0.043). Regarding the incidence of gastric cancer, the HR increased moderately up to the age of 40 years, but the increase accelerated from the age of 50 years (HR = 0.0067). CONCLUSION: Careful surveillance of the upper gastrointestinal tract in elderly patients with FAP, such as shortening the interval of follow-up according to age, may be helpful for early diagnosis of gastric cancer.

Endoscopic differential diagnosis between foveolar-type gastric adenoma and gastric hyperplastic polyps in Helicobacter pylori-naïve patients.

BACKGROUND: Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. METHODS: We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. RESULTS: FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. CONCLUSIONS: Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.

Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer?

Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.

Clinical features of gastric adenoma detected within 3 years after negative screening endoscopy in Korea.

Background: Early detection and management of gastric adenoma are important for preventing gastric cancer. The present study aimed to evaluate the predictors of missed gastric adenoma on screening endoscopy in Korea and identify the risk factors associated with interval precancerous gastric lesions. Methods: All cases of gastric adenomas diagnosed via screening endoscopy between 2007 and 2019 were reviewed. Among them, those who had undergone endoscopy within 3 years were included in the present study. Missed gastric adenoma was defined as gastric adenoma diagnosed within 3 years after negative screening endoscopy. Results: In total, 295 cases of gastric adenoma were identified. Of these, 95 (32.2%) were missed gastric adenoma cases (mean age, 60.6 years; average interval between final and index endoscopies, 12.6 months); the remaining 200 (67.8%) were newly detected adenoma cases. Univariate analysis revealed that male sex, endoscopist experience, observation time, and presence of gastric intestinal metaplasia (pathologically proven) were associated with missed gastric adenoma. Multivariate analysis revealed that gastric intestinal metaplasia (odds ratio [OR], 2.736; 95% confidence interval [CI], 1.320-5.667; P = 0.007) and shorter observation time of the index screening endoscopy (B, -0.011; OR, 0.990; 95% CI, 0.986-0.993; P < 0.001) were independent risk factors for missed gastric adenoma. The optimal cut-off for the observation time for detecting gastric adenoma was 3.53 minutes (area under curve, 0.738; 95% CI, 0.677-0.799; P < 0.001). Conclusions: Gastric intestinal metaplasia is an indication of missed gastric adenoma. Therefore, careful inspection of gastric mucosa with gastric intestinal metaplasia and proper observation time can lower the possibility of missing the gastric adenoma during screening.

Mutual association between family history of gastric and colorectal cancer and risk of gastric and colorectal cancer.

BACKGROUND AND AIM: We evaluated the associations between gastric cancer (GC) family history (FH) and colorectal cancer (CRC) risk and between CRC FH and GC/gastric adenoma risk. METHODS: We used data of participants who underwent national cancer screening between 2013 and 2014. Participants with GC or CRC FH in first-degree relatives (n = 1 172 750) and those without cancer FH (n = 3 518 250) were matched 1:3 by age and gender. RESULTS: Of the 1 172 750 participants with a FH, 871 104, 264 040, and 37 606 had FHs of only GC, only CRC, and both GC and CRC, respectively. The median follow-up time was 4.8 years. GC and CRC FHs were associated with increased GC and CRC risks, respectively. GC FH was associated with CRC risk (adjusted hazard ratio 1.05; 95% confidence interval [CI] 1.01-1.10), whereas CRC FH was not associated with the risk of GC or gastric adenoma. However, gastric adenoma risk increased 1.62-fold (95% CI 1.40-1.87) in participants with FHs of both GC and CRC, demonstrating a significant difference with the 1.39-fold (95% CI 1.34-1.44) increase in participants with only GC FH. Furthermore, GC risk increased by 5.32 times (95% CI 1.74-16.24) in participants with FHs of both GC and CRC in both parents and siblings. CONCLUSIONS: GC FH was significantly associated with a 5% increase in CRC risk. Although CRC FH did not increase GC risk, FH of both GC and CRC further increased the risk of gastric adenoma. FHs of GC and CRC may affect each other's neoplastic lesion risk.

Effect of Helicobacter pylori Eradication Treatment on Metachronous Gastric Neoplasm Prevention Following Endoscopic Submucosal Dissection for Gastric Adenoma.

The long-term effect of Helicobacter pylori eradication on metachronous gastric neoplasm prevention after endoscopic submucosal dissection (ESD) of gastric adenoma is unclear. This study included patients with confirmed H. pylori infection after ESD with curative resection for gastric adenoma. Patients were divided based on the success of H. pylori eradication treatment into two groups: eradication and non-eradication. Patients with any newly detected lesion within 1 year after ESD and recurrence at the ESD site were excluded from the analysis. Further, 1:1 propensity score matching was also performed to eliminate baseline differences between the two groups. H. pylori eradication treatment was administered to 673 patients after ESD (163 in the successful eradication group and 510 in the non-eradication group). During the median follow-up periods of 25 and 39 months in the eradication and non-eradication groups, metachronous gastric neoplasm was identified in 6 (3.7%) and 22 patients (4.3%), respectively. Adjusted Cox analysis revealed that H. pylori eradication was not associated with increased risk of metachronous gastric neoplasm after ESD. Kaplan-Meier analysis in the matched population yielded similar findings (p = 0.546). H. pylori eradication treatment was not associated with metachronous gastric neoplasm after ESD with curative resection for gastric adenoma.

Photodynamic Diagnosis for the Identification of Intestinal-Type Gastric Cancers and High-Grade Adenomas.

Gastric cancer is the second most common cancer in Japan. The incidence of gastric cancer remains high owing to the increase in the elderly population. Endoscopy outperforms radiography in identifying early gastric cancer (EGC). Furthermore, image-enhanced endoscopy (IEE) has been developed and implemented worldwide in clinical practice. Magnifying IEE images can help to visualize the microvascular pattern and microstructure architecture, which is used for the characterization of EGC. However, accurate endoscopic diagnosis requires the experience and skill of endoscopists, making an objective and simple diagnostic method desirable. In this retrospective study, we investigated the diagnostic yield of 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) for identifying gastric cancers and high-grade adenomas. In total, 52 lesions from 43 patients were ultimately included in the study. We detected 5-ALA-mediated protoporphyrin IX fluorescence in 45 of the 52 lesions that were initially intended for PDD, resulting in a detection rate of 86.5%, whereas each signet ring cell carcinoma was negative using 5-ALA PDD. In eight of the patients with multiple lesions, 17 lesions were identified using 5-ALA PDD. Again, we took biopsies from six areas that we suspected as new lesions. While 4 lesions were gastric neoplasms resected by endoscopic submucosal dissection, two other lesions were normal. Preoperative 5-ALA-PDD could provide additional diagnostic yields to detect such multiple lesions simultaneously. No severe adverse events were observed. Prospective multicenter studies are warranted to confirm the usefulness of 5-ALA PDD for EGC identification.

Prevalence and endoscopic treatment outcomes of upper gastrointestinal neoplasms in familial adenomatous polyposis.

BACKGROUND: Although upper gastrointestinal (GI) neoplasms are not rare in patients with familial adenomatous polyposis (FAP), few studies have focused on them and the long-term outcomes of their treatment by endoscopy. Therefore, we aimed to investigate the prevalence and endoscopic treatment outcomes of upper GI neoplasms in patients with FAP. METHODS: Among 215 patients diagnosed with FAP between January 1991 and December 2019, 208 who underwent esophagogastroduodenoscopy were eligible. The clinical features and endoscopic treatment outcomes of upper GI neoplasms were retrospectively investigated and analyzed. RESULTS: Among the enrolled patients, 113 (54.3%) had one or more upper GI neoplasms: gastric adenoma (n = 34), gastric cancer (n = 7), nonampullary duodenal adenoma (n = 86), and ampullary adenoma (n = 53). Among patients with gastric neoplasms (n = 37), 24 (64.9%) underwent treatment (endoscopic treatment: 22, surgery: 2). No tumor-related mortality occurred during median follow-up of 106 months (interquartile range [IQR] 63-174). Endoscopic treatment was performed in 47 (54.7%) of 86 patients with nonampullary duodenal adenoma and in 32 (60.4%) of 53 patients with ampullary adenoma. No patient underwent surgery for duodenal neoplasms, and no tumor-related mortality occurred during median follow-up of 88 months (IQR 42-145). The proportion of patients with increased Spigelman stage at 2 years after the initial diagnosis or treatment was significantly higher in untreated group than in the group treated for duodenal neoplasms (27.3% vs. 0.0%, p = 0.001). CONCLUSION: Endoscopic surveillance in FAP patients is important for the detection and treatment of upper GI neoplasms in early stage. In particular, endoscopic therapy for duodenal neoplasms can reduce the severity of duodenal polyposis.

Confusion and prospects for carcinogenesis of gastric adenoma and dysplasia: What is the correct answer currently?

There are differences in the diagnoses of superficial gastric lesions between Japan and other countries. In Japan, superficial gastric lesions are classified as adenoma or cancer. Conversely, outside Japan, the same lesion is classified as low-grade dysplasia (LGD), high-grade dysplasia, or invasive neoplasia. Gastric carcinogenesis occurs mostly de novo, and the adenoma-carcinoma sequence does not appear to be the main pathway of carcinogenesis. Superficial gastric tumors can be roughly divided into the APC mutation type and the TP53 mutation type, which are mutually exclusive. APC-type tumors have low malignancy and develop into LGD, whereas TP53-type tumors have high malignancy and are considered cancerous even if small. For lesions diagnosed as category 3 or 4 in the Vienna classification, it is desirable to perform complete en bloc resection by endoscopic submucosal dissection followed by staging. If there is lymphovascular or submucosal invasion after mucosal resection, additional surgical treatment of gastrectomy with lymph node dissection is required. In such cases, function-preserving curative gastrectomy guided by sentinel lymph node biopsy may be a good alternative.

Differences in Somatic Mutation Profiles between Korean Gastric Cancer and Gastric Adenoma Patients.

BACKGROUND: We aimed to investigate molecular factors potentially related to the progression of gastric adenoma (GA) to gastric cancer (GC) and compare the mutation characteristics between GC and GA. METHODS: We conducted custom gene panel sequencing for 135 GC-related genes and estimated the difference in somatic mutation profiles between 20 GC and 20 GA cases. RESULTS: A total of 31 somatic mutations, including 22 missense, 3 nonsense, and 6 frameshift mutations, were detected in 17 samples. We estimated an average of 1.8 mutations per sample (range, 1 to 3 mutations), with 12 in GC and 5 in GA. GC tended to have one or more mutated genes (p = 0.0217), as well as higher allele frequencies of mutated genes (p = 0.0003), compared to GA. Likewise, known driver mutations associated with GC tumorigenesis (TP53, ERBB2, PIK3CA, and RNF43) were identified in half of the GC cases (50%, 10/20; p = 0.0002). Only the mutant burden, regardless of gene type, was retained, with an odds ratio of 1.8392 (95% confidence interval (CI), 1.0071 to 3.3588; p = 0.0474). CONCLUSION: Our study demonstrates that the accumulation of mutant burden contributes to tumorigenesis progression from GA to GC in Korean patients, regardless of the kind of genes. These findings may elucidate the molecular pathogenesis of gastric carcinogenesis and malignant progression.

Role of magnifying endoscopy with narrow-band imaging in the diagnosis of noninvasive gastric neoplasia.

BACKGROUND AND AIM: There are no globally approved, distinguishing criteria enabling the classification of gastric adenomas and intramucosal carcinomas for differential diagnosis of noninvasive neoplasia (NIN). METHODS: Next-generation sequencing of 50 cancer-related genes was undertaken on 68 pathologically diagnosed microdissected gastric neoplasms (25 adenomas, 27 intramucosal carcinomas, and 16 submucosal carcinomas) obtained during endoscopic submucosal dissection. Findings from magnifying endoscopy with narrow-band imaging (M-NBI) of 52 NINs (the 25 adenomas and 27 intramucosal carcinomas) were compared with these data. RESULTS: Among all 68 neoplasms, the most frequently mutated genes were APC (76% in adenoma, 11.1% in intramucosal carcinoma, and 0% in submucosal carcinoma; P < 0.001) and TP53 in intramucosal and submucosal carcinomas (8% in adenoma, 48.1% in intramucosal carcinoma, and 75% in submucosal carcinoma; P < 0.001). Dividing the NIN neoplasms into five groups according to their mutational status (A1: APC mutation, A2: APC + α mutation, B: APC + TP53 mutation, C: TP53 mutation, D: no mutation in either APC or TP53) resulted in almost identical diagnoses by pathology and M-NBI for groups A1 (12/13, 92%), C (12/13, 92%), and D (16/17, 94%) but not for groups A2 (3/7, 43%) or B (0/2, 0%). This finding implies that NINs with the APC + α mutation have carcinoma-like endoscopic features despite most being judged as adenomas by pathology. CONCLUSION: A diagnosis of NINs by pathology or M-NBI in the subset of gastric tumors classified by cancer-related mutations is not completely identical, suggesting the possible additional role of M-NBI in diagnosing NINs. Further studies are needed to confirm this.

Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up.

INTRODUCTION: Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. METHODS: This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. RESULTS: This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. DISCUSSION/CONCLUSION: Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.

Helicobacter Infection and Gastric Adenoma.

BACKGROUND: We aimed to provide insight into the actual frequencies of gastric adenoma types and their association with gastritis status and associated mucosal changes with a focus on Helicobacter infection and the operative link on gastritis assessment (OLGA)/operative link on gastric intestinal metaplasia assessment (OLGIM) staging. METHODS: From the archive of the Institute of Pathology in Bayreuth, we collected a consecutive series of 1058 gastric adenomas diagnosed between 1987 and 2017. Clinicopathological parameters retrieved from diagnostic reports included adenoma type and localization, associated mucosal changes in antrum and corpus (i.e., type of gastritis, the extent of intestinal metaplasia and atrophy), gender, date of birth, and date of diagnosis. RESULTS: Intestinal-type adenoma was the most frequent adenoma (89.1%), followed by foveolar-type adenoma (4.3%), pyloric gland adenoma (3.4%), adenomas associated with hereditary tumor syndromes (2.8%), and oxyntic gland adenoma (0.4%). Adenomas were found in the background of Helicobacter pylori (H. pylori) gastritis in 23.9%, Ex-H. pylori gastritis in 36.0%, autoimmune gastritis in 24.8%, chemical reactive gastritis in 7.4%, and others in 0.1%. More than 70% of patients with gastric adenomas had low-risk stages in OLGA and OLGIM. CONCLUSIONS: We found a higher frequency of foveolar-type adenoma than anticipated from the literature. It needs to be questioned whether OLGA/OLGIM staging can be applied to all patients.

A case report of endoscopic submucosal dissection for a new subtype of gastric adenoma: mixed fundic and pyloric mucosa type.

Precancerous lesions of gastric cancer are classified by the WHO (2019) into low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia (HGIN), and eminence lesions are adenomas. Gastric adenoma is a benign tumor of the stomach, which is more commonly located in the gastric antrum and gastric body. Usually, there is no obvious clinical manifestation. A 48-year-old man with intermittent abdominal bloating for four months to our hospital. Esophagogastroduodenoscopy revealed a 1.2 cm superficial elevated lesion in the anterior wall of the upper gastric body. The lesion had a whitish color and coarse surface. Biopsy revealed a low-grade intraepithelial neoplasia. Narrow-band imaging with magnifying endoscopy revealed a clear demarcation line with an irregular microsurface pattern. Detection of Helicobacter by the 13C-urea breath test was positive. The patient underwent an endoscopic resection. Histological results revealed gastric adenoma with mixed fundic and pyloric mucosa type, with HGIN. The lesion contained three types of cells: pyloric gland, fundus gland and foveolar epithelium. Helicobacter pylori detection was negative in the lesion. The present case demonstrates a new histological subtype of gastric adenoma. To the best of our knowledge, this is the first case report of gastric adenoma with mixed fundic and pyloric mucosa cell types.

Role of Octreotide in Menetrier's Disease: Case Report and Review of Literature.

Menetrier's disease (MD) is a rare disease characterized macroscopically by gastric rugae thickening and microscopically by foveolar hyperplasia with glandular atrophy, resulting in luminal protein loss. Different treatment strategies, including antibiotics, prednisone, octreotide, and monoclonal antibodies, have yielded varying degrees of success. Here, we present a rare complication of MD with a gastric outlet obstruction from a large adenoma. However, prior to this complication, dramatic clinical and laboratory improvements were observed after 12 months of treatment with subcutaneous octreotide. We also present a review of the literature for the role of octreotide in the treatment of MD.

STK11 p.F354L Germline Mutation in a Case of Multiple Gastrointestinal Tumors.

Serine/threonine kinase 11 (STK11) is known as a critical tumor-suppressor gene that is frequently mutated in a broad spectrum of human cancers. Among these, the p.F354L mutation of STK11 has been identified in sporadic colon or lung cancer cases. Here, we report the case of a 75-year-old male patient who underwent surgical treatment for multiple tumors of the gastrointestinal system. Genetic mutations were screened in all resected samples, including duodenal high-grade adenoma, gastric high-grade adenoma, rectal adenocarcinoma, and liver metastasis of rectal adenocarcinoma, by next-generation sequencing for mutational hotspots involving 50 oncogenes and tumor suppressor genes. The characteristic hamartomatous polyp of Peutz-Jeghers syndrome was not detected in any tumor specimen. However, all samples as well as the normal rectal mucosa harbored the genetic mutation p.F354L in STK11. In addition, somatic mutations coexisted in the tumor samples, including KRAS p.A146T, TP53 p.G238X, and APC p.T1556fs in the duodenal adenoma; TP53 p.G238Y and APC p.T1556fs in the gastric adenoma; and TP53 p.R282W in the rectal adenocarcinoma and metastatic liver cancer. No somatic mutation was detected in the normal rectal mucosa as a control sample. To our knowledge, this is the first report of an STK11 germline mutation in a patient with multiple tumors of the gastrointestinal tract.