On the origin of gastric tumours: analysis of a case with intramucosal gastric carcinoma and oxyntic gland adenoma.

Most gastric cancers develop in inflamed gastric mucosa due to Helicobacter pylori infection, typically with metaplastic changes. However, the origins of gastric cancer remain unknown. Here, we present a case of intramucosal gastric carcinoma (IGC) and oxyntic gland adenoma (OGA) derived from spasmolytic polypeptide-expressing metaplasia (SPEM). Early gastric cancer adjacent to a polyp was found in the upper corpus of a 71-year-old woman without H. pylori infection and was endoscopically resected. Histological examination showed IGC and OGA, both of which had predominant MUC6 expression. Interestingly, gastric glands with enriched MUC6-positive mucous cells, referred to as SPEM, expanded between them. Whole-exome sequencing analysis revealed a truncating KRAS(G12D) mutation in IGC, OGA, and SPEM. In addition, TP53 and CDKN2A mutations and a loss of chromosome 17p were found in the IGC, whereas a GNAS mutation was observed in the OGA. These results indicated that IGC and OGA originated from the KRAS-mutated SPEM. © 2023 The Pathological Society of Great Britain and Ireland.

Expansion of Gastric Intestinal Metaplasia with Copy Number Aberrations Contributes to Field Cancerization.

Intestinal metaplasia (IM) is a risk factor for gastric cancer following infection with Helicobacter pylori. To explore the susceptibility of pure gastric IM to cancer development, we investigated genetic alterations in single IM gastric glands. We isolated 50 single IM or non-IM glands from the inflamed gastric mucosa of 11 patients with intramucosal gastric carcinoma (IGC) and 4 patients without IGC; 19 single glands in the noninflamed gastric mucosa of 11 individuals from our cohort and previous dataset were also included as controls. Whole-exome sequencing of single glands revealed significantly higher accumulation of somatic mutations in various genes within IM glands compared with non-IM glands. Clonal ordering analysis showed that IM glands expanded to form clusters with shared mutations. In addition, targeted-capture deep sequencing and copy number (CN) analyses were performed in 96 clustered IM or non-IM gastric glands from 26 patients with IGC. CN analyses were also performed on 41 IGC samples and The Cancer Genome Atlas-Stomach Adenocarcinoma datasets. These analyses revealed that polyclonally expanded IM commonly acquired CN aberrations (CNA), including amplification of chromosomes 8, 20, and 2. A large portion of clustered IM glands typically consisted of common CNAs rather than other cancer-related mutations. Moreover, the CNA patterns of clustered IM glands were similar to those of IGC, indicative of precancerous conditions. Taken together, these findings suggest that, in the gastric mucosa inflamed with H. pylori infection, IM glands expand via acquisition of CNAs comparable with those of IGC, contributing to field cancerization. SIGNIFICANCE: This study contributes to our understanding of gastric intestinal metaplasia as a risk factor for gastric adenocarcinoma via their multifocal expansion and acquisition of CNAs and somatic mutations.

Gastric Hyperplastic Polyps Can Shrink After Discontinuation of Proton Pump Inhibitors: A Case Series Compared With Continuation of Proton Pump Inhibitors.

GOAL: This study investigated whether gastric hyperplastic polyps (GHPs) shrink after discontinuation of proton pump inhibitor (PPI) alone. BACKGROUND: Long-term use of PPIs has been reported to increase the incidence of GHPs, which sometimes bleed and cause anemia. We experienced a patient whose recurrent hemorrhagic GHPs associated with long-term use of PPIs had disappeared after discontinuation of PPIs. STUDY: This study was conducted retrospectively at Kyoto University Hospital. Patients with histologically confirmed GHPs who had been taking PPIs for >6 months and who had undergone a repeat endoscopy within 2 years were included. Polyp shrinkage was defined as the disappearance of polyps or a reduction of >50% in the long diameter of the largest polyp. RESULTS: Six patients who discontinued PPIs were compared with 17 patients who continued PPIs. Polyp shrinkage was significantly more frequent in the PPI-discontinuation group (5/6, 83%) than in the PPI continuation group (0/17, 0%) (P<0.001). In 2 patients in the PPI-discontinuation group, the polyps completely disappeared finally. CONCLUSION: These findings suggest that discontinuation of PPIs can shrink GHPs in patients using PPIs.

[Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography].

OBJECTIVE: The aim of this study was to determine if the difference in serum amylase levels prior to, and two hours following, an endoscopic retrograde cholangiopancreatography (ERCP), or the ratio of the two-hour post-ERCP amylase level to the pre-ERCP amylase level was a better predictor of post-ERCP pancreatitis (PEP). METHODS: This was a retrospective, single-center study of consecutive patients, who underwent ERCP between April 2015 and August 2018. Serum amylase was measured before and two hours following ERCP. We compared the difference and the ratio of the two levels in predicting PEP using a receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 1029 patients underwent ERCP, with PEP occurring in 118 (11.5%). Multivariate analysis revealed that an elevated two-hour post-ERCP serum amylase level was a significant predictor of PEP. ROC analysis of the difference and the ratio of the two levels found good performance for both parameters, with an area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.823-0.900) and 0.847 (95% CI, 0.809-0.886), respectively. The difference between the values was a significantly more effective predictor of PEP, based on the AUC analysis (P = 0.011). CONCLUSION: The difference between pre and two-hour post-ERCP amylase levels is a better predictor of PEP than the ratio of the two.

[Vitamin K deficiency caused by nutritional malabsorption accompanying afferent loop obstruction:a case report].

This case involves a 73-year-old man who visited a clinic because he was experiencing dyspnea on exertion and acid reflux. He was diagnosed with anemia and referred for a medical check-up and treatment by his primary care physician. Iron deficiency anemia and prolonged prothrombin time were confirmed with a blood test and an abdominal enhanced CT revealed marked expansion of the afferent loop after a gastrectomy. The medical check-up revealed abnormal blood coagulation due to afferent loop obstruction, which resulted in vitamin K deficiency. He was supplemented with vitamin K, and surgery was performed for the afferent loop obstruction. Postoperatively, his anemia, nutritional status, serum vitamin K levels, and prothrombin time improved steadily. In conclusion, nutrient malabsorption may occur in cases of afferent loop obstruction and abnormal blood coagulation due to vitamin K deficiency.

A case of resected hepatocellular carcinoma after drug-eluting bead transarterial chemoembolization.

We report a case of resected hepatocellular carcinomas (HCCs) after drug-eluting bead transarterial chemoembolization (DEB-TACE). A 67-year-old man with alcoholic liver disease was diagnosed with HCCs. Serological markers for hepatitis B and C viruses were negative. Among tumor markers, alpha-fetoprotein was 2.7ng/mL, and protein induced by vitamin K absence II was 868mAU/mL. Two HCCs were detected using dynamic computed tomography: one was 9cm in diameter in S8 and the other was 2cm in diameter in S4. We performed DEB-TACE using HepaSphere(®) and epirubicin. DEB-TACE was repeated three times in three months. Severe postembolization syndrome was not seen with any treatment. Four weeks after the last DEB-TACE, we performed surgical resection. Histopathological study revealed dense distribution of numerous bead particles in necrotic tumor tissue. Otherwise, in non-cancerous tissue, some beads were in portal areas, without necrotic change. Granulomas from foreign body reaction with giant cells were present around the beads. There were no necrotic changes in the smaller HCC, the intrahepatic metastatic nodules, or the microscopic invasion to the portal vein. In conclusion, DEB-TACE would be a useful treatment for huge HCCs; however, patients should be monitored for early recurrence from residual tumor tissue. This study will be helpful to perform DEB-TACE in the future.