Esophageal abnormalities and the risk for gastroesophageal cancers—a histopathology-register-based study in Sweden

Background The poor survival of patients with gastroesophageal cancers may improve if additional esophageal precursor lesions to Barrett’s esophagus and squamous dysplasia are identified. We estimated the risk for gastroesophageal cancers among patients with various histopathological abnormalities in the esophagus, including Barrett’s esophagus, subdivided by histopathological types. Methods Histopathology data from esophageal biopsies obtained 1979–2014 were linked with several national population-based registers in Sweden. Patients were followed from 2 years after the first biopsy date until cancer, death, emigration, esophagectomy/gastrectomy or end of follow-up, 31st of December 2016, whichever came first. We estimated standardized incidence ratios (SIRs) as measures of relative risk with the Swedish general population as reference. Results In total 367 esophageal adenocarcinoma (EAC) cases were ascertained during 831,394 person-years of follow-up. The incidence rate (IR) for EAC was 0.1 per 1000 person-years for normal morphology, 0.2–0.5 for inflammatory changes, and 0.8–2.9 for metaplasia. The IR was 1.0 per 1000 person-years (95% confidence interval 0.7–1.3) among patients with non-dysplastic intestinal metaplasia, 0.9 (0.8–1.1) in non-dysplastic gastric/glandular metaplasia and 2.9 (2.0–4.2) among columnar metaplasia patients with low-grade dysplasia. The SIRs were 11.7 (95% confidence interval 8.6–15.5), 12.0 (10.0–14.2) and 30.2 (20.5–42.8), respectively. The SIRs for gastric cardia adenocarcinoma (GCA) were moderately elevated. Conclusions For the first time, we demonstrate that patients with esophageal inflammatory and other metaplastic abnormalities than Barrett’s esophagus have an increased risk of EAC and GCA compared to the general population. Moreover, patients with different histopathologic subtypes of Barrett’s esophagus have a comparable risk for EAC.

Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.

Novel Metabolic Biomarker for Early Detection and Prognosis to the Patients with Gastric Cardia Adnocarcinoma

Background: Gastric cardia adenocarcinoma (GCA), which has been normalized as type II of adenocarcinoma at esophagogastric junction in western countries. In clinical, most of the GCA patients are lack of early alarming symptoms, more than 90% of GCA patients were diagnosed at advanced stage, resulted in a very poor prognosis, with less than 20% of 5-year survival. Obviously, early detection for GCA plays crucial role in decreasing the high mortality. Metabolomics allows for appraisal of small molecular mass compounds in a biofluid, which may provide a way for finding biomarkers for GCA. Methods: The serum metabolic features of 276 curatively resected GCA patients and 588 healthy control participates were collected from the database of State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital of Zhengzhou University to discover the metabolic dysregulation by using the ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). Joint pathway analysis with metabolites identified, survival analysis and auxiliary diagnosis metabolites were discussed in present work. Results: A sum of 200 known differential metabolites were obtained with p＜0.05 and fold change FC≥1.25 or FC≤0.8 by comparison GCA and healthy control participates. 12 metabolites significant correlated with survival (p＜0.05) and 17 metabolites for potential auxiliary diagnosis(FC＞1.5 or FC＜0.67) for GCA. Dysregulated arginine biosynthesis was an important pathway of GCA. 9 differential metabolites of 12-ketolithocholic acid, 2-Hydroxybutanoic acid, Aldosterone, All-trans-13,14-dihydroretinol, Hododeoxycholic acid, L-histidine, Malonic acid, Prostaglandin E2 and Sphingosine were identified as potential metabolic markers for distinguishing the GCA and healthy control (AUC=0.976, sensitivity =0.913, specificity =0.027, optimal cut off value=0.470). Conclusions: This work was first identified 12 metabolites significant correlated with survival and 17 metabolites for potential auxiliary diagnosis for GCA. In addition, arginine biosynthesis pathway metabolism showed important roles in GCA. Results provide the understanding of the molecular difference between GCA and healthy control. The novel plasma biomarkers panel could clearly distinguish GCA patients from the healthy control group. This finding may form the basis for the development of a minimally invasive method for GCA detection.

743 SIEWERT TYPE II GASTRIC CARDIA CANCER: ANALYSIS OF THE RESULTS OF DIFFERENT SURGICAL OPTIONS

The management of gastric cardia tumors should be carried out from a multidisciplinary approach, there is currently a clear controversy regarding the most appropriate surgical approach to use in type II tumors. Depending on their topographic anatomical characteristics based on the degree of gastric invasion and esophageal, the surgical technique may change: esophagectomy, gastrectomy with distal esophagectomy, or total esophageal gastrectomy. Methods Retrospective and analytical study of patients diagnosed with type II gastric cardia adenocarcinoma (based on the results of the pathological study of the resection specimen) who underwent surgical treatment in our center from June 2012 to June 2020. Different preoperative parameters, the surgical techniques used and the results obtained were analyzed. Results 25 patients were studied, 84% male. 60% were locally advanced tumors with 56% affected nodes. 12 Ivor-Lewis esophagectomies, 5 esophagogastrectomies with coloplasty, and 5 extended total gastrectomies were performed. There was no resection proximal or distal margin involvement, but circumferential margin was affected in 60% of cases of extended gastrectomy and in 1 case of Ivor-Lewis esophagectomy. Median number of lymph nodes removed was 22(5–37) and 2(0–12) affected, being higher in total esophagogastrectomy. Postoperative morbidity was 40% and 90-day mortality 4% (1 case). The mean follow-up was 37 months, noting recurrence in 9 cases (36%), with disease-free survival of 44%. Conclusion The surgical treatment approach in type II gastric tumors is controversial, and there are multiple options to consider. According to the results of this study, the Ivor-Lewis esophagectomy shows to be a safe approach with satisfactory oncological results in tumors that do not require a total esophagogastrectomy.

A Retrospective Experience of Helicobacter pylori Histology in a Large Sample of Subjects in Northern Italy

Updated data about the prevalence of Helicobacter pylori (H. pylori) and its correlation with histological results are scarce. The aim of our study was to provide current data on the impact of H. pylori in a third-level endoscopy service. We performed a large, retrospective study analyzing the results of all histological samples of gastroscopy from the year 2019. In total, 1512 subjects were included. The prevalence of H. pylori was 16.8%. A significant difference between the prevalence in subjects born in Italy and those from eastern Europe, south America, or Africa was found (p < 0.0001, p = 0.006, and p = 0.0006, respectively). An association was found between H. pylori and active superficial gastritis (p < 0.0001). Current H. pylori and/or a previous finding of H. pylori was related to antral atrophy (p < 0.0001). Fifteen patients had low-grade dysplasia. There were no statistically significant associations with current or past H. pylori infection. One patient presented gastric cardia adenocarcinoma with regular gastric mucosa. One patient, H. pylori positive, was diagnosed with gastric signet ring cell adenocarcinoma in a setting of diffuse atrophy, without metaplasia.. Our study provides updated, solid (biopsy diagnosis and large population) data on the prevalence of H. pylori infection in a representative region of southern Europe.

Extrachromosomal DNA is associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

Extrachromosomal DNA plays an important role in oncogene amplification in tumour cells and poor outcomes across multiple cancers. However, the function of extrachromosomal DNA in gastric cardia adenocarcinoma (GCA) is very limited. Here, we investigated the availability and function of extrachromosomal DNA in GCA from a Chinese cohort of GCA using whole-genome sequencing (WGS), whole-exome sequencing (WES), and immunohistochemistry. For the first time, we identified the ecDNA amplicons present in most GCA patients, and found that some oncogenes are present as ecDNA amplicons in these patients. We found that oncogene ecDNA amplicons in the GCA cohort were associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits in the geographic region. Strikingly, we observed diverse correlations between the presence of ecDNA oncogene amplicons and prognosis, where ERBB2 ecDNA amplicons correlated with good prognosis, EGFR ecDNA amplicons correlated with poor prognosis, and CCNE1 ecDNA amplicons did not correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients revealed that there was a positive correlation between the presence of ERBB2 and prognosis in 2-7-year survival; however, there was a negative correlation between the presence of ERBB2 and prognosis in 0-2-year survival. Our observations indicate that the presence of ERBB2 ecDNA in GCA patients may represent a good prognosis marker.

ABO genotypes and the risk of esophageal and gastric cancers

Background Blood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC). Methods We conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer. Results Compared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07–1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P < 0.001) with risk significantly elevated in type A (1.37, 1.14–1.65) and AB (1.44, 1.10–1.89) compared to type O. Blood type was not associated with gastric cardia adenocarcinoma (P = 0.13). Conclusions This study provides novel insights into the association between blood type and the risk of ESCC and restricted previously observed association to only gastric noncardia cancer, providing important evidence to clarify the pattern of association and suggesting mechanisms of action.

Cardiac Arrest Due to Pneumomediastinum following Esophagojejunal Anastomotic Fistula: A Case Report.

Background：Cardiac arrest due to pneumomediastinum following esophagojejunal anastomotic fistula is one of the most severe postoperative complications. However，It presents with insidious symptoms and easy to be ignored.Case presentation: A 59-year-old man had total laparoscopic radical gastrectomy for gastric cardia adenocarcinoma (GCA). Since then, He began to appear shortness of breath and dyspnea gradually. The image reported severe pneumomediastinum due to esophagojejunal anastomotic fistula. Sudden cardiac arrest developed. Immediate cardiopulmonary resuscitation (CPR) and epinephrine rescue were carried out. Stents were placed to plug the fistula and drainage was performed.Conclusions: Pneumomediastinum is easily overlooked as a complication of esophagojejunal anastomotic fistula after subtotal gastrectomy. A delay in diagnosis increases the rate of cardiac arrest. At present, the treatment of esophagojejunal anastomotic fistula mainly adopts conservative treatment such as drainage and interventional therapy. But the death rate is extremely high. Early positive identification is the life-saving procedure and should not be delayed.