Genome-wide DNA methylation profiling of gastric cardia cancer.

BACKGROUND AND AIM: Aberrant DNA methylation has been found in various cancer types including gastric cancer, yet the genome-wide DNA methylation profile of gastric cardia cancer (GCC) remains unclear. Therefore, we aimed to profile the DNA methylation pattern of GCC and identify promising diagnostic epigenetic biomarkers. METHODS: We investigated the genome-wide DNA methylation pattern in eight pairs of GCC and adjacent normal tissues using Illumina 850K microarrays. Subsequently, bisulfite-pyrosequencing and quantitative real-time PCR were performed on eight pairs of GCC-adjacent normal tissues for validation. Finally, we performed immunohistochemistry to examine ADHFE1 expression on 126 pairs of GCC-adjacent normal samples. RESULTS: DNA methylome analysis showed global hypomethylation and local hypermethylation of promoter cytosine-phosphate-guanine (CpG) islands (CGIs) in GCC tissues compared with gastric cardia normal mucosa (P < 2.2 × 10-16 ). Differential methylation analysis identified a total of 91 723 differentially-methylated probes (DMPs), and the candidate gene with the largest average DNA methylation difference mapped to ADHFE1 (mean Δß = 0.53). Subsequently, three DMPs in the ADHFE1 promoter were validated by pyrosequencing. Notably, the mean methylation level of the three candidate DMPs (ADHFE1_cg08090772, ADHFE1_cg19283840, and ADHFE1_cg20295442) was negatively associated with ADHFE1 mRNA expression level (Spearman rho = -0.64, P = 0.01). Moreover, both mRNA (P = 0.0213) and protein (P < 0.0001) expression of ADHFE1 were significantly decreased in GCCs compared with the adjacent normal tissues. CONCLUSIONS: Our results reveal DNA methylation aberrations in GCC and that ADHFE1 gene DNA methylation contributes to the risk of GCC, thus providing novel mechanistic insights into gastric cardia cancer carcinogenesis.

Global and national trends in the age-specific sex ratio of esophageal cancer and gastric cancer by subtype.

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age-specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003-2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age-standardized incidence rates (ASIRs) and male-to-female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male-to-female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male-to-female incidence rate ratios increased from young ages, approaching a peak at ages 60-64, but sharply declined thereafter. Similar "low-high-low" trends of age-specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age-dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.

Recent incidence trends of oesophago-gastric cancer in Sweden.

BACKGROUND: Oesophago-gastric cancers have had sharply different and changing incidence patterns depending on subsite and histology, but incidence data for the last few years are missing. We aimed to provide updated incidence trends of oesophago-gastric tumours by subsite and histology in Sweden. MATERIAL AND METHODS: The Swedish Cancer Registry provided data for 74,303 patients with oesophago-gastric cancer aged ≥50 years in 1970-2020. The focus was on the last available 6-year period, i.e., from 2015 until 2020 inclusive. We calculated yearly age-standardized and sex-specific incidence rates per 100,000 person-years, with the age distribution (in 5-year age groups) of the Swedish population in year 2000 as reference. RESULTS: For oesophageal squamous cell carcinoma, the incidence continued to decrease between 2015 and 2020 (from 6.46 to 5.53/100,000 person-years in men, and from 4.26 to 3.78/100,000 person-years in women). For oesophageal adenocarcinoma, the earlier increasing incidence rates rather slightly decreased in men between 2015 and 2020 (from 12.39 to 11.70/100,000 person-years) and increased marginally in women (from 2.49 to 2.85/100,000 person-years). The incidence rates of cardia adenocarcinoma were stable between 2015 and 2020 (from 9.83 to 10.13/100,000 person-years in men, and from 2.21 to 2.41/100,000 person-years in women). For gastric non-cardia adenocarcinoma, the incidence rates continued to decrease between 2015 and 2020 (from 14.67 to 13.29/100,000 person-years in men, and from 9.37 to 8.14/100,000 person-years in women). There were no major age-group differences in recent incidence trends. CONCLUSION: The 6-year period from 2015 to 2020 inclusive has witnessed stabilising incidence rates of oesophageal and cardia adenocarcinoma in Sweden, whereas the incidence rates of oesophageal squamous cell carcinoma and non-cardia gastric adenocarcinoma have continued to decrease.

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.

No Difference in Survival between Neo-Adjuvant Chemotherapy and Neo-Adjuvant Chemoradiation Therapy in Gastric Cardia Cancer Patients: A Contemporary View from the National Cancer Database.

INTRODUCTION: Both neo-adjuvant chemoradiation therapy (NACRT) and neo-adjuvant chemotherapy (NAC), in addition to surgical resection of gastric cardia cancer, improves survival outcomes. We assessed whether NACRT or NAC had superior overall survival (OS) and relative survival (RS) outcomes using the National Cancer Database (NCDB). METHODS: The NCDB from 2006 to 2014 was reviewed to identify non-metastatic adult gastric cardia cancer patients who underwent surgical resection and received NACRT or NAC. Advanced statistical models were applied to assess survival outcomes. RESULTS: Of the 5,371 patients included, 4,520 (84.2%) were male, the mean age was 61.2 years (SD 10.0), 4,229 (78.7%) underwent NACRT, and 1,142 (21.3%) underwent NAC. NACRT patients more often had an R0 resection compared to NAC (91.4 vs. 86.6%, p < 0.001, respectively). Univariate 5-year OS rates were 40.0% (95% CI 38.2-41.8) for NACRT and 40.1% (37.0-43.6) for NAC (p = 0.302). No differences in OS for NAC vs. NACRT were found after multivariable analysis (hazard ratio [HR] 0.95, 95% CI 0.86-1.05, p = 0.290). There were no survival differences after stepwise, propensity score, RS analyses, nor after near-far-matching (HR 0.94, 95% CI 0.82-1.07, p = 0.332). CONCLUSIONS: NAC or NACRT yield the same survival outcome for patients with resectable gastric cardia cancer. These data support the need for randomized controlled trials comparing the 2 regimens head-to-head.

Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer.

Gastric (GC) and esophageal (EC) cancers are highly lethal. Better understanding of molecular abnormalities is needed for new therapeutic targets and biomarkers to be found. Expression of 18 cancer-related genes in 31 paired normal-tumor samples was quantified by reversely-transcribed quantitative polymerase chain reaction (RTqPCR) and systemic concentration of 27 cytokines/chemokines/growth factors in 195 individuals was determined using Luminex xMAP technology. Only Ki67, CLDN2, and BCLxL were altered in GC while Ki67, CDKN1A, ODC1, SLC2A1, HIF1A, VEGFA, NOS2, CCL2, PTGS2, IL10, IL10Ra, and ACTA2 were changed in EC. The relatively unaltered molecular GC landscape resulted from high expression of BCLxL, CDKN1A, BCL2, Ki67, HIF1A, VEGFA, ACTA2, TJP1, CLDN2, IL7Ra, ODC1, PTGS2, and CCL2 in non-cancerous tissue. The NOS2 expression and IL-4, IL-9, FGF2, and RANTES secretion were higher in cardiac than non-cardiac GC. Four-cytokine panels (interleukin (IL)-1ß/IL-1ra/IL-6/RANTES or IL-1ß/IL-6/IL-4/IL-13) differentiated GC from benign conditions with 87-89% accuracy. Our results showed increased proliferative, survival, inflammatory and angiogenic capacity in gastric tumor-surrounding tissue, what might contribute to GC aggressiveness and facilitate cancer recurrence. Further studies are needed to determine the CLDN2 and NOS2 suitability as candidate molecular targets in GC and cardiac GC, respectively, and discern the role of CLDN2 or to verify IL-1ß/IL-1ra/IL-6/RANTES or IL-1ß/IL-6/IL-4/IL-13 usefulness as differential biomarkers.

Chronological Changes in the Gastric Cancer Subsite in Akita, Japan: The Trends from the Data of a Hospital-Based Registration System.

With the decreasing global trend in the Helicobacter pylori infection rate, compositional changes in the gastric cancer subsites have occurred worldwide. However, the compositional changes in Asian countries, including Japan, remain to be clarified. The aim of this study is to investigate the latest chronological changes in the gastric cancer subsite using a hospital-based registration system in Akita prefecture in Japan. From 2007-2015, subsites of gastric cancers were coded according to the International Classification of Diseases for Oncology (ICD-03). The nine-year registration period was divided into the three 3-year periods: 2007-2009, 2010-2012, and 2013-2015. A total of 10,804 cases of gastric cancer were registered. The proportion of cardiac cancer among total gastric cancer slightly but significantly declined from 12.1% in 2007-2009 to 9.2% in 2013-2015 (P < 0.01). Among non-cardia cancer, the proportion of corpus cancer significantly increased from 41.3% to 50.2% during the study period (P < 0.01), while that of antropylorus cancer significantly decreased from 37.6% to 34.3% (P < 0.05). Such compositional changes in the gastric cancer subsite were observed largely in men, regardless of the histologic subtype of cancer. With the decreasing H. pylori infection rate, compositional changes in the gastric cancer subsite are occurring in Japan. While the proportion of cardia and antropylorus cancer is declining, that of corpus cancer is increasing, indicating diverse etiology of gastric carcinogenesis depending on the subsites. Identifying the most common sites of occurrence, may help to improve the efficiency of screening for gastric cancer.

A case report of cardia cancer complicated with idiopathic muscular hypertrophy of the oesophagus treated with thoracoscopic surgery.

The incidence of idiopathic muscular hypertrophy of oesophagus (IMHE) is low, and <100 cases of IMHE have been reported. IMHE is a benign oesophageal disease, characterised by hyperplasia of all layers of the wall and in particular, muscle layer. Only a few cases have been reported regarding its clinical symptoms and images. In this present case, we report a cardia cancer with IMHE, showing significant hypertrophy of muscular layer of middle part of the oesophagus and successfully treated with minimally invasive thoracoscopic surgery.

The clinical utility of RFA in esophageal and cardia cancer patients with severe malignant obstruction.

Malignant obstruction of esophageal and cardia cancer greatly affects the prognosis and life quality of patients. However, no better regimens have been reported up to now. In recent years, radiofrequency ablation (RFA) has been prospectively proven in the management of some tumors. So, we investigated the impact of RFA on the malignant obstruction of esophageal and cardia cancer. In this study, we evaluated the operation duration, ablation duration, immediate compilations, etc., and followed up for 12 months. Our findings showed that there existed no technical problems in all 22 patients with a mean operation duration of 58 min and mean ablation duration of 23 min. No complication was observed in addition to postoperative low pressure in one patient and retrostenal pain in another patient. Importantly, all 22 patients obtained complete remission with normal diet and felt no sense of obstruction. Mean hospitalization time was 3 days and then the 12-month follow-up continued. To our relief, re-obstruction was not observed in all patients for 2 months. In conclusion, the entire effect of RFA was satisfactory, and patients can obtain a better life quality, less pains, and complications. So RFA should be advocated and greatly investigated by more institutes and hospitals.

Clinicopathological features and prognosis of gastric cardia adenocarcinoma: a multi-institutional US study.

BACKGROUND AND OBJECTIVES: Potential differences in presentation and outcome of patients with gastric cardia adenocarcinoma (GCA) and non-cardia adenocarcinoma may exist. The aim of the present study was to compare the clinicopathological characteristics and the prognosis of GCA versus non-cardia adenocarcinoma. METHOD: Patients with gastric adenocarcinoma who underwent gastric resection between 2000-2012 were identified. Clinicopathological characteristics and outcomes were analyzed based on tumor site using a 1:2 matched-control, as well as a multivariable Cox model. RESULTS: Among 743 patients, 80 (10.7%) patients were diagnosed with GCA. Patients with GCA were more likely to have intestinal tumor type (GCA: 80.4% versus non-cardia: 64.2%, P = 0.04) or advanced AJCC T stage tumors (GCA 71.8% versus non-cardia 59.2%, P = 0.03). GCA patients more likely underwent a total gastrectomy (GCA: 85.7% vs. non-cardia: 39.8%) and had a longer length-of-stay (GCA: 10 days vs. non-cardia: 8 days) (both P < 0.05). Outcomes in early stage I patients were worse among GCA (disease-free survival, 44.2%; overall survival, 42.3%) versus non-GCA (disease-free survival, 60.8%; overall survival, 63.0%) patients(both P < 0.05). CONCLUSION: In general, disease-free survival and overall survival were similar between patients with GCA versus non-cardia adenocarcinoma. However, long-term outcome was worse among patients with GCA and early stage disease.

A 5.5-year surveillance of esophageal and gastric cardia precursors after a population-based screening in China.

BACKGROUND AND AIM: This study aimed to estimate the time to precursor progression and to identify significant predicators. METHODS: One hundred thirty-three precursor and 311 normal cases detected in a population-based screening were surveyed for 5.5 years. Precursor progression was defined as worsening of dysplasia or development of a new precursor. Time to precursor progression was estimated by the Kaplan-Meier method. Significant predicators were estimated by Cox proportional regression. RESULTS: Of the 133 precursor cases, 33.08% (44/133) progressed or recurred, 30.08% (40/133) persisted, and 36.84% (49/133) regressed; of the 311 normal subjects, 13.50% (42/311) developed a precursor. Progression occurred significantly earlier and more frequently with ncreasing histology: with mind dysplasia (mD), 7.8% progressed by 1 year and 23.3% progressed by 5 year; with moderate dysplasia (MD), 18% progressed by 1 year and 70% progressed by 5 years; and with severe dysplasia, 50% progressed by 1 year and 100% progressed by 5 years. The difference between any two groups was significant. In addition, the marginal Lugol-stained mucosa at endoscopic mucosal resection had a progressing risk similar to that of MD, and basal cell hyperplasia was similar to that of mD. Significant predicators for precursor progression included male sex (hazard ratio and 95% CI: 2.74 (1.63-4.60)), age over 50 years (2.31 (1.33-4.02)), family history of upper gastrointestinal cancer (UGIC) (1.56 (1.00-2.45)), multifocal dysplasia (5.11 (3.01-8.68)), and baseline histology. CONCLUSIONS: Sex, age, family history of UGIC, multifocal dysplasia, and baseline histology are significant independent predicators for precursor progression. Patients after endoscopic mucosal resection should be continuously surveyed.

Prevention and treatment of a positive proximal margin after gastrectomy for cardia cancer.

A tumour-positive proximal margin (PPM) after extended gastrectomy for oesophagogastric junction (OGJ) adenocarcinoma is observed in approximately 2-20% of patients. Although a PPM is an unfavourable prognostic factor, the clinical relevance remains unclear as it may reflect poor tumour biology. This narrative review analyses the most relevant literature on PPM after gastrectomy for OGJ cancers. Awareness of the risk factors and possible measures that can be taken to reduce the risk of PPM are important. In patients with a PPM, surgical and non-surgical treatments are available but the effectiveness remains unclear.

Cardiac tamponade, a rare complication of gastric cardia cancer resection after neoadjuvant chemotherapy combined with immunotherapy: a case report and literature review.

Transthoracic cardia resection is a technically well-established surgical procedure. However, acute cardiac tamponade in the early postoperative period is extremely rare. The occurrence is life-threatening to the patient. It also poses a great clinical challenge for perioperative management. To date, few cases of pericardial tamponade have been reported in gastric cancer resection performed after neoadjuvant chemotherapy combined with immunotherapy. We present the case of a 62-year-old woman who received neoadjuvant chemotherapy combined with immunotherapy before surgery, followed by transthoracic surgery. A life-threatening complication, pericardial tamponade, occurred in the early postoperative period. The successful outcome was achieved in through multidisciplinary collaboration.

Corrigendum: Cardiac tamponade, a rare complication of gastric cardia cancer resection after neoadjuvant chemotherapy combined with immunotherapy: a case report and literature review.

[This corrects the article DOI: 10.3389/fonc.2023.1189500.].

Surgical approach to advanced Siewert II cancer: beyond the borders? The West Side.

The surgical approach to Siewert type II cancer should be individualized as there is no "one size fits all" option. Criteria for individualization are epidemiological, functional, oncologic and surgical items. However, our preferred procedure for advanced adenocarcinoma of the esophagogastric junction type II is esophagectomy, if this or transhiatal extended gastrectomy are both possible with R0 resection. Esophagectomy has the advantages of a longer esophageal safety margin, complete mediastinal lymphadenectomy, easier anastomosis, routine minimal invasive gastrolysis with abdominal lymphadenectomy and preservation of a gastric reservoir.

Association analysis of apoptosis-related gene caspase3, Integrin a subunit 1 and glutathione sulfur transferase M1 gene polymorphisms and susceptibility to gastric cardia carcinoma.

Background: To explore the association of polymorphisms of apoptosis-linked genes caspase3 (CASP3), integrin a subunit 1 (ITGA1), glutathione sulfur transferase M1 (GSTM1) with susceptibility to gastric cardia carcinoma (GCC). Methods: From February 2016 to March 2018, selection of 113 GCC patients was as the gastric cancer (GC), and selection of 75 patients without gastric disease was as the control. Detection of CASP3, ITGA1 and GSTM1 gene polymorphisms in patients' peripheral blood was to analyze their association with GC. Division of the GC was into the good prognosis and the unpleasing prognosis in the light of the survival of patients after surgery of 3 years, and the predictable value of gene polymorphisms of CASP3, ITGA1 and GSTM1 in GCC patients was analyzed. Results: CASP3 gene rs12108497 locus, ITGA1 gene rs1862610 locus and GSTM1 genotype of the GC and the control were in accord with Hardy-Weinberg equilibrium (P > 0.05); The detection rate of CASP3 gene rs12108497 locus TC/CC type, ITGA1's gene rs1862610 locus AC/AA type and GSTM1 blank type in the GC was elevated vs. the control (P < 0.05); Logistic regression analysis manifested smoking, anxiety, helicobacter pylori infection, family history of gastrointestinal tumor, combination with chronic gastric disease, CASP3 gene and GSTM1 gene polymorphism were risk factors for GC (P < 0.05); Stratification was in the light of individual smoking status, discovering that the detection rates of CASP3 gene rs12108497 locus TC/CC type, ITGA1 gene RS1862610 locus AC/AA type and GSTM1 blank type in the smoking were crucially augmented vs. the smoking (P < 0.05); The detection rates of CASP3 gene rs12108497 locus TC/CC type, ITGA1 gene rs1862610 locus AC/AA type and GSTM1 blank type in the death were augmented vs. the survival (P < 0.05); Combined detection of CASP3, ITGA1 and GSTM1 gene polymorphisms was provided with predictive value for GCC's prognosis (P < 0.05). Conclusions: CASP3 and GSTM1 genes are susceptibility genes for GCC, which might be associated with the occurrence of GCC in smoking patients, and the joint detection of multiple genes is provided with predictive value for patients' prognosis.

Trends in age-standardised net survival of stomach cancer by subsite and stage: A population-based study in Osaka, Japan, 2001-2014.

INTRODUCTION: The burden of stomach cancer remains high, particularly among Asian countries. Although Japan is known to achieve high survival from stomach cancer, little is known regarding the survival trends for recent years and survival by subsite and stage. We report age-standardised 1-, 3-, 5- and 10-year net survival for patients diagnosed with stomach cancer in Osaka, Japan. METHODS: We analysed patients diagnosed with primary stomach cancer and registered in the population-based cancer registry in Osaka Prefecture between 2001 and 2014. We used the non-parametric Pohar Perme method to derive net survival for each year. Both cohort and period approaches were used. Age was standardised using weights of the external population of the International Cancer Survival Standard. Multiple imputation was applied to handle missing information on subsite and stage before estimating age-standardised net survival by subsite (cardia and non-cardia) and stage (localised, regional and distant metastasis). We then examined general trends in the cohort-based survival estimates, as well as by subsite and stage, using linear regression. RESULTS: A total of 97,276 patients were included in the analysis. Age-standardised net survival improved steadily (mean annual absolute change ≥1.2%). Net survival for both subsites improved, but cardia cancer showed 7-23% lower survival than non-cardia cancer throughout the study period. Five-year net survival remained high (≥80%) in the localised stage from the beginning of this study. Net survival increased steeply (≥1.4% per year) in the regional stage. Although 1-year net survival increased by 14% in the distant stage, 5-year and 10-year net survival remained below 10%. CONCLUSION: Age-standardised net survival for stomach cancer in Japan improved during the study period owing to an increase in the number of patients with localised stage at diagnosis and improved treatment. Monitoring both short- and long-term survival should be continued as management of stomach cancer progresses.

Alterations of Gastric Microbiota in Gastric Cancer and Precancerous Stages.

Objective: Microbial infections have been shown to contribute to gastric carcinogenesis, the knowledge of gastric microbiota alteration in this process may provide help in early diagnosis of gastric cancer. The aim of this study was to characterize the microbial changes and identify taxonomic biomarkers across stages of gastric carcinogenesis. Methods: The gastric microbiota was investigated by 16S rRNA gene analysis in gastric mucosal specimens from 47 patients including superficial gastritis (SG), atrophic gastritis (AG), gastric intraepithelial neoplasia (GIN), and gastric cancer (GC). Differences in microbial composition across the disease stages, especially in GIN and GC were assessed using linear discriminant analysis effect size. Results: There was no gradual changing trend in the richness or diversity of the gastric microbiota across stages of gastric carcinogenesis. The relative abundance of dominant taxa at phylum and genus levels didn't show a gradual shift pattern, and the only four taxa that continuously enriched from SG to GC were Slackia, Selenomonas, Bergeyella, and Capnocytophaga, all of which were oral bacteria. The most representative taxa which were enriched in GC patients were oral bacteria including Parvimonas, Eikenella and Prevotella-2, and environmental bacteria including Kroppenstedtia, Lentibacillus, and Oceanobacillus. The gastric microbiota in GIN patients were characterized by enrichment of intestinal commensals including Romboutsia, Fusicatenibacter, Prevotellaceae-Ga6A1-group, and Intestinimonas. Gastric cardia cancer and non-cardia cancer patients had significantly different microbiota profiles characterized by a higher abundance of Helicobacter in the cardia cancer patients. Conclusions: Our results provide insights on potential taxonomic biomarkers for gastric cancer and precancerous stages, and suggest that gastric microbiota might play different roles in the carcinogenesis of cardia cancer and non-cardia cancer.

Is cardia cancer a special type of gastric cancer? A differential analysis of early cardia cancer and non-cardia cancer.

Background: The prognosis of early cardia cancer and non-cardia cancer is still controversial. It is difficult to collect a large number of cases with complete information in clinical practice. Our study was aimed to identify the differences in clinicopathological characteristics and outcomes of early cardia gastric cancer and non-cardia gastric cancer. Methods: All cases analyzed were from Surveillance, Epidemiology, and End Results database. The data of the patients with early gastric cancer from 2004 to 2010 was retrospectively analyzed. Patients were distributed to cardia cancer group and non-cardia cancer group. Univariate and multivariate analyses were performed to examine differences between groups. The competitive risk model was made to compare the association with cardia cancer and non-cardia cancer about the causes of death. Propensity score matching (PSM) was performed to reduce the bias. Results: We found that cardia cancer was more common in male patients and the White than that in non-cardia cancer at early stage, signet ring cell carcinoma was more common in non-cardia cancer, and the differentiation of non-cardia cancer was worse. Univariate analysis showed that age, marital status, race, tumor location, histology, grade, stage, and operation or not can determine the prognosis. And the prognosis of patients with cardia cancer was worse than that of non-cardia cancer, according to lymph node metastasis and the depth of tumor invasion. Multivariate analysis showed cardia cancer was an independent prognostic factor for poor prognosis. After PSM, cardia cancer still exhibited poor prognosis. Conclusions: At early stage, cardia cancer had a poor prognosis compared with non-cardia cancer. The prevention and treatment of early cardia cancer need to be seriously treated.

The complexity of cancer origins at the gastro-oesophageal junction.

Chronic acid-biliary reflux and Helicobacter pylori infection are instrumental environmental drivers of cancer initiation and progression in the upper gastrointestinal tract. Remarkably, although these environmental carcinogens are quite dissimilar, the tumour progression cascade these carcinogens engender is highly comparable. For this reason, studies of malignant progression occurring at the anatomic borderland between the oesophagus and the stomach have traditionally lumped junctional adenocarcinomas with either oesophageal adenocarcinoma or gastric adenocarcinoma. Whilst studies have revealed remarkable epidemiological and genetic similarities of these cancers and their associated premalignant conditions, these works have also revealed some key differences. This highlights that further scientific effort demands a dedicated focus on the understanding of the cell-cell interaction between the epithelium and the local microenvironment in this anatomic region. We here review available evidence with regards to tumour progression occurring at the gastro-oesophageal junction and contrast it with available data on cancer evolution in the metaplastic oesophagus and distal stomach.