Delayed Presentation of Malignancy-Associated Pseudoachalasia of the Gastric Cardia.

Pseudoachalasia is a condition in which symptoms, manometry, and imaging findings highly resemble primary achalasia but has a secondary etiology. The majority of patients with pseudoachalasia have the condition as the result of a malignancy, most often at the gastroesophageal junction. There may be issues with timely identification of this malignancy as symptoms are often obscure with diagnostic testing yielding nonspecific results. We describe a case of a 65-year-old diabetic female smoker with a four-month history of intractable vomiting, abdominal pain, and weight loss who was belatedly found to have an adenocarcinoma at the gastric cardia necessitating a total gastrectomy and chemotherapy administration. The case educates clinicians on the clinical alarm symptoms related to malignant pseudoachalasia and stresses the paramount importance of performing a timely esophagogastroduodenoscopy in all cases of achalasia, even with seemingly normal imaging, to rule out pseudoachalasia related to malignancy.

Novel metabolic biomarker for early detection and diagnosis to the patients with gastric cardia adenocarcinoma.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate. METHOD: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. RESULTS: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set. CONCLUSIONS: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients.

Gastric Leiomyoma Near the Gastroesophageal Junction Causing Massive Gastrointestinal Bleeding.

Leiomyomas are rare, slow-growing submucosal tumors originating from smooth muscle cells. They are typically benign when found in the gastrointestinal tract, and they present no risk for recurrence or metastasis. In this report, we describe the case of a 64-year-old female patient presenting with severe anemia, generalized fatigue, and intermittent dark tarry stools and who was found to have a bleeding gastric cardia mass one centimeter distal to the gastroesophageal junction (GEJ) on abdominal computed tomography and confirmed with an esophagoduodenoscopy. Robotic-assisted laparoscopic wedge resection of the stomach with partial resection of the gastrohepatic ligament was performed to resect the mass. Histopathological examination revealed positivity for smooth muscle actin (SMA) and H caldesmon, consistent with a leiomyoma. In this report, we discuss this patient's clinical presentation, the method of mass resection, the importance of mass location in choosing a surgical approach for resection, and differential diagnoses for this case.

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.

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.

Revisiting the Mucosa of the Gastric Cardia: A Scope to Modify an Upper Gastrointestinal Endoscopy.

Introduction The mucosa in the cardiac region of the stomach has been less understood. Cardiac mucosa (CM) with less parietal and oxyntic cells has been defined as a normal mucosa. Studies have shown that CM can be the result of occult reflux. Oxyntic mucosa (OM) is normal, and it changes to CM with age. In advancing age, it is more common to find CM instead of OM and oxyntocardiac mucosa (OCM). This study is an attempt to examine the distribution of the three different types of mucosa in various age groups. Materials and methods The study was conducted in the Department of Anatomy and Department of Forensic Medicine and Toxicology of Gauhati Medical College, Guwahati, Assam, India, from 2017 to 2019. Once the stomach was opened, histological specimens were prepared, and the type of mucosa was observed and recorded. Then, the distribution of the types of mucosa in various age groups was analyzed. Results The distribution of mucosa varies significantly across different age groups, and CM increases with age. Conclusion Our present study suggests that CM frequency increases with age. This is in accordance with studies that suggest that CM is a result of occult reflux with age. This observation creates a scope to revise the approaches for upper gastrointestinal (GI) endoscopy.

Establishment and validation of a prognostic nomogram for postoperative patients with gastric cardia adenocarcinoma: A study based on the Surveillance, Epidemiology, and End Results database and a Chinese cohort.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram. METHODS: In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C-index, calibration curve, time-dependent ROC curve, and DCA curve. Kaplan-Meier survival curves were also generated to illustrate the differences in cancer-specific survival (CSS) between the groups. RESULTS: The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer-specific survival in the training cohort. Both the C-index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high- and low-risk groups were observed. CONCLUSIONS: Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability.

Survival influence of gender on 42,345 patients with gastric cardia adenocarcinoma.

PURPOSE: Some studies indicated that gender is associated with prognostic of cancer, However, currently the prognostic value of gender for gastric cardia adenocarcinoma (GCA) survival is unclear. The aim of our study is to reveal the influence of gender on the prognosis of patients with GCA. PATIENTS AND METHODS: A total of 42,345 cases Chinese GCA patients were enrolled from our previously established GCA and esophageal cancer databases. The clinicopathological characteristics were retrieved from medical records in hospital. The follow-up was performed through letter, telephone or home interview. Among GCA patients, there were 32,544 (76.9%) male patients with the median age 62 years (range 17-97) and 9,801 (23.1%) female patients with the median age 61 years (range 17-95 years). The Chi-square test and Kaplan-Meier method were used to compare the continuous variables and survival. Cox proportional hazards model was used for competing risk analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated. RESULTS: Men had shorter GCA-specific survival than women by multivariate analysis (HR 1.114; 95% CI 1.061 to 1.169; P < 0.001). Whether premenopausal, perimenopausal or postmenopausal, the survival of women was better than that of men (premenopausal vs. male, P < 0.001; perimenopausal vs. male, P < 0.001; postmenopausal vs. male, P = 0.035). It was worth noting that in patients with stages I, II, III, and IV, female patients survive longer than male patients (P = 0.049; P = 0.011; P < 0.001; P = 0.044, respectively). CONCLUSION: Gender is an independent prognostic factor for patients with GCA. In comparison with men, women have a significantly better outcome. Smoking and drinking may be protective factors for male GCA patients.

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.

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.].

Efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors of gastric cardia and fundus: a multicenter study / 中华消化外科杂志

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

The efficacy of full-thickness endoscopic resection of subepithelial tumors in the gastric cardia.

BACKGROUND: Gastric subepithelial tumors (SETs) may harbor potential malignancy. Although it is well recognized that large SETs should be resected, the precise treatment strategy remains controversial. Compared to surgical resection, endoscopic resection (ER) has many advantages; however, ER of SETs in the cardia is challenging. AIM: To evaluate the safety and efficacy of endoscopic full-thickness resection (EFTR) for the treatment of gastric cardia SETs. METHODS: We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER (STER) at Zhongshan Hospital Fudan University between November 2014 and May 2022. Baseline characteristics and clinical outcomes, including procedure times and complications rates, were compared between groups of patients receiving EFTR and STER. RESULTS: A total of 171 tumors were successfully removed [71 (41.5%) tumors in the EFTR and 100 (58.5%) tumors in the STER group]. Gastrointestinal stromal tumors (GISTs) were the most common SET. The en bloc resection rate was 100% in the EFTR group vs 97.0% in STER group (P > 0.05). Overall, the EFTR group had a higher complete resection rate than the STER group (98.6% vs 91.0%, P < 0.05). The procedure time was also shorter in the EFTR group (44.63 ± 28.66 min vs 53.36 ± 27.34, P < 0.05). The most common major complication in both groups was electrocoagulation syndrome. There was no significant difference in total complications between the two groups (21.1% vs 22.0%, P = 0.89). CONCLUSION: EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER. In cases of suspected GISTs or an unclear diagnosis, EFTR should be recommended to ensure complete resection.

Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal metaplasia.

Background: Intestinal metaplasia (IM) of the gastric cardia is an important premalignant lesion. However, there is limited information concerning its epidemiological and molecular features. Herein, we aimed to provide an overview of the epidemiological data for gastric cardiac IM and evaluate the role of EYA transcriptional coactivator and phosphatase 4 (EYA4) as an epigenetic biomarker for gastric cardiac IM. Methods: The study was conducted in the context of the gastric cardiac precancerous lesion program in southern China, which included 718 non-cancer participants, who undertook endoscopic biopsy and pathological examination in three endoscopy centers, between November 2018 and November 2021. Pyrosequencing and immunohistochemistry were performed to examine the DNA methylation status and protein expression level of EYA4. Results: Gastric cardiac IM presented in 14.1% (101/718) of participants and was more common among older (>50 years; 22.0% [95% CI: 17.8-26.8]) than younger participants (≤50 years; 6.7% [95% CI: 4.5-9.9]; P < 0.001). IM was more common in male participants (16.9% [95% CI: 13.2-21.3] vs. 11.3% [95% CI: 8.3-15.1]; P = 0.04). Pyrosequencing revealed that IM tissues exhibited significantly higher DNA methylation levels in EYA4 gene than normal tissues (P = 0.016). Further, the protein expression level of EYA4 was reduced in IM and absent in intraepithelial neoplasia tissues compared to normal tissues (P < 0.001). Conclusions: Detection rates of gastric cardiac IM increase with age and are higher in men. Our findings highlight the important role of promoter hypermethylation and downregulation of EYA4 in gastric cardiac IM development.

Endoscopic submucosal dissection for early esophagogastric junction adenocarcinomas: a systematic review.

Background: Esophagogastric junction adenocarcinomas (EGJAs) include esophageal and gastric cardia adenocarcinomas (GCAs). These tumors are currently regarded as a single entity, with similar surgical and oncological therapies, although they originate from different organs. Endoscopy allows an early-stage diagnosis, where both subtypes can be differentiated. With this review we aimed to describe the outcomes of endoscopic submucosal dissection for the treatment of esophageal adenocarcinomas (EAs) and GCAs. Methods: We identified studies by screening PubMed, Embase and Web of Science. We included all 19 studies that mentioned at least one of the following criteria of interest: en bloc; R0 resection; local recurrences; and/or overall survival. Results: We found an en bloc resection rate superior to 90% for both tumors. R0 resections rates were over 60% for most EAs, vs. 83% for most GCAs. We recorded less than 13% and 20% early and late adverse events for EA, and 10% and 7% for GCA. The local recurrence rate was 8% for EA and 3% for GCA. The overall survival was over 90%. Conclusions: Endoscopic submucosal dissection is safe and effective for esophageal and GCAs. These data support the extension of the use of endoscopic submucosal dissection to all EGJAs, including early EAs.

Golgi scaffold protein PAQR3 as a candidate suppressor of gastric cardia adenocarcinoma via regulating TGF-ß/Smad pathway.

OBJECTIVES: To investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial-mesenchymal transition (EMT). METHODS: We detected PAQR3 protein in 146 GCA tissues and paired normal adjacent tissues (PNTs) specimens using immunohistochemical analysis, and explored its clinical significance. The expression levels of PAQR3 protein in 20 GCA tissues, their paired PNTs, HGC27, SGC7901, and GES-1 cells were analyzed by Western blot. Wild-type PAQR3 was overexpressed in HGC27 cells. The effects of PAQR3 overexpression on the function of HGC27 cells and its underlying mechanisms were then analyzed through a series of cell and molecular biology experiments. RESULTS: PAQR3 was significantly down-regulated in GCA tissues when compared with paired PNTs (p < 0.0001). The expression level of PAQR3 in GCA tissues was significantly negatively correlated with Helicobacter pylori infection (p = 0.000), venous invasion (p = 0.000), invasion depth (p = 0.000), lymph node metastasis (p = 0.022), tumor stage (p = 0.000), and patient survival (p = 0.009). Downregulation of PAQR3 was highly correlated with increased EMT signature and activated TGF-ß/Smad pathway in GCA tissues. Overexpression of PAQR3 in HGC27 cells negatively regulates its cellular functions, such as cell proliferation and migration, and suppresses EMT. Mechanistically, overexpression of PAQR3 significantly down-regulates the protein expression levels of TGF-1, p-Smad2, and p-Smad3 in HGC27 cells. CONCLUSION: PAQR3 was significantly down-regulated in GCA tissues, HGC27, and SGC7901 cells. PAQR3 significantly inhibits the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 can inhibit the EMT process in HGC27 cells by regulating TGF-ß/Smad signaling pathway.

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.

Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients.

BACKGROUND: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. METHODS: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. RESULTS: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. CONCLUSION: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Microbial Diversity and Composition in Six Different Gastrointestinal Sites among Participants Undergoing Upper Gastrointestinal Endoscopy in Henan, China.

The objective of this study was to describe and compare the dynamic microbiota characteristics in the gastrointestinal (GI) tract in Chinese participants via high-throughput sequencing techniques. The study collected saliva, esophageal swab, cardia biopsy, noncardia biopsy, gastric juice, and fecal specimens from 40 participants who underwent upper GI tract cancer screening in Linzhou (Henan, China) in August 2019. The V4 region of 16S rRNA genes was amplified and sequenced using the Illumina MiniSeq platform. The observed amplicon sequence variants (ASVs) gradually decreased from saliva to esophageal swab, cardia biopsy, noncardia biopsy, and gastric juice specimens and then increased from gastric juice to fecal specimens (P < 0.05). Each GI site had its own microbial characteristics that overlapped those of adjacent sites. Characteristic genera for each site were as follows: Neisseria and Prevotella in saliva, Streptococcus and Haemophilus in the esophagus, Helicobacter in the noncardia, Pseudomonas in gastric juice, Faecalibacterium, Roseburia, and Blautia in feces, and Weissella in the cardia. Helicobacter pylori-positive participants had decreased observed ASVs (cardia, P < 0.01; noncardia, P < 0.001) and Shannon index values (cardia, P < 0.001; noncardia, P < 0.001) compared with H. pylori-negative participants both in cardia and noncardia specimens. H. pylori infection played a more important role in the microbial composition of noncardia than of cardia specimens. In gastric juice, the gastric pH and H. pylori infection had similar additive effects on the microbial diversity and composition. These results show that each GI site has its own microbial characteristics that overlap those of adjacent sites and that differences and commonalities between and within microbial compositions coexist, providing essential foundations for the continuing exploration of disease-associated microbiota. IMPORTANCE Upper gastrointestinal (UGI) tract cancer is one of the most common cancers worldwide, while limited attention has been paid to the UGI microbiota. Microbial biomarkers, such as Fusobacteria nucleatum and Helicobacter pylori, bring new ideas for early detection of UGI tract cancer, which may be a highly feasible method to reduce its disease burden. This study revealed that each gastrointestinal site had its own microbial characteristics that overlapped those of adjacent sites. There were significant differences between the microbial compositions of the UGI sites and feces. Helicobacter pylori played a more significant role in the microbial composition of the noncardia stomach than in that of the cardia. Gastric pH and Helicobacter pylori had similar additive effects on the microbial diversity of gastric juice. These findings played a key role in delineating the microbiology spectrum of the gastrointestinal tract and provided baseline information for future microbial exploration covering etiology, primary screening, treatment, outcome, and health care products.

Characterization of E-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis.

BACKGROUND: Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM: To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS: A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan-Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS: Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION: E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.