Cardia Adenocarcinoma Research Articles

BBOX1-AS1 promotes gastric cardia adenocarcinoma progression via interaction with CtBP2 to facilitate the epithelial-mesenchymal transition process.

It is recognized that lncRNA BBOX1-AS1 exerts a crucial oncogenic property in several cancer types. However, the functions and underlying mechanisms of BBOX1-AS1 in the epithelial-mesenchymal transition (EMT) process of gastric cardia adenocarcinoma (GCA) have remained unclarified. The findings of this study demonstrated that GCA tissues had elevated BBOX1-AS1 expression levels, which was associated with a worse prognosis in GCA patients. BBOX1-AS1 dramatically enhanced cell proliferation, invasion, and TGF-β1-induced the EMT process invitro. Further mechanism analysis revealed that BBOX1-AS1 could combine with CtBP2 and strengthen the interaction of CtBP2 and ZEB1. BBOX1-AS1 might regulate the E-cadherin expression through CtBP2/ZEB1 transcriptional complex-mediated transcriptional repression, further affecting the activation of the Wnt/β-catenin pathway and the EMT process. Overall, our findings demonstrate that BBOX1-AS1 might act as an lncRNA associated with EMT for facilitating GCA advancement via interaction with CtBP2 to facilitate the activation of Wnt/β-catenin pathway and the EMT process, which indicated that it might function as an exploitable treatment target for GCA patients.

Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/β-catenin Signaling Pathway.

Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown. SMC4 expression levels were initially detected by protein profiling in 20 pairs of CA tumor tissues and adjacent normal tissues. The level of SMC4 expression in CA cells was then evaluated using a western blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation tests. Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/β- catenin pathway were investigated using western blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice. This study showed overexpression of SMC4 in CA tissues and cells. Knockdown of SMC4 can significantly inhibit the proliferation, migration and invasion, stimulate cell apoptosis, induce cell cycle arrest in the G0/G1 phase of CA cells, and inhibit tumor growth in vivo. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, β-catenin, phosphorylated GSK-3β, N-cadherin, and Vimentin, with an increased level of proteins, i.e., Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed. SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.

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

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. 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. 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. 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.

Short-Term Prognostic Effect of Comprehensive Complication Index in Patients With Gastric Cardia Adenocarcinoma

IntroductionThe Clavien-Dindo Classification (CDC) has been traditionally used for assessing postoperative complications. Recently, the Comprehensive Complication Index (CCI) has been introduced as a new tool. However, its prognostic significance in Gastric Cardia Adenocarcinoma (GCA) is yet to be determined. MethodsThe CCI and CDC of 203 patients who underwent radical surgery for GCA at Jinling Hospital from 2016 to 2023 were evaluated. Primary outcome variables included Hospital Length of Stay, duration of intensive care unit stay postoperatively, time to return to normal activities, and total hospitalization cost. The area under the curve was used to measure the correlation strength of the CCI and CDC for these outcomes. ResultsThe CCI demonstrated superior association strength, indicated by higher area under the curve values for all primary outcome variables compared to the CDC: Hospital Length of Stay (0.956 versus 0.910), intensive care unit stay duration (0.969 versus 0.954), time to return to normal activities (0.983 versus 0.962), and total hospitalization cost (0.925 versus 0.911). ConclusionsThe CCI showed a stronger positive association than the CDC with short-term postoperative complications in GCA. It has potential implications for improving postoperative patient management.

NNMT enriches for AQP5+ cancer stem cells to drive malignant progression in early gastric cardia adenocarcinoma

ObjectiveEarly gastric cardia adenocarcinoma (EGCA) is a highly heterogeneous cancer, and the understanding of its classification and malignant progression is limited. This study explored the cellular and molecular heterogeneity in...

Independent Stage Classification for Gastroesophageal Junction Adenocarcinoma.

In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. Patients with esophageal adenocarcinoma and gastric adenocarcinoma who underwent preoperative therapy followed by surgical resection from 2006 through 2017 were identified in the National Cancer Database. To enable stage-by-stage OS comparisons, tumors were classified into four gross ypTNM groups: ypT1/2, N-negative; ypT1/2, N-positive; ypT3/4, N-negative; and ypT3/4, N-positive. Prognostic factors were examined, and an OS prediction nomogram was developed for patients with abdominal/lower esophageal and gastric cardia adenocarcinoma, representing GEJ cancers. We examined 25,463 patient records. When compared by gross ypTNM group, the abdominal/lower esophageal and gastric cardia adenocarcinoma groups had similar OS rates, differing from those of other esophageal or gastric cancers. Cox regression analysis of patients with GEJ cancers showed that preoperative chemoradiotherapy was associated with shorter OS than preoperative chemotherapy after adjustment for the ypTNM group (hazard ratio 1.31, 95% CI 1.24-1.39, p < 0.001), likely owing to downstaging effects. The nomogram had a concordance index of 0.833 and a time-dependent area under the curve of 0.669. OS prediction in GEJ adenocarcinoma cases should include preoperative therapy regimens. Our OS prediction nomogram provided reasonable OS prediction for patients with GEJ adenocarcinoma, and future validation is needed.

Adherence to the Mediterranean Diet and Risk of Gastric Cancer: A Systematic Review and Meta-Analysis.

Available results on the association between the Mediterranean diet (MD) and gastric cancer (GC) incidence are controversial. The present study aimed to determine the correlation between different subtypes of GC and MD adherence. This meta-analysis was registered on PROSPERO (CRD42021284432). We searched Embase, PubMed, Cochrane Library, and Web of Science from inception through 22 April 2023 to retrieve relevant studies. A random-effects model was used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis. Pooled analyses revealed that adherence to the MD was inversely associated with GC risk (ORcc, 0.43; 95% CI, 0.29 to 0.63; ORcoh, 0.84; 95% CI, 0.77 to 0.92). Higher MD adherence was significantly associated with a reduced GC risk in male (ORcc, 0.78; 95% CI, 0.65 to 0.93; ORcoh, 0.81; 95% CI, 0.65 to 1.01), but not in female (ORcc, 0.83; 95% CI, 0.68 to 1.01; ORcoh, 1.04; 95% CI, 0.82 to 1.31). Furthermore, adherence to the MD possibly decreased the risk of gastric cardia adenocarcinoma (GCA) (ORcc, 0.64; 95% CI, 0.49 to 0.83; ORcoh, 0.88; 95% CI, 0.76 to 1.02) and gastric non-cardia adenocarcinoma (GNCA) (ORcc, 0.68; 95% CI, 0.59 to 0.79; ORcoh, 0.85; 95% CI, 0.78 to 0.94). Our results indicate that adherence to the MD reduces the risk of GC and its subtypes.

Predicting Incident Adenocarcinoma of the Esophagus or Gastric Cardia Using Machine Learning of Electronic Health Records

Tools that can automatically predict incident esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using electronic health records to guide screening decisions are needed. The Veterans Health Administration (VHA) Corporate Data Warehouse was accessed to identify Veterans with 1 or more encounters between 2005 and 2018. Patients diagnosed with EAC (n= 8430) or GCA (n= 2965) were identified in the VHA Central Cancer Registry and compared with 10,256,887 controls. Predictors included demographic characteristics, prescriptions, laboratory results, and diagnoses between 1 and 5 years before the index date. The Kettles Esophageal and Cardia Adenocarcinoma predictioN (K-ECAN) tool was developed and internally validated using simple random sampling imputation and extreme gradient boosting, a machine learning method. Training was performed in 50% of the data, preliminary validation in 25% of the data, and final testing in 25% of the data. K-ECAN was well-calibrated and had better discrimination (area under the receiver operating characteristic curve [AuROC], 0.77) than previously validated models, such as the Nord-Trøndelag Health Study (AuROC, 0.68) and Kunzmann model (AuROC, 0.64), or published guidelines. Using only data from between 3 and 5 years before index diminished its accuracy slightly (AuROC, 0.75). Undersampling men to simulate a non-VHA population, AUCs of the Nord-Trøndelag Health Study and Kunzmann model improved, but K-ECAN was still the most accurate (AuROC, 0.85). Although gastroesophageal reflux disease was strongly associated with EAC, it contributed only a small proportion of gain in information for prediction. K-ECAN is a novel, internally validated tool predicting incident EAC and GCA using electronic health records data. Further work is needed to validate K-ECAN outside VHA and to assess how best to implement it within electronic health records.

Decreased Risk of Esophageal Adenocarcinoma After Gastric Bypass Surgery in a Cohort Study From 3 Nordic Countries.

The objective of this study was to test the hypothesis that bariatric surgery decreases the risk of esophageal and cardia adenocarcinoma. Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown. This population-based cohort study included patients with an obesity diagnosis in Sweden, Finland, or Denmark. Participants were divided into a bariatric surgery group and a nonoperated group. The incidence of esophageal and cardia adenocarcinoma (ECA) was first compared with the corresponding background population by calculating standardized incidence ratios (SIR) with 95% CIs. Second, the bariatric surgery group and the nonoperated group were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CI, adjusted for sex, age, comorbidity, calendar year, and country. Among 748,932 participants with an obesity diagnosis, 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The SIRs of ECA decreased over time after gastric bypass, from SIR=2.2 (95% CI, 0.9-4.3) after 2 to 5 years to SIR=0.6 (95% CI, <0.1-3.6) after 10 to 40 years. Gastric bypass patients were also at a decreased risk of ECA compared with nonoperated patients with obesity [adjusted HR=0.6, 95% CI, 0.4-1.0 (0.98)], with decreasing point estimates over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR=0.3, 95% CI, 0.1-0.8) but not of cardia adenocarcinoma (HR=0.9, 95% CI, 0.5-1.6), when analyzed separately. There were no consistent associations between other bariatric procedures (mainly gastroplasty, gastric banding, sleeve gastrectomy, and biliopancreatic diversion) and ECA. Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.

Sex differences in cancer incidence rates by race and ethnicity: Results from the surveillance, epidemiology, and end results (SEER) Registry (2000-2019).

10547 Background: Sex differences in cancer incidence are pronounced, with men having 2-3 times the rate of most non-reproductive cancers than women. However, whether the male predominance is due to differences in biological factors or behavior remains not well understood. This study investigated sex differences in cancer incidence by race and ethnicity to provide a greater understanding of whether differences are driven by biological factors or environmental exposures. Methods: Cancer incidence data from the Surveillance, Epidemiology and End Result (SEER) program (2000-2019) was used to calculate male-to-female incidence rate ratios (MF IRR) for each cancer site and histological subtype, stratified by race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic), and age-standardized to the 2000 U.S. population for individuals ages ≥20 years. Results: Most non-reproductive cancers had a male predominance across race and ethnicity, with the largest MF IRR seen for cancers of the tonsil, hypopharynx, larynx, and Kaposi sarcoma (MF IRR &gt; 4). Three cancers, gallbladder; peritoneum, omentum, mesenter; and thyroid, were more common among females than males across all race and ethnicity. Females had a higher incidence of anal cancer than males for all racial and ethnic groups except for non-Hispanic Black individuals where the MF IRR was &gt;1. Cancers of the stomach, skin (excluding basal and squamous cell), melanoma skin, and other non-epithelial, and myeloma had greater MF IRR among non-Hispanic White adults than all other racial and ethnic groups. Non-Hispanic Black individuals had higher MF IRR of cancers of the liver and lung and bronchus, compared to other racial and ethnic group. Non-Hispanic White males had the highest MF IRRs for esophagus adenocarcinoma and gastric cardia adenocarcinoma and the lowest MF IRR for esophagus SCC compared to other races and ethnicity. Conclusions: The MF IRR for most cancers in this study did not differ by race and ethnicity, suggesting the influence of biological factors. Differences in the MF IRR across race and ethnicity may indicate carcinogenic exposure differences leading to the development of non-sex-specific cancers. Further research is needed to identify biological drivers of cancer incidence for most non-reproductive cancers. Funding: Intramural Research Program of the Division of Cancer Epidemiology and Genetics in the National Cancer Institute, National Institutes of Health.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study

Background We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. Methods This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. Results Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). Conclusion This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

Incidence trends and survival in early-onset esophagogastric adenocarcinoma: A Swedish population-based cohort study.

Early-onset adenocarcinomas of different sites are increasing in high-income countries, data on esophagogastric adenocarcinoma are sparse. We performed a Swedish population-based cohort study over 1993-2019 to delineate differences in incidence and survival in early-onset (age 20-54 years) compared to later-onset (55-99 years) esophageal, cardia, and non-cardia gastric adenocarcinoma. Temporal incidence trends were quantified as annual percentage changes (APC) and survival differences as excess mortality rate ratios (EMRR) using Poisson regression and including 95% confidence intervals (CI). Among 27,854 esophagogastric adenocarcinoma patients, 2576 were early-onset whereof 470 were esophageal, 645 were cardia, and 1461 were non-cardia gastric. Except non-cardia gastric, the male predominance was larger in early- compared to later-onset disease. Advanced stage and signet ring cell morphology were more common among early-onset patients. Early- and later-onset APC estimates were comparable and esophageal adenocarcinoma incidence increased, cardia remained stable, and non-cardia gastric decreased. Early-onset patients had better survival than later-onset, which was amplified when adjusting for prognostic factors including stage (adjusted EMRR 0.73 [95% CI 0.63-0.85] in esophageal, 0.75 [95% CI 0.65-0.86] in cardia, and 0.67 [95% CI 0.61-0.74] in non-cardia gastric adenocarcinoma). The early-onset survival advantage was more pronounced in localized stages 0-II (all sites) and women (esophageal and non-cardia gastric). We found no major differences in incidence trends comparing early- and later-onset esophagogastric adenocarcinoma. Despite unfavorable prognostic features, early-onset esophagogastric adenocarcinoma survival was better than later-onset, particularly in localized stages and women. Our findings suggest delayed diagnosis in younger individuals and especially men.

Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort

BackgroundCertain dietary patterns (i.e., low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with the risk of gastric cancer. However, it is unclear whether overall diet quality assessed by predefined indices that consider the complexity of dietary intake is associated with gastric cardia and distal adenocarcinoma. ObjectivesTo examine the association of a variety of diet indices with the risk of gastric cardia and distal adenocarcinoma and assess whether there are any subgroups that may benefit from better diets to reduce the risk of gastric adenocarcinoma. MethodsDietary indices of interest included the Alternative Healthy Index (AHEI)-2010, Healthy Eating Index (HEI)-2015, the Dietary Approach to Stop Hypertension, alternate Mediterranean diet (aMED), and the energy-adjusted Dietary Inflammatory Index. ResultsAfter an average follow-up time of 19.2 years, there were 836 incident cases of gastric distal adenocarcinoma and 207 cases of gastric cardia adenocarcinoma. We did not observe any significant associations between the dietary indices and gastric cancer for either anatomic site. Among former aspirin users, we observed an inverse association between aMED with distal cancer (HRQ5 vs. Q1: 0.64; 95% CI: 0.33, 1.23; P-trend = 0.03). Never smokers, who showed high-quality diet according to AHEI-2010, exhibited a 40% decreased risk of gastric distal cancer compared with those with the poorest-quality AHEI-2010 diet (HRQ5 vs. Q1: 0.60; 95% CI: 0.41, 0.88; P-trend = 0.08). ConclusionsIn a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among former aspirin users and never smokers, there could be a reduction of gastric distal adenocarcinoma risk with a higher adherence to a Mediterranean diet.

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.

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

PurposeSome 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 methodsA 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.ResultsMen 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).ConclusionGender 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.

S2379 Squamous Cell Carcinoma of the Gastroesophageal Junction as an Unusual Underlying Cause of Pseudoachalasia

Introduction: Achalasia is a rare esophageal motility disorder characterized by progressive dysphagia to solids and eventually liquids[1-2]. Pseudoachalasia refers to an achalasia secondary to an underlying etiology, such as masses, post-operative complications, or paraneoplastic syndromes[1-2]. The most common cause of pseudoachalasia is adenocarcinoma of the cardia or esophagus [1] however, we discuss a rare case that deviates from the typical etiology of esophageal cancer. Case Description/Methods: This is a 71-year-old male presenting with intermittent dysphagia for years with rapid progression for a month including intolerance of oral intake and 6-pound weight loss. On examination he was hemodynamically stable with a soft, nontender abdomen. His initial barium esophagram revealed decreased esophageal peristalsis, esophageal distention, and narrowing at the gastroesophageal junction (GEJ) with “bird beak” appearance consistent with possible achalasia. Further imaging studies were performed with computed tomography (CT), esophagogastroduodenoscopy (EGD) with dilation, and endoscopic ultrasound with biopsies revealing an invasive squamous cell carcinoma of the GEJ with submucosal involvement extending into the gastric cardia (Figure). We present our patient as the first reported case of pseudoachalasia due to SCC of the GEJ. The patient underwent esophageal stenting and mediport placement with plans for neoadjuvant chemotherapy with concurrent radiotherapy followed by definitive resection. Discussion: Pseudoachalasia is often misdiagnosed for primary achalasia because of its rarity, indistinguishable symptomatology, and normal findings on CT, EGD, and biopsy[1-2]. Nearly 75% of pseudoachalasia cases are due to adenocarcinoma of the gastric cardia[1]. Only one case of pseudoachalasia has been known to be caused by SCC in the distal esophagus[3]. SCC of the GEJ is an extremely rare esophageal malignancy and has never previously been reported as an underlying cause of pseudoachalasia.Figure 1.: Esophagogastroduodenoscopy revealed severe stricture at the GEJ with a 4 cm submucosal mass at the GEJ with extension to the gastric cardia.REFERENCES 1. Campo SM, Zullo A, Scandavini CM, Frezza B, Cerro P, Balducci G. Pseudoachalasia: A peculiar case report and review of the literature. World J Gastrointest Endosc. 2013;5(9):450-454. 2. Roushan N, Zolfaghari A, Asadi M, Taslimi R. Pseudoachalasia: a diagnostic challenge. Med J Islam Repub Iran. 2014;28:54. 3. Kahrilas, P., Kishk, S., Helm, J., Dodds, W., Harig, J. and Hogan, W., 1987. Comparison of pseudoachalasia and achalasia. The American Journal of Medicine. 1987;82(3):439-446.

The impact of a healthy lifestyle on the risk of esophageal and gastric cancer subtypes

Few prospective studies have been conducted on a combined healthy lifestyle and risk of esophageal and gastric cancer, and even less on subtypes: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). The relationship of a healthy lifestyle score (HLS) with risk of these cancers was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55–69 years provided information on dietary and lifestyle habits. The HLS was derived from information on smoking, body mass index, physical activity, Mediterranean diet adherence, and alcohol intake. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 333 incident esophageal and 777 gastric cancer cases, and 3720 subcohort members with complete data on lifestyles and confounders. The impact of changing to healthy lifestyles was estimated with the rate advancement period (RAP). The HLS was significantly inversely associated with risk of esophageal and gastric cancer, and subtypes (except EAC), in a linear fashion. The observed HR decrease per 1-point increase in HLS was 31% for esophageal, and 19% for gastric cancer, 49% for ESCC, 23% for GCA, and 18% for GNCA. The RAP per 1-point increase in HLS ranged from − 11.75 years for ESCC to − 2.85 years for GNCA. Also after excluding smoking, inverse associations between the HLS and esophageal and gastric cancer risk were still apparent. These results suggest that adhering to a combination of healthy modifiable lifestyle factors may substantially reduce the risk of esophageal and gastric cancer.

Survival trends in gastric cancer patients between 1987 and 2016: a population-based cohort study in Finland

BackgroundGastric cancer is the fourth leading cause of cancer-related deaths globally. There is a paucity of national studies examining gastric cancer mortality in relation to treatment status. This study evaluated the survival trends in gastric adenocarcinoma and all gastric cancers stratified by treatment in Finland during 1987–2016.MethodsThis population-based, nationwide, retrospective cohort study included all gastric cancer patients registered in the Finnish Cancer Registry and Patient Registry. The survival rates were calculated for 1, 3, and 5 years, stratified by treatment. Prognostic factors were determined using Cox regression.ResultsA total of 18,713 non-cardia gastric adenocarcinoma, and 3617 cardia adenocarcinoma patients were included. Surgical treatment decreased for non-cardia adenocarcinoma and remained constant for cardia adenocarcinoma. In non-cardia adenocarcinoma, the 5-year survival declined from 17% to 16% from 1987–1991 to 2012–2016. In surgically treated patients, survival increased from 29% to 38%, while an increase from 4% to 7% in those undergoing chemotherapy and decrease from 6% to 3% in those not receiving any treatment were observed. In cardia adenocarcinoma, the 5-year survival increased from 10% to 18% in all patients, 16% to 40% in surgical patients, 0% to 5% in patients receiving chemotherapy, and from 5% to 9% in patients receiving no treatment. Earlier calendar periods, older age, male sex, and higher comorbidity were risk factors for poor prognosis.ConclusionsGastric non-cardia adenocarcinoma survival declined, limited to advanced stage patients not receiving any treatment. Gastric cardia cancer survival seems to have improved over time in Finland.Mini abstractThis study evaluated survival trends of gastric cancer in Finland during 1987–2016 and established that the 5-year survival is declining in non-cardia adenocarcinoma but improving in all gastric cancers.

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

ObjectivesTo investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial–mesenchymal transition (EMT).MethodsWe 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.ResultsPAQR3 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‐β/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.ConclusionPAQR3 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‐β/Smad signaling pathway.

Strategy for Oligometastatic Recurrence of Cardia Adenocarcinoma: Liver Radiofrequency Ablation Associated with PIPAC Inducing Response Permitting Cytoreductive Surgery and HIPEC.

Management of oligometastatic disease (OMD) in esophagogastric junction cancer is complex due to anatomical location and adenocarcinoma pathway. Specific curative strategy is mandatory to increase survival. A multimodal approach combining surgery, systemic and peritoneal chemotherapy, radiotherapy, and radiofrequency could be envisaged. We report a strategy proposed for a 61-year-old male with cardia adenocarcinoma, initially treated with chemotherapy and superior polar esogastrectomy. He developed at later stage an OMD with peritoneal metastasis, single liver metastasis, and single lung metastasis. Considering that peritoneal metastases were unresectable at first, he was given multiple Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with oxaliplatin, associated with intravenous docetaxel. Percutaneous radiofrequency ablation was performed during the first PIPAC procedure. Peritoneal response allowed a secondary Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.